Momordica charantia L. Extract Protects Hippocampal Neuronal Cells against PAHs-Induced Neurotoxicity: Possible Active Constituents Include Stigmasterol and Vitamin E

Polycyclic aromatic hydrocarbons (PAHs) have been recognized to cause neurobehavioral dysfunctions and disorder of cognition and behavioral patterns in childhood. Momordica charantia L. (MC) has been widely known for its nutraceutical and health-promoting properties. To date, the effect of MC for the prevention and handling of PAHs-induced neurotoxicity has not been reported. In the current study, the neuroprotective effects of MC and its underlying mechanisms were investigated in mouse hippocampal neuronal cell line (HT22); moreover, in silico analysis was performed with the phytochemicals MC to decipher their potential function as neuroprotectants. MC was demonstrated to possess neuroprotective effect by reducing reactive oxygen species’ (ROS’) production and down-regulating cyclin D1, p53, and p38 mitogen-activated protein kinase (MAPK) protein expressions, resulting in the inhibition of cell apoptosis and the normalization of cell cycle progression. Additionally, 28 phytochemicals of MC and their competence on inhibiting cytochrome P450 (CYP: CYP1A1, CYP1A2, and CYP1B1) functions were resolved. In silico analysis of vitamin E and stigmasterol revealed that their binding to either CYP1A1 or CYP1A2 was more efficient than the binding of each positive control (alizarin or purpurin). Together, MC is potentially an interesting neuroprotectant including vitamin E and stigmasterol as probable active components for the prevention for PAHs-induced neurotoxicity.     

Hypomethylation of LINE-1 but not Alu in lymphocyte subsets of systemic lupus erythematosus patients

BackgroundT lymphocytes from SLE patients have a global decrease in the 5-methylcytosine content. Previous studies have identified hypomethylation in the promoter of several genes but there is limited study in the interspersed repetitive sequences (IRSs).MethodsWe examined and compared the methylation levels of long interspersed nuclear element 1 s (LINE-1) and Alu elements in normal and SLE CD4+ T lymphocytes, CD8+ T lymphocytes and B lymphocytes by the combined bisulfite restriction analysis-interspersed repetitive sequences (COBRA-IRS).ResultsHypomethylation of LINE-1 but not Alu was found in CD4+ T lymphocytes, CD8+ T lymphocytes, and B lymphocytes of SLE patient (P = 0.005, 0.002, and 0.007, respectively). Moreover, when the SLE patients were divided into active and inactive groups, LINE-1 hypomethylation was more significantly distinguished in both CD4+ and CD8+ T lymphocytes of patients from the active SLE group when compared to the controls. Surprisingly, Alu hypomethylation was also observed in CD8+ T lymphocytes from the inactive SLE group when compared to the normal controls (P = 0.0056).ConclusionsThe hypomethylation in each lymphocyte subset of SLE was IRSs specific, mainly found in LINE-1 rather than Alu.     

Different etiologies of graft loss and death in Asian kidney transplant recipients: a report from Thai Transplant Registry

Background

Kidney transplantation is the most performed solid organ transplantation in Thailand. Over 4000 patients have received kidney transplantation from 23 centers within the kingdom. This study sought to demonstrate the causes of graft loss and death in Thai patients receiving kidney transplant during the past decade.

Patients and Methods

The Thai Transplant Registry database was used to evaluate the causes of graft loss and death. This database was established since 1997, a total of 2298 kidney transplants were available for analysis. Graft loss was defined as return to dialysis, graft removal, retransplantation, or death of the recipients. Patient survival was analyzed by all deaths.

Results

Among 2298 recipients, 59% received organs from deceased donors. The mean age at transplantation was 42 years (SD 12) and 61% were male. The most common identified causes of the end-stage renal disease were chronic glomerulonephritis (25.3%) and hypertensive nephropathy (11.3%); half of those were unknown. Actuarial graft survival rates at 1 and 5 years were 89% and 73%, respectively. The common causes of graft loss were chronic allograft nephropathy (53%), acute rejection (15%), death with a functioning graft (15%), and transplant renal artery diseases (7%). The greatest proportion (64%) of deaths was infection owing to septicemia and/or pulmonary infection. The others were from cardiovascular deaths (12%), liver disease (6%), and malignancy (4%).

Conclusion

Graft survival rates were comparable with previous reports. However, the proportion of death with functioning graft and cardiovascular death as a cause of graft and patient loss is lower than that of Caucasian populations.     

Effects of curcuminoid supplement on cardiac autonomic status in high-fat–induced obese rats

ObjectiveSudden cardiac death in obesity is frequently associated with sympathetic activation due to an elevated plasma free-fatty acid (FFA) level. Curcuminoids, the phenolic yellowish pigments of turmeric, display antioxidative and lipid-lowering activities. We hypothesized that curcuminoids ameliorate cardiac sympathovagal disturbance in high-fat–induced obese rats.MethodsMale Wistar rats were divided into five groups. A normal-diet control (NDC) group received a normal-fat diet (12% calories as fat) and a high-fat–diet control (HDC) group received a high-fat diet (60% calories as fat) for 12 wk. Three other groups received high-fat diets with curcuminoid supplement at concentrations of 30 mg (HD₃₀), 60 mg (HD₆₀), and 90 mg (HD₉₀) per kilogram of body weight every day for 12 wk. Heart rate variability was determined to assess cardiac autonomic status at weeks 0 and 12.ResultsBody weight, visceral fat mass, plasma FFA, and glucose levels increased significantly in the HDC group compared with the NDC group. Low frequency power in normalized units (LFnu) and the ratio of LF to high-frequency power (HF) in the HDC group were significantly higher, whereas HFnu in the HDC group was significantly lower than in the NDC group. Plasma FFA levels correlated significantly with LFnu and LF/HF ratio. Compared with the HDC group, plasma FFA, glucose levels, LFnu, and LF/HF ratio were significantly decreased in the HF₃₀, HF₆₀, and HF₉₀ groups.ConclusionElevated plasma FFA in high-fat–induced obese rats is associated with an increased LF/HF ratio, an expression of sympathovagal disturbance. Curcuminoid supplementation ameliorates cardiac autonomic imbalance in high-fat–fed rats, probably due to its lipid-lowering effect.     

A prevalence of posttransplantation cancers compared with cancers in people with human immunodeficiency virus/acquired immunodeficiency syndrome after highly active antiretroviral therapy

Background

Organ transplant recipients and human immunodeficiency virus & acquired Immunodeficiency Syndrome (HIV/AIDS) patients have immune deficiencies that are possible mechanisms to develop malignancy. The type of cancers associated with these 2 conditions might elucidate this premise.

Aim

Our aim was to compare prevalence and type of cancers between kidney transplant recipients and patients with HIV/AIDS.

Patients and Methods

We retrospectively reviewed 344 patients who underwent kidney transplantation from 1973 to 2007 compared them with 863 subjects with HIV/AIDS at the HIV-Netherlands/Australia/Thailand Research Collaboration (HIV-NAT) from 1997 to 2007. AIDS-defining cancers were excluded from the analysis. We compared the relative tumor risk with the age- and gender- matched general population of metropolitan Bangkok.

Results

The overall cancer risk for kidney transplant recipients (standardized incidence ratio [SIR] = 4.21) was comparable with HIV-infected patients (SIR = 3.88). Uroepithelial cancer was the most prevalent type in kidney transplant recipients, whereas cervical cancer was the most common malignancy in HIV-infected patients. The risks of developing hepatoma and non-Hodgkin's lymphoma were comparable between the groups.

Conclusion

Kidney transplant recipients and HIV-infected patients show increased overall risks of certain types of cancers.     

Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias

MS-275 is a benzamide derivative with potent histone deacetylase (HDAC) inhibitory and antitumor activity in preclinical models. We conducted a phase 1 trial of orally administered MS-275 in 38 adults with advanced acute leukemias. Cohorts of patients were treated with MS-275 initially once weekly x 2, repeated every 4 weeks from 4 to 8 mg/m2, and after 13 patients were treated, once weekly x 4, repeated every 6 weeks from 8 to 10 mg/m2. The maximum-tolerated dose was 8 mg/m2 weekly for 4 weeks every 6 weeks. Dose-limiting toxicities (DLTs) included infections and neurologic toxicity manifesting as unsteady gait and somnolence. Other frequent non-DLTs were fatigue, anorexia, nausea, vomiting, hypoalbuminemia, and hypocalcemia. Treatment with MS-275 induced increase in protein and histone H3/H4 acetylation, p21 expression, and caspase-3 activation in bone marrow mononuclear cells. No responses by classical criteria were seen. Our results show that MS-275 effectively inhibits HDAC in vivo in patients with advanced myeloid leukemias and should be further tested, preferably in patients with less-advanced disease.     

Association of interferon-gamma gene polymorphism (+874A) with arthritis manifestation in SLE

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which genetic factors strongly influence susceptibility. Cytokines such as the interferon-gamma (IFNG) gene play a key role in controlling the immunity and inflammation, and therefore their polymorphisms may affect these genes’ expression levels among individuals. We investigated the frequency of IFNG gene intron (+874) polymorphism, previously reported to be associated with IFNG production, in SLE patients compared to a control group. This population-based case–control study includes 154 SLE patients and 154 healthy control subjects with similar ethnic backgrounds. The genotyping was determined by polymerase chain reaction sequence-specific primer method and using the Chi-squared test for analyzing the association between this single-nucleotide polymorphism and SLE. The allele frequencies of the IFNG (+874) gene polymorphism were not significantly different between SLE patients and control subjects (72.7 vs 77%). However, there was a significant association between A dominance model of inheritance with arthritis (odds ratio = 7.64, 95% confidence interval = 1.56–41.64, P = 0.006, P _c = 0.03). The result suggested that the +874 intron polymorphism of IFNG can be used as the marker for SLE susceptibility with arthritis in the Thai population.     

Clinical performance of the new glucometer in the nursery and neonatal intensive care unit

Background: Performance of point‐of‐care (POC) glucometers in newborns have been unsatisfactory in low glucose concentration range and the effects of different hematocrit levels on glucose measurements have also demonstrated in currently used POC glucometers. Methods: The aim of this study was to evaluate the performance of the new glucometer (Nova‐Statstrip^®; Nova Biomedical, Waltham, MA, USA) compared to the reference method. Venous blood specimens of neonates were collected and tested by the two glucometers. Standard reference was performed using the hexokinase method within 10 min of blood collection. Hematocrit and total serum bilirubin measurements were performed simultaneously. Results: One hundred and fifty‐one blood specimens were collected and measured by the reference method with plasma glucose concentrations ranging from 12 to 371 mg/dL. Twenty‐one specimens had plasma glucose concentrations <45 mg/dL. At plasma glucose concentrations less than 75 mg/dL, the Statstrip^® achieved 93% in the tests for discrepancy < 15 mg/dL. At a glucose concentration more than 75 mg/dL, 97% of the Statstrip^® readings were within 20% of the reference values. The mean difference (±2SD) of the Statstrip^® was 2.8 (?14.1, 19.7) mg/dL. At a hypoglycemic level (<45 mg/dL), it showed a sensitivity of 95.2%. No significant interference of hematocrit or total serum bilirubin was found on the mean bias of the Statstrip^®. Conclusion: The new glucometer (Nova‐Statstrip^®) could be used for point‐of‐care blood glucose measurement in neonates as it showed a narrow margin of error and had no hematocrit or bilirubin interference.