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It is unclear how the immune system controls the transition from latent tuberculosis (TB) infection (LTBI) to active pulmonary infection (PTB). Here, we applied mass spectrometry cytometry time-of-flight (CyTOF) analysis of peripheral blood mononuclear cells to compare the immunological landscapes in patients with high tuberculous bacillary load PTB infections and LTBI. A total of 32 subjects (PTB [n = 12], LTBI [n = 17], healthy volunteers [n = 3]) were included. Participants with active PTBs were phlebotomized before administering antituberculosis treatment, whereas participants with LTBI progressed to PTB at the time of household screening. In the present study, CyTOF analysis identified significantly higher percentages of mucosal-associated invariant natural killer T (MAIT NKT) cells in subjects with LTBI than in those with active PTB and healthy controls. Moreover, 6 of 17 (35%) subjects with LTBI progressed to active PTB (LTBI progression) and had higher proportions of MAIT NKT cells and early NKT cells than those without progression (LTBI non-progression). Subjects with LTBI progression also showed a tendency toward low B cell levels relative to other subject groups. In conclusion, MAIT NKT cells were substantially more prevalent in subjects with LTBI, particularly those with progression to active PTB. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic non-infectious inflammatory skin disease caused by genetic and environmental predispositions. There is a Thai herbal remedy for psoriasis recorded in Wat Pho's marble inscriptions, consisting of Dictyophora indusiate Fisch, Psilocybe cubensis (Earle) Sing, and sesame oil. Objective: To compare the efficacy and safety of a Thai herbal remedy as an alternative treatment to the standard treatment of 0.1% triamcinolone lotion in patients with mild chronic plaque psoriasis. Materials and Methods: A randomized, split-body controlled design was conducted in 30 mild chronic plaque-type psoriasis patients with symmetrically distributed psoriasis rashes. Each patient was randomized to apply a Thai herbal remedy on a rash on one side of the body and 0.1% triamcinolone lotion on the other side, using the same dosage of twice daily for eight weeks. Efficacy was assessed at week 1, 2, 4, and 8 by the Targeted Area Score (TAS). The Self-Assessment Score (SAS) at week 8 was compared to the baseline. Safety was assessed through the interviews at each visit. Product satisfaction was evaluated by the visual analog scale (VAS). Results: The TAS and SAS for erythema, desquamation, and induration decreased in both treatment groups, with no significant difference. However, product satisfaction in color (p=0.012), odor (p=0.013), and absorption (p=0.003) were significantly higher in the 0.1% triamcinolone lotion group. Conclusion: The present study showed that the Thai herbal remedy was safe and efficacious in treating chronic plaque-type psoriasis, therefore, can be used as an alternative treatment. [ABSTRACT FROM AUTHOR]

Darier's disease is an autosomal dominantly inherited skin disorder characterized by loss of adhesion between epidermal cells, breakdown of desmosome–keratin filaments, and abnormal keratinization. ATP2A2 has been identified as the causative gene of Darier's disease. This gene encodes the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) isoform 2 pump, which transports Ca2+ from the cytosol into the endoplasmic reticulum lumen to maintain a low cytosolic Ca2+ concentration. Using indirect immunofluorescence and biochemical analysis, we investigated the distribution of key desmosomal proteins in normal human and Darier's disease keratinocytes under various calcium conditions. We show that inhibition of SERCA by thapsigargin in normal human keratinocytes impairs the trafficking of the desmoplakins, desmoglein, and desmocollin to the cell surface; these proteins show a diffuse cytoplasmic distribution and, together with plakoglobin, form detergent-insoluble aggregates. In Darier's disease keratinocytes, only the trafficking of desmoplakin is significantly inhibited; in these cells, desmoplakin forms insoluble aggregates when extracted with mild detergent. In contrast, the transmembrane proteins desmoglein and desmocollin are efficiently transported to the cell surface. These proteins, along with plakoglobin, remain equally distributed between detergent-soluble and -insoluble fractions. We also demonstrate an interaction between SERCA2 and desmoplakin during differentiation. Our results provide further insights into the critical role of calcium ATPases in maintaining epidermal integrity. [ABSTRACT FROM AUTHOR]

Darier's disease is an autosomal dominantly inherited skin disorder, characterized by loss of adhesion between epidermal cells and abnormal keratinization. ATP2A2 encoding the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA)2 has been identified as the defective gene in Darier's disease. All mutations previously reported occur in the region of ATP2A2 encoding both SERCA2a and SERCA2b isoforms. These isoforms result from alternative splicing of exon 20, with SERCA2b being the major isoform expressed in the epidermis. In this report, we studied a family affected with Darier's disease and identified a deletion (2993delTG) in a region of exon 20 of ATP2A2 , which is specific for SERCA2b. This heterozygous mutation predicts a frameshift with a premature termination codon (PTC+32aa) in the eleventh transmembrane domain of SERCA2b. It segregates with the disease phenotype in the family members tested, and functional analysis shows a drastic reduction of the expression of the mutated protein in comparison with the wild-type SERCA2b. Our result suggests that the mutated allele causes the disease phenotype through loss of function of SERCA2b isoform. This finding indicates that SERCA2b plays a key role in the biology of the epidermis, and its defects are sufficient to cause Darier's disease. [ABSTRACT FROM AUTHOR]

An abstract of the article "RV306, an Evaluation of a 48 Week ALVAC-HIV AIDSVAX B/E Vaccination Regimen in Thailand: Participation Rates for Optional Specimen Collections" by Punnee Pitisuttithum, Sorachai Nitayaphan, Suwat Chariyalertsak and colleagues is presented.

Steady-state and rapid kinetic studies were conducted to functionally characterize the overall and partial reactions of the Ca[sup 2+] transport cycle mediated by the human sarco(endo)plasmic reticulum Ca[sup 2+]-ATPase 2 (SERCA2) isoforms, SERCA2a and SERCA2b, and 10 Darier disease (DD) mutants upon heterologous expression in HEK-293 cells. SERCA2b displayed a 10-fold decrease in the rate of Ca[sup 2+] dissociation from E[sub 1]Ca[sub 2] relative to SERCA2a (i.e. SERCA2b enzyme manifests true high affinity at cytosolic Ca[sup 2+] sites) and a lower rate of dephosphorylation. These fundamental kinetic differences explain the increased apparent affinity for activation by cytosolic Ca[sup 2+] and the reduced catalytic turnover rate in SERCA2b. Relative to SERCA1a, both SERCA2 isoforms displayed a 2-fold decrease of the rate of E[sub 2] to E[sub 1]Ca[sub 2] transition. Furthermore, seven DD mutants were expressed at similar levels as wild type. The expression level was 2-fold reduced for Gly[sup 23] → Glu and Ser[sup 920] → Tyr and 10-fold reduced for Gly[sup 749] → Arg. Uncoupling between Ca[sup 2+] translocation and ATP hydrolysis and/or changes in the rates of partial reactions account for lack of function for 7 of 10 mutants: Gly[sup 23] → Glu (uncoupling), Ser[sup 186] → Phe, Pro[sup 602] → Leu, and Asp[sup 702] → Asn (block of E[sub 1]∼P(Ca[sub 2]) to E[sub 2]-P transition), Cys[sup 318] → Arg (uncoupling and 3-fold reduction of E[sub 2]-P to E[sub 2] transition rate), and Thr[sup 357] → Lys and Gly[sup 769] → Arg (lack of phosphorylation). A 2-fold decrease in the E[sub 1]∼P(Ca[sub 2]) to E[sub 2]-P transition rate is responsible for the 2-fold decrease in activity for Pro[sup 895] → Leu. Ser[sup 920] → Tyr is a unique DD mutant showing an enhanced molecular Ca[sup 2+] transport activity relative to wild-type SERCA2b. In this case, the disease may be a consequence of the low expression level and/or reduction of Ca[sup 2+] affinity and sensitivity to inhibition by lumenal Ca[sup 2+]. [ABSTRACT FROM AUTHOR]

Objective: To study and to compare the medical and economic burden among chronic hepatitis B (CHB) patients., Material and Method: A prospective observational study was conducted among 129 adult CHB patients. The medical burden was assessed by using the EuroQol-5D (EQ-5D) and the Chronic Liver Disease Questionnaire (CLDQ) at initial day, the six and 12-month follow-up. The economic burden was assessed in term of total cost per case per year, Results: At one-year follow-up, the mean age of 129 patients was 41.6 (SD = 11.8) years. For medical burden at over time, CHB with antiviral drugs (ARV) for hepatitis B infection had a significant decreased in percentage of anxiety, and increased the mean (SD) CLDQ score. The mean total costs per case per year of CHB without ARV (52 cases), CHB with antiviral drugs (50 cases), and CHB with cirrhosis/hepatocellular carcinoma (HCC) with ARV (27 cases) were significantly different (p < 0.001) with USD 615.9 (SD = 688.0), 1,777.4 (SD = 1,220.4), and 2,651.3 (SD = 3,885.0), respectively., Conclusion: CHB causes a great economic burden in Thailand Early antiviral drugs treatment prevents complication in CHB patients.

Generic fixed dose combination stavudine (d4T), lamivudine (3TC) and nevirapine (NVP), named GPO-VIR is recommended in the HIV treatment guidelines for Thailand. The long term effectiveness and adverse effects of this drug combination for the treatment of HIV were evaluated in an ambispective study at Bamrasnaradura Infectious Diseases Institute, Nonthaburi Province, Thailand from March 2002 to January 2006. A total of 152 adult treatment naive HIV patients who had received at least 12 months of GPO-VIR were enrolled. The median (IQR) CD4 cell count increased from 23 (8-94) cells/microl at baseline to 126 (38-180), 136 (98-189), 199 (141-255) and 334 (243-414) cells/microl at 3, 6, 12 and 24 months (p < 0.001), respectively. The median (IQR) percentage of body weights increased from baseline by 3.0% (0.3-6.3), 6.2% (2.2-9.3), 7.3% (3.9-10.9) and 8.1% (3.4-11.9) at 3, 6, 12 and 24 months, respectively and then remained at a plateau until the end of the 3-year study. The occurrence of new opportunistic infections decreased significantly (p < 0.001) with GPO-VIR treatment. Drug resistance occurred in 5 cases (3.3%) with a median (IQR) time of 18.0 (16.5-32.5) months to occurrence. Adverse effects included hypercholesterolemia (43.2%), lipodystrophy (35.5%), hypertriglyceridemia (25%), hypertension (13.1%), peripheral neuropathy (11.9%), hyperlactatemia (2.6%) and lactic acidosis (1.3%). Thirty-six patients (27%) switched from GPO-VIR to other anti-retroviral drugs regimens due to lipodystrophy. This study showed GPO-VIR had clinical and immunological benefits, but one-third of patients had adverse effects.

Complementary remedies represent a potential alternative treatment for chronic diseases, including HIV/AIDS cases not meeting criteria for using highly active antiretroviral therapy (HAART). This study evaluated the safety and efficacy of CKBM-A01, a Chinese herbal medicine, and patient quality of life (QoL). Asymptomatic HIV patients with CD4 counts of 250-350 cells/microl were recruited into this open-labeled trial. Liquid CKBM-A01 was prescribed for a 36-week period. Study participants recorded all symptoms themselves on diary cards. Study parameters, including CD4 cell counts, HIV viral loads, and blood chemistry, were periodically monitored and questionnaires were used to assess QoL and to help with risk reduction. Eighteen volunteers, mean age (+/- SD) 32.07 (+/- 6.88) years, had a median (interquartile range, IQR) baseline CD4 count of 292 (268.50-338.25) cells/microl. No serious drug-related adVerse events due to CKBM-A01 were detected during the study. Intermittent diarrhea was reported in 55.6%, weakness or skin rash/itching in 50%, and increased bowel movement in 33.7%. No significant changes in log viral load or CD4 cell counts were observed at the end of the study. Most of the volunteers (72.2%) expressed satisfaction with CKBM-A01 and had a positive perception. Common colds and nasal symptoms were significantly lower during treatment (p = 0.019). CKBM-A01 appeared to be safe but gave no significant improvement in QoL in asymptomatic HIV patients, and gave no significant improvement in the treatment of HIV based on CD4 cell counts and viral loads.

HIV-infected patients with active tuberculosis (TB) having CD4 counts < 100/mm3 and who were antiretroviral therapy (ART) naïve were reviewed retrospectively to determine the outcomes of their tuberculosis infection. All patients received ART at or after receiving anti-TB treatment. Clinical manifestations, treatment regimens and outcomes were analyzed. Of 101 patients, 62 (61.4%) completed TB treatment. Of these, 53.2% were treated with a 6-month standard TB regimen, while the rest were treated with prolonged TB regimens. The median interval between anti-TB treatment and ART was 68 days (range: 0-381). Among the clinically cured patients 66.1% received rifampin concomitantly with nevirapine, and 32.3% received rifampin concomitantly with efavirenz. The treatment success rate was 75.6%, with a mortality rate of 6.1%. The risk factors for death were resistant TB (p = 0.03) and poor compliance (p < 0.05). Seven point nine percent had multi-drug resistant TB. Possible or probable immune reconstitution inflammatory syndrome (IRIS) was seen in 15 cases (14.9%). No life-threatening IRIS was reported, and it did not affect disease outcome (p = 0.5). A shorter time between anti-TB treatment and ART onset was associated with the occurrence of IRIS (31 days vs 90 days; p < 0.05). Regarding adverse drug effects, 44.6% had side effects due either to anti-TB drugs or ART. Sixty-six point one percent of them occurred within the first 2 months of TB treatment, and 43 (76.8%) had to stop or change either anti-TB treatment or ART. The mortality rate with TB and HIV on ART was low and the occurrence of IRIS did not carry any additional mortality.

Objectives: To assess the efficacy and safety of generic fixed-dose combination of stavudine, lamivudine and nevirapine; GPO-vir in advanced HIV infection., Material and Method: Open-label combined prospective and retrospective study involving 102 HIV infected patients with baseline CD4 cell count < 100 cells/mm3. All patients received GPO-vir for 48 weeks. The CD4 cell count and plasma viral load (pVL) was measured at 48 weeks., Results: The median baseline CD4 cell count and pVL were 13 cells/mm3 and 363,500 copies/ml, respectively. At 48 weeks, the median CD4 cell count increased to 191 cells/mm3 and 63.7% in intention-to treat and 82.3% in on-treatment analysis had pVL < 50 copies/ml. There was no significant difference in pVL between patients with baseline pVL > 100,000 or < or = 100,000 copies/ml (p = 0.312). The incidence of hepatotoxicity, rash and peripheral neuropathy was 4.9%, 14.7% and 6.9%, respectively., Conclusion: GPO-vir was well tolerated and effective in increasing CD4 cell count and suppressing plasma viremia in advanced HIV infection during the 48 weeks follow-up period.