- Efficacious and safe dose of praziquantel for the successful treatment of feline reservoir hosts with opisthorchiasis. [JOURNAL ARTICLE]
- Parasitol Int 2016 Aug 26.
Opisthorchiasis caused by Opisthorchis viverrini is a major food-borne zoonosis in Greater Mekong sub-region. Even though campaigns discouraging the consumption of raw fish have been launched to public, the disease still remains highly endemic. The unsuccessful eradication of the disease is probably because of the persistence of the parasite in animal reservoir hosts, particularly felids. Praziquantel (PZQ) is the drug of choice for morbidity control of opisthorchiasis in humans and animals. However, there is no specific study on its dosage regimen for feline opisthorchiasis. Thus, the effective treatment dose of PZQ, as well as its adverse effects, was evaluated in O. viverrini infected cats. Twenty-eight infected male and female cats from the endemic area of Khon Kaen and Mahasarakham Provinces, Thailand were enrolled in this study. Physical, hematological, blood chemical and urine examinations were analyzed, as indicators of health status, on the day before and 30days after treatment. Intensity of the infections was determined by the formalin-ethyl acetate sedimentation technique. Cats were equally allotted into the low infection group of 14 cats with egg count per gram of feces (EPG) <300 and the high infection group of 14 cats with EPG higher than 300. Cats in each group were equally divided into two subgroups of 7 cats; thus, there were two low infection subgroups (L1 and L2 subgroups) and two high infection subgroups (H1 and H2 subgroups). A single dose of 25mg/kg PZQ was orally administered to each cat in the L1 and H1 subgroups and a single oral dose of 40mg/kg PZQ was administered to the L2 and H2 subgroups. Complete clearance of O. viverrini eggs was found in all cats in the L1, L2 and H2 subgroups; thus, the cure rate (CR) and egg reduction rate (ERR) were 100%. However, partial clearance was observed in two cats with high EPG (1502 and 1518) in the H1 subgroup, which received 25mg/kg PZQ. Regards, CR and ERR for these two animals was 71.4 and 99.5%. No significant difference among the 4 subgroups was seen. Almost all hematological, blood chemical and urinalysis data were within normal ranges, except for the eosinophilia and an increase of alanine aminotransferase (ALT). Hookworm infection seen in all cats would cause eosinophilia. As for drug safety, there was no side effect observed in any cats. In conclusion, this study suggested that 40mg/kg PZQ is a highly effective and safe dosage for the treatment of feline reservoir hosts of human opisthorchiasis.
- Identification of Blood Protein Biomarkers of Acute Liver Injury by Targeted Quantitative Proteomics in Acetaminophen and Carbon tetrachloride treated Mouse Models and Acetaminophen Overdose Patients. [JOURNAL ARTICLE]
- J Proteome Res 2016 Aug 30.
Organ-enriched blood proteins, those produced primarily in one organ and secreted or exported to the blood, potentially afford a powerful and specific approach to assessing diseases in their cognate organs. In this paper, we demonstrate that quantification of organ-enriched proteins in the blood offers a new strategy to find biomarkers for diagnosis and assessment of drug-induced liver injury (and presumably the assessment of other liver diseases). We used selected reaction monitoring (SRM) mass spectrometry to quantify 81 liver-enriched proteins plus three aminotransferases (ALT1, AST1, and AST2) in plasma of C57BL/6J and NOD/ShiLtJ mice exposed to acetaminophen or carbon tetrachloride. Plasma concentrations of 49 liver-enriched proteins were perturbed significantly in response to liver injury induced by one or both toxins. We validated four of these toxin-responsive proteins (ALDOB, ASS1, BHMT and GLUD1) by Western blotting. By both assays, these four proteins constitute liver injury markers superior to currently employed markers such as ALT and AST. A similar approach was also successful in human serum where we had analyzed 66 liver-enriched proteins in acetaminophen overdose patients. Of these, 23 proteins were elevated in patients; 15 of 23 overlapped with the concentration-increased proteins in the mouse study. A combination of 5 human proteins, AGXT, ALDOB, CRP, FBP1, and MMP9, provides the best diagnostic performance to distinguish acetaminophen overdose patients from controls (sensitivity: 0.85, specificity: 0.84, accuracy: 85%). These five blood proteins are candidates for detecting acetaminophen-induced liver injury using next-generation diagnostic devices (e.g, microfluidic ELIZA assays).
- Animal model of liver ischemia reperfusion: biochemical and histological evaluation. [JOURNAL ARTICLE]
- Tunis Med 2016 Mar; 94(3):235-243.
During last years, significant progress was made in the comprehension of the hepatic lesions after Ischemia-Reperfusion episode in order to improve the Results in practice clinical.To avoid or reduce the damage induced by Ischemia-Reperfusion, we developed a model of hepatic Ischemia-Reperfusion with variable periods of reperfusion from 0 to 24 hours. Methods:Our study related to rats Wistar males. Six various groups were studied: the first reference group (without neither ischemia and reperfusion), the second group with ischemia of 90 min and without reperfusion and the 3end , 4end, 5end and 6end groups in addition to ischemia, underwent a reperfusion of 30 min, 2h, 6h and 24h respectively. The damage of hepatic Ischemia-Reperfusion was evaluated by a biochemical test based on the proportioning of transaminases and an anatomopathologic study by optical microscopy for the determination of the degree of hepatic attack. Results:The Results obtained seem to show an aggravation of the liver lesions and an increase in the plasmatic rates of AST and ALT in relation with the duration of the reperfusion. Indeed, the maximum of damage was observed after 2 hours of reperfusion. We observed a reduction in the lesions after 6h and 24h of reperfusion. Conclusion:Our work enabled us to describe a simple model of hepatic Ischemia-Reperfusion with functional, biochemical and anatomopathologic tests.
- Blood Pressure and Hypertension in Adults Permanently Living at High Altitude: A Systematic Review and Meta-Analysis. [JOURNAL ARTICLE]
- High Alt Med Biol 2016 Aug 30.
Aryal, N., Mark Weatherall, Yadav Kumar Deo Bhatta, and Stewart Mann. Blood pressure and hypertension in adults permanently living at high altitude: a systematic review and meta-analysis. High Alt Med Biol 00:000-000, 2016.-The objective of this study was to estimate the associations between altitude and mean blood pressure (BP) (or prevalence of hypertension [HT]) in adults who live permanently at high altitude. A literature search was conducted in December 2014 using PubMed, Scopus, and OvidSP (MedLine and EMBASE) databases to identify relevant observational studies. Inclusion criteria were reports of studies in populations permanently living at an altitude of ≥2400 m and in those 18 years or older. Meta-regression was used to estimate the association between average BP and HT and altitude. We identified 3375 articles and inclusion criteria were met for 21 reports, which included a total of 40,854 participants. Random-effects meta-regression estimated that for every 1000 m elevation the average systolic BP (SBP) (95% confidence interval [CI]) increased by 17 mmHg (0.2 to 33.8), p = 0.05 and diastolic BP (DBP) by 9.5 mmHg (0.6 to 18.4), p = 0.04 in participants with Tibetan origin. By contrast, in participants with non-Tibetan origin, average SBP decreased by 5.9 mmHg (-19.1 to 7.3), p = 0.38 and DBP by 4 mmHg (-13 to 5), p = 0.38. The odds ratios (95% CI) for the proportion of participants with HT per 1000 m increment in the altitude were 2.01 (0.37 to 11.02), p = 0.446 and 4.05 (0.07 to 244.69), p = 0.489 for Tibetan and non-Tibetan participants, respectively. Sensitivity analysis excluding two studies with older participants (≥60 years) reversed the direction of this effect in non-Tibetans with odds ratio (95% CI) of 0.10 (0.004 to 2.22) per 1000 m, p = 0.143. Overall, this review suggests weak association between BP and altitude in Tibetan origin populations.
- High Altitude Pulmonary Edema Without Appropriate Action Progresses to Right Ventricular Strain: A Case Study. [JOURNAL ARTICLE]
- High Alt Med Biol 2016 Aug 30.
Mills, Logan, Chris Harper, Sophie Rozwadowski, and Chris Imray. High altitude pulmonary edema without appropriate action progresses to right ventricular strain: A case study. High Alt Med Biol. 16:000-000, 2016.-A 24-year-old male developed high altitude pulmonary edema (HAPE) after three ascents to 4061 m over 3 days, sleeping each night at 2735 m. He complained of exertional dyspnea, dry cough, chest pain, fever, nausea, vertigo, and a severe frontal headache. Inappropriate continuation of ascent despite symptoms led to functional impairment and forced a return to the valley, but dyspnea persisted in addition to new orthopnea. Hospital admission showed hypoxemia, resting tachycardia, and systemic hypertension. ECG revealed right ventricular strain and a chest X-ray revealed right lower zone infiltrates. This case demonstrates that HAPE can develop in previously unaffected individuals given certain precipitating factors, and that in the presence of HAPE, prolonged exposure to altitude with exercise (or exertion) does not confer acclimatization with protective adaptations and that rest and descent are the appropriate actions. The case additionally demonstrates well-characterized right ventricular involvement.
- Investigation of the Etiology of Anemia in Thromboangiitis Obliterans. [Journal Article]
- Int J Angiol 2016 Sep; 25(3):153-8.
During a review of patients admitted with thromboangiitis obliterans (TAO), there was evidence of normochromic normocytic anemia and abrupt changes in hemoglobin (Hgb) levels in patients with several hospital admissions. Therefore, the evidence of hemolytic anemia was evaluated based on 37 banked plasma samples taken from Caucasian male TAO patients during disease exacerbation between 2012 and 2014. The patients' hospital records, including clinical manifestations and complete blood count, were evaluated. The following tests were performed on all samples: indirect antiglobulin test (IAT), C-reactive protein (CRP), high-sensitivity CRP (hsCRP), lactate dehydrogenase (LDH), haptoglobin, indirect bilirubin, d-aspartate aminotransferase (AST), and d-alanine aminotransferase (ALT). The mean age of the patients was 40 ± 7 years. Two patients underwent below-knee amputation. The mean hospital-documented Hgb of the patients was 12.9 ± 2.6 g/dL. CRP and IAT were positive in 75.6 and 70.2% of the samples, respectively. The tests and corresponding results were as follows: hsCRP, 14.07 ± 2.37 µg/mL; LDH, 2,552 ± 315 u/L; haptoglobin, 2.27 ± 1.1 g/L; indirect bilirubin, 0.09 ± 0.04 mg/dL; AST, 67 ± 7 u/L; and ALT, 26 ± 3 u/L. There was a significant inverse correlation between hsCRP and hospital-documented Hgb level (p = 0.03). Anemia with the positive IAT in most of the samples, high LDH and AST, and normal ALT are suggestive of hemolytic anemia. Normal indirect bilirubin is consistent with intravascular hemolysis. The positive CRP and elevated haptoglobin levels could be due to systemic inflammation in TAO. However, it is not known if an autoantigen or an infectious antigen is responsible for TAO systemic inflammation and induction hemolytic anemia. As such, the underlying mechanism of anemia in TAO could be part of the footprint of its main etiology.
- MitoNEET Deficiency Alleviates Experimental Alcoholic Steatohepatitis in Mice by Stimulating Endocrine Adiponectin-FGF15 Axis. [JOURNAL ARTICLE]
- J Biol Chem 2016 Aug 29.
MitoNEET (mNT) (CDGSH iron-sulfur domain-containing protein 1 or CISD1) is an outer mitochondrial membrane protein that donates 2Fe-2S clusters to apo-acceptor proteins. In the present study, using a global mNT knock out (mNTKO) mouse model, we investigated in vivo functional role of mNT in the development of alcoholic steatohepatitis. Experimental alcoholic steatohepatitis was achieved by pair feeding wild-type (WT) and mNTKO mice with Lieber-DeCarli ethanol-containing diets for 4-wks. Strikingly, chronically ethanol-fed mNTKO mice were completely resistant to ethanol-induced steatohepatitis as revealed by dramatically reduced hepatic triglycerides, decreased hepatic cholesterol level, diminished liver inflammatory response and normalized serum ALT levels. Mechanistic studies demonstrated that ethanol administration to mNTKO mice induced two pivotal endocrine hormones, namely, adipose-derived adiponectin and gut-derived fibroblast growth factor 15 (FGF15). The elevation in circulating levels of adiponectin and FGF15 led to normalized hepatic and serum levels of bile acids, limited hepatic accumulation of toxic bile, attenuated inflammation, and amelioration of liver injury in the ethanol-fed mNTKO mice. Other potential mechanisms such as reduced oxidative stress, activated SIRT1 signaling and diminished NF-κB activity also contribute to the hepatic improvement in the ethanol-fed mNTKO mice. In conclusion, the present study identified adiponectin and FGF15 as pivotal adipose-gut-liver metabolic coordinators in mediating the protective action of mNT deficiency against development of alcoholic steatohepatitis in mice. Our findings may help to establish mNT as a novel therapeutic target and pharmacological inhibition of mNT may be beneficial for the prevention and treatment of human alcoholic steatohepatitis.
- Evaluation of Renal-Hepatic Functional Indices and Blood Pressure Based on the Progress of Time in a Rat Model of Chronic Kidney Disease. [Journal Article]
- Nephrourol Mon 2016 May; 8(3):e37840.
Chronic kidney disease (CKD) is defined as either kidney damage or a decline in renal function as determined by a decreased glomerular filtration rate (GFR) for three months or longer. CKD is an important risk factor for mortality.The aim of this study was to evaluate the effects of CKD on renal-hepatic functional indices and blood pressure in 5/6 nephrectomized (5/6 Nx) rats over the course of nine months.Male Wistar rats were subjected to either 5/6 Nx or sham operations (n = 8). Members of the sham group underwent the same procedure without surgical reduction of the kidney mass. For all animals, body weight (BW), serum creatinine (Cr), blood urea nitrogen (BUN), alanine transaminase (ALT), and aspartate transaminase (AST) levels were measured before and after surgery. After two-, three-, six-, and nine-month intervals, blood was collected to assay renal and hepatic functional indices. Tail-cuff blood pressure was recorded in each month after surgery.BW was lower for the 5/6 Nx group rats after the operations compared with the BW of those in the sham operation group. Furthermore, the 5/6 Nx group showed elevations in blood pressure, Cr, BUN, ALT, and AST levels compared with the sham group over the course of time.In summary, CKD induced by the 5/6 Nx model caused hypertension and increased serum levels of Cr, BUN, ALT, and AST. These changes are augmented by the progress of time.
- Thermally induced anchoring of fullerene in copolymers with Si-bridging atom: Spectroscopic evidences. [JOURNAL ARTICLE]
- Spectrochim Acta A Mol Biomol Spectrosc 2016 Aug 9.:376-382.
We use X-ray photoelectron spectroscopy (XPS), Near-edge X-ray absorption fine structure (NEXAFS), resonant Auger spectroscopy (RAS), Attenuation Total Reflection Infrared (ATR-IR) and Atomic Force Microscopy (AFM) to study the blend between the copolymer poly[2,7-(9,9-bis(2-ethylhexyl)-dibenzosilole)-alt-4,7-bis(thiophen-2-yl)benzo-2,1,3-thiadiazole] (PSiF-DBT) and the fullerene derivative PC71BM submitted to different annealing temperatures. Those measurements indicate that there is an incidental anchoring of a fullerene derivative to the Si-bridging atoms of a copolymer induced by thermal annealing of the film. Insights about the physical properties of one possible PSiF-DBT/PC71BM anchored structure are obtained using Density Functional Theory calculations. Since the performance of organic photovoltaic based on polymer-fullerene blends depends on the chemical structure of the blend components, the anchoring effect might affect the photovoltaic properties of those devices.
- In Children with Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but does not Reduce Disease Activity Scores. [JOURNAL ARTICLE]
- Gastroenterology 2016 Aug 25.
No treatment for nonalcoholic fatty liver disease (NAFLD) has been approved by regulatory agencies. We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD.We performed a double-masked trial of 169 children with NAFLD Activity Scores ≥ 4 at 10 centers. From June 2012 to January 2014, the patients were randomly assigned to receive CBDR or placebo twice daily (300 mg for ≤65 kg, 375 mg for >65-80 kg, 450 mg for >80 kg) for 52 weeks. The primary outcome from the intention to treat analysis was improvement in liver histology over 52 weeks, defined as a decrease in NAFLD Activity Score ≥ 2 points without worsening fibrosis; patients without biopsies from week 52 (17 in the CBDR group and 6 in the placebo group) were considered non-responders. We calculated relative risks (RR) of improvement using stratified Cochran-Mantel-Haenszel analysis.There was no significant difference between groups in the primary outcome (28% of children in the CBDR group vs 22% in the placebo group; RR, 1.3; 95% CI, 0.8-2.1; P=.34). However, children receiving CBDR had significant changes in pre-specified secondary outcomes: reduced mean levels of alanine aminotransferase (reduction of 53±88 U/L vs a reduction of 8±77 U/L in the placebo group; P=.02) and aspartate aminotransferase (reduction of 31±52 vs a reduction of 4±36 U/L in the placebo group; P=.008), and a larger proportion had reduced lobular inflammation (in 36% of patients in the CBDR group vs placebo 21% of patients in the placebo group; RR, 1.8; 95% CI, 1.1-2.9; P=.03). In a post-hoc analyses, of children ≤65 kg, those taking CBDR had a 4-fold better chance of histologic improvement (observed in 50% of children in the CBDR group vs 13% in the placebo group; RR, 4.0; 95% CI, 1.3-12.3; P=.005).In a randomized trial, we found that 1 year of CBDR did not reduce overall histologic markers of NAFLD compared with placebo in children. Children receiving CBDR did, however, have significant reductions in serum levels of aminotransferase levels and lobular inflammation. ClinicalTrials.gov no: NCT01529268.