JU-2, a novel phosphorous-containing antifungal antibiotic from Streptomyces kanamyceticus M8.

A novel phosphorous-containing antifungal antibiotic JU-2 was isolated from Streptomyces kanamyceticus M8. Quantitative chemical analysis shows the presence of two phenylalanines, two glucose, one linoleic acid, one crucic acid and one phosphonamide moiety per molcule of the antibiotic. JU-2 shows strong inhibitory activity against various pathogenic and non-pathogenic fungi but no activity against bacteria and yeast.

Carboxy terminal region of a chloroplast DNA polymerase accessory factor stimulates DNA polymerase activity.

p43, a glycoprotein of pea chloroplast (ct), acts as an accessory protein of pea chloroplast DNA polymerase. p43 binds to DNA, binds to ct-DNA polymerase and stimulates the ct-DNA polymerase activity. In the work presented here, the C-terminal domain of p43 (p22) has been overexpressed in E. coli. South Western analysis reveals that the recombinant p22 lacks in DNA binding activity. However, the recombinant p22 can form complex with the pea ct-DNA polymerase quite efficiently and stimulates the DNA polymerase activity to a greater extent than the native p43. Thus the DNA binding domain of p43 appears to be spatially separate from the domain responsible for the DNA polymerase accessory activity. The DNA binding domain is also highly O-glycosylated and loss of glycosylation of p43 leads to enhanced DNA binding as well as repression of ct-DNA polymerase activity. These findings allow us to propose a model to explain how glycosylation of p43 helps ct-DNA polymerase latch onto the DNA template for enhanced processivity. The predictive components of the model have been discussed.

Prevention of radiation induced taste aversion in rats.

Diltiazem, a calcium channel blocker, and a cardiovascular therapeutic agent offers significant protection to mice against lethal dose of ionizing radiation. Considering the potential efficacy of diltiazem as a radioprotector for human use, it was deemed necessary to investigate its influence on radiation-induced behavioural changes like nausea, vomiting, learning, memory and performance. In the present studies, conditioned taste aversion (CTA) test based on consumption of saccharin solution, was used as a marker of behavioural changes. Significant CTA (97 +/- 2%) was observed in rats irradiated with Co-60 gamma rays (absorbed dose 1 Gy). Administration of diltiazem at doses greater than 10 mg/kg, body wt, evoked CTA in a dose-dependent manner and that was found to be further aggravated on irradiation. At a lower dose of 5 mg/kg, body wt, diltiazem did not evoke CTA and protected against radiation induced aversion significantly (62 +/- 3%). The results suggest that diltiazem at concentrations lower than 10 mg/kg, body wt, in rats may be useful in preventing radiation induced behavioural changes. This observation could be of particular significance in clinical radiotherapy where radiation induced nausea and vomiting are of great concern.

Mode of action of three structurally different hypoglycemic agents: a comparative study.

The mechanism of dose-dependent hypoglycemic effect, the margin of safety and ED50 of three structurally unrelated compounds, tolbutamide (TB), centpiperalone (CP) and a swerchirin-containing fraction (SWI) from the plant Swertia chirayita, were investigated in experimental models. After a single oral administration of TB, CP and SWI to groups of normal and streptozotocin (STZ)-induced mild and severe diabetic rats, the blood sugar lowering effect and ED50 of the agents were determined. Plasma Immuno Reactive Insulin (IRI) levels and the degree of islet beta cell degranulation were assayed using RIA and histochemical staining, respectively, in normal rats treated with the agents. The percent blood sugar lowering, increase in IRI levels and beta cell degranulation were highest in CP treated normal rats (69, 124 and 75%, respectively). In addition, CP was the only agent found active in STZ-induced severely diabetic rats (P < 0.01). In STZ-mild diabetic rats, however, TB was more effective than CP and SWI. By analysis of data using Anova method, it is concluded that CP is more effective than SWI (P < 0.01) and TB. However, SWI an impure natural product showed better blood sugar lowering than tolbutamide which is a drug in use.

Parenteral ciprofloxacin in persistent diarrhoea in children.

In a controlled trial of 30 cases of persistent diarrhoea in infants, ciprofloxacin was used parenterally for systemic antibiotic therapy. Group A cases (15 in number) were treated with parenteral ciprofloxacin and group B control cases (remaining 15) were treated with parenteral ampicillin and chloramphenicol or ampicillin/amikacin along with treatment of dehydration and malnutrition. All group A cases had excellent response and 9 infants of group B had no response up to day 4. After stopping all other drugs and with parenteral ciprofloxacin they responded favourably. Follow-up of all the cases was done regularly every 2 weeks for 6 months after discharge. No toxicity of ciprofloxacin was noted.

Microbial production of L-tyrosine: a review.

Microbial production of L-tyrosine by direct fermentation and by enzymatic methods has been reviewed. Achievements in this regard made through recombinant DNA techniques have also been included. The review also includes biosynthesis and regulation of tyrosine.

Denatured supercoiled DNA--structural and biological activity.

Supercoiled DNA on treatment with NaOH followed by neutralization produces a condensed structure (form Id). This structure does not split into topoisomers when run on long gel in presence of intercalating agents and the migration of this form does not change appreciably in presence or absence of ethidium bromide. Relaxation of form Id by topoisomerase I from pea chloroplast is facilitated more than form I. Single-stranded binding (SSB) protein binds more to form Id as evidenced from gel retardation study. Hydroxyl radical nicking is facilitated in this form. Compared to form I, this form produces half the number of transformants, but adsorption and penetration remain almost same in both the forms. Post-transformational growth using 32P labelled form I and form Id showed greater amount of degradation in form Id.

Blood and hepatic glutathione in linamarin fed rats.

Female Sprague Dawley rats were fed 5 mg linamarin daily for 10 days. Reduced glutathione (GSH) levels in blood and liver of experimental rats were analysed. The results showed an increase of 45% and 33% glutathione levels in blood and liver respectively in experimental rats. This alteration in glutathione levels could be most likely either due to increased hepatic biosynthesis or as a consequence of decreased peripheral utilization which might be appreciated due to hypothyroidal status induced by linamarin feeding.

Biochemical activities of denatured covalently closed circular duplex DNA.

Covalently closed circular duplex DNA when exposed to high alkaline pH followed by neutralization yields a collapsed state structure (form I(d)) that can undergo transition to form I and was susceptible to S1 nuclease. Form I(d), in spite of its compact structure, admits specific cleavage by restriction enzymes over its entire genome. When used in a semi-in vitro replication complex, form I(d) gave significantly better template activity, and undergoes better primer extension in in vitro using Klenow. Thus form I(d) having a compact shape can behave as a better substrate in a few key enzymatic reactions.

Mechanism of blood sugar lowering by a swerchirin-containing hexane fraction (SWI) of Swertia chirayita.

Mechanism of blood sugar lowering by the crude/impure swerchirin (SWI) isolated from the hexane fraction of Swertia chirayita was investigated. Single oral administration of SWI (50 mg/kg, body wt) to fed CF rats induced about 60% (max.) fall in blood glucose by 7 hr post-treatment. This was associated with marked depletion of aldehyde-fuchsin stained beta-granules and immunostained insulin in the pancreatic islets. In vitro, glucose uptake and glycogen synthesis by muscle (diaphragm) was significantly enhanced by the serum of SWI-treated rat. At 100, 10 and 1 microM final concentration, SWI greatly enhanced glucose (16.7 mM)-stimulated insulin release from isolated islets. It is therefore concluded that SWI lowers blood glucose level by stimulating insulin release from islets of Langerhans.

Swerchirin induced blood sugar lowering of streptozotocin treated hyperglycemic rats.

Effect of Swerchirin (1:8 dihydroxy 3:5 dimethoxy xanthone) isolated from hexane fraction of Swertia chirayita on the blood sugar level of healthy and streptozotocin treated rats was studied. Streptozotocin was administered in citrate buffer (pH-4.5) intravenously / 35 and 65 mg/kg body wt to Charles Foster strain albino rats. Swerchirin (50 mg/kg, po) suspended in gum acacia was fed through cannula to the above rats and to a group of healthy rats. Blood sugar estimated at 0, 1, 3 and 7 hr after, indicated a very significant lowering in healthy and streptozotocin (35 mg/kg iv) but not in streptozotocin (65 mg/kg) treated rats.

Hypoglycemic activity of Swertia chirayita (Roxb ex Flem) Karst.

Hexane fraction of S. chirayita (250 mg/kg body wt.) induced significant fall in blood sugar and significant increase in plasma IRI simultaneously after single oral administration without influencing liver glycogen concentration in albino rats. On the other hand, daily administration for 28 days resulted in significant lowering of blood sugar and increase in plasma IRI along with a significant rise in liver glycogen. Intestinal absorption of glucose was not inhibited by hexane fraction. It is suggested that hexane fraction of S. chirayita possibly acts through its insulin releasing effect.

Potassium induced insulin release from isolated islet of Langerhans of albino rats.

The secretory effect of Potassium (K+) on endocrine pancreas was studied using collagenase digested isolated islets of Langerhans. Isolated islets of Langerhans incubated in KRB containing 5 15, 30 and 45 mM, quantity of additional K ions caused the release of insulin from beta-cells (significant release of insulin, P less than 0.01, at 15, 30 and 45 mM K+ in presence of 2.8 mM glucose and at 30 mM K in presence of 16.7 mM glucose). But lysosomal AP and CB enzymes did not record proportionate change. Thus a definite stimulation in the release of insulin without significant change in AP and CB were seen.

Effect of herbicide banvel on rabbit vaginal mucus membrane.

Effect of banvel and its active ingredient, dicamba (3,6-dichloro-o-anisic acid) was investigated employing rabbit mucus membrane irritancy test. Inflammatory changes which did not exceed an average score of 2+ were observed in the animals 48 hr after a single intravaginal application of banvel (0.1 ml/rabbit) and dicamba (100 mg/rabbit). Persistent histopathological changes were observed in 1 out of 6 banvel-treated rabbits 15 days post-application. The results suggest that banvel and dicamba are not primary irritants but should nevertheless be employed with caution.

Effect of various organic compounds on synthesis of glucoamylase by an isolated strain Penicillium italicum.

Yeast extract (0.5%) stimulates the production of glucoamylase and cell synthesis while methylene blue (0.1 mM) activates the synthesis of glucoamylase. Studies on the metabolic changes during fermentation of glucoamylase in a selected medium by P. italicum show that the rate of production of glucoamylase and cellular growth are greatly accelerated between 48 and 168 hr. Rapid growth of cells during this period may account for enhanced utilization of maltose and NH4NO3 from the medium. The acid production remains constant from 48 to 144 hr. Different forms of nitrogen decrease steadily. Although methylene blue stimulates the production of glucoamylase in the broth it has practically no effect on the rate of utilization of amino and total nitrogen from the broth.

Blood sugar lowering potentiality of selected Cucurbitaceae plants of Indian origin.

Using five experimental models, the blood sugar lowering efficacy of eight plants of Cucurbitaceae family has been assessed. The ethanolic extract of Cucumis sativus Linn, Cucumis melo utilissimum Roxb, Cucumis melo Linn, Benincasa hispida Thunb Cogn and Tricosanthes anguina Nees, when administered in 250 mg/kg dose, orally to rats failed to lower blood sugar or to depress the peak value, after glucose load. However, ethanolic extract of Momordica charantia Linn plant and Coccinia indica Whit and Arn root significantly lowered blood sugar in fasted model and depressed the peak value in glucose loaded model. Ethanolic extract of Tricosanthes dioica Roxb plant caused a significant lowering of blood sugar in fasted rats and depressed the peak value in glucose loaded single and longterm fed groups of rats. The ethanolic extract of the aerial part of T. dioica also induced significant depression in the peak values in the glucose loaded models.

Effects of prednisolone and dexamethasone on (pro)insulin biosynthesis and insulin release by rat islets of Langerhans.

Administration of either prednisolone or dexamethasone (10 mg/kg body wt/day/oral) to rats for 21 days resulted in inhibition of (pro)insulin biosynthesis and immunoreactive insulin release by isolated islets. A gradual reversal of prednisolone's effect was obtained after exposing islets to increasing glucose concentrations but glucose challenges failed to influence dexamethasone's effect.

Changes in pancreatic beta cell function during growth and reproductive maturity of rats.

An attempt has been made to study the changes, if any, in the efficiency of pancreatic beta cell function at different ages using one experimental model. For this, pancreatic islets were isolated from albino rats of 3, 8, 12 and 36 weeks of age and challenged with various concentrations of glucose (11.0, 16.7 and 22.2 mM). Significantly higher rate of glucose stimulated (pro)insulin biosynthesis was seen in the islets from 3 week old rats as compared to the islets obtained from 8, 12 and 36 week rats. On the other hand, immunoreactive insulin release was observed to be highest from islets of 8 week old rats followed by that of 12, 36 and 3 week old ones.

Anti-secretagogue effect of lithium on isolated rat islets of Langerhans.

Administration of lithium carbonate solution (50 mg/kg, po, twice daily) to Charles Foster male albino rats for 45 consecutive days caused an intolerance to oral glucose. Inhibition in (pro)insulin biosynthesis followed by a significant fall in immunoreactive insulin release was seen in islets isolated from identically treated rats. As the activities of acid phosphatase and cathepsin B were unaltered, it is possible that the anti-secretagogue effect is sequential to inhibition of (pro)insulin biosynthesis by lithium.