Observations on the development of stunting in children of the Khon Kaen region of Thailand.

A cohort of children in North-East Thailand was followed from birth to 2 years of age in an attempt to throw light on factors determining the development of stunting in linear growth. By 2 years the group as a whole had an average deficit in height of nearly -2 standard deviations. Those index children whose sibs were stunted had larger deficits than those with normal sibs. Their mothers were also shorter and lighter. These findings suggest that it is possible to think in terms of stunted families. No differences were identified in socio-economic factors and the prevalence of infection was in general low. Dietary intakes estimated by 24-hour recall, supplemented at 1 and 2 years by 24 h weighing, were satisfactory for most nutrients except iron, calcium and niacin. Intakes of Ca and P were lower in the more stunted children. A number of variables were measured in urine and blood at 1 and 2 years but few relationships could be established with the degree of stunting. Excretions of calcium and phosphorus showed weak negative correlations with height. On average the serum concentration of calcium was satisfactory but that of phosphorus was somewhat low. Concentrations of somatomedin C, thyroxin and vitamin D were within reported normal ranges, with no relation to the degree of stunting. From a comparison of the linear growth of these children with the results of other reports from Thailand it is suggested that environmental factors have produced stunting in the cohort as a whole, but the cohort is essentially homogeneous, showing within it a normal range of genetic variation. If that is so, major differences in intake or biochemistry between the taller and shorter children would not be expected. The problem remains of why the group as a whole is stunted. This is the first systematic attempt to assess biochemical factors that may be related to stunting in Third World children; these results are essentially negative, although there are hints that point at a possible deficiency of calcium.     

Roles of liver fluke infection as risk factor for cholangiocarcinoma

Several factors are known to be associated with risk of cholangiocarcinoma (CCA) and infection with the liver flukes, Opisthorchis viverrini and Clonorchis sinensis, has often been singled out as the leading risk factor in east and southeast Asia. In this review, current knowledge of their biology, life cycle, and pathogenesis of O. viverrini, and its role as a carcinogenic parasite are presented. The trends of age‐specific incidence of liver cancer in Khon Kaen, northeast Thailand are considered and compared with the prevalence profiles of O. viverrini. Potential impacts of the liver fluke control program particularly by mass drug administration (MDA) and public health education in the past and a recent drop of incidence of CCA are discussed in relation to primary prevention and control of this fatal bile duct cancer.     

Alterations of gene expression of RB pathway in Opisthorchis viverrini infection-induced cholangiocarcinoma

Opisthorchiasis has the significant relationship with the high prevalence of cholangiocarcinoma (CCA; a bile duct cancer) in the endemic areas in Southeast Asia. To reveal the molecular mechanism of the tumorigenesis induced by Opisthorchis viverrini infection, the present study investigated the kinetic expression of RB pathway genes, including RB1, p16^INK4, cyclin D1, and CDK4, during the development of opisthorchiasis-associated CCA in hamster model. The results of quantitative real-time polymerase chain reaction indicated that the expressions of RB1 and p16^INK4 were down-regulated during the development of CCA induced by infection plus N-nitrosodimethylamine treatment in a time-dependent manner. On the other hand, the expressions of cyclin D1 and CDK4 were up-regulated. The expression kinetics was corresponding to the pathological progression of the opisthorchiasis-associated CCA, revealed by histopathological observation. Moreover, the analysis of the expression of these genes in human opisthorchiasis-associated CCA cases showed the decreased expression of RB1 and p16^INK4 in 50% and 82.7% cases and overexpression of cyclin D1 and CDK4 in half cases, respectively. The results suggested that RB pathway is likely involved in the tumorigenesis of opisthorchiasis-induced CCA and proposed the potential application of some of these genes as biomarkers in predispose and molecular therapy of the parasite-associated cancer.     

Mechanisms of oxysterol-induced carcinogenesis

Oxysterols are oxidation products of cholesterol that are generated by enzymatic reactions mediated by cytochrome P450 family enzymes or by non-enzymatic reactions involving reactive oxygen and nitrogen species. Oxysterols play various regulatory roles in normal cellular processes such as cholesterol homeostasis by acting as intermediates in cholesterol catabolism. Pathological effects of oxysterols have also been described, and various reports have implicated oxysterols in several disease states, including atherosclerosis, neurological disease, and cancer. Numerous studies show that oxysterols are associated with various types of cancer, including cancers of the colon, lung, skin, breast and bile ducts. The molecular mechanisms whereby oxysterols contribute to the initiation and progression of cancer are an area of active investigation. This review focuses on the current state of knowledge regarding the role of oxysterols in carcinogenesis. Mutagenicity of oxysterols has been described in both nuclear and mitochondrial DNA. Certain oxysterols such as cholesterol-epoxide and cholestanetriol have been shown to be mutagenic and genotoxic. Oxysterols possess pro-oxidative and pro-inflammatory properties that can contribute to carcinogenesis. Oxysterols can induce the production of inflammatory cytokines such as interleukin-8 and interleukin-1β. Certain oxysterols are also involved in the induction of cyclo-oxygenase-2 expression. Inflammatory effects can also be mediated through the activation of liver-X-receptor, a nuclear receptor for oxysterols. Thus, several distinct molecular mechanisms have been described showing that oxysterols contribute to the initiation and progression of cancers arising in various organ systems.     

The levels of lycopene, alpha-tocopherol and a marker of oxidative stress in healthy northeast Thai elderly

An imbalance between oxidative stress and antioxidant capacity has been proposed to play an important role in the development and progression of chronic diseases in the elderly. The present study was carried out to investigate correlation between the serum antioxidants (lycopene and alpha-tocopherol) and malondialdehyde (MDA), a marker of oxidative stress in the healthy Thai elderly. The 207 healthy subjects aged 60-91 years old (72 males and 135 females) in Khon Kaen province, Thailand were enrolled in this study. They were interviewed by questionnaires about smoking habit. Serum lycopene and alpha-tocopherol levels were determined by high performance liquid chromatography (HPLC). MDA was measured by thiobarbituric assay. Serum lycopene and alpha-tocopherol levels in the elderly were 0.27 micromol/L (95% CI = 0.23-0.31) and 22.10 micromol/L (95% CI = 20.99-23.22), respectively. Males had significant lower serum lycopene and alpha-tocopherol levels than females (p<0.001). Of 72 males, 31.94% are current smokers whereas 1.4% of 135 females are current smokers. Current smokers had significantly lower serum lycopene (0.17 +/- 0.11 micromol/L) than current non-smokers (0.28 +/- 0.27 micromol/L) (p=0.0439) but level of alpha-tocopherol had non significance (p=0.210). Moreover, the current smokers had higher MDA malondialdehyde level (1.55 +/- 0.10 micromol/L) than the current non-smokers (1.35 +/- 0.04 micromol/L) (p=0.094). Thus, dietary antioxidant supplementation from local fruits and vegetables may have a beneficial role in the prevention of chronic diseases at high-risk oxidative stress such as smoking in these elderly.     

Annexin A1: A new immunohistological marker of cholangiocarcinoma

AIM: To evaluate a new immunohistological marker, annexin A1 (ANXA1), in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC). METHODS: Expression of ANXA1 protein was investigated in liver tissues from patients with CCA and HCC by immunohistochemistry. Its expression on differences stages of tumor development was investigated in hamster CCA tissues induced by Opisthorchis viverrini and N -nitrosodimethylamine. Moreover, mRNA expression of ANXA1 was assessed in CCA cell lines by quantitative real-time polymerase chain reaction and silencing of ANXA1 gene expression using small interfering RNA. RESULTS: In human CCA tissue arrays, immunohistochemical analysis revealed that the positive expression of ANXA1 was 94.1% (64/68 cases) consisting of a high expression (66.2%, 45/68 cases) and a low expression (33.8%, 23/68 cases). However, expression of ANXA1 protein was negative in all histologic patterns for HCC (46/46 cases) and healthy individuals (6/6 cases). In hamster with opisthorchiasis-associated CCA, the expression of ANXA1 was observed in the cytoplasm of inflammatory cells, bile duct epithelia and tumor cells. Grading scores of ANXA1 expression were significantly increased with tumor progression. In addition, mRNA expression of ANXA1 significantly increased in all of the various CCA cell lines tested compared to an immortalized human cholangiocyte cell line (MMNK1). Suppressing the ANXA1 gene significantly reduced the matrix metalloproteinase (MMP) 2 and MMP9, and transforming growth factor-β genes, but increased nuclear factor-kB gene expression. CONCLUSION: ANXA1 is highly expressed in CCA, but low in HCC, suggesting it may serve as a new immunohistochemical marker of CCA. ANXA1 may play a role in opisthorchiasis-associated cholangiocarcinogenesis.