Complementary and alternative medications in hepatitis C infection简

Chronic hepatitis C (CHC) infection affects almost 3% of the global population and can lead to cirrhosis, liver failure, and hepatocellular carcinoma in a significant number of those infected. Until recently, the only treatments available were pegylated interferon and ribavirin, which traditionally were not very effective and have considerable side effects. For this reason, interest in complementary and alternative medications (CAM) in the management of hepatitis C has been investigated. Some CAM has demonstrated therapeutic potential in chronic hepatitis C treatment. Unfortunately, some CAM has been shown to have the potential to cause drug-induced liver injury. This article will review and evaluate many of the natural molecules that interact with the hepatitis C virus (HCV) life cycle and discuss their potential use and safety in HCV therapy, as well as highlight some important interactions between medical and complementary treatments.     

Peroxisome proliferator-activated receptor-gamma agonists and diabetes: current evidence and future perspectives

Since their initial availability in 1997, the thiazolidinediones (TZDs) have become one of the most commonly prescribed classes of medications for type 2 diabetes. In addition to glucose control, the TZDs have a number of pleiotropic effects on myriad traditional and non-traditional risk factors for diabetes. TZDs may benefit cardiovascular parameters, such as lipids, blood pressure, inflammatory biomarkers, endothelial function and fibrinolytic state. In this review, we summarise the experimental, preclinical and clinical data regarding the effects of the TZDs in conditions for which they are indicated and discuss their potential in the treatment of other conditions.     

Effect of Perioperative Somatostatin Administration of Sphincteroplasty-Induced Increase of Amylase

Twenty patients undergoing sphincteroplasty for cholelithiasis were randomly divided into two groups of 10. The former (T) were treated with a 4-h somatostatin intravenous drip (250 micrograms/h), started at the beginning of operation, while the latter (C) made up the control group. Serum and urine amylase, amylase creatinine clearance ratio, and liver function tests were assessed for 2 days before surgery, after the operation and for a period of 5 postoperative days. Homogeneity between the two series was verified in experimental conditions. Statistical differences occurred postoperatively in amylase creatinine clearance ratio, which proved higher in C group, and gamma-GT, which was higher in T group. Short-term somatostatin administration proved effective in reducing the postoperative amylase creatinine clearance ratio, although more evident results are reported after long-term administration. Cholestasis or any serious impairment in liver function did not occur, suggesting the suitability of somatostatin use even in patients with jaundice. Since a relationship between postoperative amylase levels and risk of pancreatitis has not yet been proved, the value of somatostatin in the prevention of postoperative pancreatitis after sphincteroplasty needs to be further verified.     

Lactate release during the recovery period of pacing-induced angina in assessment of myocardial ischaemia

Myocardial lactate (L) metabolism was tested in 27 stable angina patients during atrial pacing (AP) and in the recovery period (R) from AP-induced angina pectoris. The recovery period was assessed in order to evaluate the changes in the rate of L release and detect possible relationships with the severity of ischaemic damage. The following variables were assessed: coronary sinus blood flow (CSBF), left ventricular end-diastolic pressure (LVEDP), lactate extraction ratio (L%), lactate extraction or release rate (LR) and myocardial oxygen consumption (MVO2) at the onset of AP (AP1), during angina (AP2), and 30 s, 2 and 4 min (R1, R2 and R3) after AP ceased. At Ap2, negative L% and LR values (-39.37 +/- 43.3, -3.2 +/- 2.9) were found, in spite of a rise in CSBF (+86%, P less than 0.001). Furthermore, LVEDP showed its maximal increase in AP2 (+27%, P less than 0.001). Compared to AP2, L% resulted unchanged in R1, while LR showed a mild decrease (from -3.2 +/- 2.9 to +2.06 +/- 2.93). Lactate production was converted to extraction in R3 only. Since lactate production and release are progressively reduced with increasing severity of ischaemic damage, AP2 coronary sinus lactate release should largely arise from the less damaged areas (i.e. the outer myocardial layers) and the contribution of the more damaged areas (i.e. the inner myocardial layers) should be more limited. After AP ceases, the mild ischaemic areas should recover more rapidly than the severely ischaemic areas, where the damage only declines, leading to a temporary increase in lactate production and release.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of Physical Activity on Gastric Emptying of Liquids in Normal Human Subjects

Liquid gastric emptying has been evaluated in 17 normal human subjects during basal conditions, after mild physical stress at 50% of the maximum predictable heart rate, and after maximal physical stress at 70% maximum heart rate. Each subject exercised on a treadmill for 30 min, its speed and inclination varied in order to obtain the desired heart rate. Immediately after the exercise, 400 ml of mineral water were drunk by each subject. Gastric emptying was evaluated by real-time ultrasonography (11 subjects) and scintigraphy (six subjects) through previously described methods. The results show similar data with both techniques. Gastric emptying of the water, considered either as reduction in gastric measurements at ultrasonography or decay in radioactivity in the region of interest corresponding to the stomach at scintigraphy, follows a linear relationship under basal conditions and during physical stress. Compared with basal conditions, gastric emptying of water after maximal stress was prolonged; after mild stress, gastric emptying of the water was accelerated. These findings may support the common belief that mild physical activity favors the digestive process.     

Sarcopenia and Vitamin D Deficiency in Patients with Crohn’s Disease: Pathological Conditions That Should Be Linked Together

Sarcopenia is a prevalent condition in patients with Crohn’s disease (CD), representing an independent predictor factor for the development of major postoperative complications. Thus, a proper assessment of the muscle strength, by using different validated tools, should be deemed an important step of the clinical management of these patients. Patients with CD are frequently malnourished, presenting a high prevalence of different macro- and micro-nutrient deficiencies, including that of vitamin D. The available published studies indicate that vitamin D is involved in the regulation of proliferation, differentiation, and regeneration of muscle cells. The relationship between vitamin D deficiency and sarcopenia has been extensively studied in other populations, with interesting evidence in regards to a potential role of vitamin D supplementation as a means to prevent and treat sarcopenia. The aim of this review was to find studies that linked together these pathological conditions.     

Gastrointestinal dysmotility in mitochondrial neurogastrointestinal encephalomyopathy is caused by mitochondrial DNA depletion

Chronic intestinal pseudo-obstruction is a life-threatening condition of unknown pathogenic mechanisms. Chronic intestinal pseudo-obstruction can be a feature of mitochondrial disorders, such as mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a rare autosomal-recessive syndrome, resulting from mutations in the thymidine phosphorylase gene. MNGIE patients show elevated circulating levels of thymidine and deoxyuridine, and accumulate somatic mitochondrial DNA (mtDNA) defects. The present study aimed to clarify the molecular basis of chronic intestinal pseudo-obstruction in MNGIE. Using laser capture microdissection, we correlated the histopathological features with mtDNA defects in different tissues from the gastrointestinal wall of five MNGIE and ten control patients. We found mtDNA depletion, mitochondrial proliferation, and smooth cell atrophy in the external layer of the muscularis propria, in the stomach and in the small intestine of MNGIE patients. In controls, the lowest amounts of mtDNA were present at the same sites, as compared with other layers of the gastrointestinal wall. We also observed mitochondrial proliferation and mtDNA depletion in small vessel endothelial and smooth muscle cells. Thus, visceral mitochondrial myopathy likely causes gastrointestinal dysmotility in MNGIE patients. The low baseline abundance of mtDNA molecules may predispose smooth muscle cells of the muscularis propria external layer to the toxic effects of thymidine and deoxyuridine, and exposure to high circulating levels of nucleosides may account for the mtDNA depletion observed in the small vessel wall.     

Involvement of cPLA2 inhibition in dexamethasone-induced thymocyte apoptosis

Various molecular mechanisms have been suggested to be involved in dexamethasone induced thymocyte apoptosis. In this study we show that pharmacological inhibition of cytoplasmic PLA2 in mouse thymocytes for 18 h with arachidonyl trifluoromethyl ketone (AACOCF3) (10 microM) and palmitoyl trifluoromethyl ketone (PACOCF3) (10 microM) induced a drastic increase of thymocyte apoptosis comparable to that observed following Dex (10(-7) M) treatment, while inhibition of secretory PLA2 with p-bromophenacyl bromide (pBPB) (20 microM) did not. AACOCF3-induced thymocyte apoptosis, similarly to Dex-induced thymocyte apoptosis, was eliminated by cell pre-treatment with the PI-PLCbeta inhibitor, U73122, but not by the PC-PLC inhibitor D609. These observations were corroborated by the ability of AACOCF3, like Dex, to induce a rapid and transient increase in DAG generation. In addition, AACOCF3-induced apoptosis involved the activation of the acidic sphingomyelinase (aSMase) but not of the neutral sphingomyelinase (nSMase), as evaluated by measurements of enzyme activity in cell extracts following thymocyte exposure to AACOCF3 and by the ability of monensin to inhibit AACOCF3-induced thymocyte apoptosis. In addition, the AACOCF3 apoptotic effect resulted in an early increase of ceramide levels. AACOCF3-induced thymocyte apoptosis involved the activation of caspase 3, and cell pre-treatment with a caspase 3 inhibitor prevented AACOCF3-induced apoptosis. These observations suggest that cPLA2 inhibition may have a role in Dex-induced thymocyte apoptosis and highlight the importance of cPLA2 activity in thymocyte survival.     

Association between immunity and prognostic factors in early stage breast cancer patients before adjuvant treatment

Objective: The association of known prognostic factors with immune cell counts and ₂-microglobulin and soluble IL-2 receptor (sIL-2r) serum levels as markers of activation of the immune system was investigated in breastcancer. Methods: Two hundred thirty five operated stage I and II breast cancer patients to receive adjuvant treatment in IBSCG trials were assessed in a cross-sectional study immediately before the first treatment. Leukocytes, lymphocytes and lymphocyte subset counts, ₂-microglobulin and sIL-2r serum levels were assessed as immunological parameters. Prognostic factors were tumor load, receptor status, patient characteristics, and contextual factors of the immune assessment (such as time of the day, time since surgery, type of surgery, concomitant medication, co-morbidity). Results: In an operated early stage breast cancer patient population, tumor load was not associated with immune cell counts, ₂-microglobulin, or sIL-2r before adjuvant treatment. There was a pattern of association of prognostically favorable factors such as estrogen receptor (ER) positive tumor and older age with higher NK cell counts or with ₂-microglobulin or sIL-2r. In addition, immune cell counts and the markers of activation of the immune system were affected by several contextual factors, such as diurnal variability, time since surgery, type of surgery, and the intake of concomitant medication. Conclusions: The association of NK cell counts and ₂-microglobulin or sIL-2r serum levels with prognostically favorable factors such as ER positive tumor and older age supports the assumption that the immune system plays a role in the course of early breast cancer. The exact nature of this role requires furtherstudy.