Levamizole enhances immune responsiveness to intra-dermal and intra-muscular hepatitis B vaccination in chronic hemodialysis patients

BACKGROUND: Hemodialysis patient are at high risk for hepatitis B virus (HBV) infection. Although preventive vaccination is done routinely, the response to vaccination is low in this patient population. The aim of this study was to evaluate the effect of Levamizol, an enhancer of the immune responsiveness, on different routs of vaccination, i.e., intradermal (ID) versus intramuscular (IM), in stable chronic hemodialysis patients. MATERIALS AND METHODS: Forty four chronic heamodialyses patient were divided into four equal groups. The first group was received 40 μg HB vaccine intramuscularly. The second group was received 20 μg HB vaccine intradermally. The third and the fourth group received 20 μg vaccine IM or ID, respectively, in three doses plus oral Levamisole (100 mg for 12 day). After one and six months from the last dose of vaccine, HBs antibody titers were measured. RESULTS: The response rate to vaccine (HBs Antibody>10 μg/L) in the routine IM HB vaccination was low (60%). It increased to 70% with ID route. Levamisole significantly raised the response rate to 90% (P < 0.01). Also in the Levamisole groups protective HB antibody titers were maintained until the end of six months. We conclude that HD patients must be vaccinated by ID route and addition of Levamisole. Levamisole also increases antibody maintenance

Effect of Nandrolone Decanoate on Serum Lipoprotein (a) and its isoforms in hemodialysis patients

Malnutrition, anemia and increased atherosclerosis are the main causes of mortality in hemodialysis patients. Therapies designed to improve the disorders might therefore be expected to improve outcome. The effects of Nandrolone Decanoate (ND), in 64 stable hemodialysis patients, were studied with respect to the following parameters: nutritional status, hematological indexes, lipid profiles including serum levels of lipoprotein(a) [Lp(a)] in terms of differences in apolipoprotein(a) [apo(a)]. The patients were treated with ND at dose of 100 mg/I.M./week for 4 months. After 2 and 4 months of treatment the elevations in the serum levels of albumin (p < 0.0001), creatinine (p < 0.009), hemoglobin (p < 0.03), hematocrit (p < 0.03), cholesterol (p = 0.007) and triglyceride (p < 0.04) were noticed. Marked decrease in the concentration of high-density lipoprotein cholesterol (p = 0.007) and Lp(a) (p < 0.0001) were also found. These effects after 2 months of treatment withdrawal were relatively constant. By dividing patients according to the baseline Lp(a) levels and molecular weight of apo(a) isoform, it was noticed that the decrease in serum Lp(a) was significant in patients with high Lp(a) (>30 mg/dl) than those of with low Lp(a) (<30 mg/dl), irrespective of apo(a) molecular weight. It may be suggested that, ND has beneficial effect on nutritional status and treatment of anemia in hemodialysis patients. In spite the adverse effect of ND on lipid profile, it decreases Lp(a) mostly in patients with high serum Lp(a) preferently by the effect on apo(a) gene transcriptional activity

Comparison between swallowing and chewing of garlic on levels of serum lipids, cyclosporine, creatinine and lipid peroxidation in Renal Transplant Recipients

Abstract Hyperlipidemia and increased degree of oxidative stress are among the important risk factors for Atherosclerosis in renal transplant recipients (RTR). The Medical treatment of hyperlipidemia in RTR because of drugs side effects has been problematic, therefore alternative methods such as using of Garlic as an effective material in cholesterol lowering and inhibition of LDL Oxidation has been noted. For evaluation of garlic effect on RTR, 50 renal transplant patients with stable renal function were selected and divided into 2 groups. They took one clove of garlic (1 gr) by chewing or swallowing for two months, after one month wash-out period, they took garlic by the other route. Results indicated that although lipid profile, BUN, Cr, serum levels of cyclosporine and diastolic blood pressure did not change, Systolic blood pressure decreased from138.2 to 132.8 mmHg (p=0.001) and Malondialdehyde (MDA) decreased from 2.4 to1.7 nmol/ml (p=0.009) by swallowing route, Cholesterol decreased from 205.1 to 195.3 mg/dl (p=0.03), triglyceride decreased from 195.7 to 174.8 mg/dl (p=0.008), MDA decreased from 2.5 to 1.6 nmol/ml (p=0.001), systolic blood pressure decreased from 137.5 to 129.8 mmHg (p=0.001), diastolic blood pressure decreased from 84.6 to 77.6 mmHg (p=0.001) and Cr decreased from 1.51 to 1.44 mg/dl (p=0.03) by chewing route too. However HDL, LDL and cyclosporine serum levels had no significant differences by both of swallowing and chewing routes. We conclude that undamaged garlic (swallowed) had no lowering effect on lipid level of serum. But Crushed garlic (chewed) reduces cholesterol, triglyceride, MDA and blood pressure. Additionally creatinine reduced without notable decrease in cyclosporine serum levels may be due to cyclosporine nephrotoxicity ameliorating effect of garlic

Protective Effect of Fish Oil Supplementation on DNA Damage Induced by Cigarette Smoking

The study examined the influence of fish oil (FO) supplementation on serum 8-hydroxy-2\u2019-deoxyguanosine (8-OHdG) levels as indicated by DNA damage markers and total antioxidant capacity (TAC) among male cigarette smokers. This double-blind, placebo-controlled randomized study was conducted among healthy cigarette smokers (n=40) who were part of a larger prospective cohort study. Twenty smokers were randomly selected to receive FO for 3 months (1 g/day), and another 20 smokers received a placebo for 3 months; 8-OHdG and TAC levels were measured in blood samples before and after the intervention. Serum 8-OHdG significantly decreased (p=0.001) and TAC increased (p&lt;0.001) after 3 months of treatment with FO. Between baseline and endline, the difference in 8-OHdG significantly correlated with the difference in TAC among smokers who received FO (r=-0.540, p=0.014). The study provides evidence that FO supplementation can modify decreased antioxidants and increased oxidative DNA damage in cigarette smokers

Characterization of human mesothelin transcripts in ovarian and pancreatic cancer

BACKGROUND: Mesothelin is an attractive target for cancer immunotherapy due to its restricted expression in normal tissues and high level expression in several tumor types including ovarian and pancreatic adenocarcinomas. Three mesothelin transcript variants have been reported, but their relative expression in normal tissues and tumors has been poorly characterized. The goal of the present study was to clarify which mesothelin transcript variants are commonly expressed in human tumors. METHODS: Human genomic and EST nucleotide sequences in the public databases were used to evaluate sequences reported for the three mesothelin transcript variants in silico. Subsequently, RNA samples from normal ovary, ovarian and pancreatic carcinoma cell lines, and primary ovarian tumors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing to directly identify expressed transcripts. RESULTS: In silico comparisons of genomic DNA sequences with available EST sequences supported expression of mesothelin transcript variants 1 and 3, but there were no sequence matches for transcript variant 2. Newly-derived nucleotide sequences of RT-PCR products from tissues and cell lines corresponded to mesothelin transcript variant 1. Mesothelin transcript variant 2 was not detected. Transcript variant 3 was observed as a small percentage of total mesothelin amplification products from all studied cell lines and tissues. Fractionation of nuclear and cytoplasmic RNA indicated that variant 3 was present primarily in the nuclear fraction. Thus, mesothelin transcript variant 3 may represent incompletely processed hnRNA. CONCLUSION: Mesothelin transcript variant 1 represents the predominant mature mRNA species expressed by both normal and tumor cells. This conclusion should be important for future development of cancer immunotherapies, diagnostic tests, and gene microarray studies targeting mesothelin

Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer

Background Mesothelin has attracted much interest as a tumor specific antigen; it has been reported to promote tumor development and to be a good target for cancer treatment. Most studies to date have used human mesothelin in immunocompromised mice. Since these models do not allow for study of the natural immune response to mesothelin expressing tumors, we have undertaken the characterization of mouse mesothelin so the effects of this protein can be assessed in immunocompetent mouse strains. Methods We analyzed mouse mesothelin expression, tissue distribution, shedding and biochemistry. In addition we constructed stable mesothelin overexpressing lines of the pancreatic cancer line Panc02 by two methods and tested them for growth and tumorigencity in vitro and in vivo. Results We show here that mouse mesothelin is similar to human mesothelin in biochemical characteristics, tumor expression and tissue distribution, suggesting the mouse may be a suitable model for study of mesothelin. Stable overexpression of mesothelin in a pancreatic cancer cell line did not increase cell proliferation or anchorage-independent growth in vitro, suggesting that mesothelin is not necessarily a tumor progression factor. Surprisingly overexpression of mesothelin inhibited tumor formation in vivo in immunocompetent mice. Conclusion The mouse may be a good model for studying mesothelin in the context of an intact immune response. Mesothelin is not necessarily a tumor progression factor, and indeed mesothelin overexpression inhibited tumor growth in immunocompetent mice

Tangeretin protects renal tubular epithelial cells against experimental cisplatin toxicity

Objective(s): Cisplatin is an effective antineoplastic agent; its clinical utility, however, is limited by a few salient toxic side effects like nephrotoxicity. This study aimed to determine the potential protective effects of tangeretin, a citrus-derived flavonoid, against renal tubular cell injury in cisplatin-induced renal toxicity of rats.Materials and Methods: Tangeretin was injected intraperitoneally at 2.5 and 5 mg/kg doses for 10 days, and a single dose of cisplatin (8 mg/kg) was injected on the 7th day. Tests of kidney function and tubular injury in renal tissues and urine together with oxidative stress and inflammation markers were examined.Results: Tangeretin ameliorated cisplatin-induced elevations in serum creatinine, BUN, and histopathologic changes. It also attenuated kidney oxidative stress elicited by cisplatin as demonstrated by reduced MDA and increased GSH, CAT, and SOD activities, elevated Nrf2 expression and protein levels of its downstream effectors, HO-1 and NQO-1. Tangeretin further alleviated inflammation evoked by cisplatin as indicated by reduced NF-κB p65 subunit phosphorylation with a simultaneous decrement in its downstream effectors IL-1β and TNF-α expression and protein levels. Moreover, it declined caspase-3 protein levels and TUNEL positive cells in the kidneys, the markers of apoptosis and DNA fragmentation, thus improving renal endurance. Additionally, tangeretin mitigated renal levels of KIM-1 and NGAL, as well as urinary cystatin C and β2-microglobulin concentrations, the markers of renal tubular injury.Conclusion: Collectively, these data signify the binary profit of tangeretin: enhancement of renal protective mechanisms against cisplatin and attenuation of renal tubular cell injuries induced by the agent

Empagliflozin alleviates renal inflammation and oxidative stress in streptozotocin-induced diabetic rats partly by repressing HMGB1-TLR4 receptor axis

Objective(s): Empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, possesses verified anti-inflammatory and anti-oxidative stress effects against diabetic nephropathy. The present investigation aims to examine empagliflozin effects on the renal levels of high mobility group box-1 (HMGB1), a potent inflammatory cytokine, and its respective receptor toll-like receptor-4 (TLR-4) in STZ-induced diabetic rats.Materials and Methods: Empagliflozin at 10 mg/kg per os (p.o.) was administered for 4 weeks, starting 8 weeks after the induction of diabetes. Renal function, kidney inflammation, oxidative stress, and apoptosis markers as well as renal HMGB1, receptor for advanced glycation end products (RAGE), and TLR-4 levels were assessed.Results: In addition to down-regulating NF-κB activity in renal cortices, empagliflozin reduced renal levels of HMGB1, RAGE, and TLR-4. It alleviated renal inflammation as indicated by diminished renal expressions of inflammatory cytokines and chemokines like tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) and also decreased urinary levels of interleukin-6 (IL-6) and alpha-1 acid glycoprotein (AGP). Moreover, empagliflozin ameliorated renal oxidative stress as demonstrated by decreased renal malondialdehyde (MDA) and elevated renal activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX). It also suppressed renal caspase-3, the marker of apoptosis; and furthermore, enhanced renal function noticed by the declined levels of serum urea and creatinine.Conclusion: These findings underline that empagliflozin is able to attenuate diabetes-related elevations in renal HMGB1 levels, an influential inflammatory cytokine released from the necrotic and activated cells, and its correspondent receptors, i.e., RAGE and TLR-4