Predisposing factors for nevirapine toxicity among AIDS patients with low baseline CD4 count

The objective of the study was to determine the predisposing factors and incidence of toxicity among AIDS patients treated with a nevirapine (NVP)-based regimen in clinical practice. A retrospective cohort study of representative samples of AIDS patients treated with a NVP-based regimen was performed. A total of 206 adult HIV/AIDS cases with median age (IQR) 33 years (range, 29-38 years), 51% male, treated between January 2004-December 2005, were included. Most (92.2%) of the patients were na?ve to antiretroviral drug. The incidence of NVP toxicity was 1.09/100 person-months. The median onset time was 4 weeks post NVP initiation (2.57 weeks for skin toxicity and 12.43 weeks for hepatic toxicity). History of drug allergy and NVP toxicity were significantly associated (p = 0.006), as were sulfamethoxazole allergy and toxicity (p = 0.015). Regarding concomitant medication, concurrent anti-tuberculosis drugs significantly increased the risk of NVP associated liver toxicity (p = 0.001). Therefore, it is important to monitor adverse events from NVP, including liver function tests among HIV/AIDS patients with history of drug allergy, especially against sulfamethoxazole, and those concurrently treated with antituberculosis drugs.     

Lysosomal enzyme activities in normals and in patients with chronic liver diseases

The maximal activities of liver lysosomal enzymes (acid phosphatase and cathepsin D) were found to be increased in patients with chronic active hepatitis, cirrhosis and primary hepatocellular carcinoma. The ratio between maximal and basal activity (an expression of the degree of retention of the enzymes to lysosome) of acid phosphatase was significantly decreased in patients with chronic active hepatitis and cirrhosis whereas that of cathepsin D did not show any significant changes between normal and various liver disorders. Serum levels of both the enzymes were elevated significantly in patients with cirrhosis and primary hepatocellular carcinoma.     

Detection of group B rotavirus in an adult with acute gastroenteritis in Yangon,Myanmar

In Yangon, Myanmar, a human group B rotavirus was first detected in 2007 in a stool specimen from a sporadic case of acute gastroenteritis in an adult. The strain was designated as MMR‐B1. The full‐length sequences of the MMR‐B1 genes encoding VP7, VP4 (VP5* and VP8*), VP6, and NSP4 were determined for genetic characterization. These four MMR‐B1 genes showed considerable higher sequence identities (97.2–98.4%) to those of group B rotaviruses detected in India (CAL‐1 in 1998) and Bangladesh (Bang373 and Bang544 in 2000 and 2001, respectively) than to those of Chinese strains (90.7–93.6%) (ADRV and WH‐1 in 1982 and 2002, respectively). Phylogenetically, the four genes of MMR‐B1 were clustered into the Indian–Bangladeshi lineage. Although the deduced amino acid sequences of MMR‐B1 were similar to those of strains CAL‐1 and Bang373, several amino acids in VP8* were found to be different from those of the group B rotaviruses described previously. The first detection in Myanmar of a human group B rotavirus suggested endemic distribution or expansion of the group B rotavirus of the Indian–Bangladeshi lineage in Southeast Asia. J. Med. Virol. 81:1968–1974, 2009. © 2009 Wiley‐Liss, Inc.     

Novel SLC4A11 mutations in patients with recessive congenital hereditary endothelial dystrophy (CHED2). Mutation in brief #958. Online

Autosomal recessive congenital hereditary endothelial dystrophy (CHED2) is a severe and rare corneal disorder that presents at birth or shortly thereafter, characterized by corneal opacification and nystagmus. Recently the gene for CHED2 was identified and seven different mutations in the SLC4A11 gene were reported. Here, we report seven novel mutations and two previously identified mutations in families from India and the United Kingdom with recessive CHED. The novel changes include two nonsense (p.Trp240X; p.Gln800X) three missense (p.Glu143Lys; p.Cys386Arg; p.Arg755Trp) and two splice site mutations (c.2240+1G>A; c.2437-1G>A). Interestingly, the c.2398C>T (p.Gln800X) and c.2437-1G>A identified in two affected siblings represent the first compound heterozygous mutations in the SLC4A11 gene.     

Long-term outcomes in asians after acute primary angle closure

PURPOSE: To determine the long-term outcome of Asian eyes with an acute attack of primary angle closure (APAC) and to identify risk factors at presentation associated with the development of glaucomatous optic nerve damage. DESIGN: Cross-sectional observational case series. PARTICIPANTS: Ninety individuals who were initially seen with APAC 4 to 10 years previously at 2 Singapore hospitals. METHODS: All subjects underwent a complete eye examination, including visual acuity, visual field testing, dilated eye examination, and optic nerve head photography. The optic discs were judged clinically and photographically as to whether there was glaucomatous optic neuropathy present, and visual fields were assessed for corresponding visual field loss. All visual fields and optic nerve photographs underwent a second evaluation by an experienced, but masked, glaucoma specialist, who assessed whether the changes were compatible with glaucoma. MAIN OUTCOME MEASURES: The main outcome measures were blindness (defined as best-corrected visual acuity worse than 6/60 and/or central visual field of less than 20 degrees in the attack eye) and glaucomatous optic neuropathy (GON). RESULTS: A total of 90 of 170 eligible subjects (65.2%) were examined. All subjects were Asian and were predominantly Chinese (78 subjects [86.7%]). There were 61 females (67.8%), and the age of the subjects was 62.0+/-9.0 years (mean +/- standard deviation) at the time of APAC, with a mean duration of 6.3+/-1.5 years from the time of the APAC episode to the study examination. Sixteen (17.8%) subjects were blind in the attack eye; half of the cases of blindness were caused by glaucoma. Forty-three subjects (47.8%) had GON, with 13 eyes (15.5%) having markedly cupped optic discs (cup-to-disc ratio >0.9). Thirty-eight eyes (58%) had best-corrected vision worse than 6/9, with cataract responsible for close to half the cases of poor vision. There were no identifiable risk factors related to the APAC episode that were significantly associated with the presence of GON. CONCLUSIONS: Several years after being seen with APAC, 17.8% of subjects examined were blind in the attack eye, and almost half had glaucomatous optic nerve damage. Vision was also reduced in a large number of individuals, largely from unoperated cataract. Subjects with APAC would benefit from regular follow-up to monitor for visual field decline and glaucoma development.     

Maintained Salivary Function after Brachytherapy in Patients with Head and Neck Carcinomas - Evaluation Using Quantitative Salivary Gland Scintigraphy

The purpose of this study was to determine whether or not salivary gland dysfunction occurs within the first three months after brachytherapy in patients with head and neck carcinoma. Of the 20 patients with head and neck squamous cell carcinoma included in this study, 11 were treated with brachytherapy and the remaining 9 patients received external irradiation. All the patients underwent a salivary gland scintigraphy before and after radiotherapy. The scintigraphic parameters of each major salivary gland were then compared before and after the radiotherapy. In the brachytherapy group, none of the scintigraphic functional parameters showed a significant change before and after the radiotherapy. In contrast, all of the parameters with the exception of the uptake ratio (UR) of the submandibular glands significantly decreased after external irradiation. This observation was to be expected owing to the different irradiation doses administered by the two techniques. The scintigraphic technique used to evaluate salivary gland function should be used in future intensity-modulated radiation therapy salivary-gland-sparing studies in order to evaluate both the acute and chronic effects of irradiation in head and neck cancer patients.     

Endothelin receptors in cultured and native human radial artery smooth muscle.

In human vascular smooth muscle cells endothelin-1, acting at both endothelin A and endothelin B receptors, has been demonstrated to be both a potent vasoconstrictor and mitogen. Our aim was to study the functional expression of endothelin receptors in human radial artery smooth muscle using both native tissue and cultured cells (RASMCs). Radial artery smooth muscle cells were cultured from arterial explants and loaded with the calcium fluorescent dye fura-2. Cells responded to endothelin-1 and a variety of other vasoconstrictors with rises in cytoplasmic calcium ([Ca2+]c). Arterial rings responded to endothelin-1 with an increase in tension. The response of both cells and arterial rings to endothelin-1 was characterized using the selective endothelin A receptor antagonist BQ123 and the endothelin B receptor antagonist BQ788. The RASMCs were found to express [Ca2+]c responses consistent with the expression of only the endothelin A receptor. Endothelin-1-mediated vasoconstriction in radial artery rings was unaffected by BQ788 but was completely blocked by BQ123. Using the selective radioligands [125I]-PD151242 and [125I]-BQ3020 and a combination of in vitro receptor autoradiography and isolated cell preparations, endothelin A receptors were confirmed to be present on RASMCs and on arterial sections, whereas endothelin B binding was barely detectable on native smooth muscle and on RASMCs.     

Sex-specific association of rs16996148 SNP in the NCAN/CILP2/PBX4 and serum lipid levels in the Mulao and Han populations

Background

This study evaluated the relationship between ulcerative colitis and obesity, which are both chronic diseases characterized by inflammation and increases in immune cells and pro-inflammatory cytokines.

Methods

Mice with chronic ulcerative colitis induced by 2 cycles of dextran sodium sulfate (DSS) in the first and fourth week of the experiment were fed a high-fat diet (HFD) to induce obesity by 8 weeks. The animals were divided into 4 \ groups (control, colitis, HFD and colitis + HFD).

Results

Obesity alone did not raise histopathology scores, but the combination of obesity and colitis worsened the scores in the colon compared to colitis group. Despite the reduction in weight gain, there was increased inflammatory infiltrate in both the colon and visceral adipose tissue of colitis + HFD mice due to increased infiltration of macrophages, neutrophils and lymphocytes. Intravital microscopy of VAT microvasculature showed an increase in leukocyte adhesion and rolling and overexpression of adhesion molecules compared to other groups. Moreover, circulating lymphocytes, monocytes and neutrophils in the spleen and cecal lymph nodes were increased in the colitis + HFD group.

Conclusion

Our results demonstrated the relationship between ulcerative colitis and obesity as aggravating factors for each disease, with increased inflammation in the colon and adipose tissue and systemic alterations observed in the spleen, lymph nodes and bloodstream.     

Asian ginseng enhances the anti-proliferative effect of 5-fluorouracil on human colorectal cancer: Comparison between white and red ginseng

Previous studies showed that Asian ginseng, Panax ginseng C.A. Meyer, may have anti-cancer properties. However, there is limited data exploring the use of Asian ginseng as an adjuvant to chemotherapy, and minimal mechanistic studies related to their possible synergistic activities. In this study, the content of 8 ginsenosides, Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1 and Rg3, in the extracts of white ginseng (WG) and red ginseng (RG) were determined by HPLC. Using HCT-116 human colorectal cancer cells, we compared the efficacy of WG and RG. We evaluated the synergy between ginseng and 5-fluorouracil (5-FU), and explored the mechanism of their anti-proliferative effects. As single extract, WG or RG used at concentrations of 0.1, 0.2 and 0.3 mg/mL, inhibited HCT-116 cell proliferation in a concentration-related manner. WG at 0.2 mg/mL did not show obvious synergy with 5-FU co-treatment, while RG at 0.2 and 0.3 mg/mL significantly enhanced the anti-proliferative effects of 5-FU at concentrations of 10, 50 and 100 μM (P < 0.05). Using flow cytometric assay, RG 0.3 mg/mL did not affect cancer cell apoptotic induction activity. However, the RG induced cell cycle arrest in the G1 phase, while 5-FU arrested the cell in the S phase. Different ginsenoside profiles are responsible for the observed differences in pharmacological effects. The effects of 8 ginsenosides on HCT-116 cells were assayed. Rd and Rg3 showed positive anti-proliferative effect. Our data suggested a potential for RG as an adjuvant therapy in the treatment of colorectal cancer, via a synergistic action.