Comparison of normal saline and balanced crystalloid (plasmalyte) in patients undergoing elective craniotomy for supratentorial brain tumors: A randomized controlled trial.

BACKGROUND: The choice of fluid is important in neurosurgical patients, who may be dehydrated due to the administration of diuretics in order to reduce cerebral edema. Normal saline, the infused fluid routinely used in neurosurgical patients, can cause hyperchloremic metabolic acidosis. A balanced crystalloid (BC) may help to maintain the metabolic status more favorably in these patients, without adversely affecting brain relaxation. METHODS: We conducted a prospective, randomized controlled trial on patients undergoing elective craniotomy for supratentorial tumor resection under general anesthesia. 44 patients were randomly allocated into two groups of 22 each to receive either normal saline or BC (Plasmalyte) as the maintenance fluid, intra-operatively. The metabolic parameters and osmolality were measured at regular intervals. Brain relaxation score was assessed by the operating surgeon. The patients were monitored with serum neutrophil gelatinase-associated lipocalin (NGAL), blood urea and serum creatinine for assessing the degree of acute kidney injury. RESULTS: The metabolic profile was better maintained with the BC. The brain relaxation score was comparable between the two groups. The postoperative NGAL, urea and creatinine values were significantly higher in the normal saline group compared to the BC group. CONCLUSION: The balanced crystalloid maintains metabolic status more favorably than normal saline in neurosurgical patients. Hyperchloremic metabolic acidosis, and the other problems which occur as a consequence of normal saline infusion may be circumvented by choosing a balanced crystalloid electrolyte solution. Neither of the crystalloids appeared to have any adverse effect on brain relaxation.

Modelling of calcium leaching and its influence on radionuclide migration across the concrete engineered barrier in a NSDF.

A multi barrier concept of disposal is adopted for both low and intermediate level radioactive waste disposal to prevent the spread of radionuclides into the human environment. Concrete engineered barrier is a part of multi barrier system for radioactive waste disposal. As long as the concrete barrier is intact, the containment of radioactive waste within the disposal facility is assured. However, every concrete structure has a finite lifetime. Concrete barriers degrade with time with lifetime dependent on type of concrete, external and internal environmental factors. This degradation allows the free moment of the radionuclides out of the concrete barrier. Hence an attempt was made to model the Calcium (Ca) leaching from side wall of a concrete engineered barrier in a Near Surface Disposal Facility (NSDF) and its influence on radionuclide migration across the concrete barrier, limited to conditions specified in the paper. The conceptual model assumes that rain water seeps into the engineered barrier through the top cover and dissolves radionuclides from the nuclear waste matrix. The modelling was attempted with Finite Difference analysis and validated with the results available in literature. The influence of Ca leaching on radionuclide migration in concrete barrier has been discussed for eight different radionuclides (Cs-137, Sr-90, I-129, H-3, Pu-239, Am-241, Co-60 and Tc-99).

The role of CXC chemokine ligand (CXCL)12-CXC chemokine receptor (CXCR)4 signalling in the migration of neural stem cells towards a brain tumour.

AIMS: It has been shown that neural stem cells (NSCs) migrate towards areas of brain injury or brain tumours and that NSCs have the capacity to track infiltrating tumour cells. The possible mechanism behind the migratory behaviour of NSCs is not yet completely understood. As chemokines are involved in the migration of immune cells in the injured brain, they may also be involved in chemoattraction of NSCs towards a brain tumour. METHODS: The expression profile of various chemokine receptors in NSCs, harvested from the subventricular zone of adult mice, was investigated by reverse transcriptase- polymerase chain reaction analysis. Furthermore, the functionality of the chemokine receptors was assessed in in vitro chemotaxis assays and calcium signalling experiments. To test the in vivo migration of NSCs, a syngeneic mouse model was developed, whereby a B16F10 melanoma cell line was grafted into one hemisphere and later NSCs were grafted in the contralateral hemisphere. Furthermore, the expression of chemokines in this melanoma cell line was investigated. RESULTS AND CONCLUSIONS: Adult mouse NSCs functionally express various chemokine receptors of which CXC chemokine receptor (CXCR)4 shows the highest mRNA levels and most pronounced functional responses in vitro. CXC chemokine ligand (CXCL)12, the ligand for CXCR4, is expressed by the melanoma cell line. In this mouse model for metastatic brain tumours, it is shown that NSCs express CXCR4 at their cell membranes while they migrate towards the tumour, which produces CXCL12. It is therefore suggested that the CXCR4/CXCL12 pathway plays a role in the mechanism underlying tumour-mediated attraction of NSCs.

Role of oregano on bacterial enzymes in 1,2-dimethylhydrazine-induced experimental colon carcinogenesis.

Colon cancer incidence is higher in developed countries than in developing countries. We determined the effect of oregano (Origanum vulgare L.) on fecal bacterial enzyme activities in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis in rats. Male Wistar albino rats were divided into 6 groups and all animals were fed with a high-fat diet (20% fat in the diet). Group 1 served as control and group 2 animals received 60 mg.kg(-1) body weight (b.w.) oregano daily for 15 weeks. To induce colon cancer, DMH (20 mg.kg(-1) b.w.) was injected subcutaneously once a week for the first 4 weeks (groups 3-6). In addition, oregano was administered at 20, 40, or 60 mg.kg(-1) b.w. each day orally for the entire 15 weeks (groups 4-6). We analyzed the fecal bacterial enzyme activities and found it to be significantly higher in the group treated with DMH alone than in the control group. Oregano supplementation at all 3 doses significantly suppressed the bacterial enzyme activities and modulated oxidative stress significantly compared with the unsupplemented DMH-treated group. Results of our present investigation therefore revealed that oregano markedly inhibited DMH-induced colon carcinogenesis and that the optimal dose of 40 mg.kg(-1) b.w. was more effective than either the higher or lower doses.

Effect of leptin on peroxidation and antioxidant defense in ethanol-supplemented Mus musculus heart.

The aim of the study was to evaluate the effect of exogenous mouse leptin on ethanol-induced cardiac toxicity in mice. Administering ethanol (6.32 g/kg body weight p.o.) to 4-week-old healthy mice for 45 days resulted in significantly elevated plasma levels of leptin, lactate dehydrogenase (LDH), cardiac lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS) and significantly decreased cardiac superoxide dismutase, catalase, vitamin C, vitamin E, reduced glutathione and glutathione-dependent enzyme levels (glutathione peroxidase and glutathione S-transferase). Subsequent to the experimental induction of toxicity (i.e., after the initial period of 30 days) exogenous leptin was administered (230 microg/kg body weight i.p.) every alternate day for 15 days along with the daily dose of ethanol. Leptin administration to ethanol-treated mice significantly elevated the levels of plasma leptin, LDH and cardiac LOOH, TBARS, whereas the activity of antioxidant enzymes and the concentrations of vitamins C and E were further decreased significantly. These findings were consistent with our histological observations, confirming that leptin enhances cardiac toxicity in ethanol-supplemented mice.

Effects of histone deacetylation inhibition on neuronal differentiation of embryonic mouse neural stem cells.

Neural stem cells (NSCs) are multipotent cells that have the capacity for self-renewal and for differentiation into the major cell types of the nervous system, i.e. neurons, astrocytes and oligodendrocytes. The molecular mechanisms regulating gene transcription resulting in NSC differentiation and cell lineage specification are slowly being unraveled. An important mechanism in transcriptional regulation is modulation of chromatin by histone acetylation and deacetylation, allowing or blocking the access of transcriptional factors to DNA sequences. The precise involvement of histone acetyltransferases and histone deacetylases (HDACs) in the differentiation of NSCs into mature functional neurons is still to be revealed. In this in vitro study we have investigated the effects of the HDAC inhibitor trichostatin A (TSA) on the differentiation pattern of embryonic mouse NSCs during culture in a minimal, serum-free medium, lacking any induction or growth factor. We demonstrated that under these basic conditions TSA treatment increased neuronal differentiation of the NSCs and decreased astrocyte differentiation. Most strikingly, electrophysiological recordings revealed that in our minimal culture system only TSA-treated NSC-derived neurons developed normal electrophysiological membrane properties characteristic for functional, i.e. excitable and firing, neurons. Furthermore, TSA-treated NSC-derived neurons were characterized by an increased elongation and arborization of the dendrites. Our study shows that chromatin structure modulation by HDACs plays an important role in the transcriptional regulation of the neuronal differentiation of embryonic NSCs particularly as far as the development of functional properties are concerned. Manipulation of HDAC activity may be an important tool to generate specific neuronal populations from NSCs for transplantation purposes.

Leptin alters brain adenosine triphosphatase activity in ethanol-mediated neurotoxicity in mice.

INTRODUCTION: This study aimed to assess the leptin dependent changes on adenosine triphosphatase (ATPase) activities of the central nervous system during chronic ethanol supplementation. METHODS: The mice were divided into four groups. Group 1 consisted of control animals that received isocaloric glucose, Group 2 animals received isocaloric glucose plus exogenous mouse recombinant leptin (230 microgrammes/kilogramme body weight intraperitoneally) every alternate day, Group 3 were alcohol-fed mice (6.32 grammes/kilogramme body weight orally), and Group 4 were alcohol-fed mice that received leptin (230 microgrammes/kilogramme body weight intraperitoneally) every alternate day. The experiment was terminated after giving the mice leptin injections for 15 days. RESULTS: Ethanol feeding for a total period of 45 days (p-value is less than 0.05) significantly elevated the brain lipid hydroperoxide levels and total ATPases, sodium, potassium-ATPase and magnesium-ATPase activities but significantly decreased the calcium-ATPase activity. Leptin injections to ethanol-fed animals further elevated the levels of lipid hydroperoxides, total ATPases, sodium, potassium-ATPase and magnesium-ATPase, while calcium-ATPase activity was reduced significantly. CONCLUSION: Leptin plays an important role in the pathogenesis of ethanol-induced neurotoxicity by enhancing brain lipid peroxidation and regulating brain ATPase activities in mice. Thus, hyperleptinaemia-induced oxidative stress and enhanced ATPase activities may be important pathogenic factors in brain toxicity.

Intraperitoneal leptin regulates lipid metabolism in ethanol supplemented Mus musculas heart.

Diseases of the heart and blood vessels are a major cause of illness and disability worldwide. The relationship between ethanol consumption and cardiovascular disease are both complex and interconnected. Our aim of this study was to explore the effect of leptin on lipid metabolism in ethanol supplemented mice. Male Swiss mice (Mus musculas) weighing 25+/-2 g were administered ethanol (6.32 g kg(-1) body weight) for the first 30 days. Subsequently, ethanol fed mice were given intraperitoneal injections of exogenous mouse recombinant leptin (230 microg kg(-1) body weight) every alternate day for 15 days. Food and water intake and total body weight were measured every day and at the end of the experimental period of 45 days, plasma and cardiac lipids were analyzed. Exogenous leptin injections to ethanol fed mice significantly (P < 0.05) prevented the accumulation of total cholesterol, phospholipids (PL), triglycerides (TG) and free fatty acids (FFA) in the mouse heart and blood as compared to the untreated ethanol fed mice whereas, the plasma concentration of free cholesterol was significantly increased on leptin administration as compared to normal untreated mice. Moreover leptin administration significantly elevated the activities of cardiac lipoprotein lipase (LPL) and plasma lecithin cholesterol acyl transferase (LCAT) and significantly reduced the activities of cardiac HMG CoA reductase and cholesterol ester synthase (CES) on leptin administration to ethanol fed mice. Thus we could postulate that an increase in systemic leptin level prevents the accumulation of lipids in the plasma and heart of ethanol treated mice.

Effect of exogenous leptin administration on high fat diet induced oxidative stress.

The objective of the present study was to explore the tissue lipid peroxidation and antioxidant status in mice receiving exogenous leptin along with high fat diet for a period of 6 weeks. Significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and significantly lowered levels of glutathione and its related enzymes were observed in the liver, heart and kidney of mice fed with a high fat diet as compared with the control mice fed with a standard pellet diet. Subsequent to the treatment with high fat diet (ie., after the initial period of 30 days) exogenous leptin (230 microg kg(-1) body weight) was simultaneously administered along with the regular high fat diet every alternate day for 15 days. Leptin administration significantly lowered the tissue levels of TBARS, CD and elevated the activities of reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione S-transferase (GST) in both the control and high fat diet fed mice. Thus leptin supplementation was found to be effective in attenuating high fat diet induced oxidative stress.

Functionally deficient neuronal differentiation of mouse embryonic neural stem cells in vitro.

Embryonic mouse neural stem cells (NSCs) were isolated from E14 mice, multiplied in medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) and plated in laminin-coated wells in basic serum-free neurobasal medium. After 7 days in vitro, approximately 20% of the embryonic mouse NSCs developed into morphologically and biochemically fully maturated neurons, with extensive dendrites and multiple synaptic contacts. However, even after 22 days of culture, none of these neurons developed voltage-dependent sodium-channels characteristic for a functional neuron. Apparently, the morphological differentiation and the electrophysiological maturation of an embryonic mouse NSC into a neuron are independently regulated.

Effect of leptin administration on plasma and tissue lipids in alcohol induced liver injury.

Previous studies suggest a possible link between leptin and hepatic inflammation; however the role of leptin in liver diseases remains unclear. The purpose of the present study was to evaluate the effect of leptin on plasma and tissue lipids in experimental hepatotoxicity. Administering ethanol (6.32 g/kg body weight) to 4-week-old healthy mice for 45 days resulted in significantly elevated levels of plasma and tissue phospholipids, triglycerides and free fatty acids as compared with those of the control animals. Subsequent to the experimental induction of hepatotoxicity (i.e., the initial period of 30 days) exogenous leptin was simultaneously administered (230 microg/kg body weight) every alternate day for 15 days along with the daily dose of alcohol. Leptin administration to control and alcohol-treated mice reduced the weight gain and significantly lowered the levels of plasma and tissue lipids as compared with the untreated control and alcohol supplemented mice. It is postulated that the increase in systemic leptin levels lower the plasma and tissue lipids of alcohol-treated mice, which operates independently of changes in food intake, body weight and the size of the fat stores.

Role of leptin on alcohol-induced oxidative stress in Swiss mice.

Previous studies suggest a possible link between leptin and hepatic inflammation; however, the role of leptin on liver disease remains unclear. The purpose of the present study was to evaluate the effect of leptin on tissue lipid peroxidation and the antioxidant status in experimental hepatotoxicity. Administering ethanol (6.32 g/kg body weight) to 4-week-old healthy mice for 45 days resulted in significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lowered activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione related enzymes such as glutathione peroxidase (GPx) and glutathione S-transferase (GST) as compared with those of the control mice. subsequent to the experimental induction of hepatotoxicity (i.e. after the initial period of 30 days) exogenous leptin was simultaneously administered (230 microg/kg body weight) every alternate day for 15 days along with the daily dose of alcohol. Leptin administration to control and alcohol-treated mice significantly reduced the weight gain, significantly elevated the liver and kidney levels of TBARS and CD, and significantly lowered the levels of enzymic and non-enzymic antioxidants as compared with the untreated control and alcohol supplemented mice. It is postulated that the increase in systemic leptin levels enhance the oxidative stress, and lower the antioxidant defence, leading to augmented hepatic inflammation in alcoholic liver disease.