Lack of augmenting effect of interferon-γ on dengue virus multiplication in human peripheral blood monocytes

The effect of interferon—γ (IFN-γ) on dengue virus multiplication in human peripheral blood mono-cytes was investigated. Enriched monocytes were treated with IFN-γ and then infected with dengue virus type 2 either directly or in the presence of optimal infection-enhancing levels of antibodies. Pretreatment of monocytes from dengue-immune donors with 100 IU/ml of IFN-γ caused 12- to 97-fold and 13- to 137-fold reduction of virus yields at 24 hr after infection in the absence and presence of an anti-flavivirus monoclonal antibody, respectively. IFN-γ also diminished virus yields when infection of monocytes from a donor who lacked anti-dengue antibody was enhanced 40-fold. The percentage of infected monocytes in IFN-γ-pretreated cultures was similarly reduced. Dominance of the antiviral effect of IFN-γ in monocytes is in contrast to an augmenting effect previously observed in the promonocytic cell line U937. © 1995 Wiley-Liss, Inc.     

Controlled Aloin Release from Crosslinked Polyacrylamide Hydrogels: Effects of Mesh Size,Electric Field Strength and a Conductive Polymer

The aim of this paper is to investigate the effects of hydrogel mesh size, a conductive polymer, and electric field strength on controlled drug delivery phenomena using drug-loaded polyacrylamide hydrogels prepared at various crosslinking ratios both with and without a conductive polymer system. Poly(p-phenylene vinylene), PPV, as the model conductive polymer, was used to study its ability to control aloin released from aloin-doped poly(p-phenylene vinylene)/polyacrylamide hydrogel (aloin-doped PPV/PAAM). In the passive release, the diffusion of aloin from five aloin-doped PPV/PAAM hydrogel systems each was delayed ranging from during the first three hours to during the first 14 h due to the ionic interaction between the anionic drug and PPV. After the delayed periods, aloin could diffuse continuously into the buffer solution through the PAAM matrix. The amount of aloin released from the aloin-doped PPV/PAAM rose with increasing electric field strength as a result of the three mechanisms: the expansion of PPV chains inside the hydrogel, iontophoresis, and the electroporation of the matrix pore size, combined. Furthermore, the conductive polymer and the electric field could be used in combination to regulate the amount of release drug to a desired level, to control the release rate, and to switch the drug delivery on/off.     

Immunosuppressive Prednisolone Enhances Early Cholangiocarcinoma in Syrian Hamsters with Liver Fluke Infection and Administration of N-nitrosodimethylamine

Chronic infection with Opisthorchis viverrini for many years has been associated with the development of hepatobiliary diseases including cholangiocarcinoma. It is well known that inflammation is a key component of the tumor microenvironment, and that chronic inflammation plays an important role in tumorigenesis. Therefore, in this study cholangiocarcinogenesis was induced in Syrian hamsters in order to observe the cancer-related inflammation. The Syrian hamsters were divided into 5 groups: uninfected controls; normal Syrian hamsters infected with O. viverrini (OV); immunosuppressed Syrian hamsters infected with O. viverrini (OVis); normal Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCA); and immunosuppressed Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCAis). Syrian hamster livers were later observed for gross pathology and histopathological changes; COX2 was analyzed by immunohistochemical staining. We found a decreased number of inflammatory cells surrounding the hepatic bile duct in the OVis group, but not in the OV and CCAis groups. However, in the CCAis group (with suppressed immunity) early appearance and greater severity of cholangiocarcinoma were observed; gross pathological examination revealed many cancer nodularities on the liver surface, and histopathological studies showed the presence of cancer cells, findings which correlated with the predominant expression of COX2. The present study suggests that host immune responses are intended to ameliorate pathology, and they are also crucially associated with pathogenesis in O. viverrini infection; the unbalancing of host immunity may enhance cancer-related inflammation.     

Factors associated with death among HIV-uninfected TB patients in Thailand, 2004–2006

Objectives  In countries with both TB and human immunodeficiency virus (HIV) epidemics, HIV is known to be the most powerful risk factor for death during tuberculosis (TB) treatment. Few recent studies have evaluated risk factors for death among HIV-uninfected TB patients in these countries. We analysed data from a multi-province demonstration project in Thailand to answer this question.
Method  We prospectively collected data from HIV-uninfected TB patients treated for TB in four provinces and the national infectious diseases hospital in Thailand from 2004–2006. Standard WHO definitions were used to classify treatment outcomes. We used log-binomial multivariate regression to calculate adjusted relative risk (aRR) and 95% confidence intervals (CI) for factors associated with death.
Results  Of 5318 cases, 441 (8%) died during TB treatment. The mean age was 47 years (range 8 months–97 years). Multidrug-resistant (MDR)-TB was diagnosed in 62 (1%). In multivariate analysis, patients older than 44 years were significantly more likely to die than patients aged 15–44 years [age 45–64, aRR 2.9 (CI 2.2–3.8)] [age > 64 years, aRR 5.0 (CI 3.9–6.6)]. Other independent risk factors for death included Thai nationality [aRR 3.9 (CI 1.6–9.5)], MDR-TB [aRR 2.8 (CI 1.7–4.8)], not being married [aRR 1.4 (CI 1.2–1.7)], and living in Chiang Rai province [aRR 2.7 (CI 1.7–4.4)].
Conclusions  The death rate was high among HIV-uninfected TB patients in Thailand. Efforts to improve TB diagnosis and treatment in the elderly and to improve MDR-TB treatment may help reduce mortality.     

Novel KIR genotypes and gene copy number variations in northeastern Thais

KIR (Killer Immunoglobulin‐like Receptor) variants influence immune responses and are genetic factors in disease susceptibility. Using sequence‐specific priming PCR, we have previously described the diversity of KIR genes in term of presence/absence in northeastern Thais (NETs). To provide additional resolution beyond conventional methods, quantitative PCR was applied to determine KIR copy number profiles. Novel expanded and contracted KIR copy number profiles were identified at cumulatively high frequencies. These all comprise haplotypes with duplication (6·9%) or deletion (2·7%) of KIR3DL1/S1 along with adjacent genes. Five expanded KIR profiles comprised haplotypes with duplications of KIR2DP1, 2DL1, 3DP1, 2DL4, 3DL1/S1 and 2DS1/4, whereas two contracted profiles contained only a single copy of KIR3DP1, 3DL1/S1 and 2DL4. Using a KIR haplotype prediction program (KIR Haplotype Identifier), 14% of NET haplotypes carried atypical haplotypes based on the gene copy number data.     

Evaluating the potential impact of the new Global Plan to Stop TB: Thailand, 2004-2005

OBJECTIVE: WHO's new Global Plan to Stop TB 2006-2015 advises countries with a high burden of tuberculosis (TB) to expand case-finding in the private sector as well as services for patients with HIV and multidrug-resistant TB (MDR-TB). The objective of this study was to evaluate these strategies in Thailand using data from the Thailand TB Active Surveillance Network, a demonstration project begun in 2004. METHODS: In October 2004, we began contacting public and private health-care facilities monthly to record data about people diagnosed with TB, assist with patient care, provide HIV counselling and testing, and obtain sputum samples for culture and susceptibility testing. The catchment area included 3.6 million people in four provinces. We compared results from October 2004-September 2005 (referred to as 2005) to baseline data from October 2002-September 2003 (referred to as 2003). FINDINGS: In 2005, we ascertained 5841 TB cases (164/100 000), including 2320 new smear-positive cases (65/100 000). Compared with routine passive surveillance in 2003, active surveillance increased reporting of all TB cases by 19% and of new smear-positive cases by 13%. Private facilities diagnosed 634 (11%) of all TB cases. In 2005, 1392 (24%) cases were known to be HIV positive. The proportion of cases with an unknown HIV status decreased from 66% (3226/4904) in 2003 to 23% (1329/5841) in 2005 (P< 0.01). Of 4656 pulmonary cases, mycobacterial culture was performed in 3024 (65%) and MDR-TB diagnosed in 60 (1%). CONCLUSION: In Thailand, piloting the new WHO strategy increased case-finding and collaboration with the private sector, and improved HIV services for TB patients and the diagnosis of MDR-TB. Further analysis of treatment outcomes and costs is needed to assess this programme's impact and cost effectiveness.     

Genetic study of KIR and HLA ligands in 235 individuals from Northeastern Thailand

The diversity of 17 KIR and HLA ligands (HLA-C1, C2, Bw4, A11) were investigated in two hundred and thirty-five unrelated healthy donors in Northeastern Thais (NETs) by the polymerase chain reaction with sequence-specific primer (PCR-SSP) method. The Hardy-Weinberg Equilibrium (HWE) was used to verify genotyping method for dimorphic KIR and HLA. They were in HWE (p > 0.05). KIR and HLA ligands frequencies, genotypes, haplotypes and linkage disequilibrium (LD) were presented. The genetic data are available in allele Frequencies Net Database.