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Capsaicin Stimulation and Neurogenic Experimentally Induced Inflammation of the Human Labial Mucosa
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1 ORIGINAL PAPERS Dent. Med. Probl. 2005, 42, 1, ISSN X GIUSEPPE A. SCARDINA 1, PIETRO MESSINA 1, FRANCESCO CARINI 2, ANGELO LEONE 3 Capsaicin Stimulation and Neurogenic Experimentally Induced Inflammation of the Human Labial Mucosa Stymulacja kapsaicyną zapalenia neurogennego błony śluzowej wargi u człowieka 1 Department of Odontostomatological Science G. Messina, University of Palermo, Italy 2 Department of Experimental Medicine, Section of Human Anatomy, University of Palermo, Italy 3 Section of Human Histology, University of Palermo, Italy Abstract Background. The neurogenic inflammation depends on the neuromodulator release by peripheral nervous termi nations. A series of different studies proved the existence of a neurogenic phlogosis (NP) in different body sites. Only experiences on rat managed to induce NP at the oral mucosa level. Objectives. Inducing NP at the human mucosa level. Material and Methods. Two groups of patients (group A: M/F: 8/7; mean: ± 12.4; range: 24 60; group B: M/F: 8/7; mean: ± 12.39; range: 23 60) were examined in authors laboratory. The NP was experimentally induced at the lower lip mucosa level after topically applying capsaicin. The vascular consequences were observed through computer videocapillaroscopy techniques (Videocap 100). The lip mucosa of the group A patients was observed in three different time periods: before capsaicin application (t 0 ), after one minute (t 1 ), and after 45 min utes (t 2 ) from capsaicin application. The lip mucosa of the group B patients was observed in four different time periods: before capsaicin application (t 0 ), after local anaesthetic injected (t 1 ), after one minute (t 2 ) and after 45 min utes (t 3 ) from capsaicin application. Results. The vascular in vivo observation, in the group A, allows to highlight after one minute application only, the axono reflected vasodilation, the real expression of NP. After 45 minutes, the vascular diameter returned to its ini tial diameter. In the group B, the vascular in vivo study allows to observe no significant modification of the vas cular diameter in the four different time periods. Conclusions. The study highlights that the NP can be induced at the human oral cavity level and such an evidence could be extremely important in the pathogenesis and treatment of the different oral pathologies (Dent. Med. Probl. 2005, 42, 1, 31 36). Key words: neurogenic inflammation, labial mucosa. Streszczenie Wprowadzenie. Zapalenie neurogenne zależy od uwalniania neuromodulatorów przez obwodowe zakończenia nerwowe. Wiele różnych badań udowodniło występowanie zapalenia neurogennego (z.n.) różnych części ciała. Za palenie neurogenne błony śluzowej jamy ustnej wywoływano tylko u szczurów. Cel pracy. Wywołanie z.n. błony śluzowej u człowieka. Materiał i metody. Dwie grupy pacjentów (grupa A: K/M: 8/7, średnia wieku 41,14 ± 12,4, zakres lat, gru pa B: K/M: 8/7, średnia wieku 41,21 ± 12,4, zakres lat) zostały zakwalifikowane do badań. Zapalenie neu rogenne wywoływano doświadczalnie w błonie śluzowej dolnej wargi po miejscowym zastosowaniu kapsaicyny. Następowe zmiany naczyniowe rejestrowano techniką wideokapilaroskopową (Videocap 100). W grupie A błona śluzowa wargi była oceniana trzykrotnie: przed podaniem kapsaicyny (t 0 ), po minucie (t 1 ) i po 45 minutach (t 2 ) po podaniu kapsaicyny. W grupie B błona śluzowa wargi była oceniana czterokrotnie: przed podaniem kapsaicyny (t 0 ), po znieczuleniu miejscowym (t 1 ), po minucie (t 2 ) oraz po 45 minutach (t 3 ) po podaniu kapsaicyny. Wyniki. Obserwacja naczyniowa in vivo w grupie A umożliwiła stwierdzanie rozszerzenia naczyń pochodzenia aksonalnego już po minucie po pobudzeniu w postaci z.n. Po 45 minutach średnica naczyń wróciła do wartości wyjściowej. W grupie B badania naczyniowe in vivo umożliwiło obserwację nieznaczących zmian średnicy naczyń w czterech różnych przedziałach czasu.
2 32 G. A. SCARDINA et al. Wnioski. Badanie dowiodło, że zapalenie neurogenne może być wywoływane w jamie ustnej człowieka. Jest to bardzo ważne w patogenezie i leczeniu różnych zmian patologicznych w jamie ustnej (Dent. Med. Probl. 2005, 42, 1, 31 36). Słowa kluczowe: zapalenie neurogenne, błona śluzowa wargi. Various observations carried out in the course of the years have shown that neuropeptides might play role as inflammation mediators [1 3]. The substances on which attention has been principal ly focused are: substance P (SP), calcitonin gene related peptide (CGRP), capsaicin and histamine [4, 5]. Knowledge acquired in this field, however, does not yet permit one to sufficiently clarify the role of these neuropeptides, although it has been confirmed that these substances are found in labo ratory animals in the course of experimentally induced neurogenic inflammation [2]. Neurogenic inflammation is a consequence of amyelinic sensitive neuron activation, followed by a neuropeptide release such as SP and CGRP by the peripheral nervous terminations [6]. Inflammatory responses elicited at the tissue level, as a consequence of nervous termination activation mainly consist of: hyperaemia, local oedema and erythema, which mainly develop even beyond the specific stimulation site and therefore can easily be followed by pain [2]. Since when scholars managed to almost defin itively correlate such unique inflammatory signs with the peripheral sensitive nervous system func tion and integrity, the elicited answer is called neu rogenic inflammation. As almost any tissue is innervated by afferent sensitive neurons, a similar mechanism could be involved in the aetiology of many different inflam matory reactions of the oral mucosa [2]. The NP can experimentally be induced by local capsaicin stimulation [7 11]. This is proved by the fact that denervation of the area prevents the development of inflammatory reactions in rats [13]. Capsaicin is a powerful local stimulator which administered in controlled doses can lead to the release of phlogistic neuromodulators and as a con sequence to NP [7, 8, 10]. Its long term administra tion leads to the small medullar fibre degeneration and reduces held SP by 50% [13]. When increasing the release and inhibiting a further undue influence of any PS, it is possible to lead to a central and peripheral nervous system depletion [2]. A single dose of capsaicin induces pain, inflammation and hypersensitivity. When its application is continued in time, it leads to hyposensitisation, antalgic and anti inflammatory activity. Any analgesia and miti gant effect possibly depends on the release and depletion of neuropeptides [13 15]. Capsaicin acts as a receptor agonist for the Vanilloids (VR1), a cationic canal, mainly expressed by small sensitive neurons [16, 17]. Axon reflected vasodilation essentially symmetri cally spreads around the nociceptive stimulations mainly extended to the afferent nociceptive stimu lation receptor fields [18]. Recent studies on ani mals proved that a similar inflammatory reaction can be induced by capsaicin through the activation of the different tissue nociceptive fibres [19, 20]. Up to now, a series of experimental studies on the oral mucosa were carried out only on animals. Such a study, on the other hand, aims at assessing the effects of capsaicin application on the human oral mucosa. More precisely, through computer videocapillaroscopy techniques, it aims at assess ing the oral micro circulation in vivo before and after the application, checking the possible phlo gistic phenomena onset. Material and Methods Two groups of patients (group A: M/F: 8/7; mean: ± 12.4; range: 24 60; group B: M/F: 8/7; mean: ± 12.39; range: 23 60) were examined in authors laboratory (Tab. 1). Table 1 Demographic characteristics of patients enrolled in the study Tabela 1. Charakterystyka pacjentów zakwalifikowanych do badań Group A Group B Significance a (Grupa A) (Grupa B) (Istotność) (n = 15) (n = 15) M/F ratio 8/7 8/7 (Płeć K/M) Age ± ± ns (Wiek) (mean ± SD) Range (Zakres) SD standard deviation. a Differences between group A and B patients were tested by Mann Whitney U test. ns not significant (p > 0.01). SD odchylenie standardowe. a Do oceny różnic między grupami A i B zastosowano test U Manna Whitneya. ns nieistotne statystycznie (p > 0.01).
3 Capsaicin Stimulation and Neurogenic Experimentally Induced Inflammation of the Human Labial Mucosa 33 The subjects were included in the study, if the accurate exam of their medical history and the objective examination of their oral mucous, reported them to be healthy and non smoker. All the subjects gave their written informed consent for processing and use of personal medical data in scientific papers, in accordance with the Italian Law. They were examined by computerised videomicroscopic techniques and related software (Videocap 100). This technique allows a continu ous observation of the labial microcirculation. The optical probe videomicroscope is com posed of a main unit, to which an optical probe with video optical terminal is connected, and by a high resolution colour monitor to view the exam ined area. The main unit is made of: a cold halo gen light source emitted by a 100 W lamp provid ed with an electronic device which controls light intensity; a processing unit for the high definition video signal (420,000 pixels) provided with a colour calibration device. The probe is equipped with a video optical terminal containing a high definition video sensor, on which different vari able magnification optics from 10 to 1000 can be applied. A technological characteristic of the video optical terminal is the possibility to focus directly from the handpiece. Image digitalization allows the analysis of the fundamental parameters of microcirculation (calibre and vessel length), and the calculation of the number of capillaries per mm 2 of the mucosa examined. The area under investigation for each patient was the inferior labial mucous in the area of the frenulum. This area was chosen because the macroscopic characteristics of the probe means that this area can be examined without causing dis comfort to the patient. The capillaroscopic investi gation was carried out with patients in a sitting position; always with the same source of light, at the same room temperature (23 C), in the morning, with the same operator, and repeated twice. The lip mucosa was observed in three different time periods for the group A patients: before cap saicin application (t 0 ), after one minute (t 1 ) and after 45 minutes (t 2 ) from capsaicin application (0.1%) directly onto the labial mucosa; the lip mucosa of the group B patients was observed in four different time periods: before capsaicin appli cation (t 0 ), after local anaesthetic injected (t 1 ), after one minute (t 2 ) and after 45 minutes (t 3 ) from cap saicin (0.1%) application. The following parameters were used: visibility of the capillary loops (score from 1 to 4): 1 simple focusing: within 30 seconds of the start of the examination; 2 average focusing: over 30 seconds and within 2 minutes; 3 difficult focusing above 2 minutes; 4 impossible focusing; orientation with respect to the surface (score A or B or AB): A course of the capillary loops parallel to the surface; B course of the capillary loops perpendicular to the surface; AB both parallel and perpendicular; capillary tortuosity (score from 0 to 3): 0 absence of crossing in the capillary loops; 1 presence of crossing; 2 presence of more cross ings; 3 complete distortion of the capillary loops; calibre of the capillary loops: before and after capsaicin application. Two independent observers examined all the images. The intraobserver and interobserver vari ability was assessed with the two observers evalu ating twice the same randomly selected images (p < 0.05). Data analysis was performed using StatView (SAS Institute Inc., Cary, NC). The results obtained for each area examined for every patient were the average of the two observations taken. Results Intrasubject variability satisfied the a priori hypothesis of a limited dispersion. For the para metric data, variability ranged between +2% and 2% with respect to the mean value. For the non parametric data, 1 score point difference at most was observed. The lip mucosa micro circulation visibility highlighted a score accounting for 1 in 100% of the patients. The loops were oriented parallel to the surface in 100% of the patients (score A) thus possibly completely assessing the capillary loops. The capillaroscopy, in the group A, highlighted that the vessel diameter after about 1 minute from capsaicin application (t 1 ), underwent a highly sig nificant increases (p < assessed through the ANOVA Test). Extremely long capillary clip like shaped and mainly volvulated loops protruded into the tissue meshes (Fig. 1). A further control at 45 minutes (t 2 ) proved that the vessel diameter and capillary tortuosity returned back to the initial values (Fig. 2a, b). In the group B, the vascular in vivo study allowed to observe no sig nificant modification of the vascular diameter and tortuosity in four different time periods (p > 0.01 assessed with the ANOVA Test) (Tab. 2). Discussion The results of function and morphological studies in rats seem to confirm the possibility of a neurogenic component of inflammatory alter ations caused by mechanical, and chemical stimuli
4 34 G. A. SCARDINA et al. a b Fig. 1. Group A patient: the vessel diameter after about 1 minute from capsaicin application (t 1 ), magni fication 200 Ryc. 1. Pacjent grupy A: średnica naczyń po koło minucie od podania kapsaicyny (t 1 ), pow. 200 Fig. 2a, b. Group A patient: the vessel diameter and capillary tortuosity returned back to the initial values (t 2 ), magnification 200 Ryc. 2a, b. Pacjent grupu A: średnica naczyń i ich prze bieg powróciły do wartości wyjściowych (t 2 ), pow. 200 in the oral mucosa [2]. A lot of observations appear to indicate that the presence of capsaicin sensitive sensory small diameter fibres is indis pensable to the development of neurogenic inflam mation [6]. Goltz in 1874 proved for the first time vasodi lation following sensitive fibre stimulation [21]. Two years after Striker (1876) got similar data after stimulating the spinal cord dorsal root. In 1901 Bayliss confirmed that when sensitive afferent pri mary fibres are electrically stimulated, a vasodila tion is induced, which can only be solved by dorsal gangliotomy after 14 days from the nervous stimu lation [21]. In 1967 Jancsò too proved plasma over flow after the sensitive nerve stimulation [12]. The inflammatory symptoms induced by local capsaicin stimulation are produced by the effects of the neuropeptides that are released at the peripheral sensory nerve terminals. This is proved by the fact that denervation of the area fully pre vents the development of inflammatory reactions in rats [12]. Capsaicin, as a substance able to experimentally induce a NP, when administered in controlled doses lead to specific effects which could be correlated with the previously considered neuromodulator release, mainly with CGRP [19, 22, 23]. Capsaicin leads to a concentration depen dent CGPR release increase, that is at the presence of capsaicin, a higher quantity of CGPR was pre sent at the tissue level, leading as a consequence to an increase of the blood overflow and to the main typical signs of phlogosis [6]. Another important information, mainly depending on the possible activity mechanism, is that the possible CGPR release induced by capsaicin seemed to depend on the absence of extra cellular calcium [23]. Mainly studies proved that CGPR is often co localised on the SP in the C sensitive fibres, and that at the oral cavity level, the rich CGPR locali sation in the trigeminal ganglions, would widely justify the role of such a substance at the oral cav ity phlogosis level [1, 23]. Nerves involved in the NP pathogenesis main ly are type C, amelynic, polymodal, afferent, cap saicin sensitive and small fibres [3]. Blood flow changes at the different organ level and the increase of the vessel permeability typical of NP mainly depends on the release of vasoactive agents at the peripheral nervous termination level, but even on other cellular components [24, 25]. However, up to now the role but mainly the pathophysiological mechanisms of the different involved mediated in the NP development were not clear yet. In fact, one of the many doubts mainly dealt with the direct activity mechanism involved, that is the activity of any released neuropeptides on the vessel plain muscle cells which would lead to their contraction and as a consequence to their diam eter change, or an indirect mechanism, mediated by histamine release which then would lead to the inflammatory symptoms [26]. The recent re defini tion of the SP central role mainly depended on gen
5 Capsaicin Stimulation and Neurogenic Experimentally Induced Inflammation of the Human Labial Mucosa 35 Table 2. The characteristics of the labial microcirculation in group A and B patients Tabela 2. Charakterystyka mikrokrążenia wargowego u pacjentów z grupy A i B Group A patients Group B patients (Pacjenci z grupy A) (Pacjenci z grupy B) score subjects score subjects Orientation with respect to the surface A 100% A 100% (Orientacja względem powierzchni) Capillary tortuosity t (Krętość naczyń dla t 0 ) Capillary tortuosity t (Krętość naczyń dla t 1 ) Capillary tortuosity t (Krętość naczyń dla t 2 ) Capillary tortuosity t (Krętość naczyń dla t 3 ) Microhemorraghes 0 100% 0 100% (Mikrokrwotoki) Calibre of the capillary loops µm t ± 0.78 t ± 1,11 (Wielkość pętli naczyń µm) t ± 1.64* t ± 1.41 (mean ± SD) t ± 0.95 t ± 0.95 t 3 13 ± 1.09 SD standard deviation. Differences between group A and B patients were tested by ANOVA Test. * significant. SD odchylenie standardowe. Różnice między grupami A i B testowano za pomocą ANOVA. * istotne statystycznie eral studies on rats and SP antagonist [23, 25, 27]. It is thus possible to come to the conclusion that pep tide nervous fibre are involved in the local regulation of the blood flow, in the vessel permeability and in the plain muscle tone; in real substances such as SP or C are directly involved in such mechanisms. In presented study, capsaicin was used, a unique substance which can lead to NP at the application site and in the surrounding areas, on the oral mucosa of 30 patients. The group A patients, results showed a power ful local stimulating effect induced by the sub stance, which in the majority of patients lead, after the application, to a pyrotic and painful sensation to heat. Such symptoms mainly depend on the inflammatory neuromodulator release by peripher al nervous terminations followed by a consequent vasodilation, by the increase of the capillary per meability finally leading to erythema, increase of temperature, oedema and pain. The capsaicin effect, however, is transitory and reversible. In fact, the vessel diameter measured after 45 min utes from the product application highlighted that capillaries were back to their original sizes. The group B patients results showed a not sig nificant modification of the diameter of the capil lary loops after local anaesthetic injected. This indicates that the capillary modifications observed in the group A patients are principally due to NP. The NP is observable in the human labial mucosa. References [1] HERBERT M. K, HOLZER P.: Neuorogenic inflammation. Anasthesiol. Intensivmed. Notfallmed. Schmerzther. 2002, 37, [2] FAZEKAS A., VINDISCH K., PÒSCH E., GYORFI A.: Experimentally-induced neurogenic inflammation in the rat oral mucosa. J. Periodont. Res. 1990, 25, [3] GYORFI A., FAZEKAS A., ROSIVALL L.: Neurogenic inflammation and oral mucosa. J. Clin. Periodontol. 1992, 19,
6 36 G. A. SCARDINA et al. [4] GAMSE R., POSCH M., SARIA A., JANCSÒ G.: Several mediators appear to interact in neurogenic inflammation. Acta Physiol. Hung. 1987, 69, [5] LEE T., KAWAI Y., SHIOSAKA S.: Coexistence of calcitonin gene related peptide and substance P like peptide in sin gle cells of the trigeminal ganglion of the rat: immunohistochemical analysis. Brain Res. 1985, 330, [6] FRANCO CERECEDA A., HENKE H., LUNDBERG J. M., PETERMANN J. B., HOKFELT T., FISCHER J. A.: Calcitonin gene related peptide (CGRP) in capsaicin sensitive substance P immunoreactive sensory neurons in animals and man: distribution and release by capsaicin. Peptides 1987, 8, [7] HOU M., UDDMAN R., TAJTI J., KANJE M., EDVINSSON L.: Capsaicin receptor immunoreactivity in the human trigeminal ganglion. Nuerosci. Lett. 2002, 330, [8] KEMPPAINEN P., AVELLAN H., HANDWERKER H. O., FORSTER C.: Difference between tooth stimulation and cap saicin induced neurogenic vasodilatation in human ginigiva. J. Dent. Res. 2003, 82, [9] VERDICKT G. M., ABBOT P. V.: Blood flow changes in human dental pulps when capsaicin is applied to the adja cent ginigival mucosa. Oral Surg. Oral Med. Oral Pathol. 2001, 92, [10] LIN Q., ZOU X., FANG L., WILLIS W. D.: Sympathetic modulation of acute flare induced by intradermal injection of capsaicin in anesthetized rats. J. Neurophysiol. 2003, 89 (2), [11] LIU M., PERTL C., MARKOWITZ K., DORSCHER K. J., KIM S.: The effects of capsaicin on pulpar blood flow. Proc. Finn. Dent. Soc. 1992, 88, [12] JANCSÒ N., JANCSÒ-GABOR A., SZOLCSÀNYI J.: Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment by capsaicin. Br. J. Pharmac. Chemother. 1967, 31, [13] SAWYNOK J.: Topical and peripherally acting analgesic. Pharmacol. Rev. 2003, 55, [14] DRAY A.: Inflammatory mediators of pain. Br. J. Anaesth. 1995, 75, [15] EPSTAIN J. B., MARCOE J. H.: Topical application of capsaicin for treatment of oral neuropatic pain and trigeminal neuralgia. Oral Surg. Oral Med. Oral Pathol. 1994, 77, [16] SZALLASI A., BLUMBERG P. M.: Vanilloid (capsaicin) receptors and mechanisms. Pharmacol. Rev. 1999, 51, [17] VYKLICKY L., LYFENCO A., SASANKOVA K., TEISINGER J., VLACKOVA V.: Reducing agent dithiothreitol facilitates activity of the capsaicin receptor VR1. Neuroscience 2002, 111, [18] WARDELL K., NAVER H. K., NILSSON G. E. WALLIN B. G.: The cutaneous vascular axon reflex in human charac terized by Laser Doppler perfusion imaging. J. Physiol. 1993, 460, [19] FLORES C. M., LEONG A. S., DUSSOR G. O., HARDINE R. C., HARGREAVES K. M., KILO S.: Capsaicin evoked CGRP release from rat buccal mucosa: development of a model system for studying trigeminal mechanisms of neuro genic inflammation. Eur. J. Neurosci. 2001, 14, [20] ULRICH LAI Y. M., FLORES C. M., HARDING ROSE C. A., GOODIS H. E., HARGREAVES K. M.: Capsaicin evoked release of immunoreactive calcitonin gene related peptide from rat trigeminal ganglion: evidence for intragan glionic neurotransmission. Pain 2001, 91, [21] CHAHAL L. A.: Antidromic vasodilatation and neurogenic inflammation. Pharmacol. Ther. 1988, 37, [22] BRAIN S. J, MORRIS H, MACINTYRE I. Calcitonin gene related peptide is a potent vasodilatator. Nature 1985, 313, [23] BRAIN S. D., WILLIAMS T. J.: Substance P regulates the vasodilatator activity of calcitonin gene related peptide. Nature 1988, 1, 335, [24] COUTURE R., CUELLO A. C., HENRY J. L.: Trigeminal antidromic vasodilatation and plasma extravation in the rat: effects of sensory, autonomic and motor denervation. Brain Res. 1985, 346, [25] ROSELL S., OLGART L., GAZELIUS B., PANOPOULOS P., FOLKERS K., HORIG J.: Inibition of antidromic and substance P induced vasodilation by a substance P antagonist. Acta Physiol. Scand. 1981, 111, [26] IZUMI H., KARITA K.: The effect of capsaicin applied topically to inferior alveolar nerve on antidromic vasodilata tion in cat gingival. Neurosci. Lett. 1990, 112, [27] KENINS P., HURLEY J. V., BELL C.: The role of substance P in the axon reflex in the rat. Br. J. Dermatol. 1984, 111, Address for correspondence: Giuseppe Alessandro Scardina Department of Odontostomatological Science G. Messina University of Palermo via Del Vespro, Palermo Italy fax: e mail: Received: Revised: Accepted: Praca wpłynęła do Redakcji: r. Po recenzji: r. Zaakceptowano do druku: r.
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text:
Warning: T-Cest TMNT Brother Love
Pairings: Leo/Don : Mikey/Leo : Raph/Don
Summery: April has officially announced her feelings for Casey and after a heart to heart with Donnie explained she just sees him as an awesome brother. However there may be something Donnie's been missing for years, he wonders why he never noticed before.
I do not own any rights to TMNT or the characters there of. All ideas are original and any similarities or names used are strictly coincidence.
Raph made his way to the garage stopping just outside the sliding metal door; he tried to think of how to tell Donnie his feelings and grunted in frustration when nothing came to mind. Finally kicking himself into gear he opened the door only to find the space vacant, looking around he found no sign of the genius or the second bike. Before his emotions could turn to darker conclusions he caught sight of his shell cycle, the old girl had a fresh coat of candy apple red paint with emerald green detailing on the sides and face. The metal had been polished to a chrome-like finish and on the freshly restored leather seat was his worn red biker's jacket. Striding up to the gift he found a quickly written note sitting on top of the old jacket.
Meet you at the docks. Just sign the back before you get there
Skeptical Raph flipped over to the blank side of the paper and saw a clear black line with an X asking for his mark. Using a sharpie left on the ground he scratched his signature and stuffed the paper quickly in his jacket pocket. As he mounted his baby he couldn't calm the butterflies in his gut as he raced off into the cloudy night. No ominous moon leering over him, no stars to witness the obvious traffic violations he pulled racing through the streets, all to get to the one calling him. He was enflamed, every muscle tensed with excitement for what was to come. Donnie always had the best ideas when he got creative, and when he was impassioned with a plan he always went over the top to get what he wanted. Right now what Donnie wanted most was him, the brainless, meat-head, prick; a guy like Don wanted him and there was nothing that was going to keep the red banded brazier from getting to him. Skidding around the last alley corner with neck breaking speed, Raph came upon his familiar crowd but nearly crashed into a stack of shipping crates when he saw what was on the runway waiting for him.
Seductively clad in his Nightwatcher leathers and boots Donnie sat with his back arched into his shell so it rested on the back end of what Raph could only describe later as sex on wheels. The old beater he'd won months ago was hidden and transformed into a sleek piece of machine, new engine and lines polished to perfection, neon lights the alternated between purple and red illuminated the fully restored body. The paint job alone had him ready to jump the genius right on the runway; all a midnight purple polished almost black into the metal, along the left side face was mask of red with brilliant gold eyes my eyes glaring at any rider who dared to challenge him. But on the right just peaking over was a mask of vibrant eggplant with the chocolate red eyes hooded by olive lids beckoning any to follow its gaze across the front to the bold stare opposite. The tail pieces were a blend of blood red and twilight indigo with the New York skyline in all its glory, the city lights gleaming like stars trapped in a swirling nova against a deep sky.
Looking back to the rider his breath caught in his chest and he once again had to recover himself. Donnie looked damn hot in black, but he's taken away the guards and metal plates replacing them with purple padding and silver is that fucking wire? He sewn the pieces with thing silver wire to glisten in the lights around him so that it looked like an illusion passing over his thin strong shoulders, succulent sides and hips, and ghosting over the strong joints in his arms and legs. Swallowing the saliva pooling in his mouth Raph finally made a move to the starting line shaking off the nerves and discomfort in his own biker leathers. As he took his set he saw Don hand off a slip of paper to the skimpy clad official, she read over it and smiled as she sauntered over to him; puzzled he looked at the other racer with confusion. Don patted his side where in Raph's own pocket was the slip of paper he'd signed, pulling it out Raph tried to make out the dark writing that had suddenly appeared above his signature. Unable to make anything out through the tinted shield of his helmet he gave up and handed it to the woman slightly annoyed at the chuckle that escaped his brother.
As the official called for the start Raph once more was amazed at the purr of the new bike next to him, the flag was dropped and to his shock Don let her loose. The roar of the engine vibrated his bones and like a streaming comet Don had pulled ahead of him, not one to loose his rep Raph pushed his baby to the brink and shifted to open it up. Much to his dismay the old girl hit 120 and began to decline once more. The finish line was only 100ft away and Don was already a good 5 feet ahead, reving up the engine again he hit the peak and again it backed down.
"What the shell?" Paniced he looked ahead to see if his brother had noticed his distress. The look he took in made his beak break out in his best grin and stoked a raging inferno in his loins.
Donnie had looked over his shoulder at his brother's second failed attempt to catch him with a gleam of mischief. Briefly opening his visor he blew a kiss to the hot head with a flirtation wink and in a shot closed it as he flew across the finish almost a full 12 yards ahead of the renowned biker. As Raph pulled up beside him he laid down his bike as gently as he could in a hurry, wrapping the thinner frame in powerful sweaty arms.
"You son of a bitch, you put a fucking limiter on my girl so you could smoke me." Squeezing the shell tighter he groaned and growled looming over the winner. "You're gonna pay for that little brotha I swear but I'm too damn horny to be mad now."
What Donnie's reply would have been to such crude words was unknown as a crowd of Raph's buddies surrounded them. The Asian official gave each racer's neck a luscious kiss and handed Donnie both papers. Soon the crowd was forced to disperse after a cocky declaration of revenge from the red racer and a promise to get even. Both brothers went home racing through the streets of New York crossing paths on the pavement and just as the neared the garage the sky let loose. Supporting his bike with his legs Don removed the helmet and tossed it in the door to the garage and beamed at Raphael who had removed his helmet as well letting the rain trace perfect wet lines over his strong features. His brilliant gold eyes glistened in the glow of the street lamps around them; laughing at himself Donnie motioned for the brawler to follow him once more and sped off toward central park. Curious and thrilled the red banded ninja followed looking at the scene ahead and more than ever thanking whatever god there may be for this moment. He slowed to a stop just on the edge of the main pond lost in the picture of Donnie leaning arms crossed against his motorbike looking up into the stormy sky.
"You sure have the best dreams Raphie." Don averted his gaze from the light show above to bask in the warmth of his brother as the large arms encircled his waist. He leaned into the fire enfolded within the flames he never more at home.
"You saw mine, heh, no fair brainiac. But now ya know, I've been burning with these feelings for years Donnie-boy an' I can't hold 'em back after tonight. I…I don't wanna be alone Don, and…the one I want ta be with foreva is you." Walking around but keeping contact he looked down at those big brilliant eyes and begged with all his soul Don felt the same.
Looking down Donnie felt his heart clench and flutter, he had to keep his cool, remain calm and not be a dork for once in his life. Sucking in deep breath timid fingers produced the documents he'd won pushing them into the broad chest adjacent his own. Watching as his brother read them over he began to become overwhelmed with uncertainly, though he knew the feelings the emerald turtle harbored for him, he hoped it wasn't too bold a step.
I the undersigned hereby agree to the terms and conditions as expressed below and under fierce penalty of death also accept responsibility for upholding these terms.
Firstly, I agree to be a servant as well as a leader within the confines of love and loyalty.
I agree to give as much as I take even giving more in appropriate conditions asking nothing of the other party.
I vow to remain persistent in my feelings for undersigned, and will not betray or be unfaithful ender strict punishment of death.
I understand that my life is not my own and will act as such considering the thoughts and opinions of the co-signed before taking risks.
I promise to share quarters and divide the estate equally within pre-set rules of cohabitation.
Lastly, I understand that this contract is legal and binding and will fulfill with the best of my ability until I can no longer do so in life.
Raph read over the agreement again and didn't care if the company saw the tears well up in his gold orbs. For on the line was his hasty mark providing a willing party and binding contract with his passionate new mate.
"Raph…I…it took me a while but you, you've always been my light. Even when I didn't think I needed it you protected me from everything heh even myself. I never noticed how much I need and rely on you. I…I love you Raphael." Eyes still cast down Donnie confessed his soul to his brother looking up he knew his feelings reached their mark. As he cried Raphael untied both their masks and locking wrists with the olive terrapin retied them together binding his own promise.
"I accept your terms Donnie and promise I'll neva lettin' ya down." With one last look at the braided fabric he swept the smaller up in his strong arms and gave him the deepest kiss he'd ever given in his life.
Donnie embraced his new mate returning the kiss with equal passion, he dared a taste of the larger male and was rewarded with a deeper examination. Never had his skin burned so hot, his shell felt so tight, and his heart so full as it did in the emerald embrace. Breathless and on cloud nine Donnie stared up doe-eyed at the musky goliath that held him.
"I've got it in writing, so by all accounts you're mine too. But you can put me down now, otherwise we'll never get home." They both erupted in childish laughter as the sky gave way to a full bright moon that seemed to shine it's silver beams on the pair. Kissing across new and old machines they shared one last breath before breaking and revving their machines to life.
"You're gonna take that damn limiter off my baby when we get back right?" Raph asked as he rolled up beside his brother's bike turning around.
"Tell ya what, I won't go over 120 if you beat me not only will I take it off, I'll let you ride me." Winking he was off like a rocket spinning up turf and rocks as he b-lined out of sight.
Gawking at the suggestive prize Raph had a late start chasing after the light stream. "I knew I loved 'im for more than his ass." Roaring with pride into the night he chased his love down the streets to their home where eager hearts awaited the outcome of their night ride.
Morning came and two pairs of lovers joined each other at the breakfast table, jeers and glances were in abundance even as their father came to join the happy frey he too picked at his sons threatening to make his own claim should new love hinder their training or teamwork. With a laugh Splinter rapped his youngest and second eldest on the heads with his cane, "You two will be grounded with each other as your partners train at the river side." Chuckling he took his tea to the living room for his stories. Leaving the dreaded thought of having to sit and do nothing as the love of their lives got hot and sweaty in clear glistening water.
"Leo I swear if you take it easy on me you won't get laid for a month!" Mikey warned as he maneuvered a strawberry of the leader's plate.
"And if I miss a chance at see'n Don wet and hot fer me I'm gonna break your face fearless."
Leo laughed and threw up his hands in surrender looking at his family with renewed love and joy, he could not help but admire the power of the passions they had found in each other. As he stood and called each of his brothers to join him in the dojo for training he could not help but muse at the thought
So this is Love
So this is Love by KaguriaKitsuneWatch
©2014-2017 KaguriaKitsune
I can't believe there is but one more peice to this story and I will move onto my main idea. So here it is Donatello's plan in all it's glory! Stay tuned for the last installment comming soon!
Shout outs to and Each have played a key role in this story's creation and development if you've not read their works please do!
Read the full story!
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Read Part 5 here- fav.me/d7ntwd7
Read Part 6 here- fav.me/d7otjm0
Read Part 7 here- fav.me/d7qxegp
Read Part 8 here- fav.me/d7re9jt
Read Part 9 here- fav.me/d7s4ibq
Read Part 10 here- fav.me/d7vbytb
Read Part 11 here- fav.me/d7wx7y3
Read Finale here- fav.me/d7yo8gq
Shout outs to and Each have played a key role in this story's creation and development if you've not read their works please do!
Read the full story!
Read Part 1 here- fav.me/d7ki01u
Read Part 2 here- fav.me/d7krzli
Read Part 3 here- fav.me/d7lszqn
Read Part 4 here- fav.me/d7mhuh8
Read Part 5 here- fav.me/d7ntwd7
Read Part 6 here- fav.me/d7otjm0
Read Part 7 here- fav.me/d7qxegp
Read Part 8 here- fav.me/d7re9jt
Read Part 9 here- fav.me/d7s4ibq
Read Part 10 here- fav.me/d7vbytb
Read Part 11 here- fav.me/d7wx7y3
Read Finale here- fav.me/d7yo8gq
Oh Donnie you little tease, he sure is creative, man in so happy!!
Donnie is by far my most inspiring turtle, I really love how he can come up with ways to get out of anything.
I've been re-watching car racing movies & anime, so I have to say that this was amazing to read. I love it! There's a gigantic grin on my face right now, it's ridiculous. Beautiful work!
My uncles do dirt bike racing so I tried to capture the excitement of two people racing for more than just victory.
I can't believe I forgot to comment on this! Donnie playing the sneaky one!? Who would have thought. He got Raph good there XD
what a fantastic plan by donatello, the perfect way to further dig himself into raphs heart
Oh wow! This was beautiful, lol and now that I've read to the end and seen there are several more
parts actually; I should go start at the beginning.
parts actually; I should go start at the beginning.
I love this fic! Beautifully written!
Love this fanfic

subset: commoncrawl


text:
Iyashi Bracelet Testimonials and Reviews
My bracelet-- a beautiful Blue Sapphire color-- arrived yesterday, and it practically flew onto my wrist. I don't every want to remove it. It's got a light, bubbly energy that, just makes me feel happy!
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Testimonials found on our website are unverified experiences individuals have sent to us. They are not indicative of expected results you will receive and we do not endorse any claims made in them. Any information provided is not intended to replace medical advice offered by a physician nor should this information be used to treat any health problems without first consulting with a physician or pediatrician.
© Copyright 2015 by iithealthstore.com


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Author | Noor Fathima Warsia | Tuesday, Apr 10,2012 12:02 PM
BBDO India has won the ATL and BTL creative duties of water heater brand, Racold Thermo. The business will be handled from BBDO's Mumbai office. The agency won the business following a multi-agency pitch involving iterations over two months.
Mathew Job, Managing Director, Racold Thermo said, "Over the last few weeks, we have gone through a rigorous process to select an advertising agency to partner with us. We are excited to travel the next phase of our brand journey in partnership with BBDO."
Commenting on the win, Ajai Jhala, CEO, BBDO India said, "Racold has been an integral part of more Indian bathrooms than any other brand and now wants to play a more active role in people's lives. We, at BBDO, are very excited that we have been chosen to take Racold the next horizon."
Racold Thermo is a fully owned subsidiary of Ariston Thermo Spa – Italy, the world leaders in the manufacturing and marketing of water and space heating products and their components. The Indian operations include India's largest and fully integrated water heater plant in Chakan near Pune, Maharashtra that has been operational since 1999.


text:
Meaning of "astronomical" - Learner's Dictionary
(Definition of "astronomical" from the Cambridge Learner's Dictionary © Cambridge University Press)
Get a quick, free translation!
- astride adverb
- astro- prefix
- astrology noun
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a feeling of respect or admiration for someone or something


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|Blessed Bishop-Martyr Vasyl Velychovsky
|panagia, Redemptorist habit, and rosary
|January 13, 1903Ukraine, Ivano-Frankivsk,
|June 30, 1973, Winnipeg,Canada
|Venerated in
|Roman Catholic Church, Ukrainian Greek Catholic Church
|27 June 2001, Lviv Hippodrome, Ukraine by Pope John Paul II
|Major shrine
|St. Joseph's Ukrainian Catholic Church, Winnipeg, Manitoba, Canada
|27 June, with Blessed Nicholas Charnetsky and 24 Companions
Blessed Vasyl Velychkovsky (June 1, 1903, Stanislawów, Austria-Hungary - June 30, 1973, Winnipeg, Canada) - blessed bishop of Ukrainian Greek-Catholic Church (Eastern rite Catholics), whose body 30 years after his death was found to be almost uncorrupt (his toes had fallen off and were subsequently divided to be used as holy relics). Beatified in 2001, the intact remains of Blessed Vasyl are enshrined at St. Joseph's Ukrainian Catholic Church in Winnipeg, Manitoba, Canada.
The Bishop Velychkovsky Martyr's shrine is located at 250 Jefferson Avenue, Winnipeg, Manitoba.
Links and references
- Bishop Velychkovsky Martyr's Shrine - Official Site
- Catholic Online: Bl. Vasyl Velychkovsky 1903-1973
- The martyr who came to stay; Blessed Vasyl Velychkovsky, who endured Soviet torture, is honoured with a shrine.
- Biography of Blessed Vasyl on CSSR Official Websiteru:Величковский, Василий


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Hobber's Gap is a landform of Turaxis II, situated between Burr's Crossing to the south and Firebase Zulu to the north. During the Guild Wars, Kel-Morian forces fought their way through it, subsequently laying waste to the Confederate-held territory that lay beyond.[1]
- ↑ Dietz, William C. (April 6, 2010). StarCraft II: Heaven's Devils. Simon & Schuster (Gallery Books). ISBN 978-1416-55084-6.


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The budget session, which started on Feb 21, and was scheduled to end on May 10.
The two houses were first adjourned till noon, within minutes of assembling at 11 am, as the BJP once again raised its pitch, demanding the resignation of the prime minister and two ministers — Ashwani Kumar and Pawan Bansal.
The scene was the same when the Lok Sabha assembled at noon. Following this, Speaker Meira Kumar adjourned the house sine die.


text:
Mhairi McDonald Model
Gillian LochheadPhotographer Female Glasgow, Scotland, United Kingdom
My Website: FlickrMy MM URL: http://www.modelmayhem.com/gillianlochhead
Mayhem # 1584093
About MeHello, I am Gillian Lochhead. A nineteen year old amateur photographer. I live in Renfrewshire area. I have completed higher photographer, and now I am in a HNC photography course in City of Glasgow College. I have been able to collect a lot of skills through out my course in which I think had improved my photographic skills.
http://www.facebook.com/profile.php?id=1598731640 - My Facebook
Have you worked with Gillian Lochhead? Add Credits for Gillian Lochhead! >>
Credit NotesPhotographers:
Cheryl Lynch #1814344
Andrew Lynch #1415596
Hannah Gale #1779937
April Luke #1203829
Kat Reilly (KD) #1949245
Joanna-Lee #1853554
Lauren Sergeant: #2214348
Leah Blackburn
Amy McFadyen
Mhairi McDonald Model
Gabriela Nicol Model
Sharrow Model
Nicole Abbott Model
Adeleviola Model
Camille Perrin Model
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text:
1- More determined and driven work ethics due to frequent variability in the weather of the:
a) Higher Latitudes b) Middle Latitudes c) Lower Latitudes d) None of these
2- Equational Paradox is an aspect of:
a) Cultural Geography b) Regional Geography c) Economic Geography d) None of these
3- Cliamtic determinism was intensely studied by:
a) Ellsworth Huntington b) Carl O Saver c) Carl Marx d) None of these
4- Environmental Problems must all be understood via:
a) Physical Processes b) Social Processes c) Commercial Process d) None
5-The study of the number of population and its variations in time and space is called:
a) Population Dynamics b) Population Density c) Population Distribution d) None
6- Rapid Population growth in Urban areas perpetuates:
a) Crimes b) safety Issues c) Poverty d) None of these
7- Sustainability of human settlements have become a matter of:
a) Global Concern b) Continental Concern c) Regional Concern d) None
8- Settlements can be ordered by size or other factors to define:
a) Morphology b) Landscape c) Hierarchy d) None of these
9- South Asian agriculture is considered to be:
a) Intensive b) substence c) Extensive d) None
10- Appalachian Industrial area hosts:
a) Iron and Steel b) Textiles c) Chemicals d) None
11- Turkey possess plenty of:
a) Power resources b) Mineral Resources c) Water Resources d) None
12- What had historicaly made geography unique was its attention to systematic description of areal variation said by:
a) Hart Shorne b) Charles Fisher c) Ann Buttimer d) None
13-Indus Water Treaty Projects were financed by:
a) Asian Development Bank b) World Bank c) Former EEC d) None
14- Ninety percent of Russia is north of the:
a) 60th Paralle b) 55th Parallel c) 50 Parallel d) None
15- Before 1950, Famine was a harsh reality in:
a) Poland b) Portugal c) India d) None
16- Waterways are common transport means in Bengal for carrying:
a) Tea b) Jute c) Animals d) none
17- Greek Culture and power expanded into the near and Middle East during:
a) Archaic Period b) Classical Period c) Hellenistic Period d) None
18- in the 5th and 4th Centuries BC the most advanced economy was founded in:
a) Italy b) France c) Greece d) None
19- Geographic regions are based on distinctive quality of
a) Variety b) Homogenity c) ORigin d) None
20- Geography affects the culture of a region by:
a) What people do b) What people possess c) What people copy d) None
Friday, December 27, 2013
Geography MCQs of PPSC SPSC KPKPSC
1- More determined and driven work ethics due to frequent variability in the weather of the:
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Rosie Cheek Model
AklayModel Female Toronto, Ontario, Canada
My MM URL: http://www.modelmayhem.com/rarore
Mayhem # 1360738
About MeI am mixed: Malaysian and American
Most of my modelling was in Singapore, I am currently attending University in Canada.
I'm interested in singing, acting and fashion. I also love photography, particularly travel photography.
***Note to Photographers.
When I do TFCD work.... I expect a CD. I don't care if it's unedited.
Feel free to contact me here or firstname.lastname@example.com
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Credit Notes***Some Photographers
Jennifer Ho
Satch satch
Jay Nodalo
Willie Arolf
Deadpoet Photography
Terry Chua
Renn Rementilla
Khairudin Sukor
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Haikhal Fuad Photographer
Peterpancake Photographer
Y_Q Model
August Prawira Photographer
Simplifai Studios Photographer
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text:
Super Mario Wave Rider is a Mario surfing game using the Wii Balance Board. It came out in the US on August 12 2008, Japan on August 28 2008, and in Europe on October 2 2008. The ESRB rated it E10+, PEGI rated it 3+, and CERO rated it A. The game is developed by UniSoft in cooperation with Nintendo. Development begone almost directly after the Wii Balance Board came out, and there where rumors of a Mario surfing game, for a while before it was announced.
The first of its kind, a Surfing/Racing Race game utilizing the Wii Balance Board, making it a very realistic gameplay. After wining a race you get money that can be used to buy things in the shop.
- Tilt left - Go left
- Tilt right - Go right
- Tilt back - Slow down
- Tilt forwards - Lean forwards
- Wii Remote - Help balance (Used for hand-gestures in Team Race Mode.), its also used for tricks
Story Mode
Trial Mode Only
- Bowser
- Princess Daisy
- Birdo
- Toadette
- Diddy Kong
- Tiny Kong
- Dixie Kong
- Dry Bones
- Bowser Jr.
- Baby Mario
- Bob-omb Buddy (Unlockable)
- Hammer Bro. (Unlockable)
- Baby Luigi (Unlockable)
- Bandit (Unlockable)
- Boo (Unlockable)
- Blooper (Unlockable)
Each stage will be listed in the order you go to them in story mode.
Yuzu Beach
A small course by the shore, very simple not many obstacles or ramps. In story mode the course is played at mid-day. There are wigglers on the shore that try to get you when you come close to it, however if you lead them to far in the water they will get stuck there, as they can't swim,and will just float there, and can be used as a ramp.
Obelisk Island
A larger course, around an island with three large towers on it. If you get to close to them they will fall on you there are several ramps that lead onto a large water-way on the island that can be a short cut, or a long cut. It is much harder then the previous course(After this the game gets harder), with many more traps around.
Ricco Harbor
A large course through a crowded harbor. There are several ramps that can help you get over some large obstacles. Gooper Blooper occasionally appears and puts ink in the water, which makes it harder to turn. Dolphins also constantly jump out of the water and try to hit the racers.
- Red Streak
- Power: 3
- Balance: 3
- Air: 3
- Green Thunder
- Power: 3
- Balance: 2
- Air: 4
- Golden Nibble
- Power: 4
- Balance: 4
- Air: 2
- Swift Shadow
- Power: 2
- Balance: 4
- Air: 5
- Shroomer
- Power: 3
- Balance: 5
- Air: 2
- Pink Flower
- Power: 2
- Balance: 3
- Air: 5
- Yew Wonder
- Power: 5
- Balance: 5
- Air: 2
- Big Egg
- Power: 5
- Balance: 1
- Air: 3


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Industry News
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July 2017: Surgical lasers
June 2017: Physiotherapy
May 2017: Medical Market India
March 2017: Big Data and medicine
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Topics of the Month 2016
December 2016: The human patient
November 2016: MEDICA 2016
October 2016: Networked healthcare
September 2016: Intraoperative Imaging
August 2016: Medical Industry Worldwide
July 2016: Sports and medicine
June 2016: Hospital hygiene
May 2016: The heart
March 2016: Paediatrics and neonatology
February 2016: Regenerative medicine
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January 2016: Infectious diseases
Topics of the Month 2015
December 2015: The brain
November 2015: MEDICA
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August 2015: Nuclear medicine
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February 2015: Pathology
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Topics of the Month 2014
December 2014: Ethics
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October 2014: Orthopedics and physical therapy
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Pneumonia in Children: Ultrasound or X-Rays?
A new broom sweeps clean? The new EU Medical Device Regulation
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Telehealthcare: networking brings relief
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Is the Russia crisis also a crisis for medical technology?
Video Background Reports
Light microscope ChipScope - a glimpse into living cells
Photochemical internalization – A new hope against bile duct cancer?
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New Protein Multiplex Assay Technologies
Axela Inc
New Protein Multiplex Assay Technologies
Toronto, Ontario, Aug. 15, 2012 – Canadian first-time exhibitor Axela Inc. will introduce ground-breaking multiplex biomarker analysis tools at MEDICA, the world's largest annual medical trade fair, Nov. 14-17 in Düsseldorf, Germany. Specifically designed to simplify the transition from clinical discovery to diagnostic implementation, Axela's novel approach to biomarker analysis provides researchers with highly flexible, user-defined, multiplex panels for real-time or end-point measurements.
"Our new products directly address the need in translational research to convert biomarker discoveries into robust diagnostic tests," says Naomi Wessel, Manager Sales Support and Tactical Marketing of Axela Inc. "Delivering on the promise of personalized medicine requires the ease of use and robustness delivered by Axela's products, enabling deployment of a new generation of multi-marker panels with higher sensitivity and specificity. The success of this approach is evidenced by the breadth of Axela's first content examples including Oncology (breast cancer prognosis), Immune Status (strongyloides) and Specialty Testing (traumatic brain injury) among others."
Axela's new panelPlus™ reagents are designed to work with multiple platforms, allowing the user to choose the technology best suited to their specific testing requirements. With the company's rapid conjugation kits, researchers can easily address the proteins of their choice for automated creation of customized multiplex panels. This greatly simplifies the validation of new biomarker panels and accelerates the transition from research assay to robust routine analysis. To fully exploit the new panelPlus technology's capabilities, Axela is offering both real time immunoassay and rapid flow-through microarray platforms.
Microarray systems utilizing proprietary porous Flow-Thru Chip® technology greatly accelerate protein binding steps in microarray analysis. These instruments, including the current Ziplex® System, fully automate sample processing, imaging, data analysis, and report generation thus enabling highly reproducible, routine biomarker assays. These features, along with mid-range (up to 150) multiplex capability, provide researchers with an ideal platform for validation and implementation of signatures derived from global discovery platforms. In addition, this automated Flow-thru Chip system offers the flexibility of running both protein and gene expression assays in the same convenient format.
Diffractive optics uniquely allow monitoring of protein interactions in real time, including binding and dissociation events, during an immunoassay. This detection approach is particularly well suited for low multiplex, rapid biomarker assays directly in crude biological samples where additional information is useful. For example, the combination of titer and avidity measurements in the same assay is ideal for immune status and serology research applications. This real-time information greatly speeds assay development and the results can be directly deployed from the diffractive optics (dot ®) platform or carried through for use on Axela's flow-through microarray platform.
About Axela Inc.
Axela's automated platforms for multiplexed nucleic acid and protein analysis are designed for rapid biomarker testing in clinical research and diagnostics. The company's approach significantly improves the amount and quality of information when compared to traditional assays and provides access to unique categories of markers that form a pipeline of diagnostic offerings. Toronto-based Axela develops research products for sale through life science distributors, and partners with diagnostic companies for clinical tests.
Please note that our current products are for research use only.
At MEDICA 2012, Axela Inc. will be exhibiting in booth H14, Hall 3 as part of the Ontario, Canada pavilion and welcomes researchers, the media, and all other visitors
For further information, visit www.axela.com/ or look us up www.medica.de
You may also contact:
Patrick Castaldi Director of Sales and Channel Management at firstname.lastname@example.com or by calling 1-416-798-1625 x 321
Axela acknowledges the generous support of the Federal Economic Development Agency of Canada