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Biomedical subjects

G P Talwar

Publications and source records attributed to G P Talwar.

At least 19 recordsLinked to original sources
PubMed2006

A polyherbal vaginal pessary with spermicidal and antimicrobial action: evaluation of its safety.

A polyherbal vaginal pessary (Praneem) has been formulated that has antimicrobial properties against genital pathogens in addition to spermicidal action. Thus, it has dual potential as a barrier method for contraception and for providing protection against some sexually transmitted infections. The present study reports the findings of a multicentre trial that was conducted to evaluate the safety of this product. Trials were carried out in 23 women in three centres in India: the Postgraduate Institute of Medical Education and Research, Chandigarh; Safdarjang Hospital, New Delhi; and Kamla Nehru Memorial Hospital, Allahabad. Thorough clinical and pelvic examinations were carried out as well as cervical cytology, blood biochemistry and haematology before and after use of the polyherbal pessary intravaginally once daily for 7 consecutive days. No toxicity was observed on clinical examination or by laboratory investigations. Daily intravaginal use of this pessary for 7 days had no adverse effects on cervical cytology or on metabolic and organ functions.

Administration, Intravaginal↗
PubMed2005

Immunoprophylactic effects of the anti-leprosy Mw vaccine in household contacts of leprosy patients: clinical field trials with a follow up of 8-10 years.

We report here a large scale, double blind immunoprophylactic trial of a leprosy vaccine based on Mycobacterium w (Mw) in an endemic area of Kanpur Dehat, Uttar Pradesh, India. A population of 420,823 spread over 272 villages was screened where 1226 multibacillary (MB) and 3757 paucibacillary (PB) cases of leprosy were detected. A total of 29,420 household contacts (HHC) of these patients were screened for evidence of active or inactive leprosy. After exclusion of 1622 contacts for any of the different exclusion criteria, a total of 24,060 HHC could be vaccinated for vaccine or placebo under coding (20,194 administered two doses and 3866 received single dose). The vaccine consisted of 1 x 10(9) heat killed bacilli (Mw) in normal saline for the first dose and half of the first dose, i.e. 5 x 10(8) bacilli for the second dose, given 6 months after the first dose. The placebo consisted of 1/8th dose of the normal dose of tetanous toxoid. Both placebo and vaccine were given under double-blind coding, The contacts were followed up during three surveys at 3, 6 and 9 years after the initial vaccination, for detection of post-vaccination cases (PVCs) and observing any side-effects caused as a result of vaccination. The codes were opened on 24th January 2001, after the analysis of the data following completion of the third and final follow-up survey. When only contacts received the vaccine, Mw vaccine showed a protective efficacy (PE) of 68-6% at the end of first, 59% at the end of the second and 39.3% at the end of the third follow-up survey. When both patients and contacts received the vaccine, the protective efficacy observed was 68%, 60% and 28% at the end of the first, second and third surveys, respectively. When patients, and not the contacts, received the vaccine, a PE of 42.9% in the first, 31% in the second and 3% in the third survey was shown. These results suggest that the vaccination of the contacts is more valuable in achieving the objective of immunoprophylaxis than that of patients, and the vaccine effects are noted maximally in children (as compared to adolescents and adults) who constitute the most responsive group The effect of vaccine is sustained for a period of about 7-8 years, following which there is a need to provide a booster vaccination for the sustained protection.

Adolescent↗
PubMed2004

A recombinant luteinising-hormone-releasing-hormone immunogen bioeffective in causing prostatic atrophy.

Previous studies with a semi-synthetic vaccine indicated the utility of immunization against luteinising-hormone-releasing-hormone (LHRH) in prostate cancers. To overcome the limitations of the previous vaccine, which caused carrier induced suppression of antibody response on repeated immunizations and was costly to synthesize, two recombinant vaccines were designed, in which diptheria or tetanus toxoid used as carriers were replaced by 4-5 T non B peptides. The paper reports the immunogenecity, efficacy and safety of these multimer vaccines in rats, a homologous experimental animal. All animals generated anti-LHRH antibodies, which caused the decline of testosterone to castration levels at and above 0.15 OD units of antibody titres. The prostate was significantly atrophied in all animals immunized with these vaccines.

Animals↗
PubMed2004

Purification, refolding, and characterization of recombinant LHRH-T multimer.

To make the native LHRH immunogenic, a multimer of LHRH interspersed with T non-B peptides (r-LHRH-d2) was expressed as recombinant protein in Escherichia coli. The expression level of the recombinant protein was around 15% of the total cellular protein and it aggregated as inclusion bodies. Inclusion bodies from the bacterial cells were isolated and purified to homogeneity. Instead of high concentrations of chaotropic agents, r-LHRH- d2 was solubilized in 50 mM citrate buffer at pH 3 containing 2 M urea. The protein was refolded by 5-fold dilution (pulsatile) with cold 10 mM citrate buffer at pH 6 in presence of 0.3 M L-arginine. Purification of r-LHRH-d2 was carried out by successive passages on CM-Sepharose column at pH 6.0 which retained extraneous proteins and pH 4.8 at which r-LHRH-d2 bound to the resin. The elution was carried out by using linear salt gradient (0.1-1 M NaCl). The overall yield of the purified r-LHRH-d2 was 40% of the initial inclusion body proteins. The purity and homogeneity were confirmed by a single homogeneous peak on analytical HPLC eluting out at 29.51 min and by single band on SDS-PAGE reactive with polyvalent anti-LHRH antibodies. Mass spectroscopic analysis indicated the protein to be of 16.6 kDa which equals the theoretically expected mass. The N-terminal amino acid analysis of r-LHRH-d2 showed the sequence which corresponded to the designed protein. The CD spectrum of the refolded r-LHRH-d2 showed that the multimer has considerable beta sheet structure like the monomeric LHRH protein.

Animals↗
PubMed2004

Engineering, cloning, and expression of genes encoding the multimeric luteinizing-hormone-releasing hormone linked to T cell determinants in Escherichia coli.

Two synthetic genes were designed and engineered to encode for multimeric luteinizing-hormone-releasing hormone (LHRH) peptides linked to T cell determinants. These genes were cloned into the prokaryotic expression vectors under control of strong inducible promoters, to overexpress the multimeric LHRH peptides as recombinant proteins. Multimeric LHRH-T cell peptides were expressed as insoluble inclusion bodies in Escherichia coli cultures. Cell extracts containing the recombinant proteins showed immunoreactivity on Western blots with monoclonal antibody recognizing the native hormonal peptide. These gene constructs have potential applications in therapy of sex-steroid-hormone-dependent cancers.

Amino Acid Sequence↗
PubMed2003

[Transient compensatory hypertrophy and limited regeneration of the surgically removed rat ventral prostate].

OBJECTIVES: To confirm whether regeneration of prostate lobe indeed takes place on surgical lobectomy and if so, to what extent. Other issues studied are 1. whether the lobe regenerated is similar morphologically to that developing normally from neonatal origin to adulthood, and 2. the consequences of partial lobectomy on the contralateral lobe and the influence of sex steroid hormones on the regeneration process. METHODS: The effect of surgical removal of one of the ventral prostate lobes on the size of the contralateral lobe has been studied at various time intervals after lobectomy. RESULTS: The surgically extirpated ventral prostate lobe in rats regenerates attaining plateau size at 8-16 weeks post lobectomy. The regenerated lobe, however, remains significantly smaller than the original size. In early phase of post lobectomy (at 2 weeks) the contralateral lobe was significantly hypertrophied. It reverts to normal size on regeneration of the extirpated lobe with time. Orchiectomy carried out at the time of lobectomy caused a drastic reduction in the size of the remaining lobe, which was prevented by exogenous treatment with androgens. In animals receiving treatment with estrogens, the remaining lobe was partially but not fully atrophied. However, estrogens did not support the regeneration of the surgically removed lobe, which requires androgens. CONCLUSIONS: These studies demonstrate that surgical removal of one of the ventral prostate lobe leads to a process of regeneration. However, the regenerated lobe does not attain the normal size.

Animals↗
PubMed2002

Efficacy of plant-produced recombinant antibodies against HCG.

BACKGROUND: Antibody engineering facilitates the construction of different antibody formats [single chain variable fragment (scFv), diabody, full-size chimeric monoclonal antibody] with ease. METHODS: We constructed recombinant antibodies against HCG, which is widely used in pregnancy testing and is also produced by a number of cancers. RESULTS: The recombinant antibodies were transiently expressed in tobacco leaves to levels of up to 40 mg of pure protein per kg fresh leaf weight. Enzyme linked immunosorbent assay (ELISA) and electrophoretic mobility assay (EMSA) confirmed antibody specificity for the beta subunit of beta-HCG. The efficacy was confirmed by inhibiting HCG induced testosterone production by Leydig cells in vitro and by blocking the HCG induced increase in mouse uterine weight in vivo. CONCLUSIONS: Passive immunization with recombinant HCG-specific antibodies may have clinical utility as (i) diagnostic and therapeutic tools for HCG-expressing cancers and (ii) contraceptive measures.

Animals↗
PubMed2001

Tetanus toxoid loaded 'preformed microspheres' of cross-linked dextran.

The conformation of an antigen and hence its biological activity may get compromised when encapsulated in controlled release microspheres during formulation. In order to obviate the need for exposure of the antigen to the inactivating conditions, such as exposure to organic solvent and the high shear stress of emulsification required for microencapsulation, an alternate strategy was employed. 'Pre-formed' microspheres (20--340 microm in size) made of cross-linked dextran (Dex) were employed as matrix for conjugation of tetanus toxoid (TT) under aqueous conditions. The native immunoreactivity of TT was completely retained after conjugation, as checked by immunofluorescence and quantitative ELISA. Immunogenicity of Dex--TT conjugate was tested in rodents. No untoward mortality or adverse effects of immunization with the test material were observed on histopathology of the site of injection. A single immunization with the long-acting depot formulation elicited anti-TT antibody response lasting for 1 year without any need of booster. The titres were comparable after 12 weeks with those obtained using the conventional alum adsorbed toxoid.

Animals↗
PubMed2001

A monoclonal antibody cytolytic to androgen independent DU145 and PC3 human prostatic carcinoma cells.

BACKGROUND: While a range of therapeutic products is available for androgen-dependent prostatic cancer, no specific intervention modality exists for androgen-independent prostatic cancer. The objective of this research was to explore whether epitopes exist on androgen-independent prostatic DU145 cancer cells, which could be susceptible to cytotoxic action of specific antibodies. METHODS: Hybrid cell clones were developed by immunization of mice with DU145 cells and tested for immunoreactivity by solid phase EIA and cytotoxicity in vitro on DU145 in the presence of the complement, employing colorimetric quantitation by MTS (3- (4-, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-(4-sulfophenyl)-2H-tetrazolium). Binding and cytotoxicity studies were also carried out by flow-cytometry. RESULTS: Of 15 stabilized clones immunoreactive with DU145 cells, one monoclonal antibody (mAb 730) manifested cytotoxicity on DU145 cells. Approximately 80% of cells in the DU145 cell line were susceptible to lysis with this antibody at saturating levels. This figure corresponded quantitatively to the number of cells binding with this antibody as determined by Flow-cytometry. Staining with ethidium monoazide bromide (EMA) showed that the cell binding the antibody was also the one killed by the antibody in the presence of the complement. MAb 730 was also cytotoxic to PC3, another androgen-independent human prostatic cancer cell line. This antibody is devoid of classical autoantibody reactivities and does not react with normal human liver, thyroid, kidney, pancreas, and adrenal tissues, as determined by immunofluorescence. Also, it shows negative immuno-reactivity to benign glandular tissue but is observed to positively react with neoplastic prostate tissue. CONCLUSIONS: Epitopes exist on androgen-independent prostatic cancer cells that are susceptible to cytolysis by monoclonal antibodies and these could be investigated for potential immunotherapy.

Animals↗
PubMed2001

Spermicidal & contraceptive properties of Praneem polyherbal pessary.

BACKGROUND & OBJECTIVES: Though a number of barrier methods and potent spermicides are available, most of these have nonoxynol-9 (N-9) as the active ingredient which is observed to cause inflammation and genital ulceration on repeated use. The present study was undertaken to develop a safe spermicide with conjoint microbicidal properties. METHODS: A polyherbal pessary was formulated with purified ingredients from neem (Azadirachta indica) leaves, Sapindus mukerossi (pericarp of fruit) and Mentha citrata oil. Spermicidal action on human sperm was tested by Sander-Cramer slide test in vitro and by post coital tests in vivo. Contraceptive action was tested in rabbits. RESULTS: The combination of the three herbal ingredients resulted in the potentiation of the spermicidal action by 8-folds. The post coital tests confirmed the spermicidal properties of the Praneem polyherbal pessary (PPP) in women with high cervical mucous score around mid estrus. It also prevented in most women the migration of sperm into the cervical mucous. In 15 rabbits studied pregnancy was prevented by the intravaginal administration of PPP, whereas 13 of the 15 animals in the control group became pregnant. INTERPRETATION & CONCLUSION: The Praneem polyherbal pessary has potent spermicidal action on human sperm in vitro and in vivo. When applied in the vagina before mating, it prevented rabbits from becoming pregnant.

Female↗
PubMed2000

Polyherbal formulations with wide spectrum antimicrobial activity against reproductive tract infections and sexually transmitted pathogens.

PROBLEM: Recent reports indicate high incidence of genital infections, most of which are sexually transmitted. Although specific drugs and antibiotics are available for some, a safe spermicidal formulation with wide spectrum antimicrobial action would be a desirable addition to the presently available spermicides. METHODS: Formulations at different dilutions were tested in culture systems on standard strains and clinical isolates including some isolates resistant to drugs. The effect on (HSV)-2 and Chlamydia trachomatis was determined in vivo in progestin sensitized mice. The effect on HIV-1 was investigated in two standardized systems. RESULTS: Polyherbal cream inhibited the growth in culture of clinical isolates of Candida albicans, Candida krusei and Candida tropicalis. Both the polyherbal cream and the Praneem polyherbal pessary inhibited urinary tract Escherichia coli (including multidrug resistant strains), and Neisseria gonorrhoeae (including 2 strains resistant to penicillin). Both formulations manifested virucidal activity against HIV-1 at >2 and 50% dilutions (in two different test systems) on contact for 1-2 min. Intravaginal inoculation of the cream and the pessary suspensions before inoculation of the pathogen prevented lesions and vaginal transmission of HSV-2 and C. trachomatis in progestin sensitized mice. CONCLUSIONS: Polyherbal formulations have wide spectrum antibacterial, antifungal and antiviral effect against the tested sexually transmitted pathogens.

Animals↗
PubMed1999

Early post implantation contraceptive effects of a purified fraction of neem (Azadirachta indica) seeds, given orally in rats: possible mechanisms involved.

Neem seed and leaf extracts have immunomodulators that induce cellular immune reactions. These aspects of neem were exploited in earlier studies, where the oral administration of the neem seed extracts in rodents and primates could completely abrogate pregnancy at an early post implantation stage. Complete restoration of fertility was observed in the animals treated in the subsequent cycles. For the purpose of using neem as a long term contraceptive, an activity guided fractionation, followed by identification and characterization of the biologically active fraction from neem seeds was carried out. Sequentially extracted fractions of neem seeds were tested orally at an early post implantation stage in rats. The hexane extract of the neem seeds was found to be biologically active and was the precursor for the final active fraction. The active fraction, identified as a mixture of six components, could completely abrogate pregnancy in rodents up to a concentration of 10%. No apparent toxic effects could be seen following treatment with the fraction. The treatment with the active fraction caused a specific activation of T lymphocyte cells of CD8+ subtype as well as phagocytic cells followed by elevation in cytokines gamma-interferon and TNF. The results of the present study show that a pure active fraction of neem seeds could be obtained for the purpose of early post implantation contraception when given orally, and its mechanism of action seems to be by activating cell mediated immune reactions.

Abortifacient Agents↗
PubMed1999

Prior immunity to a carrier enhances antibody responses to hCG in recipients of an hCG-carrier conjugate vaccine.

Pre-sensitization with carrier often leads to epitopic suppression of subsequent anti-hapten antibody responses. To ascertain whether epitopic suppression occurs in humans, we examined the effect of pre-existing anti-carrier immunity on antibody responses to hCG in volunteers of a clinical trial of an hCG-based conjugate birth-control vaccine. When we studied the correlation between pre-vaccination anti-carrier immunity and post-vaccination anti-hCG responses, we found that prior immunity to the carriers did not lead to epitopic suppression of anti-hCG responses. On the contrary, it was found that prior immunity to TT, one of the two carriers used in this vaccine, led to enhancement of anti-hCG responses. Our data indicates that prior immunity to the carriers may not be detrimental to the performance of conjugate vaccines, and may actually be beneficial in some cases.

Adult↗
PubMed1999

Vaccines and passive immunological approaches for the control of fertility and hormone-dependent cancers.

Reviewed here is the development of a vaccine against the human chorionic gonadotropin that prevents pregnancy in sexually active women without impairment of ovulation or derangement of menstrual regularity. Also reviewed are the vaccines inducing antibodies against the luteinizing hormone-releasing hormone, which have immunotherapeutic potential in prostatic hypertrophy and other sex hormone-dependent male and female cancers. The adoption of passive immunization using humanized recombinant antihormone antibodies is advocated for assured efficacy and safe, prompt therapeutic action.

Animals↗
PubMed1999

An immunotherapeutic vaccine for multibacillary leprosy.

On January 30, 1998, a vaccine for leprosy based on Mycobacterium w (the code word under which this species hitherto unspecified was investigated) was launched for public use for therapeutic purposes. The vaccine has completed phase III immunotherapeutic trials as an adjunct to chemotherapy in urban and rural leprosy control centres and has received the authorization from the Drugs Controller of India for industrial manufacture. It will be made available by M/s Cadila Pharmaceuticals, Ahmedabad. As an adjunct to chemotherapy, the vaccine expediates bacterial clearance and accelerates clinical regression of lesions. It shortens significantly the period for release from treatment (RFT) of patients. It is effective in inducing a fall of bacterial index (BI) in multibacillary patients who are either nonresponders or slow responders to the standard multidrug therapy and who have persistent BI over long periods. An additional benefit of immunization with this vaccine is the conversion of >60% of LL, 71% of BL and 100% of BB patients from lepromin negativity to lepromin positivity status. A significant number of vaccinated patients showed histopathological upgrading and eventually attainment of a state of nonspecific infiltration without dermal granulomas. The vaccine was well tolerated and the incidence of Type 2 reactions and their severity was less in combined immuno cum chemotherapy group than in the group receiving only chemotherapy. This review describes the nature of the vaccine and the way it was developed.

Animals↗
PubMed1998

Induction of early and bioeffective antibody response in rodents with the luteinizing hormone-releasing hormone vaccine given as a single dose in biodegradable microspheres along with alum.

BACKGROUND: Previous studies in animals and phase I/phase II clinical trials in humans have shown the suppressive effect of immunization with the luteinizing hormone-releasing hormone (LHRH) vaccine on prostatic hypertrophy and hyperplasia. A drawback of this vaccine was a delay of about 8 weeks in buildup of antibody titers to efficacy level and the requirement of three injections of the vaccine given at monthly interval for full primary immunization. METHODS: LHRH vaccine was encapsulated in poly-lactic-co-glycolic acid (PLGA) 50:50 copolymer microspheres of reproducible physicochemical characteristics. Immunogenicity studies were carried out in rodents and prostate weights were determined at various antibody titers. RESULTS: The vaccine entrapped in biodegradable microspheres generated high antibody response in rats, persisting for 5-7 months following a single immunization. One hundred micrograms was the optimum dose, and the intramuscular route was more immunogenic than the subcutaneous. It was further observed that coadministration of 75% of the vaccine entrapped in microspheres with 25% adsorbed on alum generated higher antibody response in rodents, exceeding the bioeffective threshold as early as day 15 postimmunization. CONCLUSIONS: Coadministration of the LHRH vaccine in biodegradable PLGA microspheres with a quarter of the dose adsorbed on alum generates high antibody titers within 15 days, which are effective in causing atrophy of the prostate.

Alum Compounds↗