Melatonin inhibits cholangiocarcinoma and reduces liver injury in Opisthorchis viverrini‐infected and N‐nitrosodimethylamine‐treated hamsters

The human liver fluke Opisthorchis viverrini infection and N‐nitrosodimethylamine (NDMA) administration induce cholangiocarcinoma (CCA) and liver injury in hamsters. Melatonin protects against liver injury and reduces the alteration of mitochondrial structure, mitochondrial membrane potential, and mitochondrial pro‐ and anti‐apoptotic pathways in various cancer types. To investigate the chemopreventive effect of melatonin on CCA genesis and liver injury, hamsters were treated with a combination of O. viverrini infection and NDMA concurrently administered with melatonin (10 mg/kg and 50 mg/kg) for 120 days. Melatonin treatment at 50 mg/kg caused a significant reduction in liver/body weight ratios and decreased tumor volumes leading to an increase in the survival of animals. In the tumorous tissues, the high‐dose melatonin reduced DNA fragmentation and mitochondrial apoptosis by inducing anti‐apoptotic protein (Bcl‐2) in the mitochondrial fraction and down‐regulating cytochrome c, pro‐apoptotic protein (Bax), and caspase‐3 in tumor cytosol. Moreover, a high‐dose melatonin treatment significantly increased mitochondrial antioxidant enzymes and prevented mitochondrial ultrastructure changes in the tumor. Overall, melatonin has potent chemopreventive effects in inhibiting CCA genesis and also reduces liver injury in hamster CCA, which, in part, might involve in the suppression of CCA by reducing tumor mitochondria alteration.     

Decreased parasympathetic activities in Malayan krait (Bungarus candidus) envenoming.

Three patients were bitten by the Malayan krait (Bungarus candidus). The patients developed ptosis and generalized muscle weakness which later progressed to respiratory paralysis. All patients showed evidence of decreased parasympathetic activity manifested by mydriasis, hypertension and tachycardia. No specific antivenom was available. All patients received assisted ventilation and supportive treatment. The other forms of treatment included administration of neostigmine, the banded krait (Bungarus fasciatus) antivenom (Thai Red Cross) and plasmapheresis without beneficial response. Two patients recovered. The other patient had permanent brain damage due to anoxia from two episodes of cardiac arrest. While hypertension resolved 6-60 days after admission, mydriasis and tachycardia persisted after discharge in all patients for between 7 days and 2 years. One patient had constipation and defect in micturition which still persisted 2 years after the bite. Decreased parasympathetic activities in Malayan krait bite are perhaps not uncommon and should be examined.     

Protective effect of melatonin against Opisthorchis viverrini‐induced oxidative and nitrosative DNA damage and liver injury in hamsters

Abstract: The liver fluke, Opisthorchis viverrini, is the risk factor of cholangiocarcinoma, which is a major health problem in northeastern Thailand. Production of reactive oxygen and nitrogen species during the host’s response leads to oxidative and nitrosative stress contributing to carcinogenesis. We investigated the protective effect of melatonin against O. viverrini‐induced oxidative and nitrosative stress and liver injury. Hamsters were infected with O. viverrini followed by oral administration of various doses of melatonin (5, 10, and 20 mg/kg body weight) for 30 days. Uninfected hamsters served as controls. Compared to the levels in O. viverrini‐infected hamsters without melatonin treatment, the indoleamine decreased the formation of oxidative and nitrosative DNA lesions, 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine and 8‐nitroguanine, in the nucleus of bile duct epithelium and inflammatory cells, in parallel with a reduction in 3‐nitrotyrosine. Melatonin also reduced the expression of heme oxygenase‐1 and cytokeratin 19, nitrate/nitrite levels, and bile duct proliferation in the liver. Alanine transaminase activity and the levels of 8‐isoprostane and vitamin E were also dose dependently decreased in the plasma of melatonin‐treated hamsters. Melatonin reduced the mRNA expression of oxidant‐generating genes [inducible nitric oxide synthase, nuclear factor‐kappa B (NF‐κB), and cyclooxygenase‐2] and proinflammatory cytokines (TNF‐α and IL‐1β), accompanied by an increase in the expression of antioxidant genes [nuclear erythroid 2‐related factor 2 (Nrf2) and manganese superoxide dismutase]. Thus, melatonin may be an effective chemopreventive agent against O. viverrini‐induced cholangiocarcinoma by reducing oxidative and nitrosative DNA damage via induction of Nrf2 and inhibition of NF‐κB‐mediated pathways.     

National Kidney Foundation Council on Renal Nutrition survey: past-present clinical practices and future strategic planning.

Early nutritional intervention is thought to play a major role in the preservation of renal function and the overall wellbeing in the renal patient. In preparation for renal replacement therapy (RRT), a consultation with the renal nutritionist to establish a diet consistent with the existing diagnosis may increase the likelihood of reducing cardiovascular risk factors, preventing malnutrition and anemia, and slowing the progression of renal disease, all of which can contribute to positive patient outcomes. In a 1999 United States Renal Data System survey of 3,468 new dialysis patients, 46% indicated that they had not consulted with a dietitian before the initiation of dialysis. To help with establishing education programs, determine staffing guidelines, and planning future endeavors, the National Kidney Foundation Council on Renal Nutrition conducted a survey of their 1,748 members. The survey was designed to assess the current demographic profile and clinical practice elements of practicing renal dietitians. Surveys were distributed as a section of the 1999-2000 winter issue of the CRN Quarterly Newsletter, with 353 of the members responding. Information collected pertained to patient care settings, number of facilities covered, patient age, patient treatment modalities, dietitian contact hours required to effectively educate pre-end-stage renal disease patients on a low-protein diet and to ensure optimal nutrition status for the chronic kidney disease patients. The dietitians of this cohort had practiced dietetics for 14.5 +/- 8.6 years and renal nutrition for 9.15 +/- 6.9 years. The survey data showed a discrepancy between what the clinical practices were in 1999 and what the current recommendations are, based on the Kidney Disease Outcomes Quality Initiatives (K/DOQI) Clinical Practice Guidelines.     

Oral health in Thai patients with metabolic syndrome

AimTo study the prevalence of oral manifestations, xerostomia, hyposalivation and level of oral microflora in a group of Thai patients with metabolic syndrome (MS) and to determine if there is any association between MS and these oral health components.MethodsData including patients’ histories, general health, dental and periodontal status, oral mucosal manifestations, xerostomia, hyposalivation and oral microflora in 369 patients with MS were collected and statistically analyzed.ResultsNinety-four subjects (25.5%) were men and 275 (74.5%) were women, with age range from 32 to 88 years (mean = 63.9 ± 10.4). Of these, 231 patients (62.6%) were older than 60 years old. Dental caries in at least 1 tooth and periodontitis were found in 184 (49.9%) and 192 (52.0%) patients, respectively. Oral mucosal manifestations were found in 203 patients (55.0%). The most prevalent manifestation was fissured tongue (41.5%), followed by denture stomatitis (9.2%) and depapillated tongue (3.0%). Dry mucosa was depicted in 203 patients (55.0%). Xerostomia was revealed in 157 patients (42.5%) while hyposalivation was detected in 202 patients (54.7%). Twenty four percent of patients had high Candida level. Significant association was found between Candida level and hyposalivation and also hyposalivation, xerostomia and dry mucosa.ConclusionsApproximately half of the patients with metabolic syndrome presented with dental caries, periodontitis, dry mouth, oral mucosal changes and approximately one fourth had high Candida level.