Can adiponectin predict gestational diabetes?

The aim of the present study was to evaluate whether adiponectin is a predictive factor for gestational diabetes mellitus (GDM) and is appropriate as a screening test for GDM. Three-hundred and fifty-nine women with singleton pregnancy and indications for GDM screening according to criteria of the American College of Obstetricians and Gynecologists were enrolled in the study between July 5, 2004 and March 11, 2005. After confirming gestational age (GA) and number of fetuses by ultrasound, all women underwent a 1-h glucose challenge test with 50 g glucose load (50-g GCT) between 21 and 27 weeks of GA. Blood samples for determination of adiponectin levels were also obtained on the same day. Subsequently, between 24 and 28 weeks of GA, the women underwent an oral glucose tolerance test with 100 g glucose load (100-g OGTT). The diagnosis of GDM was established when two or more of the following criteria were fulfilled: (1) fasting glucose >95 mg/dl; (2) 1-h glucose >180 mg/dl; (3) 2-h glucose >155 mg/dl; (4) 3-h glucose >140 mg/dl. Sixty women were diagnosed with GDM, a prevalence of 16.7%. There was no difference in age between the GDM and non-GDM groups. Pre-pregnancy and sampling-day body mass index (BMI), increase in weight and all blood glucose levels were greater in women with GDM than in those without (p < 0.05). Adiponectin concentrations were significantly negatively correlated with GA and plasma glucose levels of the GCT and each OGTT. Using logistic regression analyses, adiponectin, but not age, pre-pregnancy BMI and increase in weight, was demonstrated as an independent predictive factor for GDM. The area under the receiver-operator characteristic curve of adiponectin was significantly lower than that of the GCT [0.63 (95% confidence interval (CI) 0.53-0.67) vs. 0.73 (95% CI 0.71-0.80), p < 0.001]. At a cut-off value of 140 mg/dl of the 50-g GCT, the sensitivity and specificity of the test were 90% and 61%, respectively. The 50-g GCT could identify GDM in 54 (90%) out of 60 women. On the other hand, at an arbitrary cut-off value of 10 microg/ml for adiponectin, sensitivity of 91% and specificity of 31% were achieved. If this cut-off value was used for ruling in or out pregnant women for the GDM screening, 27% of all women could be eliminated from needing to perform an OGTT, with five women (8.3%) misclassified. In conclusion, this study demonstrated that adiponectin was an independent predictor for GDM. As for GDM screening, adiponectin was not as strong a predictor as GCT. However, with advantage of being less cumbersome, adiponectin could be used to rule out pregnant women at low risk of GDM.     

Enhanced expression of vascular endothelial growth factor by periodontal pathogens in gingival fibroblasts

Vascular endothelial growth factor (VEGF) has recently attracted attention as a potent inducer of vascular permeability and angiogenesis. Aberrant angiogenesis is often associated with lesion formation in chronic periodontitis. The aim of the present study was to investigate the properties of VEGF expression in human gingival fibroblasts (HGF) culture. HGF were stimulated with lipopolysaccharide (LPS), vesicle (Ve) and outer membrane protein (OMP) from Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. HGF constitutively produced VEGF and levels were significantly enhanced (P < 0.01) by stimulation with Ve and OMP from A. actinomycetemcomitans and P. gingivalis at concentrations of 10 microg/ml or higher. On the other hand, VEGF levels were not increased by LPS stimulation. VEGF mRNA expression was also observed in Ve- and OMP-stimulated HGF. A vascular permeability enhancement (VPE) assay was performed using guinea pigs to ascertain whether supernatant from cultures of Ve- and OMP-stimulated HGF enhance vascular permeability in vivo. Supernatant from cultures of Ve- and OMP-stimulated HGF strongly induced VPE. This was markedly suppressed upon simultaneous injection of anti-VEGF polyclonal antibodies with the supernatant. Heating and protease treatment of the stimulants reduced the VEGF enhancing levels in Ve and OMP in vitro. These results suggest that Ve and OMP may be crucial heat-labile and protease-sensitive components of periodontal pathogens that enhance VEGF expression. In addition, VEGF might be associated with the etiology of periodontitis in its early stages according to neovascularization stimulated by periodontal pathogens causing swelling and edema.     

Study of specific IgG subclass antibodies for diagnosis of<Emphasis Type="Italic"> Gnathostoma spinigerum</Emphasis>

Gnathostoma spinigerum infection is endemic in Thailand and many Asian countries. Current diagnosis is the skin test and enzyme-linked immunosorbent assay (ELISA) for IgG antibody against the G. spinigerum third-stage larvae (L3), but cross-reactivity is common. We evaluated the sensitivity and specificity of anti-G. spinigerum L3 IgG subclass antibodies for diagnosis of 43 patients with gnathostomiasis. The majority of patients with gnathostomiasis (91%) had eosinophilia. While the anti-G. spinigerum L3 IgG1 antibody provided the highest sensitivity (98%), the anti-G. spinigerum L3 IgG2 antibody had the highest specificity (88%). The ELISA that detected anti-G. spinigerum L3 IgG1 antibody could be a reliable laboratory screening test, while anti-G. spinigerum L3 IgG2 antibody could be used to confirm the diagnosis.     

Treatment of cutaneous gnathostomiasis with ivermectin

In a randomized open study, we compared the efficacy of a single dose of oral ivermectin (200 microg/kg) and oral albendazole (400 mg/day for 21 days) for the treatment of cutaneous gnathostomiasis. Thirty-one patients were randomly assigned to receive ivermectin (n = 17) or albendazole (n = 14). Thirteen of 17 patients who received ivermectin responded, 3 relapsed, and 1 was unresponsive (cure rate = 76%). Thirteen of 14 patients who received albendazole responded very well and did not relapse. Only one patient was unresponsive (cure rate = 92%; P > 0.05). No major side effects were observed in both groups. We concluded that a single dose of ivermectin (200 microg/kg) is less effective than albendazole (400 mg/day for 21 days) for treatment of cutaneous gnathostomiasis, but there was no statistically significant difference (P > 0.05).     

Economic valuation of informal care in Asia: A case study of care for disabled stroke survivors in Thailand

This study values informal care for disabled stroke survivors in Thailand. It applies the conventional recommended opportunity cost method to value informal care in monetary terms. Data were collected by means of face-to-face interviews conducted during 2006. The sample consisted of 101 disabled persons who had suffered a stroke at least six months prior to the interview, and who had a functional status score of less than 95 as measured by the Barthel Index. Average monthly time spent on informal care was 94.6 hours, and the major source of opportunity cost was forgone unpaid work (43.5%). The average monthly monetary value of informal care was 4642.6 baht, based on 2006 prices. This study shows that providing informal care involves a substantial opportunity cost, implying a hidden value to Thai society.     

Assessment of multiple different estrogen receptor-β antibodies for their ability to immunoprecipitate under chromatin immunoprecipitation conditions

Several different antibodies to total estrogen receptor (ER)β, ERβ1 and ERβ2/cx have been tested and compared for their ability to immunoprecipitate ERβ specific isoforms under chromatin immunoprecipitation conditions (ChIP). The rabbit polyclonal antibodies AP-ERβ1 and AP-ERβ2/cx, specific for ERβ1 and ERβ2/cx isoforms, respectively, were the most efficient for ChIP. The monoclonal antibody MCA1974/PPG5/10 was also able to ChIP ERβ1, but less efficiently than AP-ERβ1. All other antibodies tested were not suitable for ChIP analyses although most antibodies tested immunoprecipitated the appropriate ERβ isoforms under standard conditions. To identify antibodies that can also be used to verify in-vivo expression profiles, a comparison of the antibodies to detect ERβ isoforms by western blotting and immunohistochemistry was also undertaken. Under the tissue processing and autostaining conditions used at the Manitoba Breast Tumor Bank 385P/GC17, MCA1974/PPG5/10, Ab288/14C8 and MCA2279S/57/3 were found to be the best for IHC of ERβ isoforms in human breast tissue biopsy sections, while Ab14021, AP-ERβ1 and AP-ERβ2/cx were best for western blot detection of ERβ isoforms.     

Cost-utility analysis of treatments for stage IB cervical cancer

Objective

To analyze the cost-utility of two common clinical practices for stage IB cervical cancer patients from provider and societal viewpoints.

Methods

A decision tree model was conducted to examine value for expenditure between the following: (1) radical hysterectomy with pelvic lymph node dissection (RHPLND) with or without postoperative adjuvant therapy according to the risk of recurrence and (2) concurrent chemoradiotherapy (CCRT). The relevant studies were identified to extract the probability data, and meta-analysis was performed. Direct medical costs were estimated from hospital database and medical records review. Direct non-medical costs and utility parameters were obtained through interviews with patients to estimate quality-adjusted life years (QALYs) outcome. The time horizon was according to the life expectancy of Thai women.

Results

From provider viewpoint, RHPLND and CCRT resulted in approximate costs of US $5,281 and US $5,218, respectively. The corresponding costs from societal viewpoint were US $6,533 and US $6,335, respectively. QALYs were 16.40 years for RHPLND and 15.94 years for CCRT. The estimated incremental cost effectiveness ratio of RHPLND in comparison to CCRT from provider and societal viewpoints were US $100/QALY and US $430/QALY, respectively. RHPLND had more cost-effectiveness than CCRT if patients did not need adjuvant therapy. The most effective parameter in model was a direct medical cost of CCRT. At the current ceiling ratio in Thailand, RHPLND provides better value for money than CCRT, with a probability of 75%.

Conclusion

RHPLND is an efficient treatment for stage IB cervical cancer. This advantage is only for patients who require no adjuvant treatment.     

Humanized-VHH Transbodies that Inhibit HCV Protease and Replication

There is a need for safe and broadly effective anti-HCV agents that can cope with genetic multiplicity and mutations of the virus. In this study, humanized-camel V_HHs to genotype 3a HCV serine protease were produced and were linked molecularly to a cell penetrating peptide, penetratin (PEN). Human hepatic (Huh7) cells transfected with the JFH-1 RNA of HCV genotype 2a and treated with the cell penetrable nanobodies (transbodies) had a marked reduction of the HCV RNA intracellularly and in their culture fluids, less HCV foci inside the cells and less amounts of HCV core antigen in culture supernatants compared with the infected cells cultured in the medium alone. The PEN-V_HH-treated-transfected cells also had up-regulation of the genes coding for the host innate immune response (TRIF, TRAF3, IRF3, IL-28B and IFN-β), indicating that the cell penetrable nanobodies rescued the host innate immune response from the HCV mediated-suppression. Computerized intermolecular docking revealed that the V_HHs bound to residues of the protease catalytic triad, oxyanion loop and/or the NS3 N-terminal portion important for non-covalent binding of the NS4A protease cofactor protein. The so-produced transbodies have high potential for testing further as a candidate for safe, broadly effective and virus mutation tolerable anti-HCV agents.     

Comparison of treatment outcomes between squamous cell carcinoma and adenocarcinoma in locally advanced cervical cancer

Objective

To compare the treatment outcomes between squamous cell carcinoma (SCC) and adenocarcinoma (ACA) in locally advanced cervical cancer patients.

Methods

All medical records of stages IIB-IVA of cervical cancer patients who had completed treatment between 1995 and 2008 were reviewed. ACA 1 case was matched for SCC 2 cases with clinical stage, tumor size, treatment modalities (radiation therapy (RT) vs concurrent chemoradiation (CCRT)). Treatment outcomes including response to RT/CCRT, time to complete response (CR), patterns of treatment failure and survival outcomes were analyzed.

Results

A total of 423 patients with stages IIB-IVA (141 ACA: 282 SCC) were included. Most of the patients (about 60%) had stage IIB. The overall complete responses (CR) between ACA and SCC were 86.5% and 94.7%, respectively (p = 0.004). Median time to clinical CR from RT/CCRT of ACA were 2 months (0-5 months) compared with 1 month (0-4 months) for SCC (p = 0.001). Pelvic recurrence and distant failure were found in 2.1% and 14.9% in ACA, and corresponding with 3.9% and 15.6% in SCC. The 5-year overall survival rates of ACA compared to SCC were 59.9% and 61.7% (p = 0.191), respectively. When all prognostic factors are adjusted, clinical staging was the only factor that influenced overall survival.

Conclusion

ACA in locally advanced cervical cancer had poorer response rate from treatment and also used longer time to achieve CR than SCC. However, these effects were not determinants of survival outcomes.