Modulation of ethanol toxicity by Asian ginseng (Panax ginseng) in Japanese ricefish (Oryzias latipes) embryogenesis.

Alcohol consumption by women during pregnancy often induces fetal alcohol spectrum disorder (FASD) in children who have serious central nervous system (CNS), cardiovascular, and craniofacial defects. Prevention of FASD, other than women abstaining from alcohol drinking during pregnancy, is not known. A limitation of the use of synthetic anti-alcoholic drugs during pregnancy led us to investigate herbal products. In particular, many plants including Asian ginseng (Panax ginseng) have therapeutic potential for the treatment of alcoholism. We used Japanese ricefish (medaka) (Oryzias latipes), an animal model of FASD, for identifying herbal medicines that can attenuate ethanol toxicity. Fertilized eggs in standard laboratory conditions were exposed to ginseng (PG) root extract (0-2 mg/mL) either 0-2 (group A) or 1-3 (group B) day post fertilization (dpf) followed by maintenance in a clean hatching solution. The calculated IC50 as determined 10 dpf in A and B groups were 355.3±1.12 and 679.7±1.6 µg/mL, respectively. Simultaneous exposure of embryos in sub-lethal concentrations of PG (50-200 µg/mL) and ethanol (300 mM) for 48 h disrupted vessel circulation and enhanced mortality. However, PG (100 µg/mL) may partially protect trabecular cartilage (TC) deformities in the neurocranium in B group embryos induced by ethanol (300 mM). To understand the mechanism, embryonic ethanol concentration was measured at 2 dpf and adh5, adh8, aldh2, aldh9a, catalase, GST, and GR mRNAs were analyzed at 6 dpf. It was observed that although ethanol is able to reduce adh8 and GST mRNA contents, the simultaneous addition of PG was unable to alter ethanol level as well as mRNA contents in these embryos. Therefore, antagonistic effects of PG on ethanol toxicity are mediated by a mechanism which is different from those regulating ethanol metabolism and oxidative stress.

The treatment of skin carcinoma, induced by UV B radiation, using 1-oxo-5beta, 6beta-epoxy-witha-2-enolide, isolated from the roots of Withania somnifera, in a rat model.

Histopathological studies of the cutaneous tissues of Wistar rats exposed to UV B radiation (294 nm) for 20 days and rats exposed to UV B radiation for 20 days, followed by topical treatment with benzoyl peroxide, a tumor promoter (20 mg/animal/0.2 ml acetone) twice a week for 1 month, and kept under observation for 12 weeks, demonstrate the development of malignancy. Pretreatment of the animals with 1-oxo-5beta, 6beta-epoxy-witha-2-enolide (20 mg/kg bwt.), isolated from the roots of Withania somnifera, prior to exposing the animals to UV B radiation, prevents the incidence of skin carcinoma. The administration of 1-oxo-5beta, 6beta-epoxy-witha-2-enolide, to the animals after exposing them to UV B radiation/UV B radiation and benzoyl peroxide also prevents the occurrence of malignancy in the cutaneous tissue. Immunohistochemical staining of the cutaneous tissues of rats exposed to UV B radiation show the presence of p53 + foci (clusters of cells containing the mutated p53 protein), whereas an absence of p53 + foci is observed in animals pretreated with 1-oxo-5beta, 6beta-epoxy-witha-2-enolide. These results prove that 1-oxo-5beta, 6beta-epoxy-witha-2-enolide has the potential for acting as an effective agent to prevent the incidence of skin carcinoma induced by UV B radiation.

Evaluation of five essential oils from aromatic plants of Cameroon for controlling food spoilage and mycotoxin producing fungi.

Five essential oils (EO) extracted from Cymbopogon citratus, Monodora myristica, Ocimum gratissimum, Thymus vulgaris and Zingiber officinale were investigated for their inhibitory effect against three food spoilage and mycotoxin producing fungi, Fusarium moniliforme, Aspergillus flavus and Aspergillus fumigatus. Five strains of each fungus were tested. The agar dilution technique was used to determine the inhibitory effect of each EO on the radial growth of the fungus, and a dose response was recorded. The EO from O. gratissimum, T. vulgaris and C. citratus were the most effective and prevented conidial germination and the growth of all three fungi on corn meal agar at 800, 1000 and 1200 ppm, respectively. Moderate activity was observed for the EO from Z. officinale between 800 and 2500 ppm, while the EO from M. myristica was less inhibitory. These effects against food spoilage and mycotoxin producing fungi indicated the possible ability of each essential oil as a food preservative. A comparative test on the preservative ability of the EO from O. gratissimum and potassium sorbate against A. flavus at pH 3.0 and 4.5 showed that the EO remained stable at both pH, whereas the efficacy of potassium sorbate was reduced at higher pH. We concluded that the EO from O. gratissimum is a potential food preservative with a pH dependent superiority against potassium sorbate, and these are novel scientific information.

Hypophosphatemic rickets and osteomalacia in polyostotic fibrous dysplasia.

A 17 year-old girl with polyostotic fibrous dysplasia and hypophosphatemia had inappropriately low tubular reabsorption of phosphate. She had radiological evidence of rickets and osteomalacia. The patient showed clinical improvement after treatment with phosphate supplementation, active vitamin D (calcitriol) and alendronate. It is postulated that either a phosphaturic substance elaborated from the dysplastic bone or target-organ (kidney) unresponsiveness may interfere with phosphate reabsorption in the renal tubule.

A biologically active constituent of withania somnifera (ashwagandha) with antistress activity.

In Ayurvedic medicine,Withania somnifera (Ashwagandha) is well known for its anti-stress activity. A passive rat experimental model, where the animals are subjected to multiple stress of cold, hypoxia, restraint (C-H-R) has been developed to evaluate adaptogenic properties of various fractions of W. somnifera root extracts. We have carried out extraction of roots of W. somnifera with water and further isolated one of the active constituents called compound X and also tested its anti-stress activity in C-H-R model. The effect of administration of W. somnifera water suspension (360 mg/Kg bw) and compound X (20mg/Kg bw) on the fall and recovery of colonic temperature was noted. There was an increase of ≈38% and ≈54% in the time taken to attain T(rec) 23°C by rats given a single dose of fresh aqueous suspension and biologically active constituent (Compound X) respectively, where as decrease in the recovery time to attain T(rec) 37°C is ≈13% and ≈33% respectively, as compared to control group. It is clear that rats treated with the fresh aqueous suspension and compound X ofWithania somnifera, could withstand the multiple stress of C-H-R better than control group.

Effects of high peak power microwaves on the retina of the rhesus monkey.

We studied the retinal effects of 1.25 GHz high peak power microwaves in Rhesus monkeys. Preexposure fundus photographs, retinal angiograms, and electroretinograms (ERG) were obtained to screen for normal ocular structure and function and, after exposure, as endpoints of the study. Histopathology of the retina was an additional endpoint. Seventeen monkeys were randomly assigned to receive sham exposure or pulsed microwave exposures. Microwaves were delivered anteriorly to the face at 0, 4.3, 8.4, or 20.2 W/kg spatially and temporally averaged retinal specific absorption rates (R-SAR). The pulse characteristics were 1.04 MW ( approximately 1.30 MW/kg temporal peak R-SAR), 5.59 micros pulse length at 0, 0.59, 1. 18, and 2.79 Hz pulse repetition rates. Exposure was 4 h per day and 3 days per week for 3 weeks, for a total of nine exposures. The preexposure and postexposure fundus pictures and angiograms were all within normal limits. The response of cone photoreceptors to light flash was enhanced in monkeys exposed at 8.4 or 20.2 W/kg R-SAR, but not in monkeys exposed at 4.3 W/kg R-SAR. Scotopic (rod) response, maximum (combined cone and rod) response, and Naka-Rushton R(max) and log K of scotopic b-waves were all within normal range. Retinal histopathology revealed the presence of enhanced glycogen storage in photoreceptors among sham (2/5), 8.4 W/kg (3/3), and 20.2 W/kg (2/5) exposed monkeys, while enhanced glycogen storage was not observed in the 4.3 W/kg (0/4) exposed group. Supranormal cone photoreceptor b-wave was R-SAR dependent and may be an early indicator of mild injury. However no evidence of degenerative changes and ERG depression was seen. We concluded that retinal injury is very unlikely at 4 W/kg. Functional changes that occur at higher R-SAR are probably reversible since we saw no evidence of histopathologic correlation with ERG changes. Bioelectromagnetics 21:439-454, 2000. Published 2000 Wiley-Liss, Inc.

Calf circumference as a predictor of low birth weight babies.

PIP: To identify an inexpensive, reliable predictor of low birth weight capable of being utilized by untrained personnel, anthropometric measures were performed on 1600 newborns in Kanpur, India. This analysis indicated that, for a birth weight of 2500 g, the critical limit of calf circumference was 10.8 cm or less. Critical limits for crown-heel length, head circumference, chest circumference, midarm circumference, and thigh circumference were equal to or less than 45.2 cm, 32.2 cm, 30.1 cm, 9.0 cm, and 15.4 cm. All these measurements were significantly correlated with birth weight. This correlation was highest for calf circumference (r = 0.98), thigh circumference (r = 0.93), and chest circumference (r = 0.86). The highest sensitivity of detecting low-birth-weight infants was found for calf circumference (98.4%), followed by thigh circumference (91.6%) and head circumference (76.7%); specificity was 98.2% for thigh circumference and 90.0% for calf circumference. Traditional birth attendants can be trained easily to screen out high-risk newborns by measuring calf circumference.^ieng

Protection of CCL4-induced liver damage in rats by some calcium channel blockers.

Liver necrosis was produced in rats by administering 3 doses o a mixture o carbon tetrachloide+olive oil, 2 ml/kg, ip. The liver damage was evidenced by the elevated levels serun aspartate aminotrans ferase (AST), alanine aminotransferase (AIT) and gamma glutamyl transpeptidase (gamma-GT) and by histopathological observations of liver sections. Nitrendipine, nimodipine and nisoldipine (1 mg/100 g of rat, ip) significantly reduced these elevated levels of AST, AIT and gamma-GT. Carbon tetrachloride induced liver necrosis was also found to be significantly reduced in nitrendipine, nimodipine and nisoldipine pre-treated animals as observed macroscopically and histologically.

Protective action of a herbal preparation Liv-52 against beryllium toxicity in rats.

An Ayurvedic medicine, Liv-52 has been studied as a prophylactic against beryllium induced toxicity in rats. Administration of beryllium per se caused severe degenerative and necrotic changes in liver, kidney, lungs and spleen. Its administration reduced glycogen content, activity of alkaline phosphatase and adenosine triphosphatase in these organs. On the contrary, activities of acid phosphatase and glucose-6-phosphatase were increased significantly. In Liv-52 primed rats significant recoupment was observed in all the parameters.

Role of Liv-52 in protection against beryllium intoxication.

An ayurvedic medicine, Liv-52, was studied as a prophylactic agent against beryllium-induced toxicity in rats. Administration of beryllium per se caused severe degenerative and necrotic changes in kidneys, liver, and uterus. Beryllium exposure also reduced glycogen content, activities of alkaline phosphatase, succinate-dehydrogenase, and adenosine-triphosphatase in these organs. On the contrary, activities of acid phosphatase and glucose-6-phosphatase showed marginal increase. Liv-52-primed rats exhibited comparatively less marked toxic effects.

Mobilization and distribution of beryllium over the course of chelation therapy with some polyaminocarboxylic acids in the rat.

The efficacy of three common polyaminocarboxylic acids in the treatment of experimental beryllium intoxication was investigated in male rats. N-(2-hydroxyethyl) ethylene diamine triacetic acid (HEDTA) was more effective than calcium disodium ethylenediamine tetraacetic acid (CaNa2EDTA) in reducing the beryllium concentration of the blood, kidneys and spleen and reducing beryllium-induced inhibition of hepatic alkaline phosphatase activity. HEDTA was also most effective in reducing histopathological lesions in the liver and spleen. Compared to these two chelators, the third amino chelator, calcium trisodium diethylene triaminepenta acetic acid (CaNa3DTPA) produced severe deleterious effects in the liver and systemic toxicity. The results suggest that HEDTA is a promising chelator for beryllium toxicity while DTPA enhances the toxic manifestation of beryllium.

Liv-52 protection against beryllium toxicity in female albino rats.

Toxic effects of beryllium salts on the reproductive organs of cyclic adult female albino rats have been studied. An attempt was made to overcome these effects using an Ayurvedic medicine Liv-52 (Himalaya Drug Co., Bombay). Liv-52-primed rats (1 mL/rat/day for 15 days) were exposed to beryllium nitrate intravenously and were sacrificed at different time intervals. At autopsy ovary, uterus, cervix, and vagina were processed for biochemical and histopathologic examination. Histoarchitecture of the ovary, uterus, cervix, and vagina revealed severe necrotic changes with beryllium nitrate treatment. Tissue glycogen content and the activity of alkaline phosphatase were inhibited significantly after beryllium treatment. Total and esterified cholesterol levels increased significantly in these organs when exposed to beryllium salts. However, a significant improvement was observed in the biochemical parameters and histoarchitecture of these organs when beryllium was injected into Liv-52-primed animals.

Effect of feeding Gymnema sylvestre leaves on blood glucose in beryllium nitrate treated rats.

The feeding of powdered leaves of Gymnema sylvestre in the diet of rats for 10 days prior and 15 days after i.v. beryllium nitrate significantly protected the animals from the full fall of blood glucose seen in rats receiving beryllium nitrate alone. The feeding of the leaves for 25 days to normal rats did not alter blood glucose significantly. The leaves may contain a principle that could be useful as a prophylactic against beryllium toxicity.

Anti-implantation activity of some indigenous plants in rats.

Various extracts of one hundred and eight medicinal plants were screened for their anti-implantation activity in female albino rats. Out of these, 50% ethanolic extract of Codonospis ovata Benth (PL); 50% ethanolic, acetone and benzene extracts of Puararia tuberosa DC (TUB); aqueous and methanolic extracts of Punica granatum Linn. (PX) and ethanolic and acetone extracts of Rubus ellipiticus Smith (PX) inhibited pregnancy in 70-90% of rats. Similarly ethanolic extract of Adhatoda vasica Nees (LF) and Kigelia pinnata DC (PL); ethanolic and acetone extracts of Acrostichum aureum Linn. (PL), Juniperus communis Linn. (SD), Lepidium capitatum H.f. & T. (PL); ethanolic and benzene extracts of Citrulus colocynthus Schrad (LF) and acetone extract of Codonopsis ovata Benth (PL) showed 60-70% anti-implantation activity. Extracts of a few plants VIZ. Dolichos biflorus Linn. (SD), Ferule orientalis Linn. (PL), Nerium odoratum Lamk (RT), Randia dumetorum Lamk (SD) and Ruta graveolens Linn. (PL) could inhibit pregnancy in 50-60% of rats. The rest of the plants were either inactive or showed insignificant antifertility activity.