Biomedical subjects

N H Shah

Publications and source records attributed to N H Shah.

At least 19 recordsLinked to original sources

PubMed2006

UK acquired hepatitis E--An emerging problem?

Eight cases of hepatitis E acquired in the UK are reported. These cases presented to an inner city hospital in Birmingham, UK, over a 5-month period in 2005. HEV is considered unusual in the UK and generally occurs after travel to endemic regions. Only five cases of hepatitis E acquired in the UK have been reported in the literature. This series represents an increase in the local incidence of hepatitis E, particularly that of UK-acquired infection. HEV should be considered in all patients with acute hepatitis, irrespective of travel history.

Adult↗

PubMed2004

HyBrow: a prototype system for computer-aided hypothesis evaluation.

MOTIVATION: Experimental design, hypothesis-testing and model-building in the current data-rich environment require the biologists' to collect, evaluate and integrate large amounts of information of many disparate kinds. Developing a unified framework for the representation and conceptual integration of biological data and processes is a major challenge in bioinformatics because of the variety of available data and the different levels of detail at which biological processes can be considered. RESULTS: We have developed the HyBrow (Hypothesis Browser) system as a prototype bioinformatics tool for designing hypotheses and evaluating them for consistency with existing knowledge. HyBrow consists of a modeling framework with the ability to accommodate diverse biological information sources, an event-based ontology for representing biological processes at different levels of detail, a database to query information in the ontology and programs to perform hypothesis design and evaluation. We demonstrate the HyBrow prototype using the galactose gene network in Saccharomyces cerevisiae as our test system, and evaluate alternative hypotheses for consistency with stored information. AVAILABILITY: www.hybrow.org

Computational Biology↗

PubMed2004

CLENCH: a program for calculating Cluster ENriCHment using the Gene Ontology.

SUMMARY: Analysis of microarray data most often produces lists of genes with similar expression patterns, which are then subdivided into functional categories for biological interpretation. Such functional categorization is most commonly accomplished using Gene Ontology (GO) categories. Although there are several programs that identify and analyze functional categories for human, mouse and yeast genes, none of them accept Arabidopsis thaliana data. In order to address this need for A.thaliana community, we have developed a program that retrieves GO annotations for A.thaliana genes and performs functional category analysis for lists of genes selected by the user. AVAILABILITY: http://www.personal.psu.edu/nhs109/Clench

Abstracting and Indexing↗

PubMed2004

Screening time for extra-capsular proximal femoral fracture fixation; the difference between extra-medullary and intra-medullary implant usage.

The aim of this study was to compare the fluoroscopic screening time used for treatment of fractures of the trochanteric region of the femur using two different implant systems. Data were collected from 277 proximal femoral fracture fixations. A dynamic hip screw (DHS) was used in 145, and an intra-medullary hip screw (IMHS) was used in 132. There was no difference between the two groups with respect to age, gender or side. Altogether, there were 42% two parts, 35% were three parts and 23% were four parts extra-capsular neck fractures. There was no statistical difference in ionising radiation exposure in closed reduction of these fractures regardless of the fracture configuration or surgical experience of the surgeon. The mean screening time to implant a DHS in two part fractures was 0.48 min, for three part fractures it was 0.45 min and for four part fractures it was 0.46 min. The mean screening time to implant IMHS was 1.02 min for two part fractures, 0.96 min for three part fractures and 1.03 min for four part fractures. These differences were statistically significant (P < or = 0.05).

Adult↗

PubMed2003

A tool-kit for cDNA microarray and promoter analysis.

We describe two sets of programs for expediting routine tasks in analysis of cDNA microarray data and promoter sequences. The first set permits bad data points to be flagged with respect to a number of parameters and performs normalization in three different ways. It allows combining of result files into comprehensive data sets, evaluation of the quality of both technical and biological replicates and row and/or column standardization of data matrices. The second set supports mapping ESTs in the genome, identifying the corresponding genes and recovering their promoters, analyzing promoters for transcription factor binding sites, and visual representation of the results. The programs are designed primarily for Arabidopsis thaliana researchers, but can be adapted readily for other model systems. Availability and Supplementary information: http://www.personal.psu.edu/nhs109/Programs/

Algorithms↗

PubMed2002

Critical processing factors affecting rheological behavior of a wax based formulation.

The use of a wax-based vehicle is one approach to stabilize a drug which is susceptible to hydrolysis and/or oxidation. The drug used in the study, as a microfine powder, is dispersed in the wax mixture and encapsulated in a soft gelatin capsule. To ensure reproducibility of drug content uniformity and encapsulability of the soft gelatin capsule dosage form, optimal viscosity and lot to lot uniformity of the viscosity of the suspension are required. The objective of the study was to identify the critical processing factors which could affect the rheological behavior of the wax based vehicle. Rheological behavior of the vehicle at temperatures ranging from 15 to 90 degrees C was evaluated using a CSL Rheometer equipped with parallel plates and a shear rate sweep mode, unless otherwise specified. Viscosity vs. temperature profiles of the vehicle were determined using the same conditions at different cooling rates ranging from 1.3 to 20 degrees C per min. Three distinct regions of phase transition of the wax mixture can be seen in the Arrhenius plot: (i) a sol region at temperatures above 50 degrees C, (ii) a transition of gel to sol at temperatures ranging from 30 to 45 degrees C, and (iii) a gel region at temperatures below 30 degrees C. The vehicle in a sol region behaved as a Newtonian fluid, indicating minimal interactions between the hydrocarbon chains of the vehicle. The vehicle in a gel region behaved thixotropic in nature, as indicated by a hysteresis loop. The shear rate had a more pronounced effect on the area of thixotropy than the shear time. The cooling rate had a pronounced effect on the resultant viscosity. At the same applied shear rate, the vehicle which was cooled at a faster rate, may cause a recrystallization of the wax mixture in different crystalline forms, resulting in a higher viscosity than the vehicle cooled at a slower rate. This effect was more pronounced when the shear was applied at a lower rate. The results of this study indicate that shear rate and cooling rate are the critical processing factors in controlling the viscosity of the final product and must be well controlled in the manufacturing procedure.

Calorimetry, Differential Scanning↗

PubMed2001

Safety and efficacy of an oil-adjuvant vaccine against haemorrhagic septicaemia in buffalo calves: cross-protection between the serotypes B:2,5 and E:2,5.

The safety, efficacy and duration of immunity of an improved oil-adjuvant vaccine against haemorrhagic septicaemia, containing inactivated cells of Pasteurella multocida serotype B:2,5, were tested in young buffalo calves in Pakistan. For safety testing, five buffalo calves were vaccinated intramuscularly with twice the normal dose, and six weeks later with a normal dose. Except for a transient rise in rectal temperature at six hours after the vaccinations, no systemic reactions were observed. The buffaloes remained in good condition and had a normal appetite. No local reactions were observed at the injection site. For efficacy testing two trials were carried out. In the first, buffalo calves were vaccinated intramuscularly either with two doses two-and-a-half months apart, or with a single dose, or left unvaccinated. They were challenged subcutaneously with virulent P multocida after eight, 13 or 15 months. After challenge at eight months the four buffaloes given two doses and the buffalo given one dose were protected, whereas the control animal developed the typical signs of the disease. After the challenges at 13 and 15 months, the vaccinated animals were still protected whereas the control animals died. In the second trial, buffalo calves were vaccinated intramuscularly either with two doses two months apart, or with a single dose at two months or left unvaccinated. The buffaloes were challenged after eight or 14 months. After challenge at eight months the four control animals died, whereas three of the four buffaloes given a single dose were protected. After challenge at 14 months, the three control animals died, whereas four of the five buffaloes given two doses and both the buffaloes given a single dose were protected. To test for cross-protection against the heterologous serotypes E:2,5 and B:3,4, groups of mice were vaccinated once or left unvaccinated. Four weeks later, the vaccinated and control groups were challenged with a dilution series of the different challenge cultures. The vaccine appeared to induce protection against challenge with different strains of serotypes B:2,5 and E:2,5 but not against strains of serotype B:3,4.

Adjuvants, Immunologic↗

PubMed2001

Release performance of a poorly soluble drug from a novel, Eudragit-based multi-unit erosion matrix.

Mechanisms governing the release of drugs from controlled delivery systems are mainly diffusion, osmosis and erosion. For poorly soluble drugs, the existing mechanisms are limited to osmosis and matrix erosion, that are commonly observed in single unit matrix dosage forms. This study reports formulation and dissolution performance of Eudragit L 100 55 and Eudragit S 100 based multi-unit controlled release system of a poorly soluble thiazole based leukotriene D(4) antagonist, that was obtained by an extrusion/spheronization technique. Effect of triethyl citrate, that was incorporated in the matrix, on the dissolution performance of the drug was also evaluated. In vitro matrix erosion and drug release from the pellets were determined by the use of USP Dissolution Apparatus I, pH 6.8 phosphate buffer, gravimetry and UV spectrophotometry, respectively. Results obtained demonstrated that matrix erosion and drug release occurred simultaneously from the pellets. Pellets eroded with a consequent reduction in size without any change in the pellet geometry for over 12 h. Matrix erosion and drug release followed zero order kinetics. Data obtained strongly suggested a polymer controlled, surface erosion mechanism.

Acrylic Resins↗

PubMed2001

Properties of tablets containing granulations of ibuprofen and an acrylic copolymer prepared by thermal processes.

The objective of this study was to investigate the properties of tablets containing granulations of ibuprofen (Ibu) and Ammonio Methacrylate Copolymer, Type B (Eudragit RS PO) prepared by hot-melt processing. Tablets were compressed from granules prepared by hot-melt granulation (HMG) or direct compression (DC). For the hot-melt extrusion (HME) process, tablets were prepared by cutting the extrudate, manually. The physicochemical properties of tablets were investigated using thermal analysis, powder X-ray diffraction analysis, tablet hardness, and drug dissolution. The effect of thermal treatment of tablets on the dissolution characteristics of Ibu was also investigated. The results demonstrated that the Ibu lowered the glass transition temperature (Tg) of the Eudragit RS PO and the softened polymer functioned as a thermal binder in the granulation. Ibu was demonstrated to be an effective plasticizer for Eudragit RS PO in the thermal processes. The efficiency of the granulation process increased with increasing levels of Eudragit RS PO in the powder blend. Higher levels of Eudragit RS PO in the tablets prepared by HMG or HME resulted in a decrease in the dissolution rate of the Ibu. An increase in the amount of Ibu in the tablets prepared by HMG or DC led to a decrease in the initial dissolution rate of the Ibu. Following the thermal treatment of the Ibu tablets prepared by HMG, the dissolution rate was significantly decreased due to structural changes in the tablets that resulted from the fusion and coalescence of plasticized polymer particles, causing a reduction in tablet porosity. The Ibu tablets prepared by HME demonstrated minimal changes in their release properties following thermal treatment even at temperatures higher than the Tg of the polymer. HME was shown to be a novel method to prepare matrix tablets and stable dissolution properties were obtained when tablets were stored at 40 degrees C for 30 days.

Acrylic Resins↗

PubMed2000

Effect of formulation and process variables on porosity parameters and release rates from a multi unit erosion matrix of a poorly soluble drug.

The effect of drug loading, water required for granulation and spheronization time on porosity parameters (intrusion-extrusion isotherms, pore size distribution, total pore surface area, mean pore diameter, shape and morphology of pores) and drug release rates from pellets of a poorly soluble drug was investigated. Porosity parameters were determined by mercury intrusion porosimetry. The drug loading was found to have a profound effect on the porosity parameters. Pellets with low drug loading showed increased pore surface area with small mean pore diameters and an increased number of total pores. On the other hand, pellets with high drug loading had decreased pore surface areas with larger mean pore diameters and a reduction in the total number of pores. With high drug loading, the drug release rate decreased. Water required for granulation had a direct effect on the total porosity of the pellets. Spheronization time from 2 to 10 min had a pronounced effect on porosity parameters and release rates. No changes in porosity parameters and release rates were observed from 10 to 20 min of spheronization time. It was shown that each porosity parameter investigated was well correlated with drug release rates and thus it is important to study the effect of porosity parameters in evaluating the in vitro performance of the multi-unit erosion matrix for the controlled release of a poorly soluble drug.

Chemistry, Pharmaceutical↗

PubMed2000

Controlled release of drugs from injectable in situ formed biodegradable PLGA microspheres: effect of various formulation variables.

A novel in situ method for the preparation of injectable biodegradable poly(lactide-co-glycolide) (PLGA) microspheres for the controlled delivery of drugs is described here. A stable dispersion of PLGA microglobules ('premicrospheres' or 'embryonic microspheres') in a vehicle mixture on injection, comes in contact with water from aqueous buffer or physiological fluid, thereby hardening the microglobules into solid matrix type microparticles entrapping the drug (in situ formed microspheres). The drug is then released from these microspheres in a controlled fashion. The effect of the following formulation variables on the characteristics of the novel drug delivery system (NDDS) was investigated: (i) the concentrations of polyethylene glycol 400 (PEG 400), the encapsulated drug, and the hydrophilic excipient (mannitol); and (ii) the types of encapsulated drug (micromolecules and macromolecules such as protein) and vehicles (replacing triacetin and Miglyol 812 by triethyl citrate and soybean oil respectively). Also, the effect of formulation, process, and storage (15 days/4 degrees C) conditions on the physical stability of the encapsulated protein was evaluated. The in vitro drug release was enhanced with decrease in the PEG 400 concentration and increase in the drug and mannitol concentration. The drug release was retarded with increase in the molecular weight of the encapsulated drug. Substitution of triacetin by triethyl citrate and miglyol 812 by soybean oil resulted in variation in the release of the drug from the in situ formed microspheres. A preliminary investigation of the physical stability of the myoglobin revealed that the alpha-helical structure was unaffected by the formulation, process, and the storage conditions.

Chemistry, Pharmaceutical↗

PubMed2000

Comparison of various injectable protein-loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices: in-situ-formed implant versus in-situ-formed microspheres versus isolated microspheres.

The purpose of this research was to prepare various injectable, protein (cytochrome c)-loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices by a novel microencapsulation method and to compare their characteristics. Syringeable mixtures of polymer and protein solidified upon injection when coming in contact with water, and formed a solid matrix-type implant or microspheres (in-situ-formed implant or in-situ-formed microspheres, respectively) with cytochrome c entrapped. These devices exhibited different characteristics in terms of in vitro cytochrome c release profile, percentage cytochrome c encapsulation efficiency, and particle size. The burst effect from these devices exhibited the following trend: in-situ-formed implant > in-situ-formed microspheres > isolated microspheres. The in-situ-formed microspheres were larger in size than the isolated microspheres. Also, the isolated microspheres exhibited the slowest release of cytochrome c, whereas the in-situ-formed implant exhibited the fastest release. The microencapsulation process can produce various drug-loaded injectable biodegradable PLGA devices having different characteristics.

Cytochrome c Group↗

PubMed1998

Stability of a hydrophobic drug in presence of hydrous and anhydrous lactose.

The chemical stability of a hydrophobic Leukotriene receptor antagonist drug was investigated in the presence of lactose (both hydrous and anhydrous) under various humidity and temperature conditions. The effect of wet-granulation and direct-mixing on the stability of the drug was also studied. Mixtures of drug:lactose in the ratio 1:25, 1:50 and 1:100 were prepared and analyzed over a 6 week period after storage at 40, 83 and 97% RH (all at 25 degreesC) and 75% RH at 40 degreesC. The mixtures were subjected to LOD, Karl--Fischer titrimetry, HPLC and DSC analysis to evaluate the amount of moisture pickup, percent potency and presence of drug-moisture-lactose interaction. Mixtures containing lactose anhydrous picked up more moisture and exhibited greater drug degradation than those containing lactose hydrous. Also, mixtures stored under high temperature and humidity condition showed greater moisture uptake than those stored at high humidity alone. Lactose anhydrous becomes hydrated on exposure to high humidity/temperature and storage conditions. The transition state of lactose and not its stable state may be responsible for its greater interaction and subsequent degradation of the drug. Therefore, the normal belief that lactose anhydrous, which has less than 0.5% moisture, should provide greater stability as compared to lactose hydrous, needs to be properly evaluated.

Calorimetry, Differential Scanning↗

PubMed1998

Screening for novel antimicrobials from encoded combinatorial libraries by using a two-dimensional agar format.

A sensitive lawn-based format has been developed to screen bead-tethered combinatorial chemical libraries for antimicrobial activity. This method has been validated with beads linked to penicillin V via a photocleavable chemical linker in several analyses including a spike-and-recover experiment. The lawn-based screen sensitivity was modified to detect antibacterial compounds of modest potency, and a demonstration experiment with a naive combinatorial library of over 46,000 individual triazines was evaluated for antibacterial activity. Numerous hits were identified, and both active and inactive compounds were resynthesized and confirmed in traditional broth assays. This demonstration experiment suggests that novel antimicrobial compounds can be easily identified from very large combinatorial libraries of small, nonpeptidic compounds.

Bacillus subtilis↗

PubMed1998

Controlled drug delivery by biodegradable poly(ester) devices: different preparative approaches.

There has been extensive research on drug delivery by biodegradable polymeric devices since bioresorbable surgical sutures entered the market two decades ago. Among the different classes of biodegradable polymers, the thermoplastic aliphatic poly(esters) such as poly(lactide) (PLA), poly(glycolide) (PGA), and especially the copolymer of lactide and glycolide referred to as poly(lactide-co-glycolide) (PLGA) have generated tremendous interest because of their excellent biocompatibility, biodegradability, and mechanical strength. They are easy to formulate into various devices for carrying a variety of drug classes such as vaccines, peptides, proteins, and micromolecules. Most importantly, they have been approved by the United States Food and Drug Administration (FDA) for drug delivery. This review presents different preparation techniques of various drug-loaded PLGA devices, with special emphasis on preparing microparticles. Certain issues about other related biodegradable polyesters are discussed.

Absorption↗

PubMed1997

Protection against haemorrhagic septicaemia induced by vaccination of buffalo calves with an improved oil adjuvant vaccine.

An experimental oil adjuvant vaccine was developed against haemorrhagic septicaemia, a disease of cattle and buffalo caused by Pasteurella multocida serotype B and E. Mineral oil, Mercol 52, was used as adjuvant together with Span 85 and Tween 85 as emulsifiers. The vaccine was evaluated by single dose intramuscular immunisation of 1-2 year old buffalo calves. IgG and IgM class antibodies were determined by ELISA. The group of animals immunised with the experimental oil adjuvant vaccine showed a high titre of the IgG class of antibodies measured at 300 days post vaccination. To compare the protective efficacy of the vaccine with the commonly used broth bacterin, another group of buffalo calves was immunised by broth bacterin. This group showed a low level of IgG antibodies. Protection was assessed by challenge with 10(9) viable bacteria of P. multocida type B:2,5 administered subcutaneously, 250 days post vaccination. Animals vaccinated with the experimental oil adjuvant vaccine were fully protected. The other groups of animals, vaccinated with broth bacterin or used as control (non-vaccinated), developed symptoms of haemorrhagic septicaemia. A strong relationship between IgG but not IgM class antibody level and resistance to challenge was observed. The experiment demonstrated that the experimental oil adjuvant vaccine was superior to broth bacterin in providing protection against experimental haemorrhagic septicaemia in young buffalo calves beyond 250 days.

Adjuvants, Immunologic↗

PubMed1997

Development of a novel controlled-release system for gastric retention.

PURPOSE: We report on the development of a novel controlled-release gastric retention system, which consists of a matrix tablet, coated with a permeable membrane. When immersed in simulated gastric fluid, the tablet expands. The tablet remains expanded for eighteen to twenty hours, during which time the drug is released. The tablet then either disintegrates into fragments or loses its integrity. METHODS: Tablets containing a soluble drug (chlorpheniramine maleate, i.e., CPM) and a poorly soluble drug (riboflavin 5' phosphate, i.e., R5'P) were compressed. They were coated with a permeable and elastic polymer (Eudragit). Dissolution profiles of these tablets were studied. The changes in the pH, viscosity, and deformation characteristics as a function of time were measured. RESULTS: Carbopol provided a firm structure to the swollen tablet. Polyvinyl pyrrolidone XL (PVP XL) contributed to the swelling of the tablet. Carbonates provided the initial alkaline micro-environment for Carbopol to gel and conferred buoyancy to the tablet. Coating provided the support needed for the core to remain intact during drug release and, at the same time, it allowed drug release due to its permeable nature. During release, the gelling properties of Carbopol lessened, resulting in a decrease in the firmness of the core. This was evident from the decrease in the viscosity of the core. The energy required at 50% strain also decreased as the drug release progressed. CONCLUSIONS: When this tablet is ingested, the chances of its elimination through the pylorus should be greatly reduced due to tablet's expansion, and due to its disintegration or loss in integrity it should then be expelled out of the stomach at the end of the drug release.

Acrylic Resins↗

PubMed1996

Vacuolating cytotoxic activity of Pasteurella multocida causing haemorrhagic septicaemia in buffalo and cattle.

The toxic activity of Pasteurella multocida strains which cause haemorrhagic septicaemia (HS) in buffalo and cattle was examined in a mouse model. Mice were injected intraperitoneally with 10(2) cells of P. multocida serotype B:2,5. Electron microscopy of peritoneal macrophages obtained 6 h after injection revealed strong induction of cytoplasmic vacuolation, macrophage lysis and death. In vitro experiments with the mouse macrophage cell line RAW 264 incubated with cultures of various HS- and non-HS-associated strains of P. multocida or with culture supernatants revealed macrophage vacuolation when HS-associated strains were used. On pre-incubation of the strains with antiserum obtained from buffalo infected with P. multocida serotype B:2,5 no vacuolation was observed. These results are indicative of the presence of vacuolating cytotoxic activity in HS-associated strains of P. multocida.

Animals↗