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Staphylococcus Ebooks Catalog
Staph Infection Secrets By Dr. Walinski
Discover a Simple 3-Step Program to Permanently Eradicate Mrsa & Staph Infections Without Using Antibiotics. Here is what's provided in Staph Infection Secrets. Get Rid of Your Staph / Mrsa Infection. Best ways to quickly get rid of the most common conditions caused by Mrsa and Staph, such as: Impetigo, Cellulitis, Folliculitis, Boils / Carbuncles and more. An easy remedy for nasal infections than can completely eradicate the presence of the bacteria in less than 7 days. How to treat internal infections using a naturally occurring powerful antibiotic with a proven success rate. Learn how to get the most out of Western medicine learn what kinds of treatment is available and how to work with your doctor for best results.
Staph Infection Secrets By Dr Walinski Summary
Contents: 82 Pages EBook
Author: Dr. Hubert Walinski
Price: $29.95
My Staph Infection Secrets By Dr Walinski Review
The author presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this book are precise.
When compared to other e-books and paper publications I have read, I consider this to be the bible for this topic. Get this and you will never regret the decision.
Principles of Tapms Method
A typical TAP tag consists of the calmodulin-binding protein (CBP), a tobacco etch virus (TEV) protease cleavage site, and the immunoglobulin G-binding (IgG) units of protein A (ProtA) of Staphylococcus aureus (Fig. 2B). The binding properties of ProtA to IgG-coupled and CBP to calmodulin-coupled sepharose beads permit the capture and purification of low abundant fusion protein complexes by affinity column chromatography.
Hydrogen and 1alkylazoles
Unsubstituted pyrazole shows no antimicrobial activity, but 3-, 4- and or 5-alkyl or phenylpyrazoles 2.01 inhibit Aspergillus niger, 2.004 and Staphylococcus aureus. 2.005 Another highly active compound 2.04 of this series inhibits Bacillus subtilis, Staph. aureus and Piricularia oryzae. 2.025 M.smegmatis k Staph. aureus M.smegmatis k Staph. aureus Staph, aureus
The ATPBinding Cassette Superfamily
In 2006, the multidrug transporter Staphylococcus aureus Sav1866 was determined by X-ray crystallography at 3.0 A resolution in an outward-facing conformation, reflecting the ATP-bound state 88 . Sav1866 belongs to the ABC superfamily and shows sequence similarity to human P-glycoprotein (P-gp). The transporter consists of two subunits, each with a trans-membrane domain-nuclear binding domain (TMD-NBD) topology, with six TMHs in each TMD. The two subunits are twisted and embracing each other, and both the TMDs and NBDs are tightly interacting. Towards the extracellular side, bundles of TMHs diverge into two wings , with each wing consisting of TMH1 and TMH2 from one subunit and TMH3-TMH6 from the other subunit. The crystal structure of Sav1866 indicates that ABC transporters may use an alternating access and release mechanism where ATP binding and hydrolysis control the conversion of one state into the other, and that domain swapping and subunit twisting takes place in the transport...
Historical introduction
Pope (1945) reported that using Staphylococcus aureus and a papain digest medium produced a turbidity-penicillin concentration curve that was considerably steeper than with most other media (unpublished data reported in Garrod and Heatley, 1944). The curve, which was sigmoid in shape, had an unusually long and straight central portion, and by extrapolating this back to the axis representing penicillin concentration, a very high degree of accuracy was obtainable.
Secondary structure base pairing
The base sequence along the chain of a DNA contains the genetic information. Samples of DNA isolated from different tissues of the same species have the same proportions of heterocyclic bases, but the samples from different species often have different proportions of bases. For example, human thymus DNA comprises 30.9 adenine, 29.4 thymine, 19.9 guanine and 19.8 cytosine, while the bacterium Staphylococcus aureus contains 30.8 adenine, 29.2 thymine, 21 guanine and 19 cytosine. In these examples, it is clear that the bases in DNA occur in pairs. Adenine and thymine are usually present in equal amounts so are cytosine and guanine. In the late 1940s, E. Chargaff pointed out these regularities and summarized as follows.
Measurement of response
Hewitt (1975) compared the responses of three instruments to a series of suspensions of Staphylococcus aureus. The organism from an overnight slant was suspended in normal saline, treated with formalin, and diluted to give a suspension having a transmittance of about 50 using a simple absorptiometer at 650 nm (Coleman Junior). This suspension (arbitrarily denoted 100) was further diluted to give a series of suspensions of relative concentrations 20, 40, 60, and 80. The absorbancies of these suspensions were measured using two absorptiometers, the Coleman Junior and a Spectronic 20. The results of this work are shown in Figure 4.1, in which the absorbances are plotted against relative cell concentration (RCC). In both cases, the lines are curved due to deviations from the Beer-Lambert law. Deviations from the law would have been less using instruments with monochro-mators, which give a narrower spread of wavelengths around the peak, that is, a narrower half-band width.
ABCB1ABCC5 Structural Considerations Molecular Modelling Approach
In order to understand the molecular concepts underlying the substrate difference between ABCB1 and ABCC5, we have used the Staphylococcus aureus Sav1866 X-ray crystal structure 88 to construct models of ABCB1 and ABCC5 122 . Modelling indicated that the electrostatic potential surface of the substrate translocation area of ABCB1 is neutral with negative and weakly positive areas, while the electrostatic potential surface of the ABCC5 substrate translocation chamber generally is positive. These results indicate that ABCB1, transporting cationic amphiphilic and lipophilic substrates, has a more neutral substrate translocation chamber than ABCC5, which has a positive chamber transporting organic anions. Structural information about the ABCB1 and ABCC5 substrate binding sites might be useful in the design of inhibitor multidrug efflux by these transporters.
Multidrug Resistance and Antibiotic Treatment
The major mechanism of resistance to tetracycline in Gram-negative bacteria is drug-specific efflux. Drug efflux pumps are involved in fluoro-quinolone resistance of Staphylococcus aureus and Streptococcus pneumo-niae, and the antiseptic resistance of Staphylococcus aureus. When multidrug pumps are overexpressed, resistance levels are elevated. Efflux pumps are thus potential antibacterial targets, since inhibitors of bacterial efflux pumps may restore the activity of an antibiotic which otherwise is effluxed 124 . Structural knowledge at the atomic level from X-ray crystallographic studies of bacterial multidrug transporters is rapidly growing. Examples are the E. coli EmrD 68 , E. coli AcrB 73-78 , E. coli EmrE 82,83 , and Staphylococcus aureus Sav1866 88 crystal structures.
NOTEFor Pseudomonas aeruginosa ATCC 25619 in the assay of Carbenicillin use 05 mL of a 125 dilution of the stock
Preparatory to an assay, remove the growth from a recently grown slant or culture of the organism, with 3 mL of sterile saline TS and sterile glass beads. Inoculate the surface of 250 mL of the agar medium specified for that organism in Table 3 and contained on the flat side of a Roux bottle except in the case of Enterococcus hirae and Staphylococcus aureus (ATCC 9144), which are grown in a liquid medium. Spread the suspension evenly over the surface of the agar with the aid of sterile glass beads, and incubate at the temperature shown for approximately the indicated length of time. At the end of this period, prepare the stock suspension by collecting the surface growth in 50 mL of sterile saline TS, except for Bleomycin (use 50 mL of Medium 34).
Antimicrobial Drugs I
Staphylococcus aureus Staphylococcus epidermidis Streptococcus pyogenee Streptococcus agalactiae Streptococcus pneumoniae Streptococcus faecalis terminal D-alanine of the peptide side chain of one muropeptide is attached to an adjacent polysaccharide either directly or through another short polypeptide chain's e-NH2 group of lysine (as in Staphylococcus areus, Fig. 6-2). The result is a three-dimensional lattice-type structure that envelopes the cell as a net. This net is closed on all sides, making a completely covalent structure. No ionic or hydrogen bonds are involved. This meshwork can be tightly woven (e.g., S. aureus) or be loose (e.g., E. coif), depending on the nature of the cross-linkages. Cell wall structures for gram-positive organisms such as S. aureus are usually less complex than those of gram-negative bacteria. The elucidation of the S. aureus cell wall by Strominger et al. (1967) represented a milestone achievement.
Protein A Quality Attributes Introduction
Protein A is coupled to a resin support in order to create protein A affinity chromatography media commonly used in the manufacturing of recombinant therapeutic monoclonal antibodies. Natural protein A is derived from Staphylococcus aureus and contains five homologous antibody binding regions and a C-terminal region for cell wall attachment. In addition to naturally derived protein A, recombinant material manufactured in Escherichia coli, as well as several engineered versions of the protein, also manufactured recombinantly, have entered the market place. When immobilized on a column, protein A provides a highly efficient and robust purification method for purifying antibodies at various scales. However, protein A ligand from the column can co-elute with the antibody during purification, an effect which is often referred to as protein A leaching. This tendency increases as the chromatography medium ages. Engineered versions of protein A may improve the pH tolerance of the medium, but...
Modifications of the scoring function in FlexX for virtual screening applications
An X-ray structure ofhuman a-thrombin complexed with NAPAP (PDB 63 code ldwd) was chosen as thrombin target structure. All protein atoms within a distance of 8 A, of any NAPAP ligand atom were defined as active site atoms. The water molecule 47 in the P1 pocket was retained as an active site atom. In-house X-ray structures of Staphylococcus aureus DHFR 64 and COX2 were prepared in a similar way. All libraries were docked into the thrombin active site by means of the standard scoring scheme for hydrogen bonds. The WDI and thrombin libraries were also docked using a modified version employing accessibility scaling (vide infra). FlexX default settings were used except for AGrol, which was set to 0.7 kJ mol1. Automatic base placement was used for the WDI, thrombin and COX2 libraries (average execution time per molecule 2 min on an SGI R10K processor). The DHFR library was docked using a fixed placement of the diaminopyrimidine moiety that was taken from the X-ray structure (average...
Standard vs accessibilityscaled Hbond score
It can be concluded that at least for this application, AS H-bond scoring is a significant improvement over the standard scoring scheme. AS H-bond scoring can help to focus the inhibitor search for targets where active site cavities contain a number ofburied donors and acceptors that must be satisfied. It has meanwhile been successfully applied in a number of Roche projects that fulfill these criteria, e.g. p38 MAP kinase and Staphylococcus aureus gyrase B. It might also be useful for the assembly of motif libraries (small, weakly but specifically binding molecules) for SAR by NMR experiments 69-71 .
PsaA Subunit Ia and PsaB Subunit Ib
Which showed that the N terminal sequence of PsaB is just as predicted from the gene except for the N terminal methionine 35 . A similar fragment with the predicted N-terminal sequence of PsaA without the N-terminal methionine has been isolated by using HPLC from a Staphylococcus V8 protease digest of a spinach PsaA PsaB preparation (A. Ohinata, H. Hir-ata, H. Hiraiwa, and T. Hiyama, unpublished results). These results suggest that the N terminal residues of the mature PsaA and PsaB are possibly unprocessed formylmethionine. From these sequences, the molecular weights of these two polypeptides would be calculated as 82,000 to 83,000 with 750 to 800 amino acid residues. These two have some 40 homologies to each other.
Growth promotion test of aerobes anaerobes and fungi
Inoculate portions of fluid thioglycollate medium with a small number (not more than 100 CFU) of the following micro-organisms, using a separate portion of medium for each of the following species of micro-organism Clostridium sporogenes, Pseudomonas aeruginosa, Staphylococcus aureus. Inoculate portions of soya-bean casein digest medium with a small number (not more than 100 CFU) of the following micro-organisms, using a separate portion of medium for each of the following species of micro-organism Aspergillus niger, Bacillus subtilis, Candida albicans. Incubate for not more than 3 days in the case of bacteria and not more than 5 days in the case of fungi.
Antivirals and antibacterials
While the substitution of sulfur for selenium in traditional -lactam antibiotics has been met with limited success,111 113 several selenium-containing heterocyclic compounds, for example 1,3 selenazine 15, have shown strong inhibitory activity against several pathogenic strains including Staphylococcus aureus.1,114 It is interesting to note that the sulfur homologue in this case displayed little analogous activity, indicating the selenium atom was a key factor in their antibacterial properties. A similar result was observed in the anti-mycobacterial activity of seleno-azole derivatives 23 and 24 and the thio-azole analogues.115 Ebselen 1 has also been shown to possess anti-bacterial activity in vitro against S. aureus and it is thought that this activity comes about through the selenium atom interfering with the action of an essential thiol group.116
Formulation Additives Surfactants
The types of microorganisms found in various products are Pseudomonas species (including Pseudomonas aeruginosa), Salmonella species, Staphylococcus aureus, and Escherichia coli. The USP and other pharmacopoeias recommend certain classes of products to be tested for specified microbial contaminants, e.g., natural plant, animal, and some mineral products for the absence of Salmonella species, suspensions for the absence of E. coli, as well as topically administered products for the absence of P. aeruginosa and S. aureus. Emulsions are particularly susceptible to contamination by fungi and yeasts. Consumer use may also result in the introduction of microorganisms. For aqueous-based products, it is therefore mandatory to include a preservative in the formulation to provide further assurance that the product retains its pharmaceutically acceptable characteristics until the patient uses it.
Mechanism Of Action
Classification Cephalosporins are classified by generations. The first-generation cephalosporins (e.g., cephalothin and cefazolin) have good activity against gram-positive bacteria and relatively modest activity against gram-negative microorganisms. Most gram-positive cocci (with the exception of enterococci, methicillin-resistant S. aureus, and S. epidermidis) are susceptible. Most mouth anaerobes are sensitive, but the B. fragilis group is resistant. Second-generation cephalosporins have somewhat increased activity against gram-negative microorganisms but are much less active than the third-generation agents. A subset of second-generation drugs (e.g., cefox-itin, cefotetan, and cefmetazole) also is active against B. fragilis. Third-generation cephalosporins generally are less active than first-generation agents against gram-positive cocci but are much more active against the Enterobacteriaceae, including -lactamase-producing strains. A subset of third-generation agents (e.g.,...
Blactamase Inhibitors
Amoxicillin plus clavulanate is effective for p-lactamase-producing strains of staphylococci, H. influenzae, gonococci, and E. coli. It also is effective in the treatment of acute otitis media in children, sinusitis, animal or human bite wounds, cellulitis, and diabetic foot infections. The addition of clavulanate to ticarcillin (timentin) extends its spectrum to include aerobic gram-negative bacilli, S. aureus, and Bacteroides spp. There is no increased activity against Pseudomonas spp. The combination is especially useful for mixed nosocomial infections and often is used with an aminoglycoside. The dosage should be adjusted in patients with renal insufficiency.
Mechanisms Of Action And Resistance
Teicoplanin inhibits cell-wall synthesis by binding to the d-Ala-d-Ala terminus of cell wall precursor units (Figure 46-4) and is active only against gram-positive bacteria. It is bactericidal against susceptible strains, except for enterococci. It is active against methicillin-susceptible and methicillin-resistant staphylococci, Listeria monocytogenes, Corynebacterium spp., Clostridium spp., and anaerobic gram-positive cocci. Nonviridans and viridans streptococci, S. pneumoniae, and enterococci generally are highly sensitive. Some strains of coagulase-positive and coagulase-negative staphylococci, as well as enterococci and other organisms that are intrinsically resistant to vancomycin, are resistant to teicoplanin. Resistance can emerge in susceptible staphylococci during therapy. The Van A phenotype of vancomycin resistance also confers resistance to teicoplanin by altering the cell-wall target so that the glycopeptide does not bind. Strains of enterococci with Van B resistance...
From Protein Subunit Vaccines to Antibody Treatments of Bacterial Infections
Infectious diseases remain a major threat against human life. Microbial infections are still out of control in many parts of the less developed world where they count for most of the deaths, but also cause an often underestimated toll of death (e.g., community acquired Pneumococcal diseases and Pseudomonas infections in patients in intensive care), life-long mutilation (infertility due to Chlamydia trachomatis), medical complication due to nosocomial infections caused most often by Staphylococcus aureus, Enterococcus faecalis, Klebsiella ssp and fungi. It is estimated that nosocomial infections annually add US 5-10 billion to the cost of the national healthcare system in the United States.1 Apart from infections caused by viruses and protozoa that only in specific instances can The capability of the human immune system to identify and eliminate pathogens and pathogen-infected cells is the cornerstone of immunization, the most effective strategy to prevent infectious disease. However,...
Metal complexes of drugs used as ligands
Two complexes of Pd(II) with diphenylpyraline (DPH) and isothipendyl (IPH), showing anti-serotonin, -histaminic, -convulsant and -fungal activity, of formulae Pd(DPH)2Cl2 and Pd(IPH)Cl2 , were synthesized and studied for their anti-bacterial and -fungal activities against Alternaria alternata, A. tenius, Aspergillus flavus, A. niger, Staphylococcus aureus and E. coli. Their antimicrobial activity was higher than that of the free ligands.20
Title compounds 5.31 have been claimed as bactericides which inhibit Staph. aureus, antimycotics against Candida albicans, and fungicides which control Podosphaera leu-cotricha on apple seedlings, Cercospora spp., and Erysiphe graminis on wheat. 5.146, 5.147, 5.148, 5.149, 5.150, 5.151, 5.152, 5.153, 5.154
Receptor Proteins And Genes In Leukocytes
Binding studies have determined the opioid receptor subtypes bind a wide range of agonists and antagonists with differences in specificity, affinity, and selectivity. Neutralizing antibodies specific for a an N-terminal sequence of the human kappa receptor anti-kR-(33-52) blocks KOR-specific agonist U50,488H-mediated immunosuppression of 1) Staphylococcus aureus Cowen strain I-induced B- and T-lymphocyte proliferation 2) PHA-induced T-lym-phocyte proliferation and 3) S. aureus Cowen strain I-induced IgG synthesis. This suggests that this antibody does not bind to the effector portion of the KOR but inhibits agonist binding, and that the antiserum interacts with a site on the KOR important for ligand binding without intracellular second-messenger system modulation.
Synthetic Antibacterial Agents
Some synthetic anti-bacterial agents have been developed which act on nucleic acid transcription and replication. A family of quinolones and fluoroquinolones including nalidixic acid 6.49 and ciprofloxacin 6.50 have been discovered recently, which bind to DNA gyrase and prevent the coiling of DNA to form its tertiary structure. The widespread appearance of MRSA in hospitals has provided the stimulus for the synthesis of novel anti-bacterial compounds. A new class of antibacterial agents have been developed that contains an oxazolidinone ring and which inhibit protein synthesis in bacteria. These include linezolid 6.51 which was introduced as Zyvoxs in 2001.
Thiolactone Peptides as Antibacterial Peptidomimetics
Biological target Thiolactone peptides are macrocyclic peptides that bind, on the surface of Staphylococcus aureus bacteria, to the accessory gene regulator C. This acts as a receptor for auto-inducing and quorum-sensing peptides produced by the bacteria and regulates the bacterial growth.
Clostridium botulinum ADPribosyltransferase C3
The C3 ADP-ribosyltransferase gene was shown to be located on a DNA bacteriophage together with neurotoxin CI and D (Popoff eta ., 1991 Hauser et al., 1993). Various isoforms of the C3 transferase have C3 isoforms been described (Popoff et al., 1990 Nemoto et al., 1991 Popoff et al., 1991 Moriishi et al., 1991 Moriishi et al., 1993). Whereas the gene for C3 from C. botulinum strain C468 encodes a protein of 211 amino acids (without signal peptide) with a molecular mass of 23546 Da (Popoff et a I., 1990 Popoff etal., 1991), C3 from C. botulinum strain C 003-9 encodes a protein of 204 amino acids with a molecular mass of 23119 Da (Nemoto etal., 1991) showing about 65 identity with the other C3 isoform. Moreover, C3-related transferases are produced by Clostridium limosum (C. limosum exoenzyme) (Just et al., 1992a), Staphylococcus aureus (EDIN epidermal differentiation inhibitor) (Inoue etal., 1991), and Bacillus cereus (8. cereus exoenzyme) (Just et al., 1992b Just etal., 1995). Amino...
Stereoselective Approach to the Axially Chiral Biaryl System the Case of Vancomycin
Vancomycin is a broad spectrum antibacterial, which acts to inhibit the construction of the bacterial cell wall by forming a complex with d-alanyl-d-alanine, required for the synthesis of an essential membrane protein, murein. The antibiotic is administered by infusion and is most commonly used to treat infections with organisms that are resistant to other commonly used antibacterials. Today, this is frequently the case with Gram-positive bacteria such as Staphylococcus aureus.
Antibacterial and Antiparasitic Activity
The binuclear rhodium(II) complexes Rh2(RCOO)2(N-N)2(H2O)2 (RCOO)2, Rh2Cl2(RCOO)2(N-N)2 and Rh2Cl2(MeCOO)(tpy)2 (H3O)Cl2-9H2O (R H, Me, Bu, Ph, PhCHOH N-N 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (dmp) and (dmpq) tpy 2,20 60,200-terpyridine) are effective anti-bacterial agents against Staphylococcus aureus and Escherichia coli. The most active anti-bacterial agents against S. aureus were Rh2(PhCOO)2(phen)2(H2O)2 (PhCOO)2, Rh2 (PhCOO)2(dmpq)2(H2O)2 (PhCOO)2, Rh2(BuCOO)2(phen)2(H2O)2 (BuCOO)2 and Rh2(BuCOO)2(bpy)2(H2O)2 (BuCOO)2. These complexes show rather low activity against E. coli. The most active anti-bacterial agents against E. coli were Rh2(RCOO)2(N-N)2(H2O)2 (RCOO)2 and Rh2Cl2(RCOO)2(N-N)2 (R H and Me). These complexes exhibit low activity against S. aureus. The activity of the complexes Rh2(RCOO)2(N-N)2(H2O)2 (RCOO)2 against E. coli decreases in the series R H ffi CH3 C2H5 C3H7 ffi C4H9. The reverse order was found in the case of S....
And 41HAzol1ylmethyl13dioxolanes
Title compounds inhibit Staphylococcus aureus and Epidermophyton flocco-sum, 6.063 and control Helminthosporium gramineum on wheat grains, Puccinia graminis on wheat, Drechslera graminea on barley, Pyricularia oryzae and Valsa mali. Some also show plant growth inhibiton.
The Sulfonamide Antibacterial Agents
It was known that the sulfamyl (-NHSO2_) group facilitated the binding of dyestuffs to wool protein. Hence, Domagk (1932) investigated the anti-bacterial activity of some dyestuffs including prontosil red 6.12. Unlike today, the primary bioassay included whole animal tests and he was able to show that the compound was active against a Streptococcus infection in mice and a Staphylococcus infection in rabbits. Again unlike today, the compound was rapidly tested in humans where it was shown to control septicaemia in children including Domagk's daughter. It had a significant effect on infant mortality. It was soon realized (1935) that the active compound was a bio-transformation product, sulfanilamide 6.13. However, although this was used as an anti-bacterial agent, it was accompanied by a side effect. The amino group was acetylated in man and the acetate crystallized out in the kidneys. A series of structural modifications were then made to overcome this problem.
Chemical Structure Of Oxytetracycline
Perhaps the most outstanding property of minocycline is its activity toward Gram-positive bacteria, especially staphylococci and streptococci. In fact, minocycline has been effective against staphylococcal strains that are resistant to methicillin and all other tetracyclines, including doxycycline.186 Although it is doubtful that minocycline will replace bactericidal agents for the treatment of life-threatening staphylococcal infections, it may become a useful alternative for the treatment of less serious tissue infections. Minocycline has been recommended for the treatment of chronic bronchitis and other upper respiratory tract infections. Despite its relatively low renal clearance, partially compensated for by high serum and tissue levels, it has been recommended for the treatment of
The Agar Diffusion Assay Its Quantitative Basis
Sterile nutrient agar was poured into a petri dish and allowed to cool and set. Plates were seeded by pouring on a broth culture of the test organism (Staphylococcus aureus). After tilting and shaking the plate to spread the culture it would be left at an angle of 20 to the horizontal to allow the cultures to drain for a short time then the surplus suspension was drawn off. The edge of the plate was marked at the point where the surplus liquid had been drained off. The plates were then dried in an incubator for 1-2 hours. Cylinders of glass or vitreous porcelain were sterilised by dry heat in a petri dish. They were picked from the dish with forceps, then momentarily flamed so that on placing on the agar surface a fluid-tight seal was produced by melting of the agar at the point of contact. Four cylinders were placed on each plate. Test solutions were added to fill the cylinders (although it had been observed that the exact volume seemed to make little difference). Plates were...
O Alcohols And Related Compounds
The antibacterial potencies of the primary alcohols (against test cultures of Staphylococcus aureus) increase with molecular weight until the 8-carbon atom octanol is reached. In general, one oxygen atom is capable of solubi-lizing seven or eight carbon atoms in water. As the primary alcohol chain length increases, van der Waals interactions increase, and the ability to penetrate microbial membranes increases. As water solubility decreases, the apparent antimicrobial potency diminishes with molecular weight. Branching of the alcohol chain decreases antibacterial potency weaker van der Waals forces brought about by branching do not penetrate bacterial cell membranes as efficiently. The isomeric alcohols' potencies decrease in the order primary secondary tertiary. Despite this fact, 2-propanol (isopropyl alcohol) is used commercially instead of n-propyl alcohol, because it is less expensive. Isopropyl alcohol is slightly more active than ethyl alcohol against vegetative bacterial...
Halogenated furanones
Halogenated compounds elatol extracted from the marine red algae Laurencia majuscule elatol has shown activity against the human pathogenic bacteria species Staphylococcus epidermis, Klebsiella pneumonia, and Salmonella, whereas iso-obtusol shown action on K. pneumonia and Salmonella species (Vairappan, 2003). Halogenated furanone isolated from the marine algae Delisea pulchra has shown broad spectrum antibiotic action against the bacterial bio film formation, quorum sensing (QS), and swarming, but the molecular mechanism is completely not elucidated. Studies on action of halogenated furanones on biosynthetic pathway AI-2, which is found in most of the Gram-positive and Gramnegative bacteria and will covalently modify the LuxS enzyme (S-ribo-sylhomocysteine lyase, EC 188.8.131.52) which produces autoinducers-2 (AI-2), thereby showing action on bacterial QS therefore, these furanones can be used for clearing the bacterial films on the ponds and lakes (Zang et al., 2009).
O Historical Background
Sir Alexander Fleming's accidental discovery of the antibacterial properties of penicillin in 19291 is largely credited with initiating the modern antibiotic era. Not until 1938, however, when Florey and Chain introduced penicillin into therapy, did practical medical exploitation of this important discovery begin to be realized. Centuries earlier, humans had learned to use crude preparations empirically for the topical treatment of infections, which we now assume to be effective because of the antibiotic substances present. As early as 500 to 600 bc, molded curd of soybean was used in Chinese folk medicine to treat boils and carbuncles. Moldy cheese had also been used for centuries by Chinese and Ukrainian peasants to treat infected wounds. The discovery by Pasteur and Joubert in 1877 that anthrax bacilli were killed when grown in culture in
O Microbial Resistance
That can attack the same microorganism by different pathways. The diversity of antibiotic structure has proved to be of real clinical value. As the pathogenic cell develops drug resistance, another antibiotic, attacking another metabolic process of the resisting cell, remains effective. The development of new and different antibiotics has been very important in providing the means for treating resistant strains of organisms that previously had been susceptible to an older antibiotic. More recently, the elucidation of biochemical mechanisms of microbial resistance to antibiotics, such as the inactivation of penicillins and cephalosporins by j-lactamase-producing bacteria, has stimulated research in the development of semisynthetic analogs that resist microbial biotransformation. The evolution of nosocomial (hospital-acquired) strains of staphylococci resistant to penicillin and of Gram-negative bacilli (e.g., Pseudomonas and Klebsiella spp., Escherichia coli, and others) often...
Alkenyl and alkinyl1Hazoles and their halogen derivatives
Fitting structure 2.35 with R', R H and R C6H4Cl or C6H3-2,4Cl2 produces compounds with moderate antifungal activity. 2.233 However from similar series, compounds with R Me3C-, R' 2,4-Cl2C6H3CH2-, and R H show strong inhibition of Staphylococcus aureus and Trichophyton mentagrophytes. 2.236 One other example of compounds 2.35 with Az Tr, R 2-(4-chlorophenylethyl)-, R' tert. butyl and R H strongly inhibits Fusarium oxysporum, Phytophthora infestans, and Sclerotium rolfsii. 2.234
Fourthgeneration Cephalosporins
Cefepime and cefpirome (not available in U.S.) are fourth-generation cephalosporins. Cefepime resists hydrolysis by many of the plasmid-encoded f-lactamases. It is a poor inducer of, and is relatively resistant to, chromosomally encoded and some extended-spectrum f-lactamases. Thus, it is active against many Enterobacteriaceae that are resistant to other cephalosporins via induction of f-lactamases but remains susceptible to many bacteria expressing extended-spectrum f-lactamases. Against H. influenzae, N. gonorrhoeae, and N. meningitidis, cefepime has comparable or greater activity than cefotaxime. For P. aeruginosa, cefepime has comparable activity to ceftazidime, although it is less active for other Pseudomonas spp. and X. maltophilia. Cefepime has higher activity than ceftazidime and is comparable to cefotaxime for streptococci and methicillin-sensitive S. aureus. It is inactive against methicillin-resistant S. aureus, penicillin-resistant pneumococci, ente-rococci, B. fragilis,...
Firstgeneration Cephalosporins
Cephalexin has the same antibacterial spectrum as the other first-generation cephalosporins. It is somewhat less active against penicillinase-producing staphylococci. Oral therapy with cephalexin provides peak plasma concentrations adequate to inhibit many gram-positive and gram-negative pathogens. The drug is not metabolized and 70 100 is excreted in the urine.
Cephalosporins General Antimicrobial Spectrum
1st generation gram positive (including Staph aureus) basic gram neg. coverage 2nd generation diminished Staph aureus, improved gram negative coverage compared to 1st generation some with anaerobic coverage 3rd generation further diminished Staph aureus, further improved gram negative coverage compared to 1st & 2nd generation some with Pseudomonal coverage & diminished gram positive coverage 4th generation same as 3rd generation plus coverage against Pseudomonas
Animal Preparation and Surgery
Free rats, it has been the experience of several researchers (D. C. McIntyre, personal communication) that this is no longer the case. Aseptic surgery procedures will reduce greatly the chance of introducing pathogens during surgery. Pathogens, such as Staphylococcus epidermitis, are known to be associated with disintegration of the skull surface and increased loss of headcaps. Given the prolonged duration of many kindling experiments, it is critical that the integrity of the skull be maintained for an extended period. Use of gloves and mask, as well as application of a penicillin G solution (personal observation) onto the cranial surface prior to the drilling of electrode holes are important to reduce or prevent the likelihood of postsurgical infections.
Colloidal Silver Dictionary
Gastroenteritis An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species consumption of irritating food or drink or psychological factors such as anger, stress, and fear. Called also enterogastritis. EU
Antibacterial Activity
Erythromycin usually is bacteriostatic. It is most active in vitro against aerobic gram-positive cocci and bacilli. Cross-resistance is complete. The prevalence of macrolide resistance among group A streptococcal isolates is related to consumption of macrolide antibiotics within the population. Only 5 of penicillin-susceptible strains are macrolide-resistant, whereas 50 or more of penicillin-resistant strains may be macrolide-resistant. Staphylococci are not reliably sensitive to erythro-mycin. Macrolide-resistant strains of S. aureus are potentially also resistant to clindamycin and streptogramin B (quinupristin). Gram-positive bacilli are sensitive to erythromycin, including Clostridium perfringens, Corynebacterium diphtheriae, and Listeria monocytogenes. Clarithromycin is slightly more potent than erythromycin against sensitive strains of streptococci and staphylococci and has modest activity against H. influenzae and N. gonorrhoeae. Clarithromycin has good activity against M....
Test Organisms
Use cultures of the following microorganisms1 Candida albicans (ATCC No. 10231), Aspergillus niger (ATCC No. 16404), Escherichia coli (ATCC No. 8739), Pseudomonas aeruginosa (ATCC No. 9027), and Staphylococcus aureus (ATCC No. 6538). The viable microorganisms used in the test must not be more than five passages removed from the original ATCC culture. For purposes of the test, one passage is defined as the transfer of organisms from an established culture to fresh medium. All transfers are counted. In the case of organisms maintained by seed-lot techniques, each cycle of freezing, thawing, and revival in fresh medium is taken as one transfer. A seed-stock technique should be used for long-term storage of cultures. Cultures received from the ATCC should be resuscitated according to directions. If grown in broth, the cells are pelleted by centrifugation. Resuspend in 1 20th the volume of fresh maintenance broth, and add an equal volume of 20 (v v in water) sterile glycerol. Cells grown...
Crude extracts, purified diverse phlorotannins (phloroglucinol, eckol, phlorofucofuroeckol A, dieckol and 8.8'-beckol) extracted from brown algae, Ecklonia kurome tested on multiresistant Staphylococcus aureus and foodborne pathogens exhibited the antibacterial activity on Grampositive bacteria, S. aureus, B. Cereus and Gram-negative bacteria C. jejuni, E. coli, S. Enteritidis, S. typhimurium, V. parahaemolyticus (Nagayama et al., 2002). Antibacterial mechanism of action of phlorotannins is not precisely known but one study supports that it may be due to the interaction of phlorotannins with the bacterial proteins and enzymes which will result in the bactericidal action. The toxicity of phlorotannins was evaluated by the studies on the mice and it found to be safe without causing toxicity to the animals, moreover in some parts of Japan, it is consumed as food so that this can be used as food supplement or drug for the treatment (Gopal et al., 2008 Schulz et al., 1992).
Inoculate portions of Alternative Fluid Thioglycollate Medium with a small number (not more than 100 cfu) of Clostridium sporogenes.4- Inoculate portions of Soybean-Casein Digest Medium with a small number (not more than 100 cfu) of the following microorganisms, using a separate portion of medium for each of the following species of microorganism Aspergillus niger, Bacillus subtilis, and Candida albicans. Incubate for not more than 3 days in the case of bacteria and not more than 5 days in the case of fungi.
Recent data indicate that garlic may be an effective treatment against methicillin-resistant Staphylococcus aureus (MRSA) infection. In a study using mice, investigators demonstrated that the garlic extracts, diallyl sulfide and diallyl disulfide, showed protective qualities against MRSA infection. Such conclusions, coupled with further investigation, may result in the use of such extracts in MRSA infection treatment (Tsao et al. 2003).
Drug Resistance
Drug resistance is an issue of great concern in medicine. The rise of drug-resistant strains gives antibiotics and antivirals a limited useful life. In order to slow the emergence of drug-resistant strains, physicians are encouraged to prescribe these treatments sparingly. Of even greater concern is the emergence of multidrug-resistant strains of some particularly virulent pathogens, such as multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA).
One unusual therapeutic suggestion utilizing manganese as a remedy is for acute atopic dermatitis.57 Historically, balneotherapy or bathing in hot springs was used in the treatment for leprosy and syphilis in Japan. This bathing has been shown to be effective for patients with acute atopic dermatitis, who exhibit exacerbations associated with increased density of Staphylococcus aureus. The bactericidal activity of the water, as determined by growth of bacteria on soybean casein digest agar plates, was due to the presence of manganese and iodide ions at the pH and concentration found in the hot baths.
Protein A
Protein A is derived from Staphylococcus aureus. The structure is composed of a single polypeptide chain containing four IgG binding domains. With the exception of IgG3, all other human IgGs bind to protein A. Each molecule of Protein A is capable of binding two IgG molecules. It is manufactured as a bulk solution at a concentration of greater than 20 mg Protein A is a component of the cell wall of Staphylococcus aureus. Recombinant Protein A (rProtein A) consists of five homologous immunoglobulin (IgG) binding domains (E, D, A, B, C) followed by a partial X domain sequence. It is expressed in Escherichia coli and purified via a column chromatography process. IgG columns are not used in the purification process. It is manufactured as a bulk solution with an IgG-binding potency greater than 95 . Release testing methods and specifications are described below. Because rProtein A is used as an ancillary material in the manufacture of recombinant therapeutic drugs, regulatory requirements...
Bacitracin is available in ophthalmic and dermatologic ointments the antibiotic also is available as a powder for the preparation of topical solutions. The ointments are applied directly to the involved surface one or more times daily. A number of topical preparations of bacitracin, to which neomycin or polymyxin or both have been added, are available, and some contain the three antibi-oticsplus hydrocortisone. For open infections such as infected eczema and infected dermal ulcers, the local application of the antibiotic may be of some help in eradicating sensitive bacteria. Bac-itracin rarely produces hypersensitivity. Suppurative conjunctivitis and infected corneal ulcer respond well to the topical use of bacitracin when caused by susceptible bacteria. Bacitracin has been used with limited success for eradication of nasal carriage of staphylococci. Oral bacitracin has been used with some success for the treatment of antibiotic-associated diarrhea caused by C. difficile. Serious...
Protein Scaffolds
Scaffold libraries have been created for several applications in affinity chromatography, or for the generation of ligands to disease-related targets. The most developed scaffold is a two alpha helix-containing variant of protein A from Staphylococcus, protein Z. so called 'Affi-bodies' 44 , showing selective binding to respiratory syncytial virus (RSV) G protein, have been selected 45 . Some libraries have been used for the transfer of bioactive peptides or functional residues from one protein to a new protein scaffold. In our laboratory, human cy-totoxic T lymphocyte associated protein-4 (CTLA-4) has been used as a protein scaffold to display the 14mer somatostatin hormone, or RGD sequence-containing peptides. This has produced a series of ligands to the somatostatin receptor and av 3 integrin respectively, the
Other Biosurfactants
Precursors and degeneration products of sphingolipids biosurfactants were found to inhibit the interaction of Streptococcus mitis with buccal epithelial cells and of Staphylococcus aureus with nasal mucosal cells.101 Gram-positive Bacilluspumilis cells were found to produce pumilacidin A, B, C, D, E, F and G which exhibited antiviral activity against herpes simplex virus 1 (HSV-1), inhibitory activity against H+, K+-ATPase and were found to be protective against gastric ulcers44 probably through inhibiting microbial activity contributing to these ulcers.
LPS stimulation, decreased the expression of TNF-a in murine macrophages. This effect was reversible by naloxone and dose dependent, indicating an opioid receptor stimulation event. Despite evidence leading to a direct effect, suppression of the sympathetic nervous system blocks morphine's inhibitory results 88 . Staphylococcus aureus, Cowen strain I (SAC) induced inhibition of IL-6 production in intact PBMCs 89 . The inhibitory affects of opioids also affect the production of nitric oxide (NO) by macrophages as well. Among the many biological activities of NO, limiting the proliferative response of lymphocytes is critical to immune function. Acute central administration of morphine or the mu-selective agonist DAMGO is followed by an increase in production of NO in macrophages leading to suppression of T-cell proliferation in vivo 90 . Conversely, the mu receptor agonist DAGO and morphine inhibited NO production in murine macrophages before LPS induction in vitro. However, morphine...
Other Antibiotics
Some antibiotics produced by Streptomycetes, block protein synthesis in bacteria by binding to various units of the ribosome. Thus chloro-tetracycline (aureomycin) 6.46, isolated from S. aureofaciens in 1945, inhibits protein synthesis by binding to the 30S sub-unit of the ribosome. This prevents the aminoacyl tRNA from binding to the ribosome. It was introduced in 1948 and its structure was established in 1952. Chloramphenicol 6.47 and erythromycin 6.48 also affect the bacterial ribosomes. They bind to the 50S subunit and prevent the translocation of peptide groups. Erythromycin 6.48 is an example of a macrolide antibiotic, so called because it possesses a large ring lactone. A complex antibiotic, vancomycin, was isolated from S. orientalis in the mid-1950s. Although this antibiotic targets the bacterial cell wall, it does so in a different way to the penicillins. It is a valuable antibiotic because it is active against penicillin resistant strains of Staphylococci and it can be used...
Biological Activity
Alpha-toxin from Staphylococcus aureus (strain Wood 46, ATCC 10832, DSM 20491) was kindly provided by S. Bhakdi, Institut f r Medizinische Mikrobiologie und Hygiene, Johannes Gutenberg Universit t, Mainz, Germany. The toxin can be easily purified from the culture supernatant (Lind et al., 1987 Palmer et al., 1994). The purified toxin can be lyophilized or if necessary dialyzed against an intracellular buffer (see below). Dissolved alpha-toxin can be stored in aliquots at -20 C for months without loss of activity.
Wound inflammation
Chronic wounds are an important problem worldwide. These wounds are characterized by a persistent inflammatory stage associated with excessive accumulation and elevated cell activity of neutrophils, suggesting that there must be a persistent stimulus that attracts and recruits neutrophils of the wound. The cellular inflammatory response against the bacteria in the chronic wounds, the amount of neutrophils accumulated at the site of infection, was evaluated through differential neutrophil counting on the tissue sections from wounds containing either P. aeruginosa or Staphylococcus aureus. Such bacteria are morphologically and physiologically different from free-living planktonic bacteria and have been implicated in numerous chronic infections ranging from cystic fibrosis to prostatitis (Costerton et al., 1995, 1999). The existence of biofilms in an acute partial-thickness wound (Serralta et al., 2001) and in chronic human wounds (Bello et al., 2001) has been documented.
Infectious diseases of the skin, eyelids, conjunctivae, and lacrimal excretory system are encountered regularly in clinical practice. Periocular skin infections are divided into preseptal and post-septal or orbital cellulitis. Depending on the clinical setting (i.e., preceding trauma, sinusitis, age of patient, relative immunocompromised state), oral or parenteral antibiotics are administered. Dacryoadenitis, an infection of the lacrimal gland, is most common in children and young adults. It may be bacterial (typically Staphylococcus aureus, Streptococcus species) or viral (most commonly seen in mumps, infectious mononucleosis, influenza, and herpes zoster). In infants and children, the disease usually is unilateral and secondary to an obstruction of the nasolacrimal duct. In adults, dacryocystitis and canalicular infections may be caused by S. aureus, Streptococcus species, Diphtheroids, Candida species, and Actinomyces israelii. Any discharge from the lacrimal sac should be sent for...
Rifampin (Rifadin, Rimactane, Rifampicin) is the most active agent in clinical use for the treatment of tuberculosis. A dosage of as little as 5 g mL is effective against sensitive strains of m. tuberculosis. Rifampin is also highly active against staphylococci and Neisseria, Haemophilus, Legionella, and Chlamydia spp. Gram-negative bacilli are much less sensitive to rifampin. However, resistance to rifampin develops rapidly in most species of bacteria, including the tubercle bacillus. Consequently, rifampin is used only in combination with other antitubercular drugs, and it is ordinarily not recommended for the treatment of other Other, nonlabeled uses of rifampin include the treatment of serious infections such as endocarditis and osteomyelitis caused by methicillin-resistant s. aureus or s. epidermidis, Legionnaires disease when resistant to erythromycin, and prophylaxis of H. influenzae-induced meningitis.
O Polypeptides
The isolation of the glycopeptide antibiotic vancomycin (Vancocin, Vancoled) from Streptomyces orientalis (renamed A. orientalis) was described in 1956 by McCormick et al.232 The organism originally was obtained from cultures of an Indonesian soil sample and subsequently has been obtained from Indian soil. Vancomycin was introduced in 1958 as an antibiotic active against Gram-positive cocci, particularly streptococci, staphylococci, and pneumococci. It is not active against Gram-negative bacteria, with the exception of Neisseria spp. Vancomycin is recommended for use when infections fail to respond to treatment with the more common antibiotics or when the infection is known to be caused by a resistant organism. It is particularly effective for the treatment of endocarditis caused by Gram-positive bacteria. Vancomycin hydrochloride is always administered intravenously (never intramuscularly), either by slow injection or by continuous infusion, for the treatment of systemic infections....
Methicillin-susceptible strains of S. aureus usually are susceptible to clindamycin, but methicillin-resistant strains of S. aureus and coagulase-negative staphylococci frequently are resistant. antibacterial activity Quinupristin dalfopristin is active against gram-positive cocci and organisms responsible for atypical pneumonia (e.g., M. pneumoniae, Legionella spp., and Chlamydia pneumoniae), but largely inactive against gram-negative organisms. The combination is bactericidal against streptococci and many strains of staphylococci, but bacteriostatic against E. faecium. resistance Resistance to quinupristin is mediated by genes encoding a ribosomal methy-lase that prevents binding of drug to its target or encoding lactonases that inactivate type B strep-togramins. Resistance to dalfopristin is mediated by genes that encode acetyltransferases, which inactivate type A streptogramins, or by staphylococcal genes that encode ATP-binding efflux proteins that pump type A...
Surfactins were quite different from similar molecules reported earlier26 and thus production of various isoforms not only depends on the culture conditions but also on the bacterial strain. These variations in molecular structures may confer certain bioactive properties to these molecules. Recently we reported a marine Bacillus circulans that was isolated from sea water sample from Andaman and Nicobar Islands. The crude lipopeptide biosurfactants obtained from this culture was resolved into six major fractions using RP-HPLC. Only one of these fractions was found to possess profound antimicrobial action against various Gram-positive and Gram-negative bacterial strains. Mild antimicrobial action was also shown against multi-drug resistant Staphylococcus aureus (MRSA) and other MDR strains.8 The biosurfactants from this strain also increased the bioavailability of hydrophobic polyaromatic hydrocarbons (PAH) such as anthracene and facilitated their biodegradation.28 Similar lipopeptide...
Othe penicillins
Because the penicillin first used in chemotherapy was not a pure compound and exhibited varying activity among samples, it was necessary to evaluate it by microbiological assay. The procedure for assay was developed at Oxford, England, and the value became known as the Oxford unit 1 Oxford unit is defined as the smallest amount of penicillin that will inhibit, in vitro, the growth of a strain of Staphylococcus in 50 mL of culture medium under specified conditions. Now that pure crystalline penicillin is available, the United States Pharmacopoeia (USP) defines unit as the antibiotic activity of 0.6 g of penicillin G sodium reference standard. The weight-unit relationship of the penicillins varies with the acyl substituent and with the salt formed of the free acid 1 mg of penicillin G sodium is equivalent to 1,667 units, 1 mg of penicillin G procaine is equivalent to 1,009 units, and 1 mg of penicillin G potassium is equivalent to 1,530 units.
It combines good skin penetration with broad-spectrum activity against dermatophytes, yeasts, 2.367 Aspergillus, Malassezia furfur, and inhibits Corynebacte-rium minutissimum, Staphylococci, Streptococci which all may accompany myco-tic infections. In the treatment of tinea infections and cutaneous candidiasis of skin and mucous membranes such as vaginal candidiasis, clotrimazole can be used as a single dose. 2.366
Newer Carbapenems
The extended spectrum of antibacterial activity associated with the carbapenems together with their resistance to inac-tivation by most S-lactamases make this class of S-lactams an attractive target for drug development. In the design of new carbapenems, structural variations are being investigated with the objective of developing analogs with advantages over imipenem. Improvements that are particularly desired include stability to hydrolysis catalyzed by DHP-I,62 stability to bacterial metallo-jS-lactamases ( carbapene-mases )56 that hydrolyze imipenem, activity against MRSA,31 and increased potency against P. aeruginosa, especially imipenem-resistant strains. Enhanced pharmacokinetic properties, such as oral bioavailability and a longer duration of action, have heretofore received little emphasis in car-bapenem analog design. Meropenem is a second-generation carbapenem that, to date, has undergone the most extensive clinical evaluation.66 It has recently been approved as Merrem for...
Diabetic foot ulcer
A diabetic foot ulcer is an excellent example of a chronic wound that responds well to management using biofilm principles (Dowd et al., 2008). Bacteria within biofilms have been reported to be up to 500 times more resistant to antibiotics than planktonic (unattached, freely living) cells (Donlan, 2001 Donlan and Costerton, 2002). Most of the chronic wound pathogens, such a methicillin-resistant S. aureus (MRSA) and Pseudomonas
O Newer Antibiotics
Tigecycline is recommended for the treatment of complicated skin and skin structure infections caused by E. coli, E. faecalis (vancomycin-susceptible isolates), S. aureus (methicillin-susceptible and methicillin-resistant isolates), S. pyogenes, and B. fragilis among others. Tigecycline is also indicated for complicated intra-abdominal infections caused by strains of Clostridium, Enterobacter, Klebsiella, and Bacteroides. To reduce the development of resistance to tigecycline, it is recommended that this antibiotic be used only for those infections caused by proven susceptible bacteria. Ertapenem is indicated for the treatment of moderate to severe infections caused by susceptible strains causing complicated intra-abdominal infections such as Escherichia, Clostridium, Peptostreptococcus, and Bacteroides. The antibiotic is also indicated for complicated skin and skin structure infections including diabetic foot infections (without osteomyelitis). Treatable strains include...
Mupirocin (bactroban) is active against many gram-positive and selected gram-negative bacteria. It has good activity against S. pyogenes and methicillin-susceptible and methicillin-resistant strains of S. aureus. It is bactericidal at concentrations achieved with topical application.
Penicillinase-producing strains), and Listeria are all susceptible. Although some strains of methicillin-resistant staphylococci are susceptible, many are not. Activity is excellent against the Enterobacteriaceae, including organisms that are cephalosporin-resistant by virtue of expression of extended-spectrum b-lactamases. Most strains of Pseudomonas and Acinetobac-ter are inhibited. Anaerobes, including B. fragilis, are highly susceptible.
Therapeutic Uses
Teicoplanin has been used to treat a wide variety of infections, including osteomyelitis and endocarditis, caused by methicillin-resistant and methicillin-susceptible staphylococci, streptococci, and enterococci. Teicoplanin generally is comparable to vancomycin in efficacy, except for treatment failures from low doses used for such serious infections as endocarditis. Teicoplanin is not as efficacious as antistaphylococcal penicillins for treating bacteremia and endocarditis caused by methicillin-susceptible S. aureus (cure rates of 60 70 vs. 85 90 for the penicillins). The efficacy of teicoplanin against S. aureus may be improved by adding an aminoglycoside (e.g., gentamicin) to provide a synergistic effect. Strains of streptococci are uniformly susceptible to teicoplanin. This drug has been very effective in a once-daily regimen for patients with strepto-coccal osteomyelitis or endocarditis. Teicoplanin is among the most active drugs against entero-cocci and apparently is effective,...


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Optional Purchased 1 Year Extended Warranty
There are a number of reasons why a plant can perish, which is why we offer a 1-year, one-time Replacement Warranty (shipping costs not included) available for purchase at the time of checkout.
The 1 Year Warranty is 15% of the total cost of your plants (excluding gardening supplies, tax and shipping).
To claim your warranty we require a photo to verify that your plant is in fact perished. Once we receive your picture we will promptly send you a 100% store credit for the amount of that plant.
Note: Shipping costs for the replacement plant are at the customer's expense.
Warranty must be purchased at the time of checkout and cannot be added after your order has been completed. Plants purchased must be within our zone recommendations and must be planted in the ground; we cannot warranty plants in planters.

subset: commoncrawl


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This all over lace halter tank is in a gorgeous light apricot color. This is a two piece tank with a cami insert and lace tank overlay. This top runs small, we recommend sizing up.
Model is 5 6" 125lbs wearing a size Medium
This open back oversized sweater is both soft and fashionable. Pair with your choice of bottoms and enjoy a look that is effortlessly comfortable and cute.
100% Viscose
Model is 5 6" 125lbs wearing a size Small/Medium
This tie front jumpsuit is a fashion forward head turning show stopper!
Model is 5 6" 125lbs wearing a size Small
This V Neck romper is a sure showstopper featuring a tie around waist and its super trendy striped pattern. We recommend sizing up as this piece runs small.
Model is 5 6" 125lbs wearing a size Medium
This short sleeved floral maxi dress is delicate and flowy. It brings softness to your look but still makes a loud fashion statement.
This ruffled babydoll tank has a sheer crochet back detail that makes it a must have for your wardrobe.
100% Cotton. Contains: 100% cotton Lining: 100% Cotton
In celebration of the launch of our online boutique we are offering 10% off to our first 100 customers!!
Use code: WELCOME100 at checkout to receive your discount!


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Taekwon-Do is a version of an ancient form of unarmed combat practised for many centuries in the Orient. Taekwon-Do became perfected in its present form in Korea.
Taekwon-Do was officially founded in Seoul, South Korea by Major General Choi Hong Hi 9th DAN in 1955
Although a relatively new martial art, modern Taekwon-Do is based on the Korean arts of Soo-Bak & Taek Kyon, and these arts date back over 2000 years. The best hand techniques from Japanese & Okinawan systems were also added to the spectacular foot techniques of the indigenous Korean arts to make one of the most effective & dynamic martial arts in the world.
Consisting of around 3,500 techniques, Taekwon-Do teaches the student to employ the hands and feet as tools of personal protection.
ITF Taekwon-Do teaches scientific principles allowing the students to develop tremendous power with minimum effort, thus allowing a small person to defend themselves against a larger, stronger aggressor.
The Tenets of Taekwon-Do
Taekwon-Do places equal emphasis on the importance of spiritual as well as physical training. All the years of hard training would mean nothing without the proper adherence to modesty and propriety - which are the very essence of oriental philosophy.
Students are encouraged to go beyond the technical aspects of the art and establish a lifestyle based on a solid code of morality.
Taekwon-Do is more than just the effective use of attacking & defensive techniques, true martial arts also enrich the spirit, calm the ego and create a strong sense of morality that will benefit the student, their friends & family for the rest of their lives.
Click here to book a half price unlimited 30-day membership for only £15 per person!
© 2019 Universal Martial Arts.


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이탈리아의 겨울용 타이어(Winter Tire) 시장에 대해 업계의 다수 전문가로부터 얻은 데이터, 정보와 함께 시장 성장 촉진요인, 시장이 해결해야 할 과제, 시장 동향, 시장 경쟁 상황의 상세한 분석을 바탕으로 현재 시장 시나리오 분석 및 2015-2019년 시장 예측을 전해드립니다.
Winter tires, also referred to as snow tires, cold weather tires, and thermal tires, improve the road safety for vehicles during winter, and thus play an important role in reducing road accidents. These tires are made of soft rubber compared to the all-season or summer tires, which help achieve better grip during winters. Furthermore, the newer generation of winter tires is designed with a more flexible rubber compound that is less prone to stiffening in colder temperatures. Its tread is designed to provide improved traction on wet, slushy, snowy, icy, and dry cold surfaces. Winter tires are fitted in sets of four, because fitting only a pair affects the balance and stability of the automobile. Winter tires are of three types: performance, studded, and non-studded.
TechNavio's analysts forecast the winter tire market in Italy to grow at a CAGR of 1.11 percent over the period 2014-2019.
This report covers the present scenario and the growth prospects of the winter tire market in Italy for the period 2015-2019. Forecasts and analysis of the market have been done in terms of volume. The market size is calculated on the basis of the unit sales of winter tires in Italy. The market includes the following segments:
TechNavio's report, Winter Tire Market in Italy 2015-2019, has been prepared based on an in-depth market analysis with inputs from industry experts. It covers the market landscape and its growth prospects in the coming years. The report also includes a discussion of the key vendors operating in this market.


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Ah, J Dilla. His influence and production style brought forth beat-makers carrying their backpacks filled with treasures from the basement into the mainstream. Even more so after his death. A cult-like following surrounds his legacy. Born James Dewitt Yancey in February 1974, Dilla grew up in Detroit and made his mark crafting beats for our favorite rappers and singers, giving new meaning to the word "donut." It's Dilla Day all over the hip-hop world, and today, Sounds of Blackness salutes the man and the music.
The list of artists J Dilla has worked with is pages long, from A Tribe Called Quest and the Pharcyde to Common and the Roots. The MCs whose gruff vocals he so elegantly made melodic range from Busta Rhymes to Talib Kweli. Dilla's freedom in music is the underlying current keeping his legacy alive through producers like Flying Lotus, Madlib and Exile, as well as MCs like Blu and combination talents like J-Live.
Of his countless contributions, one of the most compelling can be heard on Erykah Badu's "Didn't Cha Know," from her sophomore album, Mama's Gun. Flipping a sample of Tarika Blue's "Dreamflower," Dilla's production gave Badu's voice a trance-like quality.
Later, Badu wrote the song "Telephone" after a conversation with Dilla's mom, who revealed that the producer said he was receiving a message from Ol' Dirty Bastard in a dream prior to his death.
Long before he passed, Dilla maintained a swelling constituency of backpackers, headwrapped hip-hoppers and tons of beat nerds who followed his life and his shows wherever he would touch down. Early rumors of his illness circulating among the underground constituency of his fans were later confirmed when he performed in Europe from a wheelchair.
J Dilla released Donuts on Stonesthrow Records three days before he passed. His repertoire and unmistakable style is reinvented every day through beatmakers all over the world. On days like today, many remember the man, and everyone remembers the music. A hip-hop enthusiast with boom-bap appeal and an appreciation of music that carried him through the ages, Jay Dee was a genius, and we are all better for his contributions. Check Raekwon's DIlla joint, "House of Flying Daggers," below.
And, of course, who can forget Slum Village's "Fall in Love"?
February has traditionally been the month when the contributions, traditions and historical facts about African-Americans are celebrated the most. In honor of Black History Month, Backbeat will be celebrating iconic figures in the world of black music.
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To honor Franco Buzzis memory, Buzzi Unicem has developed an initiative that could reflect things that Franco loved: the company, to which he dedicated his life; brilliant young people, who could represent the companys future nourishment; the USA and in particular Texas.
This is why Buzzi Unicem will award every year, on a continuing basis, a scholarship that will provide the employees sons and daughters with the unique opportunity to attend a Master in Business and Administration at the prestigious McCombs School of Business - University of Texas, at Austin.
We chose one of the best schools in the USA: it ranks #15 in US News 2014 Best Business School ranking and #20 as for selectiveness, as it only accepts 24% of applicants. Austin is a vibrant, friendly city, with a high quality of life and a dynamic business ecosystem.
The program we selected is a 2-year, full-time MBA, that Buzzi Unicem will fully fund, thus covering not only tuition and fees, but also standard ancillary costs (travel, insurance, living costs ). All employees sons and daughters, from all of the groups countries, can apply. They must meet the requirements set by the Business Schools admissions criteria, regarding age, bachelors degree, work experience, English proficiency and analytical skills.
Transparency and meritocracy are key to us, so Buzzi Unicem cannot interfere, in any way, with the valuation and selection process, that will be managed in full by the University of Texas. The only way to submit the application is online, on the schools website. Once the selection phase is ultimate, the first endowed student will attend the MBA program according to the university schedule.
As a company, we are proud to launch this project. We know for sure that this could be a turnaround opportunity for focused, committed people. And we like to think of Franco as a significant part of this growth process, too.


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Are your Newfoil Machines in need of a service?
Find your local Worldwide Agent
Contact your local agent for details.
To find your local agent, click on "Agent Links"
or Please Contact Us
By always providing genuine and original parts, reliability and cost-effectiveness are assured. Newfoil Machines' policy of total customer support provides real value for money. Cost of ownership is a crucial factor for the operator and Newfoil Machines fully recognises this by offering parts at competitive prices together with a complete back-up service.
Section 16 – Troubleshooting X-500 Series machines
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Venturi Tube Principle
flow element used to create a pressure change by accelerating a fluid stream is the venturi tube: a pipe purposefully narrowed to create a region of low pressure. As shown previously, venturi tubes are not the only structure capable of producing a flow-dependent pressure drop. You should keep...Continue reading »


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Participate in our next TrailBlazing Volunteer Training on Saturday, November 16th. Click here for more info.
We are a Field of Interest fund formed under the guidance of the Community Foundation for the Greater Capital Region. Youth2 has been created to engage young people to think about issues that they care about and to create volunteer or social action projects for youth and by youth. Youth2 is committed to giving financial and thoughtful organizational support to help interested young people turn their ideas into realities.
- Do you want to design your own volunteer project?
- Do you want to be able to make a difference in the lives of youth in your own community or in the world?
- Do you want to reach more people, but need matching funds to begin?
- Did you ever wonder about how to get your project started?
YouthSquared Participates in "March for our Lives" on March 2018
July 2018 15th Anniversary Gala – Recap & Images!
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Youth2 can help you! How can you get involved?
- Learn how to write a grant
- Tell a friend about us
- Attend and support another person's social action project
- Become an Advisory Council Member
- Invite a Youth2 Advisory Council member to come and speak to your group or Organization
- Give part of your babysitting money, or part of your birthday gifts as a Donation to Youth2
- Tell your club leader about us
- Get involved in a volunteer job by looking through the Book of Good Deeds, our collection of volunteer opportunities for youth
- Add your organization to the Book of Good Deeds
- Help out with events.


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Legendary turntablist and Beat Junkies member J Rocc combines two music icons – J Dilla and Michael Jackson – to form "Dil Jackson" and releases a couple of mashups on Soundcloud.
It's the kind of unofficial fantasy collaboration everyone wanted and it took J Rocc to put it all together. As part of J Dilla Month, the Beat Junkies deejay threw together a couple of Dil Jackson tracks – a combination of J Dilla beats and Michael Jackson acapellas. On this occassion, J Rocc chose Michael Jackson's Beat It and Another Part Of Me for the vocals and used a couple of instrumentals that some Dilla fans will already know. The result is literally a match made in heaven and will surely gas fans of both camps (and we're pretty sure those camps cross over for most of you).
What Dil Jackson combos do you think would work well and why? Stream the tracks below and let us know in the comments.
(via Okayplayer)


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I was contacted by the great people at the Yale Heart Study to post a link so that you can help them gather research on your experiences. Please take some time to help them out here. or the link on the right side.
1 thought on "Yale Heart Study"
Hi Eric, thanks for a wonderful blog. I just spent 2 hours reading all the articles and taking the Yale Heart Study. It's been cathartic for me. I found your site after searching for "i had a heart attack at 36", because I did this past December while on vacation and had a stent installed. I just started cardiac rehab this week, and have been feeling 'off' despite all the good news I have on my health. Someone told me this in the beginning, but it finally clicked here for me while reading all of this… Despite being very supported by my wife, co-workers and friends I've gone through this alone, mainly because an active 36 year old isn't the prime demographic of those that have heart disease and heart attacks. I haven't found a lot to relate to until now. Thanks.


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Friday, October 30, 2015
Thanks for all you do
18 comments:
- Replies
Thank you, Jean!!!Delete
very nice Wanda. Have a great dayReplyDeleteReplies
Thank you, Yogi!!!Delete
Very pretty - love the big vibrant leaf especially.ReplyDeleteReplies
Thank you, Diana!!! Yep, I like that one best too :)Delete
Both cards show the simplicity of our craft in perfect sinc. You do beautiful work with and without the layers and frills. I love your style and you are always an inspiration.ReplyDeleteReplies
Thanks so much, Coleen!!!Delete
Really lovely cards Wanda.ReplyDelete
Beautiful job on these. My favorite is the first card. Well done.ReplyDeleteReplies
Thank you, Jean!!! Mine too!!!Delete
Both cards are very pretty! TFSReplyDeleteReplies
Thank you, Jutta!!!!Delete
These are simply wonderful! Love the elegance and the bright, vibrant colors! Great job! Thanks for being such a wonderful artist and friend.ReplyDeleteReplies
Thank you, Tea!!! YOU are the wonderful friend!!!Delete
Wow....gorgeous cards!ReplyDeleteReplies
Thank you, Yvonne!!!!Delete


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Zweeler Winners!
Europa League (Teams) 6 - 2
- kris-boys: € 63,50
- passioneel: € 43,66
- Dilligaf: € 40,75
- RacingTOM: € 35,72
- dove18: € 27,79
- haboka: € 22,68
Main content
Game rulesBACK TO GAME
Before you can participate to this game, you need to be registered with Zweeler Ltd. Once registered for one of the games, you can play them all!!
After registration you can start creating your team(s). The teams can be submitted and changed until the start of the game on Friday 21 June 2019 22:00 hours.
You have a 52 million budget to buy 8 football teams of which you think are going to win the most points in the Africa Cup of Nations (Teams) Round 1 - 1.
Your teams can score points in different ways. A team can get 100 points for winning a match and 50 points for a draw. In addition there are multiple statistics which can earn you extra points or negative points. Like the number of goals, goal attempts, corners, percentage of ball possession, goalkeeper saves, penalty saves and clean sheets. Negative points can be earned with fouls, yellow cards and red cards. Please check "The Points" table for more details.
An example: England plays against Germany and wins this match with 3-1. England will receive 100 points for a win and 3 x 20 points = 60 points for the goals. 160 points in total. England will not get points for a clean sheet. The rest of the statistics for England are: 11 goal attempts (22 points), 7 corners (21 points), 6 goalkeeper saves (24 points), 57 procent ball possession (0 points), 21 fouls (-21 points) and 3 yellow cards is -15 points. In total England will earn 191 points in total for this match.
- The result after 90 minutes, including injury time, will be used for this game.
- When a match is postponed or not finished, we need to wait with the results for this game till the match is played.
- When the match is postponed indefinitely, the game will be finished without this match.
- It is not allowed to create more then 3 teams for this game.
- The values of the football teams can be found through this link: click here
- The pay out of the prizes will be done after the data entry is checked. This can take several hours and sometimes the next morning before all final data is received. When changes are being added at flashscore.com after the prizes are paid out, the final result will not be changed anymore.
It is allowed to submit multiple teams per player. There is only 1 restriction: Different teams of the same participant need to differ by a minimum of 3 football teams* from each other.
* The software will give a message when this rule is broken!
|Clean sheet
|60% or more ball possession
|Goal Attempt
|Goalkeeper Save
|Per red card
|Per yellow card
|Penalty Save
2 yellow cards for the same player in one match, are always counted as 1 red card.
For all statistics we follow the site of www.flashscore.com. Their decision is always binding and there cannot be any correspondence about it.
The matches which count for the Africa Cup of Nations (Teams) Round 1 - 1 can be found by following this link: calendar
The following prizes can be won in the game:
- The best teams in the general classification.
The prizes can be also found via this link: prizes.
When teams have an equal amount of points, the total of the prizes will be added up, and divided by the number of winners!! We will give a few examples to prevent discussions:
- 1 Marco and Tom 25 points
- 3 Martin 15 points
Marco en Tom share the 1st and 2nd prize together, and Martin will get the 3rd prize
- 1 Simon 25 points
- 2 Servee, Eddy, Michel, Bram 20 points
- 6 Peter 18 points
Simon gets the 1st prize, and Servee, Eddy, Michel and Bram share the 2nd and 3rd prize!! And Peter has bad luck!!
The prizes will be added to your account when the final results are published.
The costs per team are €5.00.
There are different ways to deposit money on your account to pay your team(s). You can use our payment providers like Ideal, Direct Banking, bank transfer or Credit Card. Please make sure you have enough money to pay your teams, because your team can not participate if it is not paid when the game starts.
If you pay through Credit card, Ideal or Direct banking you are account will be credited within a few minutes. With a bank transfer this could take 4 to 5 days and sometimes even longer. If you use a bank transfer please be on time, this will make sure you won't be disappointed.
Should there be any discrepancy between the game rules in the English language version and the version in any other language, the English version will supersede.
If something is not clear, please send us an email on the following address: firstname.lastname@example.com


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When you use this method during the Spring, you always need to revisit the sites to be sure that young fruits are following the flowers. It can be difficult to spot immature fruit initially, because it is camouflaged very effectively by the green leaves.
|Apple Blossom
It's a little early yet to tell whether the army of Apple trees that I have spotted will eventually produce good fruit. many of them may turn out to be Crab Apples, which can also be used in many interesting ways.
|Elder Flower
At the Urbane Forager, the first things we pick each year are Elder-flowers. We make cool Cordial and chaotic Champagne from these delicately scented ivory blooms.
Elderflower drinks are soon followed by waves of sweet, dark Cherries, and then bucket loads of multi-coloured wild plums. Hopefully, Summer will be in full swing by this time.


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A line of continuous-flex interconnect motor cables are harnessed in accordance with manufacturers that include Siemens, Rexroth (formerly Indramat), Fanuc, and Allen-Bradley. The cables, available for drive, control, motor, and robotic functions, come equipped with different cable connectors, including those with flying leads, adapter plugs, and extensions.
igus Inc., Box 14349, East Providence, RI 02914, (800) 521-2747, www.igus.com
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Orcas, or killer whales, are the largest of the dolphins and one of the world's most powerful predators. They feast on marine mammals such as seals, sea lions, and even whales, employing teeth that can be four inches long. They are known to grab seals right off the ice. They also eat fish, squid, and seabirds.
Orcas hunt in deadly pods, family groups of up to 40 individuals. There appear to be both resident and transient pod populations of orcas. These different groups may prey on different animals and use different techniques to catch them. Resident pods tend to prefer fish, while transient pods target marine mammals. All pods use effective, cooperative hunting techniques that some liken to the behavior of wolf packs.
Fast Facts
Common Name: Orca (Killer Whale)
Scientific Name: Orcinus orca
Type: Mammals
Diet: Carnivores
Group Name: Pod
Average life span in the wild: 50 to 80 years
Size: 23 to 32 ft
Weight: Up to 6 tons
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Every election now gets compared to America's 2016 presidential contest, but the analogy fits really well in today's election in Ontario, Canada's largest province. Read more
Joseph Shupac
Technology Could Help Mend Italy's North-South Divide
The results of the 2018 election in Italy reflected two main economic realities: the economic struggles in Italy relative to northern Europe and the economic struggles in southern Italy relative to northern Italy. The former helped anti-establishment parties to gain a large share of the country's vote. The latter resulted in Lega Nord and center-right parties performing well throughout much of the north of Italy and the Five Star Movement performing well in the south of Italy.
In geopolitics — the school of thought that argues that geography is the most significant or fundamental element in politics — these two economic realities have the same obvious source: mountains. Italy and southern Europe are much more mountainous than northern Europe and southern Italy is much more mountainous than northern Italy.
Mountainous regions tend to be much poorer than non-mountainous regions. Italy is no exception. Read more
Democratic Ideals and Reality: An Enduring Tension
A century ago, a British member of Parliament and geographer, Halford Mackinder, wrote one of the famous books of geopolitics, Democratic Ideals and Reality. The book discussed the tension between what nations want ("democratic ideals") and what they often get (geographic "reality").
That tension seems especially topical this week. Read more
North Korea in the Next Five Years
The Korean War, fought from 1950-53, was a result of two earlier wars in the 1940s: the American-Japanese War, which ended with the destruction and occupation of Japan in 1945, and the Chinese Civil War, which ended in a Communist victory (and Nationalist retreat to Taiwan) in 1950.
With the Communists and Americans as the only powers in East Asia following these wars, the Korean Peninsula was split in two, each side taking a piece for itself. Read more
Can Canada Resist Trump's Offensive on NAFTA?
NAFTA stands for the North American Free Trade Act, but President Donald Trump does not.
After campaigning on a promise to repeal the act, then adapting his position to that of merely supporting the act's renegotiation, Trump recently announced that he would no longer tolerate the status quo arrangement for American imports of dairy and forestry products originating from Canada. Read more
Trump and the Turks
As Donald Trump returns from his first international tour as American president, one thing that stands out is, as usual, the difference between his and Barack Obama's approach to diplomacy. Whereas Obama's first Mideast destinations were Turkey and Iraq, Trump's were Saudi Arabia and Israel, a country Obama did not even visit until his second term in office.
Trump's trip also included stops in Brussels, Sicily and the Vatican in Rome. Along with Saudi Arabia and Israel, these represent four of the five most significant allies of the United States within the Middle East and Eastern Mediterranean region: Italy, Israel, the Saudis and the EU.
The fifth ally, which appears to have been snubbed, is Turkey. The Turks were not honored with a stop during Trump's first trip to the region, as they were during Obama's.
Turkey failing to make it onto Trump's travel itinerary might seem to be of little significance, if it were not for the flurry of unpleasant events involving the Turks and Americans that have occured this same month. Read more
Why Ontario Plays Such a Central Role in Canadian Politics
Canada is often considered to be a haven from geopolitics, a nation relatively free from economic want or political cant. But if by geopolitics we refer simply to the influence of geography upon politics, Canada may in fact be a prime place to study it, if only because the country posseses so much of the former when in comparison to the latter.
The basic fact of Canadian geopolitics is this: more Canadians live in the city of Toronto than live in the 2,500-kilometer expanse of land separating Toronto from Alberta. Read more


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Glen Campbell Photography
Glen Campbell released over 70 albums across five decades, making him one of the most prolific performers of all time. This singer/songwriter/guitarist became a true crossover success when he racked up both country and pop Grammy Awards in 1967. He found additional fame hosting The Glen Campbell Goodtime Hour in the late '60s and early '70s.
Some of Campbell's most beloved recordings include "Rhinestone Cowboy," "Gentle on My Mind," "By the Time I Get to Phoenix," "Wichita Lineman," "Galveston," and "Southern Nights." And much like Johnny Cash, he also scored a resurgence in popularity during the twilight of his career by covering the likes of Green Day, Foo Fighters, U2, and others.
In 2011, Campbell went public with his diagnosis of Alzheimer's disease and became a celebrity advocate for Alzheimer's awareness and research. Shortly thereafter, he released the extraordinary Ghost on the Canvas album of originals and staged an emotional "Glen Campbell Goodbye Tour" prior to his passing in 2017. He was honored with a Grammy Lifetime Achievement Award in 2012.


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Sheriff Bill Crocker, school teacher Summer Dayes and newspaper reporter, Clive Parker--3 people whose lives are inexplicably intertwined in a tale of greed, lust, betrayal and the quest for the truth no matter where it leads.
In this Florida panhandle town, Bill Crocker rules like a dictator and thinks of himself as a southern "Tony Soprano" where sometimes you do good things and sometimes you don't. All is going smoothly for the sheriff until a seemingly innocent fender bender becomes the catalyst for the spiral descent of his power. Crocker was drunk when he hit the car and without thinking, he leaves the scene of the accident. When the whole incident is covered up, it piques the interest of reporter Clive Parker. Clive doesn't like people who think they are above the law. The more he researches the dealings of the sheriff, the more he uncovers mistresses, illegal land holdings, embezzlement of funds and corruption at its worst.
Ms. Francisco does an excellent job of pulling you into the story from the opening pages when a school girl discovers a body. Who is it and what happened? The story is well-developed and I found her characters realistic, especially Bill Crocker. Just when you thought you had everything figured out, the author reveals another piece of the puzzle. Just how far will Sheriff Bill Crocker fall? If you like a good mystery, definitely 1-click SUNSHINE HIGHWAY.
Disclosure policy: http://twoendsofthepen.blogspot.com/p/review-policy.html
Disclosure policy: http://twoendsofthepen.blogspot.com/p/review-policy.html


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Madison -- With Republicans holding on to the state Senate Tuesday, Democrats emerged from the recall elections saying they would still consider the much larger enterprise of recalling Gov. Scott Walker.
But in falling one short Tuesday of the three seats needed to pick up the Senate amid massive spending by both sides, Democrats failed to gain valuable momentum for that larger goal. Plus, they could suffer a further setback on Tuesday of next week, when two Democratic senators face recall elections and the potential of losing their own seats.
In an interview Wednesday morning in his Capitol office, Walker dismissed talk of any possible recall against him, saying the message of Tuesday's results was that voters want politicians of both parties to work together.
"I've heard repeatedly from people who are just disgusted at all the (campaign) ads, disgusted at all the money. They're tired of seemingly year round campaigning and whether it's a gubernatorial recall, any other recall, I don't think there's a whole lot of enthusiasm for having a whole another wave of ads and money come into the state of Wisconsin," Walker said.
To trigger a recall election of Walker, Democrats would need to gather 540,208 signatures, or one-quarter of the nearly 2.2 million votes cast 2010 gubernatorial election. Recall petitions cannot be circulated until early November and cannot be offered for filing with state elections officials until Jan.3 of next year, according to the state Government Accountability Board.
Stephan Thompson, executive director of the state Republican Party, said that holding onto the Senate Tuesday by a slim 17-16 majority made a recall of the GOP governor a much more difficult task. Walker has faced a contentious first year over his legislation to end most union bargaining for public workers.
"This a huge blow to Democrats. They wanted to use this to build momentum against Walker," Thompson said. "They fell short and this is a huge victory for Wisconsin's middle-class taxpayers."
But Democrats like state party chairman Mike Tate said that successfully recalling two GOP senators — doubling the number of lawmakers recalled in Wisconsin's history — was a big achievement. In a memo released Wednesday, Tate said that Tuesday's vote showed Walker is vulnerable to a recall attempt after he becomes eligible for that later this year.
Tate also signaled that Democrats would seek to time the Walker recall for the November 2012 presidential election.
Tate also signaled in a memo that Democrats would seek to time the Walker recall for the November 2012 presidential election, but in a conference call with reporters he said any timeline would be determined by grassroots activists, not the party.
"I would like to do it as soon as feasible," Tate said.
Holding the recall election in November 2012 would likely be difficult to achieve on many levels, though if successful it could also drive turnout of Democratic voters for both President Obama and an open U.S. Senate seat.
Scot Ross, executive director of the liberal group One Wisconsin Now, said he believed there was still an appetite among Democrats to take on Walker in a recall election.
"Gov. Walker has divided the state of Wisconsin like no other state official has and I think a recall of Scott Walker is still very real," said Ross, whose group weighed in repeatedly on the Senate recall elections.
Walker has one enormous ace in the hole — he raised funds at a furious pace in the first half of 2011, bringing in $2.5 million. That was nearly five times as much as then-Gov. Jim Doyle, a Democrat, raised in the first half of 2007 after his re-election and it left Walker with $1.8 million in his campaign account after accounting for the $1 million he spent in the first half of the year.
State Democratic Party spokesman Phil Walzak said that, with one Republican opposed to Walker's union bargaining plan, it could not have passed the state Senate with Republicans holding a 17-16 majority. The makeup of the Senate could change next week however if Democrats lose one or two of the recall elections.
"Wisconsin voters have delivered a Senate that would have blocked at least a part of that (Walker) agenda," he said.


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Weekdays 07:30 to 17:30 Saturdays 08:00 to 12:00
(When agents are available)
Express your love to the greatest mom in the world with a luscious array of sweet and savoury concoctions! Our Mother's Day bakery delights boast an extraordinary variety of Mother's Day cakes, cupcakes and delectable cupcake jars uniquely made for a great mother. Touch her heart with a sweet and happy Mother's Day by surprising mom with our delicious array of bakery Mother's Day gifts online. Put the cherry on top with incredible Mother's Day chocolate confectioneries or fine alcohol that will leave a palatable taste that lingers, or adds a little bit of magic with the natural radiance of Mother's Day flowers and Mother's Day plants. NetFlorist offers nationwide gift delivery to areas across South Africa, including areas in Cape Town such as Houtbay, Constantia, Fresnaye, and many more!
Sweeten her day with our delectable Mother's Day baked gifts. Exquisitely baked to perfection, our Mother's day cakes, cupcakes and cupcake jars are confectionery masterpieces, delightfully made for the wonderful mother with impeccable taste! Explore our online bakery for the most decadent Mother's Day gifts and treats for her to indulge in this Mother's Day 2019. Whether it's chocolate that tugs at her heartstrings or vanilla, our fresh bakery delights come in a variety of flavours that will give her the happy Mother's Day gift she deserves. If you'd like to give her a furry little friend to cuddle with as she enjoys her tasty favourites, our soft Mother's Day teddy bears are a wonderful touch that will touch your mother's heart. The sweet bakery items from our bakery are made with the finest ingredients and boast a sweet and sensational lingering taste. The flower folk at NetFlorist also have a radiant array of Mother's Day flowers as well as Mother's Day plants, so whichever gift that you settle with, you can make it a personalised Mother's Day gift and put her name on it. Let her experience the unforgettable combination of sweet and savoury with our wonderful treats from our Mother's Day bakery range. From palatable Mother's Day fine alcohol to delectable Mother's Day coffee and tea, NetFlorist has an extensive range of options to add to your Mother's Day gift ideas to give her a perfect Mother's Day!


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Bhutan Royal Wedding Pictures
Bhutan's King Marries in Dazzling Royal Wedding
Bhutan's King Marries in Dazzling Royal Wedding
While this royal wedding includes a "Prince Charming" and a beautiful bride, take one look at the brightly colored celebration and you know it's not Will and Kate we're talking about. Bhutan's popular King Jigme Khesar Namgyel Wangchuck, 31, married Queen Ashi Jetsun Pema today in an exuberant ceremony at the same venue where his coronation took place in 2008. This is a joyful day for the adorable couple, but the king's female fans may be distraught. Back when he was the young Crown Prince of Bhutan, Jigme made such an impression with the women on a 2006 visit to Thailand the Thai press nicknamed him Prince Charming.
The new queen is 10 years younger than her husband, but in the Bhutan king's May announcement of the engagement he said, "While she is young, she is warm and kind in heart and character." Maybe it's their mutual love of basketball that brought them together? The king represents Bhutan in international basketball events, and his wife was the captain of her high school basketball team. And both have studied in the UK, as King Jigme graduated from Oxford and Queen Jetsun is currently attending Regents College in London, majoring in international relations with minors in psychology and art history.
See photos of the Bhutanese royal newlyweds in their sweet wedding moments now!