Non-alcoholic steatohepatitis: From cell biology to clinical practice

2006 ◽  
Vol 44 (1) ◽  
pp. 197-208 ◽  
Author(s):  
Helena Cortez-Pinto ◽  
Miguel Carneiro de Moura ◽  
Christopher Paul Day
2017 ◽  
Vol 41 (S1) ◽  
pp. S370-S371
Author(s):  
C. Pavan ◽  
A. Rimessi ◽  
B. Zavan ◽  
V. Vindigni ◽  
P. Pinton

Antipsychotic drugs are currently used in clinical practice for a variety of mental disorders. Clozapine is the most effective medication for treatment-resistant schizophrenia, in controlling aggression and suicidal behavior in psychosis. Although clozapine is associated with a low likelihood of extrapyramidal symptoms and other neurological side effects, weight gain and metabolic side effects are well known in clinical practice exposing the patient to a greater risk of cardiovascular disorders, premature death, as well as psychosocial issues leading to non-adherence. The mechanisms underlying this pharmacologically activated disorders are still controversial. Based on our in vitro results, we have characterized in vivo the effects of the selective PKCβ inhibitor, Ruboxistaurin (LY-333531) on a preclinical model of long-term clozapine-induced weight gain. Cell biology, biochemistry and psychomotor tests have been performed on wild type and PKCβ (-/-) mutant mice to investigate the contribution of endogenous PKCβ and its pharmacological inhibitor on the neuroleptic effect of clozapine. Lastly, we also shed light on a novel aspect of the mechanism underlying of clozapine-induced weight gain, demonstrating that the clozapine-dependent PKCβ activation promote the inhibition of the lipid droplet-selective autophagy process, opening the way to new therapeutic intervention approach.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2004 ◽  
Vol 6 (3) ◽  
pp. 303-311

Transplantation of human fetal dopamine (DA) neurons to patients with Parkinson's disease (PD) has given proof of the principle that new neurons can survive for at least a decade, and then functionally integrate and provide significant symptomatic relief. Unfortunately, the ethical, technical, and practical limitations of using fetal DA neurons as the source for cell transplantation in PD, in combination with the development of unwanted grafting-related side effects, have put a halt to the spread of this treatment into clinical practice. Hopefully, recent advances in the fields of stem cell biology and adult neurogenesis research will lead totamen in new exciting ways to better understand and control the biological parameters necessary for achieving safe and successful neuronal replacement in PD patients.


2021 ◽  
Author(s):  
Jing Guo ◽  
Ying Xu ◽  
Li-Jie Chen ◽  
Song-xia Zhang ◽  
Tai Rao ◽  
...  

Abstract Background: Pharmacokinetic variability in disease state is common in clinical practice, but the underlying mechanism remains unclear. We aim to investigate the effects of gut microbiota and host Cyp450s on pharmacokinetic variability in mice with non-alcoholic steatohepatitis (NASH).Methods: The pharmacokinetic variability of mice with NASH was explored under intragastric and intravenous administration of a cocktail mixture of omeprazole, phenacetin, midazolam, tolbutamide, chlorzoxazone, and metoprolol compared with the control group. The pharmacokinetic variability of the drugs and its relation with changes of gut microbiota and host Cyp450s were compared and analyzed.Results: The exposure of all drugs, except metoprolol, significantly increased in the NASH group under intragastric administration. However, no significant increase in the exposure of all drugs, except tolbutamide, was observed in the NASH group under intravenous administration. The pharmacokinetic variabilities of phenacetin, midazolam, omeprazole, and chlorzoxazone were mainly associated with decreased elimination activity of the gut microbiota. By contrast, the pharmacokinetic variability of tolbutamide was mainly related to the change in host Cyp2c65. However, gut microbiota and host Cyp450s exerted minimal effect on the pharmacokinetic variability of metoprolol.Conclusions: Gut microbiota and host Cyp450s co-contribute the pharmacokinetic variability in mice with NASH, and the degree of contribution varies from drug to drug.


Author(s):  
Hitoshi Yoshiji ◽  
Sumiko Nagoshi ◽  
Takemi Akahane ◽  
Yoshinari Asaoka ◽  
Yoshiyuki Ueno ◽  
...  

AbstractThe first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.


2021 ◽  
Vol 17 (2) ◽  
pp. 112
Author(s):  
Sherwyn Schwartz ◽  
Jean Lucas ◽  
Mark H DeLegge ◽  
◽  
◽  
...  


JHEP Reports ◽  
2021 ◽  
pp. 100411
Author(s):  
Quentin M. Anstee ◽  
Kate Hallsworth ◽  
Niall Lynch ◽  
Adrien Hauvespre ◽  
Eid Mansour ◽  
...  

2015 ◽  
Vol 64 (6) ◽  
pp. 68-77 ◽  
Author(s):  
Elena Olegovna Usoltceva ◽  
Alexander Mkrtichevich Gzgzyan ◽  
Liailia Kharryasovna Dzhemlikhanova ◽  
Dariko Aleksandrovna Niauri

Recent findings in stem cell biology and cell engineering cannot be left without physicians’ attention. Endometrium as actively regenerating tissue represents also a source of endometrial stem cells. Endometrial stem cells have specific properties that distinguish them from other somatic stem cells. Endometrial stem cells have already shown their therapeutic efficiency and safety in a number of experimental and clinical trials. The biological basis of endometrial stem cells therapeutic potential and recent data on their use in clinical practice are discussed in the article.


Author(s):  
William H. Zucker

Planktonic foraminifera are widely-distributed and abundant zooplankters. They are significant as water mass indicators and provide evidence of paleotemperatures and events which occurred during Pleistocene glaciation. In spite of their ecological and paleological significance, little is known of their cell biology. There are few cytological studies of these organisms at the light microscope level and some recent reports of their ultrastructure.Specimens of Globigerinoides ruber, Globigerina bulloides, Globigerinoides conglobatus and Globigerinita glutinata were collected in Bermuda waters and fixed in a cold cacodylate-buffered 6% glutaraldehyde solution for two hours. They were then rinsed, post-fixed in Palade's fluid, rinsed again and stained with uranyl acetate. This was followed by graded ethanol dehydration, during which they were identified and picked clean of debris. The specimens were finally embedded in Epon 812 by placing each organism in a separate BEEM capsule. After sectioning with a diamond knife, stained sections were viewed in a Philips 200 electron microscope.


Author(s):  
W. Bernard

In comparison to many other fields of ultrastructural research in Cell Biology, the successful exploration of genes and gene activity with the electron microscope in higher organisms is a late conquest. Nucleic acid molecules of Prokaryotes could be successfully visualized already since the early sixties, thanks to the Kleinschmidt spreading technique - and much basic information was obtained concerning the shape, length, molecular weight of viral, mitochondrial and chloroplast nucleic acid. Later, additonal methods revealed denaturation profiles, distinction between single and double strandedness and the use of heteroduplexes-led to gene mapping of relatively simple systems carried out in close connection with other methods of molecular genetics.


Author(s):  
K. Jacobson ◽  
A. Ishihara ◽  
B. Holifield ◽  
F. Zhang

Our laboratory is concerned with understanding the dynamic structure of the plasma membrane with particular reference to the movement of membrane constituents during cell locomotion. In addition to the standard tools of molecular cell biology, we employ both fluorescence recovery after photo- bleaching (FRAP) and digitized fluorescence microscopy (DFM) to investigate individual cells. FRAP allows the measurement of translational mobility of membrane and cytoplasmic molecules in small regions of single, living cells. DFM is really a new form of light microscopy in that the distribution of individual classes of ions, molecules, and macromolecules can be followed in single, living cells. By employing fluorescent antibodies to defined antigens or fluorescent analogs of cellular constituents as well as ultrasensitive, electronic image detectors and video image averaging to improve signal to noise, fluorescent images of living cells can be acquired over an extended period without significant fading and loss of cell viability.


Sign in / Sign up

Export Citation Format

Share Document