Synthesis and characterization of monodispersed water dispersible Fe3O4 nanoparticles and in vitro studies on human breast carcinoma cell line under hyperthermia condition.

Monodispersed Fe3O4 magnetic nanoparticles (MNPs) having size of 7 nm have been prepared from iron oleate and made water dispersible by functionalization for biomedical applications. Three different reactions employing thioglycolic acid, aspartic acid and aminophosphonate were performed on oleic acid coated Fe3O4. In order to achieve a control on particle size, the pristine nanoparticles were heated in presence of ferric oleate which led to increase in size from 7 to 11 nm. Reaction parameters such as rate of heating, reaction temperature and duration of heating have been studied. Shape of particles was found to change from spherical to cuboid. The cuboid shape in turn enhances magneto-crystalline anisotropy (Ku). Heating efficacy of these nanoparticles for hyperthermia was also evaluated for different shapes and sizes. We demonstrate heat generation from these MNPs for hyperthermia application under alternating current (AC) magnetic field and optimized heating efficiency by controlling morphology of particles. We have also studied intra-cellular uptake and localization of nanoparticles and cytotoxicity under AC magnetic field in human breast carcinoma cell line.

Purification and characterization of pectin lyase secreted by Aspergillus flavus MTCC 10938.

An indigenously isolated fungal strain Aspergillus flavus MTCC 10938 was subjected to pectin lyase (PNL) production under submerged fermentation conditions. The enzyme was purified to homogeneity from the culture filtrate of the fungus involving concentration by ultrafiltration, anion exchange chromatography on DEAE cellulose and gel filtration chromatography on Sephadex G-100. The purified PNL gave a single protein band in SDS-PAGE analysis with a relative molecular mass corresponding to 50 kDa. Using citrus pectin as the substrate the K(m) and k(cat) values of the enzyme lyase were obtained as 1.7 mg/mL and 66 s(-1), respectively. The optimum pH of the purified PNL from A. flavus MTCC 10938 was 8.0 and up to 90% of its activity retained in the pH range from 3.0 to 11.0 after 24 h incubation. The optimum temperature of the purified enzyme was revealed at 55 degrees C and it was completely stable up to 40 degrees C when exposed for 30 min. The purified A. flavus MTCC 10938 PNL showed efficient retting of Crotalaria juncea fibres.

Ginkgo biloba--an appraisal.

Ginkgo biloba has been used in traditional Chinese medicine for about 5000 years. A standardized preparation, EGb 761 has been recently prepared. The pharmacologically active constituents, flavonol glycosides and the terpene lactones are standardized. The terpene lactones comprise of ginkgolides A, B, C and bilobalides. The extract scavenges excess free radicals and pretreatment with EGb 761 reduces damage by free radicals in patients undergoing coronary bypass surgery. The action of platelet activating factor is antagonized and platelet aggregation is reduced. Blood flow is increased. Release of prostacyclines and nitric oxide was shown to be stimulated. Ginkgo biloba has been found to be useful in the treatment of Alzheimers disease and cognitive impairment. EGB 761 has shown beneficial effect in aging and mild cognitive impairment. Bilobalide has been shown to be protective against glutamate-induced excitotoxic neuronal death. Early studies indicate a potential role in age-related macular degeneration and some types of glaucoma. Anticancer action is related to antioxidant, anti-angiogenic and gene regulatory actions. Ginkgo biloba has shown overall improvement in about 65% of patients with cerebral impairment and a similar percentage suffering from peripheral vascular diseases. A recent study suggested that phytoestrogens in Ginkgo biloba may have a role as alternative hormone replacement therapy. Recent trials have not shown a beneficial effect of Ginkgo biloba in tinnitus and acute mountain sickness. Ginkgo biloba increased the bioavailability of diltiazem. The extract has been shown to protect against doxorubicin-induced cardiotoxicity and gentamicin-induced nephrotoxicity in animals. Ginkgo biloba inhibits microsomal enzymes and has a potential for drug interactions. Further studies to establish the efficacy of Ginkgo biloba are required.

In the rhesus monkey (Macaca mulatta), the negative feedback regulation of follicle-stimulating hormone secretion by an action of testicular hormone directly at the level of the anterior pituitary gland cannot be accounted for by either testosterone or estradiol.

In the male rhesus monkey, the negative feedback regulation of gonadotropin secretion by the gonad appears to involve a specific inhibitory action of testicular hormone on FSH release at the level of the anterior pituitary gland. The purpose of the present study, which used the hypophysiotropic clamp preparation, was to determine whether circulating testosterone (T) or estradiol (E) comprises a major component of the testicular FSH-inhibiting factor in this species. Endogenous hypothalamic GnRH secretion was abolished or severely compromised in five adult male rhesus monkeys by placement of radiofrequency lesions in the region of the arcuate nucleus. Subsequently, an episodic pattern of activity in the pituitary-Leydig cell axis of these animals was restored by a chronic and unchanging intermittent iv infusion of GnRH (0.1 microgram/min for 3 min ever 3 h), which appears to provide the gonadotropes of lesioned animals with a hypophysiotropic drive comparable to that produced by the hypothalamus of animals with an intact central nervous system. Treatment of three animals with a specific anti-E-gamma-globulin fraction resulted in a marked and sustained rise in E-binding activity in serum, but this neutralization of circulating E did not elicit hypersecretion of FSH. In all five animals, initiation of T replacement on the day of orchidectomy, which maintained circulating T concentrations in the high testis-intact control range, failed to prevent the postcastration hypersecretion of FSH that is evoked after removal of testis in the hypophysiotropic clamp preparation. As expected, the changes in circulating LH levels during immunoneutralization and after orchidectomy and T replacement were unremarkable. These findings indicate that neither circulating T nor E can account for the testicular inhibition of FSH secretion in the rhesus monkey and thus lead, by a process of exclusion, to the view that in this species the negative feedback regulation of FSH release by the testis is mediated directly at the level of the gonadotrope by an inhibitory action of a nonsteroidal hormone, most probably the recently identified gonadal peptide inhibin.

A suppression of gonadotropin secretion by cortisol in castrated male rhesus monkeys (Macaca mulatta) mediated by the interruption of hypothalamic gonadotropin-releasing hormone release.

Four orchidectomized rhesus monkeys (3-3.5 yr of age) were treated for 62 days with daily i.m. injections of hydrocortisone acetate (HCA) at a dose of 10-20 mg/(kg BW X day), and blood samples were obtained daily or every other day before, during, and after treatment. Hydrocortisone acetate injections resulted in a progressive rise in mean plasma cortisol from basal concentrations of 17-35 micrograms/100 ml prior to initiation of steroid treatment to approximately 150 micrograms/100 ml 5 wk later. When serum cortisol concentrations reached 100 micrograms/100 ml, 3-4 wk after the initiation of HCA treatment, circulating luteinizing hormone (LH) and follicle-stimulating hormone (FSH) began to decline, reaching nondetectable concentrations 35 days later. Withdrawal of HCA resulted in a return in plasma cortisol concentrations to pretreatment control levels, which was associated with a complete restoration of gonadotropin secretion. In 2 animals, administration of an intermittent i.v. infusion of gonadotropin-releasing hormone (GnRH) (0.1 micrograms/min for 3 min once every hour), which appears to stimulate the gonadotropes in a physiologic manner, reversed the cortisol-induced inhibition of gonadotropin secretion, restoring circulating LH and FSH concentrations to within 80-100% of control. These results suggest that, in the rhesus monkey, the major site of the inhibitory action of cortisol on gonadotropin release resides at a suprapituitary level and is mediated by interruption of hypothalamic GnRH release.

Evidence from the rhesus monkey (Macaca mulatta) for the view that negative feedback control of luteinizing hormone secretion by the testis is mediated by a deceleration of hypothalamic gonadotropin-releasing hormone pulse frequency.

The site and mode of the feedback actions of testicular hormones on gonadotropin secretion in the adult rhesus monkey were investigated using the arcuate-lesioned preparation previously employed by others to study cognate problems in the female. The negative feedback loop that governs LH and FSH release in the male monkey was opened without changing either the frequency or amplitude of intermittent GnRH stimulation of the pituitary gonadotrophs, which was clamped by exogenous GnRH replacement at a level that approximated the intact or closed loop hypophysiotropic signal. In this manner, the relative importance of adenohypophysial vs. hypothalamic sites of feedback action of testicular hormones on LH and FSH secretion was assessed. To accomplish the foregoing, radiofrequency lesions were placed in the region of the arcuate nucleus to abolish endogenous hypothalamic GnRH secretion. Patterns of temporally coupled episodes of pituitary LH and testicular testosterone discharge that in nonlesioned animals characteristically occur, on the average, once every 3 h throughout the 24-h light-dark cycle were restored in lesioned animals by an intermittent iv infusion of GnRH (0.1 micrograms/min for 3 min every 3 h). Bilateral orchidectomy in this experimental paradigm elicited only small increments in LH pulse amplitude and mean plasma LH concentration, a response in striking contrast to the dramatic postcastration LH hypersecretion observed in animals with intact hypothalami that respond to the opening of the negative feedback loop with an apparent acceleration in the endogenous frequency of intermittent GnRH secretion. A marked rise in mean plasma LH concentration in arcuate-lesioned males, however, was forth-coming when the frequency of intermittent exogenous GnRH stimulation was increased 2-3 weeks after castration from one pulse every 3 h (intact frequency) to one pulse per h (castrate frequency). These findings fail to provide evidence for a major inhibitory feedback action of the testes on LH secretion at the level of the adenohypophysis. They are entirely consistent, however, with the hypothesis that the negative feedback control of LH release by the male gonad is mediated, principally, via the central nervous system by an action of testicular hormone, most probably testosterone, to retard the frequency of the neural timing mechanism that governs the intermittent pattern of GnRH release by the hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)