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Biomedical subjects

P S Kulkarni

Publications and source records attributed to P S Kulkarni.

At least 19 recordsLinked to original sources
PubMed2006

Immunogenicity of a new, low-cost recombinant hepatitis B vaccine derived from Hansenula polymorpha in adults.

BACKGROUND: Hepatitis B virus (HBV) infection is highly prevalent world over, especially in developing countries. A new recombinant hepatitis B virus (GeneVac-B; Serum Institute of India Ltd.) vaccine is developed using Hansenula polymorpha yeast. We decided to assess the immunogenicity, and reactogenicity of this vaccine in a large adult population. MATERIAL AND METHODS: Seven hundred eighty-eight adults subjects (age: 19-57 years, male:female ratio 35:1) received three 20 microg doses of a H. polymorpha-derived recombinant hepatitis B vaccine in months 0, 1, and 6. All the eligible subjects had negative baseline serum HBs Ag, and anti-HBs. The anti-HBs titer was obtained 1 month after the last dose of vaccine and was considered seroconverted if more than 1 mIU/ml, and seroprotective if more than 10 mIU/ml. RESULTS: The seroprotection rate was 96% and seroconversion rate was 97%. Seroconversion and seroprotection rates declined with increasing age. The minimum geometric mean titre of anti HBs was 443 mIU/ml (95% CI 407-482). Seroprotection was 96% in age group<40 years, while the same was 91% in >40 years group (Odd's ratio-2.9100, Z value-2.6183, highly significant). No other factor like smoking, tobacco-chewing, alcohol consumption, chronic diseases, and obesity, affected the immune response. No significant adverse reactions were reported in any of the subjects. CONCLUSIONS: Three standard doses of the H. polymorpha-derived recombinant HBV vaccine are highly immunogenic and safe in a predominantly male adult population. Young adults respond better with this vaccine. Because of its low cost, the vaccine may be a good choice in prevention of hepatitis B infection.

Adult↗
PubMed2006

Comparison of two hepatitis B vaccines (GeneVac-B and Engerix-B) in healthy infants in India.

Hepatitis B is a major problem in many parts of the world. The WHO has recommended the inclusion of hepatitis B vaccines in routine immunization schedules. We wanted to compare two recombinant hepatitis B vaccines in an infant population for immunogenicity and reactogenicity when given at 6, 10, and 14 weeks of age. One hundred seventy-three infants meeting eligibility criteria were given either GeneVac-B (Serum Institute of India Ltd.) or Engerix-B (GlaxoSmithKline Beecham) in a random fashion. Three 0.5-ml (10-mug) doses of the vaccines were given at 6, 10, and 14 weeks of age along with diphtheria-pertussis (whole cell)-tetanus (DTPw) vaccine. Blood samples were collected at baseline and 1 month after administration of the third dose of the vaccines to measure anti-HBs antibody levels. Seroconversion was defined as a titer of more than 1 x 10(-3) IU/ml, while seroprotection was defined as a titer of more than 10 x 10(-3) IU/ml. Of the GeneVac-B recipients, 98% seroconverted versus 99% of the Engerix-B group. The anti-HBs geometric mean titer was slightly greater for GeneVac-B (229 x 10(-3) IU/ml) than for Engerix-B (167 x 10(-3) IU/ml), but the difference was not significant. The seroprotection rates were similar for both vaccines (96% and 95%, respectively). The most common systemic reaction events were mild to moderate fever, excessive crying, local swelling, rash, and irritability, and the local reactions were redness, induration, and edema, which most probably were caused by the simultaneously administered DTPw vaccine. All events were transient and resolved without sequelae. Reactogenicity was similar for the two vaccines. The present study shows that GeneVac-B is as immunogenic and as well tolerated as Engerix-B when administered with DTPw vaccine at 6, 10, and 14 weeks of age.

Dose-Response Relationship, Immunologic↗
PubMed2005

No definitive evidence for L-Zagreb mumps strain associated aseptic meningitis: a review with special reference to the da Cunha study.

The study by da Cunha et al. published in 2002 reported that MMR vaccine containing L-Zagreb mumps strain manufactured by Serum Institute of India Ltd. caused a high incidence of aseptic meningitis (AM) from routine surveillance during two mass immunization campaigns (MIC) conducted in 1998 in two states in Brazil. Since the results were contrary to those in India, Egypt and Bahamas, a critical analysis of the study was done. Several inconsistencies were found in the study, which undermined the conclusions drawn. Two similar studies from Brazil reported similar results. Review of these studies and those done on the vaccine from Zagreb, Croatia showed that in no study the L-Zagreb mumps virus has been isolated from cerebrospinal fluid (CSF) of an AM case. Isolation of the vaccine virus is necessary for definite causal association of AM with the vaccine. There is no such evidence to causally link MMR vaccine containing L-Zagreb mumps strain with AM.

Brazil↗
PubMed2005

Use of liposomal amphotericin B in bone marrow transplant.

Increasing number of transplants worldwide has resulted in an increase in the incidence of fungal infections. Prolonged neutropenia, immunosuppression and graft vs. host disease all result in high predisposition to fungal infections. The likelihood of developing a fungal infection increases with the severity and duration of neutropenia, which, in the case of cancer or chemotherapy for the treatment of hematological malignancies, can range from a few days to several weeks. Invasive fungal infections are difficult to diagnose and neutropenic patients with fever often receive empirical antifungal therapy. This provides a rationale for the prophylactic use of antifungal agents. The empirical use of liposomal amphotericin B has overcome some of the difficulties usually found in this setting. The majority of clinical efficacy data related to liposomal amphotericin B are derived from compassionate use studies and case series. The major advantage of these liposomal formulations of amphotericin B is a reduction in amphotercin toxicity. Use of liposomal amphotericin has been shown to be a cost-effective approach abroad and the same has been our experience also. Commercially ambisome and Fungisome are the only products that contain true liposomes. Unlike ambisome, which needs to be used in dose of 3 mg/kg/day Fungisome is effective in the dose of 1-3 mg/kg bodyweight. The Indian liposomal preparation has shown to be safe and effective used in over 150 transplant patients in our experience. We conclude that the liposomal amphotericin is better-tolerated and also gives,better responses in documented fungal infections.

Amphotericin B↗
PubMed2001

Vasorelaxant effects of racemic betaxolol and its R- and S- isomers on bovine retinal vessels.

PURPOSE: RS-Betaxolol (equimolar R- and S- isomers) lowers intraocular pressure and dilates precontracted retinal and posterior ciliary arteries in vitro. Betaxolol's vasorelaxant effect is thought to involve the inhibition of calcium influx into vascular smooth muscle and is unrelated to its stereoselective beta-adrenergic blocking action. The authors assessed the vasodilatory effect of RS-betaxolol on different diameters of bovine retinal arterioles and venules, and these responses were compared with the responses induced by R- and S-betaxolol isomers in vitro. METHOD: In-vitro preparations of the bovine retinal microcirculatory system were perfused continuously with oxygenated, heparinized physiological salt solution at 37 degrees C. Diameters of retinal arterioles and venules were measured using video imaging. The retinal vessels were preconstricted with 40 mM KCl, and concentration-response curves for vasodilation were obtained for RS-betaxolol, R-betaxolol, and S-betaxolol. RESULTS: Baseline diameters of first-order (A1) and second-order (A2) branches of retinal arterioles were 50 +/- 0.6 microm and 39 +/- 1 microm, respectively (n = 20), whereas diameters of first-order (V1) and second-order (V2) branches of venules were 75 +/- 0.8 microm and 50 +/- 0.4 mM, respectively (n = 20). The diameters of all sizes of retinal arterioles and venules were significantly reduced (i.e., vasoconstricted) in the presence of 40 mM KCl (n = 20). These preconstricted vessels were relaxed in a dose-dependent manner by cumulative additions of RS-betaxolol, R-betaxolol, and S-betaxolol. The dose-response curves of these compounds were not significantly different. CONCLUSION: RS-Betaxolol, R-betaxolol, and S-betaxolol were equiactive and produced concentration-dependent vasodilatation of all sizes of retinal arterioles and venules studied.

Adrenergic beta-Antagonists↗
PubMed1999

Angiotensin II-induced constrictions are masked by bovine retinal vessels.

PURPOSE: To unmask the vasoconstricting effect of angiotensin II (Ang II) on retinal smooth muscle by studying its interaction with endothelium-derived paracrine substances. This study focused specifically on determining the changes in vascular diameter and the release of endothelial-derived vasodilators, nitric oxide (NO) and prostaglandin (PG) I2, from isolated retinal microvessels. METHODS: Bovine retinal central artery and vein were cannulated, and arterioles and venules were perfused with oxygenated/heparinized physiological salt solution at 37 degrees C. This ex vivo perfused retinal microcirculation model was used to observe the contractile effects of Ang II on arterioles and venules of different diameters. The NO and PGI2 synthase inhibitors, 1-NOARG and flurbiprofen, respectively, were used to unmask Ang II vasoconstriction; the changes in vascular diameters were then measured. Enzyme immunoassays were used to measure the release of cGMP (an index of NO release) and 6-keto-PG-F1alpha (a stable metabolite of PGI2) from isolated bovine retinal vessels. RESULTS: Topically applied Ang II (10(-10) M to 10(-4) M) caused significant (P < 0.05) arteriolar and venular constrictions in a dose-dependent manner, with the smallest retinal arterioles (7+/-0.2 microm luminal diameter) and venules (12+/-2 microm luminal diameter) significantly more sensitive than larger vessels. After the inhibition of endogenous NO and PGI2 synthesis by 1-NOARG and flurbiprofen, respectively, the vasoconstriction effects of Ang II became more pronounced. Again, the smallest vessels tested were significantly more sensitive, and synthesis of endothelial-derived relaxing factor (EDRF), therefore, may be most important in these vessels. Vasoactive doses of Ang II (10(-10) M to 10(-4) M) caused a dose-dependent increase in the release of NO and PGI2 from isolated bovine retinal vessels, indicating that the increase in EDRF may nullify direct Ang II-induced vasoconstriction. Interestingly, intraluminal administration of Ang II caused only vasodilation. CONCLUSIONS: This study demonstrates that the retinal vascular endothelium acts as a buffer against the vasoconstricting agent Ang II via release of vasodilators NO and PGI2, and the vasoconstriction effects due to Ang II are most prominent in the smallest diameter vessels.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Cyclooxygenase-2 inhibitors: a new approach to the therapy of ocular inflammation.

Prostaglandins (PGs) can be synthesized through the activities of two cyclooxygenase (COX) isoforms. COX-1 is constitutively expressed in most tissues and its activity provides for the relative small amounts of PGs required for the mediation and modulation of normal physiological functions. In inflammatory conditions, COX-2 is rapidly induced by cytokines, growth factors and bacterial endotoxin, and its enzymatic activity accounts for the large amounts of PGs produced during inflammation. The currently used nonsteroidal anti-inflammatory drugs (NSAIDs) are nonselective inhibitors of both COX isoforms. Inhibition of COX-2 leads to the therapeutically desired inhibition of the synthesis of pro-inflammatory PGs, but at the same time produces side effects associated with inhibition of COX-1 and the consequent suppression of the production of PGs necessary for normal cellular functions. Selective inhibition of COX-2 expression explains, at least in part, the potent anti-inflammatory activity of corticosteroids. However, the systemic and ocular side effects of these steroids have greatly limited their use, especially their long-term use for the management of chronic inflammatory conditions. The current effort to develop highly selective nonsteroidal COX-2 inhibitors for the treatment of arthritis and other inflammatory diseases can also be expected to yield a new approach to the treatment of uveitis and other ocular inflammatory conditions. This new class of NSAIDs will provide anti-inflammatory and analgesic activity while circumventing the most serious side effects of the current available NSAIDs, resulting from their inhibition of the physiologically required COX-1 activity.

Animals↗
PubMed1997

O6-methylguanine-DNA methyltransferase activity in human buccal mucosal tissue and cell cultures. Complex mixtures related to habitual use of tobacco and betel quid inhibit the activity in vitro.

Extracts prepared from tissue specimens of normal, non-tumourous human buccal mucosa, and cultured buccal epithelial cells and fibroblasts, exhibited O6-methylguanine-DNA methyltransferase (MGMT) activity by catalysing the repair of the premutagenic O6-methylguanine lesion in isolated DNA with rates of 0.2 to 0.3 pmol/mg protein. An SV40 T antigen-immortalized buccal epithelial cell line termed SVpgC2a and a buccal squamous carcinoma line termed SqCC/Y1, both of which lack normal tumour suppressor gene p53 function, exhibited about 50 and 10% of the MGMT activity of normal cells, respectively. The normal, experimentally transformed and tumourous buccal cell types showed MGMT mRNA levels which correlated with their respective levels of MGMT activity. Exposure of buccal cell cultures to various organic or water-based extracts of products related to the use of tobacco and betel quid, decreased both cell survival (measured by reduction of tetrazolium dye) and MGMT activity (measured subsequently to the exposures in cellular extracts). Organic extracts of bidi smoke condensate and betel leaf showed higher potency than those of tobacco and snuff. An aqueous snuff extract also decreased both parameters, whereas an aqueous areca nut extract was without effect. The well-established sulph-hydryl-reactive agent Hg2+, a corrosion product of dental amalgam, served as a positive control and decreased MGMT activity following treatment of cells within a range of 1-10 microM. Taken together, significant MGMT activities were demonstrated in buccal tissue specimens and in the major buccal mucosal cell types in vitro. Lower than normal MGMT activity in two transformed buccal epithelial cell lines correlated with decreased MGMT mRNA and lack of functional p53. Finally, in vitro experiments suggested the potential inhibition of buccal mucosal MGMT activity by complex mixtures present in the saliva of tobacco and betel nut chewers.

Areca↗
PubMed1995

Characterization of human buccal epithelial cells transfected with the simian virus 40 T-antigen gene.

Serum-free cultures of normal human buccal epithelial cells were transfected with a plasmid containing the SV40 T-antigen (SV40T) gene. Two major lines developed that showed extended lifespans (between 30 and 40 weeks) as compared with the controls (approximately 6 weeks). Continued growth through one or two crises generated several sublines. They expressed the epithelial marker keratin and also exhibited nuclear expression of SV40T. The lines showed abnormal karyotypes with both numerical and structural aberrations and variably responded to agents that normally inhibit growth and/or induce terminal differentiation, i.e. transforming growth factor-beta 1 and fetal bovine serum. One of the lines, termed SVpgC2a, developed into an apparently immortal line, since it had undergone more than 700 population doublings from over 2 years in culture. Further characterization of this line demonstrated its clonal origin, with integration of two copies of SV40T at the same site and the presence of both normal retinoblastoma and wild-type p53 proteins. This line showed high resistance to growth inhibition by transforming growth factor-beta 1 and serum similar to that shown by buccal carcinoma cell line SqCC/Y1. Neither SVpgC2a nor its parental lines were tumorigenic when injected into athymic nude mice, whereas the SqCC/Y1 cells induced tumors. The various lines with extended but finite lifespans, complemented by one immortalized line, which retained non-malignant properties upon extended culture, provide a battery of model systems that will be useful for studying mechanisms of human oral carcinogenesis.

Animals↗
PubMed1994

Steroidal and nonsteroidal drugs in endotoxin-induced uveitis.

Various classes of anti-inflammatory compounds like steroids (dexamethasone), cyclooxygenase inhibitors (indomethacin and flurbiprofen), 5-lipoxygenase inhibitors (BWA 218C and BWA 4C), immunosuppressive drugs (cyclosporin and rapamycin) and cod liver oil were tested for their antiinflammatory activities in endotoxin-induced uveitis model in rabbits. Intraocular inflammation was assessed in terms of two inflammatory responses i.e. breakdown of blood-aqueous barrier (BAB) and leukocyte infiltration into aqueous humor and iris ciliary body (ICB). Prostaglandin (PG) E2 and leukotriene (LT) B4 release into aqueous humor was also measured. Indomethacin significantly inhibited PGE2 release without affecting leukocyte or BAB response. Flurbiprofen prevented leukocyte, PGE2 and LTB4 release into aqueous humor but not ICB chemotaxis. BWA 218C and BWA 4C also significantly inhibited leukocyte and LTB4 release but not BAB responses. Dexamethasone (2mg/kg, i.m.) and cyclosporin A (25 mg/kg i.m.) significantly inhibited leukocyte infiltration into aqueous humor and ICB, and PGE2 release but they failed to inhibit breakdown of BAB and LTB4 release. On the other hand, rapamycin (10mg/kg i.m.) and cod liver oil (1 ml daily i.m. up to 15 days) significantly prevented leukocyte and BAB response. Cod liver oil also significantly inhibited PGE2 and LTB4 release but rapamycin affected only PGE2 release into aqueous humor. It is concluded that arachidonic acid metabolites may not play a vital role in this uveitis model and additional proinflammatory mediators like cytokines may be involved.

Animals↗
PubMed1993

Studies on intraocular inflammation produced by intravitreal human interleukins in rabbits.

Recombinant human interleukin-1 alpha, interleukin-1 beta (10, 80 or 200 units), interleukin-8 (10 or 40 units) or endotoxin was injected intravitreally into rabbit eyes. Twenty-four hours thereafter aqueous humor protein, leukocyte number, prostaglandin E2, leukotriene B4 and rabbit interleukin-1 beta were measured. In addition, synthesis of prostaglandin E2 and leukotriene B4 in iris-ciliary body and myeloperoxidase (MPO) activity were determined. Recombinant human interleukins 1 alpha and 1 beta, but not interleukin-8 induced signs of uveitis, i.e. protein and leukocytic infiltration into aqueous humor. At 200 unit activities, human interleukin-1 beta was significantly greater than interleukin-1 alpha in causing leukocyte infiltration response. Interleukin-1 alpha did not stimulate the release of prostaglandin E2 or leukotriene B4. In fact, interleukin-1 beta significantly inhibited the synthesis of prostaglandin E2 in iris-ciliary body. Both of these human interleukins caused a release of rabbit interleukin-1 beta in aqueous achieving a level significantly higher than observed after endotoxin injection. This study demonstrates that intravitreal injections of human IL-1 alpha and IL-1 beta induce uveitis by releasing rabbit interleukin-1 beta within the eye.

Animals↗
PubMed1992

Effects of steroids and immunosuppressive drugs on endotoxin-uveitis in rabbits.

Anti-inflammatory actions of dexamethasone (DEXA), Cyclosporin A (CSA) and Rapamycin (RAPA) were assessed on uveitis induced by intravitreal E-coli Endotoxin (100ng) in rabbits at 24 hrs. In this model, endotoxin caused a breakdown of the blood-aqueous barrier (BAB) and polymorphonuclear neutrophils (PMN) infiltration into the aqueous humor (AH) and iris-ciliary body (ICB). Intramuscular (I.M.) DEXA (2mg/kg) but not topical DEXA (0.1% 6 x daily) inhibited AH leukocytes and protein level. However, both routes caused an inhibition of AH Prostaglandin E2 (PGE2) and Leukotriene B4 (LTB4). In the ICB, I.M. DEXA significantly inhibited PGE2 synthesis and myeloperoxidase (MPO) activity. I.M. CSA (25mg/kg) and I.M. RAPA (10mg/kg) inhibited the AH leukocytes and protein content and MPO activity in the ICB. RAPA also inhibited AH protein and eicosanoid (except AH LTB4) levels in both the AH and ICB. Interestingly, castor oil, a vehicle of CSA, also inhibited AH leukocytes and the release of PGE2 into AH and from ICB. In summary, systemic administration of DEXA and other immunosuppressive drugs CSA and RAPA significantly inhibited endotoxin-induced uveitis in rabbits.

Animals↗
PubMed1991

Arachidonic acid metabolism in human and bovine retina.

Arachidonic acid (AA) metabolism in the human and bovine retina was assessed. This study demonstrates that the human and bovine retina can synthesize prostaglandin (PG) E2, F2 alpha, I2, D2 and thromboxane A2 from 14C-AA. This tissue also synthesized leukotriene (LT) B4 and 12-hydroxyeicosatetraenoic acid (12-HETE). Although human and bovine retina metabolized AA into PGs and LTs, the ability to synthesize these products was considerably less than some other ocular tissues of various species.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1991

The role of endogenous eicosanoids in rabbit-intraocular inflammation.

The role of endogenously released eicosanoids in intraocular inflammation was assessed in two rabbit models. The models were: (1) paracentesis in which only breakdown of blood-aqueous barrier (BAB) occurs and (2) uveitis induced by endotoxin in which the disruption of the BAB and polymorphonuclear leukocyte infiltration are the predominant events. Indomethacin (a specific cyclooxygenase inhibitor) applied topically inhibited both the disruption of the BAB and increased levels of aqueous humor 6-keto-Prostaglandin (PG)F1 alpha. However, indomethacin and flurbiprofen applied topically and BWA4C or BWA218C (both selective lipoxygenase inhibitors) given parenterally, did not inhibit BAB response in endotoxin-induced uveitis. The cyclooxygenase inhibitors attenuated PGE2 release into aqueous humor. The 5-lipoxygenase inhibitors reduced the PMN infiltration as well as LTB4 release into aqueous humor. However, myeloperoxidase activity (an index for PMN chemotaxis) in iris-ciliary body was not affected by these drugs. Furthermore, concentrations of LTB4 in aqueous humor after paracentesis and uveitis-induced by endotoxin were similar, although in the former model there was no leukocyte infiltration, but in the latter model this leukocyte response was predominant. The results of this study suggest that locally released autocoids may not initiate ocular inflammation and other mediators such as cytokines may be involved in the inflammatory responses of the rabbit eye. We tried to detect IL-1 activity in aqueous humor following endotoxin. However, we could not detect the presence of IL-1-like activity, possibly because endotoxin also releases PGs, which inhibit IL-1 bioassay.

Animals↗
PubMed1989

Inhibitors of the arachidonic acid cascade in the management of ocular inflammation.

At the present time, corticosteroids are still the most effective class of drugs for the treatment of ocular inflammation. However, since their prolonged use may result in severe ocular side effects, it would be therapeutically beneficial to develop nonsteroidal anti-inflammatory drugs that have similar or greater efficacy than steroids, but do not share their ocular side effects. Several currently available non-steroidal drugs have been used clinically as prophylactic or therapeutic agents for the following: 1. Prevention of pupillary constriction during intraocular surgery (cataract extraction). 2. Prevention of postoperative inflammation, i.e., incidence of anterior chamber cellular reaction and aqueous flare (breakdown of blood-aqueous barrier) and IOP rise following cataract surgery, intraocular lens implantation, and argon laser trabeculoplasty. 3. Prevention of contact lens induced corneal neovascularization. 4. Improvement of lens opacity (bendazac). 5. Prevention of cystoid macular edema following intraocular surgery. Treatment over long-term period may be effective; postoperative treatment is ineffective. 6. Prevention of conjunctival hyperemia. Some prophylactic ocular uses such as prevention of surgical miosis or postoperative fluorescein leakage have been reported to be successful. However, it is unclear whether the reported success reflected the pharmacological effects due to inhibition of the AA cascade - and hence, reflects the role of some eicosanoids in surgical miosis or postoperative fluorescein leakage - or reflect the effects of these drugs on unexplored physiological or pharmacological mechanisms. For example, pretreatment with flurbiprofen to prevent surgical miosis was based on the assumption that PGs are potent miotic agents in all mammals, including humans. It remains to be established however, whether the small reduction in the extent of pupillary miosis is due to prevention of PG synthesis by this drug or to the prevention of the synthesis of other AA products, such as prostacyclin and thromboxane or possibly to some entirely different mechanism. Prevention of post-surgical fluorescein leakage by prophylactic pre and/or post surgical treatment with a variety of nonsteroidal anti-inflammatory agents is also assumed to be due to inhibition of intraocular PG synthesis, although the possibility that it is due to prevention of the synthesis of prostacyclin or TxA2 has not been ruled out. Even more important, it has not been demonstrated that prevention of this post operative fluorescein leakage reflects the prevention or inhibition of true CME and associated loss of visual acuity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗