Biomedical subjects

Gopal Gupta

Publications and source records attributed to Gopal Gupta.

8 recordsLinked to original sources

PubMed2006

Rat testicular germ cell type(s) targeted by anti-spermatogenic agents in vivo and their recovery on withdrawal of treatment--a flow cytometric study.

Spermatogenesis goes through very critically and precisely balanced ratios of germ cells with diverse DNA ploidies (1C, 2C and 4C). Antispermatogenic agents that reversibly interrupt spermatogenesis may have a contraceptive relevance. With a view to study the precise mechanism of action of antispermatogenic agents and identify the germ cell type(s) targeted by various agents in vivo, spermatogenic cells with diverse DNA ploidies were measured in rat testis during treatment and recovery with compounds CDRI-84/35, gossypol and estradiol, using Flow Cytometry. Rats were treated with either CDRI-84/35 (100mg/(kg day) for 15 days followed by 25mg/(kg day) for 55 days) or gossypol (20mg/(kg day) for 70 days) or estradiol benzoate (2.5microg/(rat day) for 70 days) and 3 rats from each group were sacrificed after 22, 41, 53 and 70 days of treatment to monitor the changes in population of 1C, 2C, S-phase and 4C germ cell types. Treatment with CDRI-84/35 resulted in a significant and rapid drop in 1C population with a concomitant and parallel rise in 2C population. In gossypol-treated animals 1C peak disappeared gradually and the arrest was seen predominantly at 2C stage and partially at 4C stage. At the end of the treatment most of the germ cells were arrested at 2C stage. Estradiol affected spermatogenesis differently with 1C population falling in complement to rise in both 2C and 4C peaks. Germ cells were mainly arrested at the 4C stage after the treatment. The data suggest that germ cells fail to enter meiosis in CDRI-84/35-treated rats. Few cells entering meiosis do not complete the cell division and remain arrested at 4C stage. However in case of estradiol and gossypol the meiotic 4C cells become incapable of further differentiation into haploid cells. After receiving 70 days of treatment a few rats were allowed to recover for 60, 90 and 120 days. The population of various germ cell types in the testis of recovery-group animals indicated that spermatogenesis resumes substantially in case of estradiol treatment and partially in case of treatment with the other two agents.

Animals↗

PubMed2006

Synthesis of benzenepropanamine analogues as non-detergent spermicides with antitrichomonas and anticandida activities.

Fifteen analogues of benzenepropanamine were synthesized and evaluated for their spermicidal as well as microbicidal activities against Trichomonas vaginalis and Candida spp. Several compounds showed appreciable dual activities. Compound 12 exhibited good spermicidal (MEC=0.1%) along with substantial anticandidal (MIC=0.05%) activities, while compounds 3 and 6 showed significant microbicidal activities with moderate spermicidal effect. The SAR of these structures is being discussed here in this communication. It is concluded that suitable structural modifications in this class of compounds at 3-amino position may lead to a potent spermicide with associated microbicidal activity.

Adult↗

PubMed2006

The spermicidal and antitrichomonas activities of SSRI antidepressants.

The study investigated spermicidal and antitrichomonas activities of selective serotonin reuptake inhibitor (SSRI) antidepressants with a view to generate new lead for development of dual-function spermicidal microbicides, which is an urgent global need. Fluoxetine, Sertraline, and Fluvoxamine exhibited both spermicidal and anti-STI (antitrichomonas) activities in vitro, whereas Paroxetine and Citalopram showed only the spermicidal activity. Fluoxetine exhibited better activity profile than the other antidepressant drugs with its spermicidal and antitrichomonas activities being comparable to that of the OTC contraceptive Nonoxynol-9. The non-detergent nature of Fluoxetine and a much lower spermicidal ED50 value (than N-9) may add considerably to its merit as a candidate for microbicidal contraceptive. Thus, the antidepressants exhibiting both spermicidal and antitrichomonas activities might provide useful lead for the development of novel, dual-function spermicidal contraceptives.

Animals↗

PubMed2005

Effect of antispermatogenic agents on cell marker enzymes of rat Sertoli cells in vitro.

OBJECTIVE: To examine the role of Sertoli cells in the antispermatogenic action of two nonsteroidal male contraceptive compounds (CDRI-84/35 and gossypol) by evaluating their effect on some key parameters of Sertoli cell function in vitro. METHODS: Primary cultures of Sertoli cell were established from 18-day-old rat testis and treated on day 5 with different concentrations (1.0, 0.1, 0.01, and 0.001 mM) of either CDRI-84/35 or gossypol in vitro. Lactate (secretion), along with beta-glucuronidase, gamma-glutamyl transpeptidase, lactate dehydrogenase (LDH) and aromatase activities, was measured in these cells to examine the functions targeted by antispermatogenic agents in Sertoli cells. RESULTS: CDRI-84/35 significantly affected Sertoli cell parameters (stimulation in most of the cases) that are important for germ cell development like lactate secretion, LDH activity, aromatase activity (estradiol secretion) and so on. Gossypol in comparison to CDRI-84/35 had a more severe effect on Sertoli cells with complete inhibition of enzyme activities at higher concentrations. CONCLUSION: It is probable that the antispermatogenic action of CDRI-84/35 and gossypol is routed through Sertoli cells by disruption of important cell functions that support spermatogenesis in vivo. However, the two compounds appear to have different course of action in Sertoli cells, ultimately leading to spermatogenic failure.

Animals↗

PubMed2005

Microbicidal spermicide or spermicidal microbicide?

Vaginal contraception, the oldest method of fertility regulation that remained virtually forgotten for a few decades has recently come under focal review due to an increase in STDs and HIV infections worldwide. Today it is being considered very strongly that a conceptual microbicidal spermicide can tender protection against pregnancy as well as STDs (including AIDS), simultaneously. However the two activities (spermicidal and microbicidal) need to be integrated in vaginal preparations, as many women across the world may be concerned more about the unwanted pregnancy rather than the STI during a coital act. A strong detergent like nonoxynol-9 (N-9) has been used as a spermicide in many local contraceptive preparations and studies have shown that it also exhibits significant microbicidal activity in vitro. However, recent clinical trials have shown that detergent spermicides do not provide any protection against STDs and AIDS but may in fact even promote their transmission. This anomaly has largely been attributed to their surfactant nature that irritates the vagina and kills the normal vaginal flora making it more susceptible to STD infections. An urgent need for a suitable non-detergent spermicide has thus emerged to replace N-9 in local contraceptive preparations. Anticipating the potential of spermicide-based vaginal contraceptives in the reproductive health of women, a large number of synthetic, non-detergent molecules were designed and evaluated at this Institute over recent years. Simultaneously, a number of natural products from terrestrial plants and marine flora/fauna were also evaluated for spermicidal activity. A local contraceptive preparation incorporating the active ingredient from the fruit pericarp of Sapindus mukorossi has successfully completed Phase III clinical trials in India and is ready for marketing. Recent studies have indicated that in comparison to N-9, this ingredient is much less toxic to Lactobacillus spp. and effectively inhibits the growth of Trichomonas vaginalis in vitro. Other candidate spermicides/microbicides under development worldwide have been reviewed briefly.

Administration, Intravaginal↗

PubMed2004

Role of energy metabolism in the pregnancy interceptive action of Ferula assafoetida and Melia azedarach extracts in rat.

Ethanolic extract of Ferula assafoetida and chloroform fraction of Melia azedarach, both devoid of estrogenic activity, were examined for their pregnancy interceptive property. Treatment of rats from days 1 to 7 of pregnancy with either of the plant extracts resulted in pregnancy failure in about 65-85% of the animals. The possible role of energy metabolism in the antifertility action was investigated by measuring changes in activities of the key enzymes of carbohydrate metabolism in uterus on day 7 of pregnancy. It was observed that on the day 7 of pregnancy, one key enzyme of glycolytic pathway (phosphofructokinase) was significantly reduced in the uteri of treated rats as compared to controls. Hexosemonophosphate pathway also appeared to be sensitive to treatment with the plant extracts and showed an inhibitory effect on the enzyme activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Oxidative energy metabolism through tricarboxylic acid cycle, which is considered to be the main source of energy to the uterus at this stage, was maximally affected by the treatment with several enzymes showing significant inhibition. The two plant materials appeared to interrupt the latter metabolic pathway more significantly. It is thus concluded that plants lacking phytoestrogens may intercept pregnancy by their ability to disrupt energy metabolism in rat uterus during implantation, especially the oxidative pathway.

Animals↗

PubMed2003

Design and implementation of a domain specific language for phylogenetic inference.

Domain experts think and reason at a high level of abstraction when they solve problems in their domain of expertise. We present the design and motivation behind a domain specific language, called phi LOG, to enable biologists to program solutions to phylogenetic inference problems at a very high level of abstraction. The implementation infrastructure (interpreter, compiler, debugger) for the DSL is automatically obtained through a software engineering framework based on Denotational Semantics and Logic Programming.

Algorithms↗

PubMed2002

Substituted acrylophenones and related mannich bases as possible spermicides and inhibitors of HIV envelope glycoprotein-CD4 interaction.

Several appropriately substituted 4-(dialkylamino-alkyl)-substituted-styryl-alkyl ketones or acetophenones were prepared and subjected to the Mannich reaction to yield compounds that would incorporate both alpha,beta-unsaturated keto groups and a substituted aminomethyl function with or without another olefinic moiety at position 4. The spermicidal activity of the prepared compounds was evaluated. Several compounds 2d, 4a and 4e were found to possess spermicidal activity at 0.005% concentration, while compounds 2a, 2c, 2f, 3a and 4b were active at 0.01% concentration. Compounds 2a, 2c, 3a, 4a and 4e also inhibited the interaction between recombinant HIV Env and CD4. Out of these, compound 2c was found to be most active.

Anti-HIV Agents↗