Formulation and evaluation of controlled release matrix tablet of diltiazem HCl by using HPMC and guar gum as polymeric matrix material.

Objetivos: En el presente trabajo se describe el desarrollo de comprimidos matriciales de clorhidrato de diltiazem.Métodos: Se obtienen comprimidos matriciales mediante el uso de goma guar y HPMC. Se estudian distintas formulaciones en las que se cambia la composición de estos materiales matriciales como controladores de la cesión. Los comprimidos se prepararon por el método de granulación húmeda y se evaluaron uniformidad de contenido, índice de hinchamiento, estabilidad y velocidad de liberación.Resultados: La capacidad de hinchamiento aumenta con el porcentaje utilizado de HPMC. Las formulaciones F7, F8 y F9 son las que muestran mejores características de liberación. Los estudios de estabilidad de la formulación seleccionada demuestran una buena resistencia a la rotura, capacidad de hinchamiento y control de la velocidad de disolución durante el estudio de estabilidad.Conclusiones: Las formulaciones F7, F8 y F9 tienen unas buenas propiedades de control de liberación del fármaco durante al menos 8 horas. La cinética de liberación se pueden ajustar a un orden cero.Aim: The present investigation concerns the development of controlled release matrix tablet of Diltiazem HCl.Methods: Matrix tablet of Diltiazem HCl was formulated by using HPMC and Guar gum as a polymeric matrix forming materials in various concentrations (%w/w) to study their ability to retard the release. The tablets were prepared by wet granulation method and evaluated for physical properties, content uniformity, swelling index, stability and in-vitro drug release.Results: Swelling was increased as the concentration and viscosity of HPMC increases. Tablets formulated using guar gum and HPMC alone were gave initial burst effect followed by controlled release for 8 hr. It was evident from the study that the formulationsF7,F8 &F9 have optimum swelling index and in vitro drug release up to 44% in 8hrs. The stability studies of optimized batch showed that there was no change in hardness, swelling index and in-vitro release up to 12 weeks.Conclusions: The batches F7, F8 and F9 possessed the high potential to release the drug gradually for more than 8 hours. The zero-order release kinetic indicates concentration independent drug release ensuring that the formulated tablet showed promising result to be a sustained release formulation

Effects of a single exercise session on pain intensity in adults with chronic pain: a systematic review and meta-analysis

Background: Chronic pain is prevalent amongst society, making it necessary to find strategies to manage chronic pain. Regular exercise is efficacious; however, pain is a barrier to initiating exercise. A single exercise session is also believed to acutely reduce pain, however, the evidence for this is less robust. Objectives: This systematic review and meta-analysis aimed to identify the effect of a single exercise session on pain intensity in adults with chronic pain. Methods: We searched eight databases and trial registries to identify randomised controlled trials evaluating the effect of a single exercise session on pain intensity in adults with chronic pain compared to a non-exercise control. Literature screening, data extraction, risk of bias (Cochrane 2.0) and quality assessment (GRADE) were conducted independently and in duplicate. Random-effects meta-analyses were performed using the metafor package in R. Results: We included 17 trials (46 study arms with 664 adults [44% female]). There were no significant differences in pain intensity (mean difference on a 0-10 scale) immediately post-exercise −0.02 (95% CI = −0.06, 0.62; I2 = 77.1%) or up to 45-min post-exercise −0.17 (95% CI = −0.49, 0.16; I2 = 34.2%). All trials were at high risk of bias and the overall confidence in these findings was very low. Conclusion: A single exercise session did not reduce pain intensity up to 1-h post-exercise. Notably, increases in pain were not observed either, suggesting that while pain can be a barrier to initiating exercise, clinicians can educate patients on the unlikelihood of exercise acutely increasing pain intensity

The association of lyme disease with loss of sexual libido and the role of urinary bladder detrusor dysfunction.

PURPOSE: The primary aim was to carry out a pilot study to compare the loss of sexual libido between a group of Lyme disease patients and a group of matched controls. The secondary aim was to evaluate whether loss of libido in Lyme disease patients is associated with urinary bladder detrusor dysfunction. METHODS: A group of 16 serologically positive Lyme disease patients and 18 controls were queried directly about loss of libido. RESULTS: The 2 groups were matched with respect to age, sex, body mass index, and mean arterial blood pressure. None of the 34 subjects was taking medication that might affect sexual libido or had undergone a previous operative procedure involving the genitourinary tract. Of the 16 Lyme disease patients, 8 (50%) had no loss of libido, and of the 18 controls, none had loss of libido (P<0.001). In the Lyme disease patient group, there was no statistically significant relationship between loss of libido and urinary bladder detrusor dysfunction (P=0.61). CONCLUSIONS: This pilot study suggested an association between Lyme disease and loss of libido. Moreover, this loss of libido did not seem to be associated with urinary bladder detrusor dysfunction. Given these results, we recommend further studies to confirm the association

Urinary bladder detrusor dysfunction symptoms in lyme disease.

PURPOSE: Symptoms of urinary bladder detrusor dysfunction have been rarely reported in Lyme disease. The aim was to carry out the first systematic study to compare the prevalence of such symptoms in a group of Lyme disease patients and a group of matched controls. METHODS: A questionnaire relating to detrusor function was administered to 17 serologically positive Lyme disease patients and to 18 control subjects. RESULTS: The two groups were matched in respect of age, sex, body mass, and mean arterial blood pressure. None of the 35 subjects was taking medication which might affect urinary function and none had undergone a previous operative procedure on the lower urinary tract. Six of the Lyme patients (35%) and none of the controls (0%) had symptoms of detrusor dysfunction (P<0.01). CONCLUSIONS: This first systematic controlled study confirms that Lyme disease is associated with urinary bladder detrusor dysfunction. Further evaluation of detrusor function is warranted in this disease

Recovery from Cogwheel Rigidity and Akinesia and Improvement in Vibration Sense and Olfactory Perception following Removal of an Epoxy-Oleic Acid DNA Adduct

+e epoxy fatty acid cis-12,13-epoxy-oleic acid, which acts as a DNA adduct, may be generated during long-term storage of many seed oils, including those used in cooking, with frying oils and fried foods being a major source in the modern human diet. Removal of this epoxy fatty acid from the locus of the N-formyl peptide receptors was associated with recovery from cogwheel rigidity and akinesia as well as with improvement in vibration sense and olfactory perception

Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr

Background: Angiogenesis, the formation of new blood vessels, has become an important target in cancer therapy. Angiogenesis plays an important role in tumor growth and metastasis. Koetjapic acid (KA) is a seco-A-ring oleanene triterpene isolated from S. koetjape. The solvent extract of this plant species was shown previously to have strong antiangiogenic activity; however the active ingredient(s) that conferred the biological activity and the mode of action was not established. Given the high concentration of KA in S. koetjape, an attempt has been made in this study to investigate the antiangiogenic properties of KA.Results: Treatment with 10-50 μg/ml KA resulted in dose dependent inhibition of new blood vessels growth in ex vivo rat aortic ring assay. KA was found to be non-cytotoxic against HUVECs with IC40.97 ± 0.37 μg/ml. KA inhibited major angiogenesis process steps, endothelial cell migration and differentiation as well as VEGF expression.Conclusions: The non-cytotoxic compound, KA, may be a potent antiangiogenic agent; its activity may be attributed to inhibition of endothelial cells migration and differentiation as well VEGF suppression

A systematic review of current knowledge of HIV epidemiology and of sexual behaviour in Nepal

OBJECTIVE: To systematically review information on HIV epidemiology and on sexual behaviour in Nepal with a view to identifying gaps in current knowledge. METHODS: Systematic review covering electronic databases, web-based information, personal contact with experts and hand searching of key journals. RESULTS: HIV-1 seroprevalence has been rising rapidly in association with high-risk behaviours, with current levels of 40% amongst the nation's injecting drug users and approaching 20% amongst Kathmandu's female commercial sex workers (FCSWs). HIV seroprevalence remains low in the general population (0.29% of 15–49 year olds). There are significant methodological limitations in many of the seroprevalence studies identified, and these estimates need to be treated with caution. There are extensive migration patterns both within the country and internationally which provide the potential for considerable sexual networking. However, studies of sexual behaviour have focused on FCSWs and the extent of sexual networks within the general population is largely unknown. CONCLUSIONS: Whilst some of the ingredients are present for an explosive HIV epidemic in Nepal, crucial knowledge on sexual behaviour in the general population is missing. Research on sexual networking is urgently required to guide HIV control in Nepal. There is also a need for further good-quality epidemiological studies of HIV seroprevalence

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

Use of Whole-genome Sequencing of Adenovirus in Immunocompromised Paediatric Patients to Identify Nosocomial Transmission and Mixed-genotype Infection

Background: Adenoviruses are significant pathogens for the immunocompromised, arising from primary infection or reinfection. Serotyping is insufficient to support nosocomial transmission investigations. We investigate whether whole-genome sequencing (WGS) provides clinically relevant information on transmission among patients in a paediatric tertiary hospital. Methods: We developed a target-enriched adenovirus WGS technique for clinical samples and retrospectively sequenced 107 adenovirus-positive residual diagnostic samples, including viraemias (>5x104 copies/ml), from 37 patients collected January 2011 - March 2016. WGS was used to determine genotype and for phylogenetic analysis. Results: Adenovirus sequences were recovered from 105/107 samples. Full genome sequences were recovered from all 20 non-species C samples and from 36/85 species C viruses, with partial genome sequences recovered from the rest. Whole genome phylogenetic analysis suggested linkage of three genotype A31 cases and uncovered an unsuspected epidemiological link to an A31 infection first detected on the same ward four years earlier. In nine samples from one patient who died we identified a mixed genotype adenovirus infection. Conclusions: Adenovirus WGS from clinical samples is possible and useful for genotyping and molecular epidemiology. WGS identified likely nosocomial transmission with greater resolution than conventional genotyping, and distinguished between adenovirus disease due to single or multiple genotypes