Inflammatory bowel disease in Thai children: presentations and outcomes of treatment

Inflammatory bowel disease (IBD) is characterized by idiopathic chronic intestinal inflammation, due to abnormalities in gastrointestinal immunoregulation. Pediatric IBD has been rarely reported in Thailand. We describe eight children, five girls and three boys, who were diagnosed with IBD at Ramathibodi Hospital during 1999-2005 and had a follow-up of more than one year. Four cases had Crohn's disease (CD) and four cases had ulcerative colitis (UC). The ages at diagnosis ranged from 3.5 to 15.5 years. Diagnosis of IBD was delayed for more than 12 months in five patients. Five out of eight patients had early onset of disease, before 6 years of age. The manifestations included chronic diarrhea, abdominal pain, rectal bleeding and perianal lesions. The common extraintestinal manifestations were oral ulcer, anemia, weight loss and failure to thrive. Most patients had moderate to severe diseases and ileocolic fistula developed in one patient with CD. The disease was controlled with 5-aminosalicylic acid and corticosteroid in most patients. Four patients required additional therapy with azathioprine. Infliximab was used in two patients who were chronically steroid-dependent CD, one also had persistent ileocolic fistula and both patients responded well. During the follow-up period ranging from 1.1 to 5.8 years, three patients remained growth retardation; all had early onset of disease before 6 years of age, long duration of symptoms of more than 3 years before diagnosis and had multiple relapses. It is concluded that there is an increasing number of IBD in Thai children during the recent years. Most patients had moderate to severe diseases. Early onset of disease, delay in diagnosis and treatment are responsible for more complications, particularly persistent growth impairment. Early recognition of IBD and treatment are essential for a satisfactory long-term outcome.     

Cytochemical flow analysis of intracellular G6PD and aggregate analysis of mosaic G6PD expression

Background

Medicines that exert oxidative pressure on red blood cells (RBC) can cause severe hemolysis in patients with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency. Due to X‐chromosome inactivation, females heterozygous for G6PD with 1 allele encoding a G6PD‐deficient protein and the other a normal protein produce 2 RBC populations each expressing exclusively 1 allele. The G6PD mosaic is not captured with routine G6PD tests.

Methods

An open‐source software tool for G6PD cytofluorometric data interpretation is described. The tool interprets data in terms of % bright RBC, or cells with normal G6PD activity in specimens collected from 2 geographically and ethnically distinct populations, an African American cohort (USA) and a Karen and Burman ethnic cohort (Thailand) comprising 242 specimens including 89 heterozygous females.

Results

The tool allowed comparison of data across 2 laboratories and both populations. Hemizygous normal or deficient males and homozygous normal or deficient females cluster at narrow % bright cells with mean values of 96%, or 6% (males) and 97%, or 2% (females), respectively. Heterozygous females show a distribution of 10‐85% bright cells and a mean of 50%. The distributions are associated with the severity of the G6PD mutation.

Conclusions

Consistent cytofluorometric G6PD analysis facilitates interlaboratory comparison of cellular G6PD profiles and contributes to understanding primaquine‐associated hemolytic risk.     

Regulatory mechanisms of helper T cell differentiation: new lessons learned from interleukin 17 family cytokines

Interleukin 17 (IL-17) family consists of six cytokines in mammals. Among them, IL-17 and IL-17F are expressed by a novel subset of CD4+ helper T (Th) cells and play critical function in inflammation and autoimmunity. On the other hand, IL-17E, also called IL-25, has been associated with allergic responses. Here we summarize recent work by us as well as other investigators in understanding the regulation and function of these three cytokines. From these studies, IL-17 family cytokines may serve as novel targets for pharmaceutical intervention of immune and inflammatory diseases.     

Intraspecies variation of Brugia spp. in cat reservoirs using complete ITS sequences

The internal transcribed spacer (ITS) region was used to study the intraspecies variation of Brugia spp. in cat reservoirs. Blood specimens from seven naturally infected cats were collected from two different geographical brugian-endemic areas in Thailand. The DNAPAR tree of these Brugia spp. was constructed using a maximum likelihood approach based on ITS nucleotide sequences and was compared to those of Brugia malayi, Brugia pahangi, and Dirofilaria immitis that were previously reported in GenBank. The phylogenetic trees inferred from ITS1, ITS2, and complete ITS sequences indicated that B. malayi and B. pahangi were separated into two clades, and subgroups were generated within each clade. The data revealed that ITS2 sequences were less informative than ITS1 for studying intraspecies variation of Brugia spp. Our results are primary data for intraspecies variation of B. malayi and B. pahangi in cat reservoirs. The information could be applicable for studying the molecular epidemiology and the dynamic nature of the parasites. GenBank accession numbers of Brugia malayi and Brugia pahangi complete ITS regions using in this study were EU373601-EU373625 and EU373626- EU373655, respectively.     

Protease Allergens Induce the Expression of IL-25 via Erk and p38 MAPK Pathway

Allergic diseases, including asthma, are characterized by T helper type 2 (Th2) cell-mediated inflammations, coupled with tissue infiltration by eosinophils. In this study, we demonstrate that multiple protease allergens, including papain and DerP1, efficiently induce interleukin (IL)-25 and thymic stromal lymphopoietin (TSLP) gene expression, and this phenomenon is dependent on the protease activities of these allergens. The IL-25 cytokine level in bronchial alveolar lavage (BAL) was also profoundly and significantly increased after treatment with papain. Additionally, the levels of Th2 cytokines were significantly increased, as compared to those in the OVA-only treatment group. The various protease allergens triggered the expression of IL-25 and TSLP mRNA in mouse lung epithelial cells (MLE12) and primary mouse lung epithelial cells; these effects were inhibited by the deactivation of the protease activity of papain. The allergen papain activates the ErK and p38 MAP pathways; the inhibition of these pathways, but not the NFκB or PI-3 kinase pathways, impairs the induction of IL-25 and TSLP expression by proteases. In this study, we demonstrate that the protease allergens induce IL-25 and TSLP via the MAP kinase signal pathways, and their protease activities are essential to this pathway.     

Thailand's national strategic plan on antimicrobial resistance: progress and challenges

Antimicrobial resistance is a serious threat that affects all countries. The Global Action Plan on antimicrobial resistance and the United Nations Political Declaration on antimicrobial resistance set standards for countries to resolve antimicrobial resistance challenges under the One Health approach. We assess progress and challenges in implementing Thailand’s national strategic plan on antimicrobial resistance 2017–2022, discuss interim outcomes and share lessons learnt. Major progress includes: establishing a national governance mechanism that leads high-impact policy on antimicrobial resistance and consolidates actions and multisectoral collaboration; creating a monitoring system and platform to track implementation of the strategic plan; and converting strategies of the strategic plan into actions such as controlling the distribution and use of antimicrobials in humans and animals. Interim results indicate that antimicrobial consumption in animals has nearly halved (exceeding the national goal of a 30% reduction) whereas other goals have not yet reached their targets. We have learnt that elevating antimicrobial resistance to high-level visibility and establishing a national governance mechanism is an important first step, and a monitoring and evaluation system should be developed in parallel with implementation. Securing funds is crucial. Policy coherence is needed to avoid duplication of actions. Highly ambitious goals, although yet to be achieved, can advance actions beyond expectations. Political commitment and collaboration across different sectors will continue to play important roles but might not be sustained without a well-designed governance structure to support long-term actions to address antimicrobial resistance.     

Expression and characterization of Cu/Zn superoxide dismutase from <Emphasis Type="Italic">Wuchereria bancrofti</Emphasis>

The Cu/Zn superoxide dismutase gene from Wuchereria bancrofti (Cu/Zn WbSOD) was isolated by PCR using degeneracy primers. The complete Cu/Zn WbSOD consisted of 1,032 nucleotides containing 4 exons (477 nucleotides) and 3 introns. The molecular phylogenetic analysis of the Cu/Zn WbSOD gene in comparison with those from other organisms revealed that the gene was classified in the same clade to those of filarial Brugia malayi and Brugia pahangi (bootstrap value at 90). The nucleotide and deduced amino acid sequences of Cu/Zn WbSOD exhibited the similarity to those of intracellular Cu/Zn SOD of B. malayi and B. pahangi. The amino acid comparison of Cu/Zn WbSOD to others revealed that the binding sites and active sites were conserved. The expression of this gene yielded 16.366 kDa in size. After Ni-IDA column purification, the enzyme showed specific activity of 8.5 U/mg and 42.1% yield. The enzyme activity was inhibited when 6 mM KCN was added.     

Motor recovery of stroke patients after rehabilitation: one-year follow-up study

Purpose To investigate motor recovery of stroke patients 1 year after rehabilitation. Materials and Methods A cross-sectional study of 192 stroke patients discharged from rehabilitation wards in nine tertiary hospitals was conducted. Motor recovery was assessed using the Brunnstrom motor recovery stages (BMRS), at 6 and 12 months after discharge. Factors related to the BMRS of the hand, arm and leg were analyzed. Results The mean age of patients was 62.2 years (57.3% male). Significantly more patients presented improvement of at least one BMRS of the hand, arm and leg compared with those with decreasing BMRS (p < 0.001). The percentage of patients with BMRS III– VI at 6 months was greater than that at discharge, but the recovery at 12 months was slightly higher than that at 6 months. It seems that motor recovery from stroke was near maximal at six months. Regarding the factors related to motor recovery, only lengths of stay (LOS) <30 d during the first admission and Barthel index at discharge ≥10 were related to the improvement of BMRS of the hand, arm and leg on multivariate analysis. Additionally, no complication at discharge was associated with the improvement of BMRS of the leg. Conclusions Approximately half of our stroke patients had motor improvement of at least one stage of BMRS at one year. Motor recovery after stroke at the end of the first year was associated with shorter LOS during the first admission, higher discharge Barthel index score and absence of complications at discharge.