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Table of Contents - Current issue
July-December 2011
Volume 18 | Issue 2
Page Nos. 87-174
Online since Friday, August 26, 2011
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REVIEW ARTICLE
Mechanisms pertaining to arsenic toxicity
p. 87
Amrit Pal Singh, Rajesh Kumar Goel, Tajpreet Kaur
DOI
:10.4103/0971-6580.84258
Arsenic is an environmental pollutant and its contamination in the drinking water is considered as a serious worldwide environmental health threat. The chronic arsenic exposure is a cause of immense health distress as it accounts for the increased risk of various disorders such as cardiovascular abnormalities, diabetes mellitus, neurotoxicity, and nephrotoxicity. In addition, the exposure to arsenic has been suggested to affect the liver function and to induce hepatotoxicity. Moreover, few studies demonstrated the induction of carcinogenicity especially cancer of the skin, bladder, and lungs after the chronic exposure to arsenic. The present review addresses diverse mechanisms involved in the pathogenesis of arsenic-induced toxicity and end-organ damage.
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ORIGINAL ARTICLES
Ameliorative effects of
Tinospora Cordifolia
root extract on histopathological and biochemical changes induced by Aflatoxin-B
1
in mice kidney
p. 94
Rekha Gupta, Veena Sharma
DOI
:10.4103/0971-6580.84259
The present study was planned to investigate the ability of the
Tinospora cordifolia
to scavenge free radicals generated during aflatoxicosis. A total no. of 48 male Swiss albino mice (30 ± 5 g) were exposed to Aflatoxin B
1
(AFB
1
) (2 μg/30 g b.wt, orally) either individually or in combination with
T. cordifolia
(50, 100, 200 mg/kg, orally) once daily for 25 days. AFB
1
exposure led to significant rise in thiobarbituric acid reactive substances (TBARS) and fall in superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), ascorbic acid, and protein content.
T. cordifolia
was found to show protective effect by lowering down the content of TBARS and enhancing the GSH, ascorbic acid, protein, and the activities of antioxidant enzymes viz., SOD, CAT, glutathione peroxidase, GST, and GR in kidney. Histopathological analysis of kidney samples also confirmed the protective values and antioxidant activity of ethanolic extract of herb.
T. cordifolia
showed protection against aflatoxin-induced nephrotoxicity due to the presence of alkaloids such as a choline, tinosporin, isocolumbin, palmatine, tetrahydropalmatine, and magnoflorine.
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Chronic fluoride toxicity and myocardial damage: Antioxidant offered protection in second generation rats
p. 99
Mahaboob P Basha, NS Sujitha
DOI
:10.4103/0971-6580.84260
This experiment was designed to investigate the extent of peroxidative changes and histological alterations in the myocardium of rats exposed to high fluoride for two generations, in addition to ameliorative role of selenium and vitamin E on the above indices. Adult albino Wistar rats were given fluoride through drinking water (200 ppm F) and maintained subsequently for two generations, while they were exposed to fluoride throughout the experiment. Fluoride treatment significantly increased the lipid peroxidation and decreased the activity of antioxidant enzymes, viz., catalase, superoxide dismutase, and glutathione level in auricle and ventricle regions of the heart. Decreased feed and water consumption, organ somatic index and marginal drop in body growth rate were observed. Decreased antioxidant enzymes and increased malondialdehyde levels might be related to oxidative damage that occurs variably in the myocardium of rats. Biochemical changes were supported by the histological observations, which also revealed that chronic exposure to fluoride causes damage to the myocardium. Results of this study can be taken as an index of cardio-toxicity in rats exposed to water fluoridation. Further, oral supplementation of selenium and vitamin E not only inhibited oxidative stress but also enhanced the activities of antioxidant enzymes. Administration of antioxidants during fluoride exposure significantly overcame cardiac fluoride toxicity and therefore may be a therapeutic strategy for fluorotic victims.
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Effect of
Trans
-resveratrol on rotenone-induced cytotoxicity in human breast adenocarcinoma cells
p. 105
MA Siddiqui, Q Saquib, M Ahamed, J Ahmad, AA Al-Khedhairy, FM Abou-Tarboush, J Musarrat
DOI
:10.4103/0971-6580.84261
Rotenone, a botanical insecticide is known to cause apoptosis in various cell types.
Trans
-resveratrol, a natural phytophenol present in red grapes and wine, is also well documented for its antioxidant, anti-inflammatory, anti-mutagenic, and anticarcinogenic activities. Therefore, the present investigations were carried out to assess the protective effect of trans-resveratrol against rotenone-induced cell death in human breast adenocarcinoma (MCF-7) cells. MCF-7 cells were exposed with various concentrations of rotenone for 24 h, and the loss in percent cell viability was evaluated by MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] and neutral red uptake (NRU) assays. A significant decrease in percent cell viability in MCF-7 cells was observed at 50 μM and above concentrations of rotenone, as compared to untreated control. Furthermore, various concentrations (5, 10, and 25 μ
M
) of trans-resveratrol were used to see its protective role on cell viability in rotenone-induced cell death in MCF-7 cells. Pre- or post- treatment of trans-resveratrol for 24 h was given to the cells. The data exhibited a significant dose dependent increase in the percent cell viability under pre- and post-treatment conditions. However, post-treatment of trans-resveratrol for 24 h after rotenone exposure to the cells was relatively less effective. Overall, the results suggest that trans-resveratrol significantly protects MCF-7 cells from rotenone-induced cell death. This model can be used as an effective and economical alternative to animal models for screening the antioxidant activity of a variety of natural compounds/drugs.
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Identification of limiting factors for the optimum growth of
Fusarium oxysporum
in liquid medium
p. 111
Shilpi Srivastava, Neelam Pathak, Prachi Srivastava
DOI
:10.4103/0971-6580.84262
Fusarium oxysporum
is a highly ubiquitous species that infects a wide range of hosts causing various diseases such as vascular wilts, yellows, rots, and damping-off. Despite the immense economic significance of this phytopathogen, few workers have reported growth studies in this genus in submerged culture. In the present study, several parameters such as change in media pH, biomass, pattern of substrate utilization, viability of the fungal cells, and protein content were observed over a period of time. The fungal biomass increased at a slow rate for the initial 48 h and thereafter increased at an exponential rate. However, after about 8 days the rapid growth stabilized and the trend became more toward stationary phase. The concentration of glucose in the liquid media decreased rapidly up to the initial 4 days, followed by a slow decrease. The pH of the medium gradually decreased as the fungal growth progressed, the reduction being more pronounced in the initial 48 h. This study would be of immense importance for utilization of
F. oxysporum
for diverse applications because we can predict the growth pattern in the fungus and modulate its growth for human benefit.
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Serum creatine phosphokinase: A probable marker of severity in organophosphorus poisoning
p. 117
Kuntal Bhattacharyya, Sibaji Phaujdar, Rathindranath Sarkar, Omar S Mullick
DOI
:10.4103/0971-6580.84263
Organophosphorus (OP), the commonest agent for poisoning in India due to its easy availability, acts by inhibiting acetylcholinesterase at muscarinic and nicotinic receptors. Erythrocyte cholinesterase (EchE) and plasma cholinesterase (PchE) are reduced in OP poisoning, but their estimation is costly and not regularly performed. There are emerging options for new cheaper biochemical markers in relation to OP poisoning. Serum level of creatine phosphokinase (CPK) is often found to be elevated in OP poisoning. This study was conducted to see if CPK may be used as an alternative of cholinesterase levels in blood to assess the severity of OP poisoning. This was a prospective and observational study. Sixty-three patients of OP poisoning without any prior treatment, presenting within 6 hours, were selected and their clinical severity was categorized according to Peradeniya organophosphorus poisoning (POP) scale. Level of serum CPK, blood EchE and pH were measured following admission, and total dose of atropine (mg) until the final clinical outcome (complete recovery or death) was calculated. Student's
t
-test and Pearson's correlation coefficient was used for the assessment of statistical significance. According to POP scale, clinical severity was mild (score 0-3) in 17 (27%), moderate (score 4-7) in 32 (50.8%) and severe (score 8-11) in 14 (22.2%) patients. Serum CPK, EchE level, blood pH and total atropine dose strongly correlated with clinical severity. Our study recommends serum CPK as an alternative marker.
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Hepatoprotective effect of curcumin on lindane-induced oxidative stress in male wistar rats
p. 124
Rambir Singh, Poonam Sharma
DOI
:10.4103/0971-6580.84264
Lindane, an organochlorine pesticide, is recognized as a major public health concern because of its potential toxic effects on human health. Its persistence in the body fluids may lead to continuous blood circulation, liver exposure and hepatotoxicity. The present study was undertaken to evaluate the possible protective role of curcumin on lindane-induced hepatotoxicity. Forty-two healthy adult male Wistar rats were divided into seven groups of six rats each. Group I was given dimethylsulfoxide. A single dose of lindane (60 mg/kg bw) was given to group II. Lindane (30 mg/kg bw) was given daily to group III for 14 days. Treatment with curcumin (100 and 200 mg/kg) was given to groups IV and V before (pretreatment) and to groups VI and VII after (post-treatment) 14 days exposure of lindane. Oxidative stress parameters and antioxidative enzymes were investigated in the liver of exposed and treated rats. A significant increase in lipid peroxidation, and decrease in glutathione level, Superoxide dismutase catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase and NADPH quinine reductase activities was observed in liver of rats exposed to lindane. Curcumin (Pre- and post-treatment) nearly normalized all these parameters. Histological alterations were also observed in the liver tissue after lindane exposure. Treatment with curcumin significantly prevented the lindane-induced histological alterations. In conclusion, curcumin has protective effect over lindane-induced oxidative damage in rat liver.
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Ameliorative effect of
Ocimum Sanctum
on meloxicam induced toxicity in wistar rats
p. 130
R Mahaprabhu, AG Bhandarkar, Babu Lal Jangir, SP Rahangadale, NV Kurkure
DOI
:10.4103/0971-6580.84265
An ameliorating effect of
Ocimum sanctum
on the toxic effect of meloxicam, a new non-steroidal anti-inflammatory drug was studied by evaluating haemato-biochemical parameters, oxidative stress, gross and histopathological changes in various organs of Wistar rats. A total of thirty-six male rats were divided in six experimental groups each comprising of six rats and numbered from G
1
to G
6
. Meloxicam toxicity was induced by oral feeding of meloxicam at 1.2 mg/kg and 2.4 mg/kg body weight in G
2
and G
3
respectively for 28 days. Group G
4
and G
5
were fed with 1.2-mg/kg body weight and 2.4-mg/kg body weight of meloxicam along with 200 mg/kg body weight of aqueous extract of
Ocimum sanctum
. Group G
1
serve as control while group G
6
was kept as treatment control and fed only aqueous extract of
Ocimum sanctum
at 200 mg/kg body weight. Clinical finding showed mild diarrhea from 23
rd
day onwards in-group treated with 2.4-mg/kg body of meloxicam. Significant reduction of hemoglobin and packed cell volume (PCV) was observed in both the group treated with 1.2 mg/kg and 2.4-mg/kg body wt. of meloxicam.
Ocimum sanctum
could restore the hemoglobin and PCV value in-group treated with meloxicam at low dose level. Serum alkaline phosphatase, serum glutamic pyruvic transaminase, Serum glutamic oxaloacetic transaminase and total bilirubin were found elevated in meloxicam treated groups and indicated hepatotoxic activity of meloxicam.
Ocimum sanctum
could reduce hepatotoxic activity of meloxicam in group G4 receiving meloxicam at lower dose rate along with
Ocimum sanctum
failed to regulate creatinine level in meloxicam treated groups. In meloxicam toxicity elevated Lipid peroxidation values was noticed in liver and kidneys, while superoxide dismutase and glutathione did not revealed any change. Stomach and intestine revealed hemorrhagic gastroenteritis and ulcers. Perivascular necrosis with infiltration with inflammatory cells was evident in liver. Interstitial nephritis, myocardial necrosis and spongiform encephalopathy were important lesions. The
Ocimum sanctum
could only counteract the toxic effect of meloxicam in liver and gastrointestinal tract.
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Chronic arsenicosis of cattle in West Bengal and it's possible mitigation by sodium thiosulfate
p. 137
Choton K Ghosh, Bakul K Datta, Suman Biswas, Chinmoy Maji, Samar Sarkar, Tapan K Mandal, Debasish Majumder, Animesh K Chakraborty
DOI
:10.4103/0971-6580.84266
Thirty milch cows having arsenic concentration in hair varying from 3 to 4 mg/kg from Dakhin Panchpota village of Nadia district, West Bengal, were divided into three equal groups where high amount of arsenic is reported to be present in soil and ground water. Groups II and III received, respectively, sodium thiosulfate 20 and 40 g to each animal for 30 days as a pilot study, whereas group I served as untreated control. Arsenic content of milk, feces, hair, and urine was estimated before and after administration of sodium thiosulfate orally at two dose level once daily for 1 month. Paddy straw, mustard oil cake, and water fed by animals were also assayed. Sodium thiosulfate significantly decreased arsenic load in milk, urine, and hair after 1 month. In milk, arsenic concentration was decreased significantly which may be beneficial for animal and human beings.
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Ameliorative potential of quercetin against paracetamol-induced oxidative stress in mice blood
p. 140
Sujata Singh, Shanker K Singh, Mritunjay Kumar, Kalpana Chandra, Rashmi Singh
DOI
:10.4103/0971-6580.84267
The aim of the present study was to evaluate the ameliorative potential of quercetin (QC) against paracetamol (PCM)-induced oxidative stress and biochemical alterations in mice blood. A total of 36 mice were randomly allocated into six groups, six mice in each. Group I served as healthy controls, while groups II and III were administered with
N
-acetylcysteine (NAC) and QC alone respectively. Group IV was administered with PCM alone. Groups V and VI were administered with PCM on day 0 followed by NAC and QC, respectively, for 6 consecutive days. On day 7
th
blood samples were obtained and subjected for the assays of oxidative stress and serum biochemical panels. Erythrocytic lipid peroxides contents of alone PCM-intoxicated mice were significantly higher, while reduced glutathione contents were found to be significantly lower in comparison with the healthy controls. The activities of antioxidant enzymes were also found to be singnificantly lower in these mice. Additionally, significantly increased activities of serum aspartate transaminase, alanine transaminase and alkaline phosphatase, as well as levels of bilirubin, urea and creatinine were revealed by these mice. Postadministration with QC remarkably alleviated the over production of MDA and improved GSH levels in PCM-intoxicated mice blood. In addition, antioxidant enzymes; glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase activities were also improved significantly in these mice. QC had also considerably ameliorated the altered biochemical parameters toward normalcy. Thus, it can be concluded that QC may constitute a remedy against PCM-induced oxidative stress and reno-hepatic injuries.
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A 4-week repeated dose oral toxicity and cytotoxicity study of gumiganghwaltang in Crl:CD (SD) rats
p. 146
Mee-Young Lee, In-Sik Shin, Chang-Seob Seo, Jung-Hoon Kim, Heykyung Ha, Jung-Im Huh, Hyeun-Kyoo Shin
DOI
:10.4103/0971-6580.84268
Gumiganghwaltang (GGT) is a traditional oriental herbal prescription commonly used to treat colds and inflammatory diseases in Korea. This study reports the first evaluation of the oral toxicity and cytotoxicity effects of repeat doses of GGT. GGT was orally administered daily at doses of 0, 500, 1000, and 2000 mg/kg for 4 weeks. Analysis of body weight gain, mortality, clinical observations, urinalysis, blood biochemistry, hematology, organ weight, and histopathological data revealed no significant differences between the V.CONTROL and GGT-treated groups. In addition, we investigated the cytotoxicity of GGT against LNCaP, RBL-1, and BEAS-2B cell lines, and splenocytes. Based on the results, we conclude that GGT orally administered to rats is safe with no drug-related toxicity, even at the highest dose, in 4-week repeated dose studies. Thus, this concentration is considered the non-observable effect dose in rats.
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Cytogenetic evaluation of the physiological saline extract of a newly developed dental material ''ORMO-48''
p. 155
PV Mohanan, Lizzy Mol
DOI
:10.4103/0971-6580.84269
The ORMO-48 is a new indigenous material for dental applications, developed by the Dental Products Laboratory of our Institute. The aim of the present study was to evaluate the genotoxic effect of an indigenously developed dental material in Swiss albino mice. The genotoxic effect was evaluated by micronucleus and chromosomal aberration tests. Two grams of dental material was extracted in 10.0 ml of physiological saline at 70
o
C for 24 h. The extract was cooled to room temperature and was used for the experiment. The experimental designed had three groups each (six mice in each group) for micronucleus and chromosomal aberration tests. The first, second, and third groups were given a single exposure of physiological saline alone (control), dental material's extract (test), and cyclophosphamide (positive control) respectively for micronucleus and chromosomal aberration tests. The result of the study indicated that, the percentage of micronucleated PCE (polychromatic erythrocytes) and NCE (normochromatic erythrocytes) induced by the dental material (extract) treated group was well comparable with control group, whereas the positive control induced significantly high (
P
< 0.001) micronucleated PCE when compared to control. The PCE and NCE ratio of the dental material extract treated group was similar to that of control group. The chromosomal anomalies such as chromatid/chromosomal breaks, centric rings, exchanges, dicentric, and acentric fragments were evaluated. The result showed that the anomalies of the dental material extract treated group were similar to control group, however, significant anomalies were observed in the cyclophosphamide treated group. Hence, the present study concluded that the indigenously developed biocompatible dental material, ORMO-48 is non genotoxic at our laboratory conditions.
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Experimental hepatotoxicity produced by Ethinyl estradiol
p. 160
Govind Pandey, SP Pandey, Madhuri Sharma
DOI
:10.4103/0971-6580.84270
Ethinyl oestradiol (EO) is the most commonly used as a component of oral contraceptive and hormonal replacement therapy (HRT) in women. However, its excessive and prolonged use may cause cytotoxicity, including cancer of many organs. Hence, the present study was performed to produce the experimental hepatotoxicity in female albino rats. EO was administered to different groups of rats, respectively @ 250, 500 and 750 μg/kg body weight, orally, weekly for 16 and 20 weeks. One group of rats was administered with saline alone to serve as control. The rats were sacrificed after their respective experimental periods, and the livers were collected and preserved in 10% buffered formalin. Later on, the histopathological study of liver tissues was done. On the 17
th
week, the hepatic tissues showed severe congestion, focal areas of hemorrhage, extreme vacuolation of cytoplasm, distended sinusoids with dilated central veins. Degeneration and necrosis of hepatocytes as evidenced by increased cytoplasmic granularity, and dissolution of nuclear materials were seen. On the 21
st
weeks, these changes were extremely severe and quite conspicuous. Distinct fibrosis was also noticed. EO caused hepatotoxicity, the extent and severity of which were dose and time dependent, indicating that this drug at higher dose after prolonged duration (500 or 750 μg/kg, orally, weekly for 20 weeks) may cause the standard experimental hepatotoxicity in rats.
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Metal analysis in
Citrus Sinensis
fruit peel and
Psidium Guajava
leaf
p. 163
Anju Dhiman, Arun Nanda, Sayeed Ahmad
DOI
:10.4103/0971-6580.84271
The determination of metal traces is very important because they are involved in biological cycles and indicate high toxicity. The objective of the present study is to measure the levels of heavy metals and mineral ions in medicinally important plant species,
Citrus sinensis and Psidium guajava
. This study investigates the accumulation of Copper (Cu), Zinc
(
Zn), Cadmium (Cd), Aluminum (Al), Mercury (Hg), Arsenic (As), Selenium (Se) and inorganic minerals like Calcium (Ca) and Magnesium (Mg) in
C. sinensis
(sweet orange) fruit peel and
P. guajava
(guava) leaf, to measure the levels of heavy metal contamination. Dried powdered samples of the plants were digested using wet digestion method and elemental determination was done by atomic absorption spectrophotometer. Results are expressed as mean standard deviation and analysed by student's 't' test. Values are considered significant at
P
< 0.05. The results were compared with suitable safety standards and the levels of Cu, Zn, Cd, Mg and Ca in
C. sinensis
fruit peel and
P. guajava
leaves were within the acceptable limits for human consumption. The order of concentration of elements in both the samples showed the following trend: Mg > Ca > Al > Zn > Cu > Cd > Hg = As = Se. The content of Hg, As and Se in
C. sinensis
fruit peel and
P. guajava
leaves was significantly low and below detection limit. The content of toxic metals in tested plant samples was found to be low when compared with the limits prescribed by various authorities (World Health Organization, WHO; International Centre for Materials Research, ICMR; American Public Health Association, APHA). The content of Hg, As and Se in
C. sinensis
fruit peel and
P. guajava
leaves was not detectable and met the appropriate safety standards. In conclusion, the tested plant parts taken in the present study were found to be safe.
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Association of circulating resistin with metabolic risk factors in Indian females having metabolic syndrome
p. 168
V Gupta, AK Singh, Vani Gupta, S Kumar, N Srivastava, T Jafar, AB Pant
DOI
:10.4103/0971-6580.84272
Role of resistin in insulin sensitivity and metabolic syndrome (MetS) is controversial till date. Increased serum resistin levels are associated with MetS and insulin resistance. The aim of this study was to investigate the relationship between serum resistin levels with markers of the MetS in females. In a cross-sectional study, a total of 170 healthy female subjects were selected for the study. Out of which 71 (age 31.59 ± 4.88 years) were with MetS and 99 (age 31.75 ± 6.34 years) were without MetS. Different parameters of MetS and serum resistin level were measured according to the standard protocols as given in NCEP ATP III 2001 guideline. Serum resistin levels were significantly higher in subjects with MetS when compared with subjects without MetS [13.54 ± 4.14 ng/ml (n = 71) vs. 7.42 ± 2.31 ng/ml (n = 99);
P
≤ 0.001]. Resistin levels were positively associated with waist circumference, systolic and diastolic blood pressure, plasma glucose, waist/hip ratio, serum triglycerides, serum cholesterol, serum VLDL, plasma insulin, and insulin resistance, while it was negatively associated with high-density lipoprotein. This study demonstrates a positive correlation between resistin and factors of MetS except high-density lipoprotein which was found to be negatively correlated in Indian female subjects.
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LETTERS TO THE EDITOR
Metal concentration in soil
p. 173
Viroj Wiwanitkit
DOI
:10.4103/0971-6580.84273
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Diagnostic dilemma in a child with tuberculous meningitis on haloperidol therapy
p. 173
Syed Ahmed Zaki, Vijay Lad, Preeti Shanbag
DOI
:10.4103/0971-6580.84274
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