Pharmacokinetics And Metabolism Studies Of Antifilarial Drugs Derivatives Of Benzimidazole Carbamate

Farmakokinetik dan metabolisme dua jenis drug ani filaria baru UMF-078 dan UMF-058 telah dikaji dalam model haiwan yang sesuai dengan perekaan bagi aspek penyerapan drug dan metabolisme The pharmacokinetics and metabolism of two new antifilarial drugs, UMF-078 and UMF-058 have been investigated in suitable animal models with special emphasis on drug absorption and drug metabolis

A Resolution Based Automated Theorem Proving System Using Concurrent Processing Approach

Semenjak pembangunan sistem pembuktian teorem automatik berdasarkan resolusi yang pertama di pertengahan 1960an, terdapat penyelidikan yang berterusan di dalam bidang ini untuk mempertingkatkan proses penyelesaian masalah di dalam sistemsistem pembuktian teorem. Penyelidikan pada masa kini di dalam bidang ini adalah tertumpu kepada penggunaan kaedah-kaedah pengideksan pangkalan data dan pemprosesan selari untuk mempertingkatkan kecekapan sistem-sistem tersebut. Apa yang dimaksudkan tentang kecekapan sistem adalah tertumpu kepada kelajuan pedaksanaan sistem di dalam pembuktian teorem oleh suatu sistem pembuktian teorem automatik. Ever since the first resolution based automated theorem proving system was developed on a computer in the mid 1960s, there has been constant research in this area on enhancing the problem solving process of the theorem provers. The recent trend in this area is towards exploiting database indexing and parallel processing in increasing the efficiency of these systems, in particular the execution speed of the theorem prover in proving a theorem

The Influence of Electrospinning Parameters and Drug Loading on Polyhydroxyalkanoate (PHA) Nanofibers for Drug Delivery

The impact of polymer concentration and drug loading on nanofiber morphology and diameter were investigated during electrospinning of polyhydroxyalkanoate nanofibrous films. Low molecular weight poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-95 mol% 4HB)] required a 5-fold higher solution concentration than high molecular weight poly(3-hydroxybutyrate) [P(3HB)] to produce bead-free nanofibers. Loading the films with paclitaxel increased the initial polymer solution viscosity allowing larger diameter nanofibers to form. Furthermore, paclitaxel added at 1% (w/w) into 8 % (w/v) P(3HB-co-95 mol% 4HB) solution eliminated the formation of beads seen in solutions without the drug, at the same initial polymer solution concentration. In preliminary drug release studies, nanofiber mats consisting of large-diameter nanofibers with high drug loading released paclitaxel at a faster rate due to larger pore sizes. This was a consequence of the random packing of larger diameter nanofibers. However, the release pattern of nanofibers with low drug loading was much more consistent and controlled. Lastly, we have shown the potential applications of P(3HB-co-4HB) drug loaded nanofibers in the development of biocompatible drug eluting stents by directly coating a metal stent with a homogeneous layer of electrospun polymer

U.S. Army Installation Climate Resilience Initiatives

Energy Academic Group (EAG) New

Antiradical and Cytotoxic Activities of Varying Polarity Extracts of the Aerial Part of Euphorbia hirta L.

Euphorbia hirta is a well-known ethnomedicinal plant with diverse biological activities.The aim of the present study is to investigate the antiradical activities of various solvent extracts of the aerial part of E. hirta as well as to determine the possible cytotoxicity of these extracts. The aerial part of E. hirta was extracted with different solvent systems in order to increase polarity. The solvents used were hexane, dichloromethane (DCM), ethyl acetate (EA), ethanol (EtOH), and methanol (MeOH). The contents of total phenols and total flavonoids were analyzed byUVspectrophotometry, whereas the potential free radical-scavenging activities of the extracts were evaluated using the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), th

EFFICACY OF CLITORIA TERNATEA LEAF EXTRACT AGAINST EXPERIMENTAL ASPERGILLOSIS

Objective: To evaluate the efficacy of methanolic extract of Clitoria ternatea leaf in experimental murine systemic aspergillosis. Methods: The investigation of methanolic extract of C. ternatea leaf against experimental murine systemic aspergillosis was assessed by the survival rates, quantitative determination of fungal burden in spleen, kidney and lung organs, histopathological evaluation and serum galactomannan index. Results: Methanolic extract of C. ternatea and amphotericin B demonstrated survival benefits over control. All untreated animals died by day 14. Similarly, both treated groups had significant reductions (P< 0.05) in the fungal burden of lungs, kidneys and spleen. By day 28, there was a complete clearance of the fungi from these organs. A decline was also observed in serum galactomannan level of treated animals. Conclusion: The methanolic extract of C. ternatea was effective against aspergillosis in immunocompromised mice comparable to that of amphotericin. This study merits further clinical investigations of this extract as well as isolation and characterization of their bioactive antifungal chemical constituent(s)

Ultrastructural Study of Elaeis guineensis (Oil Palm) Leaf and Antimicrobial Activity of its Methanol Extract against Staphylococcus Aureus

Purpose: To evaluate the antimicrobial activity of the methanol extract of Elaeis guineensis leaf against Staphylococcus aureus and to determine the effect of extract treatment on the microstructure of the microbeMethods: The antimicrobial activity of the methanol leaf extract of the plant against S. aureus was examined using disc diffusion and broth dilution methods. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were carried out to determine the major alterations in the microstructure of S. aureus after treatment with the extract.Results: The extract showed a good antimicrobial activity against S. aureus with a minimum inhibition concentration (MIC) of 6.25 mg/mL and for Chloramphenicol was 30.00 ìg/mL. The main changes observed under SEM and TEM were structural disorganization of the cell membrane which occurred after 12 h and total collapse of the cell 36 h after exposure to the extract.Conclusion: We concluded that the methanolic extract of E. guineensis leaf exhibited good antimicrobial activity against S. aureus and this is supported by SEM and TEM.Keywords: Antimicrobial activity, Elaeis guineensis, Staphylococcus aureus, Scanning electron microscopy, Transmission electron microscop

Impact of COVID-19 pandemic on surgical neuro-oncology multi-disciplinary team decision making: a national survey (COVID-CNSMDT Study).

OBJECTIVES: Pressures on healthcare systems due to COVID-19 has impacted patients without COVID-19 with surgery disproportionally affected. This study aims to understand the impact on the initial management of patients with brain tumours by measuring changes to normal multidisciplinary team (MDT) decision making. DESIGN: A prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020. SETTING: Regional neurosurgical units outside London (as the pandemic was more advanced at time of study). PARTICIPANTS: Representatives from all units were invited to collect data on new patients discussed at their MDT meetings during the study period. Each unit decided if management decision for each patient had changed due to COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures included number of patients where the decision to undergo surgery changed compared with standard management usually offered by that MDT. Secondary outcome measures included changes in surgical extent, numbers referred to MDT, number of patients denied surgery not receiving any treatment and reasons for any variation across the UK. RESULTS: 18 units (75%) provided information from 80 MDT meetings that discussed 1221 patients. 10.7% of patients had their management changed-the majority (68%) did not undergo surgery and more than half of this group not undergoing surgery had no active treatment. There was marked variation across the UK (0%-28% change in management). Units that did not change management could maintain capacity with dedicated oncology lists. Low volume units were less affected. CONCLUSION: COVID-19 has had an impact on patients requiring surgery for malignant brain tumours, with patients receiving different treatments-most commonly not receiving surgery or any treatment at all. The variations show dedicated cancer operating lists may mitigate these pressures. STUDY REGISTRATION: This study was registered with the Royal College of Surgeons of England's COVID-19 Research Group (https://www.rcseng.ac.uk/coronavirus/rcs-covid-research-group/)

Adapting Yeast as Model to Study Ricin Toxin A Uptake and Trafficking‡

The plant A/B toxin ricin represents a heterodimeric glycoprotein belonging to the family of ribosome inactivating proteins, RIPs. Its toxicity towards eukaryotic cells results from the depurination of 28S rRNA due to the N-glycosidic activity of ricin toxin A chain, RTA. Since the extention of RTA by a mammalian-specific endoplasmic reticulum (ER) retention signal (KDEL) significantly increases RTA in vivo toxicity against mammalian cells, we here analyzed the phenotypic effect of RTA carrying the yeast-specific ER retention motif HDEL. Interestingly, such a toxin (RTAHDEL) showed a similar cytotoxic effect on yeast as a corresponding RTAKDEL variant on HeLa cells. Furthermore, we established a powerful yeast bioassay for RTA in vivo uptake and trafficking which is based on the measurement of dissolved oxygen in toxin-treated spheroplast cultures of S. cerevisiae. We show that yeast spheroplasts are highly sensitive against external applied RTA and further demonstrate that its toxicity is greatly enhanced by replacing the C-terminal KDEL motif by HDEL. Based on the RTA resistant phenotype seen in yeast knock-out mutants defective in early steps of endocytosis (∆end3) and/or in RTA depurination activity on 28S rRNA (∆rpl12B) we feel that the yeast-based bioassay described in this study is a powerful tool to dissect intracellular A/B toxin transport from the plasma membrane through the endosomal compartment to the ER

Environmental isolation of black yeast-like fungi involved in human infection

The present study focuses on potential agents of chromoblastomycosis and other endemic diseases in the state of Paraná, Southern Brazil. Using a highly selective protocol for chaetothyrialean black yeasts and relatives, environmental samples from the living area of symptomatic patients were analysed. Additional strains were isolated from creosote-treated wood and hydrocarbon-polluted environments, as such polluted sites have been supposed to enhance black yeast prevalence. Isolates showed morphologies compatible with the traditional etiological agents of chromoblastomycosis, e.g. Fonsecaea pedrosoi and Phialophora verrucosa, and of agents of subcutaneous or systemic infections like Cladophialophora bantiana and Exophiala jeanselmei. Some agents of mild disease were indeed encountered. However, molecular analysis proved that most environmental strains differed from known etiologic agents of pronounced disease syndromes: they belonged to the same order, but mostly were undescribed species. Agents of chromoblastomycosis and systemic disease thus far are prevalent on the human host. The hydrocarbon-polluted environments yielded yet another spectrum of chaetothyrialean fungi. These observations are of great relevance because they allow us to distinguish between categories of opportunists, indicating possible differences in pathogenicity and virulence