ABSTRACT
Liver diseases constitute a major healthcare burden globally, including acute hepatic injury resulted from acetaminophen overdose, ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Attainable treatment strategies for most liver diseases remain inadequate, highlighting the importance of substantial pathogenesis. The transient receptor potential (TRP) channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver. It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels. Here, we discuss recent findings revealing TRP functions across the fundamental pathological course from early hepatocellular injury caused by various insults, to inflammation, subsequent fibrosis and hepatoma. We also explore expression levels of TRPs in liver tissues of ALD, NAFLD and HCC patients from Gene Expression Omnibus (GEO) or The Cancer Genome Atlas (TCGA) database and survival analysis estimated by Kaplan-Meier Plotter. At last, we address the therapeutical potential and challenges by pharmacologically targeting TRPs to treat liver diseases. The aim is to provide a better understanding of the implications of TRP channels in liver diseases, contributing to the discovery of novel therapeutic targets and efficient drugs.
ABSTRACT
Chronic subdural hematoma (CSDH), which rarely happens in the young, is thought to be a disease of the elderly. Whereas unspecific symptoms and insidious onset in juveniles and young adults, as a result of its relative low morbidity, CSDH is usually neglected even undertreated in the young. Through the three cases and review of the current literature on this subject, we tried to illustrate the clinical and etiopathological characteristics of this entity and find out the most appropriate treatment strategy. We report three young CSDH patients with different but similar symptoms. The present histories, tests and examinations revealed different predisposing factors accounting for the genesis of CSDH. Their preoperative symptoms were all resolved with burr hole and drainage operation. Juveniles and young adults suffering from CSDH differ from that of their elderly counterparts in their clinical and etiopathological characteristics. Although trauma is the most important risk factor in young and old CSDH patients, some other predisposing factors may exist. Burr hole and drainage surgery could resolve the problem most of the time. But further tests and examinations even specific management should be made in some cases.
Subject(s)
Aged , Humans , Young Adult , Causality , Drainage , Hematoma, Subdural, Chronic , Intracranial Hypotension , Risk FactorsABSTRACT
As a novel drug in the treatment of cardiac diseases, dl-praeruptorin A [Pd-Ia] is the major active component of traditional herbal medicine Peucedanum praeruptorum Dunn and is metabolized primarily via cytochrome P450 isozymes [CYP] 3A1 and 3A2 in rats. In the present study, the influence of liver cirrhosis on pharmacokinetics of Pd-Ia and hepatic mRNA expression of CYP3A1 and 3A2 in rats with experimental liver cirrhosis [LC rats] were evaluated. Pd-Ia was given intravenously [5 mgúkg-1] to LC rats induced by dimethylnitrosamine and pharmacokinetic variables were measured. Enzyme kinetic metabolism of Pd-Ia in rat hepatic microsomes was also investigated and hepatic mRNA expression of CYP3A1 and 3A2 were measured by real-time PCR. After intravenous administration in LC rats, the area under the plasma concentration-time curve from time zero to infinity [AUC0-infinity] was significantly greater than that in control rats, which might be due to slower rate of the hepatic blood flow and significant slower hepatic intrinsic clearance [CL int] in rats. The decreased metabolic clearance of Pd-Ia in LC rats might be at least partly caused by the decreased levels of CYP3A1 and 3A2 responsible for Pd-Ia metabolism. These findings may provide new insights into the inter- and intra-individual pharmacokinetic variability of Pd-Ia
ABSTRACT
OBJECTIVE: To investigate the possible effects of recruitment maneuver (RM) imposing on extravascular lung water (EVLW) in patients with acute respiratory distress syndrome (ARDS). METHODS: Twenty patients with ARDS who were eligible for the study were randomized to two groups, one group of which received regular therapy+RM (RM group), and to the other group only regular therapy was given (control group). Mechanical ventilation of all the patients was performed on the principles of lung protective ventilation. RM was carried out in bi-level positive airway passage (BIPAP) mode, and repeated every 8 hours per day until on the 7th day or before weaning of mechanical ventilation. The treatment was same between the two groups except RM. Baseline data and the influencing factors of EVLW were all recorded, which included everyday EVLW, extravascular lung water index (EVLWI) after RM, respiratory mechanics, oxygenation parameters, central venous pressure (CVP), plasma colloid osmotic pressure (COP), dosage of corticosteroid and adrenergic drugs, 24-hour net fluid balance. RESULTS: EVLW and EVLWI in RM and control group showed a tendency of decrease with passage of time, but the difference between both groups had no statistical significance (all P>0.05). The comparisons between the influencing factors of the groups, consisting of CVP, COP, noradrenalin and hydrocortisone, had no significant difference either (all P>0.05). Dopamine dosage in RM group on the 4th day was smaller than that of control group (P0.05). CONCLUSION: RM for the patients with ARDS can merely improve lung mechanics without obvious effect on EVLW. Neither of the influencing factors involved in the study has impact on emergence and clearance of EVLW.