JOURNAL OF FOOD SAFETY, Issue 3 2002
K. DE REU
ABSTRACT In total, 71 samples of retail raw milk cheeses produced or imported in Belgium and samples of Belgian farmhouse cheeses were examined for cotiforms, ,-glucuronidase positive Escherichia coli, Escherichia coli O157, Staphylococcus aureus, Salmonella spp., Listeria spp. and Listeria monocytogenes. The presence of staphylococcal enterotoxins was investigated on samples with S. aureus counts higher than 103 cfu/g. The incidence of coliforms, ,-glucuronidase positive E. coli and S. aureus was higher in soft than in blue veined, semi-hard, hard and fresh cheeses. Four mold-ripened soft cheeses were positive for E. coli O157. One of the 4 cheeses was positive for verotoxin VT2. Staphylococcal enterotoxins were detected in 1 soft redsmear cheese, which was positive for L. monocytogenes. L. monocytogenes was also detected in one fresh cheese. Salmonella was not detected in any of the 71 raw milk cheeses. [source]

PRODUCTION OF PARALYTIC SHELLFISH TOXINS BY APHANIZOMENON SP.

JOURNAL OF PHYCOLOGY, Issue 4 2002
LMECYA 31 (CYANOBACTERIA)
We examined intracellular and extracellular paralytic shellfish toxins (PST) in a strain of Aphanizomenon sp. (LMECYA31) isolated from a Portuguese freshwater reservoir throughout the growth cycle and under different conditions affected by temperature and nitrate and phosphate availability. PST concentrations and compositions were greatly influenced by cell density, growth stage, and temperature and nutrients conditions. On a per-cell basis results showed (1) the enhancement of PST cell quota after the end of exponential growth phase in nutrient replete batch cultures, (2) the absence of a PST increment at late growth stages under phosphate limitation, (3) a rise in PST maximum cell quota under nitrate depletion, and (4) the enhancement of toxin production at higher temperatures. The relative proportion of the four toxins detected, neoSTX, dcSTX, STX and GTX5, also changed within and between culture settings. While growing under phosphate rich media cells produced mainly GTX5 and neoSTX, whereas under phosphate limitation the proportion of STX and dcSTX increased substantially with culture age. Large amounts of extracellular toxins were found in the culture medium, increasing during culture time. Extracellular toxin composition in each culture was fairly constant and always similar to the intracellular composition found at late stages of growth. This further supported other research that indicates that PSTs are released to the water through cell lysis, and a significant concentration of PST may be expected to remain in the water upon the collapse of a toxic bloom or after cells removal by water treatment. [source]

Prepubertal Hidradenitis Suppurativa Successfully Treated with Botulinum Toxin A

DERMATOLOGIC SURGERY, Issue 8 2009
MARTA FEITO-RODRÍGUEZ MD
No abstract is available for this article. [source]

Use of Intraoperative Botulinum Toxin in Facial Reconstruction

DERMATOLOGIC SURGERY, Issue 2 2009
TIMOTHY CORCORAN FLYNN MD
BACKGROUND Botulinum toxin is a potent neuromodulator that temporarily relaxes muscles and can improve wound healing. OBJECTIVE This retrospective analysis assessed the use of intraoperative botulinum toxin type A or B in patients undergoing surgical reconstruction after Mohs micrographic surgery for treatment of skin cancer. The primary effect of intradermal botulinum toxin on wound healing was also studied. METHODS & MATERIALS Charts of patients who received intraoperative botulinum toxin type A (n=9) or B (n=9) in conjunction with reconstructive surgery after Mohs micrographic surgery were reviewed. Three volunteers also underwent dermal injections of botulinum toxin type A followed by erbium laser resurfacing. RESULTS Outcomes did not differ in patients treated with botulinum toxin type A and type B. Patients had excellent apposition of wound edges and smooth skin overlying soft tissue; no significant complications were noted. Healing of erbium laser ablation did not differ between botulinum toxin type A,treated skin and control skin. CONCLUSIONS Administration of botulinum toxin type A or B after reconstruction after Mohs micrographic surgery aided wound healing; botulinum toxin type A and botulinum toxin type B were equally effective. Intradermal botulinum toxin type A demonstrated no primary effect on healing of erbium laser,resurfaced skin. [source]

Treatment of Botulinum Toxin,Induced Eyelid Ptosis with Anticholinesterases

DERMATOLOGIC SURGERY, Issue 11 2007
MOJTABA KARAMI MD
First page of article [source]

Botulinum Toxin Type A Treatment of Multiple Upper Facial Sites: Patient-Reported Outcomes

DERMATOLOGIC SURGERY, Issue 2007
JEAN CARRUTHERS MD
BACKGROUND Aesthetic treatment planning must address subjects' goals and include subject-reported outcomes. OBJECTIVE The objective was to compare the effect of botulinum neurotoxin type A (BoNTA) with placebo on subject-reported outcomes and to assess the utility of 64 U of BoNTA to treat the entire upper face. METHODS Forty female subjects were randomized to receive 64 U of BoNTA or identical placebo injections (double-masked) divided among 16 sites of the upper face and were followed for 12 weeks. Subjects unimproved at Week 4 were eligible for open-label BoNTA treatment and were followed through Week 16. Main outcome measures were scores on seven items of the Facial Line Outcomes Questionnaire (FLO-7) and results on the Self-Perception of Age (SPA) for assessing age of appearance relative to actual age. RESULTS BoNTA treatment resulted in significant improvements on the FLO-7 scores that were maintained throughout the study. BoNTA treatment also reduced age of appearance in a majority of subjects. Placebo had no effects on any measure. No serious adverse events occurred. CONCLUSION Sixty-four-unit BoNTA treatment of upper facial rhytids safely and significantly improves subject-reported outcomes, as measured by the FLO-7 and SPA, and results in a younger, more satisfying, relaxed appearance. [source]

A Case of Foul Genital Odor Treated with Botulinum Toxin A

DERMATOLOGIC SURGERY, Issue 9 2004
Jae-Bong Lee MD
Background. Genital odor is an uncommon condition characterized by an offensive and malodorous smell in the genital area. Although the etiology of foul genital odor is multifactorial, an important cause is sweat secretion and decomposition of sweat components by bacteria. Different methods are effective in reducing body odor secondary to bromhidrosis. Conservative methods only act for a short period of time, and more invasive surgical methods carry risk of complications or are inapplicable for the genital region. Methods. A patient with localized foul odor in the genital hair bearing area was treated with botulinum toxin A. Results. Botulinum toxin A was effective in creating an odorless and anhydrous response in the genital region, and no major adverse effects were noted during a follow-up of 9 months after injection. Conclusion. Local injection of botulinum toxin A appears to be a useful treatment for foul genital odor related to sweat glands activity. [source]

The Effect of Full-Face Broadband Light Treatments Alone and in Combination With Bilateral Crow's Feet Botulinum Toxin Type A Chemodenervation

DERMATOLOGIC SURGERY, Issue 3 2004
Jean Carruthers MD
Background. Broadband light (BBL; Intense Pulsed Light; Lumenis Ltd., Yokneam, Israel) is a powerful, nonablative, light-based technology that targets melanin and hemoglobin and stimulates the formation of collagen and elastin. Botulinum toxin type A (BTX-A; BOTOX; Allergan Inc., Irvine, CA) treatment of the lateral periocular region relaxes the vertical fibers of the orbicularis oculi and results in softening of the lateral orbital crow's feet rhytides and widening of the palpebral aperture. Objective. To compare the effects of full-face BBL in combination with BTX-A and BBL alone in female subjects with Fitzpatrick I,III skin types, Glogau II,III rhytides, and significant associated facial lentigines and telangiectasia. Methods. This was a prospective, randomized study of 30 women with moderate to severe crow's feet rhytides. Half of the subjects were treated with BTX-A and BBL and the other half with BBL alone. Their response was assessed clinically and photographically. Skin biopsies of the temporal skin were taken from two subjects in each group and were stained with Masson trichrome. Results. Patients treated with a combination of BTX-A and BBL experienced a better response to treatment, both at rest and on maximum smile, as well as a slightly improved response in associated lentigines, telangiectasia, pore size, and facial skin texture compared with patients who received BBL treatment alone. Skin biopsies showed an increase in dermal collagen in each group. Conclusions. The patients in this study benefited from both treatments. Although BBL led to a remarkable improvement in full-face telangiectasias, lentigines, and skin texture, the improvement increased in all categories with combination therapy. In addition, an added improvement in the full-face aesthetic with both BTX-A and BBL therapy combined was obvious. These results suggest that both treatments,although evidently complementary,may also act synergistically to produce optimal clinical effects, revolutionizing the treatment of facial aging. [source]

Botulinum Toxin for the Treatment of Facial Flushing

DERMATOLOGIC SURGERY, Issue 1 2004
Melanie Yuraitis MS
Background. Facial flushing is a common problem that is encountered by fair-skinned patients of Celtic and Northern European descent. Although usually transient in nature, some patients display a persistent reddened skin tone, with periods of increased erythema. Treatment of this condition is limited. Objective. To describe a novel method for the treatment of persistent facial flushing. Method. We report a case of persistent facial flushing that was resistant to multiple pulsed dye laser treatments and was successfully treated with botulinum toxin A. Results. The posttreatment appearance was dramatic, and the patient was highly satisfied with the cosmetic outcome. Conclusion. Botulinum toxin A can be used in small quantities to decrease persistent facial flushing temporarily. [source]

Botulinum Toxin Type B (MYOBLOC) Versus Botulinum Toxin Type A (BOTOX) Frontalis Study: Rate of Onset and Radius of Diffusion

DERMATOLOGIC SURGERY, Issue 5 2003
Timothy Corcoran Flynn MD
Background. Botulinum toxin types A and B can improve the appearance of facial wrinkles. Differences in the time until onset and the degree of diffusion have been observed anecdotally, but no direct comparative studies have been done. Objective. To compare the rate of onset and the radius of diffusion of botulinum toxin types A and B in the rhytides of the forehead. Methods. Adults with symmetrical moderate to severe forehead wrinkles at full contracture received botulinum toxin type A (BOTOX; 5 U) on one side of the forehead and type B (MYOBLOC; 500 U) on the other side. Photographs taken at rest and full frontalis contracture were analyzed by computer, and a time-lapse motion picture was created. Radius of diffusion and time until full effect were measured. Results. Botulinum toxin type B had a slightly faster onset of action than type A. All patients responded to type B quickly, whereas some had a delayed response to type A. A greater radius of diffusion was consistently observed with botulinum toxin type B, as measured by the greater area of wrinkle reduction at the doses used. Conclusions. In this comparative study of patients with symmetrical forehead wrinkles, botulinum toxin type B produced a greater area of diffusion and a more rapid onset of action than type A. [source]

Metallic Taste: An Unusual Reaction to Botulinum Toxin A

DERMATOLOGIC SURGERY, Issue 5 2003
Christian Murray MD
BACKGROUND Botulinum neurotoxin formulations are safe and effective agents for the treatment of facial rhytides. OBJECTIVES A patient is described who complained of metallic taste after each treatment with botulinum toxin A (BTX-A). RESULTS The sensation of metallic taste diminished after successive treatments with BTX-A, despite adequate dosing for cosmetic purposes. CONCLUSION Metallic taste is associated with the use of numerous medications; however, the pathogenesis remains unclear. Alteration in zinc metabolism, which may occur with BTX-A administration, has been suggested as a possible mechanism. Although this is the first known report of dysgeusia after BTX-A, physicians and patients may be reassured that the taste alteration was self-limited and was not significantly problematic for the patient in our case. [source]

Decreased Tear Expression with an Abnormal Schirmer's Test Following Botulinum Toxin Type A for the Treatment of Lateral Canthal Rhytides

DERMATOLOGIC SURGERY, Issue 2 2002
Seth L. Matarasso MD
background. Inactivation of muscles of facial expression by chemodenervation with botulinum toxin remains an off-label indication. Nevertheless, it continues to be a safe and effective technique to improve dynamic rhytides and is the treatment of choice for the hypertrophic lateral fibers of the orbicularis oculi muscle that can cause the superimposed crow's feet. objective. Although infrequent and self-limiting, the complication of unexpected muscle weakness from toxin diffusion or erroneous placement is documented. methods. However, injection into the pretarsal portion of the orbicularis oculi muscle resulting in unilateral ocular irritation and diminished tear expression as evidenced by a dry eye and an abnormal Schirmer's test has rarely been reported. Direct injection into the pretarsal fibers of the muscle as opposed to diffusion of the toxin into the muscle fibers or the lacrimal gland was consistent with the onset of action of the toxin and the prolonged duration of the ocular symptoms. results. Treatment consisted of ocular lubrication until the effects of the toxin dissipated and muscle tone returned. Subsequent treatment did not result in a result in a recurrence of adverse sequelae. conclusions. Facial muscles are small, not isolated, and often have fibers that interdigitate. An important factor in the administration of botulinum toxin is the identification of the muscles responsible for the corresponding rhytide. Precise knowledge of muscular anatomy and function will aid in minimizing this and other potential complications. [source]

Botulinum Toxin Type A (Botox) for Prophylactic Treatment of Chronic Daily Headache: A Response

HEADACHE, Issue 3 2006
Ninan T. Mathew MD
No abstract is available for this article. [source]

Botulinum Toxin Type A for the Treatment of Headache: Pro

HEADACHE, Issue 8 2004
Andrew Blumenfeld MD
First page of article [source]

Botulinum Toxin Type A: Myths, Facts, and Current Research

HEADACHE, Issue 2003
Stephen D. Silberstein MD
No abstract is available for this article. [source]

EFFECT OF ETHANOL VAPOR ON GROWTH AND TOXIN PRODUCTION BY CLOSTRIDIUM BOTULINUM IN A HIGH MOISTURE BAKERY PRODUCT

JOURNAL OF FOOD SAFETY, Issue 2 2000
DAPHNE PHILLIPS DAIFAS
ABSTRACT To determine the effect of ethanol vapor on toxin production by Clostridium botulinum, studies were done in English style crumpets (aw 0.990, pH 6.5) challenged with 500 spores/g C. botulinum types A and proteolytic B and packaged in high gas barrier bags [ethanol transmission rate (ETR) 0.21 g/m2/day @ 25 C]. Crumpets were packaged in air with either commercially available ethanol vapor generators (Ethicap® 2, 4 or 6G) or cotton wool pads saturated with 2, 4 or 6 g of 95% food grade ethanol and stored at 25C. Toxin was detected in all inoculated control crumpets (0% ethanol) after 5 days at ambient temperature (25C). Ethicap® 2G delayed toxicity for 10 days while complete inhibition (>21 days) was observed in all crumpets packaged with 4 or 6G Ethicap® or with 2, 4 or 6 g of ethanol per pad. However, all crumpets were overtly spoiled by this time. Both headspace ethanol and absorption of ethanol by crumpets increased as a function of Ethicap® size/weight of ethanol. Based on these preliminary studies, ethanol vapor would appear to be an effective additional barrier to control the growth and toxin production by C. botulinum in high moisture bakery products and ensure the safety of these products at ambient temperature. [source]

Production and Stability Studies of a Neurotoxin Produced by Clostridium sp.

JOURNAL OF FOOD SCIENCE, Issue 3 2006

ABSTRACT: A neurotoxigenic Clostridium sp. (RKD) isolated from intestine of decaying fish produced a neurotoxin that was neutralized by botulinum antitoxin (A+B+E) when tested by mouse protection bioassay. An amplicon of expected size (approximately 700 bp) was generated with primers specific for BoNT/B. Toxin was maximally released in the culture supernatant in the late stationary phase and was dependent on media composition. Growth was optimal in trypticase peptone yeast-extract glucose (TPYG) medium in a pH range of 7.5 to 8.0 and at a temperature between 35°C to 40°C while toxin production was optimum at 37°C (3 to 4 × 103 minimum lethal dose per milliliter) without any protease treatment. There was no correlation between growth and toxin production when cells were grown in media containing different concentrations of NaCl (0% to 5%). Toxin in the culture supernatant was more stable (50% reduction at 50°C in 90 min) than the partially purified fraction. Toxicity was destroyed gradually after increasing the number of freeze-thaw cycles and was almost completely inactivated after 5 cycles. It was completely inactivated by overnight treatment of 1 N NaOH while it retained 1.5% activity with a similar treatment with 1 N HCl. [source]

Prevalence of Diarrhea and Enteropathogens in Racing Sled Dogs

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2010
E. McKenzie
Background: Diarrhea is highly prevalent in racing sled dogs, although the underlying causes are poorly understood. Hypothesis: Clostridium perfringens enterotoxin (CPE) and Clostridium difficile Toxin A and B are associated with diarrhea in racing sled dogs. Animals: One hundred and thirty-five sled dogs. Methods: Freshly voided feces were obtained from 55 dogs before racing and from 80 dogs after 400 miles of racing. Samples were visually scored for diarrhea, mucus, blood, and melena. CPE and C. difficile Toxin A and B were detected by ELISA. Samples were cultured for C. perfringens, C. difficile, Campylobacter, Salmonella, and Escherichia coli 0157; Giardia and Cryptosporidium spp. were detected via immunofluorescence. Results: Diarrhea occurred in 36% of dogs during racing, and hematochezia, fecal mucus or melena, or all 3 occurred in 57.5% of dogs. Salmonella was isolated from 78.2% of dogs before racing, and from 71.3% of dogs during racing. C. perfringens and C. difficile were isolated from 100 and 58.2% of dogs before racing, and from 95 and 36.3% of dogs during racing. Dogs were more likely to test positive for CPE during than before racing (18.8 versus 5.5%, P= .021); however, no enteropathogens or their respective toxins were significantly associated with hematochezia or diarrhea. Conclusions and Clinical Importance: Sled dogs participating in long distance racing have a high prevalence of diarrhea and hematochezia that is not associated with common enteropathogens. It is possible that diarrhea and hematochezia represent the effect of prolonged exercise on the gastrointestinal tract. [source]

Effects of ,-Toxin of Staphylococcus aureus on Ciliary Activity of Nasal Epithelial Cells ,

THE LARYNGOSCOPE, Issue 12 2000
Chung Seop Kim MD
Abstract Objectives To investigate the in vitro effects of staphylococcal ,-to-in on ciliary activity and the in vivo effects on sinusitis induction. Study Design The in vitro effects of staphylococcal ,-to-in on ciliary activity were investigated at different concentrations and e-posure times. E-perimental sinusitis was induced in rabbits with application of ,-to-in and confirmed 7 days later. Methods Ciliated epithelial cells were taken from the ma-illary sinus mucosa of 10 rabbits. Five culture dishes from each rabbit were used for the e-perimental group, and one culture dish from each rabbit was used for the control group. In the experimental group, ciliary beat frequency (CBF) was measured at concentrations of 0.1, 1, 2, 5 and 10 U/mL of ,-toxin using a video-computerized analysis technique, while in the control group, culture medium containing no toxin was used. CBF was measured 1, 2, 4, 6, 8, 12, 24, and 48 hours after administration of ,-toxin. To induce experimental sinusitis, 2 U/mL of ,-toxin was percutaneously applied to the maxillary sinus of 10 rabbits without occlusion of the natural ostium, while normal saline was percutaneously applied to the right-side maxillary sinus of 4 rabbits in the control group. At 7 days, mucosal membranes were taken from the inferomedial wall of the maxillary sinus for light microscopic study. Results CBF dropped significantly after an 8-hour incubation at 2, 5, and 10 U/mL of ,-to-in. No ciliary activity was observed after a 24-hour incubation at 2 and 5 U/mL and a 12-hour incubation at 10 U/mL of ,-to-in. Mucoid, purulent discharge was observed in the ma-illary sinuses of the ,-to-in,applied group. Prominent epithelial disruption and infiltration of inflammatory cells into the epithelium and lamina propria were observed in the ,-to-in,applied group. Conclusions Staphylococcal ,-to-in may reduce ciliary activity and induce sinusitis without occlusion of the natural ostium of the ma-illary sinus in rabbits. This study provides another animal model of sinusitis for understanding the pathogenesis of sinusitis induced by bacterial e-oto-ins. [source]

Enantioselective Total Synthesis of the Marine Toxin (,)-Gymnodimine Employing a Barbier-Type Macrocyclization,

ANGEWANDTE CHEMIE, Issue 40 2009
Ke Kong
Exoten des Meeres: tert -Butyllithium vermittelt bei Umgebungstemperatur eine Barbier-Makrocyclisierung in der ersten Totalsynthese von (,)-Gymnodimin (Ts: Toluol-4-sulfonyl; TBS: tert -Butyldimethylsilyl), einem marinen Toxin aus der Familie der spirocyclischen Imine. Die Synthese enthält außerdem eine vinyloge Mukaiyama-Aldolreaktion zur Kupplung der labilen Butenolidgruppe an eine makrocyclische Keton-Zwischenstufe. [source]

Botulinum Toxin, Physical and Occupational Therapy, and Neuromuscular Electrical Stimulation to Treat Spastic Upper Limb of Children With Cerebral Palsy: A Pilot Study

ARTIFICIAL ORGANS, Issue 3 2010
Gerardo Rodríguez-Reyes
Abstract Spasticity has been successfully managed with different treatment modalities or combinations. No information is available on the effectiveness or individual contribution of botulinum toxin type A (BTA) combined with physical and occupational therapy and neuromuscular electrical stimulation to treat spastic upper limb. The purpose of this study was to assess the effects of such treatment and to inform sample-size calculations for a randomized controlled trial. BTA was injected into spastic upper limb muscles of 10 children. They received 10 sessions of physical and occupational therapy followed by 10 sessions of neuromuscular electrical stimulation on the wrist extensors (antagonist muscles). Degree of spasticity using the Modified Ashworth scale, active range of motion, and manual function with the Jebsen hand test, were assessed. Meaningful improvement was observed in hand function posttreatment (P = 0.03). Median spasticity showed a reduction trend and median amplitude of wrist range of motion registered an increase; however, neither of these were significant (P > 0.05). There is evidence of a beneficial effect of the combined treatment. Adequate information has been obtained on main outcome-measurement variability for calculating sample size for a subsequent study to quantify the treatment effect precisely. [source]

Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human ,-Fetoprotein Gene

CANCER SCIENCE, Issue 3 2000
Michito Kunitomi
We constructed a plasmid containing human ,-fetoprotein (AFP) promoter/enhancer to direct the cell type-specific expression of diphtheria toxin fragment A (DTA), designated as pAF-DTA, to AFP-producing hepatocellular carcinoma cells. The transfection was carried out with cationic liposomes (DMRIE-C) and the expression of the DTA gene was confirmed by a northern blot analysis. When pAF-DTA was transfected, the growth of AFP-positive HuH-7 cells was inhibited, whereas growth inhibition was not observed in AFP-negative MKN45 cells. In this experiment, the secretion of AFP was similarly suppressed, but the secretion of carcinoembryonic antigen from MKN45 was not altered. pAF-DTA could also exert its growth inhibitory effect on PLC, a cell line with a low level of AFP. However, no inhibitory effect of pAF-DTA was observed on the proliferation of primary hepatocyte cells. Furthermore, transfection experiments in which HuH-7 and splenic stromal cells were co-cultured revealed the growth inhibition by pAF-DTA to be selective in HuH-7 cells. Finally, the growth of HuH-7 transplanted on BALB/c nu/nu mice was inhibited by the direct injection of pAF-DTA/liposome complex into a tumor mass. These results suggest that use of pAF-DTA may be potentially useful as a novel approach for the selective treatment of tumor cells producing AFP even at low levels, without affecting other types of cells. [source]

A Novel Mycolactone Toxin Obtained by Biosynthetic Engineering

CHEMBIOCHEM, Issue 17 2007
Hui Hong Dr.
A novel structural variant of the mycobacterial polyketide toxin mycolactone has been obtained by cloning a P450 hydroxylase gene from a related strain. This technique increases the range of available mycolactones for studies on the mode of action of the toxin. [source]

Multivalent Drug Design and Inhibition of Cholera Toxin by Specific and Transient Protein,Ligand Interactions

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2008
Jiyun Liu
Multivalent inhibitors of the cholera toxin B pentamer are potential therapeutic drugs for treating cholera and serve as models for demonstrating multivalent ligand effects through a structure-based approach. A crucial yet often overlooked aspect of multivalent drug design is the length, rigidity and chemical composition of the linker used to connect multiple binding moieties. To specifically study the role of chemical linkers in multivalent ligand design, we have synthesized a series of compounds with one and two binding motifs connected by several different linkers. These compounds have affinity for and potency against the cholera toxin B pentamer despite the fact that none can simultaneously bind two toxin receptor sites. Results from saturation transfer difference NMR reveal transient, non-specific interactions between the cholera toxin and linker groups contribute significantly to overall binding affinity of monovalent compounds. However, the same random protein,ligand interactions do not appear to affect binding of bivalent molecules. Moreover, the binding affinities and potencies of these ,non-spanning' bivalent ligands appear to be wholly independent of linker length. Our detailed analysis identifies multiple effects that account for the improved inhibitory potencies of bivalent ligands and suggest approaches to further improve the activity of this class of compounds. [source]

Total Synthesis of Polycavernoside A (I), a Lethal Toxin of the Red Alga Polycavernosa tsudai.

CHEMINFORM, Issue 49 2005
Paul R. Blakemore
No abstract is available for this article. [source]

Structure Determination of Hydroxytrypargine: A New Tetrahydro-,-carboline Toxin from the Venom of the Spider Parawixia bistriata.

CHEMINFORM, Issue 37 2005
Lilian M. M. Cesar
No abstract is available for this article. [source]

A Novel Dipeptide, N-,-Glutamyl Boletine, and a Cyclic Iminium Toxin from the Mushroom Tylopilus sp. (Boletaceae).

CHEMINFORM, Issue 50 2002
Reiko Watanabe
No abstract is available for this article. [source]

Synaptic Transmission: Inhibition of Neurotransmitter Release by Botulinum Toxins

HEADACHE, Issue 2003
Oliver Dolly MSc
Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation. At the neuromuscular junction, the presynaptic nerve ending is packed with synaptic vesicles filled with acetylcholine, and clustered at the tip of the folds of the postsynaptic muscle membrane are the acetylcholine receptors. Synaptic vesicles fuse with the membrane in response to an elevation of intraneuronal calcium concentration and undergo release of their transmitter by exocytosis. Intracellular proteins that contribute to the fusion of the vesicles with the plasma membrane during exocytosis include synaptosomal protein with a molecular weight of 25 kDa (SNAP-25); vesicle-associated membrane protein (VAMP), also known as synaptobrevin; and syntaxin. Through their proteolytic action on these proteins, botulinum toxins prevent exocytosis, thereby inhibiting the release of acetylcholine. There are 7 serotypes of this toxin,A, B, C1, D, E, F, and G,and each cleaves a different intracellular protein or the same target at distinct bonds. The separate cleavage sites in SNAP-25 for botulinum toxin types A and E contribute to their dissimilar durations of muscle relaxation. This report describes the molecular basis for the inhibition by botulinum toxins of neuroexocytosis and subsequent functional recovery at the neuromuscular junction. [source]

Uremic Toxins: Removal with Different Therapies

HEMODIALYSIS INTERNATIONAL, Issue 2 2003
Raymond C. Vanholder
A convenient way to classify uremic solutes is to subdivide them according to the physicochemical characteristics influencing their dialytic removal into small water-soluble compounds (<500 Da), protein-bound compounds, and middle molecules (>500 Da). The prototype of small water-soluble solutes remains urea although the proof of its toxicity is scanty. Only a few other water-soluble compounds exert toxicity (e.g., the guanidines, the purines), but most of these are characterized by an intra-dialytic behavior, which is different from that of urea. In addition, the protein-bound compounds and the middle molecules behave in a different way from urea, due to their protein binding and their molecular weights, respectively. Because of these specific removal patterns, it is suggested that new approaches of influencing uremic solute concentration should be explored, such as specific adsorptive systems, alternative dialytic timeframes, removal by intestinal adsorption, modification of toxin, or general metabolism by drug administration. Middle molecule removal has been improved by the introduction of large pore, high-flux membranes, but this approach seems to have come close to its maximal removal capacity, whereas multicompartmental behavior might become an additional factor hampering attempts to decrease toxin concentration. Hence, further enhancement of uremic toxin removal should be pursued by the introduction of alternative concepts of elimination. [source]