Biomedical subjects

N K Lohiya

Publications and source records attributed to N K Lohiya.

At least 19 recordsLinked to original sources

PubMed2005

Safety evaluation of long-term vas occlusion with styrene maleic anhydride and its non-invasive reversal on accessory reproductive organs in langurs.

AIM: To evaluate the safety of the long term vas occlusion with styrene maleic anhydride (SMA) and its non-invasive reversal at the level of accessory reproductive glands ARGs in langurs. METHODS: The morphology of seminal vesicle and ventral prostate was evaluated by light as well as transmission electron microscopy. Serum clinical chemistry and urine albumin were evaluated in an autoanalyzer using reagent kits. Fructose, acid phosphatase and zinc in the seminal plasma were evaluated spectrophotometrically according to the WHO manual. Serum testosterone, prostate specific antigen and sperm antibodies were evaluated by enzyme-linked immunosorbent assays (ELISA) using reagent kits and hematology was estimated according to standard procedures. RESULTS: The morphological features and secretory activity of the seminal vesicle and prostate were normal as evidenced by the presence of well-developed mitochondria, rough endoplasmic reticulum, Golgi bodies, secretory granules and normal nuclear characteristics throughout the course of investigation. Serum testosterone and prostate specific antigen remained unaltered and serum antisperm antibodies level presented negative titres. Urine albumin was nil. Total red blood corpuscles (RBC), white blood corpuscles (WBC), hemoglobin (Hb) and red cell indices, serum protein, glucose, cholesterol, creatinine, creatine kinase (CK), serum glutamate oxalate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), lactate dehydrogenase (LDH), bilirubin, urea, triglycerides and high-density lipoprotein (HDL) did not show appreciable changes following vas occlusion and after its non-invasive reversal. Although fructose, acid phosphatase (ACP) and zinc in the seminal plasma showed a significant reduction following vas occlusion, it could not be related to the morphology of seminal vesicle and prostate. CONCLUSION: SMA vas occlusion and its non-invasive reversal do not damage the accessory reproductive organs.

Anhydrides↗

PubMed2005

Perspectives of contraceptive choices for men.

Apart from condoms and vasectomy, which have several limitations of their own, no other methods of contraception are available to men. Various chemical, hormonal, vas based and herbal contraceptives have been examined and few of them have reached the stage of clinical testing. Promising leads have been obtained from testosterone buciclate/undecanoate, alone or in combination with levonorgestrel butanoate or cyproterone acetate, RISUG, an injectable intravasal contraceptive and a few herbal products, particularly the seed products of Carica papaya. It is feasible that an ideal male contraceptive, that meets out all the essential criteria will be made available to the community in the near future.

Carica↗

PubMed2004

Ultrastructural changes in the testis and epididymis of rats following treatment with the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya.

The benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya at a dose of 10 mg/rat/day for 150 days, which has shown a total inhibition of motility, reduced sperm count and infertility, was tested to de fi ne the mode of action at the subcellular level in the testis and epididymis. The ultrastructure of the testis of the treated animals revealed no appreciable changes in the subcellular characteristics. The mechanism of protein synthesis as well as steroidogenesis were evident in the Sertoli cells while the spermatogonia, spermatocytes and spermatids, both round and elongated, depicted a prominent nucleus, distinct nuclear membrane and cytoplasmic characteristics indicating normal germ cell differentiation. The principal cells of the cauda epididymis were characterized by the presence of well-de fi ned rough endoplasmic reticulum, mitochondria, Golgi bodies and secretary granules, suggesting active secretory functions. The absorptive function of the cauda epididymis was evidenced by the presence of numerous vesicles and multivesicular bodies adjacent to stereocilia. It is concluded that the inhibition of sperm motility by the drug could be due to other epididymal factors rather than the subcellular characteristics of testis and epididymis.

Animals↗

PubMed2003

Plants for male fertility regulation.

The importance of drugs of plant origin in the pursuit of fertility regulating agents for the male from natural products has long been recognized. This review includes 80 plants with 205 references, up to year 2002. The type of extract, dose, animal model and pharmacological activity of these materials have been reviewed in this paper to add impetus to further research and collaboration to resolve the problem of population explosion.

Animals↗

PubMed2002

Chloroform extract of Carica papaya seeds induces long-term reversible azoospermia in langur monkey.

AIM: To evaluate the antifertility activity of the chloroform extract of Carica papaya seeds by oral administration in langur monkey, Presbytis entellus entellus. METHODS: The chloroform extract of Carica papaya seeds, 50 mg/kg/day, was administered orally for 360 days to adult male langur monkeys. The sperm characteristics by light and electron microscopy, the sperm functional tests, the semen biochemistry, the serum testosterone level, the Leydig cell function, and the histology and ultrastructure of testis were determined to evaluate the antifertility activity and the blood biochemistry and hematology, to evaluate the toxicology. RESULTS: The extract gradually decreased the sperm concentration since days 30-60 of treatment with a total inhibition of sperm motility, a decrease in sperm viability and increase in sperm abnormality. Azoospermia was observed after day 90 of treatment and continued during the whole treatment period. Treatment withdrawal resulted in a gradual recovery in these parameters and 150 days later they reverted to nearly the pretreatment values. Morphological observation of the ejaculated sperm by light and scanning electron microscopy showed deleterious changes, particularly on the mid-piece. Sperm functional tests, viz., sperm mitochondrial activity index, acrosome intactness test and hypo-osmotic swelling test scored in the infertile range during treatment and returned to the fertile values 150 days after drug withdrawal. Histology of the testis revealed shrunken tubules, germ cell atrophy and normal Leydig cells. Ultrastructure of the testis showed vacuolization in the cytoplasm of Sertoli cells and germ cells. Loss of cytoplasmic organelles were evident in the spermatocytes and spermatids. Round spermatids showed loss of Golgi bodies, peripheral mitochondria and vacuolated cytoplasm, indicating maturational arrest. Leydig cell functional test indicated a mild inhibition of steroidogenic function. Haematology and serum biochemistry study disclosed no significant toxicological effect and the serum testosterone level was not affected. CONCLUSION: Carica papaya seed extract may selectively act on the developing germ cells, possibly mediated via Sertoli cells, leading to azoospermia.

Animals↗

PubMed2001

Vas deferens, a site of male contraception: an overview.

The vas deferens is a site which can be exploited for male contraception without undue side effects. The only effective technique available for male contraception is vasectomy, being practiced world wide, despite that it is a permanent surgical procedure and its successful reversal is not assured. Although no-scalpel vasectomy minimizes surgical procedures, the fate of its reversal is akin to that of vasectomy. Several occlusive and non-occlusive vasal procedures which claim to be reversible without surgical intervention, possess more disadvantages than advantages. Vas occlusion with plug, 'Shug' or medical grade silicone rubber, although claimed to produce reversible azoospermia without affecting spermatogenesis, requires skilled microsurgery for their implantation and later removal. RISUG, a non-sclerotic polymer styrene maleic anhydride (SMA), could be more advantageous than vasectomy and other vas occlusive procedures in that it could be a totally non-invasive procedure by "no-scalpel injection" and "non-invasive reversal". It is claimed to offer long-term contraception without adverse side effects and also to be possible as a male spacing method by repeated vas occlusion and non-invasive reversal. The drug is currently under multicentre Phase III clinical trial.

Animals↗

PubMed2000

Contraceptive evaluation and toxicological study of aqueous extract of the seeds of Carica papaya in male rabbits.

The contraceptive evaluation and toxicological effects of the aqueous extract of the seeds of Carica papaya in adult male rabbits have been reported. Thirty adult male rabbits were divided into five groups of six animals each; Group I, control; Groups II-V were administered orally with aqueous extract of the seeds of C. papaya at doses of 20, 50, 75 and 100 mg/kg per day for 150 days, respectively. The body weight, reproductive organs weight, semen analysis, semen biochemistry, toxicological profiles and the fertility status have been recorded. The aqueous extract failed to exhibit contraceptive effects at any of the dose regimens tested, contrary to the observations made in the previous studies. Unaltered toxicological profiles indicated that the drug was free of side effects. The results suggest that the failure of contraceptive effects may be due to species specificity, relative resistance of the animals to the drug or lack of potency of the extract due to factors generally affect biological activity of the plant preparations.

Animals↗

PubMed2000

Sterility due to inhibition of sperm motility by oral administration of benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rats.

The contraceptive effects of benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya have been reported in male albino rats at the dose regimens 5 and 10 mg/animal/day; oral for 150 days. The body weight, weight of testis, epididymis, seminal vesicle and ventral prostate remained unaltered during the entire course of the investigation. Total suppression of cauda epididymal sperm motility coincided with a decrease in sperm count, viability and an increase in per cent abnormal spermatozoa during 60-150 days observation period. Minor changes in the germ cell proliferations in the testis and vacuolization and pyknotic nuclei in the few epithelial cells of the cauda epididymis were observed. Histology and biochemical composition of testis and accessory sex organs, haematology and serum clinical biochemistry and serum testosterone levels remained unchanged throughout the course of the investigation. Test for estrogenicity indicated mild estrogenicity. Monthly fertility test showed negative fertility. All the altered parameters returned to normal level following 60 days withdrawal of the treatment. The results suggest that the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya exerts antifertility effects in rats without adverse toxicity and that the effects may be directly rendered on the spermatozoa.

Administration, Oral↗

PubMed2000

Repeated vas occlusion and non-invasive reversal with styrene maleic anhydride for male contraception in langur monkeys.

The feasibility of a spacing method for contraception, using Styrene Maleic Anhydride (SMA) as a vas occlusive agent, has been assessed in male langur monkeys. The vas deferens of 6 animals were occluded with 60 mg SMA in 120 microL DMSO. After 150 days, the occlusion was reversed by a technique which involved palpation, percutaneous electrical stimulation, forced vibratory movement, suprapubic percussion and per-rectal digital massage of the vas segments. The vas deferens were then re-occluded with SMA and reversed by the non-invasive method after three consecutive azoospermic samples. The second vas occlusion resulted in uniform azoospermia after the third ejaculation and reversal caused the reappearance of spermatozoa in the semen to severe oligozoospermic levels in the first two ejaculations and rising to normospermia in the subsequent ejaculations. Ultrastructure of the spermatozoa by SEM and TEM and sperm function tests revealed that the spermatozoa had recovered normal morphology. Vas morphology also regained a normal pseudostratified columnar epithelium containing basal and principal cells. The results suggest that the SMA-based spacing technique for male contraception could be extrapolated to the human by use of no-scalpel injection and non-invasive reversal.

Animals↗

PubMed2000

Ultrastructure of langur monkey epididymidis prior to and following vasectomy and vasovasostomy.

The ultrastructural changes in langur monkey epididymis prior to and following vasectomy or vasovasostomy were studied. The epididymal epithelium of the intact langur monkey was found to consist mainly of principal cells and basal cells and frequently apical or mitochondria rich cells were found. Besides these cells intraepithelial lymphocytes were also a consistent feature of the epididymal epithelium. Principal cells identified by means of the tuft of the stereocilia on their apical surface, bear well developed Golgi bodies, endoplasmic reticulum, vesicles, vacuoles and multivesicular bodies. This suggests their active involvement in absorption and secretion. Basal cells present at the base of the lamina bear a few cellular organelles and strong interdigitations with the adjacent cells. Apical or mitochondria rich cells were characterized by clusters of mitochondria in the apical region of the cell and few microvilli on their apical surface. Lymphocytes with a large nucleus and a pale rim of cytoplasm were also found at the base of the epithelium. Secretory and absorptive functions of principal cells of the epididymal epithelium were found to be increased after vasectomy, as indicated by bulging of the apical portion of the principal cells and membrane bound structure in the lumen. An extensive increase in the number of lysosomes, vesicles and vacuoles was also observed. An increase in the number of macrophages with spermatozoa remnants in the lumen of epididymis suggests that the principal mechanism for spermatozoa disposal following vasectomy is intraluminal endocytosis by macrophages. Changes following vasectomy persisted in vasovasostomized animals even after 12 months of recanalization, which may contribute to the failure of functional reanastomosis.

Animals↗

PubMed2000

Human sperm immobilization effect of Carica papaya seed extracts: an in vitro study.

AIM: To examine if the seed extracts of Carica papaya, which showed antispermatogenic/sperm immobilization properties in animal models, could cause human sperm immobilization in vitro. METHODS: Chloroform extract, benzene chromatographic fraction of the chloroform extract, its methanol and ethyl acetate sub-fractions and the isolated compounds from the sub-fractions i.e., ECP 1 & 2 and MCP 1 &2, of the seeds of Carica papaya were used at concentrations of 0.1%, 0.5%, 1% and 2%. Sperm motility was assessed immediately after addition of extracts and every 5 minutes thereafter for 30 minutes. RESULTS: There were dose-dependent spermicidal effects showing an instant fall in the sperm motility to less than 20% at 2% concentration. Isolated compounds ECP 1 & 2 were more effective inducing a motility of less than 10%. Many of the spermatozoa became vibratory on the spot. Total inhibition of motility was observed within 20-25 min at all concentrations of all products. Scanning and transmission electron microscopy revealed deleterious changes in the plasma membrane of the head and mid-piece of spermatozoa. Sperm viability test and the number of abnormal spermatozoa after completion of incubation suggested that the spermatozoa were infertile. The effects were spermicidal but not spermiostatic as revealed by the sperm revival test. CONCLUSION: The results reveal spermicidal activity in vitro of the seed extracts of Carica papaya.

Fruit↗

PubMed1999

Ultrastructural changes in the vas deferens of langur monkeys Presbytis entellus entellus after vas occlusion with styrene maleic anhydride and after its reversal.

Ultrastructural changes in the vas deferens of langur monkeys after 150 days of vas occlusion with styrene maleic anhydride (SMA) and after 150 days of noninvasive reversal are reported. The vas deferens of the sham-operated control animals revealed active secretory and absorptive functions. The basal cells showed prominent nucleus and sparse cytoplasmic organelles, and the principal cells characterized by oval or irregular nucleus, well developed mitochondria, Golgi bodies, rough endoplasmic reticulum, secretory granules in the Golgi area, free ribosomes, and glycogen granules in the supranuclear region suggesting secretory function. Vesicles and stereocilia in the apex region suggested absorptive functions of the vas deferens. Vas occlusion by SMA resulted in exfoliation of epithelial cells, pyknotic nuclei, and vacuolated cytoplasm virtually devoid of cytoplasmic organelles and stereocilia. After noninvasive reversal, the vas epithelium regained a state of normalcy as evidenced by prominent plasma membrane, nucleus, cytoplasmic organelles, and stereocilia. The results suggest that the exfoliation of the epithelium due to vas occlusion by SMA regains normalcy after 150 days of noninvasive reversal.

Animals↗

PubMed1999

Reversible antispermatogenic effect of gossypol in langur monkeys (Presbytis entellus entellus).

The present investigation reports the antispermatogenic effect of the orally active highly purified gossypol acetic acid at 7.5 mg and 10 mg/day for 180 days in langur monkeys. The results revealed a dose-dependent response in semen analysis as well as testicular morphology. Uniform severe oligospermia was observed in the lower dose (7.5 mg) group, while azoospermia was observed in 2 out of 5 animals in the higher dose (10 mg) group and the remaining animals showed severe oligospermia. Scanning electron microscopy of spermatozoa revealed deleterious abnormalities in the head and midpiece. Testicular morphology revealed a decrease in the seminiferous tubule diameter and arrest of spermatogenesis. The lower dose group had a germ cell population up to primary spermatocytes while the higher dose group had only Sertoli cells and spermatogonia. Withdrawal of treatment for 180 days led to the recovery of all the parameters studied, to normalcy.

Animals↗

PubMed1999

Reversible azoospermia by oral administration of the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rabbits.

Contraceptive efficacy, reversibility and toxicity, if any, of the benzene, chloroform and ethyl acetate chromatographic fractions of the chloroform extract of the seeds of Carica papaya have been investigated in adult male rabbits at a dose regimen of 50 mg/animal/day for 150 days of treatment. Body weight, semen analysis, hematology, serum clinical biochemistry and the fertility status of control and treated animals were evaluated. Chloroform and ethyl acetate chromatographic fractions did not produce appreciable changes in these parameters. However, the benzene chromatographic fraction resulted in uniform azoospermia after 15 days of treatment, which was maintained for the remainder of the 150-day observation period. The levels of fructose, glycerophosphocholine, acid phosphatase and lactate dehydrogenase in the seminal plasma were within the control range. Hematology and the serum clinical parameters showed no appreciable changes, indicating lack of toxicity. The libido of the treated animals was normal and the fertility rate was zero. Complete normalcy of altered parameters was observed 60 days following withdrawal of treatment. It is concluded that the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya possesses reversible male contraceptive potential and the effects appear to be mediated through the testis.

Acetates↗

PubMed1999

Fine structure of the langur monkey vas deferens and possible role of changes following vasectomy in the success or failure of the vasovasostomy.

Studies on the ultrastructure of the vas deferens have been carried out in control, vasectomized (6 and 24 months) and vasovasostomized (12 months) langur monkeys (Presbytis entellus entellus Dufresne). Vas deferens epithelium of the control animals depicted four types of cells, viz. the basal cells, principal cells, mitochondria-rich or apical cells and pencil or dark cells. The basal cells were short, cuboidal in nature with prominent nuclei, and contained sparse cytoplasmic organelles. The principal cells were characterized by the presence of nuclei with irregular outline and intranuclear electron-dense granules, well-developed Golgi bodies with prominent secretory vesicles, cisternae of rough endoplasmic reticulum, mitochondria, free ribosome particles, lysosomes and stereocilia in the cytoplasm, suggesting an active secretory role, as well as the absorptive functions of the cells. The mitochondria-rich cells consisted of numerous mitochondria, and other cytoplasmic organelles were sparse. The pencil cells were dark, slightly compressed and situated between the principal cells. Vasectomy resulted in reduction of cytoplasmic volume and vacuolization of the cytoplasm, especially in the Golgi region of the principal cells. Rough endoplasmic reticulum and mitochondria were poorly defined. Vasovasostomy showed no appreciable improvement in the configuration of the cytoplasmic organelles. The results suggest that a persistent reduced secretory activity of the cells following vasectomy and vasovasostomy might also be one of the factors responsible for unsuccessful vasovasostomy.

Animals↗

PubMed1998

Ultrastructural changes in the spermatozoa of langur monkeys Presbytis entellus entellus after vas occlusion with styrene maleic anhydride.

Changes in the physical characteristics of semen and ultrastructure of the spermatozoa of langur monkeys after vas occlusion with styrene maleic anhydride (SMA), a polymer with pH-lowering action, are reported. Vas occlusion resulted in severe reversible hypospermia. Severe oligospermia was observed in the majority of animals (five of eight) in the first ejaculation, 30 days after vas occlusion, and in two animals in the second ejaculation, 60 days after vas occlusion. Subsequent monthly ejaculations for 5 months revealed uniform azoospermia. The voided spermatozoa were immotile and supravital staining confirmed necrospermia. Scanning electron microscopy (SEM) revealed severe coiling of tail, rupture of acrosomal envelope, and bent midpiece associated with damaged mitochondrial sheath. Observations by transmission electron microscopy (TEM) revealed vacuolization in the nucleus, membrane damage in the acrosome, loss of segmented columns, and numeric aberrations in the centriole of the neck, as well as degeneration of mitochondrial sheath and axoneme in the midpiece, and absence of outer plasma membrane in the midpiece and tail. The results indicate that the necrospermic status of the spermatozoa during initial ejaculations may offer instant sterility after vas occlusion with SMA.

Animals↗

PubMed1998

Long-term sequelae of tolnidamine on male reproduction and general body metabolism in rabbits.

The long-term effects of tolnidamine on male reproduction and general body metabolism were studied in rabbits (Oryctolagus cuniculus). The study was divided into three groups of 10 animals each. The first group (A) received vehicle alone to serve as controls. The second and third groups (B and C) of animals were administered tolnidamine orally at 50 mg/kg body weight/week and 50 mg/kg body weight/day, respectively, for a period of 150 days. The animals of group B exhibited a sperm density of 23.60 million/mL +/- 4.87 million/mL (vs 453.00 million/mL +/- 65.30 million/mL in group A) after 150 days of treatment. In group C, all animals were azoospermic after 135 days of treatment. A reversible impairment of sperm motility, vitality and morphology was noticed. Semen weight, volume, color, pH, libido, and circulatory levels of testosterone remained unchanged. In group B animals, sperm density did not return to control levels even at 150 days after cessation of treatment (37.40 million/mL +/- 4.46 million/mL, vs 380.00 +/- 40.80 million/mL in group A). However, spermatozoa reappeared in animals treated daily (group C) after 30 days of recovery but remained < 5 million/mL during the entire recovery period. A reversible, significant depletion was recorded in seminal glycerylphosphorylcholine (GPC) levels. Fertility was unimpaired in group B animals when compared with those in group A. In group C, fertility was reduced to zero after 150 days of treatment and at 90 days and 150 days after cessation of treatment. No significant alterations were observed in other semen biochemical, hematologic, or blood/serum biochemical parameters with either dose regimen. It is concluded that tolnidamine administration induced dose dependent, irreversible inhibition of sperm production without altering general body metabolism in male rabbits.

Animals↗

PubMed1998

Intravasal contraception with styrene maleic anhydride and its noninvasive reversal in langur monkeys (Presbytis entellus entellus).

In male langurs with azoospermia induced by vas occlusion with styrene maleic anhydride (SMA), the exploratory feasibility of azoospermia reversal by a new noninvasive reversal procedure has been assessed. Palpation, percutaneous electrical stimulation of the vas deferens, forced vibratory movement, suprapubic percussion, and per rectal digital massage of the vas deferens are the components of the multimodal noninvasive reversal procedure. The exploratory investigation reveals that a single application of the procedure leads to reversal of azoospermia. Normospermia with normal motility and viability appears after third ejaculation onwards after reversal manipulations. Ultrastructure of the spermatozoa, using scanning and transmission electron microscopy, revealed that the spermatozoa attained normalcy and sperm functional tests (i.e., hypo-osmotic swelling test, slide test for acrosome intactness, and test for sperm mitochondrial activity index) further confirmed the normalcy of the spermatozoa toward their fertilizing ability. Semen biochemistry appeared normal throughout the course of investigation. The morphology of the vas deferens, which showed exfoliation of the epithelium, was in the process of regaining normalcy after 90 days of reversal manipulations. The results suggest that noninvasive reversal technique offers the possibility of the functional azoospermia reversal within a short period of time.

Animals↗