Phosphorous magnetic resonance spectroscopy-based skeletal muscle bioenergetic studies in subclinical hypothyroidism.

BACKGROUND: Subclinical hypothyroidism (sHT) is considered to be a milder form of thyroid dysfunction. Few earlier studies have reported neuromuscular symptoms as well as impaired muscle metabolism in sHT patients. AIM/OBJECTIVE: In this study we report our findings on muscle bioenergetics in sHT patients using phosphorous magnetic resonance spectroscopy (31P MRS) and look upon the possibility to use 31P MRS technique as a clinical marker for monitoring muscle function in subclinical thyroid dysfunction. SUBJECTS AND METHODS: Seventeen normal subjects, 15 patients with sHT, and 9 patients with hypothyroidism performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MR Spectroscopy measurements of inorganic phosphate (Pi), phosphocreatine (PCr), and ATP of the calf muscle were taken during rest, at the end of exercise and in the recovery phase. PCr recovery rate constant (kPCr) and oxidative capacity were calculated by monoexponential fit of PCr vs time (t) at the beginning of recovery. RESULTS: We observed that changes in some of the phosphometabolites (increased phosphodiester levels and Pi concentration) in sHT patients which were similar to those detected in patients with hypothyroidism. However, our results do not demonstrate impaired muscle oxidative metabolism in sHT patients based upon PCr dynamics as observed in hypothyroid patients. CONCLUSIONS: 31P MRS-based PCr recovery rate could be used as a marker for monitoring muscle oxidative metabolism in sub clinical thyroid dysfunction.

Potential of Complementary and Alternative Medicine in Preventive Management of Novel H1N1 Flu (Swine Flu) Pandemic: Thwarting Potential Disasters in the Bud.

The emergence of novel H1N1 has posed a situation that warrants urgent global attention. Though antiviral drugs are available in mainstream medicine for treating symptoms of swine flu, currently there is no preventive medicine available. Even when available, they would be in short supply and ineffective in a pandemic situation, for treating the masses worldwide. Besides the development of drug resistance, emergence of mutant strains of the virus, emergence of a more virulent strain, prohibitive costs of available drugs, time lag between vaccine developments, and mass casualties would pose difficult problems. In view of this, complementary and alternative medicine (CAM) offers a plethora of interesting preventive possibilities in patients. Herbs exhibit a diverse array of biological activities and can be effectively harnessed for managing pandemic flu. Potentially active herbs can serve as effective anti influenza agents. The role of CAM for managing novel H1N1 flu and the mode of action of these botanicals is presented here in an evidence-based approach that can be followed to establish their potential use in the management of influenza pandemics. The complementary and alternative medicine approach deliberated in the paper should also be useful in treating the patients with serious influenza in non pandemic situations.

Mint oil (Mentha spicata Linn.) offers behavioral radioprotection: a radiation-induced conditioned taste aversion study.

Mentha spicata Linn. (mint), a herb well known for its gastroprotective properties in the traditional system of medicine has been shown to protect against radiation-induced lethality, and recently its constituents have been found to possess calcium channel antagonizing properties. The present study examined the behavioral radioprotective efficacy of mint oil (obtained from Mentha spicata), particularly in mitigating radiation-induced conditioned taste aversion (CTA), which has been proposed as a behavioral endpoint that is mediated by the toxic effects of gamma radiation on peripheral systems, primarily the gastrointestinal system in the Sprague-Dawley rat model. Intraperitoneal administration of Mentha spicata oil 10% (v/v), 1 h before 2 Gy gamma radiation, was found to render significant radioprotection against CTA (p < 0.05), by blocking the saccharin avoidance response within 5 post-treatment observational days, with the highest saccharin intake being observed on day 5. This finding clearly demonstrates that gastroprotective and calcium channel antagonizing properties of Mentha spicata can be effectively utilized in preventing radiation-induced behavioral changes.

Whole body protection against lethal ionizing radiation in mice by REC-2001: a semi-purified fraction of Podophyllum hexandrum.

The current study has concentrated on assessment of the radioprotective potential of REC-2001, a semi-purified fraction of rhizomes of Podophyllum hexandrum, in Swiss albino Strain 'A' mice exposed to 10 Gy whole-body gamma radiation. Animals were treated with 10 and 15 mg/kg b wt (i.p.) of REC-2001 1h prior to exposure to a lethal dose of gamma-radiation (10 Gy) and observed upto 30 days. For analysis of maximum tolerable dose (MTD), LD(50) and acute toxic dose, different concentrations of the extract were administered to animals and their mortality and morbidity status was observed upto 72 h and one week, respectively. Dose reduction factor (DRF) was determined by exposing REC-2001 pre-treated mice to supra-lethal doses of gamma-radiation. Endogenous spleen colony forming units (CFU), DNA strand breaks in thymocytes (alkaline halo assay) and lipid degradation was studied to understand the mechanism of radioprotection. A single dose of REC-2001 (10 and 15 mg/kg b wt i.p.) exhibited >90% survival in the pre-treated irradiated group versus no survival in radiation control group. Single doses of upto 75 mg/kg b wt (i.p.) did not cause any mortality (MTD) in mice. REC-2001, a dose of 90 mg/kg b wt, resulted in 50% mortality (LD(50)), while the LD(100) was 115 mg/kg b wt REC-2001 exhibited a DRF of 1.62. CFU counts in the REC-2001 treated group were found significantly high (5.33/spleen) as compared to controls. Exposure of thymocytes to 10 Gy radiation resulted in increased halo diameter (45+/-3 microm) in comparison to untreated controls (8+/-1 microm). REC-2001 administration (500 microg/ml) decreased the halo diameter to 15+/-2 microm. Radiation-induced lipid degradation was also inhibited by REC-2001. The present study has revealed that REC-2001 is a promising radioprotective fraction that can be effectively used against lethal doses of gamma-radiation after further investigations in higher animal models.

Modulation of gamma radiation-inflicted damage in Swiss albino mice by an alcoholic fraction of Podophyllum hexandrum rhizome.

A partially characterized extract of Podophyllum hexandrum rhizomes was studied for its radioprotective potential in mice. A major portion of the podophyllotoxin was obtained from the extract by further fractionation. Acute toxicity and maximum tolerated dose (MTD) of a single intraperitoneal dose of the extract were studied in mice to evaluate the toxicity of the extract, if any. Radioprotective efficacy was determined in terms of survival against 10 Gy whole-body irradiation (WBI), protection against 1 Gy-induced chromosomal aberration (CA), and estimation of dose reduction factor (DRF) in irradiated and extract pretreated mice. The MTD was observed to be 60 mg/kg of body weight, whereas a dose of 90 mg/kg of body weight yielded 50% death in mice within 72 hours of intraperitoneal administration of the extract. A dose range of 15-20 mg/kg of body weight administered 2 hours before 10 Gy WBI of mice yielded 66% survival, while administration of 10-15 mg/kg of body weight of the extract 1 hour before WBI yielded more than 90% survival. A DRF of 1.625 was estimated for 10 and 15 mg/kg of body weight of the extract administered 1 hour before WBI. Further studies on modulation of 1 Gy-induced CA revealed significant radioprotective efficacy of the extract in mouse bone marrow cells. Partial removal of podophyllotoxin was useful in reducing toxicity of the extract without altering its radioprotective efficacy.

Radiomodulatory and free-radical scavenging activity of the fractionated aquo-alcoholic extract of the adaptogenic nutraceutical (Rhodiola imbricata)--a comparative in vitro assessment with ascorbate.

OBJECTIVE: Immense interest has been generated in recent years for the development of drugs of herbal origin for the mitigation of deleterious effects of environmental pollutants like ionizing radiation, mainly to protect against radiation leakages resulting from mishaps in nuclear reactors, deliberate use of dirty bombs, etc. METHOD: The radio modifying effects of a fractionated extract of the high-altitude Himalayan plant species Rhodiola imbricata, along with its electron-donation potential, super-oxide ion scavenging (IC50 ≤ 0.025 mg/ml), nitric oxide (NO) scavenging potential (IC(50) = 0.5 mg/ml), and antihemolytic activity were evaluated in the present study. Reducing power, superoxide ion (O(2)(•-)), and nitric oxide scavenging ability of the fractionated extract increased in a dose-dependent manner. Rhodiola imbricata also exhibited antihemolytic potential preventing radiation-induced membrane degeneration of human erythrocytes. CONCLUSION: Thus, it can be stated that Rhodiola imbricata provides protection against gamma radiation via multifarious mechanisms that act in a synergistic manner. Rhodiola imbricata is widely used as a nutraceutical supplement in the trans-Himalayan region nations, and the current study shows that Rhodiola has immense potential for alleviation of biological damage in a radiation environment.

Protective efficacy of semi purified fraction of high altitude podophyllum hexandrum rhizomes in lethally irradiated Swiss albino mice.

A fraction of high altitude Podophyllum hexandrum rhizome, REC-2006, was evaluated for its radioprotective efficacy against lethal gamma-irradiation (10 Gy, whole body) in Swiss albino mice. The maximum tolerated dose (MTD) and LD50 of this fraction were found to be 45 mg/kg b.w. and 74 mg/kg b.w. respectively. Pre-irradiation (- 2 h, ) administration (i.p.) of 6 or 8 mg/kg b.w. of REC-2006 rendered > 90% survival in lethally irradiated mice. The dose reduction factor was calculated to be 1.62 considering survival as the end point. REC-2006 treatment marked in significant increase in endogenous spleen colony forming units. In REC-2006 treated group, super oxide dismutase activity was increased significantly compared to the radiation control group (Liver, p = 0.00, Jejunum p = 0.00). The extract also inhibited radiation induced lipid peroxidation in liver (p = 0.00) at 24 h. REC-2006 administration (100-200 microg/ml) significantly reduced the halo diameter in mice thymocytes. Nearly 10 fold difference between the effective dose (6 mg/kg b.w.) and LD50 and the high degree of whole body survival (> 90% against 10 Gy irradiation) indicates REC-2006 to be safe and highly promising to achieve significant radioprotection against lethal radiation. Further purification and identification of active molecules and their efficacy studies in higher animals therefore demand attention.

Cytoprotective effect of Podophyllum hexandrum against gamma radiation is mediated via hemopoietic system stimulation and up-regulation of heme-oxygenase-1 and the prosurvival multidomain protein Bcl-2.

The radioprotective effect of a hydroalcoholic extracted material (REC-2000) from the rhizome of Podophyllum hexandrum was studied in mice exposed to lethal gamma radiation (10 Gy). The extract (REC-2000) was found to restore the hemoglobin content (14.73 +/- 0.33) and total leukocyte count (TLC) (4166.66 +/- 0.02) in lethally (10 Gy) gamma-irradiated mice on the 15th day in comparison to the radiation control mice. The hemoglobin content of the drug + radiation group was observed to be significantly (21.25%) higher than the radiation control group on the 10th day. Similarly, the TLC was significantly increased (83.33 times) in the drug + radiation group as compared to a radiation (10 Gy) only group on the 10th day. Enhanced expression of heme-oxygenase-1 and Bcl-2 protein observed by Western blotting further supports the observation of hemopoietic recovery in irradiated mice. These findings indicate that the bioactive constituents present in REC-2000 exert the radioprotective effect by modulating the hemopoietic system.

Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans.

We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited significant (P < 0.05) antioxidant activity in different metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 mug ml(-1). S1 exhibited 58.40 +/- 0.8% inhibition (at 0.025 mug ml(-1)) of the formation of reactive nitrite radicals, comparable to S2 (52.45 +/- 0.825%), and also showed 45.01% site-specific activity (1000 mug ml(-1)), along with significant (P < 0.05) electron donation potential (50-2000 mug ml(-1)) compared to S2. Such activities of S1 could be attributed to the significantly (P < 0.05) higher levels of podophyllotoxin beta-d-glucopyranoside (16.5 times) and demethyl podophyllotoxin glucoside (2.9 times) compared with S2. Together, these findings clearly prove that aryl-tetralin lignan content influences the radiation protective potential of the Podophyllum fractions to a great extent.

Zingiber officinale exhibits behavioral radioprotection against radiation-induced CTA in a gender-specific manner.

At the organismic level, exposure to radiation can produce taste aversion (CTA) learning and emesis, which have been proposed as behavioral endpoints that are mediated by harmful effects of radiations on peripheral systems, primarily the gastrointestinal system. Thus, the aim of the present investigation was to study the gastroprotective action of hydroalcoholic extract of zingiber rhizome (Zingiber officinale Rosc.) against radiation-induced conditioned taste aversion (CTA) in both male and female species of animals, for testing its potential as a behavioral radioprotector. Administration of zingiber extract 1 h before 2-Gy gamma-radiation was significantly effective in blocking the saccharin avoidance response, with 200 and 250 mg/kg b.wt. i.p., being the most effective doses for male and female rats, respectively. A comparison of the efficacy of zingiber extract with two antiemetic drugs, ondansteron and dexamethasone, revealed that the extract rendered comparable protection against radiation-induced CTA. Our experiments also confirmed the existence of sex dichotomy (i.e., the sex of animal greatly influenced response towards radiation exposure) in relation to behavioral responses (CTA) or differential metabolism. The observed gender variations were hypothesized to be a result of hormonal fluctuations and differences in pharmacological parameters in male and female rats. To correlate the mechanism of action, the free-radical-scavenging potential of zingiber extract to scavenge hydroxyl ion and nitric oxide was also tested, in cell-free system and a concentration of 1000 microg/ml, was found to be the most potent, which has been proposed as one the many activities assisting in its overall ability to modulate radiation-induced taste aversion. The results demonstrate that Z. officinale possesses antioxidant, radioprotective and neuromodulatory properties that can be effectively utilized for behavioral radioprotection and for efficiently mitigating radiation-induced CTA in both males and females species.

Atypical diffusion-weighted magnetic resonance findings in glioblastoma multiforme.

The present report describes two patients with glioblastoma multiforme with the tumour demonstrating low central apparent diffusion coefficient values similar to those found in cerebral abscesses. Although conventional MR images were fairly specific for tumour, the cases illustrate the need for exercising caution when using diffusion-weighted (DW) MR images for the differentiation of necrotic brain tumours from abscesses. The DW MR imaging information should always be integrated with the conventional spin-echo MR images.

Synthesis and antileishmanial activity of alpha-cyano ethyl propenoates--a new class of antileishmanials.

A number of alpha-cyano-beta-substituted ethyl propenoates were synthesised by condensation of appropriate aldehydes with ethyl cyanoacetate in basic medium. These compounds have been studied for their antileishmanial activities in vivo in hamsters. Two compounds exhibited 70-77% activities both by intramuscular and oral routes.

Frontal lobe proton magnetic-resonance spectroscopy in Graves' disease: a pilot study.

Patients with hyperthyroidism may show impaired performance on several neuropsychological tests that require complex visual discrimination, conceptualization, mental flexibility or organization. These neurocognitive impairments appear to be consistent with prefrontal lobe dysfunction. This pilot study was undertaken to characterize the metabolite profile in the right prefrontal cortex in six patients with untreated Graves' disease by using in vivo proton magnetic-resonance spectroscopy (1H-MRS). For comparison, 1H-MRS was also carried out in seven healthy controls. The choline/creatine (Cho/Cr) and N-acetyl aspartate/creatine (Naa/Cr) ratios were determined. Cho/Cr ratios of the hyperthyroid patients were significantly lower than that of controls (means +/- SD = 0.61 +/- 0.09 vs. 0.90 +/- 0.18, p = .05). The two groups did not differ in their Naa/Cr ratios. Follow-up data after antithyroid treatment were available in three patients: Cho/Cr ratios were higher after treatment (euthyroidism) than before treatment (1.06 vs. 0.55; 0.82 vs. 0.54; 1.15 vs. 0.76). Tentatively, these preliminary data are most consistent with reversible reductions in the concentrations of choline-containing compounds (especially glycerophosphocholine and phosphocholine) in the prefrontal area during hyperthyroidism. However, these findings await confirmation by a definitive study with a larger sample size. A possible explanation of the findings is an altered brain cholinergic-adrenergic balance in hyperthyroidism.