Anti-hyperglycemic and anti-hyperlipidemic effects of a methanolic extract of Debregeasia salicifolia in Alloxan-induced diabetic albino mice

Abstract Diabetes mellitus (DM), an endocrine syndrome characterized by high blood glucose levels due to abrogated insulin activity. The existing treatments for DM have side effects and varying degrees of efficacy. Therefore, it is paramount that novel approaches be developed to enhance the management of DM. Therapeutic plants have been accredited as having comparatively high efficacy with fewer adverse effects. The current study aims to elucidate the phytochemical profile, anti-hyperlipidemic, and anti-diabetic effects of methanolic extract D. salicifolia (leaves) in Alloxan-induced diabetic mice. Alloxan was injected intraperitoneally (150 mg kg-1, b.w), to induced diabetes in mice. The mice were divided into three groups (n=10). Group 1 (normal control) received normal food and purified water, Group II (diabetic control) received regular feed and clean water and group III (diabetic treated) received a methanolic extract of the plant (300 mg kg-1) for 28 days with a typical diet and clean water throughout the experiment. Blood samples were collected to checked serum glucose and concentration of LDL, TC, TG. The extract demonstrated significant antihyperglycemic activity (P 0.05), whereas improvements in mice's body weight and lipid profiles were observed after treatment with the extract. This study establishes that the extract has high efficacy with comparatively less toxicity that can be used for DM management.

Resumo Diabetes mellitus (DM) é uma síndrome endócrina caracterizada por níveis elevados de glicose no sangue devido à atividade anulada da insulina. Os tratamentos existentes para o DM têm efeitos colaterais e vários graus de eficácia. Portanto, é fundamental que novas abordagens sejam desenvolvidas para aprimorar o manejo do DM. As plantas terapêuticas foram acreditadas como tendo eficácia comparativamente alta com menos efeitos adversos. O presente estudo visa elucidar o perfil fitoquímico, efeitos anti-hiperlipidêmicos e antidiabéticos do extrato metanólico de D. salicifolia (folhas) em camundongos diabéticos induzidos por aloxana. Alloxan foi injetado por via intraperitoneal (150 mg kg-1, b.w), para induzir diabetes em camundongos. Os camundongos foram divididos em três grupos (n = 10). Grupo 1 (controle normal) recebeu ração normal e água purificada, Grupo II (controle diabético) recebeu ração regular e água limpa, e o grupo III (tratamento diabético) recebeu extrato metanólico da planta (300 mg kg-1) por 28 dias com uma dieta típica e água limpa durante todo o experimento. Amostras de sangue foram coletadas para verificar a glicose sérica e a concentração de LDL, TC, TG. O extrato demonstrou atividade anti-hiperglicêmica significativa (P 0,05), enquanto melhorias no peso corporal e no perfil lipídico dos camundongos foram observadas após o tratamento com o extrato. Este estudo estabelece que o extrato tem alta eficácia com comparativamente menos toxicidade e pode ser usado para o controle do DM.

Comparative Analysis of the Efficacies of the GeneXpert and Solid Culture Media Techniques in the Diagnosis of Mycobacterium Tuberculosis.

Tuberculosis is one of the predominant infectious diseases causing significant deaths worldwide. Detection of Mycobacterium tuberculosis bacilli (MTB) using culture media was officially recognized by World Health Organization. However, there is a significant limitation in the authenticity of evaluation for its effectiveness on clinically important attributes. GeneXpert detects the presence of Mycobacterium tuberculosis (M. tuberculosis) based on the detection of nucleic acid and is able to identify the resistance of both isoniazid (INH) and Rifampicin (RIF) drugs. In this technique, DNA amplification is done using the GeneXpert instrument in the suspected sample with a specific reagent cartridge. Although GeneXpert is a rapid technique compared to other diagnostic tools for MTB identification due to false-negative results, the culture media technique is still considered the gold standard in detecting M. tuberculosis. The current study was designed to evaluate the comparative efficacies of GeneXpert and the solid culture media technique in identifying MTB. Sputum samples of 250 (n=250) suspected tuberculosis (TB) patients were investigated using both diagnostic techniques. The results revealed that out of the 250 suspected patients, 30 (12%) samples were positive with the culture media technique, while only 17 (6.8%) samples showed positive results with GeneXpert. Culture tests and GeneXpert are not equally efficient in detecting M. tuberculosis. The current study's findings showed that the culture-based detection method for M. tuberculosis is more efficient and reliable than GeneXpert.

Anti-hyperglycemic and anti-hyperlipidemic effects of a methanolic extract of Debregeasia salicifolia in Alloxan-induced diabetic albino mice.

Diabetes mellitus (DM), an endocrine syndrome characterized by high blood glucose levels due to abrogated insulin activity. The existing treatments for DM have side effects and varying degrees of efficacy. Therefore, it is paramount that novel approaches be developed to enhance the management of DM. Therapeutic plants have been accredited as having comparatively high efficacy with fewer adverse effects. The current study aims to elucidate the phytochemical profile, anti-hyperlipidemic, and anti-diabetic effects of methanolic extract D. salicifolia (leaves) in Alloxan-induced diabetic mice. Alloxan was injected intraperitoneally (150 mg kg-1, b.w), to induced diabetes in mice. The mice were divided into three groups (n=10). Group 1 (normal control) received normal food and purified water, Group II (diabetic control) received regular feed and clean water and group III (diabetic treated) received a methanolic extract of the plant (300 mg kg-1) for 28 days with a typical diet and clean water throughout the experiment. Blood samples were collected to checked serum glucose and concentration of LDL, TC, TG. The extract demonstrated significant antihyperglycemic activity (P<0.05), whereas improvements in mice's body weight and lipid profiles were observed after treatment with the extract. This study establishes that the extract has high efficacy with comparatively less toxicity that can be used for DM management.

Tophaceous pseudogout of the temporomandibular joint with erosion into the middle cranial fossa.

This report presents a case of extensive tophaceous pseudogout involving the temporomandibular joint (TMJ), causing erosion into the middle cranial fossa. Pseudogout is a benign metabolic arthropathy caused by calcium pyrophosphate dihydrate crystal deposition within joints and peri-articular tissue. Pseudogout more frequently occurs in large joints such as the knee, wrist, symphysis pubis, and shoulder. Tophaceous pseudogout involving the TMJ is rare, with only seven cases involving erosion into the middle cranial fossa reported previously. Despite skull base erosion being a rare consequence of this erosive disease, this case highlights the importance of appropriate investigation and multidisciplinary team management.

L-Citrulline Supplementation Increases Plasma Nitric Oxide Levels and Reduces Arginase Activity in Patients With Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is becoming a major contributor to cardiovascular disease. One of the early signs of T2DM associated cardiovascular events is the development of vascular dysfunction. This dysfunction has been implicated in increasing the morbidity and mortality of T2DM patients. One of the important characteristics of vascular dysfunction is the impaired ability of endothelial cells to produce nitric oxide (NO). Additionally, decreases in the availability of NO is also a major contributor of this pathology. NO is produced by the activity of endothelial NO synthase (eNOS) on its substrate, L-arginine. Reduced availability of L-arginine to eNOS has been implicated in vascular dysfunction in diabetes. Arginase, which metabolizes L-arginine to urea and ornithine, competes directly with NOS for L-arginine. Hence, increases in arginase activity can decrease arginine levels, reducing its availability to eNOS and decreasing NO production. Diabetes has been linked to elevated arginase and associated vascular endothelial dysfunction. We aimed to determine levels of plasma NO and arginase activity in (T2DM) patients and the effects of L-citrulline supplementation, a natural arginase inhibitor, on inhibiting arginase activity in these patients. Levels of arginase correlated with HbA1c levels in diabetic patients. Twenty-five patients received L-citrulline supplements (2000 mg/day) for 1 month. Arginase activity decreased by 21% in T2DM patients after taking L-citrulline supplements. Additionally, plasma NO levels increased by 38%. There was a modest improvement on H1Ac levels in these patients, though not statistically significant. The effect of L-citrulline on arginase activity was also studied in bovine aortic endothelial cells (BAECs) grown in high glucose (HG) conditions. HG (25 mM, 72 h) caused a 2-fold increase in arginase activity in BAECs and decreased NO production by 30%. L-citrulline (2.5 mM) completely prevented the increase in arginase activity and restored NO production levels. These data indicate that L-citrulline can have therapeutic benefits in diabetic patients through increasing NO levels and thus maintaining vascular function possibly through an arginase inhibition related pathway.

Biochemical changes in cultivars of sweet oranges infected with citrus tristeza virus / Mudanças bioquímicas em vários cultivares de laranjas doces infectadas com o vírus citrus tristeza

Abstract Citrus fruit production occupies a place of considerable importance in the economy of the world including Pakistan. Tristeza disease caused by Citrus Tristeza Virus (CTV) exists in various forms that may or may not cause symptoms in the plants. The bioactive compounds and antioxidants are naturally present in plants and provide a defense mechanism that is generally accelerated in response to a stress. The objective of the present study was to target and analyze the citrus plants that were CTV positive to observe the changes in the enzymatic and non-enzymatic antioxidants of citrus (Sweet Oranges only). It was observed that in response to CTV infection, both the non-enzymatic antioxidants (total flavonoid, ascorbic acid, phenolic acid) and enzymatic antioxidants (catalase, superoxide dismutase and peroxidase) activities showed an increasing trend overall. The profiling of antioxidants in response to a viral infection may help in the discovery of new biomarkers that can be used as a monitoring tool in disease management.

Resumo As frutas cítricas ocupam um lugar de considerável importância na economia do Paquistão, assim como o resto do mundo. A doença da tristeza causada pelo Vírus da Tristeza dos Citros (CTV) existe em várias formas que podem ou não apresentar sintomas nas plantas. Os compostos bioativos e antioxidantes estão naturalmente presentes nas plantas e fornecem um mecanismo de defesa que é geralmente acelerado em resposta a um estresse. O objetivo do presente estudo foi analisar as alterações causadas pelo CTV nos antioxidantes enzimáticos e não enzimáticos de laranjas doces. Foi observado que, em resposta ao ataque de CTV, os antioxidantes não enzimáticos como flavonoides totais, ácido ascórbico, ácido fenólico e antioxidantes enzimáticos, como as atividades de catalase, superóxido dismutase e peroxidase, geralmente mostram uma tendência crescente. O perfil de antioxidantes em resposta a um ataque viral pode ajudar na descoberta de novos biomarcadores que podem ser usados ​​como uma ferramenta de monitoramento no gerenciamento de doenças.

Biochemical changes in cultivars of sweet oranges infected with citrus tristeza virus.

Citrus fruit production occupies a place of considerable importance in the economy of the world including Pakistan. Tristeza disease caused by Citrus Tristeza Virus (CTV) exists in various forms that may or may not cause symptoms in the plants. The bioactive compounds and antioxidants are naturally present in plants and provide a defense mechanism that is generally accelerated in response to a stress. The objective of the present study was to target and analyze the citrus plants that were CTV positive to observe the changes in the enzymatic and non-enzymatic antioxidants of citrus (Sweet Oranges only). It was observed that in response to CTV infection, both the non-enzymatic antioxidants (total flavonoid, ascorbic acid, phenolic acid) and enzymatic antioxidants (catalase, superoxide dismutase and peroxidase) activities showed an increasing trend overall. The profiling of antioxidants in response to a viral infection may help in the discovery of new biomarkers that can be used as a monitoring tool in disease management.

Monte Carlo ray-trace diffraction based on the Huygens-Fresnel principle.

The goal of this effort is to establish the conditions and limits under which the Huygens-Fresnel principle accurately describes diffraction in the Monte Carlo ray-trace (MCRT) environment. This goal is achieved by systematic intercomparison of dedicated experimental, theoretical, and numerical results. We evaluate the success of the Huygens-Fresnel principle by predicting and carefully measuring the diffraction fringes produced by both single slit and circular apertures. We then compare the results from the analytical and numerical approaches with each other and with dedicated experimental results. We conclude that use of the MCRT method to accurately describe diffraction requires that careful attention be paid to the interplay among the number of aperture points, the number of rays traced per aperture point, and the number of bins on the screen. This conclusion is supported by standard statistical analysis, including the adjusted coefficient of determination, Radj2, the rms deviation, and the reduced chi-square statistic, χv2.

Novel phase separated polycaprolactone/collagen scaffolds for cartilage tissue engineering.

Osteoarthritis is the leading cause of pain and disability worldwide. Despite treatment availability, fully functional and suitable long term treatments for large cartilage defects are yet to be sought. Cartilage tissue engineering provides an alternative treatment option with the potential of cartilage regeneration. Previously, scaffolds have been enhanced through coating with collagen type I, however, equal distribution of collagen and collagen penetration throughout the scaffold have been poor. Herein, this study aims to employ thermally induced phase separation to fabricate porous hybrid polycaprolactone (PCL)/collagen type I scaffolds, with equally distributed collagen type I throughout the scaffold. PCL/collagen scaffolds were produced using polycaprolactone, varying concentrations of collagen type I and acetic acid as the solvent. Scaffolds were seeded with chondrocytes for 14 days. Scaffolds possessed an interconnected and porous structure, which altered with an increase in collagen concentration. Collagen type I antibody staining revealed the presence of equally distributed collagen within the PCL fibres. A reduction in collagen type I concentration influenced the compressive properties of the PCL/collagen type 1 scaffolds. Specifically, 0.2% wt/vol concentration of collagen presented to have compressive properties similar to that of the native cartilage at 10% strain. All scaffolds allowed cell attachment and collagen scaffolds showed a greater number of viable chondrocytes after 14 days of culture, compared to PCL control. This study demonstrated the ability of fabricating PCL/collagen type I scaffolds which exhibit easily tuneable porosity and compressive properties. Further investigation on the long term feasibility of these scaffolds is warranted.

The effect of ethyl acetate extract of pomelo mix on systemic exposure of verapamil in rabbits.

The effect of ethyl acetate extract of pomelo fruit on systemic exposure of verapamil was explored in rabbits. Two groups each of 8 locally-inbred New Zealand male rabbits were used. The first group was used for single-dose treatment (both verapamil and pomelo extract). The second group was used for multiple-dose treatment, pomelo extract (once daily for 14 days) and verapamil single doses (at days 7 and 14). A verapamil dose of 30 mg/kg and a pomelo extract dose of 45 mg/kg were used. Single-dose treatment with pomelo extract resulted in a minor change in mean C(max) of verapamil in plasma, while a decrease of 37.8% in AUC(0-24) and 28.3% in AUC(0-∞) was observed but did not reach statistical significance. After the first period of multiple dose treatment (pomelo extract for 7 days), the combination increased the concentration of verapamil in plasma with a significant increase in mean C(max), AUC(0-24) and AUC(0-∞) by 461.9%, 299.7%, and 261.1%, respectively (p values were 0.005, 0.002, and 0.006, respectively). In contrast, after the second period (day 14 of pomelo extract use), the combination decreased the concentration of verapamil in the plasma with a substantial decrease in mean C(max), AUC(0-24), and AUC(0-∞), by 68.2%, 69.7% and 58.3%, respectively. This decrease did not reach statistical significance (p values were 0.073, 0.081 and 0.083, respectively). The T(max) was not affected significantly in both studies. The study illustrates a complex time-dependent interaction between verapamil and the ethyl acetate extract of pomelo mix. More intensive studies are needed to further understand the nature of the interaction.

Lessons learnt from an audit of 95 cases of major nasal reconstruction.

BACKGROUND: Several texts detail the possible complications of nasal reconstruction but few critically describe a series. We present an audit of the complications of 95 major nasal reconstructions. METHODS: This is a retrospective analysis of 95 consecutive major nasal reconstructions (49 male, 46 female, aged between 4 and 92 years) over a 16-year period treated in a tertiary refer-ral centre. RESULTS: Fifty-eight patients in our series required nasal reconstruction after Moh's Micrographic surgery for a morpheiform basal cell or a squamous cell carcinoma. Eight patients had further removal using frozen section to determine the margins, as the disease was very extensive. Minor procedures with local random flaps or full thickness skin grafts were excluded. Ninety-five patients underwent major reconstructive procedures and had an average of 2.8 operations. SUMMARY: The main problem was the suboptimal contouring of the alar margin in 6 of 54 patients who had a full thickness defect repaired. Other complications included telangectasia or hair growth requiring laser ablation (13), stenosis of the nasal valve area (2), ectropion after a cheek advancement flap, donor site haematoma of the pinna, and neuropathic pain.

Ethyl methanesulphonate in a parenteral formulation of BMS-214662 mesylate, a selective farnesyltransferase inhibitor: formation and rate of hydrolysis.

The objectives of the present study were to investigate the formation and rate of hydrolysis of ethyl methanesulphonate (EMS) in BMS-214662 mesylate drug substance and parenteral formulation by a gas chromatographic/mass spectrometric (GC/MS) method. EMS levels in the drug substance ranged between 0.3 microg/g and 0.8 microg/g. The parenteral formulation contains ethanol and the reaction between residual free methane sulphonic acid and ethanol may lead to the formation of EMS. Given that EMS is a potent mutagen, it is therefore of vital importance to eliminate or reduce the risk of human exposure. Data indicate no significant increase in the levels of EMS following storage of the drug product for 18 weeks at 25 degrees C or six weeks at 60 degrees C indicating that the potential reaction between ethanol and free methane sulphonic acid may not occur in the BMS-214662 formulation under the storage conditions evaluated and therefore causes no plausible safety concerns of EMS exposure in humans. Kinetic studies were conducted by spiking 200 ppb of EMS into water and the diluted and undiluted parenteral formulation. The rates of hydrolysis of EMS at 25 degrees C followed pseudo-first order kinetics and were determined to be 2.35 x 10(-4)min(-1), 67.4 x 10(-4)min(-1), and 1.32 x 10(-4)min(-1) in water, undiluted, and diluted drug product, respectively.

Effect of cations and anions on glass transition temperatures in excipient solutions.

The purpose of this study was to investigate the effects of cations and anions of various electrolytes on the glass transition temperature (Tg') of frozen solutions of excipients commonly used in freeze-drying. The effect of electrolyte concentration on freezable water content was also investigated by measuring the enthalpy of melting (DeltaH) using Differential Scanning Calorimetry (DSC). Cations and anions induce changes in Tg' of frozen solutions of commonly used parenteral excipients. These changes are dependent on the properties of the excipients used. Tg' values of 5% w/v solutions of maltose, trehalose, sucrose, dextran 40, and polyvinylpyrrolidone (PVP, 17K) were determined as a function of sodium chloride (NaCl) or potassium chloride (KCl) concentrations. In general, a significant decrease in Tg' was observed as a function of increasing the electrolyte concentration. For the disaccharide solutions, the decrease in Tg' due to the addition of NaCl or KCl was similar in magnitude, indicating that changing the cation from K+ to Na+ had no effect on Tg'. However, the decrease in Tg' for the PVP solution due to the addition of KCl was greater than that observed by the addition of NaCl . The differences in the electrolyte-induced changes on Tg' between the disaccharides and PVP may be potentially attributed to the formation of complexes between the cations and the properly oriented hydroxyl groups in the sugars leaving the anions (Cl- ions) to exert their effect on Tg'. While zero cation effect would be consistent with these results for the disaccharides, these results do not mean that the cation effects are zero; they only mean that the cation effects are the same. For the PVP solution, K+ and Na+ ions are not engaged in complex formation with PVP due to the lack of hydroxyl groups. We hypothesize that the structure-breaking K+ ions increase the fluidity of water and exert a greater plasticizing effect on Tg', leading to a more significant decrease in Tg' than the structure-making Na+ ions, which increase the viscosity of water. The decrease in Tg' of frozen solutions of pharmaceutical excipients caused by the addition of electrolytes may be primarily attributed to an increase in the unfrozen plasticizing water surrounding the excipient molecules. Formulation scientists should evaluate the use of electrolytes in the formulation development of lyophilized products containing commonly used excipients. Electrolytes are often needed as stabilizers for protein formulations; however, their selection and use should be properly evaluated. Because electrolytes cause a decrease in Tg' as a function of electrolyte concentration, it is recommended that the minimum electrolyte concentration needed to maintain product stability should be used to minimize the effect of the electrolyte on lowering the Tg'.

Rhinocerebral mucormycosis with orbital and intracranial extension: a case report and review of optimum management.

Rhinocerebral mucormycosis is a devastating, rapidly progressive and often fatal opportunistic fungal infection predominantly affecting individuals with underlying metabolic and/or immunological compromise. Intracranial extension of the disease has invariably been associated with mortality.We present a review of optimum management of rhinocerebral mucormycosis and a case report of sinonasal mucormycosis with intracranial and orbital extension which was treated successfully with a combination of systemic liposomal amphotericin B therapy and wide surgical debridement.

Response to cotrimoxazole in the management of childhood pneumonia in first-level health care facilities.

BACKGROUND: Reports of high levels of antimicrobial resistance to cotrimoxazole in children with non-severe pneumonia (NSP) have prompted calls for a change to amoxicillin in the therapeutic guidelines at the first-level health care facility (FLHF). FLHFs lack data about the use of World Health Organization (WHO) acute respiratory infection (ARI) standard case management (SCM). OBJECTIVE: To apply ARI SCM guidelines at the FLHF, assess clinical outcome of NSP with oral cotrimoxazole and determine the risk factors influencing treatment outcome. DESIGN: Health care workers (HCWs) at 14 health centres managed children aged 2-59 months with NSP according to ARI SCM guidelines. The primary outcome was treatment failure, including change of antibiotic therapy and loss to follow-up. RESULTS: Of 949 children enrolled, 110 (11.6%) failed therapy with oral cotrimoxazole. Clinical failure was significantly higher among children presenting with a fast respiratory rate of > or = 15 breaths/min above normal for age and wheezing on examination. CONCLUSIONS: To treat children with NSP at the FLHF, oral cotrimoxazole is an acceptable treatment choice in view of the efficacy, cost and ease of use. In children with wheezing and signs of pneumonia, the decision to use antibiotic therapy should be made after a trial of bronchodilator therapy.

Impurities in a lyophilized formulation of BMS-204352: identification and role of sanitizing agents.

The purpose of this study was to identify two impurities in the parenteral lyophilized formulation of BMS-204352, investigate the role of sanitizing agents as their potential source, evaluate their effect on drug product stability, and develop a strategy to prevent their contamination of the drug product. The two impurities were identified as o-phenylphenol and 4-t-amylphenol based on liquid chromatography/mass spectroscopy (LC/MS) and chromatographic comparison to authentic samples. The LC/MS spectra of commercially available o-phenylphenol and 4-t-amylphenol showed identical patterns of fragmentation and the same retention times as the impurities identified in the BMS-204352 lyophilized product. Levels of these impurities were low and ranged between 0.2-0.3 microg/vial as determined by HPLC and using an authentic external reference standard. To confirm the hypothesis that the commercial sanitizing agents used in the sterile area were the source of these phenolic impurities, several product samples were spiked with the sanitizing agents. Both o-phenylphenol and 4-t-amylphenol were detected in the spiked samples. Further investigation revealed that o-phenylphenol and 4-t-amylphenol are active ingredients of these commercial sanitizing agents. Drug product samples containing the phenolic impurities showed no potency loss following storage at 30, 50, and 70 degrees C indicating these impurities had no adverse effect on product stability. These studies suggest that sanitizing agents used in the sterile area, although may be present at trace levels below typical cleaning procedure detection methods, need to be properly controlled and closely monitored during the manufacturing of injectable products, particularly highly potent drugs. Sanitizing agents, even though not used on product contact surfaces, may potentially contaminate a product through vapor transfer in an open environment.

A new approach: regional nerve blockade for angioplasty of the lower limb.

PURPOSE: An audit study investigated the pilot use of regional nerve block analgesia (as an alternative to sedative/opiate, general or central neuraxial anesthesia) performed by radiologists with the assistance of imaging techniques during complex prolonged angiography. METHODS: Radiologists were trained by anesthetic consultants to administer and use lower limb peripheral nerve block for difficult prolonged angioplasty procedures for patients with severe lower limb rest pain who were unable to lie in the supine position. In a pilot study 25 patients with limb-threatening ischemia received sciatic and femoral nerve blockade for angioplasty. The technique was developed and perfected in 12 patients and in a subsequent 13 patients the details of the angiography procedures, peripheral anesthesia, supplementary analgesia, complications, and pain assessment scores were recorded. Pain scores were also recorded in 11 patients prior to epidural/spinal anesthesia for critical ischemic leg angioplasty. RESULTS: All patients with peripheral nerve blockade experienced a reduction in their ischemic rest pain to a level that permitted angioplasty techniques to be performed without spinal, epidural or general analgesia. In patients undergoing complex angioplasty intervention, the mean pain score by visual analogue scale was 3.7, out of a maximum score of 10. CONCLUSIONS: The successful use of peripheral nerve blocks was safe and effective as an alternative to sedative/opiate, epidural or general anesthesia in patients undergoing complex angiography and has optimized the use of radiological and anesthetic department resources. This has permitted the frequent radiological treatment of patients with limb-threatening ischemia and reduced delays caused by the difficulty in enlisting the help of anesthetists, often at short notice, from the busy operating lists.

Degradation of a lyophilized formulation of BMS-204352: identification of degradants and role of elastomeric closures.

The purpose of this study was to identify two degradation products formed in the parenteral lyophilized formulation of BMS-204352, investigate the possible role of elastomeric closures in their formation, and develop a strategy to minimize/control their formation. The first degradant was identified as the hydroxymethyl derivative (formaldehyde adduct, BMS-215842) of the drug substance formed by the reaction of BMS-204352 with formaldehyde. Structure confirmation was based on liquid chromatography/mass spectroscopy (LC/MS), nuclear magnetic resonance (NMR), and chromatographic comparison to an authentic sample of the hydroxymethyl degradation product, BMS-215842. To confirm the hypothesis that formaldehyde originated from the rubber closure, migrated into the product, and reacted with BMS-204352 drug substance to form the hydroxymethyl degradant, lyophilized drug product was manufactured, the vials were stoppered with two different rubber closure formulations, and its stability was monitored. The formaldehyde adduct degradant was observed only in the drug product vials stoppered with one of the rubber closures that was evaluated. Although formaldehyde has not been detected historically as leachable and is not an added ingredient in the rubber formulation, information obtained from the stopper manufacturer indicated that the reinforcing agent used in the stopper formulation may be a potential source of formaldehyde. The second degradant was identified as the desfluoro hydroxy analog (BMS-188929) based on LC/MS, NMR, and chromatographic comparison to an authentic sample of the desfluoro hydroxy degradation product.

Influence of formaldehyde impurity in polysorbate 80 and PEG-300 on the stability of a parenteral formulation of BMS-204352: identification and control of the degradation product.

The purpose of this study was to identify a degradation product formed in the clinical parenteral formulation of BMS-204352, investigate the role of excipients in its formation, and develop a strategy to minimize/control its formation. The degradant was identified as the hydroxy methyl derivative (formaldehyde adduct, BMS-215842) of the drug substance based upon liquid chromatography/mass spectroscopy (LC/MS), liquid chromatography/mass spectroscopy/mass spectroscopy (LC/MS/MS), nuclear magnetic resonance (NMR), and chromatographic comparison to an authentic sample of hydroxymethyl degradation product, BMS-215842. An assay method for the detection of formaldehyde based on HPLC quantitation of formaldehyde dinitrophenylhydrazone was developed to quantitate its levels in various Polysorbate 80 and PEG 300 excipient lots. A direct relationship between the levels of formaldehyde in the excipients and the formation of the hydroxymethyl degradant was found. To confirm the hypothesis that the formaldehyde impurity in these two excipients contributed to the formation of the hydroxymethyl degradant, several clinical formulation lots were spiked with formaldehyde equivalent to 1, 10, and 100 mg/g of BMS-204352. A correlation was found between the formaldehyde level and the quantity of the hydroxymethyl degradant formed upon storage at 5 and 25 degrees C. From these experiments, a limit test on the formaldehyde content in polysorbate 80 and PEG 300 can be set as part of a strategy to limit the formation of the degradation product.

Helminth parasites of the western sandpiper, Calidris mauri (Aves), from El Paso and Hudspeth counties, Texas.

Fifty western sandpipers, Calidris mauri, from El Paso and Hudspeth counties, Texas, were collected and examined for helminth parasites. Fifty-three helminths (means abundance = 1.06, SD = 2.31) consisting of 4 cestode and 1 nematode species were collected. The helminth community showed low species richness (5), low diversity and evenness (0.05, 0.14), low concentration for dominance (0.19), and all species were contagiously distributed. There were no clearly identifiable core species.