A re-appraisal of treatment in chronic bacterial prostatitis. The pH of normal human expressed prostatic secretion in 136 samples from 93 men was 7.28 +/- 0.04. In 41 samples from 14 patients with documented chronic bacterial prostatitis the alkalinity of prostatic fluid was increased 10-fold (1 pH unit) and was 8.32 +/- 0.07. We believe these studies account for the failure of trimethoprim to eradicate human bacterial prostatitis effectively despite the experimental data documenting diffusion and concentration of trimethoprim in the acidic prostatic fluid of the normal dog. The factors governing drug diffusion into the prostate and the influence of pH on the concentration of trimethoprim in the expressed prostatic secretion are discussed.


Testicular microlithiasis in 2 children with bilateral cryptorchidism. Testicular microlithiasis, associated with bilateral cryptorchidism, is studied in 2, 6-year-old children. In case 1 autopsy revealed that 60 per cent of the seminiferous tubules contained completely calcified microliths. Similar mineralized concretions also were found in different areas of the cerebrum and cerebellum. In the testicular biopsy obtained from case 2, 30 per cent of the seminiferous tubules contained microliths showing different degrees of calcification. The study of such calcifications supports the hypothesis that the mineralization process occurs according to the following stages: 1) accumulation of cellular debris in the tubular lumen, 2) deposit of concentric rings of glycoprotein material surrounding the central core and 3) calcification of the glycoprotein lamellar material. The presence of similar concretion in the nervous system as well as the lung in other reported cases suggests that microlithiasis could be a systemic disease.


Urinary lithogenesis in Sudanese patients: a study of stone formers. This prospective study confirms the previously reported high incidence of uric acid lithiasis in the Sudan. Despite this fact urinary pH in patients in whom stones formed was not significantly different from controls (p greater than 0.05). However, a significantly high serum uric acid level (p less than 0.01) was associated with recurrent and/or bilateral stones. In patients with single episodes of stones significant hyponatremia (p less than 0.001) may indicate excessive sweating. The resulting low urine output supersaturated with crystals may explain lithogenesis in this group of patients.


Clinical and laboratory evaluation of the antibody-coated bacteria test in children. The antibody-coated bacteria test can distinguish upper from lower urinary tract infection. In this study 67 bacteriuric children were selected from meningomyelocele and urology clinics. There was close correlation between radiological evidence of upper tract changes and the presence of antibody-coated bacteria. There was a distinct lack of correlation between serum antibody titers to the infecting organism and antibody-coated bacteria. In vitro laboratory studies indicated that 1) antibody coating in the urine occurred immediately upon exposure of the infecting isolate to the urine of the patient, 2) only the homologous isolate was coated and 3) the pH range for antibody coating was wide (pH 4.0 to 9.0).


Medical management of chronic cancer pain. Management of the chronic pain of cancer is a common and difficult problem. In addition to a medical examination of the patient, it is necessary to perform a psychological assessment of his premorbid personality, current mental status, and coping mechanisms to devise an individualized approach to his pain. The mainstay of cancer pain control are the narcotics, which differ primarily in potency and duration of action. Nonnarcotic analgesics are equianalgesic with the less potent narcotics. Antipsychotic drugs are useful as tranquilizers, antiemetics, and analgesic potentiators. Antidepressants and hypnotics permit the patient a more normal life-style. Stimulants such as cocaine and amphetamines both potentiate narcotic analgesia and reduce narcotic-induced somnolence and respiratory depression. Tetrahydrocannabinol offers no advantage over traditional analgesics. With care and patience, the physician can render practically any cancer patient pain-free.


Effects of anti-anginal agents on cyclical reductions of coronary blood flow. The effects of coronary vasodilating agents and alpha- and beta-adrenergic blocking agents on cyclical reductions of blood flow in the partially constricted coronary artery of anesthetized dogs were examined. Intravenous injections of nitroglycerin (50 microgram/Kg), SG 75 (150 microgram/Kg), papaverine (1 mg/Kg), and nicotinic acid (10 mg/Kg) eliminated both cyclical reductions of flow and ST elevation (group 1). Nifedipine (10 microgram/Kg), verapamil (500 microgram/Kg), diltiazem (500 microgram/Kg), and propranolol (500 microgram/Kg) suppressed ST elevation, but they could not eliminate cyclical reductions of flow (group 2). Dipyridamole (1 mg/Kg) and phenotolamine (500 microgram/Kg) augmented both ST elevation and cyclical reductions of flow (group 3). The results indicate that ST elevation due to cyclical reductions of coronary blood flow was eliminated by spasmolytic actions of group 1 on coronary artery, was suppressed by negative chronotropic and/or inotropic actions of group 2, and was augmented by peripheral actions of group 3.


Prognostic factors in pediatric cases of drowning and near-drowning. Ninety-three cases of drowning or near-drowning in the pediatric age group between 1972 and 1976 were reviewed. A scoring system for prognostic factors was developed using one point for each of five unfavorable factors involved in the drowning or near-drowning of each patient. The prognostic factors were 1) age less than three years; 2) maximum submersion time estimated longer than five minutes; 3) resuscitation not attempted for at least ten minutes after rescue; 4) patient in coma on admission to hospital, and 5) arterial blood pH of less than or equal to 7.10. This scoring system significantly predicted the eventual outcome of patients who had experienced the postsubmersion syndrome. Patients with scores of less than or equal to 2 had a 90% chance of full recovery; those with scores of greater than or equal to 3 had only a 5% probability of survival. The early institution of resuscitative efforts was the single most important factor influencing survival.


Metabolic acidosis with pneumatic trousers in hypovolemic dogs. To evaluate the possibility of anaerobic metabolism occurring beneath pneumatic trousers because of the decreased circulation, 20 mongrel dogs were evaluated for central and femoral vein levels of lactic acid, potassium and central pH changes when the trouser pressure was both above and below systolic arterial pressure. The results indicate that if the systolic pressure is less than trouser pressure, there is a significant increase in both potassium and lactic acid levels. There was a drop in the central pH accompanying these metabolic changes. When the pneumatic trouser pressure was less than systolic arterial pressure, changes in anaerobic metabolism were present but not nearly as great. This change was much closer to that in the central circulation and may result from other factors. Based on these results, trouser inflation pressure should not exceed that required to achieve adequate arterial pressure. Deflation should be started as soon as possible and be gradual.


Induction and properties of aryl hydrocarbon hydroxylase in bovine pancreatic ducts. Inducibility and characteristics of aryl hydrocarbon hydroxylase (AHH) in cultured bovine pancreatic ducts were studied by the fluorometric method. AHH was present and inducible in all the pancreatic ducts studied when they were exposed to 20 microgram benz[a]anthracene (BA)/ml medium. AHH activity in the control tissue ranged from 1.0 to 3.0 U/mg DNA, whereas the activity in the BA-treated tissue was 4.2--28.5 U/mg DNA, which resulted in the induction of 5- to 18-fold activity. At 12 hours of BA exposure, AHH activity in the treated tissue was 12-fold that in the control tissue and continued to increase to 15-, 19-, and 31-fold that in the control tissue at 24, 48, and 72 hours, respectively. The BA-induced AHH activity had a broad pH optimum between 7.1 and 7.7, and the maximum activity was found at pH 7.4. The AHH activity was linear with respect to the incubation time up to 30 minutes. The effect of the benzo[a]pyrene concentration on AHH activity was studied on the BA-induced enzyme. The apparent Michaelis constant for the substrate was 0.5 microM, and the maximum velocity was 8.6 U/mg DNA. BA-induced AHH activity was inhibited 65% by 100 microM 7,8-benzoflavone, whereas the control enzyme activity was stimulated 100% by the same concentration of 7,8-benzoflavone.


[Dynamics of the echocardiographic indices of myocardial contractile function in chronic ischemic heart disease under treatment with blockaders of the cardiac beta-adrenergic receptors]. The article discusses the results of dynamic echocardiographic examination of 46 patients with chronic ischemic heart disease before and after 15-day treatment with agents capable of blocking beta-receptors: propranolol (anaprilin), pindolol (visken), talinolol (cordan) which were prescribed in mean therapeutical doses. It is shown that agents blocking beta-adrenergic receptors lead to regular decrease in the indices of myocardial contractility. The character of changes in the volumetric characteristics of the left ventricle depends on the initial levels of arterial pressure and the degree of its dynamics during treatment with beta-adrenergic blocking agents. In patients with chronic ischemic heart disease developing against the background of hypertensive disease the dynamics of changes in the volumetric indices depends on the degree of arterial pressure reduction.


Effects of potassium depletion on renal tubular chloride transport in the rat. Potassium depletion (KD) causes renal chloride-wasting. To investigate the effects of KD on renal tubular reabsorption of chloride, balance, clearance, micropuncture, and microinjection studies were performed on potassium-depleted rats. KD was produced by omitting potassium from the diet and by administration of DOCA on days 2 and 3; rats were studied on days 9 to 12. Diets were chloride-free in both control and KD groups. In the KD group, balance experiments confirmed greater chloride depletion and continued chloride-wasting, and clearance studies showed an increased FECl. Muscle potassium was reduced by 27% as compared to control. Whole kidney and single nephron GFR were reduced in KD rats to 72 and 74% of control. Fractional (6 +/- 6% vs. 22 +/- 4%, P less than 0.05) and absolute chloride reabsorption in the proximal tubule was not different. Fractional reabsorption of delivered chloride was reduced in the loop of Henle (92 +/- 0.8% in KD vs. 95 +/- 0.7% in control, P less than 0.02). Transtubular chloride ratio (0.28 +/- 0.02 vs. 0.21 +/- 0.02, P less than 0.02) was increased at the early distal tubule. Fractional delivery of chloride (8 +/- 0.9 vs. 5 +/- 0.5%, P less than 0.02), and fluid (26 +/- 1 vs. 22 +/- 1%, P less than 0.05) were also increased in KD at the early distal tubule. Recovery of chloride 36 injected into late distal tubules was 88 +/- 1% on a normal chloride intake, 62 +/- 2% in chloride depletion, and 88 +/- 2% in potassium and chloride depletion. Thus, KD depresses chloride reabsorption in the proximal tubule and in the loop of Henle, and it decreases chloride 36 efflux from the collecting duct.


Mechanism of the metabolic acidosis of selective mineralocorticoid deficiency. The mechanism of generation of metabolic acidosis in selective mineralocorticoid deficiency was investigated in bilaterally adrenalectomized (ADX) rats treated with dexamethasone and in sham-operated (S) rats. ADX rats had significantly lower plasma sodium and bicarbonate concentrations and significantly higher plasma potassium concentrations than S rats did. ADX rats developed negative sodium balance when fed a "zero" sodium diet. The minimum urine pH achieved during sodium sulfate infusion and during ammonium chloride administration was not significantly different between ADX and S rats. Bicarbonate reabsorption and urine minus blood PCO2 gradient were not different between ADX and S rats. For any given urine pH, absolute ammonium excretion was significantly lower in ADX than it was in S rats, both during sodium sulfate infusion and during chronic ammonium chloride administration. Glomerular filtration rate (GFR) was significantly lower in ADX than it was in S rats; ammonium excretion corrected for GFR was not different between the two groups. To determine the role of decreased distal sodium delivery (secondary to decrease in GFR and enhanced proximal sodium reabsorption which resulted from distal sodium chloride wastage) on ammonium excretion, ADX rats were fed 0.9% sodium chloride in an effort to keep body weight constant. Salt-loaded ADX rats had a plasma bicarbonate concentration higher than did S rats. Salt-loading also led to a significant increase in GFR; absolute ammonium excretion was significantly higher than that of other ADX rats with the same degree of acidosis. At comparable levels of GFR, there was no difference in ammonium excretion between ADX and S rats. Ammonium excretion was linearly related to GFR. ADX rats fed a zero potassium diet had significantly greater ammonium excretion than did all other groups of ADX or S rats receiving a normal potassium intake. These data suggest that volume contraction is a major factor responsible for the acidosis of selective mineralocorticoid deficiency.


[Hemodynamic and humoral changes during administration of a sympathomimetic and a sympatholytic drug with special notes on the regulation of renin release (author's transl)]. Studies in normal volunteers documented the positive inotropic effects of Etilefrin-HCL, a direct sympathomimetic drug, with increases of systolic blood pressure, renal blood flow and glomerular filtration rate. Sodium and potassium excretion as well as serum potassium decreased. After an additional injection of Metoprolol, a beta 1-sympatholytic drug, blood pressure, renal blood flow and glomerular filtration rate normalized, whereas electrolyte excretion decreased further. Renin release was decreased during administration of Etilefrin as well as during combined Etilefrin and Metoprolol application. Reziprocal to changes of blood pressure, plasma norepinephrine concentration decreased during Etilefrin and increased during combined administration of Etilefrin and Metoprolol. The results lead to the following interpretation: Changes of blood pressure and renal hemodynamics are mediated by beta 1-adrenergic effects of Etilefrin, whereas the electrolyte excretion is influenced by beta 2-adrenergic effects. Renin release seems to be influenced by beta 1 as well as beta 2-adrenergic receptors.


[Ileofemoral flaps--a clinical study (author's transl)]. The authors reveiw the anatomy, circulation, planning and techniques of preparing ileofemoral flaps. The possibilities of application of these flaps, advantages and disadvantages of the procedure are discussed. The authors use ileofemoral flaps as a new effective procedure for covering sores of the trochante area.


[Talus neck fractures associated to subtalar dislocations (author's transl)]. The survey literary data on the mechanism, symptoms and treatment of vertical talus neck fractures associated to subtalar dislocations, they present five cases in their practice. Reducement of the fracture dislocation, fixation by Kirschner wire was accomplished and a plaster cast was applied, for twelve weeks as an average. Avascular necrosis of the bone did not occur. The authors lay emphasis on the importance of early careful reducement and immobilization.


[Operative treatment of fractures of the sternum (author's transl)]. Following a survey of different means for the treatment of sternal fractures, the authors report their own operative procedure, that was performed in three cases with success. The operation is based on the tightened loop principle. Indications and operative techniques are discussed in the paper.


[Axial roentgenogram of the acetabulum (author's transl)]. The authors report the technical skills and diagnostic values of axial roentgenograms of the acetabulum. This procedure usefully completes the traditional method of examination of the hip joint and it is more informative in many cases. The method is advised in the modern examination and treatment of acetabular fractures, whether isolated or complicated by traumatic hip dislocation. Apart from its application in traumatology, this special technique is valuable in orthopedics as well.


[Anatomy of the hand arteries based on angiographic studies (author's transl)]. The authors report conclusions drawn from anatomical studies on ninety-two hand angiographies. The superficial and deep volar arcs were classified according to Coleman and Anson. The superficial arc was found to be incomplete in 66.3%, the deep arc in 9.8% of all cases. Variations in ramification of the digital arteries were divided in two groups, as they belonged to either the ulnar or the radial arterial system. In the view of the extreme variability of the arterial network, the authors warn against operations on the hand arteries without angiography.


[Ulnar artery aneurysm on the hand (author's transl)]. A cured case of ulnar artery aneurysm on the hand is reported in the article, that is worth publishing because of its rarity.


[Caloric substitution in the septic phase of burn disease (author's transl)]. Energy turnover of septic burned patients was favourably influenced by infusion of glucose 40% one unit of Insulin for each 3 grams of glucose along with 0.5% protein preparate and 50-100 grams of aminoacids, administered by way of a cave cathether. The burned patients treated according to this protocol need less amount of blood, apart from the protein sparing effect, as it may be deduced from the studies on forty severely burned patients.


[Surgical view of the treatment of hand burns (author's transl)]. In the primary and early operative treatment of deep burns of the hand necrectomy is the main point. Grafting of skin is urgent, too, but it is secondary to necrectomy. The hazard to the deep structures on the hand make a primary flap plasty necessary. However, if it is about a relative indication or the personal and material conditions are missing, a temporary skin replacement (biological bandage) is appropriate.


[Isolated dislocation of the os hamatum (author's transl)]. A case of inveterated dislocation of the os hamate is reported in this paper. Deficiencies in the diagnosis of the injury are pointed out. The patient had to take on rehabilitated work because of this unrecognized and unreduced dislocation. The authors refers to the scanty data in medical papers, that can be hardly found, he briefly discusse the anatomy of this small bone, problems in diagnosis and treatment.


[Reconstruction following severe open maxillofacial injuries (author's transl)]. The authors introduce the definitive treatment according to the current principles in traumatology by demonstrating the reconstruction of a severe open maxillofacial injury. Attention is drawn to the most frequent mistakes.


[Spontaneous tendon ruptures of identified etiology (author's transl)]. The authors found in the material of the National Institute of Traumatology among the 650 cases of spontaneous tendon ruptures seven cases of rupture, when an identified disease localized on the tendon was the precipitating cause. Aetiology of the rupture has been as follows: tendon tuberculosis, rheumatic tendinitis xantoma tuberosum, haemangioma and pseudocyst of the tendon. In two other cases muscle biopsy revealed a concealed myopathy (central core disease and centronuclear myopathy) that may responsible for the rupture of the tendon.


[Our experiences with the Kiel type heterolog conserved bone graft (author's transl)]. The authors survey data in the medical literature on Kiel type heterolog conserved bones and report their own experiences. Forty-nine cases altogether, the authors grafted bone manufactured by the Braun firm, in seven patients; a Kiel type bone conserved by the method of the authors in forty-two patients; The grafts were used mostly in patients with solitaer bone cysts, in a smaller number in patients with bone cavities following impression fractures, pseudarthrosis and arthrodesis. Their results were excellent, minor complications occured in only four cases. Finally some up-to-date problems of bone grafting, regeneration are discussed in this paper.


[Complaints after fractures of the os calcis-significance of the peroneal tendons (author's transl)]. In complaints following fractures of the os calcis a peroneal synovitis arisen from side plate dislocation has a share. This alteration may be securely diagnosed by making tenosynoviagrams. The side plate that healed in a bad position must be chiselled off subperiostally so that the complaints be stopped. A suitable first treatment may have prevented a large portion of after-complaints.


[The use of a new hook plate for the operate treatment of ankle fractures (author's transl)]. Authors describe their methods of treatment and results in 137 inpatients with ankle fractures treated during a period of one and half year. Analysing this material the indications and methods of surgical treatment for ankle fractures are dealt with. In order to facilitate the surgical treatment of the most common type of ankle fractures (i.e. pronation fractures in group B of Weber) authors constructed a hook plate, adapted to the external malleolus, which proved good in their practice. Within this material it was used for 38 patients. 77 per cent of the displaced ankle fractures were treated surgically. After an average of 13.8 months follow up time the results were found satisfactory, using an evaluation system adequat for international comparison. With their data the efficiency of the surgical treatment for displaced ankle fractures is emphasized. The new hook plate is first of all used for the operative treatment of pronation fractures in level of the syndesmosis, and is recommended on basis of good experiences.


[Ligamentous injuries of the wrist joint (author's transl)]. Author deal with some basic type of ligamentous injuries around the wrist. Attention is drown to the significance of injuries to the distal radio-ulnar ligamentsystem, the triangular fibrocartilage, and ulnar carpal ligament. Diagnostic and therapeutic methods are recommended. The importance for treatment of ligamentous injuries around the wrist joint is emphasized.


[The importance of primary operation from the point of view of mortality in patients with femoral neck fractures. I. Comparative study of mortality after primary and delayed operations. The part played by the patients age (author's transl)]. Authors with regard to primary or delayed surgical treatment analyse the mortality of 2,612 patients with proximal femur fractures treated in the National Institute of Traumatology during the years 1971--75. Within this material 2,055 case history of surgically treated femoral neck and pertrochanteric fractures are evaluated. An important difference in favour of primary intervention was found between the mortality of primary and delayed operations both in femoral neck and pertrochanteric fractures. In pertrochanteric fractures the mortality increased gradually starting from the day of injury. Regarding age related mortality, there was a significant difference in each age group in favour of primary operations. Thus the increased mortality encountered after delayed operations can't be explained by a selection with regard to age.


[The results of experimental and clinical use of Gentamycin PMMA balls (author's transl)]. Authors describe a new method of treatment for bone and soft tissue infections using polymethyl methacrylate balls containing Gentamycin. Advantages of this method can be summarized in 3 points: 1. From the patients point of view saving the rinsing-sucking drainage, early mobilisation etc. 2. From nursing point of view a significant facilitation of the patient's care. 3. From the hospital management's point of view: improved hygienic conditions by eliminating the possible infections related to a rinsing-sucking wet system. Cutting down hospital expences both by abbreviation of the time of hospitalization and saving on expensive antibiotics.


[The effect of fracture and blood loss on the medullary circulation (author's transl)]. The blood flow of the cancellous bone of femoral head and diaphyseal bone marrow of the femur and humerus in dogs were measured by means of 133Xe and Hydrogen wash out methods. The blood flow rate of bone marrow in the femur counted from the Hydrogen wash out curves was 0,207 ml min-1 . g-1. Fracture and haemorrhagic hypotension decreased the blood flow rate in bone marrow. After bleeding there was an exponential relation between the arterial pressure and effective marrow flow or muscle flow. The relation between arterial and intramedullar pressure was exponential, but a linear correlation existed between the changes in marrow blood flow after haemorrhage and the changes in intramedullar pressure.


[Investigation on the construction and spacial structure of human tendons (author's transl)]. According to their investigations there is a surface phenomen not only on the surface of intact tendons, but after longitudinal disruption it appears on spontaneously formed inside surfaces as well. The structures responsible for its production are not identical, the outside cover of the tendon is s thick, gelatinous, amorphous sheet in which a reinforcing fibersystem can be demonstrated. This latter works on a "Mädchenfänger" concept. On the arteficially exposed inside surface of a disrupted tendon the periodically striped design of small fiber groups in different layers summarizes in an oblique or transversal drawing. The authors stereomicroscopic findings need further investigations on biopsy tendons in order to determine the morphological changes in relation to tendon tension during in vivo function.


[Surgical and radiological anatomy of the mandibula (author's transl)]. One of the risks in dysgnathia-operations performed on the mandibula is the injury to the anatomic formations inside the mandibular channel. The paper deal with anatomic sites recommended in the literature for measurements. The occurrence of a sulcus colli mandibulae and the depth of the bone groove is investigated, and their part as an operative risk factor is presented. Attention is drawn consequently to individual variations and a careful surgical technique is recommended.


[Ganglion in the ulnar nerve groove (author's transl)]. Two cases of a rare localisation of ganglion is reported in this paper. A ganglion in the ulnar nerve presented by complete loss in ulnar nerve function. Attention is drawn to the importance of early diagnosis, and to the fact, that in cases of ulnar nerve lesions of unknown origin tumors in the ulnar groove must be considered.


[Fixation of laterofacial fractures by means of ballon-tampon (author's transl)]. Author performed measurements to assess the efficiency of ballon-tampons used for fixation of laterofacial fractures. According to these measurements the necessary amount of fluid (15--35 cm3) assure a pressure of 240 mercurymm and this is not diminished after 10 days beyond a level of 170 mercurymm. These values are adaequat both for the reduction and retention.


[Hand injuries caused by high pressure lubricants (author's transl)]. Author describes the consequences of hand injuries caused by high pressure lubricants. The importance of adaequat primary treatment is emphasized and attention is drawn to the possible severe damages as a result of careless, tardy treatment.


Choline acetyltransferase activity in human blood and its diurnal oscillation--an artifact? Diurnal oscillation of choline acetyltransferase (ChAT)-like activity in human blood has recently been reported in the literature. From studies on the pH-optimum of acetylcholine synthesizing activity in human blood we suggest, however, that this activity is only partly related to ChAT, and that the diurnal oscillation observed might be an artifact resulting from the analytical procedure.


Testicular acid phosphatases of the mouse. Characterization after chromatographic fractionation. The testicular homogenate of adult mice was eluted by DEAE-cellulose chromatography. Four peaks of acid phosphatase were identified. The pooled samples of each peak were used to determine substrate specificity, pH-optima, modifier characteristics, thermal stability, and Km-values. The results obtained suggest that each peak may represent a separate and distinct type of acid phosphatase. These observations are very similar to those previously obtained with the rat testis. The acid phosphatase activities in the mouse seem, however, to differ biochemically to some extent from those in the rat.


Effect of clofibrate treatment on acylcarnitine oxidation in isolated rat liver mitochondria. The oxidation of palmitoyl- and octanoylcarnitine in liver mitochondria from normal and clofibrate-treated male rats was studied by measuring the ADP-stimulated oxygen consumption and acetyl group production (the sum of formed ketone bodies, acetylcarnitine and citrate). In the absence of malate the treatment approximately doubled the rate of acylcarnitine oxidation. In normal mitochondria the acetyl groups consisted almost totally of ketone bodies. The clofibrate-induced increase in acetyl group production was attributable to enhanced rates of ketone body and acetylcarnitine formation. The observed increase in acylcarnitine oxidation was associated with an elevated beta-hydroxybutyrate: acetoacetate ratio, reflecting an increased mitochondrial NADH:NAD+ ratio. In normal mitochondria the addition of malate in the presence of fluorocitrate doubled the rate of beta oxidation by forming citrate. The beta oxidation in mitochondria from clofibrate-treated rats was virtually unresponsive to added malate. The clofibrate-induced increase in ketogenesis was confirmed in disintegrated mitochondria. The treatment approximately doubled the rate of ketone body production from acetyl-CoA in disrupted organelles. The enhanced capacity of ketogenesis was accompanied by increased activity of the specific acetoacetyl-CoA thiolase (EC 2.3.1.8), which is the first step enzyme of the pathway. Clofibrate administration also increased the activities of general oxoacyl-CoA thiolase (EC 2.3.1.16), palmitoyl-CoA dehydrogenase (EC 1.3.99.3), and butyryl-CoA dehydrogenase (EC 1.3.99.2), which all take part in the beta oxidation of fatty acids.


Linoleic acid absorption in the unanesthetized rat: mechanism of transport and influence of luminal factors on absorption. Linoleic acid intestinal absorption was studied in the unanesthetized rat. At low (21-1260 micrometer) intraluminal concentrations, absorption took place by facilitated diffusion; while at high (1.26-2.5 mM) concentrations, simple diffusion was the predominant mechanism of transport. At low concentrations (840 micrometer), the equimolar additions of oleic, linolenic, and arachidonic acids or lecithin inhibited the absorption of linoleic acid. Substitution of potassium for sodium in the buffer solution, substitution of Tween 80 for sodium taurocholate, or decrease in the hydrogen ion concentration all resulted in decreased rate of linoleic acid absorption. Increase in sodium taurocholate concentration, or perfusate flow rate increased linoleic acid's absorption. These experiments demonstrate that linoleic acid is absorbed by a concentration-dependent dual mechanism of transport. The absorption rate is modified by the pH, surfactant type and concentration, the simultaneous presence of other polyunsaturated fatty acids, and the thickness of the unstirred water layer.


Stearoyl-coenzyme A desaturase activity in Novikoff hepatoma. The activities of microsomal stearoyl-CoA desaturation, NADH-cytochrome b5 reductase, NADH-cytochrome c reductase, and the content of cytochrome b5 were similar in livers of normal and host rats. On the other hand, stearoyl-CoA desaturation activity was absent in Novikoff hepatoma. The activities of NADH-cytochrome b5 and NADH-cytochrome c reductases in the hepatoma microsomes were 4.8% and 2.2%, respectively, of those in normal liver. Furthermore, in hepatoma microsomes, cytochrome b5 was absent. An active stearoyl-CoA desaturation was reconstituted only on addition of both cytochrome b5 and the terminal desaturase enzyme to the hepatoma microsomes. These results indicated that a complete absence of cytochrome b5 and terminal desaturase is responsible for the lack of stearoyl-CoA desaturation in Novikoff hepatoma microsomes.


[Mathematical model of Thiobacillus ferrooxidans growth on a medium with ferrous iron]. A mathematical model is proposed for the growth of Thiobacillus ferrooxidans in the process of Fe2+ oxidation depending on the active acidity and temperature of the medium. The model was used to establish the correlation between the action of temperature and pH of the medium on the bacterial growth and oxidation of Fe2+. The range of pH values which had no effect on the bacterium is broader at 28 degrees C (from 2.5 to 2.8) than at 12 degrees C (from 2.3 to 2.4). Apparently, the growth of the bacterium and the enzymatic processes of Fe2+ oxidation are more susceptible to changes in the pH than in temperature, at least when it is lowered to 12 degrees C.


[Effect of heat shock on the amino acid makeup of the whole cells and walls of Candida utilis yeasts in chemostat cultivation]. The amino acid composition of intact cells and cell walls was determined in Candida utilis AUCMY-1,668 growing in the regime of chemostat with limitation by glycerol or ethanol deficiency at a temperature of 30 degrees C (control) or with inhibition by an elevated temperature of 40 degrees C (experiment). In the control, intact cells contained 43-44% of amino acids, and cell walls, about 10% (per the weight of dry cell walls); the following amino acids prevailed in the cell walls: threonine, glutamic acid, serine and leucine. The content of amino acids decreased in both the intact cells and cell walls at the elevated temperature (40 degrees C). The content of leucine, methionine, tyrosine and cystine decreased in the cell walls more than in the intact cells (with regard to the total amino acid content of the cell walls and intact cells, respectively). Under the action of the elevated temperature, the cells became larger and did not separate: the scar formed at the end of budding stretched between the mother and daughter cells holding them together.


[More active synthesis of the polysaccharide, pullulan, by polyploid cultures of Pullularia pullulans]. The polyploid strains of Pullularia pullulans differ from each other and from the haploid strain in the amount of the polysaccharide pullulan liberated into the cultural broth. The highest pullulan synthesizing activity (per unit of the assimilated carbon source and the synthesized biomass) was manifested by the diploid strain of P. pullulans 1125(13) whose cells produced more pullulan (by 75%) within three days of growth than the cells of the haploid culture. The content of pullulan calculated per unit area of the cell surface increased with the level of ploidy: 1.5-1.8 times in the diploid cultures and 3.4 times in the tetraploid culture cf. the parent haploid culture. Apparently, the polyploidy of the P. pullulans culture was accompanied with mutations involved in the synthesis of the extracellular polysaccharide.


Histidine degradation enzymes in rat liver: induction by high protein intake. High protein dietary content stimulates urea formation in ureotelic animals but does not exert almost any effect on ammonia production from L-amino acids in vitro. L-histidine and L-threonine are the only amino acids which are most actively deaminated by ureotelic animals fed on a high protein diet. All the steps of L-histidine metabolism have been studied: it has been found that both the histidine transaminase pathway and the histidase pathway are stimulated. Glutamic acid is also a product of histidine catabolism through the histidase pathway, but its catabolism is unaffected by the dietary protein content. These data suggest the existence of independent mechanism controlling the catabolism of the two amino acids.


Specific thymic peptides-DNA interaction. Correlation with the possible stereochemical kinking scheme of DNA. Low molecular weight peptides from calf thymus cause a strong dose-dependent stabilization of the DNA. The strength od DNA-peptide interaction is pH-dependent and decreases repidly above pH 6.5. Moreover the complete kinetics of DNA denaturation and renaturation demonstrates that the peptide fraction increases significantly the DNA renaturation mostly at low temperature, showing that the interaction DNA-thymic effector helps the recombination of complementary DNA segments. The DNA stabilization rate by the peptide fraction is comparable to that obtained by means of high concentration of histones or synthetic polycationic peptides. However, the lack of basic amino acids in the peptide structure is not in favor of strong electrostatic interactions and implies a specific binding of peptide to DNA. The possible correlation of the specific thymic peptides-DNA interaction with the stereochemical kinking scheme of DNA is discussed.


The effect on sister-chromatid exchanges of drugs and dyes by intercalation and photoactivation. Intercalating dyes (acridine orange, proflavin and methylene blue) and drugs (chlorpromazine, promazine and chlorprothixene) were tested for their ability to induce sister-chromatid exchanges (SCEs) with and without photoactivation by visible light. Whereas in the dark all substances tested increased the frequency of SCEs, a superimposed effect of visible light on SCE formation was observed for the acridines proflavin and acridine orange, but not for the pheneothiazine derivatives methylene blue and chlorpromazine. These results are discussed in connection with the known mutagenic effects of these substances and with the factors that may be involved in SCE formation induced by intercalating molecules in the absence and presence of visible light.


Single-strand breaks in DNA during repair of UV-induced damage in normal human and xeroderma pigmentosum cells as determined by alkaline DNA unwinding and hydroxylapatite chromatography: effects of hydroxyurea, 5-fluorodeoxyuridine and 1-beta-D-arabinofuranosylcytosine on the kinetics of repair. A simple and sensitive technique for detection of strand breaks in DNA has been further developed. The method has been used to follow UV-induced excision-repair in human fibroblasts. It has been possible to study the kinetics of enzymic reactions in intact cells, in which strand breaks in DNA are produced and sealed again. Hydroxyurea, 5-fluorodeoxyuridine and 1-beta-D-arabinofuranosylcytosine, potent inhibitors of DNA synthesis, drastically increased the number of breaks observed during the repair process. This was probably due to a decreased polymerase activity, which will cause the strand breaks formed by endonuclease to remain open longer. The initial rate of strand-break formation did not seem to be influenced by hydroxyurea or araC, and was about 4000 breaks per minute in a diploid genome, at a dose of 20 J/m2. After 5--30 min, depending on the dose of UV, the number of breaks reached a maximum and started to decrease again. Hydroxyurea decreased the rate of polymerization in the sites under repair. However, there was no concomitant reduction of repair-induced incorporation of [3H]thymidine and no reduction of the excision of pyrimidine dimers. It therefore seems that the action of the polymerase was not a rate-limiting event, but rather an earlier step. It is likely that the endonucleolytic activity determined the rate of repair. As a consequence, the endonuclease and polymerase cannot be bound in a permanent complex. Under certain assumptions, the time for repair of a site, i.e. the time from incision to final ligase sealing, can be estimated as between 3 and 10 min. Essentially no breaks were produced in Xeroderma pigmentosum cells belonging to complementation group A, and there was no enhancement by hydroxyurea. Cells from the variant type of Xeroderma pigmentosum behaved like normal cells in this respect.


Absence of noxious effects of selected neuroleptics in dominant-lethal mutagenesis assay. In a dominant-lethal assay in mice the following tricyclic neuroleptics were tested: prothiaden, imipramine, oxyprothepin decanoate and docloxythepin. No dominant-lethal effect was induced by these neuroleptics, even when administered at doses many times as great as clinical doses. The reduced percentages of pregnancies, in females who had copulated with males receiving docloxythepin, observed during and immediately after its administration, were directly connected with marked sedation induced in the males by this neuroleptic.


Myosin polymorphism in human skeletal muscles. Myosins isolated from individual human muscles (primarily normal muscles) were investigated with respect to their structural and catalytic properties. The results indicate unexpected elements of uniformity shared by the several myosins, such as a three-banded, electrophoretic pattern of light chains in sodium dodecylsulfate (SDS) gels and a low degree of alkaline lability. The pH activity profile and the effect of KCl on myosin ATPase activities were also found to be the same for the myosins from predominantly fast (e.g., vastus lateralis and rectus abdominis) and slow (e.g,, soleus and pectoralis minor) muscles. Coelectrophoretic experiments lend further credence to the interrelationship between human myosin light chains and the light chains of rabbit fast-muscle myosin. However, several kinds of circumstantial evidence, such as that derived from the study of myosin in nemaline myopathy, suggest that one shoould exercise caution in interpreting these results. On the other hand, human muscle myosins, like those of other mammalian species, can be divided into two main categories according to the peptide composition of tryptic heavy meromyosin (HMM) and the banding pattern of light meromyosin (LMM) paracrystals. These results, which are indicative of differences in the primary structure of the heavy chains, allow us to identify these heavy chains as the main site of heterogeneity among myosins in human mucles.


Muscular dystrophy and activation of proteinases. Evidence is presented for the existence of many different systems of proteolytic enzymes in human skeletal muscle. These include the lysosomal system of cathepsins as well as proteinases and peptide hydrolases that are optimally active at neutral and alkaline pH ranges. The majority of proteolytic enzymes examined are found to show increased activity in dystrophic human muscle. Moreover, a high initial rise is observed in cathepsin B1, a thiol-dependent endopeptidase of lysosomes, and in dipeptidyl peptidase IV, a membrane-associated peptidase. In addition, a calcium-activated neutral proteinase is found to be significantly elevated in muscle from patients with Duchenne dystrophy. The possible roles of these proteinases in intracellular protein catabolism and muscle wasting are discussed.


Studies on the PR toxin of Penicillium roqueforti. A mycotoxin, confirmed by chemical, physical and spectroscopic data as the PR toxin described by Ru-Dong Wei and coll. (15) has been isolated from culture filtrates of Penicillium roqueforti Thom. Factors affecting the toxin and mycelium production, acute and chronic toxicity in experimental animals and the frequency of toxinogenesis of 21 isolates of P. roqueforti (including a brown mutant) isolated from different materials, foods especially, were also studied. An hypothesis on the absence of PR toxin in cheeses fermented with P. roqueforti is also advanced.


Acid-base, calcium, potassium and aldosterone metabolism in renal tubular acidosis. Classic renal tubular acidosis is characterized by a primary defect in establishment of a large hydrogen ion gradient across the distal renal tubule. Thus the development of hyperchlorenic metabolic acidosis follows. In addition, hypokalemia results from renal potassium wasting secondary hyperaldosteronism from sodium wasting and contraction of the extracellular fluid. The presenting signs and symptoms are growth retardation, fatigue, periodic paralysis, polyuria, polydipsia, vomiting and constipation as well as nephrocalcinosis and nephrolithiasis. It is suggested that effective treatment with alkali therapy requires markedly higher doses than formerly recommended, and may related to a higher rate of endogenous acid production from (1) intermediary metabolism of sulfur amino acids and organic acids, (2) impaired tubular reabsorption of bicarbonate and (3) hydrogen ion release from hydroxyapatite formation. It is also suggested that acidosis may interfere with vitamin D metabolism and thus play an important role in the pathoetiology of the growth failure in children with this disorder.


Effect of narcotic analgesics and naloxone on proestrous surges of LH, FSH and prolactin in rats. Morphine (50 mg/kg), given at 12:00 h and 14:00 h to proestrous rats, completely inhibited the proestrous surges of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (Prl). However, when it was given at 16:00 h, the inhibitory effect of morphine (Mor) was decreased. Pethidine and nalorphine inhibited the proestrous surges, while pentazocine showed a weaker inhibitory effect. Naloxone (Nx), given simultaneously or 2 h after morphine (Mor), at 1/20 the dose of Mor, inhibited the blockade of the proestrous gonadotropin release exerted by Mor, while the onset of the surges was delayed when it was given 3 h after Mor.


Evaluation of clorazepate (Tranxene) as an anticonvulsant--a pilot study. Desmethyldiazepam--providing the long-term anticonvulsant effect when diazepam is given orally--is conveniently administered as clorazepate (Tranxene). In this study, clorazepate was compared to phenobarbital as a secondary anticonvulsant in eight ambulatory, adult outpatients. Stable doses of phenytoin were maintained throughout. Drowsiness was present in all on phenobarbital, but there were no clorazepate-related side effects. Seizure control did not differ for each treatment. Addition of common side effects of phenytoin and phenobarbital limited the attained serum levels of each when used together. Clorazepate doses in the 0.56-mg-per-kilogram range gave desmethyldiazepam levels in the 1.0-microgram-per-milliliter range. Induction of metabolism was suggested by falling desmethyldiazepam levels despite increasing doses. Clorazepate is an effective, nontoxic secondary anticonvulsant.


[The prehypophyseal-gonadal system in the normal male and in some forms of testicular dyscrinism. Evaluation studies in basic conditions and after stimulation]. The secretion values of the two seric gonadotropins and of plasmatic testosterone have been estimated in a casuistry of normal males subdivided in groups of 8 to 95 years of age, and of primitive and secondary testicular dyschrinia. In one part of this casuistry, normal and primitive hypogonadics, we have estimated the response to the intravenous administration of Gn-RH. Among the results which have been obtained, it appears that physiologic hypogonadism of the elderly is a primary phenomenum, not hypophyso-dependent. In the hypophysiary stimulus test, the response of gonadotropins in those old men moves away from the response of hypogonadics considered, by a behaviour much more similar to that of normal adults, even if delayed and prolonged. In all the cases, normal and pathologic, the response of testosterone is variable, perhaps owing to the relation with the various factor which have been noted.


[Treatment of chronic respiratory insufficiency of pulmonary origin. Clinical considerations]. The key-points of the physiopathological treatment of chronic pneumogenous respiratory insufficiency are: correction of distribution defects, suitable local adjustment of the ventilation: perfusion ratio, and correction of obstacles to alveolocapillary diffusion. Many drugs can be used to obtain these results; bronchodilators, vasoactive drugs, cortisones, cardiokinetics, antibiotics, analeptics. Reference is also made to oxygen therapy, depletion management (bloodletting and-or diuretics, and their possible mechanisms. Lastly, attention is given to disturbances, in acid-base equilibrium in chronic respiratory insufficiency and their correction.


Central action of narcotic analgesics. Part IV. Noradrenergic influences on the activity of analgesics in rats. The effect of clonidine, naphazoline and xylometazoline on analgesia induced by morphine, codeine, fentanyl and pentazocine, and on cataleptic effect of morphine, codine and fentanyl was studied in rats. The biochemical assays on the influence of four analgesics on the brain concentration and turnover of noradrenaline (NA) were also performed. It was found that three drugs stimulating central NA receptors failed to affect the analgesic ED50 of all antinociceptive agents and they enhanced catalepsy induced by morphine and fentanyl. Codeine catalepsy was increased by clonidine and decreased by naphazoline and xylometazoline. The brain concentration of NA was not changed by morphine and fentanyl, but one of the doses of codeine (45 mg/kg) slightly enhanced it. Pentazocine dose-dependently decreased the brain level of NA. The rate of NA turnover was not altered by analgesics except for the higher dose of fentanyl (0.2 mg/kg) following which the disappearance of NA from the brain was diminished. The results are discussed in the light of various and non-uniform data from the literature. It is suggested that in rats the brain NA plays a less important function than the other monoamines in the behavioural activity of potent analgesics.


Potentiation of cataleptogenic effects of neuroleptics by prostaglandins. Prostaglandins (PGs) E1, E2, F2alpha injected intracerebroventricularly (icv) in rats, potentiated chlorpromazine (CPZ) and pimozide (PI) catalepsy similarly. Cataleptogenic effect of haloperidol (HL) was potentiated specifically be PGE2. These phenomena were diminished by apomorphine (AP). Phenoxybenzamine (PB) diminished the potentiating effect of PGE2 and PGF2alpha on CPZ catalepsy, and strongly inhibited PGE2 the potentiating effect on HL and on PI catalepsy. Propranolol (PN) diminished the potentiating effect on HL and on PI catalepsy. Propranolol PN) diminished potentiating effect of PG on HL catalepsy and increased this effect of PGE1 on PI catalepsy. All examined PG induced catalepsy only when given in high doses (50 or 100 microgram icv). Cataleptogenic effect of PGE2 and PGF2 but not of PGE1, was evidently inhibited by AP. PGS inhibited AP stereotypy. The results suggest that the central dopaminergic receptors blockade is involved in the mechanism of potentiation of neuroleptic induced catalepsy by PGs, and that PGs are similar to neuroleptics in some aspects of central action.


Purification of uricase from mammalian tissue. A simple, rapid procedure for the purification of uricase from mammalian tissue is reported. The procedure is based on the precipitation of mammalian uricase under certain dialysis conditions, and on its low solubility near neutral pH. Exceptionally high yields of homogeneous enzyme are obtained.


The influence of alpha-adrenergic drugs on catalepsy induced by haloperidol or fluphenazine in rats. Clonidine (ip) and methoxamine (ivc) inhibit the catalepsy produced by haloperidol or fluphenazine. Naphazoline and xylometazoline antagonize the catalepsy produced by haloperidol, but do not affect significantly that produced by fluphenazine. Phenylephrine did not affect the catalepsy produced by either neuroleptic. The results indicate that drugs stimulating central noradrenergic receptors antagonize the action of compounds blocking the central dopaminergic receptors.


The effect of antihistamine drugs on the neuroleptic-induced catalepsy. The effect of atropine on the spiperone- or reserpine-induced catalepsy was compared with the effect pure antihistamines (chlorcyclizine, diphenhydramine, mepyramine) and antiserotonin -- antihistamine drugs (cyproheptadine, danitracen). All the drugs were used in equipotent doses in respect of their central cholinolytic action, assassed previously on the basis of the tremorine test. The potency of the antiserotonin action of chlorcyclizine, diphenhydramine and mepyramine was estimated by assessing the ID50 values of these compounds in the test based on antagonism to L-5-hydroxytryptophan action in the mouse. The spiperone-induced catelepsy, was most effectively inhibited by classical histaminolytics and less by drugs of a combined antiserotonin and antihistamine action. For the reserpine-induced catalepsy, differences in action of the two groups of drugs were less distinct. In both cases atropine produced the weakest anticataleptic effect. Amodiaquine, an inhibitor of histamine degradation, enhanced the catalepsy induced by either neuroleptic (the reserpine-induced catalepsy in a statistically significant menner). A possibility that the anticataleptic action of chlorcyclizine, cyproheptadine, diphenhydramine, mepyrymine and danitracen depends on the blockade of the histamine receptors in the brain is discussed.


Polarographic behaviour of 2-(5-nitro-2-furyl)-5-(2-aminoethoxy)- pyrimidine derivatives. Polarographic reduction of the title compounds in mixtures of Britton-Robinson buffers and methanol (1:1) or DMF (3:1) for compound 10 at the pH range of 2.8--11.3 is described. In strongly acid medium the compounds were reduced in two diffusion governed waves corresponding to the consecutive reduction of NO2-group (6-electron wave) and pyrimidine ring (2-electron wave) to amine and dihydropyrimidine, respectively; with increasing pH the second wave became, however, much worse shaped. In alkaline medium a third wave appeared, the limiting current of which corresponded to a 2-electron process; the wave corresponds probably to the further reduction of pyrimidine ring to tetrahydroderivative. Mechanism of the reduction of the title compounds  has been suggested and discussed.


Dark field imaging of biological macromolecules with the scanning transmission electron microscope. A scanning transmission electron microscope (STEM) equipped with a field emission gun has been employed for the examination of biological macromolecules at high resolution. The quality of micrographs obtained with the STEM is dependent upon the quality of the substrate used to support biological objects because the image contrast in dark field is proportional to the mass density of the specimen. In order to reduce deleterious effects of the substrates on the image quality, we have developed a method of fabricating substrates consisting of very thin, very clean carbon films supported on very clean fenestrated plastic films. These films are approximately 15 A thick. Well-known biological macromolecules such as glutamine synthetase and tobacco mosaic virus (both stained) and low-density lipoprotein and ferritin (both unstained were placed on these substrates and examined with the STEM by using various modes of contrast. The micrographs obtained by using the dark field mode of contrast employing an annular detector were free from phase contrast, as expected. Using this contrast mode, we have been able to directly observe (in-focus) 2.5- to 4.4-A lattice spacings in the ferritin core. The effect of electron radiation damage on the helical structure of tobacco mosaic virus was also examined. Micrographs as well as corresponding optical diffraction patterns obtained with moderately low doses showed very clear helical structure from both sides of the virus. In addition, the (11.5 A)(-1) layer lines indicated the effective resolution attained on these particles.


Chemical characterization of decomposition products of drugs. Part 6. Mass spectrometry of some perazine derivatives. Mass spectra of perazine, prochlorperazine, tiethylperazine, trifluperazine, butaperazine and thioproperazine were obtained. All possible fragmentation routes were discussed. The mechanism of fragmentations, their similarities and differences within the investigated group of compounds were established. The Hammett type relationship was found between the intensities of some ions and the kind of substituents at the C2 position. The utility of mass spectra for the prediction of drug stability was demonstrated.


A peptide as a possible transmitter in sympathetic ganglia of the frog. A search was made in sympathetic ganglia of the bullfrog for a noncholinergic, nonaminergic transmitter that is released by a distinct group of preganglionic axons. These initiate a late slow excitatory postsynaptic potential which lasts for many minutes. The most promising candidate for the role of transmitter is a peptide that resembles luteinizing hormone-releasing hormone (LHRH; luliberin). The reasons are: (i) LHRH (1 muM) and some of its analogs cause a slow depolarization of ganglion cells. (ii) Radioimmunoassays established that 100-800 pg of a LHRH-like substance is contained in the lumbar chain of sympathetic ganglia. (iii) The LHRH-like material is specifically distributed in those spinal nerves that contain axons that initiate the slow noncholinergic synaptic responses. (iv) Five days after ipsilateral preganglionic axons are cut, 95% of the LHRH-like substance disappears from ganglia, while the LHRH immunoreactivity triples in the spinal nerves proximal to the cut region. (v) About 0.6% of the LHRH-like material within ganglia can be collected from the perfusate after 30 min of incubation in isotonic KC1; this release is Ca dependent. (vi) The candidate for transmitter has several chemical characteristics of a peptide and has a Mr near 1000.


Effects of gonadectomy and hormone replacement on brain monoamine synthesis in male rats. The synthesis of catecholamines and serotonin in the brains of castrated male rats was analyzed at either various times after castration or at various ages. It was found that (a) castration of rats at 50 days or later causes an increase in brain monoamine synthesis, and (b) this phenomenon was not observed until 20 days after castration. The increase in brain monoamine synthesis following castration was counteracted by treatment with testosterone, thus relating the biochemical consequences of castration with changed hormonal conditions of the animal. It is suggested that testosterone exerts an inhibitory influence on monoamine synthesis.


Effects of food deprivation on etonitazene consumption in rats. One group of free-feeding rats was given a 5 microgram/ml etonitazene HCl solution as their sole liquid. This group increased their drug intake by 100% when they were partially food-deprived during a 23-day period. Another group that remained food-satiated and received etonitazene for an equal number of days did not show similar increases in drug intake. However, this group drank greater volumes of the etonitazene solution than a food-satiated control group drank of water. These results are contrasted with a fourth group showing a 50% decrement in water intake during similar food-deprived conditions. The food-deprived group drinking etonitazene showed highly erratic drinking patterns compared to all the other groups. Daily liquid intake ranged from 30 to 250 ml in this group, and volumes oscillated from high to low on alternating days. When the food-deprived/food-satiated conditions were replicated in this experimental group, corresponding increases and decreases in drinking reliably occurred. However, during the second food-deprived phase, the large increases occurred almost immediately as contrasted with a gradual increase over 17 days during the first food-deprived phase. This would suggest a learning mechanism may be involved. Self-mutilation and other forms of stereotypy were noted only in food-deprived rats consuming etonitazene.


Abomasal function following injections of elfazepam and 9-aza-cannabinol. The feed intake stimulants elfazepam (E), a benzodiazepine, and 9-aza-cannabinol (9-AC) decrease rumen contractions and abomasal acid content in sheep and E increases rumen fluid volume, digestibility and overall nutrient availability. E has been hypothesized to decrease the propulsive activity of the entire GI tract. To further examine the effects of E and 9-AC on gastric function, 4 ewes were prepared with abomasal cannulas and 3 silver/silver chloride monopolar electrodes alternated with 2 strain gauges on the distal one-third of the abomasal serosa. Electromyographical (slow waves and action potentials) and contractile (rates and forces) activities and abomasal pH were measured. Treatment of 8 and 16 mg E had no effect on slow wave frequency, action potential rate, contraction rate, or contraction force. Abomasal content pH was decreased with 8 mg E. Treatments of 125 and 250 microgram 9-AC depressed action potential and contraction rates and contraction force but had no effect on slow wave frequency or pH.


Cariogenicity and acidogenicity of food, confectionery and beverages. The advantage of pH-telemetry of plaque and mixed saliva in the evaluation of the cariogenic potential is that, in contrast to in vitro measurements, in vivo telemetry discriminates among pH variations in plaque and saliva as a result of substrate fermentation and those due to dietary acids, acids formed by the oral mucosal microflora and adequately registers salivary buffers. This is illustrated with a summary of acido- hypo- and nonacidogenic products tested.


A new analytical procedure for two-dimensional electrophoresis of cellular proteins: comparison of protein compositions of parent strain and a K+-accumulation mutant of E. coli. An improved two-dimensional analytical electrophoretic technique fractionates according to molecular weight in the presence of dedecyl sulfate in the first dimension, then fractionates according to isoelectric point in a perpendicular dimension. Electrofocusing in the second dimension achieves nearly complete removal of most protein components while providing true estimates of their isoelectric points. Because not all proteins penetrate isoelectric focusing gels, some proteins may go unrecognized using conventional two-dimensional systems where isoelectric focusing precedes electrophoresis. However, such components do enter dodecyl sulfate gels; hence the presence and molecular weight of those components can be established by the new procedure. A concurrent finding was that, in general, penetration of isoelectric focusing gels by discrete protein subunits dissolved in 9 M urea is an all-or-none phenomenon depending on the solubility of the specific subunit. The procedure was applied to comparison of the protein compositions of a parental strain (CBH) of Escherichia coli and a derived mutant strain (RD-2) deficient in ability to accumulate K+. The strains showed similar two-dimensional patterns except for one discrete isoelectric component absent in the parent strain but present in the mutant.


Oxidation of hypotaurine to taurine by ultraviolet irradiation. Oxidation of hypotaurine to taurine is known to occur in vivo. Search for an enzyme performing that oxidation has been unsuccessful. However, fast and quantitative oxidation of hypotaurine (and other sulfinates) by ultraviolet irradiation has now been observed. The reaction is first order and pH-dependent, and its rate depends strongly on the kind of sulfinate irradiated. Only the corresponding sulfonate is recovered as the product under the relatively mild conditions used. Catalase or superoxide dismutase does not affect the oxidation, which is oxygen-dependent. A simple reaction scheme is proposed to account for the findings.


Effects of thioproperazine and sulpiride on the locomotor rhythms in the decorticate cat. The decorticate cat develops sequences of locomotor movements, especially in the two posterior limbs: those appear either spontaneously, or following a single shock applied to L7 dorsal root. Using this preparation, we tested the effects of two neuroleptic agents, Thioproperazine (TZ) and Sulpiride (S), through either systemic administration or local injection into the lateral-posterior hypothalamus and into the lumbar spinal cord. TZ administered i.v. (0.5 mg/kg) suppressed all locomotor rhythms, while S induced unclear effects. The tested drugs clearly acted at the hypothalamic level, but the effects of the drugs were opposite; TZ (70 microgram) suppressed rhythms, while S (350 microgram) increased or even induced them. T2 (50 microgram) injected at the L7 cord-level abolished rhythms, and S (350 microgram) reduced their amplitude but increased the duration of locomotor sequences. The flexion reflex was never affected by these drugs. The two drugs seem to act at the spinal and the hypothalamic levels. The possible mechanisms involved in their action are discussed.


The effect of neuroleptic drugs on drinking induced by central administration of angiotensin or carbachol. The effect of a series of neuroleptic drugs on the drinking response elicited by intracerebroventricular injection of either angiotensin or carbachol into conscious rats was studied. The i.p. injection of haloperidol, cis-flupenthixol, or fluphenazine antagonized both angiotensin-induced and carbachol-induced drinking. When injected into the lateral ventricles, the neuroleptics haloperidol, fluphenazine, cis-fluphenthixol and sulpiride were potent inhibitors of angiotensin-induced drinking, but had little effect on the dipsogenic action of carbachol. Clozapine, administered centrally, antagonized drinking caused by both angiotensin and carbachol. Pimozide and chlorpromazine were also potent inhibitors of angiotensin-induced drinking, while trans-flupenthixol was inactive. Our results support the concept of an involvement of dopamine in angiotensin-induced drinking.


Benzodiazepine blockade of passive-avoidance task in mice: a state-dependent phenomenon. Four benzodiazepines (diazepam, chlordiazepoxide, halazepam, lorazepam) were tested for their effects on the acquisition of a passive-avoidance task in mice. This was done to determine whether amnesic effects, as reported in humans after diazepam and lorazepam, could be demonstrated by blockade of passive-avoidance responding in mice and, if so, to investigate the possible causes of the blockade by studying the relationships between the blockade and times of drug administration. Each of these benzodiazepines, at doses that did not alter overt behavior, blocked acquisition of the passive-avoidance response when they were administered to mice prior to the training session, but not when they were administered after the training session or prior to testing 24 h later. The block of avoidance responding was reversed, however, when the drugs were administered prior to both training and test sessions. These results suggest that state-dependent learning occurred; i.e., apparent amnesia occurred in the test session with untreated mice that had undergone passive-avoidance learning 24 h earlier under the influence of drug.


Impairment by apomorphine of one-trial passive avoidance learning in mice: the opposing roles of the dopamine and noradrenaline systems. Pretraining administration of the dopaminergic stimulant apomorphine (0.25--16 mg/kg) impaired retention performance of mice on a one-trial passive avoidance task. Only with a very high dose (16 mg/kg) of this drug did the effect seem related to an interference with memory formation processes. Of the dopamine receptor-blocking agents used, haloperidol (0.125--1 mg/kg), but not chlorpromazine or clozapine (0.25--4 mg/kg), prevented the apomorphine effect. Phenoxybenzamine (8 mg/kg), a noradrenaline receptor-blocker, antagonized the haloperidol effect and, when combined with a subeffective dose of apomorphine, impaired passive avoidance learning. The results obtained are interpreted in terms of the proposed inhibitory actions exerted by central noradrenaline on dopamine systems of the brain.


Diazepam and flurazepam: effects on conditioned fear as measured with the potentiated startle paradigm. Diazepam (0.3, 0.6, 1.2, or 2.5 mg/kg) produced a dose-dependent reduction of the potentiated startle effect where acoustic startle amplitude is normally increased in the presence of a light previously paired with a shock. Even the lowest dose tested (0.3 mg/kg) significantly attenuated potentiated startle. The effect was selective since the same doses did not depress baseline startle amplitude measured in the same animals in the same test session. A 2 X 2 design in which rats were trained and tested under the same or different drug condition (diazepam or saline) showed the results could not be explained by state-dependent learning. The primary effect of diazepam was to block expression of rather than acquisition of fear as measured by potentiated startle. Flurazepam (2.5, 10, or 20 mg/kg) also reduced potentiated startle selectively but was 6--8 times less potent than diazepam. These and other results suggest that the potentiated startle paradigm, as a measure of classical conditioning that involves no operant, might provide a useful adjunct to behavioral methods currently being used to analyze antianxiety compounds.


Chlordiazepoxide loses its anxiolytic action with long-term treatment. The biochemical and behavioural effects of acute, 5, 15 and 25 days treatment with chlordiazepoxide (CDP, 5 mg/kg) were examined in the rat. After 5 days of drug treatment, 5-hydroxytryptamine (5HT) levels in the midbrain, hypothalamus and cortex were significantly higher than those of the corresponding controls, and the level of 5-hydroxyindoleacetic acid (5HIAA) was significantly lower, indicating reduced turnover. After 15 days of drug treatment, 5HIAA levels were significantly elevated, compared with the controls, possibly indicating that CDP was blocking the transport of 5HIAA from the brain. This effect appears to be independent of the reduced turnover. After 25 days of drug treatment there were no significant differences compared with the controls. There were no marked changes in noradrenaline and dopamine in any of the areas investigated. It appears that the reduction in 5HT turnover is linked to the anxiolytic effects of CDP; the latter were found after 5 days of drug treatment, but not after 15 or 25 days, using the social interaction test of anxiety.


[The gamma-glutamyltransferase (GGT) isoenzymes in human serum (author's transl)]. With this report we communicate the results of a method for the fractionation of the isoenzymes of gamma-GT in human serum based on a modified technique of Hetland et al., using cellulosa acetate. With this method we observed the appearance of a complex of four band representing: gamma-GT1 = prealbumin-albumin, gamma-GT3 = alpha 1-globulin, gamma-GT3 = alpha 2-globulin, gamma-GT4 = beta-globulin. It has been noted that the gamma-GT2 is the only fraction which constantly appears. This isoenzyme also corresponds to the form, fisiologically present in serum and is presumably preduced in the cells of the bileduct. In the results we observed the appearance of gamma-GT1 only in the course of processes involving certainly cholestasis. This fraction was once reported by other AA., but it has an unknown origin. It was not possible to correlate the appearance of the fractions gamma-GT3 and gamma-GT4 with any specific pathology alterations even though Hetland et al. have affirmed that the gamma-GT3 band derives from hepatic parenchyma.


Gastroesophageal reflux in children: evaluation of the water siphon test. Fifty-nine symptomatic children were radiologically evaluated for gastroesophageal reflux with the water siphon test and also with the acid reflux test and esophageal manometry. Of those with reflux on pH testing, 95% had positive water siphon tests, and 38% also had spontaneous barium reflux. Of those with negative acid reflux tests, 29% had positive water siphon tests. Lower esophageal sphincter pressure did not correlate with either test unless the pressure was less than 10 mm Hg. Barium esophagography with the water siphon test is the appropriate initial examination in symptomatic patients, but the false-positive rate is high.


Production of prostacyclin-like substance in stroke-prone and stroke-resistant spontaneously hypertensive rats. Activities of aortae to produce prostaglandin (PG) I2-like substance in stroke-prone spontaneously hypertensive rats (SHRSP), stroke-resistant SHR (SHRSR) and normotensive control rats from the Wistar-Kyoto (WK) colony were compared. PGI2-like substance was produced by the incubation of the aortic ring in pH 9.0 borate-buffered saline and the amount produced was estimated by comparison of its anti-aggregatory activity with that produced by known amounts of the sodium salt of synthetic PGI2. Before the development of stroke, amounts of this substance generated in SHRSP and SHRSR were significantly higher than those in WK rats (p less than 0.01 and p less than 0.02, respectively). Remarkably reduced capacity to generate PGI2-like substance was observed in some SHRSP after the development of stroke.


Cyclic AMP formation and release by cultured bone cells stimulated with prostaglandin E2. PGE2 produced a marked and dose-related increase in cAMP content of cultured bone cells and in the release of cAMP into the incubation medium. The amount of cAMP released from the cells by PGE2 was proportional to the cellular concentration, and was dependent upon the time of incubation with PGE2. The cAMP levels released into the media increased slowly at a linear rate during a 60 min treatment with PGE2. This release was blocked by theophylline, probenecid, ouabain and dinitrophenol, suggesting that the release of cAMP was not a simple diffusive process and required energy. SC-19220 reduced the formation of cAMP more than the release, suggesting that the formation and the release may arise from separate events. Inability of D600 to inhibit PGE2-induced release of cAMP indicates that the release does not require calcium.


[Tumor hyperacidification through glucose infusion enhanced by local hyperthermia (author's transl)]. Local tumor hyperthermia (42--43 degrees C) during moderate whole body hyperthermia (40 degrees C) and hyperglycemia (5 . 10(-3) g ml-1) led to an amplification of tumor hyperacidification of deltapH = 0,47 +/- 0,19 In 12 from 20 animals. As cause of this phenomenon the stimulation of glycolysis by temperature increase (van't Hoff's law) and the stop of microcirculation by hyperthermia plus decrease of erythrocyte flexibility was discussed 5 tumors regressed totally.


The relapse-preventing effect of methyl-salazosulphapyridine compared to salazosulphapyridine during long-term treatment of ulcerative colitis. A double-blind controlled trial. In an attempt to improve the relapse-preventing effect of salazosulphapyridine (SASP) and to encircle the part of the molecule essential for therapeutic actin, methyl-SASP was compared to SASP in a controlled double-blind trial without cross-over. The patient group comprised 33 patients with ulcerative colitis who had been symptom-free for 1--6 months on continuous treatment with SASP (on an average 2 g daily). The daily doses were SASP 1 g X 3 and methyl-SASP 125 mg x 3. Thirty patients completed the trial, 14 on SASP and 16 on methyl-SASP. Applying clinical criteria, the relapse rate after 6 months was 0.14 in the SASP group and 0.69 in the methyl-SASP group. The difference is highly significant. The blood concentrations of SASP, methyl-SASP, sulphapyridine (SP), and methyl-sulphapyridine (methyl-SP) were measured after 3 and 6 months. The methyl-SASP concentration was on an average twice as high as that of SASP, and the methyl-SP on an average 1/10 of SP (the differences are significant). It is concluded that whereas SASP showed a relapse-preventing effect in ulcerative colitis in this study comparable to that previously reported, the effect of methyl-SASP was only comparable to that of placebo, and the active substance in SASP does not seem to be unsplit SASP.


The influence of cimetidine on basal gastro-oesophageal sphincter pressure, intargastric pH, and serum gastrin concentration in normal subjects. A pressure and pH-sensitive probe has been constructed for simultaneous measurement of gastro-oesophageal sphincter pressure and intragastric pH. The coefficient of variation for measurements of the gastro-oesophageal sphincter was 0.24, and for the intragastric pH, 0.09. After peroral ingestion of 400 mg of cimetidine or placebo, simultaneous measurements of gastro-oesophageal sphincter pressure and intragastric pH were made at fixed time intervals, and at the same time blood samples were taken for determination of serum gastrin and serum cimetidine concentrations. No demonstrable difference was found in the time-course of the gastro-oesophageal sphincter pressure after ingestion of cimetidine or placebo. After ingestion of cimetidine a significant rise in intragastric pH (p less than 0.05) occurred after 40 min, and this increased pH was maintained for the remainder of the experimental period, corresponding to a serum cimetidine concentration of over 1.00 mg/l. Similarly, there was a significant rise (p less than 0.05) in serum gastrin concentration after 150 min. There was a significant direct correlation between corresponding measurements of intragastric pH and serum gastrin (p less than 0.001), between intragastric pH and serum cimetidine (p less than 0.001), and between serum gastrin and serum cimetidine (p less than 0.05). Ingestion of cimetidine results in an increase in the serum gastrin concentration in healthy subjects, presumably as a result of reduced secretion of acid in the stomach. Neither the endogenous increase in serum gastrin concentration nor the increase in intragastric pH causes alteration in the gastro-oesophageal sphincter pressure.


The prerequisites for local lysolecithin formation in the human gallbladder. III. Demonstration of two different phospholipase A activities. The positional specificity of the phospholipase A (EC 3.1.1.4) in human gallbladder epithelium has been studied using 14C-phosphatidylethanolamine radiolabeled either in the 1-acyl or in the 2-acyl position. After heating of homogenized epithelial cells at 70 degrees C for 2 min, their lysophospholipase activity was lost.  In contrast, the ability to hydrolyze 14C-phosphatidylethanolamine in biosynthetically radiolabeled Escherichia coli was largely retained. The amounts of radioactivity found in the products of hydrolysis under different conditions suggest that there are two different phospholipase A activities in the gallbladder epithelium: one, with optimal activity at pH 7, that requires Ca2+ and is specific for the 2-acyl position, and another, with optimal activity at pH 4, that does not require Ca2+ and that, apart from the 2-acyl position, attacks the 1-acyl position as well. It is possible, therefore, that a complete deacylation of diacylphosphoglycerides in the gallbladder wall is brought about in two different ways: at neutral pH through a combined action of phospholipase A2 and lysophospholipase, the latter being able to hydrolyze the 1-acyl-lysophosphoglyceride, and, at acid pH, through the action of phospholipase A1 and A2 activity, presuming 1-acyl- and 2-acyl-lysophosphoglycerides are also attacked. Both these processes have to be considered in order to explain a turnover of diacylphosphoglycerides that physiologically would prevent the accumulation of lytic lysophosphoglycerides. The possible relevance of these findings to the pathogenesis of aseptic cholecystitis is inferred.


Prolonged inhibition of neurons by neuroendocrine cells in Aplysia. In the abdominal ganglion of Aplysia, a burst of action potentials in peptide-secreting neuroendocrine cells, the bag cells, produces slow inhibition of two identified bursting pacemaker neurons. The inhibition is due to slow hyperpolarizing potential that reduces bursting pacemaker activity for 3 hours or more. The slow inhibitory potential results from a large and prolonged increase in membrane conductance to potassium ions as well as a slower ionic process that is relatively independent of membrane conductance.


Intercellular communication in pancreatic islet monolayer cultures: a microfluorometric study. Single islet cells in monolayer cultures of neonatal rat pancreas were microinjected with fluorescein and scanned topographically by microfluorometry. Fluorescein spread from an injected islet cell directly into neighboring islet cells, and, in the presence of 16.7 millimolar glucose, significantly more islet cells communicated with the injected cell than in glucose-free medium. Islet cells were also microinjected with glycolytic substrates and activators that produced transient changes in cellular levels of reduced pyridine nucleotides-nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate [NAD(P)H]. Changes in NAD(P)H fluorescence were observed in islet cells incubated first for 18 hours in very low glucose concentrations and then in a glucose-free medium and injected with glycolytic substrates and activators; however, little change of fluorescence occurred in adjacent islet cells. In contrast, after adding 16.7 millimolar glucose to the medium, injection of glycolytic substrates and activators produced transient changes in NAD(P)H fluorescence in the injected cell and in neighboring cells.


beta1- and beta2-Adrenergic receptors in rat cerebral cortex are independently regulated. Repeated administration of the tricyclic antidepressant desmethylimipramine to adult rats for 10 days caused a 40% decrease in the density of beta1-adrenergic receptors in the cerebral cortex but had no effect on the density of beta2-adrenergic receptors. Conversely, destruction of noradrenergic neurons by administration of 6-hydroxydopamine to neonatal rats caused a 64% increase in the density of beta1-adrenergic receptors in adult cerebral cortex with no change in the density of beta2-adrenergic receptors. These results suggest that the beta-adrenergic receptors in rat cortex involved in neuronal function are primarily of the beta1 subtype.


[The acute manifestations of alcoholism and their treatment (author's transl)]. The effect of the ethyl alcohol on the system involves a symptomatology of clinical variable expression. The ethanol has an incontestable psychotrope effect. In small dose it calms anxiety but in large dose it mostly has an anesthesic effect and disturbs consciousness. The well-known acute inebriety beside, there is the pathologic hallucinatory and delusive inebrieties. The practitioner must affirm the correlation between the observed perturbations and the absorption of alcohol, eliminate some disease simulating an acute inebriety and take the therapeutic decisions which assert themselves in a dramatic atmosphere. In that emergency treatment, the use of the new neuroleptic, the tiapride looks us very interesting for it has a sedative effect on agitation; it respects the vigilance and it improves the consciousness.


[The present treatment of headaches (author's transl)]. Considered from the point of view of clinical practice, the treatment of chronic headache may be either symptomatic and etiological or physiopathological. Progress in symptomatic treatment depends first on the reasonable and graduated use of pure analgesics, looking out for the toxic side effects of the usual drugs and then the fairly definite efficacy of certain psychotropic drugs. The discovery of an etiology gives a specific dimension to the treatment: either anti-cerebral oedema drugs with above all tetracosactide, a diagnostic test of cerebral tumours, or antidepressor or tranquillizer drugs, depending on the variety of disturbance to be corrected. An attack of migraine always benefits from ergotamine used occasionally and in limited dosage (not more than 6 mg daily or 10 mg per week). For the basic treatment the drugs act mainly peripherally and fairly regularly in the following order: methysergide, beta-blockaders, pizotifene, cyproheptadine, oxetorone. Other drugs have a central effect, Tiapridal, MAO inhibitors which are too often neglected, and clonazepam which is not very easy to use.


[Horton's disease. Current problems].

[Horton's disease. Current problems]. Much that has been written in the last few years concerning temporal arteritis has allowed us to better clarify the clinical picture, and for example frequency of hepatic involvement. The atypical forms of the disease such as those that involves large arteries, or those in which sedimentation rate is normal, are better known. It is in such atypical cases, particularly in a young patient, that an external carotid arteriography is most useful. Though the pathophysiology of the disease is not well understood, serologic and histologic arguments  exist in favor of an autoimmune etiology, in which the antigen would be the alestin, found in the internal elastic lamina of the artery. Temporal arteritis is theorically well classified amongst the giant cell granulomatous arterities but there are some atypical forms difficult to distinguish from Takayasu's arteritis or even periarteritis nodosa.


The vectors of Brugia malayi in Southern Thailand. Mansonia uniformis, with an infective rate of 0.02, was incriminated as the vector of periodic Brugia malayi in Pattani province. Mansonia bonneae and Ma. dives, with infective rates of 0.18 and 0.20 respectively, were the vectors of B. malayi in Narathiwat, where the microfilarial periodicity was the subperiodic form.


[A therapeutic trial in a neurology department]. A study of the therapeutic efficacy of tiapride in various neurological disorders was carried out during the period October 1974 to May 1975. Good results were obtained in headaches following lumbar puncture and removal of CSF, and in agitated states, especially those associated with alcoholism.


[Management of drug withdrawal. Apropos of the treatment of 150 chronic alcoholics]. The authors research work brings out the privileged place occupied by tiapride in the course of weaning 150 chronic alcoholics. This product enabled them, whatever the initial symptoms presented by the patient might be (DT, pre-DT or chronic alcoholism), to carry out a quick weaning while preserving the patient's lucidity, his freedom to move about and his ability to satisfy his physiological needs. A number of drawbacks are avoised thanks to the procedure the authors have developed, such as: the prescription of the usual psychotropic medicines and, consequently, the side effects associated with them; the complications caused by a prolonged confinement to bed; the over-demanding involvement of the nursing staff; finally, the atmosphere of struggle which accompanies the admission of a delirium tremens. Therefore the use of tiapride seems to be a turning point in the treatment of the chronic alcoholic.


A quantitative mosquito survey of 7 villages in Punjab Province, Pakistan with notes on bionomics, sampling methodology and the effects of insecticides. A total of 451,337 female and male mosquitoes comprising 43 species in 9 genera were collected during a quantitative survey of 7 suburban and rural villages in the Lahore area during 1976 and 1977 using larval, indoor resting, outdoor resting, biting and light trap collections at weekly intervals. Culex tritaeniorhynchus was the most abundant species collected comprising 51.8% of the total specimens, followed by Cx. quinquefasciatus (16.4%), Cx. pseudovishnui (6.8%), An. subpictus (4.8%) and An. culicifacies (4.7%). Bovid bait collections provided the greatest diversity and highest numbers of mosquitoes per unit of collection effort, while light traps provided the poorest diversity and lowest numbers of specimens. Most species exhibited a bimodal seasonal abundance pattern, with peaks occurring in late spring and after the cessation of the heavy monsoon rains. The spraying of houses and cattle sheds with organophosphorous insecticides was effective in controlling the endophilic resting vectors of human Plasmodia, An. culicifacies and An. stephensi, but had little effect on the partially or completely exophilic resting species.


[Tolerance of sultopride (author's transl)]. Especially used in the psychiatric emergency field for the rapidity of its action, sultopride, a sedative but not ataraxic drug, has been used for prolonged cures in 45 patients with important characterial disturbances. Heavy doses sometime needed for achieving aggressive tendions were not an obstacle in regard of the tolerance of these prolonged cures, as proves the cases of a mental deficient patient whom agitated and aggressive drug resistant episodes recovered with a barnetil continued treatment by 3,600 mg a day (nine tablets) for more than a year without any sign of intolerance.


[A case of hemiballism and a case of senile chorea]. Tiapride is potent on anormal movements. Its utilisation for aged persons seems to have good results. An hemiballism at a woman 83 years old had not regressed very much and the reapprenticeship of walking was possible again. The choreic movements of a woman 90 years old had disappeared and the walk was possible again. These two notes show us the possibilities of improvements in acting obtained even for the very old patients and good tolerance of tiapride.


Acid-base balance made simple.

Acid-base balance made simple. The control of extracellular acid-base balance is difficult to grasp unless it is realized that the pH of the blood depends upon the ratio H2CO3/NaHCO3 and that, without alteration of pulmonary ventilation, the H2CO3 neither rises nor falls. It must also be understood that the H+ ions, excreted by the kidneys, are byproducts of NaHCO3 reclamation and neogenesis and are not derived from metabolic acids.


Influence of flunitrazepam on body functions. The effects of intravenous flunitrazepam (Rohypnol, Roche) on various body functions were studied and the following conclusions were reached: it is a very potent sedative/hypnotic even in small doses, it may cause depression of spontaneous breathing, it does not give rise to raised cerebrospinal fluid or intra-ocular pressure, it does not adversely affect renal function, and it can be used quite safely in combination with fentanyl or pentazocine in anaesthetic practice.


Intracranial vasospasm: a study with iron compounds. The effects of topically applied hemoglobin, methemoglobin, hemin, ferrous chloride (FeCl2) and ferric chloride (FeCl3) were investigated by observation through the operating microscope to determine their effect on the normal and spastic canine basilar artery. Following transclival exposure, the artery was made spastic by puncture or topical barium chloride. No consistent changes in arterial diameter were seen with topical hemoglobin, methemoglobin, or hemin. The buffered ferrous ion (Fe++) caused marked vasodilation at concentrations of 10 microgram/ml. The buffered ferric ion (Fe++) caused mild vasoconstriction at similar concentrations. The possible role of iron (a component of hemoglobin) in vasospasm following subarachnoid hemorrhage and subsequent hemoglobin degradation is discussed.


[Decontamination of hot beef carcases with organic acids (author's transl)]. The decontamination effect of spraying hot beef carcases with solutions of lactic acid and solutions of the commercial preparation of pH liquid was studied. Spraying a 0.5 per cent lactic acid solution only resulted in a significant reduction of aerobic, gram-negative and gram-positive bacterial counts on severely contaminated areas. Treatment with a 0.75 per cent solution of lactic acid caused a significant decrease of almost all bacterial counts, whereas a 1 per cent lactic solution produced a significant reduction of all bacterial counts at the sites sampled. The maximum reduction was 2 log units per sq.cm. and varied with the level of contamination. A 5 per cent pH Liquid solution was ineffective and a 20 per cent pH Liquid solution had an effect similar to that of a 0.5 per cent lactic acid solution. The reduced bacterial counts persisted during three days of storage in the chilling room. When the above concentrations are applied, this will not cause any permanent changes of colour of the treated carcases. These changes do occur when a 10 per cent solution of lactic acid is used. This treatment can only be used to spray severely contaminated superficial layers which are to be removed. Recommendations are made for the possible use of organic acids in the slaughter line. The legal aspects are discussed.


Physico-chemical properties and local toxic effects of injectables. In Japan, many cases of muscle contracture as a sequela of injections have been reported. We studied the physico-chemical properties and muscle-damaging potential of many injectables which are commonly used in hospitals. Contrary to our expectations, the pH of the injectables was found to range widely from 1.4 to 12.8, and the osmotic ratio from 0.2 to 36. It was also found that their hemolytic potential was closely related to the severity of the muscle lesions in animal experiments and that there were many injectables with strong muscle-damaging potentials. Therefore, doctors should be informed of the physico-chemical properties and tissue-damaging potential of each injectable; pharmaceutical companies should exert all possible efforts to improve injectables; and doctors should keep the administration of intramuscular injections to a minimum and use them only in cases of actual need.


The effect of bile acids on "solubilized" cholesterol 7 alpha-hydroxylase activity in swine. Optimal assay conditions for cholesterol 7 alpha-hydroxylase activity in swine liver microsomes were determined. The enzyme activity is induced three-fold by feeding cholestyramine to the swine. This suggests that cholesterol 7 alpha-hydroxylase is likely to be the rate-limiting enzyme for biosynthesis of bile acids in swine. The effects of various bile acids on cholesterol 7 alpha-hydroxylase in swine microsome and "solubilized" cholesterol 7 alpha-hydroxylase activity have been studied. There is no significant reduction of native microsomal enzyme activity. However, except for chenodeoxycholic acid, most of the bile acids tested exerted significant inhibition on "solubilized" cholesterol 7 alpha-hydroxylase. This finding suggests that bile acids could interact with and regulate the rate-limiting enzyme for bile acid formation in swine.


Neurologic and cardiovascular effects of hypotension in the monkey. Thirty monkeys were exposed to controlled systemic hypotension of different magnitudes and duration to determine factors leading to brain injury or cardiovascular failure. Fourteen monkeys developed brain injury. Of these, 6 survived indifinitely and 8 were sacrificed or died within 12-62 hours due to neurologic deterioration accompanied by respiratory failure. Sixteen animals did not develop brain injury, but 9 of these died within 24 hours from documented cardiovascular failure with the remaining 7 survived indefinitely. A highly reproducible threshold for the development of brain injury was found at a mean arterial blood pressure (MABP) of 25 mm Hg. Maintenance MABP was less than or equal to 25 mm Hg in 13 of 14 lesioned monkeys and greater than 25 mm Hg in 15 of 16 non-lesioned monkeys. Maintenance MABP averaged 20.1 +/- 1.1 mm /g in lesioned and 32.1 +/- 1.7 mm Hg in non-lesioned animals (p less than 0.001). Among the non-lesioned animals, death from delayed cardiovascular failure ensued when MABP was maintained between 27 and 35 mm Hg for 90 min or longer. Animals exposed to this range of hypotension for less than 90 min or to MABP exceeding 35 mm Hg for as long as 3 h survived intact. EEG changes occurring during hypotension most accurately predicted neurologic outcome. The threshold MABP required to produce cerebral electric silence was 21-22 mm Hg. Monkeys developing marked brain injury had greater than 25 minutes of EEG flattening, while slightly injured animals had it for 5-15 minutes and those without injury for less than 5 min. Changes in acid-base state, common carotid artery blood flow, and cerebral uptake of glucose and oxygen during hypotension also correlated with neurologic and cardiovascular outcome. Hypoxemia and hypercarbia were not contributory factors in the production of brain injury in this study.


Extracorporeal glass-wool filtration of whole blood enhances post-ischemic recovery of the cortical sensory evoked response. In twenty dogs, anticoagulated with heparin 300 units/kg, the right cortical sensory evoked response (CSER) to contralateral median nerve stimulation was suppressed during 60 min ischemia induced by periodic infusion of 50 to 100 microliter increments of air via the right internal carotid artery. The post-ischemic recovery of the CSER was followed an additional 60 min in 19 of these animals divided into 2 groups. Ten dogs were subjected to glass-wool filtration of their blood by extracorporeal shunting from femoral artery to femoral vein for one hr prior to infusing air. Nine dogs did not receive glass-wool filtration. Post-ischemic recovery of CSER amplitude, a quantifiable electrophysiologic index of neuronal function, was significantly greater in the filtered group than in the non-filtered group. 14C-antipyrine autoradiographic blood flow studies were performed in 3 dogs. One was studied at the end of a 60 min ischemic CSER suppression period and showed severe flow disruption by air embolism. Two dogs, one from each group, were studied at the conclusion of the 60 min recovery period. In the filtered animal, cortical blood flow exceeded the threshold for CSER maintenance while cortical flow rates in the unfiltered animal fell below this threshold. The enhanced postischemic neuronal recovery in the filtered group as indicated by the CSER in attributed to the preservation of injury zone nutrient blood flow that is supported by collateral circulation.