Nickel-induced oxidative stress causes cell death in testicles: implications for male infertility.

Aligarh region is well known for its lock industry. This lock industry utilises nickel for electroplating. There have been informal reports of infertility in men and women living near the lock industry. We analysed field water samples to investigate this link, and the results showed considerable nickel contamination. To further validate our results, we exposed male rats to relevant nickel levels in drinking water. This experimental exposure resulted in abnormal sperm morphology, decline in sperm count, significant change in activities of antioxidant enzymes, pronounced oxidative stress in the rat spermatocytes and decrease in serum testosterone level, as well as damage in the hypothalamus and pituitary (in all cases, the changes were most significant at the highest concentration used i.e 2.5 mg/l). The breeding experiments showed decline in live birth rate, while pups did not survive post birth in cages where males were given 2 and 2.5 mg/l concentrations of nickel in drinking water prior to mating. Our data strongly indicate a link between industrial nickel exposure and male infertility.

Zizyphus mauritiana seed extract: Paving the way for next-generation bone constructs with nano-fluorohydroxyapatite/carboxymethyl chitosan nanocomposite scaffold.

This is the first study that explored the potential use of Zizyphus mauritiana seed extract (ZSE) to synthesize nano-fluorohydroxyapatite/carboxymethyl chitosan nanocomposite scaffolds at different concentrations (CFZ1, CFZ2 and CFZ3) using co-precipitation method. The proposed scaffolds showed presence of intermolecular H bonding interactions between the constituents, according to the FTIR. The mechanical studies revealed shore hardness of 72 ± 4.6 and optimal compressive modulus in case of CFZ3 [1654.48 ± 1.6 MPa], that was comparable with that of human cortical bone. The SEM, TEM and platelet adhesion images corroborated uniformly distributed needle like particles in case of CFZ3 with an average size ranging from 22 to 26 nm, linked rough morphology, and appropriate hemocompatibility. The markedly up regulation in the ALP activity and protein adsorption upon increasing ZSE concentration demonstrated that CFZ nanocomposite scaffolds were compatible with osteoblastic cells relative to CF nanocomposite. The cytotoxicity study indicated that CFZ nanocomposite do not induce toxicity over MG-63 and did not aggravate LDH leakage in contrast to CF. The histopathological investigations on albino rats confirmed significantly improved regeneration of bone in the repair of a critical-size [8 mm] calvarium defect. Therefore, CFZ3 nanocomposite scaffold represents a simple, off-the-shelf solution to the combined challenges associated with bone defects.

Pentachlorophenol-induced hemotoxicity diminishes antioxidant potential and oxidizes proteins, thiols, and lipids in rat blood: An in vivo study.

Pentachlorophenol (PCP) is an excessively used wood preservative and pesticide, which has resulted in human exposure raising concerns about its potential toxic effects. This study is designed to evaluate the hemotoxicity of PCP in adult rats. Wistar rats were orally administered PCP (25-150 mg/kg bw) for five days while untreated (control) rats received corn oil. Animals were sacrificed, blood was taken and fractionated into plasma and red blood cells (RBC). PCP administration increased methemoglobin formation but decreased methemoglobin reductase activity. Significantly increased hydrogen peroxide level indicates initiation of oxidative stress condition in blood. PCP increased the oxidation of thiols, proteins and lipids, lowered glutathione levels, and compromised the antioxidant status of RBC in treated rats. Enzymes of the pathways of glucose breakdown, glycolysis and phosphogluconate pathway, were inhibited. Markers of liver damage were increased in the plasma of PCP-treated rats suggesting hepatotoxicity. This was confirmed by histopathological analysis of stained liver sections. Activity of xanthine oxidase, a reactive oxygen species (ROS) generating pro-oxidant enzyme, was increased. These hematological changes could be a result of the increased generation of ROS or direct chemical transformation by transient reaction species. These results show that PCP induces redox imbalance, diminishes antioxidant potential, inhibits metabolic pathways, and oxidizes cellular components in rat blood. This study suggests an elaborated possible molecular mechanism of PCP toxicity, and similar compounds so that methods can be devised to minimize its damaging effect.

Oral administration of curcumin and gallic acid alleviates pentachlorophenol-induced oxidative damage in rat intestine.

INTRODUCTION: Pentachlorophenol (PCP) is used as pesticide and wood preservative. We have previously shown that PCP causes oxidative damage in rat intestine. AIM: This study aimed to delineate the possible therapeutic potential of curcumin (CUR) and gallic acid (GA) against PCP-induced damage in rat intestine. METHODS: PCP alone group received 125 mg PCP/kg body weight/day orally for 4 days. Animals in combination groups received CUR or GA (100 mg/kg bw) for 18 days and PCP (125 mg/kg bw) for the last four days. Rats were sacrificed and intestinal preparations were analyzed for various parameters. RESULTS: Administration of PCP alone altered the activities of metabolic, antioxidant and brush border membrane enzymes. It also increased DNA-protein crosslinking and DNA-strand scission. Animals in combinations groups showed significant amelioration against PCP-induced oxidative damage. Histological abrasions were seen in PCP alone group which were reduced in the intestines of combination groups. CUR was more effective protectant than GA. CONCLUSIONS: CUR and GA protected rat intestine from PCP-mediated changes in the activities of metabolic, antioxidant and brush border membrane enzymes. They also prevented DNA damage and histological abrasions. The antioxidant character of CUR and GA may be responsible for the diminution of PCP-mediated oxidative damage.

Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma.

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma.

Pentachlorophenol causes redox imbalance, inhibition of brush border membrane and metabolic enzymes, DNA damage and histological alterations in rat kidney.

Pentachlorophenol (PCP) is a synthetic organochlorine compound that is widely used in biocide and pesticide industries, and in preservation of wood, fence posts, cross arms and power line poles. Humans are usually exposed to PCP through air, contaminated water and food. PCP enters the body and adversely affects liver, gastrointestinal tract, kidney and lungs. PCP is a highly toxic class 2B or probable human carcinogen that produces large amount of reactive oxygen species (ROS) within cells. This work aimed to determine PCP-induced oxidative damage in rat kidney. Adult rats were given PCP (25, 50, 100, 150 mg/kg body weight), in corn oil, once a day for 5 days while control rats were given similar amount of corn oil by oral gavage. PCP increased hydrogen peroxide level and oxidation of thiols, proteins and lipids. The antioxidant status of kidney cells was compromised in PCP treated rats while enzymes of brush border membrane (BBM) and carbohydrate metabolism were inhibited. Plasma level of creatinine and urea was also increased. Administration of PCP increased DNA fragmentation, cross-linking of DNA to proteins and DNA strand scission in kidney. Histological studies supported biochemical findings and showed significant damage in the kidneys of PCP-treated rats. These changes could be due to redox imbalance or direct chemical modification by PCP or its metabolites. These results signify that PCP-induced oxidative stress causes nephrotoxicity, dysfunction of BBM enzymes and DNA damage.

Orally fed EGCG coronate food released TiO2 and enhanced penetrability into body organs via gut.

Owing to unique nano-scale properties, TiO2-NPs (T-NPs) are employed as food-quality enhancers in >900 processed food products. Whereas, epigallocatechin-3-gallate (EGCG), a green tea polyphenol is consumed in traditional brewed tea, globally. Taken together, we aimed to investigate whether human gastric-acid digested T-NPs and complex tea catechins yield ionic species (Ti4+, Ti3+ etc.) and active EGCG forms to meet favourable conditions for in vivo bio-genesis of EGCG-coronated TiO2-NPs (ET-NPs) in human gut. Secondly, compared to bare-surface micro and nano-scale TiO2, i.e., T-MPs and T-NPs, respectively, how EGCG coronation on ET-NPs in the gut facilitates the modulation of intrinsic propensity of internalization of TiO2 species into bacteria, body-organs, and gut-microbiota (GM), and immune system. ET-NPs were synthesized in non-toxic aqueous solution at varied pH (3-10) and characterised by state-of-the-arts for crystallinity, surface-charge, EGCG-encapsulation, stability, size, composition and morphology. Besides, flow-cytometry (FCM), TEM, EDS, histopathology, RT-PCR, 16S-rRNA metagenomics and ELISA were also performed to assess the size and surface dependent activities of ET-NPs, T-NPs and T-MPs vis-a-vis planktonic bacteria, biofilm, GM bacterial communities and animal's organs. Electron-microscopic, NMR, FTIR, DLS, XRD and EDS confirmed the EGCG coronation, dispersity, size-stability of ET-NPs, crystallinity and elemental composition of ET-NPs-8 and T-NPs. Besides, FCM, RT-PCR, 16S-rRNA metagenomics, histopathology, SEM and EDS analyses exhibited that EGCG coronation in ET-NPs-8 enhanced the penetration into body organs (i.e., liver and kidney etc.) and metabolically active bacterial communities of GM.

Oral Administration of Copper Chloride Damages DNA, Lowers Antioxidant Defense, Alters Metabolic Status, and Inhibits Membrane Bound Enzymes in Rat Kidney.

Copper (Cu) is a heavy metal that is widely used in industries and is also an essential micronutrient for living beings. However, excess Cu is toxic and human exposure to high levels of this metal results in numerous adverse health effects. We have investigated the effect of oral administration of copper chloride (CuCl2), a Cu(II) compound, on various parameters of oxidative stress, cellular metabolism, and DNA integrity in the rat kidney. This was done to delineate the molecular mechanism of Cu(II) toxicity. Adult male rats were randomly divided into five groups. Animals in four CuCl2-treated groups were separately administered single acute oral dose of CuCl2 at 5, 15, 30, and 40 mg/kg body weight. Animals in the fifth group were not given CuCl2 and served as the control. All rats were sacrificed 24 h after the dose of CuCl2 and their kidneys removed. CuCl2 administration led to significant alterations in enzymatic and non-enzymatic parameters of oxidative stress. It changed the activities of metabolic and membrane bound enzymes and also decreased the activities of brush border membrane enzymes. CuCl2 treatment dose-dependently enhanced DNA damage and DNA-protein crosslinking in renal cells, when compared to the control group. The administration of CuCl2 also resulted in marked morphological changes in the kidney, with more prominent alterations at higher doses of CuCl2. These results clearly show that CuCl2 impairs the antioxidant defense system resulting in oxidative damage to the kidney.

Dosimetric analysis of intracavitary brachytherapy applicators: a practical study.

PURPOSE: Intracavitary brachytherapy is one of the important methods of gynecological cancer treatment. The effect of attenuation is not considered in the dose calculation method released by the American Association of Physicists in Medicine (AAPM) Task Group No. 43 Report (TG-43). In this study, the effect of high-dose rate (HDR) brachytherapy applicators on dose distribution was measured using Gafchromic films and well-type ionization chamber. MATERIALS AND METHODS: A plan created by the treatment planning system was first executed using a well-type ionization chamber with a water equivalent elasto-gel in place for charge collection. Again, same plan was executed using central tandems of various angulations with different diameters of vaginal cylinders and charge collection was measured. For in vitro dose measurements this plan was also executed on tandem and vaginal cylinder assembly with Gafchromic films fixed on the surface of vaginal cylinder. RESULTS: The results show that the central tandem when used with different vaginal cylinders resulted in increase in effective attenuation of the beam. The central tandem of 300 angulations when used with a 35-mm diameter vaginal cylinder results in maximum attenuation whereas the 0º tandem when used with 20-mm diameter vaginal cylinder results in least attenuation of the beam. CONCLUSION: Due to the attenuation by various applicators used in brachytherapy for the treatment of gynecological cancers, it can be concluded that the difference between practical dose and the treatment planning system calculated dose should be considered for the correct estimation of the dose to the target and the organs-at-risk.

Oral administration of pentachlorophenol impairs antioxidant system, inhibits enzymes of brush border membrane, causes DNA damage and histological changes in rat intestine.

Pentachlorophenol (PCP) is a broad spectrum biocide that has many domestic and industrial applications. PCP enters the environment due to its wide use, especially as a wood preservative. Human exposure to PCP is through contaminated water and adulterated food products. PCP is highly toxic and is classified as class 2B or probable human carcinogen. In this study, we explored the effect of PCP on rat intestine. Adult rats were orally given different doses of PCP (25-150-mg/kg body weight/day) in corn oil for 5 days, whereas controls were given similar amount of corn oil. The rats were sacrificed 24 h after the last treatment. A marked increase in lipid peroxidation, carbonyl content, and hydrogen peroxide level was seen. The glutathione and sulfhydryl group content was decreased in all PCP treated groups. This strongly suggests the generation of reactive oxygen species (ROS) in the intestine. PCP administration suppressed carbohydrate metabolism, inhibited enzymes of brush border membrane (BBM), and antioxidant defense system. It also led to increase in DNA damage, which was evident from comet assay, DNA-protein cross-linking, and DNA fragmentation. Histological studies supported the biochemical results showing marked dose-dependent tissue damage in intestines from PCP treated animals. This study reports for the first time that oral administration of PCP induces ROS, impairs the antioxidant system, damages DNA, and alters the enzyme activities of BBM and metabolic pathways in rat intestine.

Oral administration of thiram inhibits brush border membrane enzymes, oxidizes proteins and thiols, impairs redox system and causes histological changes in rat intestine: A dose dependent study.

Pesticides are extensively employed worldwide, especially in agriculture to control weeds, insect infestation and diseases. Besides their targets, pesticides can also affect the health of non-target organisms, including humans The present study was conducted to study the effect of oral exposure of thiram, a dithiocarbamate fungicide, on the intestine of rats. Male rats were administered thiram at doses of 100, 250, 500 and 750 mg/kg body weight for 4 days. This treatment reduced cellular glutathione, total sulfhydryl groups but enhanced protein carbonyl content and hydrogen peroxide levels. In addition, the activities of all major antioxidant enzymes (catalase, thioredoxin reductase, glutathione peroxidase and glutathione-S-transferase) except superoxide dismutase were decreased. The antioxidant power of the intestine was impaired lowering the metal-reducing and free radical quenching ability. Administration of thiram also led to inhibition of intestinal brush border membrane enzymes, alkaline phosphatase, γ-glutamyl transferase, leucine aminopeptidase and sucrase. Activities of enzymes of pentose phosphate pathway, citric acid cycle, glycolysis and gluconeogenesis were also inhibited. Histopathology showed extensive damage in the intestine of thiram-treated rats at higher doses. All the observed effects were in a thiram dose-dependent manner. The results of this study show that thiram causes significant oxidative damage in the rat intestine which is associated with the marked impairment in the antioxidant defense system.

Copper chloride inhibits brush border membrane enzymes, alters antioxidant and metabolic status and damages DNA in rat intestine: a dose-dependent study.

Copper (Cu) is an extensively used heavy metal and an indispensible micronutrient for living beings. However, Cu is also toxic and exerts multiple adverse health effects when humans are exposed to high levels of this metal. We have examined the effect of single acute oral dose of copper chloride (CuCl2) on parameters of oxidative stress, cellular metabolism, membrane and DNA damage in rat intestine. Adult male Wistar rats were divided into four groups and separately administered a single oral dose of 5, 15, 30 and 40 mg CuCl2/kg body weight. Rats not administered CuCl2 served as the control. Oral administration of CuCl2 led to significant alterations in the activities of metabolic and membrane-bound enzymes; brush border enzymes were inhibited by 45-75% relative to the control set. Inhibition of antioxidant enzymes diminished the metal-reducing and free radical quenching ability of the cells. Oxidative damage caused cellular oxidation of thiols, proteins and lipids. Diphenylamine and comet assays showed that CuCl2 treatment enhanced DNA damage while DNA-protein crosslinking was also increased in the intestinal cells. Examination of stained sections showed that CuCl2 treatment led to marked histological changes in the intestine. All the changes seen were in a CuCl2 dose-dependent manner with more prominent alterations at higher doses of CuCl2. These results clearly show that oral administration of CuCl2 results in oxidative damage to the intestine which can impair its digestive and absorptive functions.

Diagnostic and investigative approach of consultant neurologists in a real-world clinical setting: A pilot study.

PURPOSE: Whilst core curricula in neurology are nationally standardised, in real-world clinical practice, different approaches may be taken by individual consultants. The aims of this study were to investigate differences by assessing: (a) variance in diagnostic and investigative practice, using a case-based analysis of inter-rater agreement; (b) potential importance of any differences in terms of patient care; (c) relationships between clinical experience, diagnostic certainty, diagnostic peer-agreement and investigative approach. The objective was to develop novel individualised metrics to facilitate reflection and appraisal. METHODS: Three neurologists with 6-23 years' experience at consultant level provided diagnosis, certainty (10-point Likert scale), and investigative approach for 200 consecutive general neurology outpatients seen by a newly qualified consultant in 2015. Diagnostic agreement was evaluated by percentage agreement. The potential importance of any diagnostic differences on patient outcome was assigned a score (6-point Likert scale) by the evaluating neurologist. Associations between diagnostic agreement, certainty and investigative approach were assessed using Spearman correlation, logistic and ordinal regression, and reported as individualised metrics for each rater. RESULTS: Diagnostic peer-agreement was 3/3, 2/3 and 1/3 in 55.5%, 31.0% and 13.5% of cases, respectively. In 15.5%, differences in patient management were judged potentially important. Investigation rates were 42%-73%. Mean diagnostic certainty ranged from 6.63/10 (SD 1.98) to 7.72/10 (SD 2.20) between least and most experienced consultants. Greater diagnostic certainty was associated with greater diagnostic peer-agreement (individual-rater regression coefficients 0.33-0.44, P < .01) and lower odds of arranging investigations (individual-rater odds ratios 0.56-0.71, P < .01). CONCLUSIONS: It appears that variance in diagnostic and investigative practice between consultant neurologists exists and may result in differing management. Mean diagnostic certainty was associated with greater diagnostic peer-agreement and lower investigation rates. Metrics reflecting concordance with peers, and relationships to diagnostic confidence, could be developed in larger cohorts to inform reflective practice.

Comparison of efficacy of dexamethasone and methylprednisolone in moderate to severe covid 19 disease.

BACKGROUND: The first case of Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were diagnosed in Wuhan, China in 2019. In the first half of 2020 this disease has already converted into a global pandemic. Various treatment options were being tried all over the world. Some studies showed beneficial effects of corticosteroids in covid 19. Hence, we designed this study to compare the effect of two steroids in moderate to severe covid 19 disease. OBJECTIVES: To compare the efficacy and safety of dexamethasone and methylprednisolone in moderate to severe covid 19 disease. STUDY SETTINGS: Fatima Memorial Hospital, Lahore and Ganga Ram hospital, Lahore. STUDY DESIGN: Quasi experimental, interventional study. DURATION OF STUDY: From 1st June 2020 to 30th June 2020. METHODOLOGY: Sample size and technique: there were total 100 patients; 35 patients received dexamethasone and 65 were kept in methylprednisolone receiving group. RESULTS: The mean age of patients was 57.91 years in dexamethasone group and 54.86 years in methylprednisolone group. In dexamethasone group, there were 15 (42.8%) critically ill patients who were shifted to Intensive care unit (ICU) and seven (20%) of them needed ventilatory support, whereas in methylprednisolone group 22 (33.8%) had to be admitted in ICU with eight (12.3%) patient needing ventilator. As outcome measure, patients in both the groups showed marked improvement in temperature, oxygen requirement and C-reactive protein (CRP) on day 5. Only six (17.1%) patient died who received dexamethasone while 10 (15.3%) patients died among those receiving methylprednisolone. CONCLUSION: Dexamethasone and methylprednisolone both are equally effective in treating moderate to severe covid 19 disease.

Evaluation of semi-quantitative compared to quantitative cultures of tracheal aspirates for the yield of culturable respiratory pathogens - a cross-sectional study.

BACKGROUND: Diagnosis of lower respiratory tract infections (LRTI) depends on the presence of clinical, radiological and microbiological findings. Endotracheal suction aspirate (ETSA) is the commonest respiratory sample sent for culture from intubated patients. Very few studies have compared quantitative and semi-quantitative processing of ETSA cultures for LRTI diagnosis. We determined the diagnostic accuracy of quantitative and semi-quantitative ETSA culture for LRTI diagnosis, agreement between the quantitative and semi quantitative culture techniques and the yield of respiratory pathogens with both methods. METHODS: This was a cross-sectional study conducted at the Aga Khan University clinical laboratory, Karachi, Pakistan. One hundred and seventy-eight ETSA samples sent for routine bacteriological cultures were processed quantitatively as part of regular specimen processing method and semi-quantitatively. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy was calculated for both methods using clinical diagnosis of pneumonia as reference standard. Agreement between the quantitative and semi quantitative methods was assessed via the kappa statistic test. Pathogen yield between the two methods was compared using Pearson's chi-square test. RESULTS: The quantitative and semi-quantitative methods yielded pathogens in 81 (45.5%) and 85 (47.8%) cases respectively. There was complete concordance of both techniques in 155 (87.1%) ETSA samples. No growth was observed in 45 (25.3%) ETSA specimens with quantitative culture and 37 (20.8%) cases by semi-quantitative culture. The diagnostic accuracy of both techniques were comparable; 64.6% for quantitative and 64.0% for semi-quantitative culture. The kappa agreement was found to be 0.84 (95% CI, 0.77-0.91) representing almost perfect agreement between the two methods. Although semi-quantitative cultures yielded more pathogens (47.8%) as compared to quantitative ETSA cultures (45.5%), the difference was only 2.3%. However, this difference achieved statistical (chi-square p-value < 0.001) favoring semi-quantitative culture methods over quantitative culture techniques for processing ETSA. CONCLUSION: In conclusion, there is a strong agreement between the performances of both methods of processing ETSA cultures in terms of accuracy of LRTI diagnosis. Semi-quantitative cultures of ETSA yielded more pathogens as compared to quantitative cultures. Although both techniques were comparable, we recommend processing of ETSA using semi-quantitative technique due to its ease and reduced processing time.

Tremor after long term lithium treatment; is it cortical myoclonus?

INTRODUCTION: Tremor is a common side effect of treatment with lithium. Its characteristics can vary and when less rhythmical, distinction from myoclonus can be difficult. METHODS: We identified 8 patients on long-term treatment with lithium that developed upper limb tremor. All patients were assessed clinically and electrophysiologically, with jerk-locked averaging (JLA) and cross-correlation (CC) analysis, and five of them underwent brain MRI examination including spectroscopy (MRS) of the cerebellum. RESULTS: Seven patients (6 female) had action and postural myoclonus and one a regular postural and kinetic tremor that persisted at rest. Mean age at presentation was 58 years (range 42-77) after lengthy exposure to lithium (range 7-40 years). During routine monitoring all patients had lithium levels within the recommended therapeutic range (0.4-1 mmol/l). There was clinical and/or radiological evidence (on cerebellar MRS) of cerebellar dysfunction in 6 patients. JLA and/or CC suggested a cortical generator of the myoclonus in seven patients. All seven were on antidepressants and three additionally on neuroleptics, four of them had gluten sensitivity and two reported alcohol abuse. CONCLUSIONS: A synergistic effect of different factors appears to be contributing to the development of cortical myoclonus after chronic exposure to lithium. We hypothesise that the cerebellum is involved in the generation of cortical myoclonus in these cases and factors aetiologically linked to cerebellar pathology like gluten sensitivity and alcohol abuse may play a role in the development of myoclonus. Despite the very limited evidence in the literature, lithium induced cortical myoclonus may not be so rare.

Ameliorative effect of carnosine and N-acetylcysteine against sodium nitrite induced nephrotoxicity in rats.

The widespread use of sodium nitrite (NaNO2 ) for various industrial purposes has increased human exposure to alarmingly high levels of nitrate/nitrite. Because NaNO 2 is a strong oxidizing agent, induction of oxidative stress is one of the mechanisms by which it can exert toxicity in humans and animals. We have investigated the possible protection offered by carnosine (CAR) and N-acetylcysteine (NAC) against NaNO 2 -induced nephrotoxicity in rats. Animals orally received CAR at 100 mg/kg body weight/d for seven days or NAC at 100 mg/kg body weight/d for five days followed by a single oral dose of NaNO 2 at 60 mg/kg body weight. The rats were killed after 24 hours, and the kidneys were removed and processed for various analyses. NaNO 2 induced oxidative stress in kidneys, as shown by the decreased activities of antioxidant defense, brush border membrane, and metabolic enzymes. DNA-protein crosslinking and DNA fragmentation were also observed. CAR/NAC pretreatment significantly protected the kidney against these biochemical alterations. Histological studies supported these findings, showing kidney damage in NaNO 2 -treated animals and reduced tissue impairment in the combination groups. The protection offered by CAR and NAC against NaNO 2 -induced damage, and their nontoxic nature, makes them potential therapeutic agents against nitrite-induced nephrotoxicity.

Peripheral neuropathic pain in idiopathic Parkinson's disease: Prevalence and impact on quality of life; a case controlled study.

BACKGROUND AND PURPOSE: Pain is a frequent and debilitating non-motor symptom of Idiopathic Parkinson's Disease (IPD). The present study investigated the prevalence of pain and specifically peripheral neuropathic pain (PNP) in IPD, and ascertained any impact of PNP on quality of life (QoL). METHODS: Patients with IPD and age- and gender-matched controls were screened for overall pain using the King's Parkinson's Pain Scale (KPPS). PNP was assessed using the Michigan Neuropathy Screening Instrument (MNSI). QoL was assessed using the 36-Item Short Form Survey (SF-36). RESULTS: Fifty-one patients and 51 age and gender matched controls were recruited. The prevalence of overall pain was similar in the two groups (88.2% versus 94.1%, p = 0.487). However, patients with IPD had higher KPPS scores in fluctuation-related (4.9 ±â€¯6.9 vs 1.1 ±â€¯2.6, p < 0.001), nocturnal (6.6 ±â€¯7.5 vs 1.7 ±â€¯4.2, p < 0.001) and oro-facial (0.6 ±â€¯2.0 vs 0.0 ±â€¯0.0, p = 0.040) domains compared to controls. Patients with IPD experienced more PNP compared to healthy control subjects (35.3% versus 13.7%, p = 0.011). After adjusting for age, gender, disease duration and overall KPSS score, PNP correlated negatively with physical functioning score (beta -0.290, p = 0.036), emotional role limitations score (beta -0.319, p = 0.032) and general health perception score (beta -0.342, p = 0.014) domains of SF-36. CONCLUSION: Peripheral neuropathic pain is prevalent in IPD and has a significant impact on QoL. The presence of burning pain is suggestive of small fibre neuropathy, but this symptom is not featured in KPSS and, therefore, a revision of the KPSS should be considered.

Acute renal toxicity of sodium chlorate: Redox imbalance, enhanced DNA damage, metabolic alterations and inhibition of brush border membrane enzymes in rats.

Sodium chlorate (NaClO3 ) is widely used in paper and pulp industries and as a non-selective herbicide. Humans can be exposed to NaClO3 through contaminated drinking water due to its improper and unchecked usage in industries and as herbicide. NaClO3 is also present as a major stable by-product in drinking water that has been disinfected with chlorine dioxide. In this study, we have investigated the effect of a single acute oral dose of NaClO3 on rat kidney. Adult male Wistar rats were divided into one control and four NaClO3 treated groups that were orally given different doses of NaClO3 and euthanized 24 hr after the treatment. Oral administration of NaClO3 resulted in increased hydrogen peroxide levels, lipid, and protein oxidation while thiol and glutathione content and activities of brush border membrane enzymes were decreased in kidney in a NaClO3 dose-dependent manner. Significant alterations in the activities of enzymes involved in carbohydrate metabolism and antioxidant defense were also observed. Administration of NaClO3 induced DNA fragmentation and increased DNA-protein cross-linking. Histological studies showed marked damage in kidney from NaClO3 treated animals. These results strongly suggest that NaClO3 induces nephrotoxicity via redox imbalance that results in DNA and membrane damage, metabolic alterations and brush border membrane enzyme dysfunction.