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- Phenol Toxicity Following Cutaneous Exposure to Creolin®: A Case Report. [JOURNAL ARTICLE]
- J Med Toxicol 2014 Oct 18.
Phenol is a caustic that may cause cutaneous or gastrointestinal burns depending on the route of exposure. Significant absorption may result in systemic toxicity. We present a case of topical phenol exposure resulting in cutaneous burns and systemic phenol toxicity.A 9-year-old girl was exposed to Creolin®, a general-purpose disinfectant containing phenol, when her mother applied this product to her head and upper torso. The patient required endotracheal intubation due to depressed mental status; she had cutaneous erythema in the distribution of contact with the cleanser. An initial EKG revealed sinus tachycardia with brief runs of monomorphic ventricular tachycardia. On hospital day (HD) 1, the area of erythema extended to both upper extremities and hyperpigmentation developed over the affected areas, which continued to darken during the hospital course. The patient was extubated late on HD 1. On HD 2, the patient's urine was noted to be a dark green color that resolved later that day. On HD 3, areas of desquamation and decreased sensation developed in skin areas of maximal contact with the cleanser. The patient developed a mild transaminitis with peak AST and ALT levels of 84 units/l and 99 units/l, respectively. The patient was discharged to home on HD 4.Our patient presented with signs of cutaneous and systemic phenol toxicity characterized by dermal burns, depressed mental status, cardiac dysrhythmias, and elevated hepatic transaminases. Phenol exposure may cause systemic toxicity following limited dermal exposure.
- Evaluation of the safety and adverse effects of goreisan/wulingsan, a traditional Japanese-chinese herbal formulation (kampo), in a rat model: a toxicological evaluation. [Journal Article]
- Trop Med Health 2014 Sep; 42(3):127-32.
Diarrhea is the second leading cause of death among children less than 5 years of age. Most of these deaths occur in developing countries in the tropical areas of Africa and South Asia. Goreisan/Wulingsan, a formula of Japanese-Chinese medicinal herbs (Kampo), has been used for the treatment of diarrhea and vomiting from ancient times in East Asia. Therefore, we planned a randomized controlled clinical trial of Goreisan/Wulingsan in Bangladeshi children. Although it is believed to be safe in East Asia, information regarding its toxicity on animals is scarce. Since Goreisan/Wulingsan has never been used in Bangladesh, it was necessary to ensure the safety of the formula in an animal experiment. Rats were assigned to a control group (normal saline, n = 4) or various Goreisan/Wulingsan groups (n = 26) receiving doses of 1 to 8 mg/g/day (7.7 to 61.5 times the recommended pediatric dose) over a period of 25 days. Their activities and health conditions were observed until they were sacrificed, after which blood samples were collected for biochemical liver function tests. The kidneys, liver and heart tissue were collected for histopathological study. No lethality was observed during the experiment. All of the rats consumed the doses completely and no constipation was observed, suggesting the absence of any inhibitory effect on intestinal motion. Also, no abnormal neurological activity was detected, nor any significant elevation of AST, ALT or ALP levels, except for AST and ALT at the highest dose of 8 mg/g/day. Histopathological studies of the kidneys, liver and heart tissues revealed no abnormalities. In conclusion, our results showed that Goreisan/Wulingsan is safe for rats, thereby justifying the use of the drug in a human trial.
- Function of interleukin‑17 and ‑35 in the blood of patients with hepatitis B‑related liver cirrhosis. [JOURNAL ARTICLE]
- Mol Med Rep 2014 Oct 16.
Intrahepatic T helper (Th)17 cytokine and serum interleukin (IL)‑17 levels in patients with hepatitis B are positively correlated with the progression of liver cirrhosis (LC). IL‑35 can significantly inhibit the differentiation of Th17 cells and the synthesis of IL‑17. The present study aimed to investigate the function and expression of IL‑17 and IL‑35 in the blood of patients with hepatitis B‑related LC. The levels of IL‑17 and IL‑35 in the peripheral blood of 30 patients with chronic hepatitis B (CHB), 79 with LC, 14 with chronic severe hepatitis B (CSHB), and 20 normal controls were detected by ELISA. Quantitative polymerase chain reaction was used to evaluate Epstein‑Barr virus‑induced gene 3 (EBI3), forkhead box (FOX)P3 and IL‑17 mRNA expression levels in peripheral blood mononuclear cells (PBMCs). Western blotting was used to determine protein expression. The liver function of patients and normal controls was measured. EBI3, IL‑17 and FOXP3 mRNA expression levels in PBMCs from patients with LC, CHB and CSHB were higher than those in cells from the controls. IL‑17 mRNA levels differed significantly according to the Child‑Pugh classification and exhibited an upward trend over time in contrast to a downward trend for EBI3 and FOXP3 mRNA. The changes in protein expression in the peripheral blood were consistent with the changes in mRNA expression. Serum IL‑17 levels were positively correlated with total bilirubin (TBIL), alanine aminotransferase (ALT) and Child‑Pugh grade, and were negatively correlated with albumin. These observed differences were significant. Serum IL‑35 levels were negatively correlated with albumin, but not with Child‑Pugh grade, ALT and TBIL. IL‑17 and IL‑35 may be critically involved in the pathogenesis of hepatitis B‑related LC.
- Processing follows function: Pushing the formation of self-assembled monolayers to high throughput compatible timescales. [JOURNAL ARTICLE]
- ACS Appl Mater Interfaces 2014 Oct 17.
Self-Assembled Monolayers (SAMs) of organic molecules can be used to tune interface energetics and thereby improve charge carrier injection at metal-semiconductor contacts. We investigate the compatibility of SAM formation with high throughput processing techniques. Therefore we examine the quality of SAMs, in terms of work function shift and chemical composition as measured with photoelectron and infrared spectroscopy and in dependency to molecular exposure during SAM formation. The functionality of the SAMs is determined by the performance increase of organic field effect transistors upon SAM treatment of the source/drain contacts. This combined analytical and device based approach enables us to minimize the necessary formation times via an optimization of the deposition conditions. Our findings demonstrate that SAMs composed of partially fluorinated alkanethiols can be prepared in ambient atmosphere from ethanol solution using immersion times as short as 5 seconds and still exhibit almost full charge injection functionality if process parameters are chosen carefully. This renders solution processed SAMs compatible with high throughput solution based deposition techniques.
- Tenofovir disoproxil fumarate monotherapy for nucleos(t)ide-naïve chronic hepatitis B patients in Korea: data from the clinical practice setting in a single-center cohort. [Journal Article]
- Clin Mol Hepatol 2014 Sep; 20(3):261-6.
This study assessed the antiviral efficacy and safety of tenofovir disoproxil fumarate (TDF) for up to 12 months in Korean treatment-naïve chronic hepatitis B (CHB) patients.A total of 411 treatment-naïve CHB patients who had been treated with TDF for at least 3 months (median 5.6) were consecutively enrolled. Clinical, biochemical, virological parameters and treatment adherence were routinely assessed every 3 months.The median age was 51.3 years, 63.0% of the patients were male, 49.6% were HBeAg (+), and 210 patients had liver cirrhosis. The median baseline HBV DNA was 5.98 (SD 1.68) log10 IU/mL. Among the patients completing week 48, 83.3% had a complete virologic response (CVR, <12 IU/mL by HBV PCR assay), and 88.2% had normalized levels of alanine aminotransferase (ALT). The cumulative probabilities of CVR at 3, 6, 9 and 12 months were 22.8%, 53.1%, 69.3% and 85.0%. During the follow-up period, 9.8% patients achieved HBeAg loss and 7.8% patients achieved HBeAg seroconversion. There was no virological breakthrough after initiating TDF. The most common TDF-related adverse event was gastrointestinal upset, and three patients discontinued TDF therapy. However, no serious life-threatening side effect was noted.In a clinical practice setting, TDF was safe and highly effective when administered for 12 months to Korean treatment-naïve CHB patients.
- Risk stratification of HBV infection in Asia-Pacific region. [REVIEW]
- Clin Mol Hepatol 2014 Sep; 20(3):223-227.
Hepatitis B virus (HBV) infection is the major etiology of chronic liver disease worldwide and thus a global health problem, especially in Asia-Pacific region. The long-term outcomes of Asian HBV carriers vary widely; however, a significant proportion of them will finally develop end-stage liver disease. Over the past decade, several host and HBV factors predictive of clinical outcomes in Asian HBV carriers have been identified. The community-based REVEAL-HBV study illustrated the strong association between HBV-DNA level at study entry and risk of HCC over time, and male gender, older age, high serum alanine aminotransferase (ALT) level, positive HBeAg, higher HBV-DNA level, HBV genotype C infection and core promoter mutation are independently associated with a higher hepatocellular carcinoma (HCC) risk. Another hospital-based ERADICATE-B cohort further validated the HCC risk started to increase when HBV-DNA level was higher than 2,000 IU/mL. Of particular note, in patients with low viral load (HBV-DNA level <2,000 IU/mL), HBsAg level ≥1,000 IU/mL was a new independent risk factor for HCC. With the results from REVEAL-HBV study, a risk calculator for predicting HCC in adult non-cirrhotic patients has been developed and validated by independent international cohorts (REACH-B). With the combination of HBV-DNA, HBsAg, and ALT levels, ERADICATE-B study proposed an algorithm to predict disease progression and categorize risk levels of HCC as well as corresponding management in Asian HBV carriers. The introduction of transient elastography may further enhance the predictive power. In conclusion, HBsAg level can complement HBV-DNA level for the risk stratification of disease progression in Asian adult patients with chronic HBV infection.
- Liver enzymes and psychological well-being response to aerobic exercise training in patients with chronic hepatitis C. [Journal Article]
- Afr Health Sci 2014 Jun; 14(2):414-9.
Chronic hepatitis C (CHC) is a medical condition that has broad implications for a person's physical and psychological health.The aim of this study was to detect changes in liver enzymes and psychological well-being in response to aerobic exercise training in patients with CHC.Fifty CHC patients were included in two equal groups. The first group (A) received aerobic exercise training in addition to their regular medical treatment. The second group (B) received no training and only has their regular medical treatment. The program consisted of three sessions per week for three months.There was a significant decrease in mean values of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma - Glutamyltransferase (GGT), Beck Depression Inventory (BDI ) & Profile of Mood States(POMS) and increase in Rosenberg Self-Esteem Scale (RSES) in group (A) after treatments, but the changes in group (B) were not significant. Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study.Aerobic exercise training improves hepatic enzymes and psychological well-being in patients with chronic hepatitis C.
- A comparative evaluation of hematological, biochemical and pathological changes among infected sheep with Cysticercus tenuicollis and non-infected control group. [Journal Article]
- J Parasit Dis 2014 Dec; 38(4):399-403.
Cysticercus tenuicollis, the metacestode stage of Taenia hydatigena are responsible for a high degree of morbidity and mortality in livestocks. This study was performed in order to investigate the variations of blood parameters (hematological and biochemical) and pathological changes in 50 sheep infected with C. tenuicollis in comparison with 50 non-infected control group. The blood samples were taken from the sheep that were slaughtered in the Kerman slaughterhouse. Blood and sera samples were analyzed for hematology and biochemical parameters and infected livers, were transported to the pathology laboratory for further examinations. According to the analyses performed on the animals blood, a significant increase was detected in number of white blood cells, activities of AST, ALT and levels of total bilirubin in animals with cysticercosis (p < 0.05). Also in infected animals, a significant reduction was observed in number of red blood cells, hemoglobin concentration and hematocrit values (p < 0.05). In histopathological examination, hepatocellular degeneration and necrosis, fibrosis, mucus gland and biliary hyperplasia, mild lymphocytic hepatitis, granuloma and telangiectasis were observed. It seems that the increased and reduction of significant blood parameters, may be due to liver failure and pathological changes following larval migration and stimulating of immune responses.
- Intratracheal administration of cyclooxygenase-1-transduced adipose tissue-derived stem cells ameliorates monocrotaline-induced pulmonary hypertension in rats. [Journal Article]
- Am J Physiol Heart Circ Physiol 2014 Oct 15; 307(8):H1187-95.
The effect of intratracheal administration of cyclooxygenase-1 (COX-1)-modified adipose stem cells (ASCs) on monocrotaline-induced pulmonary hypertension (MCT-PH) was investigated in the rat. The COX-1 gene was cloned from rat intestinal cells, fused with a hemagglutanin (HA) tag, and cloned into a lentiviral vector. The COX-1 lentiviral vector was shown to enhance COX-1 protein expression and inhibit proliferation of vascular smooth muscle cells without increasing apoptosis. Human ASCs transfected with the COX-1 lentiviral vector (ASCCOX-1) display enhanced COX-1 activity while exhibiting similar differentiation potential compared with untransduced (native) ASCs. PH was induced in rats with MCT, and the rats were subsequently treated with intratracheal injection of ASCCOX-1 or untransduced ASCs. The intratracheal administration of ASCCOX-1 3 × 10(6) cells on day 14 after MCT treatment significantly attenuated MCT-induced PH when hemodynamic values were measured on day 35 after MCT treatment whereas administration of untransduced ASCs had no significant effect. These results indicate that intratracheally administered ASCCOX-1 persisted for at least 21 days in the lung and attenuate MCT-induced PH and right ventricular hypertrophy. In addition, vasodilator responses to the nitric oxide donor sodium nitroprusside were not altered by the presence of ASCCOX-1 in the lung. These data emphasize the effectiveness of ASCCOX-1 in the treatment of experimentally induced PH.
- Serum Biomarkers Predictive of Significant Fibrosis and Cirrhosis in Chronic Hepatitis B. [JOURNAL ARTICLE]
- J Clin Gastroenterol 2014 Oct 14.
Aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 index are noninvasive biomarkers to evaluate hepatic fibrosis. However, their usefulness in chronic hepatitis B (CHB) patients remains unclear.A total of 631 CHB patients were enrolled and randomly divided into a training set (n=420) and a validation set (n=211). Areas under receiver operating characteristic (AUROC) curves for FIB-4 index and APRI were compared to evaluate their diagnostic values in identifying significant fibrosis and cirrhosis.The AUROC of FIB-4 index for the diagnosis of significant fibrosis and cirrhosis in the entire cohort was higher than that of APRI (0.769 vs. 0.704, P=0.0003 and 0.869 vs. 0.706, P<0.0001). By using cutoff APRI of 0.38 and 4.04 in the validation set, the diagnostic accuracy for absence of significant fibrosis and presence of cirrhosis was 67.7% and 76.8%. At cutoff FIB-4 index of 0.87 and 3.40 in the validation set, the diagnostic accuracy for absence of significant fibrosis and presence of cirrhosis was 69.2% and 84.4%. Compared with patients with concordance, patients with overestimated score by FIB-4 index had a significantly higher serum alanine aminotransferase (ALT) level (299±245 vs. 168±196 U/L, P=0.001) as well as a higher ratio of hepatitis flare (ALT>400 U/L) (25% vs. 7.9%, P=0.008).FIB-4 index proves to be more reliable than APRI in predicting significant fibrosis and cirrhosis in CHB patients. By using FIB-4 index, a substantial proportion of patients could be identified correctly as significant fibrosis and cirrhosis without further invasive liver biopsy.