Omentin, vaspin and irisin in chronic liver diseases.

Omentin and vaspin are adipokines potentially considered in the development of liver pathology. Irisin is new myokin potentially participating in energy processes in the organisms. The aim of this study was to evaluate the plasma concentration of these cytokines and the relationships of them with selected parameters of laboratory tests and of histopathological changes in selected chronic liver diseases: non-alcoholic fatty liver diseases (NAFLD), primary biliary cholangitis (PBC) and alcoholic cirrhosis (AC). The plasma concentration of omentin was the highest in AC group and the lowest in control group (CG). Irisin plasma concentration was the highest in CG and the lowest in AC. Mean vaspin concentrations did not differ significantly between groups. Among many laboratory parameters, only in the AC group positive relationships were found between omentin concentration and bilirubin, as well as glucose, and negative between omentin level and the number of platelets and erythrocytes; there was a positive relationship between the concentration of vaspin and bilirubin, as well as negative between vaspin level and the number of erythrocytes or hematocrit value in this group. INR value had positive correlation with vaspin concentration and negative with irisin level in NAFLD group. No significant dependences between the concentrations of explored cytokines and laboratory tests were found in PBC group. It was found the positive correlation between the plasma concentration of irisin and fibrosis as well as inflammation in PBC group. The negative correlation between irisin level and inflammation in NAFLD was also showed. Omentin can be considered as an indicator for predicting inflammation, steatosis and balloon degeneration in NAFLD and PBC. Summarizing, it is unclear but possible that explored cytokines have some relationships with certain features of liver damage and development of chronic diseases of this organ.

Hawthorn revisited: time- and dose-dependent cardioprotective action of WS-1442 special extract in the reperfusion-induced arrhythmia model in rats in vivo.

Standardized WS-1442 extract from Crataegus oxycantha (hawthorn) leaves and berries is one of the most widely studied preparations received from hawthorn. This popular substance is known from its positive influence on the cardiovascular system. The current research aimed to evaluate the optimal dose of standardized WS-1442 extract and the most beneficial period for its use. The study analysis was based on experiments previously conducted on male Sprague-Dawley rats (n = 152). The animals were divided into subgroups to examine the relationship between the dose-dependent (n = 96) and time-dependent (n = 56) effects of the mentioned extract. The research was performed based on the modified early reperfusion-induced arrhythmias model in vivo. The following parameters were assessed during the study: efficiency of mortality index reduction, reduction of ventricular arrhythmias incidences as well as the influence of standardized WS-1442 extract on hemodynamic parameters and amount of biochemical marker of cardiac tissue damage (creatine kinase). The current study revealed the dose- and time-dependent cardioprotective effect of standardized WS-1442 extract. It was expressed by mortality index reduction, decrease in the incidence and duration of severe ventricular arrhythmias and decline in the total amount of creatine kinase. Analyzed data coming from a model of reperfusion-induced arrhythmias in rats suggests that standardized WS-1442 extract is a potent cardioprotective agent whose action depends on both dose and intake time.

Pharmacological and dietary factors in prevention of colorectal cancer.

Colorectal cancer (CRC) is the third most prevalent neoplasm worldwide and fourth most frequent reason of cancer-related death throughout the world. About 70% of malignant tumors are related to lifestyle and environmental factors, and better knowledge of their significance might reduce the prevalence of CRC. The cyclooxygenase-2 (COX-2) inhibitory and other direct and indirect pathways of aspirin are translated to inhibition proliferation and enhanced apoptosis of cancer cells. Many studies showed the benefits of aspirin in reducing the risk of CRC development, cancer-related mortality and adenoma prevalence rate in general population, but not in high risk populations. The role of sulindac in CRC prevention is uncertain and the use of this drug is rather uncommon. Celecoxib - COX-2 selective inhibitor- showed efficacy in decreasing of colon adenoma recurrence only in some studies. The protective role of microelements is controversial. The beneficial effects of supplementation of selenium, calcium, folic acid, methionine, antioxidant supplements and probiotics are still not certain. A high energy diet consisting of red meat, animal fat, highly processed foods and unsaturated fats increases the risk of CRC. Carcinogenic role of fat and cholesterol depends on increased production of primary bile acids. The importance of milk and dairy products in CRC prevention is controversial. Fruits, vegetables and grain are considered to have protective effects against adenoma and CRC. Excessive alcohol consumption, smoking, physical inactivity are considered as important CRC risk factors. This article briefly summarizes current state of knowledge about the role of pharmacological and dietary prevention of colorectal cancer. Moreover, it indicates that despite many studies some aspects of this issue are not clear and require future studies.

Crataegus special extract WS 1442: up-to-date review of experimental and clinical experiences.

Extracts and tinctures made from Crataegus spp. (Hawthorn) have been used as cardioprotective remedies since ancient times. WS 1442 special extract, manufactured by Dr. W. Schwabe Pharmaceuticals©, made from Crataegus spp. Leaves and flowers is one of the most studied and popular of preparations received from Hawthorn. It is integral, and most important active component of such herbal drugs as Crataegutt® novo 450, and CardioMax®. This standardized extract contains 18.75% oligomeric procyanidins (OPC), which have beneficial cardioprotective values and play a role as free-radicals scavengers, that protect the ischemic heart tissue from neutrophile elastase action successions. Moreover, WS 1442 also carries proven vasorelaxant activity, via affecting eNOS synthase, and prevents ischemic heart tissue swelling by influence on calcium signaling pathways, and thus detain hyperpermeability of endothelium. Actions of WS 1442 special extract were investigated in in vitro as well as in vivo studies including large clinical trials. In this review authors present current state of knowledge about possible beneficial effects of WS 1442 special extract on cardiovascular system.

Fibroblast growth factor-21 and omentin-1 hepatic mRNA expression and serum levels in morbidly obese women with non-alcoholic fatty liver disease.

Fibroblast growth factor-21 (FGF21) and omentin-1 have been recognized as potent antidiabetic agents with potential hepatoprotective activity. The aim of this study was to evaluate hepatic FGF21 and omentin-1 mRNA expression as well as their serum levels as predictive markers of liver injury and insulin resistance in morbidly obese women with non-alcoholic fatty liver disease (NAFLD). This study included 56 severely obese women who underwent intraoperative wedge liver biopsy during the bariatric surgery. Hepatic FGF21 and omentin-1 mRNA were assessed by quantitative real-time PCR, while their serum concentrations were measured with commercially available enzyme-linked immunosorbent assays. The FGF21 serum level was significantly higher in patients with a greater extent of steatosis (grade 2 and 3) compared to those without or with mild steatosis (grade 0 and 1) (P = 0.049). Receiver Operating Characteristic analysis, however, showed poor discriminant power for the FGF21 serum levels in differentiating between more and less extensive steatosis with an AUC = 0.666. There was a tendency towards higher levels of hepatic FGF21 mRNA in patients with lobular inflammation and fibrosis and towards lower levels in the case of hepatocyte ballooning and steatosis. There was a positive mutual correlation between hepatic FGF21 and omentin-1 mRNA levels (r = 0.78; P < 0.001). Fibrosis stage was associated with serum glucose and homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.03 and P = 0.02, respectively). Serum omentin-1 was not associated with histopathological features. The hepatic omentin-1 mRNA levels showed a tendency to be lower in patients with advanced steatosis and hepatocyte ballooning. In conclusion, our study, which focused on hepatic FGF21 and omentin-1 mRNA expression, confirmed marked expression of both molecules in the liver of morbidly obese patients with NAFLD. More extensive steatosis was associated with evident changes in the serum FGF21 concentration in morbidly obese women with NAFLD, but the difference did not reach statistical significance. The vast amount of fat, both visceral and subcutaneous, in severely obese patients may be the additional source and influence the FGF21 and omentin-1 serum levels.

Differential action of two prolactin isoforms on ischemia and re-perfusion-induced arrhythmias in rats in vivo.

BACKGROUND: The different influences of one of the PRL isoforms (PRL I) on the cardiovascular system have been described in the past. AIM: Our goal was to establish an appropriate iv dose of 2 PRL isoforms (PRL I and PRL II) in intact rats. After establishing this dose, PRL I (0.01 mg/kg) or PRL II (0.001 mg/kg) was administered in bolus 10 min before left anterior descending coronary artery occlusion (7 min) followed by re-perfusion (15 min). We then aimed to study and compare the effects of these isoforms on ischemia- and re-perfusion-induced arrhythmias in the ischemia and re-perfusion-induced arrhythmias model in rats. MATERIALS AND METHODS: Mortality index, ventricular fibrillation and tachycardia (VF, VT) incidence and duration, systolic, diastolic, and mean arterial blood pressure, heart rate and myocardial index of oxygen consumption [pressure rate product (PRP)] were measured and calculated. RESULTS: Both PRL isoforms reduced animal mortality (from 50 to 18.75 and 25%, respectively). PRL II significantly reduced VF incidence (to 25%) as well as VT duration (18.21 ± 3.09) and these effects were markedly different from PRL I and from the control group (p<0.05). Both PRL reduced PRP in the recovery phase (p<0.05). CONCLUSIONS: We proved that supraphysiological doses of PRL isoforms administered in bolus could protect against sudden cardiac death as well as severe arrhythmias episodes during re-perfusion. Because of PRL's positive influence on the cardiovascular system and as an endogenous, well-tolerated substance, it might be of potential clinical use.