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Biomedical subjects

S K Jain

Publications and source records attributed to S K Jain.

At least 19 recordsLinked to original sources

Freezing of fluids confined in a disordered nanoporous structure.

Freezing of a simple fluid in a disordered nanoporous carbon is studied using molecular simulations. Only partial crystallization occurs, and the confined phase is composed of crystalline and amorphous nanodomains. This freezing behavior departs strongly from that for nanopores of simple geometry. We present a method for analyzing the freezing in such disordered materials in terms of a transition in the average size and number of crystalline clusters. The results provide a basis for the interpretation of experiments on freezing in such materials, particularly 1H-NMR and scattering experiments.

Journal Article↗

Demonstration of uterine receptivity in vitro by co-culture of rat epithelial cells and blastocyst.

Uterine receptivity is prerequisite for the attachment of the embryo to the uterine epithelium and involves a specialized polarity-dependent property of uterine epithelial (UE) cells. These UE cells, when polarized in culture, behave like cells in utero by exhibiting apico-basal polarity. In order to develop an implantation model in vitro, UE cells were polarized on extracellular matrix (ECM), and polarity was validated by response to estradiol-17beta administered exogenously. UE cells of pregnant rats at day-3 and day-4 post-coitum (p.c.) and of non-pregnant rats were cultured on bare and extracellular-matrix-coated petri dishes until confluency. Hatched blastocysts were transferred to the cultures, and adhesion was monitored every 24 h. Although blastocysts attached to UE cells that were taken from non-pregnant rats and from rats of day-3 p.c. and cultured on bare plastic, they failed to attach to these cells polarized on ECM. However, blastocysts attached firmly to UE cells that had been taken from rats of day-4 p.c. and polarized on ECM. Receptivity of UE cells taken from non-pregnant and pregnant (day-4 p.c.) rats was quantitated by flow cytometric estimation of cellular levels of beta3 integrin. The expression of beta3 integrin in UE cells from rats of day-4 p.c. was highly significant (P<0.01) when compared with its expression in UE cells from non-pregnant rats. The expression of beta3 integrin in UE cells of day-4 p.c. confirmed the receptivity of these cells to blastocyst implantation. Uterine receptivity was also validated in vivo by inducing the decidual cell reaction in rats ovariectomized on day-3 and day-4 p.c. Whereas remarkable deciduoma was noticed in the animals of day-4 p.c., it was absent in the animals of day-3 p.c., thereby indicating that the uterus was receptive on day-4 p.c. only. Thus, blastocysts do not attach to polarized UE cells that have been obtained from a non-receptive uterus. Attachment will occur only if the cells are obtained from a receptive uterus. UE cell receptivity is therefore essential for mimicking the process of implantation in vitro.

Animals↗

A novel recombinant multiepitope protein as a hepatitis C diagnostic intermediate of high sensitivity and specificity.

A novel recombinant multiepitope protein has been designed that consists of six linear, immunodominant, and phylogenetically conserved epitopes from hepatitis C virus. Five of these antigens (core, NS3, NS4I, NS4II, and NS5) are being used in many of the third-generation kits while sixth epitope (core3g) is an additional sequence from a newly identified Indian isolate. The genes for these epitopes have been joined together to code for a single multiepitope protein that has been evaluated for its diagnostic potential for the detection of anti-HCV antibodies in human plasma. Two separate synthetic genes have been designed, both encoding the same six epitopes in a single open reading frame along with spacers having additional amino acids to function as flexible (r-HCV-F-MEP) or rigid (r-HCV-R-MEP) linkers. High-level expression of hepatitis C multiepitope protein in Escherichia coli has been achieved. The protein has been purified using a single affinity step yielding >25 mg pure protein/liter culture and used as the coating antigen in anti-HCV EIA. The use of this multiepitope protein eliminates the requirement for multiple diagnostic intermediates for the development of anti-HCV diagnostic kit. The sensitivity and specificity of the HCV multiepitope protein was evaluated by Boston Biomedica Worldwide Performance Panels, HCV Seroconversion Panels and Viral Co-infection Panels, and was found to be comparable with commercially available anti-HCV EIA kits. This analysis indicated its unequivocal performance as capture antigen in anti-HCV EIA. The high epitope density, careful choice of epitopes and use of E. coli system for expression, coupled with simple purification protocol provides the potential for the development of an inexpensive diagnostic test with high degree of sensitivity and specificity.

Amino Acid Sequence↗

Child survival and safe motherhood program in Rajasthan.

OBJECTIVE: This study was planned to evaluate the MCH services, particularly immunization in rural areas of the poor-performing state of Rajasthan. METHODS: A community-based, cross-sectional survey using the WHO 30 cluster technique was carried out as a field exercise by participants of 9th Field Epidemiology Training Programme (FETP) course by National Institute of Communicable Diseases (NICD) in rural areas of Alwar district of Rajasthan. RESULTS: Less than one third (28.9%) of children, aged 12-23 months, were fully immunized with BCG, 3 DPT, 3 OPV and Measles vaccines; around a quarter (26.5%) had not received even a single vaccine (non immunized), and little less than half (44.5%) were found partially immunized. Around half of the eligible children were vaccinated for BCG (55.9%) and Measles (43.6%). Though nearly two-third (66.8%) were covered with first dose of DPT and OPV, but about one third of these children dropped out of third dose of DPT and OPV for various reasons. National Family Health Survey (NFHS) data also had revealed that BCG coverage was 64.3%; measles was 36.2%; and coverage by DPT 1, 2, 3 and Polio 1,2 and 3 were 64.4%, 57.0%, 46.6% and 77.5%, 71.1% and 54.4% respectively in rural areas. The main reasons for drop-out or non-immunization was "lack of information about the immunization programme" (41.3%). Though nearly all (more than 96%) of the children were immunized through Government established centers, but immunization cards/documents were made available only to 27.6% of children. CONCLUSION: The problem of low coverage and high drop-out rate of immunization could be overcome by creating awareness of the program and relevance of 2nd and 3rd doses of DPT and polio vaccines. Increasing community participation through intensive and extensive health education campaign should also be undertaken. Since most of the deliveries were done at home under the supervision of untrained midwives, training programme as well as involving them in IEC activities should be contemplated.

Communicable Disease Control↗

Transdermal atenolol releasing system: an approach towards its development.

A polymer matrix system for transdermal delivery of atenolol was developed for its prolonged and controlled release using different ratios of ethylcellulose and hydroxypropyl methylcellulose. These polymeric matrix films were characterized for thickness, tensile strength, moisture content and drug content. They were also studied for in vitro drug release and in vitro drug skin permeation. The drug release from the films was found to be Fickian diffusion type and exhibiting linear relationship between drug release (Q) vs. square root of time (t0.5). The in vitro skin permeation of drug from transdermal drug delivery system (TDDS) was evaluated using dermatomed pig skin. The product which shows in vitro drug skin permeation near to 64 mcg/h/ml was selected for in vivo studies. The in vivo studies revealed that Ma EC HPMC 46 is most effective among the other polymeric matrix TDDS. The AUC0-28 with Ma EC HPMC 46 was better than orally administered conventional doses at twelve hours interval (AUC0-28 1587 ng h/ml) as well as no trough and peaks in drug plasma level was recorded with TDDS. Hence, it could be concluded that the designed polymeric matrix TDDS of atenolol could be used successfully for effective and prolonged delivery of atenolol. However, it further demands exploration in clinic, an insight vision towards the development of TDDS for commercial use.

Administration, Cutaneous↗

Design and development of multivesicular liposomal depot delivery system for controlled systemic delivery of acyclovir sodium.

The aim of the present study was to design a depot delivery system of acyclovir sodium using multivesicular liposomes (MVLs) to overcome the limitations of conventional therapies and to investigate its in vivo effectiveness for sustained delivery. MVLs of acyclovir were prepared by the reverse phase evaporation method. The loading efficiency of the MVLs (45%-82%) was found to be 3 to 6 times higher than conventional multilamellar vesicles (MLVs). The in vitro release of acyclovir from MVL formulations was found to be in a sustained manner and only 70% of drug was released in 96 hours, whereas conventional MLVs released 80% of drug in 16 hours. Following intradermal administration to Wistar rats, the MVL formulations showed effective plasma concentration for 48 hours compared with MLVs and free drug solution (12-16 hours). C(max) values of MVL formulations were significantly less (8.6-11.4 microg/mL) than MLV and free drug solution (12.5 microg/mL). The AUC(0-48) of the MVL formulations was 1.5- and 3-fold higher compared with conventional liposomes and free drug solution, respectively. Overall, formulations containing phosphatidyl glycerol as negatively charged lipid showed better results. The MVL delivery system as an intradermal depot offers the advantage of a very high loading and controlled release of acyclovir for an extended period of time. The increase in AUC and decrease in C(max) reflects that the MVL formulations could reduce the toxic complications and limitations of conventional iv and oral therapies.

Acyclovir↗

Skew flap technique in trans-tibial amputation.

The long posterior flap technique is an established technique for trans-tibial amputation in ischaemic limbs. Despite its success, it has a few drawbacks. It may be time-consuming and requires considerable planning, and at times the dog-ears cannot be avoided. The suture line passes over the distal end of the stump, which is usually a problem during prosthetic use. The skew flap technique retains the advantages of the long posterior flap technique and eliminates the difficulties of prosthetic fitting. The equal skin flaps are skewed so that the flaps become anteromedial and posterolateral, whereas the calf muscle flap remains long underneath the skewed skin flaps. The posterior muscles are brought anteriorly covering the cut ends of the bones and are buried in between the tibia and its anterior periosteum, by suturing their margins with the periosteum. The skew flap procedure was perceived in 1980 and was started at the Artificial Limb Centre, Pune in 1983 by the author. This procedure underwent many changes during the initial 5 years and by the end of April 1992, 85 trans-tibial amputations were performed using this technique. A 9-year follow-up of these patients, who had been using prostheses with ease and without any discomfort or problem, had been exceptionally good. Encouraged by the results, this technique is now being practised as routinely. By March 1998, a total of 125 such trans-tibial amputations had been performed in 119 patients, with excellent results.

Adolescent↗

Transferrin coupled liposomes as drug delivery carriers for brain targeting of 5-florouracil.

Diseases and disorders of the brain are extremely difficult to treat pharmacologically because most drugs are unable to pass across the blood--brain barriers. Complex multi-strand tight junctions between adjacent cerebral endothelial cells and between choroid plexus epithelial cells form a physical barrier and prevent the passage of water soluble drugs from the blood into the brain, whereas the inward passage of lipid soluble drugs is restricted by drug efflux pumps which act as a functional barrier. In the present work, a transferrin-coupled liposomal system for brain delivery of 5-florouracil has been investigated.5-florouracil and (99m)Tc-DTPA bearing non-coupled liposomes were prepared by cast film method, which were coupled with the transferrin by incubating these liposomes with transferrin in the presence of the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in saline phosphate buffer (pH 7.4). These liposomal systems were characterized for vesicle size, percent drug entrapment, and in vitro drug release. The size of the liposomes was increased on coupling with transferrin while percent drug entrapment reduced. The results of the in vitro release profile demonstrated that non-coupled liposomal formulation releases a comparatively higher percent (i.e. 74.8+/-3.21%) of drug than coupled liposomes. Results of in vivo study suggested a selective uptake of the transferrin-coupled liposomes from the brain capillary endothelial cells. In case of coupled liposomes, the level of radioactivity was 17-fold more as compared to the free radioactive agent and 13 times more with the non-coupled liposomes. Therefore, it could be concluded that using transferrin coupled liposomes the brain uptake of the drug could be enhanced.

Animals↗

Chitosan hydrochloride based microspheres of albendazole for colonic drug delivery.

Microspheres of chitosan hydrochloride (CH) were prepared in order to deliver albendazole specifically into the colon. Microspheres were prepared by an emulsion method using different ratios of drug and CH (1:1 to 1:5), agitation speeds (500 to 1500 rpm) and concentrations of glutaraldehyde in toluene as the cross-linking agent (0.25 to 1.0% w/v). The effect of polymer concentration, stirring rate and concentration of cross-linking agent on the particle size and drug loading was studied. With an increase in CH concentration, the average particle size was increased. Increased agitation speed reduced the size of the microspheres but higher agitation speed resulted in irregularly shaped microspheres. Increasing the concentration of cross-linking agent produced more regularly shaped microspheres of smaller size. The drug loading was highest at a drug: CH ratio of 1:3, stirring speed 1000 rpm and 0.75% w/v concentration of cross-linking agent. The effect of CH concentration on in vitro drug release from the microspheres was evaluated in simulated g.i.t fluids. A comparative in vitro drug release study of the optimized formulation was carried out in simulated colonic fluid, with and without 2% rat caecal content. The drug release in 24 h was 48.9% in colonic fluid without rat caecal content, and 76.5% in colonic fluid with rat caecal contents.

Albendazole↗

Radioactive iodine therapy in Graves' hyperthyroidism: a prospective study from a tertiary referral centre in north India.

BACKGROUND: Radioactive iodine has gained widespread acceptance as the first-line therapy for Graves' hyperthyroidism and is the preferred treatment option in most situations. OBJECTIVE: A prospective study was conducted to look at the therapeutic practice of use of radioactive iodine in the treatment of Graves' hyperthyroidism, to determine whether the expected or desired therapeutic outcome is achieved. SETTINGS: A tertiary referral centre in north India, Delhi that caters to patients with thyroid disorders. METHODS: One hundred and seventy four consecutive subjects with Graves' hyperthyroidism, who were given radioactive iodine were followed up. RESULTS: There were 59 (33.9%) males and 115 (66.1%) females. The mean age was 41.8 +/- 9 years. The dose of radioactive iodine ranged from 2 mCi to 15 mCi and the mean dose administered was 5.2 +/- 1.9 mCi. After one year following radioactive iodine therapy, 29 (16.7%) subjects were euthyroid, 51 (29.3%) were hypothyroid and the remaining 94 (54%) had persisting hyperthyroidism. Those subjects with persisting hyperthyroidism at one year after radioactive iodine had received a significantly lower dose compared to the groups who had achieved cure (either euthyroidism or hypothyroidism). CONCLUSION: The study shows that the current practice of empirical low dose radioactive iodine therapy to avoid hypothyroidism results in majority of patients having persisting hyperthyroidism. There is a need to take a new look at the current practice to increase the cure rate.

Adult↗

Indian homemade firearm--a technical review.

A wide variety of homemade (country made) firearms are involved in crime cases in India. These firearms are made up of very cheap material and are not safe for firing. Moreover, the country made firearms are different in their design, loading and locking mechanism, cocking and firing arrangements. In this paper we have studied the characteristic features of 300 country made firearms received for examination in the Central Forensic Science Laboratory (CFSL), Chandigarh during last two decades. The characteristic features of these firearms are so unique that the fired crime bullets or cartridges can easily be matched with the test. It is hoped that such information will be useful for firearm experts in case of interpretation.

Equipment Design↗

Maroteaux-Lamy syndrome.

Mucopolysaccharidoses are a type of lysosomal storage disorders characterized by defect in the degradation of Mucopolysaccharides due to deficiency of specific lysosomal enzymes leading to their accumulation in various tissues. MPS -VI (Maroteaux-Lamy Syndrome) is an autosomal recessive syndrome due to deficiency of enzyme Aryl- Sulfatase -B, and is characterized by characteristic facies, normal intelligence, Dysostosis multiplex, organomegaly, joint stiffness, corneal clouding and striking inclusions in peripheral blood leucocytes. We present an 8-year-old male child with MPS-VI syndrome, confirmed by enzyme assay.

Abnormalities, Multiple↗

Macrophages in the development of protective immunity against experimental Brugia malayi infection.

The present report compares the macrophage function in rodent hosts susceptible and resistant to the human lymphatic filariid Brugia malayi. Macrophages from both mastomys (resistant) and gerbil (susceptible) infected intraperitoneally (i.p.) with the infective larvae (L3) of B. malayi were isolated from peritoneal lavage at different time-intervals and formation rate of NO, H2O2, O2-, TNF-alpha, glutathione peroxidase and reductase was assayed. NO release was found to be significantly increased in resistant mastomys as compared to gerbils and the release was markedly suppressed by i.p. administration of the NOS inhibitor aminoguanidine (AG). The AG-treated mastomys also demonstrated significantly greater establishment of larvae which correlated well with suppressed formation of NO. Nitric oxide synergizes with superoxide to form peroxynitrite radical (potent oxidant), which is known to be more toxic per se than NO. Results indicate the possible involvement of peroxynitrite in the rapid killing of larvae in the peritoneal cavity of mastomys. In contrast, the production of H2O2 was found to be enhanced in both species indicating that B. malayi L3 could withstand the toxic effects of H2O2. The higher level of glutathione peroxidase and reductase, as observed in mastomys compared with the gerbil after larval introduction, possibly protects the cell against the injurious effect of H2O2. The TNF-alpha level remained virtually unchanged in both the hosts, suggesting an insignificant role for this cytokine in parasite establishment.

Animals↗

Potential of guar gum microspheres for target specific drug release to colon.

Various approaches for colon targeted drug delivery have been studied over the last decade including, pro-drugs, timed-released systems, coating of pH-dependant polymer and the use of polysaccharides. In the present work, a novel formulation consisting of cross-linked microspheres of guar gum has been investigated for colon-targeted delivery of metronidazole. An emulsification method involving the dispersion of aqueous solution of guar gum in castor oil was used to prepare spherical microspheres. Process parameters were analyzed in order to optimize the formulation. Shape and surface morphology of the microspheres were examined using scanning electron microscopy. Placebo microspheres exhibited a smooth surface while the incorporation of drug imparted a slight roughness to the surface texture. Particle size of the microspheres was determined using laser diffraction particle size analyzer. The in vitro drug release studies were performed in simulated gastric fluid for 2 h and intestinal fluid for 3 h, which revealed that the drug was retained comfortably inside the microspheres and that only 15.27+/-0.56% of the drug was released in 5 h. In vitro release rate studies were also carried out in simulated colonic fluid (SCF) in the presence of rat cecal contents, which showed improved drug release. Moreover, to induce the enzymes that specifically act on guar gum, the rats were treated with 1 ml of 1% w/v dispersion of guar gum for 2, 4 and 6 days and release rate studies were repeated in SCF in the presence of 2 and 4% w/v of cecal matter. A marked improvement in the drug release was observed in presence of cecal matter obtained after induction when compared to those without induction. In vitro release studies exhibited 31.23+/-1.49% drug release in 24 h in dissolution medium without rat cecal matter. However, the incorporation of 4% w/v cecal matter obtained after 6 days of enzymes induction increased the drug release to 96.24+/-4.77%.

Animals↗

Evaluation of expression of apoptosis-related proteins and their correlation with HPV, telomerase activity, and apoptotic index in cervical cancer.

OBJECTIVE: The aim of this study was to examine the expression of apoptosis-related proteins in cervical cancer, and investigate their correlation with the apoptotic index (AI), telomerase activity, human papilloma virus (HPV) infection and clinicopathological characteristics. METHODS: Fifty cervical cancer samples and 20 normal cervical tissues were assessed for the protein expression of survivin, Bcl-2, Cox-2, p53 and p73 by immunohistochemistry. HPV DNA was detected by PCR, telomerase activity by PCR-ELISA, and AI by TUNEL assay. RESULTS: 46/50 cervical tumors (92%) showed an increased telomerase activity as compared to 3/20 (15%) controls. 45/50 (90%) cervical tumors were positive for HPV, of which 30 were HPV-16 positive and 5 were HPV-18 positive. 24/50 (48%) tumors were positive for survivin, 14 (28%) for Bcl-2, 13 (26%) for Cox-2, 19/45 (42%) for p73, 10/45 (24%) for p53. Telomerase activity was highest in tumors with the poorest grade. A positive correlation was seen between survivin and Bcl-2, survivin and tumor stage, Bcl-2 and Cox-2, p73 and p53 and p73 and the AI. Despite the overexpression of various antiapoptotic proteins, no significant difference was observed in the AI between tumors and controls. CONCLUSIONS: Since deregulation of the apoptotic pathway appears to occur in cervical cancer, some apoptosis-related proteins could be assessed as potential markers for progression/prognosis in cervical cancer. Additionally, newer proteins such as p73 may play a compensatory role for the nonfunctional proteins such as p53.

Adult↗

Preparation and characterization of reverse micelle based organogels of piroxicam.

The solubilization of piroxicam to increase transdermal permeation rate was attempted by incorporating the drug in reverse micelle systems consisting of lecithin/isopropyl myristate/water [RMS-1] and sodium bis(2-ethylhexyl) sulfosuccinate (AOT)/isooctane/water [RMS-2]. The change in polarity of water present in the water pool formed by reverse micelles resulted in a solubilization of piroxicam. These systems were used for the formation of reverse micellar organogels RMO-1 and RMO-2 by means of either varying hydration ratio (Wo) or by addition of a macromolecule, e.g. gelatin, into the system or by taking both the parameters in consideration. These systems were evaluated for physical properties, toxicology, in vitro and in vivo transdermal permeation. Significant (p < 0.01) inhibition of carrageenan induced rat paw oedema was observed for products RMO-1 and RMO-2 and a marketed transdermal product after 3 h.

Administration, Topical↗