Reversible induction of azoospermia in rhesus monkeys by constant infusion of a gonadotropin-releasing hormone agonist using osmotic minipumps

This study documents the long term, reversible, antireproductive effects of GnRH agonist treatment in adult male rhesus monkeys. Constant sc infusion of the GnRH agonist buserelin by osmotic minipumps over 20 weeks resulted in an initial rise in serum LH, followed by a decline to undetectable levels, indicating pituitary desensitization. This rise and fall of plasma LH was paralleled by serum testosterone concentrations. The RHLH response to an iv bolus injection of GnRH was completely abolished, and the corresponding Leydig cell response was also lost. Testicular volumes decreased markedly, and spermatogenesis was inhibited to azoospermic levels. Spontaneous and electrostimulated ejaculatory activities were lost under prolonged buserelin infusion. The animals were then supplemented with exogenous testosterone to reestablish ejaculatory behavior which had been curtailed under low circulating androgen levels, and azoospermia persisted. Such pronounced effects could not be demonstrated in our previous studies using daily or twice daily injections with higher agonist doses. When treatment was stopped after 20 weeks, the inhibitory effects of the GnRH agonist were reversible, and full pituitary and gonadal functions were recovered. It is concluded that constant infusion of GnRH agonist is far more effective in male rhesus monkeys than daily injections and that the suppressive effects of GnRH agonist application are fully reversible. Thus, a suitable primate model for further research on a GnRH agonist-based male contraceptive has been established.     

Diabetes-induced renal vascular dysfunction is normalized by inhibition of epidermal growth factor receptor tyrosine kinase

Contribution of receptor tyrosine kinase activation to development of diabetes-induced renal artery dysfunction is not known. We investigated the ability of a chronic administration of genistein, a broad-spectrum inhibitor of tyrosine kinases (TKs), and AG1478, a specific inhibitor of epidermal growth factor receptor (EGFR) TK activity, to modulate the altered vasoreactivity of isolated renal artery ring segments to common vasoconstrictors in streptozotocin-induced diabetes. In diabetic renal artery, the vasoconstrictor responses induced by norepinephrine, endothelin-1 and angiotensin II were significantly increased. Inhibition of TKs or the EGFR pathway did not affect the agonist-induced vasoconstrictor responses in the non-diabetic control animals. However, inhibition of TKs by genistein or EGFR TK by AG1478 treatment produced a significant normalization of the altered agonist-induced vasoconstrictor responses without affecting blood glucose levels. Treatment with diadzein, an inactive analogue of genistein, did not affect the vasoconstrictor responses in the diabetic animals. Western blotting showed that phosphorylated EGFR protein levels were increased in vehicle-treated diabetic animals. In renal arteries from AG1478-treated diabetic animals, EGFR protein levels were similar to non-diabetic control animals. These data suggest that activation of TK-mediated pathways, including the EGFR TK signalling pathway, are involved in the development of diabetic vascular dysfunction in the renal artery.     

Spontaneous idiopathic subcapsular biloma

Spontaneous biloma is an uncommon entity. We report a case of subcapsular biloma in an elderly patient with a nonobstructed biliary channel, without prior history of surgery, instrumentation, or trauma. Computed tomography (CT) and magnetic resonance imaging are described. We believe that this is the first reported case of spontaneous subcapsular biloma of idiopathic origin.     

Antiobesity,hypolipidemic, antioxidant and hepatoprotective effects of Achyranthes aspera seed saponins in high cholesterol fed albino rats

Introduction

Numerous herbal medicines have been recommended for the treatment of different diseases. Achyranthes aspera, Linn. (Family: Amaranthaceae), popularly known as Charchitta or Pitpapra, is commonly used by traditional healers for the treatment of fever, malaria, dysentery, asthma, arterial hypertension, pneumonia, and diabetes. The root extract is well reputed for its insect molting hormonal activity. This investigation was conducted to evaluate the effects of saponins from Achyranthes aspera seeds on the serum lipid profile of albino rats fed a high cholesterol diet.

Material and methods

Hypolipidemic, antioxidant and hepatoprotective activities of these saponins were tested as described previously. To determine the mechanism underlying the observed effects, serum antioxidant status was assessed according to ABTS (2,2’-azino-bis-3-ethylbenzo-thiazoline-6-sulfonic acid), superoxide dismutase and ferric ion reducing antioxidant power (FRAP) assays in saponin-treated hyperlipidemic animals. Liver enzyme levels were determined to reveal any possible hepatotoxicity.

Results

Four-week oral administration of A. aspera seed saponins produced a significant (p < 0.05) decrease of total cholesterol, total triglycerides and LDL-C and a significant increase of HDL-C level in hyperlipidemic rats. Treatment with A. aspera seed saponins also showed a significant (p < 0.01) improvement of serum antioxidant status in tested animals. No significant hepatotoxicity was produced by such treatment as the serum liver enzyme activity remained unaltered.

Conclusions

Saponins from A. aspera seeds possess antihyperlipidemic and antioxidant properties which might lead to improvement of serum lipid profile and blood antioxidant status. Our findings support the folkloric use of this indigenous plant in the treatment of hyperlipidemia. However, its exact mechanism of action remains to be elucidated.     

Antibody Avidity in Humoral Immune Responses in Bangladeshi Children and Adults following Administration of an Oral Killed Cholera Vaccine

Antibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies.     

Progress and prospects in the management of bacterial infections and developments in Phytotherapeutic modalities

The advent of antibiotics revolutionized medical care resulting in significantly reduced mortality and morbidity caused by infectious diseases. However, excessive use of antibiotics has led to the development of antibiotic resistance and indeed, the incidence of multidrug-resistant pathogens is considered as a major disadvantage in medication strategy, which has led the scholar's attention towards innovative antibiotic sources in recent years. Medicinal plants contain a variety of secondary metabolites with a wide range of therapeutic potential against the resistant microbes. Therefore, the aim of this review is to explore the antibacterial potential of traditional herbal medicine against bacterial infections. More than 200 published research articles reporting the therapeutic potential of medicinal plants against drug-resistant microbial infections were searched using different databases such as Google Scholar, Science Direct, PubMed and the Directory of Open Access Journals (DOAJ), etc., with various keywords like medicinal plants having antibacterial activities, antimicrobial potentials, phytotherapy of bacterial infection, etc. Articles were selected related to the efficacious herbs easily available to local populations addressing common pathogens. Various plants such as Artocarpus communis, Rheum emodi, Gentiana lutea L., Cassia fistula L., Rosemarinus officinalis, Argemone maxicana L, Hydrastis canadensis, Citrus aurantifolia, Cymbopogon citrates, Carica papaya, Euphorbia hirta, etc, were found to have significant antibacterial activities. Although herbal preparations have promising potential in the treatment of multidrug-resistant bacterial infection, still more research is required to isolate phytoconstituents, their mechanism of action as well as to find their impacts on the human body.