Screening Ethanolic Extract Of Aerva Lanata For Α-Amylase Inhibition And In Vitro Uptake Of Glucose In Adipose Tissue And Psoas Muscle Of Male Sprague Dawley Rats

The study was intended to investigate anti-diabetic efficacy of Aerva lanata by determining its α-amylase inhibition activity and in vitro uptake of glucose in adipose tissue and psoas muscle isolated from male Sprague Dawley (SD) rats. Aerva lanata is reported to have many traditional and Ayurvedic uses. Male SD rats (n=3) of 150 g were sacrificed and 250 mg of respective tissues were isolated for the study. Aerva lanata ethanolic extract (ALE) (5-20 mg/mL) showed 13.30 to 54.08% α-amylase inhibition activity. Glucose uptake studies in in vitro conditions were carried out in both adipose tissue and psoas muscle in different sets - tissue alone, tissue along with (Aerva lanata extract: 50µg, 100µg, 150µg, insulin: 25 mU/L, insulin: 50 mU/L and Aerva lanata extract: 50µg + insulin: 25 mU/L, Aerva lanata extract: 100µg + insulin: 25 mU/L, Aerva lanata extract: 150µg + insulin: 25 mU/L, Aerva lanata extract: 50µg + insulin: 50 mU/L, Aerva lanata extract: 100µg + insulin: 50 mU/L, Aerva lanata extract: 150µg + insulin: 50 mU/L). The rate of glucose uptake by insulin action in these tissues was stabilized by ethanolic extract of Aerva lanata and this shows synergetic activity of insulin and Aerva lanata.

Radiomodulatory Role of Psidium guajava Leaf Extracts against X-ray Induced Genotoxicity, Oxidative stress and Apoptosis in albino Wistar Rat Model.

In the present study we investigated the radioprotective activity of hydroalcoholic leaf extracts of Psidium guajava (P.G) against rats exposed to X rays. Exposure to ionizing radiation like X rays induces oxidative damage in normal tissues leading to their death or transforming them into cancerous tissues. To study the optimum dose of radioprotection, rats were administered with different doses (50,100,200,400 mg/kg body weight) of Psidium guajava leaf extracts daily for five consecutive days. One hour after last administration of leaf extracts the rats were treated with 6.6 Gy of x rays.200 mg/kg body weight was selected as an optimum dose for radioprotection based on survival analysis. Pretreatment of 200 mg/kg body weight of P.G leaf extract increased the levels of antioxidant enzymes such as superoxide dismutase, catalase, reduced glutathione and lowered the levels of lipid peroxidation, protein carbonyls and nitric oxide when compared to irradiated group in liver tissue homogenates. DNA damage indicators analyzed through comet assay showed a reduction in Olive tail movement and percentage DNA in tail significantly in P.G pretreated group when compared to irradiated group alone. Pretreatment of P.G leaf extract at a dose of 200mg/kg body weight protected cells from apoptosis which was analyzed microscopically by Ethidium bromide /Acridine orange staining. Our findings demonstrate the role of P.G leaf extract as a radio modulator in vivo, consequent to its powerful antioxidant activity in vitro and could be beneficial in combating radiation induced damage in living systems.

Androgen & vitamin D nuclear receptor expression in archival breast tumour samples.

BACKGROUND & OBJECTIVE: Breast tumour cells have receptors for androgen and vitamin D and their clinical significance is not completely understood. Therefore, the present study was undertaken to analyze androgen and vitamin D receptor levels in human primary infiltrating ductal breast carcinomas (IDC) and benign breast tumour archival samples and to find out their correlation, if any, with the clinical findings. METHODS: Paraffin blocks of benign and malignant breast tumours were sectioned, deparaffinized, and nuclei released by pepsin digestion. After antigen retrieval, nuclei were stained with primary antibodies for androgen or vitamin D receptors and secondary fluorescein isothiocyanate (FITC) labeled antibodies and propidium iodide respectively, to quantitative receptor expression and DNA content by flow cytometry. RESULTS: Androgen receptor positive nuclei ranged from 16-66 per cent in the IDC tumours as compared to 36-67 per cent in the benign tumours. Based on flow cytometric comparison of AR expression in AR positive and negative cell lines established earlier, 24 of 28 tumours from postmenopausal women were AR positive compared to all benign tumours and 32 of 33 tumours from pre-menopausal patients. Vitamin D receptor positive nuclei ranged from 14-89 and 2-75 per cent in IDC and benign tumours, respectively. All pre- or post-menopausal tumours were VDR positive as compared to 10 of 15 benign tumours that were VDR positive. No correlation was seen between nuclear androgen and vitamin D receptor expression of the IDC or benign tumours. There was a positive correlation between per cent of receptor positive nuclei and antigen density as measured by ratio of the mean log fluorescence channel value (MFC). No statistically significant correlation was found between nuclear receptor expression (per cent positive nuclei or antigen density) with that of tumour stage, lymph node status, tumour grade, patient age or menopausal status. INTERPRETATION & CONCLUSION: There was no significant correlation between androgen or vitamin D receptor expression and clinical findings. The expression of AR and VDR and the antigen density in the nuclei of the archival breast tumour samples were highly variable because of the tumour heterogeneity. Future studies with fresh biopsy samples of tumour on AR and VDR levels and their up- or down-regulation may be useful while stratifying the patients for hormonal therapy.

Response of S 180 murine tumor to bleomycin in combination with radiation and hyperthermia using micronucleus assay: a multimodality approach for therapeutic augmentation.

Response of a transplantable tumor, S180, grown intradermally in inbred Balb/c mice, was assessed by using micronucleus assay after treating the solid tumors with bleomycin (BLM), radiation (RT) and hyperthermia (HT) vis-a-vis multimodality approach. The frequency of micronuclei (MN) though did not vary greatly during the one week of observation in untreated tumors, it significantly increased in the drug and RT groups at 24 hr post-treatment. However, MN frequency was non-significant in the HT group from the control. A drug dose dependent linear increase in the frequency of MN induction was evident in 10, 15 and 20 mg/kg body weight BLM alone treated groups. Combination of radiation with BLM or HT further increased the MN counts in the bimodality groups. But, MN induction at 24 hr post-treatment in the trimodality group (BLM + RT + HT) was non-significant from that of the bimodality treatments. However, the tumors treated with trimodality treatment presented severe tumor necrosis, indicating increased cell loss, and resulting in immediate tumor regression. In all the bi-modality groups MN counts though declined 3 or 5 days post-treatment, the values remained significantly higher than the control, on day 7 post-treatment. Micronucleus assay could be used as a predictive parameter for the assessment of post-irradiation tumor regression response. However, the tumor response assessment with MN assay alone may not be sufficient and the role of other parameters, such as apoptosis and necrosis, in immediate tumor regression, especially radiosensitive/thermosensitive tumors can not be ignored while taking multimodality approach into consideration for cancer therapy.

Treatment of recurrent attacks of supraventricular tachycardia during pregnancy causing complications in both mother and fetus.

Cardiac arrhythmias including supraventricular tachycardia are commonly encountered during pregnancy. The case of a young Indian woman with recurrent attacks of supraventricular tachycardia during pregnancy which was managed with adenosine and verapamil is reported. The possible mechanisms of maternal and fetal complications are discussed.

Ganglioneuroma of small intestine presenting with perforation peritonitis.

We report a 42-year-old man with benign solitary small intestinal ganglioneuroma presenting with perforation peritonitis. The patient had no evidence of MEN IIB syndrome. Simple segmental resection was done; the patient is well on follow up one year later.

A double blind controlled study of propranolol and cyproheptadine in migraine prophylaxis.

Role of propranolol and cyproheptadine in the prophylaxis of migraine was studied in a controlled double blind trial. Two hundred fifty-nine patients were divided into four groups. Each group was either given a placebo, cyproheptadine, propranolol or a combination of the latter two drugs. The patients were followed for a period of three months. Significant relief in frequency, duration and severity from migranous attacks was seen in all drug treated groups over placebo. Significant correlation in response was seen in frequency, duration and severity in all the groups which received drugs. Statistically more significant relief was seen in cyproheptadine and propranolol treated group as compared to individual drug treated groups. In cyproheptadine and propranolol treated groups, the dropout rate was lower and associated symptoms were better relieved than in other groups. The study shows efficacy of combination of cyproheptadine and propranolol in migraine prophylaxis.

Radiosensitization of a mouse melanoma by withaferin A: in vivo studies.

The radiosensitizing effect of a plant withanolide, withaferin A, on the B16F1 mouse melanoma was studied in vivo. Treatment of 100 mm3 tumours with 10 to 60 mg/kg withaferin A intraperitoneally produced a dose dependent increase in growth delay and volume doubling time. Injection of 30-50 mg/kg withaferin A, followed by 30 Gy local gamma irradiation, significantly enhanced the tumour response. No systemic or local adverse reactions were noted in these groups. The drug was most effective when injected intraperitoneally 1 h before irradiation. However, neither the individual agents nor their combination could produce any complete response (tumour cure). Melanoma is a relatively radioresistant tumour. The present results indicate that the radiation response of this tumour can be significantly enhanced by pretreatment with withaferin A.

HIV infection among dental patients.

Oral manifestations may be the important indicators of ongoing human immunodeficiency virus (HIV) infection. Serum samples were collected from 100 patients repeatedly attending dental outpatients' department of SV Medical College and SVRR Hospital, Tirupati and tested for the presence of HIV antibodies. HIV 1 antibodies were detected in one person, the seropositivity rate being 1%.

Effect of plumbagin on the radiation induced cytogenetic and cell cycle changes in mouse Ehrlich ascites carcinoma in vivo.

The effect of plumbagin, a naphthoquinone from the roots of the Indian medicinal plant Plumbago rosea, and Cobalt-60 gamma radiation was studied on Ehrlich ascites carcinoma in vivo, taking cytogenetic damage and cell cycle changes as experimental endpoints. Plumbagin (5 mg/kg body wt, P1) administered intraperitoneally produced a significant increase in the percentage of S-phase as well as G2-M cells with a corresponding decrease in the G1 phase at different post-treatment times. Radiation (7.5 Gy, RT) alone produced the classical G2 block at 1 hr, which persisted with a continuous increase throughout the post-treatment observation period. The combination treatment produced a similar effect as that of RT on G2-M cells, but its effect on the G1 phase was more pronounced than the latter. While P1 treatment produced a small increase in the percentage of labeled S-phase cells, combination treatment significantly reduced the labeled S-phase cells with a corresponding increase in the unlabeled fraction. Drug or radiation alone significantly increased micronuclei induction at various post-treatment times and the combination of the two further enhanced this effect additively. The mechanism of interaction of P1 with radiation in bringing about this effect is not clear.

The role of artificial drainage devices in glaucoma surgery.

The use of artificial drainage devices (ADDs) or "setons" in glaucoma surgery is generally restricted to patients with refractory glaucoma at high risk for failure from conventional filtration surgery. ADDs, both valved and nonvalved are currently available in this country. Recently, some of these devices have been propogated as primary treatment even for primary glaucomas. This article examines the role of ADDs in the modern management of the glaucomas. Specific indications for ADDs and methods to reduce the complication of overfiltration are discussed. The use of antimitotics, such as 5-fluorouracil or mitomycin, with traditional filtration has decreased the indications for ADDs. The literature and our experience confirm that currently there is no role for use of ADDs as a primary procedure in most glaucomas.

Hyperthermic modification of radiation induced gene conversion in Saccharomyces cerevisiae.

Effect of pre- and post-irradiation hyperthermia on the induction of gene conversion (non-reciprocal recombination) in diploid yeast cells was investigated. Post irradiation heat treatment does not significantly modify the frequency of gene conversion. Both low-level (51 degrees C-10 min) and lethal (51 degrees C, 40 min) pre irradiation heat treatments enhanced the gene conversion frequency by 17-49%. There was no quantitative correlation between the observed enhancement and the radiation dose. These results suggest that hyperthermia given prior to radiation not only sensitizes the cells to killing but also increases their convertogenic response. It has been suggested that recombination may be involved in carcinogenesis and tumour promotion. Based on these observations along with other reports, wherein hyperthermia was shown to modify the carcinogenic effects in animals as well as the genetic effects of radiation in vitro, it is possible to suggest that hyperthermia may have a potential to increase the second primary cancers, especially in long term survivors. Certain differences in the mechanism of interaction between radiation and heat in the pre- irradiation and post irradiation modalities appear likely.

Ontogeny of taste sense.

Developmental changes in the taste receptors and CNS, in physiological and behavioural patterns in fetus and postnatal animals constitute the ontogeny of taste. Tongue epithelial cells are modified into taste buds only with innervation and are seen to degenerate on denervation. On removal of a portion of the tongue, with its taste buds, the central projections of gustation also atrophy, indicating an interdependence of taste receptors and central areas for their development. Gradual transitions in electrical responses to taste stimuli are shown from fetal to adult stage. While responses to ammonium chloride are marked in early fetus, with advancements in age responses to a wide variety of chemicals are shown. Again, early in the development, fibers responsive to chloride are predominant while at a later stage fibers responsive to sodium increase in number. Behaviourally, human fetus and neonatal mammals showed increased swallowing movements on sweet taste and decreased movements on bitter taste which is somewhat at variance with electrophysiological evidence and reflects on the multimodal involvement of taste cell functional and behavioural dynamics with age.

Effect of schedule feeding on water intake and urine output in rats.

Water intake of schedule feeding rats was correlated to food intake through variations in calorie content of food. On intake time restriction (3 h) schedule, it was positively correlated while on amount restriction schedule (25% and 15% food) correlation was negative. Water-to-food ratio (W/F) of 3 hFW rats was decreased whereas W/F of 25% and 15% food animals, it was increased as compared to ad lib W/F. On calorically rich (3.2 cal/gr) diet 3 hFW rats food intake (7.8 +/- 0.6 gr) and water intake (4.7 +/- 0.3 ml) remained unaltered, while ad lib rats food intake (14.7 +/- 0.9) was decreased and water intake (16.2 +/- 1.1) increased as compared to their intake on calorically poor (2.8 cal/gr) diet. Urine percent over water intake (u/w x 100) was inversely related to food intake of rats (on ad lib food, 13.8%; on 25% food 29.1% on 15% food 31.8%) excepting for urine percent of 3 hFW rats which was (7.6%) disproportionately decreased.

Prognostic assays in multiple myeloma: correlated with flow cytometry.

DNA ploidy of plasma cells in bone marrow has been indicated to play a role in treatment response of multiple myeloma. Therefore, a prospective study was done to test this correlation. Univariate DNA flow cytometry was done on 13 proved multiple myeloma patients. Patients aged below 50 years showed hypodiploidy, irrespective of 'S' phase population, where as all patients above 50 years had diploidy or hyperdiploidy, except for one patient. Early stage patients (I & II) with less than 25% plasma cells in bone marrow were all aneuploids. Patients belonging to advanced clinical stage with more than 60% plasma cells in bone marrow with aneuploidy, especially hyperdiploidy (DI > 1.15), carried a poor prognosis. It was difficult to correlate the 'S' phase fraction with other parameters from the present data. Further study with BrdU labelling to determine the proliferative status of the 'S' phase cells is needed.

Radiosensitizing effect of plumbagin on mouse melanoma cells grown in vitro.

Mouse melanoma cells were treated with plumbagin, a naphthoquinone, from the plant Plumbago rosea at 0.5 microgram/ml (PI) for 60 min either alone or followed by 2 Gy gamma radiation (RT). Response to the different treatments was assessed by following the cell growth up to 5 days post treatment. PI alone produced a significant decrease in the cell count on days 3 and 4, whereas RT treatment significantly enhanced the growth inhibitory effect when compared to RT or PI alone. These findings suggests the radiosensitizing effect of PI on mouse melanoma cells in vitro, supporting the earlier in vivo findings.

Multimodality treatment using AK-2123, hydralazine, radiation & hyperthermia on a transplantable mouse tumour.

The in vivo response of a transplantable mouse tumour, Sarcoma 180 to AK-2123 (AK), local irradiation (RT) and local hyperthermia, as influenced by a vasoactive drug, hydralazine (HDZ), was assessed on the basis of tumour cure (complete response CR), volume doubling time (VDT), regrowth delay (RD) and animal survival up to 120 days. A single ip injection of 200 mg/kg b.wt. AK produced more than 15 per cent CR. Combination of any two agents resulted in a better response than the single agent treatments. AK in combination with 43 degrees C, 30 min (HT) was more effective than HT combination with 10 Gy. The presence of 5 mg/kg HDZ, injected immediately after 5 Gy, in combination with AK increased the therapeutic effect over that produced by AK+10Gy. Combination of all the three agents (AK+10Gy+HT) produced 100 per cent CR and prolonged disease free animal survival. A similar response could be obtained by the presence of HDZ with a lower radiation dose of 5 Gy in combination with AK and HT (AK+5Gy+HDZ+HT). This multimodality treatment offers the possibility of further reduction in the doses of individual agents, and in the possible side effects on normal tissues without compromising the tumour cure effect.