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Biomedical subjects

V L Kumar

Publications and source records attributed to V L Kumar.

At least 19 recordsLinked to original sources

A comparative study on the efficacy of rofecoxib in monoarticular arthritis induced by latex of Calotropis procera and Freund's complete adjuvant.

The role of prostaglandins in Calotropis procera latex induced inflammation and hyperalgesia has been well established. The acute inflammation induced by the dried latex (DL) of this plant could be effectively ameliorated by standard anti-inflammatory drugs. In present study we have evaluated the efficacy of rofecoxib, a COX-2 inhibitor in monoarthritis induced by intra-articular injection of DL and compared it with that against Freund's Complete Adjuvant (FCA). DL and FCA were injected into the right ankle joint of the rat and the joint diameter was measured by a micrometer screw gauge on day 0, 4, 8, 12, 20 and 28. Concomitantly the hyperalgesic response was also evaluated by motility test, stair climbing ability test, dorsal flexion pain test and compression test. The effect of rofecoxib was evaluated on these parameters in both the models. Both DL and FCA produced peak inflammation on day 4 that was associated with decreased pain threshold and functional impairment. Although rofecoxib was more effective in improving motility in the DL model, its effect on joint inflammation, hyperalgesia and stair climbing ability was comparable in both the models. Thus, our study indicates that DL induced monoarthritis could be used as a model for the screening and evaluation of anti-inflammatory and anti-arthritic drugs.

Administration, Oral↗

Evaluation of cytotoxic potential of latex of Calotropis procera and podophyllotoxin in Allium cepa root model.

In the present study we have utilized the Allium cepa root tip meristem model to evaluate the cytotoxic and anti-mitotic activities of latex of Calotropis procera (DL) and podophyllotoxin. Standard cytotoxic drug cyclophosphamide and non-cytotoxic drugs cyprohcptadine and aspirin served as controls. Like cyclophosphamide, both DL and podophyllotoxin significantly inhibited the growth of roots and mitotic activity in a dose-dependent manner. However, podophyllotoxin was more potent in this regard and produced root decay. Cyproheptadine and aspirin, on the other hand, showed a marginal effect on the root growth and mitotic activity at much higher concentrations.

Calotropis↗

Antioxidant and protective effect of latex of Calotropis procera against alloxan-induced diabetes in rats.

In the present study, dry latex (DL) of Calotropis procera possessing potent anti-inflammatory activity was evaluated for its antioxidant and anti-hyperglycemic effects against alloxan-induced diabetes in rats. Daily oral administration of DL at 100 and 400 mg/kg doses produced a dose-dependent decrease in the blood glucose and increase in the hepatic glycogen content. DL also prevented the loss of body weight in diabetic rats and brought down the daily water consumption to values comparable to normal rats. DL also produced an increase in the hepatic levels of the endogenous antioxidants, namely superoxide dismutase (SOD), catalase and glutathione, while it brought down the levels of thiobarbituric acid-reactive substances (TBARS) in alloxan-induced diabetic rats. The efficacy of DL as an antioxidant and as an anti-diabetic agent was comparable to the standard anti-diabetic drug, glibenclamide.

Alloxan↗

In vivo and in vitro effect of latex of Calotropis procera on gastrointestinal smooth muscles.

The present study was carried out to evaluate the effect of dry latex (DL) of Calotropis procera on smooth muscles of gastrointestinal tract. Oral administration of DL to rats (50-1000 mg/kg) produced a dose-dependent decrease in intestinal transit along with a decrease in intestinal content as compared to control group. At lower doses DL produced dose-dependent contractions of gastrointestinal smooth muscles in vitro (rabbit ileum and fundus of rat stomach) that was followed by desensitization at higher doses.

Administration, Oral↗

In vivo modulation of androgen receptor by androgens.

AIM: To study the effect of androgen and antiandrogen on the level of androgen receptor (AR) mRNA. METHODS: The total RNA was extracted from the prostate and analyzed by slot blot analysis. The blots were hybridized with AR cDNA probe and 1A probe (internal control) and autoradiography was performed. The intensity of signal was measured with a densitometer and the ratio of AR RNA and 1A RNA was calculated. RESULTS: Androgenic deprivation produced by castration decreased the weight of the prostate and increased the levels of AR mRNA. Treatment of the castrated rats with testostrone increased the weight of prostate and decreased the levels of AR mRNA. Treatment of normal rats with flutamide decreased the weight of the gland and increased the levels of AR mRNA. CONCLUSION: Androgens produce proliferative effect on the prostate and negatively regulate the AR transcription.

Animals↗

Anti-diarrhoeal activity of the latex of Calotropis procera.

The dry latex (DL) of Calotropis procera (Asclepiadaceae), a potent anti-inflammatory agent has been evaluated for anti-diarrhoeal activity. Like atropine and phenylbutazone (PBZ), a single oral dose of DL (500 mg/kg) produced a significant decrease in frequency of defecation, severity of diarrhoea and afforded protection from diarrhoea in 80% rats treated with castor oil. To understand the mechanism of its anti-diarrhoeal activity, we further evaluated its effect on intestinal transit, castor oil induced intestinal fluid accumulation (enteropooling) and electrolyte concentration in the intestinal fluid. DL produced a decrease in intestinal transit (27-37%) as compared to both normal and castor oil treated animals. Unlike atropine, DL significantly inhibited castor oil induced enteropooling. However, it did not alter the electrolyte concentration in the intestinal fluid as compared to castor oil treated rats.

Animals↗

Preliminary studies on the analgesic activity of latex of Calotropris procera.

In this study we have evaluated the analgesic activity of dry latex (DL) of Calotropis procera. A single oral dose of DL ranging from 165 to 830 mg/kg produced a significant dose dependent analgesic effect against acetic acid induced writhings. The effect of DL at a dose of 415 mg/kg was more pronounced as compared to a 100 mg/kg oral dose of aspirin. On the other hand DL (830 mg/kg) produced marginal analgesia in a tail-flick model which was comparable to aspirin. The analgesic effect of DL was delayed by 1 h by naloxone at a dose of 0. 5 mg/kg, i.p., which completely blocked the analgesic effect of morphine (10 mg/kg, i.p.). However, the effect of aspirin was not blocked by naloxone. The 830 mg/kg oral dose of DL did not produce toxic effects in mice and the LD(50) was found to be 3 g/kg.

Acetic Acid↗

Alpha adrenergic blockers in the treatment of benign hyperplasia of the prostate.

Benign prostatic hyperplasia (BPH), a common benign tumor in men has been attributed to age and male androgen functions. Of the various management options for treatment of BPH, medical therapy is the first line treatment modality involving either blockade of alpha adrenergic receptors or inhibition of 5-alpha reductase. Amongst these, the alpha-1 blockers are used most frequently. The association of numerous adverse effects with non selective and short acting alpha-1 blockers (like phenoxybenzamine, prazosin and alfuzosin) has led to the development of long acting alpha-1 adrenoceptor blockers (doxazosin, terazosin, tamulosin) which being uroselective significantly reduce the incidence of cardiovascular side effects and increase patient compliance. The review gives a brief account of pharmacological properties and efficacy of alpha adrenergic receptor blockers in the treatment of BPH.

Adrenergic alpha-Antagonists↗

Observations on EGFR gene amplification and polymorphism in prostatic diseases.

This study was designed to determine the amplification and polymorphism of epidermal growth factor receptor (EGFR) gene in prostatic diseases like benign hypertrophy (BPH) and carcinoma (CaP). The EGFR gene was found to be amplified in grade IV BPH as compared to grade II BPH. Digestion of genomic DNA with MspI and HpaII revealed the presence of a 5kb band following southern blot analysis. This 5kb band was present in all the CaP cases and in one out of three BPH cases. It is possible that such a polymorphism is associated with the type or extent of tumor progression.

Aged↗

Comparative analysis of epidermal growth factor receptor mRNA levels in normal, benign hyperplastic and carcinomatous prostate.

Epidermal growth factor receptor (EGFR), a mediator of mitogenic activity of epidermal growth factor and transforming growth factor-alpha, has been shown to be associated with tumour progression. We have detected a level of EGFR transcript in normal, hyperplastic (BPH) and carcinomatous (CaP) prostate tissues by cytoplasmic dot hybridization. Our results show that the majority of CaP cases (62% of untreated cases and 71% of treated cases) were positive for EGFR mRNA while about 50% of normal and BPH cases were positive for EGFR mRNA. The level of EGFR transcript was significantly higher in the untreated CaP group as compared to the normal group (P < 0.05), while the difference in the normal and BPH groups was not statistically significant.

Adult↗

Detection of receptor transcripts for androgen, epidermal growth factor and basic fibroblast growth factor in human prostate postmortem.

RNA isolated from frozen human postmortem prostate tissue was evaluated for its utility in molecular biological studies based on RNA analysis. Our results on slot-blot analysis show the presence of receptor transcripts for androgen, epidermal growth factor and basic fibroblast growth factor in postmortem prostate tissue obtained 20-120 hrs after death. However, the RNA in these samples was found to be degraded as revealed by the absence of ribosomal bands on gel electrophoresis. AR mRNA was found to be present in one of the five samples when analysed by northern blotting.

Adult↗

Androgen receptor mRNA detection in the human foetal prostate.

In order to get an insight into androgen-mediated differentiation and development of the prostate, we detected the androgen receptor (AR) mRNA in the urogenital sinus of human foetuses at 12 and 16 weeks of gestation. Cytoplasmic dot hybridization using radiolabelled cDNA probe for human androgen receptor (AR) was performed. The AR mRNA could be detected at 12 weeks of gestation and its level was higher at 16 weeks of gestation.

Autoradiography↗

Androgen deprivation causes up-regulation of androgen receptor transcript in the rat prostate.

We have studied the effect of androgenic deprivation on the level of androgen receptor transcript in the rat ventral prostate. The rats were treated with estradiol benzoate, flutamide and [D Trp6, des Gly10]gonadotropin releasing hormone (GnRH) for different time periods. These treatments produced a significant decrease in the weight of prostate. Total RNA isolated from the ventral prostates was hybridized with the cDNA probe for androgen receptor. Densitometric analysis of the autoradiographic signal revealed a rise in the level of androgen receptor RNA following treatment of rats with estradiol benzoate and flutamide. Treatment of rats with [D Trp6, des Gly10] GnRH brought about a transient rise in the level of androgen receptor RNA. Thus, our results indicate that androgenic deprivation up-regulates the level of androgen receptor transcript.

Androgens↗

Androgen receptor transcript level in benign hypertrophy and carcinoma of the human prostate.

OBJECTIVE: Current reports suggest the presence of androgen receptor (AR) defects in prostate cancer. We have detected the AR mRNA in normal, benign hypertrophied (BPH) and carcinomatous (CaP) prostate tissues and evaluated the difference in the level of AR transcript in these groups. MATERIALS AND METHODS: Cytoplasmic dot hybridization assay was used to measure the levels of AR mRNA in 21 normal, 45 BPH and 30 CaP specimens. Tissue samples of 14 CaP patients receiving endocrine treatment were also analyzed. Blots were autoradiographed and the intensity of the signal was measured by densitometry. RESULTS AND CONCLUSIONS: The majority of cases in all the 3 groups were positive for the AR mRNA. All the patients who had received endocrine treatment were also positive for the AR mRNA. The level of the AR mRNA was significantly higher in BPH and treated CaP cases as compared to normal cases (p < 0.05). Among the CaP cases the level of AR transcript was significantly higher in the treated group as compared to the untreated group.

Adult↗

Prostate gland: structure, functions and regulation.

The prostate gland plays an important role in male reproduction. It secretes enzymes, lipids, amines and metal ions essential for the normal function of spermatozoa. Development, differentiation and maintenance of the prostate gland depend on steroid and peptide hormones. Beside hormones growth factors also regulate the prostate gland. This review will focus on the structure, functions and mode of regulation of the prostate gland.

Animals↗

In vivo functional analysis of the mouse estrogen receptor gene promoter: a transgenic mouse model to study tissue-specific and developmental regulation of estrogen receptor gene transcription.

Understanding the molecular and morphological basis of estrogen responsiveness in the various tissues and organs that make up an adult organism and its onset during ontogenesis requires identification of the genetic controls that determine timed expression of the estrogen receptor (ER) gene in multiple cell types. With this goal in mind, we describe here the results of the functional analysis of the mouse (m) ER gene promoter, carried out in vivo in transgenic mice. The mER gene promoter was cloned and spliced to the coding sequence of the bacterial lacZ gene (fused to the nuclear localization signal of SV40 large T: nls-beta-GAL) and then stably reintegrated into the genome of mice. Analysis of beta-GAL mRNA and protein expression in multiple organs of both female and male transgenic animals was then performed. Results show that the transgenic mER promoter, much like the endogenous one, is active in several organs and tissues of adult female and male mice. The first 0.4 kilobases of 5'-flanking DNA (up to -364) are sufficient to direct widespread expression of the transgene in mouse organs. This indicates that genetic elements functional in various cell types are included in this segment. Furthermore, the first exon and intron of the mER gene are necessary to achieve sexually dimorphic expression of the transgene in neurons located at specific sites within the central nervous system. These mER promoter transgenic mice will be useful in mapping estrogen- responsive cell types under different physiological and pathological conditions in vivo, in defining ontogenesis of estrogen action in the mouse, and in studying the mechanisms that regulate ER gene transcription.

Animals↗

Inhibitory effects of formaldehyde on the reproductive system of male rats.

Formaldehyde, when administered to rats at a dose of 10 mg/kg body weight/day for a period of 30 days, resulted in a significant fall in sperm motility, viability and count. In addition, the DNA content was significantly lower in testis and prostate while the tissue protein content of prostate and epididymis had decreased in the treated rats. In vitro exposure to formaldehyde also inhibited the sperm motility and viability.

Animals↗

Anti-inflammatory activity of the latex of Calotropis procera.

The anti-inflammatory property of the latex of Calotropis procera was studied on carrageenin- and formalin-induced rat paw oedema model. A single dose of the aqueous suspension of the dried latex was effective to a significant level against the acute inflammatory response.

Animals↗