Association between cigarette smoke exposure and urinary bladder cancer in Scottish terriers in a cohort study.

Canine urothelial carcinoma (UC) initially responds favorably to treatment, but is ultimately lethal in most cases. Research to identify modifiable risk factors to prevent the cancer is essential. The high breed-associated risk for UC, e.g. 20-fold higher in Scottish terriers, can facilitate this research. The objective was to identify environmental and host factors associated with UC in a cohort of Scottish terriers. Information was obtained through dog owner questionnaires for 120 Scottish terriers ≥ 6 years old participating in a bladder cancer screening study, with comparisons made between dogs that did or did not develop UC during the 3 years of screening. Univariable models were constructed, and variables with P < 0.20 were included when building the multivariable model, and then removed using a backward stepwise procedure. P < 0.05 was considered statistically significant. Urine cotinine concentrations were measured by liquid chromatography-mass spectrometry to further investigate potential cigarette smoke exposure. Biopsy-confirmed UC which was found in 32 of 120 dogs, was significantly associated with the dogs living in a household with cigarette smokers (odds ratio [OR], 6.34; 95 % confidence intervals [CI], 1.16-34.69; P = 0.033), living within a mile of a marsh or wetland (OR, 21.23; 95 % CI, 3.64-123.69; P = 0.001), and history of previous bladder infections (OR, 3.87; 95 % CI, 1.0-14.98; P = 0.050). UC was diagnosed in 18 of 51 dogs (35.3 %) with quantifiable cotinine concentrations, and six of 40 dogs (15.0 %) without quantifiable cotinine concentrations in their urine (P = 0.0165). In conclusion, the main modifiable risk factor for UC in this cohort of dogs was exposure to second-hand tobacco smoke.

68Ga-Glutathione radio-complex as a new diagnostic probe for targeting colon cancer in rats.

OBJECTIVE: Glutathione (GSH) plays an important role in a horde of cellular events that include cell proliferation and apoptosis.The present study describes the radio-synthesis and characterization of gallium-68 (68Ga)-labelled glutathione for its application in radionuclide imaging of cancer. SUBJECT AND METHODS: The radio-synthesis of radio-complex 68Ga-GSH was performed by the direct labeling method. The developed radio-complex was subjected to quality control tests. Colon tumors were developed in healthy male Sprague Dawley (S.D) rats by giving subcutaneous injections of dimethylhydrazine (DMH) in order to monitor the uptake of 68Ga-GSH radio-complex. RESULTS: Gallium-68-labelled glutathione was synthesized with a labeling efficiency of 73.5%±1%. Percentage plasma protein binding and log Po/w values for the radio-complex were found to be 20%-30% and -0.223±0.12, respectively. A significantly higher percentage specific uptake value of newly developed 68Ga-GSH complex was observed in colon tumor in comparison to soft tissue at 90 minutes post administration thereby exhibiting specificity for cancerous cells, which was also witnessed significantly increased overtime from the ratio of colon tumor uptake to normal colon uptake (P≤0.05). CONCLUSION: Therefore, 68Ga-labelled glutathione can further be exploited for radionuclide imaging and assessment of tumor drug resistance in patients.

White tea - A cost effective alternative to EGCG in fight against benzo(a)pyrene (BaP) induced lung toxicity in SD rats.

Tea is a natural resource of catechins and exhibits antioxidative and anticancer activities. This study was designed to elucidate the comparative efficacy of white tea and pure EGCG in containing benzo (a) pyrene (BaP)-induced pulmonary stress. Rats were treated with white tea extract (WT) (1%) and pure EGCG at a dose of 80µg/ml in drinking water on alternate days for 12 weeks (4 weeks prior, during and after BaP treatment). BaP(50 mg/kg b. wt) was administered to rats orally in olive oil twice a week for four weeks. The indices such as stress biomarkers (LPO, PCC & ROS), antioxidant enzymes (SOD, CAT, GSH, GST, GR, GPx) activities and lung histoarchitecture were assessed. BaP administration enhanced the levels of inflammatory markers (NO and citrulline) and reduced activities of antioxidant enzymes. We observed similar antioxidant efficacy by both WT and EGCG as seen by their ameliorative action in restoring BaP induced oxidative and inflammatory stress as well as lung histoarchitecture. Our findings suggest that WT is equally beneficial as EGCG in maintaining the integrity of alveoli and is a potential candidate to be used as a cost effective and protective agent in conditions of BaP-induced lung damage.

A concept of radiation hormesis: stimulation of antioxidant machinery in rats by low dose ionizing radiation.

OBJECTIVE: The concept of radiation hormesis has been the matter of discussion with regard to beneficial effects to biological systems from low doses of ionizing radiations. However, its molecular basis is not well understood till now and the present study is a step forward to elucidate how low levels of ionizing radiation prove beneficial for functioning of biological systems. MATERIAL AND METHODS: Female Wistar rats weighing 100-120g were divided into four different groups. Each group consisted of eight animals. The animals in Group I served as normal controls for Group II animals which were subjected to whole body X-rays exposure of 20rads and were sacrificed 6 hours following exposure. Group III animals served as normal controls for group IV animals which were given whole body X-rays radiation of 20rads and were sacrificed 24 hours following exposure. RESULTS: The levels of reduced glutathione (GSH), total glutathione (TG) were increased in liver, kidney, brain and blood after 6hrs as well as 24hrs following X-rays exposure. On the contrary, no significant change in the oxidized glutathione (GSSG) content was observed following X-rays irradiation in any of the organs. Further, the low dose of X-rays resulted in a significant decrease in the lipid peroxidation (LPO) in liver, kidney and brain, whereas it caused an increase in LPO levels in blood. The enzyme activities of catalase (CAT) as well as glutathione-S-transferase (GST) were also increased in different organs after X-rays exposure. Furthermore, low dose irradiation with X-rays caused a significant increase in the counts of total leukocytes, lymphocytes and eosinophils, whereas it decreased the counts of neutrophils as well as monocytes. Hence, our results clearly indicate that low dose X-rays radiation exposure stimulates endogenous antioxidant defense machinery and also causes an increase in whole blood lymphocytes and eosinophils responsible for providing key defenses. CONCLUSION: Low doses of X-rays exposure may afford radiation hormesis by providing protection to organs from oxidative injury and support immune reaction.

Neuro-protective potential of quercetin during chlorpyrifos induced neurotoxicity in rats.

Chlorpyrifos (CPF) has been considered as one of the most potent organophosphates and is linked to several neurological disorders. On the other hand, Quercetin is a vital plant flavanoid and has been reported to regulate a number of physiological processes in the central nervous system. The present study was conducted to investigate the protective potential of quercetin during chlorpyrifos induced neurotoxicity. Female Wistar rats weighing 150-200 g were divided into four different groups viz: Normal control, CPF treated (13.5 mg/kg.b.wt. every alternate day), Quercetin treated (50 mg/kg.b.wt./day) and combined CPF and quercetin-treated. All the treatments were carried out for a total duration of eight weeks. Chlorpyrifos treatment showed significant alterations in the cognitive behavior and motor activities of rats, which were appreciably improved upon simultaneous supplementation with quercetin. Further, CPF treatment caused a significant inhibition in the enzyme activities of acetylcholinesterase and choline acetyltransferase, but caused an increase in the levels of acetylcholine in the brain. Further, chlorpyrifos exposure significantly elevated the levels of lipid peroxidation and protein carbonyl contents as well as the activities of catalase, superoxide dismutase, which were interestingly found to be decreased following co-treatment with quercetin. In contrast, CPF treatment decreased the activities of glutathione reductase, transferase, as well as levels of reduced and total glutathione in both the cerebrum and cerebellum but co-administration of quercetin, increased these levels. Chlorpyrifos treatment altered the neuro-histoarchitecture, which showed improvement upon quercetin supplementation. Hence, this study suggests that quercetin can be used as a prophylactic intervention to prevent CPF induced neurotoxicity.

Evidence of similar protective effects afforded by white tea and its active component 'EGCG' on oxidative-stress mediated hepatic dysfunction during benzo(a)pyrene induced toxicity.

The present study was conducted to unravel the comparative efficacy of White Tea (WT) and Epigallocatechin gallate (EGCG) in affording protection against benzo (a) pyrene (BaP) induced hepatotoxicity. The animals were randomly divided into six groups viz., normal control (NC), BaP, EGCG, WT, WT + BaP and EGCG + BaP treated. 50 mg/kg of BaP was given orally twice a week for 4 weeks. WT extract (1%) and EGCG (1% WT equivalent) were given on alternate days for 12 weeks (4 weeks prior, during and after BaP treatment). BaP treated animals showed a significant increase in the activities of biomarkers in conditions of inflammatory, oxidative and liver stress. However, the levels of these biomarkers were decreased appreciably upon treatment with WT and EGCG. Interestingly, no marked differences in these indices were experienced in animals treated with either EGCG or WT. Further, BaP treatment decreased significantly the amount of endogenous antioxidants which however were increased substantially when WT and EGCG were supplemented to BaP treated animals. BaP induced hepatic histoarchitectural alterations also showed an appreciable improvement when these animals were supplemented with WT or EGCG. The present study thus recommends the usefulness of WT extract vis-a -vis EGCG in mitigating BaP induced hepatic dysfunctions.

Chemoprevention by Probiotics During 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats.

BACKGROUND: Probiotics are believed to have properties that lower the risk of colon cancer. However, the mechanisms by which they exert their beneficial effects are relatively unknown. AIM: To assess the impact of probiotics in preventing induction of colon carcinogenesis in rats. METHODS: The rats were divided into six groups viz., normal control, Lactobacillus plantarum (AdF10)-treated, Lactobacillus rhamnosus GG (LGG)-treated, 1,2-dimethylhydrazine (DMH)-treated, L. plantarum (AdF10) + DMH-treated and L. rhamnosus GG (LGG) + DMH-treated. Both the probiotics were supplemented daily at a dose of 2 × 1010 cells per day. DMH at a dose of 30 mg/kg body weight was administered subcutaneously twice a week for the first 4 weeks and then once every week for a duration of 16 weeks. Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase as protein expression of genes involved in apoptosis were assessed during DMH-induced colon carcinogenesis in rats. RESULTS: DMH treatment decreased the activity of GSH, GPx, GST, SOD and catalase. However, AdF10 and LGG supplementation to DMH-treated rats significantly increased the activity of these enzymes. Further, DMH treatment revealed alterations in the protein expressions of various genes involved in the p53-mediated apoptotic pathway such as p53, p21, Bcl-2, Bax, caspase-9 and caspase-3, which, however, were shifted towards normal control levels upon simultaneous supplementation with probiotics. CONCLUSION: The present study suggests that probiotics can provide protection against oxidative stress and apoptotic-related protein disregulation during experimentally induced colon carcinogenesis.

Physiological uptake and retention of radiolabeled resveratrol loaded gold nanoparticles (99mTc-Res-AuNP) in colon cancer tissue.

When tagged with a suitable radionuclide, the cancer targeting properties of trans-resveratrol could be utilized to locate cancerous sites in the body using radionuclide imaging technique. However, the polyphenol due to its rapid and extensive metabolism exhibits low bioavailability in vivo. The study was designed to enhance the cancer targeting efficacy of radiolabeled resveratrol using nano-based technology. Technetium-99m labeled resveratrol loaded gold nanoparticles (Res-AuNP) were synthesized, characterized and evaluated for their cancer targeting efficacy in HT29 colon cancer cells and in animal cancer model. Results of various investigations were compared to corresponding results obtained for 99mTc-AuNP and 99mTc-resveratrol. Cancer cell internalization observed for 99mTc-Res-AuNP was significantly higher than that of 99mTc-AuNP and 99mTc-resveratrol. Also, a gradual rise in target to nontarget uptake with time was observed following i.v. administration of 99mTc-Res-AuNP to colon tumor bearing rats, demonstrating better in vivo targeting of colon adenocarcinoma with 99mTc-Res-AuNP when compared to 99mTc-resveratrol.

Understanding the role of 3-O-Acetyl-11-keto-ß-boswellic acid in conditions of oxidative-stress mediated hepatic dysfunction during benzo(a)pyrene induced toxicity.

The present study was planned to see whether 3-O-Acetyl-11- keto-ß-boswellic acid has any protective effects against benzo(a)pyrene (BaP) induced toxicity or not. In vitro studies show concentration dependent linear association of radical scavenging activity of AK which is comparable to ascorbic acid taken as reference compound. For in vivo studies, the animals were divided randomly into five groups which included a) normal control, b) vehicle treated (olive oil), c) BaP treated, d) AK treated and e) AK + BaP (combined treated). BaP was administered at a dose of 50mg/kg in olive oil twice a week orally for 4 weeks and AK (50mg/kg) was given in olive oil thrice a week for 4 weeks before and after BaP exposure. BaP treated animals showed a significant increase (p < 0.001) in lipid peroxidation (LPO) and protein carbonyl contents (PCC) in hepatic tissue. Further, a significant increase (p < 0.001) in the liver marker enzymes as well as citrulline and nitric oxide levels in the hepatic tissue was also observed. Interestingly, AK when supplemented to BaP treated animals ameliorated the above said biochemical indices appreciately. The histopathological observations also showed appreciable improvement when BaP treated animals were supplemented with AK, thus emphasing the protective potential of AK.

Evidence of Zinc in Affording Protection Against X-Ray-Induced Brain Injury in Rats.

In the present world, X-rays have been regarded as one of the most efficient tools in medicine, industry and research. On the contrary, extensive human exposure to these rays is responsible for causing detrimental effects on physiological system. The aim of the present study was to investigate the role of zinc (Zn), if any, in mitigating the adverse effects induced by fractionated X-irradiation on rat brain. Female Sprague-Dawley rats weighing 170-200 g were divided into four different groups viz.: (a) normal control, (b) X-irradiated (21Gy), (c) zinc treated (227 mg/L in drinking water) and (d) X-irradiated + zinc treated. The skulls of animals belonging to groups (b) and (d) were exposed to X-rays in 30 fractions. Each fraction delivered a radiation dose of 70 rads, and rats were exposed to two fractions every day for 15 days, consecutively. X-ray treatment resulted in significant alterations in the neurobehavior, neurotransmitter levels and neuro-histoarchitecture of rats, whereas zinc co-treatment with X-rays resulted in significant improvement in these parameters. X-ray exposure also caused a significant increase in the levels of lipid peroxidation as well as activities of catalase and superoxide dismutase, which however were decreased upon simultaneous Zn treatment. On the contrary, X-ray treatment down-regulated the glutathione system, which were found to be up-regulated by zinc co-treatment. Further, protein expressions of p53 and NF-ҚB were found to be significantly elevated after X-irradiation, which were reversed following Zn supplementation. Hence, Zn seems to be an effective agent in mitigating the detrimental effects caused by exposure to X-rays.

Pharmacokinetics and toxicity of the novel oral demethylating agent zebularine in laboratory and tumor bearing dogs.

The purpose of this study was to determine the plasma pharmacokinetics (PK) and toxicity of zebularine, an oral cytidine analog with demethylating activity, in dogs. Plasma zebularine concentrations were determined by HPLC-MS/MS following an oral zebularine dose of 8 or 4 mg kg-1 . Plasma zebularine clearance was constant. Mean maximum concentration (Cmax ) was 23 ± 4.8 and 8.6 ± 1.4 µM following 8 and 4 mg kg-1 , respectively. Mean half-life was 5.7 ± 0.84 and 7.1 ± 2.1 following 8 and 4 mg kg-1 , respectively. A single 8 mg kg-1 dose was well tolerated. Daily 4 mg kg-1 treatment in three laboratory dogs resulted in grade 4 neutropenia (n = 3), grade 1 anorexia (n = 2) and grade 1 or 2 dermatologic changes (n = 2). All adverse events resolved with supportive care. A 4 mg kg-1 dose every 21 days was well tolerated. A follow-up dose escalation study is in progress with a lower starting dose.

Zinc Improves Cognitive and Neuronal Dysfunction During Aluminium-Induced Neurodegeneration.

Metals are considered as important components of a physiologically active cell, and imbalance in their levels can lead to various diseased conditions. Aluminium (Al) is an environmental neurotoxicant, which is etiologically related to several neurodegenerative disorders like Alzheimer's, whereas zinc (Zn) is an essential trace element that regulates a large number of metabolic processes in the brain. The objective of the present study was to understand whether Zn provides any physiological protection during Al-induced neurodegeneration. Male Sprague Dawley rats weighing 140-160 g received either aluminium chloride (AlCl3) orally (100 mg/kg b.wt./day), zinc sulphate (ZnSO4) in drinking water (227 mg/L) or combined treatment of aluminium and zinc for 8 weeks. Al treatment resulted in a significant decline in the cognitive behaviour of rats, whereas zinc supplementation caused an improvement in various neurobehavior parameters. Further, Al exposure decreased (p ≤ 0.001) the levels of neurotransmitters, acetylcholinesterase activity, but increased (p ≤ 0.001) the levels of L-citrulline as well as activities of nitric oxide and monoamine oxidase in the brain. However, zinc administration to Al-treated animals increased the levels of neurotransmitters and regulated the altered activities of brain markers. Western blot of tau, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ubiquitin, α-synuclein and Hsp 70 were also found to be elevated after Al exposure, which however were reversed following Zn treatment. Al treatment also revealed alterations in neurohistoarchitecture in the form of loss of pyramidal and Purkinje cells, which were improved upon zinc co-administration. Therefore, the present study demonstrates that zinc improves cognitive functions by regulating α-synuclein and APP-mediated molecular pathways during aluminium-induced neurodegeneration.

Evaluation of 99m Tc-resveratrol as a colon cancer targeting probe.

The study aimed to evaluate cancer-targeting potential of a newly synthesised radiopharmaceutical, 99m Tc-resveratrol in vivo, using colon cancer model. Colon cancer was induced in 20 male Sprague-Dawley rats by subcutaneous administration of 1,2-dimethylhydrazine (DMH), dissolved in 1 mM EDTA-normal saline, at a dose of 30 mg/kg body weight twice a week for first 4 weeks and once a week for next 12 weeks. A control group containing normal rats was used for result comparison. Colon cancer in DMH-treated group was confirmed by gross analysis of the colon, by histopathological analysis and molecular marker study in tumour tissue. At the end of the treatment period, the animals from the two groups were used for bio-distribution evaluation of 99m Tc-resveratrol at different time intervals. High uptake of 99m Tc-resveratrol was recorded in rat liver, spleen and kidneys, and the ratio of colon tumour uptake to normal colon uptake in DMH-treated rats increased significantly (P ≤ 0.01) with time, to reach a maximum value at 2 h but decreased thereafter. High uptake at the tumour site as compared to normal colon tissue was observed; however, the uptake by cancer cells at the target site was limited by high reticulo-endothelial uptake and rapid metabolism.

Role of angiogenic factors of herbal origin in regulation of molecular pathways that control tumor angiogenesis.

The formation of blood capillaries to sustain development and growth of new tissues is referred to as angiogenesis. Angiogenesis is pivotal in both carcinogenesis and metastasis since capillaries are the sole source of supplying nutrients and oxygen to the proliferating tumor cells; therefore, this dependency of tumor growth on angiogenesis challenges researchers to halt tumor growth by targeting angiogenesis with the help of either synthetic or natural inhibitors. Many synthetic inhibitors of angiogenesis have not only come into force but also resulted in some severe adverse effects. Natural compounds may effectively fit into this condition and possibly decrease the time of treatment. In the recent past, literature is replete with evidences advocating the usefulness of natural compounds that target multiple biochemical pathways. The additional advantage of natural compounds is that their active principles interact with one another and work synergistically to give more meaningful and reliable effects than individual principle. Hence, if we are somehow able to combine more than two natural compounds, then it may be possible to enhance their potential by many folds, which shall prove to be very effective in combating tumor angiogenesis. This review shall discuss the concept of angiogenesis, molecular pathways, and angiogenic inhibitors and their specific targets and potential of natural compounds to greatly enhance the current knowledge of angiogenesis-inhibiting factors.

Low dose X-irradiation mitigates diazepam induced depression in rat brain.

Depression is considered as one of the most prevalent health ailments. Various anti-depressant drugs have been used to provide succour to this ailment, but with little success and rather have resulted in many side effects. On the other hand, low dose of ionizing radiations are reported to exhibit many beneficial effects on human body by stimulating various biological processes. The present study was conducted to investigate the beneficial effects of low doses of X-rays, if any, during diazepam induced depression in rats. Female Sprague Dawley rats were segregated into four different groups viz: Normal control, Diazepam treated, X-irradiated and Diazepam + X-irradiated. Depression model was created in rats by subjecting them to diazepam treatment at a dosage of 2 mg/kg b.wt./day for 3 weeks. The skulls of animals belonging to X-irradiated and Diazepam + X-irradiated rats were X-irradiated with a single fraction of 0.5 Gy, given twice a day for 3 days, thereby delivered dose of 3 Gy. Diazepam treated animals showed significant alterations in the neurobehavior and neuro-histoarchitecture, which were improved after X-irradiation. Further, diazepam exposure significantly decreased the levels of neurotransmitters and acetylcholinesterase activity, but increased the monoamine oxidase activity in brain. Interestingly, X-rays exposure to diazepam treated rats increased the levels of neurotransmitters, acetylcholinesterase activity and decreased the monoamine oxidase activity. Further, depressed rats also showed increased oxidative stress with altered antioxidant parameters, which were normalized on X-rays exposure. The present study, suggests that low dose of ionizing radiations, shall prove to be an effective intervention and a novel therapy in controlling depression and possibly other brain related disorders.

Modulation of (14) C-labeled glucose metabolism by zinc during aluminium induced neurodegeneration.

Aluminium (Al) is one of the most prominent metals in the environment and is responsible for causing several neurological disorders, including Alzheimer's disease. On the other hand, zinc (Zn) is an essential micronutrient that is involved in regulating brain development and function. The present study investigates the protective potential of Zn in the uptake of (14) C-labeled amino acids and glucose and their turnover in rat brain slices during Al intoxication. Male Sprague Dawley rats (140-160 g) were divided into four different groups: normal control, Al treated (100 mg/kg body weight/day via oral gavage), Zn treated (227 mg/liter in drinking water), and Al + Zn treated. Radiorespirometric assay revealed an increase in glucose turnover after Al exposure that was attenuated after Zn treatment. Furthermore, the uptake of (14) C-labeled glucose was increased after Al treatment but was appreciably decreased upon Zn supplementation. In addition, the uptakes of (14) C-lysine, (14) C-leucine, and (14) C-aspartic acid were also found to be elevated following Al exposure but were decreased after Zn treatment. Al treatment also caused alterations in the neurohistoarchitecture of the brain, which were improved after Zn coadministration. Therefore, the present study suggests that Zn provides protection against Al-induced neurotoxicity by regulating glucose and amino acid uptake in rats, indicating that Zn could be a potential candidate for the treatment of various neurodegenerative disorders.

Zinc down regulates Apaf-1-dependent Bax/Bcl-2 mediated caspases activation during aluminium induced neurotoxicity.

Aluminium (Al), a ubiquitous element in nature is associated with the onset of Alzheimer's disease. On the other hand, zinc (Zn) is an essential trace element that regulates large number of physiological processes in the human body. The present study was conducted to explore the role of zinc, if any, in regulating apoptotic machinery during Al induced neurodegeneration in rat. Male sprague dawley rats weighing 140-160 g were divided into four different groups viz: Normal control, Al treated (100 mg/kg b.wt./day), Zn treated (227 mg/l) and combined Al and Zn treated. All the treatments were carried out for a total duration of 8 weeks. Al treatment resulted in a significant increase in the protein expressions of cytochrome c, Bax, Apaf-1, caspase 9, caspase 3 (p17), caspase 8, caspase 6, caspase 7 but decreased the Bcl-2 in both the cerebrum and cerebellum. However, Zn supplementation to Al treated rats resulted in a reduction in the protein expressions of cytochrome c, Bax, Apaf-1, caspase 9, caspase 3 (p17), caspase 8, caspase 6 and caspase 7 whereas it elevated the Bcl-2 in both the regions. Further, gene expressions of caspase 3 and caspase 9 were also found to be elevated after Al treatment, which however were reduced following Zn co-treatment. The electron-microscopic analysis of brain revealed that Al intoxication resulted in a number of degenerative signs at ultrastructural level, which were appreciably improved upon Zn supplementation. The present study suggests that Zn provides protection against Al induced neurotoxicity by triggering anti-apoptotic machinery.

Adiponectin correlates with obesity: A study of 159 childhood acute leukemia survivors from India.

BACKGROUND: Acute lymphoblastic leukemia survivors are predisposed to obesity. However, the exact underlying mechanisms are not known. AIMS: The study was done to assess the role of biomarkers of obesity in acute leukemia survivors. SETTINGS AND DESIGNS: This is a cross-sectional study conducted at All India Institute of Medical Sciences in survivors of acute leukemia who had completed treatment at least 1 year before enrollment in this study. MATERIALS AND METHODS: Obesity was studied by determining the body mass index. Potential biomarkers were studied by assessing serum leptin, resistin, and adiponectin by enzyme-linked immunosorbant assay, and the results were compared in obese versus nonobese survivors. STATISTICAL ANALYSIS: Descriptive analysis for baseline demographic factors and Student's t-test for comparing the mean levels of biomarkers among the obese and nonobese survivors. RESULTS: One hundred and fifty-nine acute leukemia patients were enrolled in this study with a median follow-up of 36.8 months. The median age was 10 (range: 3-18) years, and 123 (77.3%) patients were males. The overall prevalence of overweight/obesity was 26.4%, and this was similar in acute myeloid leukemia and acute lymphoblastic leukemia sub-groups (26.2% vs. 27.3%, P = 0.9). Mean serum leptin and resistin were similar in obese and nonobese leukemia survivors (3.7 vs. 2.85 pg/mL, P = 0.064; 8.01 vs. 9.33 ng/mL, P = 0.36). However, mean serum adiponectin was significantly lower in obese leukemia survivors (7.97 vs. 11.5 µg/mL, P = 0.023). CONCLUSIONS: Obese leukemic survivors had lower serum adiponectin levels than nonobese survivors. However, serum resistin and leptin levels were similar in the two groups.

Indicators of malnutrition in children with cancer: A study of 690 patients from a tertiary care cancer center.

BACKGROUND: Large data pertaining to indicators of malnutrition in children with cancer is lacking from India. In view of this, we prospectively analyzed consecutive de novo childhood patients with cancer presenting at a tertiary care center. MATERIALS AND METHODS: Height and weight of each child (n = 690) were compared with World Health Organization child growth standards-2006 for that particular age and sex to get weight-for-age, height-for-age, and weight-for-height indices and below 2SD of the reference median on these indices were considered as underweight, stunted, and wasted, respectively. Body mass index (BMI) for age was also analyzed for thinness and obesity. RESULTS: Prevalence of malnutrition based on Z-score for weight-for-age, height-for-age, weight-for-height, and BMI-for-age was 30%, 31%, 35%, and 41%, respectively. Weight-for-age (underweight) was significantly associated (P = 0.018) with solid tumors. Height-for-age, weight-for-age, and BMI-for-age were significantly associated (P = 0.007, P = 0.016, and P ≤ 0.001, respectively) with rural community. CONCLUSION: Malnutrition was observed in approximately one-third of children with cancer. Malnutrition is associated with solid tumors and those coming from rural community. Wasting has a higher prevalence in children with cancer in <5 years of age group.

Zinc modulates aluminium-induced oxidative stress and cellular injury in rat brain.

Dysregulation of metal homeostasis has been perceived as one of the key factors in the progression of neurodegeneration. Aluminium (Al) has been considered as a major risk factor, which is linked to several neurodegenerative diseases, especially Alzheimer's disease, whereas zinc (Zn) has been reported as a vital dietary element, which regulates a number of physiological processes in central nervous system. The present study was conducted to explore the protective potential of zinc, if any, in ameliorating neurotoxicity induced by aluminium. Male Sprague Dawley rats received either aluminium chloride (AlCl3) orally (100 mg kg(-1) b.wt. per day), zinc sulphate (ZnSO4) at a dose level of 227 mg L(-1) in drinking water or combined treatment of aluminium and zinc for 8 weeks. Aluminium treatment significantly elevated the levels of lipid peroxidation and reactive oxygen species as well as the activities of catalase, superoxide dismutase and glutathione reductase, which however were decreased following Zn co-treatment of Al-treated rats. In contrast, Al treatment decreased the activities of glutathione-S-transferase as well as the levels of reduced glutathione, oxidised glutathione and total glutathione, but co-administration of Zn to Al-treated animals increased these levels. Furthermore, Al treatment caused a significant increase in the levels of Fe and Mn as well as of Al but decreased the Zn and metallothionein levels. In the Zn-supplemented animals, the levels of Al, Fe, Mn were found to be significantly decreased, whereas the levels of metallothionein as well as Zn were increased. Moreover, histopathological alterations such as vacuolization and loss of Purkinje cells were also evident following Al treatment, which showed improvement upon Zn supplementation. Therefore, zinc has the potential to alleviate aluminium-induced neurodegeneration.