- Inhibition of Glycogen Synthase II with RNAi Prevents Liver Injury in Mouse Models of Glycogen Storage Diseases. [Journal Article]
- MTMol Ther 2018 Apr 27
- Glycogen storage diseases (GSDs) of the liver are devastating disorders presenting with fasting hypoglycemia as well as hepatic glycogen and lipid accumulation, which could lead to long-term liver da...
Glycogen storage diseases (GSDs) of the liver are devastating disorders presenting with fasting hypoglycemia as well as hepatic glycogen and lipid accumulation, which could lead to long-term liver damage. Diet control is frequently utilized to manage the potentially dangerous hypoglycemia, but there is currently no effective pharmacological treatment for preventing hepatomegaly and concurrent liver metabolic abnormalities, which could lead to fibrosis, cirrhosis, and hepatocellular adenoma or carcinoma. In this study, we demonstrate that inhibition of glycogen synthesis using an RNAi approach to silence hepatic Gys2 expression effectively prevents glycogen synthesis, glycogen accumulation, hepatomegaly, fibrosis, and nodule development in a mouse model of GSD III. Mechanistically, reduction of accumulated abnormally structured glycogen prevents proliferation of hepatocytes and activation of myofibroblasts as well as infiltration of mononuclear cells. Additionally, we show that silencing Gys2 expression reduces hepatic steatosis in a mouse model of GSD type Ia, where we hypothesize that the reduction of glycogen also reduces the production of excess glucose-6-phosphate and its subsequent diversion to lipid synthesis. Our results support therapeutic silencing of GYS2 expression to prevent glycogen and lipid accumulation, which mediate initial signals that subsequently trigger cascades of long-term liver injury in GSDs.
- [Clinical and laboratory features of cholelithiasis in patients with type 2 diabetes by gender]. [Journal Article]
- WLWiad Lek 2018; 71(3 pt 1):534-536
- CONCLUSIONS: Conclusions: Established a significant prevalence of female subjects among patients with combined pathology. There were no reliable signs of clinical symptoms and changes in biochemical parameters, depending on sex. A reliable method for diagnosing the changes in the gall bladder in both women and men is ultrasound.
- Epidemiological, Clinical, and Laboratory Evaluation of Plasmodium falciparum Malaria Cases Followed in Firat University Hospital: A 6-Year Retrospective Analysis. [Journal Article]
- TPTurkiye Parazitol Derg 2018; 42(1):1-5
- CONCLUSIONS: The number of import cases is increasing owing to tourism, migration, and deficiency in eradication programs. Malaria caused by P. falciparum is an import case in Turkey. The current study emphasizes on the necessity of providing proper education to Turkish individuals traveling to endemic areas for the purpose of work or travel and on the necessity of initiating chemoprophylaxis.
- [Clinical analysis of 70 chronic lymphocytic leukemia patients with trisomy 12 detected by FISH]. [Journal Article]
- ZXZhonghua Xue Ye Xue Za Zhi 2018 May 14; 39(5):387-391
- Objective: To summarize and investigate the characteristics, prognosis and treatments of chronic lymphocytic leukemia (CLL) patients with trisomy 12 by using FISH (CEP12). Methods: Clinical data of...
Objective: To summarize and investigate the characteristics, prognosis and treatments of chronic lymphocytic leukemia (CLL) patients with trisomy 12 by using FISH (CEP12). Methods: Clinical data of 330 CLL patients were analyzed retrospectively by using FISH (CEP12) to detect trisomy 12 from May 2003 to April 2015. The clinical data and laboratory characteristics of CEP12 positive patients (70 cases) were compared with those CEP12 negative patients (260 cases). Results: Compared with CEP12 negative CLL patients, the proportion of hepatomegaly (13.6% vs 4.0%, P=0.011) and LDH>247 U/L (43.3% vs 18.5%, χ(2)=15.892, P<0.001) in CEP12 positive CLL patients were much higher, respectively. There were no significant differences between age, sex, clinical stage, β(2)-microglobulin level, IGHV mutation ratio and splenomegaly/lymphadenopathy in these two subgroups. However, compared with CEP12 negative patients, CEP12 positive patients had higher ratio of FMC7 (23.8% vs 12.7%, χ(2)=4.730, P=0.030), and lower ratio of CD23 (95.2% vs 99.6%, P=0.033). The overall response rates (ORR) in Fludarabine (without Rituximab), Rituximab (with or without Fludarabine) and the traditional chemotherapy group (chlorambucil, CHOP or CHOP-like) were 77.5% (31/40), 84.8% (56/66) and 45.4% (50/110), respectively. The ORR of the traditional chemotherapy group was lower than that of the Fludarabine group and Rituximab group. For CEP12 positive patients, the ORR was inferior to CEP12 negative patients when only using Fludarabine (P<0.05). However, when using Rituximab, the difference could be eliminated, and the ORR was even a little higher in CEP12 negative patients (91.7% vs 81.0%, P=0.306). Compared with CEP12 negative patients, there were no significant differences in progression-free survival (PFS) (χ(2)=0.410, P=0.478) and overall survival (OS) (χ(2)=0.052, P=0.180) for CEP12 positive patients whom the median time from diagnosis to start treatment and OS time was 22.6 (95%CI 15.4-31.7) and 118.5 (95%CI 74.5-162.4) month while the 5-year PFS and OS were (52.9±7.6)% and (74.8±6.6)%. Conclusions: CEP12 positive CLL patients are more common in hepatomegaly and higher level of LDH. The traditional chemotherapy treatment had the lowest efficacy, and the curative effect of single use of fludarabine is not as good as that of CEP12 negative patients, however, when using Ritaximab, the efficacy could be comparable.
- Cholesteryl Ester Storage Disease: Fatal Outcome without Causal Therapy in a Female Patient with the Preventable Sequelae of Progressive Liver Disease after Many Years of Mild Symptoms. [Journal Article]
- AJAm J Case Rep 2018 May 18; 19:577-581
- CONCLUSIONS: LAL-D should be included in the differential diagnosis of lipid metabolism disorder, hepatomegaly, and non-alcoholic fatty liver disease with fibrosis or cirrhosis. Causal treatment with sebelipase alfa should be introduced even in patients who have LAL-D and many years of clinically mild symptoms of this disease to prevent the serious sequelae of cirrhosis or cardiovascular complications.
- Pathological and molecular characterization of systemic isosporosis (atoxoplasmosis) in captive green-winged saltator (Saltator similis). [Journal Article]
- VPVet Parasitol 2018 May 15; 255:98-101
- Systemic isosporosis, also called atoxoplasmosis or visceral coccidiosis, is a disease that affects birds in general. Pathogenesis of systemic isosporosis and its etiologic agent have not been well c...
Systemic isosporosis, also called atoxoplasmosis or visceral coccidiosis, is a disease that affects birds in general. Pathogenesis of systemic isosporosis and its etiologic agent have not been well characterized, but taxonomically Atoxoplasma is currently considered a junior objective synonym of Isospora. The present report aimed to describe pathological and molecular findings of systemic isosporosis in captive green-winged saltators (Saltator similis) from the State of Espírito Santo, Brazil. In a commercial breeding facility eleven birds with two to nine months of age died from 2015 to 2016. These birds developed nonspecific clinical signs, including bristly feathers, hyporexia, loss of weight, and apathy. Two birds were necropsied, and grossly there were hepatomegaly, splenomegaly, necrosis of lymphoid follicles, hepatic necrosis, and severe enteritis. Merozoites were observed in the heart, small intestine, proventriculus, brain, liver, spleen, and kidneys. 23 S RNA PCR amplicons from DNA extracted from the liver and the intestinal contents had 99% identity with Atoxoplasma sp., whereas amplicons of mitochondrial cytochrome c oxidase subunit 1 ha d 97% identity with Isospora greineri. In conclusion, this report indicates that systemic isosporosis in green-winged saltator is a disease that affects the spleen, liver, and small intestine, with high mortality for young birds, resulting in significant loses to commercial breeding facilities.
- Genistein Ameliorates Non-alcoholic Fatty Liver Disease by Targeting Thromboxane A2 Pathway. [Journal Article]
- JAJ Agric Food Chem 2018 May 17
- Non-alcoholic fatty liver disease (NAFLD) is now a public health issue worldwide, but no drug has received approval yet. Genistein, an isoflavonoid derived from soybean, ameliorates high fat diet-ind...
Non-alcoholic fatty liver disease (NAFLD) is now a public health issue worldwide, but no drug has received approval yet. Genistein, an isoflavonoid derived from soybean, ameliorates high fat diet-induced NAFLD in mice, but the molecular underpinnings remain largely elusive. Arachidonic acid is a major ingredient of animal fats, and arachidonic acid cascade has been implicated in chronic inflammation. In this study, we investigated whether genistein against NAFLD by targeting arachidonic acid cascade. By using a mouse model, we showed that genistein supplementation improved high-fat diet induced NAFLD by normalizing hepatomegaly, liver steatosis, aminotransferase abnormalities and glucose tolerance. Thromboxane A2 (TXA2) pathway was aberrantly active in NAFLD, evidenced by an elevation of circulating TXA2 and hepatic thromboxane A2 receptor (TBXA2R) expression. Mechanistically, we found that genistein directly targeted cyclooxygenase-1 (COX-1) activity as well as its downstream TXA2 biosynthesis, while TXA2 pathway might mediate NAFLD progression by impairing insulin sensitivity. Taken together, our study revealed a crucial pathophysiological role of TXA2 pathway in NAFLD and provided an explanation as to how genistein against NAFLD progression.
- Clinical outcomes and risk factors for death from disseminated histoplasmosis in patients with AIDS who visited a high-complexity hospital in Campo Grande, MS, Brazil. [Journal Article]
- RSRev Soc Bras Med Trop 2018 Mar-Apr; 51(2):155-161
- CONCLUSIONS: The mortality rate for DH is high among severely immunocompromised patients with AIDS. The risk factors for death were those traditionally associated with blood dyscrasia, inflammatory activity, as well as increased renal and nutritional impairment.
- Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset. [Journal Article]
- HCHepatol Commun 2018; 2(5):504-514
- Genetic variants in the adenosine triphosphate-binding cassette subfamily B member 4 (ABCB4) gene, which encodes hepatocanalicular phosphatidylcholine floppase, can lead to different phenotypes, such...
Genetic variants in the adenosine triphosphate-binding cassette subfamily B member 4 (ABCB4) gene, which encodes hepatocanalicular phosphatidylcholine floppase, can lead to different phenotypes, such as progressive familial intrahepatic cholestasis (PFIC) type 3, low phospholipid-associated cholelithiasis, and intrahepatic cholestasis of pregnancy. The aim of this multicenter project was to collect information on onset and progression of this entity in different age groups and to assess the relevance of this disease for the differential diagnosis of chronic liver disease. Clinical and laboratory data of 38 patients (17 males, 21 females, from 29 families) with homozygous or (compound) heterozygous ABCB4 mutations were retrospectively collected. For further analysis, patients were grouped according to the age at clinical diagnosis of ABCB4-associated liver disease into younger age (<18 years) or adult age (≥18 years). All 26 patients diagnosed in childhood presented with pruritus (median age 1 year). Hepatomegaly and splenomegaly were present in 85% and 96% of these patients, respectively, followed by jaundice (62%) and portal hypertension (69%). Initial symptoms preceded diagnosis by 1 year, and 13 patients received a liver transplant (median age 6.9 years). Of note, 9 patients were misdiagnosed as biliary atresia, Alagille syndrome, or PFIC type 1. In the 12 patients with diagnosis in adulthood, the clinical phenotype was generally less severe, including intrahepatic cholestasis of pregnancy, low phospholipid-associated cholelithiasis, or (non)cirrhotic PFIC3. Conclusion: ABCB4 deficiency with onset in younger patients caused a more severe PFIC type 3 phenotype with the need for liver transplantation in half the children. Patients with milder phenotypes are often not diagnosed before adulthood. One third of the children with PFIC type 3 were initially misdiagnosed, indicating the need for better diagnostic tools and medical education. (Hepatology Communications 2018;2:504-514).
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- 18F-FDG PET/CT findings in hepatosplenic Gamma-Delta T-cell lymphoma: case reports and review of the literature. [Journal Article]
- AJAm J Nucl Med Mol Imaging 2018; 8(2):137-142
- Hepatosplenic Gamma Delta T cell lymphoma (γδHSTL) is a rare, highly aggressive, and rapidly lethal T cell lymphoma which manifests 18F-FDG PET/CT findings that can mimic benign conditions. Patients ...
Hepatosplenic Gamma Delta T cell lymphoma (γδHSTL) is a rare, highly aggressive, and rapidly lethal T cell lymphoma which manifests 18F-FDG PET/CT findings that can mimic benign conditions. Patients with γδHSTL present with unexplained symptoms of a hematologic malignancy like the B symptoms of lymphoma including weight loss, fevers, and night sweats, as well as, splenomegaly and hepatomegaly. Thrombocytopenia, anemia, or neutropenia are also common due to spleen, liver and bone marrow involvement. The peripheral blood, however, typically does not show abnormal T cells. The clinical and 18F-FDG PET/CT findings are presented for 3 patients with γδHSTL. Patients with γδHSTL may have a normal 18F-FDG PET/CT or an 18F-FDG PET/CT with any combination of the three findings: splenomegaly with intense FDG uptake; hepatomegaly with increased FDG uptake; and diffuse, increased FDG uptake in the bone marrow. Importantly, lymphadenopathy is usually absent, and most patients show morphologically normal lymph nodes with normal FDG uptake. Due to the aggressive nature of the disease, γδHSTL is a critical diagnosis to consider in patients who present with clinical signs of suspected hematologic malignancy and variable 18F-FDG PET/CT findings. The absence of lymphadenopathy and normal FDG uptake in lymph nodes are typical pertinent negative findings that differentiate γδHSTL from other lymphomas. A bone or liver biopsy is frequently necessary to establish the diagnosis and should be recommended.