Effects of morning versus evening intake of atorvastatin on major cardiac event and restenosis rates in patients undergoing first elective percutaneous coronary intervention

It is not known whether taking atorvastatin in the morning versus in the evening has a different effect on major cardiac event and restenosis rates in patients undergoing percutaneous coronary intervention. Therefore, the aim of the present study was to investigate the effects of morning versus evening intake of atorvastatin on major cardiac events and restenosis rates and also on serum lipid and high sensitivity C-reactive protein levels in patients with single-vessel disease who underwent first elective percutaneous coronary intervention.     

Blockade of endocannabinoid hydrolytic enzymes attenuates precipitated opioid withdrawal symptoms in mice

Δ(9)-Tetrahydrocannbinol (THC), the primary active constituent of Cannabis sativa, has long been known to reduce opioid withdrawal symptoms. Although THC produces most of its pharmacological actions through the activation of CB(1) and CB(2) cannabinoid receptors, the role these receptors play in reducing the variety of opioid withdrawal symptoms remains unknown. The endogenous cannabinoids, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), activate both cannabinoid receptors but are rapidly metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. The objective of this study was to test whether increasing AEA or 2-AG, via inhibition of their respective hydrolytic enzymes, reduces naloxone-precipitated morphine withdrawal symptoms in in vivo and in vitro models of opioid dependence. Morphine-dependent mice challenged with naloxone reliably displayed a profound withdrawal syndrome, consisting of jumping, paw tremors, diarrhea, and weight loss. THC and the MAGL inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) dose dependently reduced the intensity of most measures through the activation of CB(1) receptors. JZL184 also attenuated spontaneous withdrawal signs in morphine-dependent mice. The FAAH inhibitor N-(pyridin-3-yl)-4-(3-(5-(trifluoromethyl)pyridin-2-yloxy)benzyl)-piperdine-1-carboxamide (PF-3845) reduced the intensity of naloxone-precipitated jumps and paw flutters through the activation of CB(1) receptors but did not ameliorate incidence of diarrhea or weight loss. In the final series of experiments, we investigated whether JZL184 or PF-3845 would attenuate naloxone-precipitated contractions in morphine-dependent ilea. Both enzyme inhibitors attenuated the intensity of naloxone-induced contractions, although this model does not account mechanistically for the autonomic withdrawal responses (i.e., diarrhea) observed in vivo. These results indicate that endocannabinoid catabolic enzymes are promising targets to treat opioid dependence.     

皮肤渗透促进剂桉叶素的研究

研究了桉叶素促进５－氟尿嘧啶渗透通过离体大鼠皮肤的作用,其增加药物渗透系数约达９３倍。桉叶素提高了分配系数,但对扩散系数的增加更大。去除角质层,药物的渗透障碍完全消失。与全皮相比,角质层去除后药物的渗透系数增加１６６倍,表明影响极性药物渗透的主要障碍是角质层。促渗效果可能是扩散和分配综合作用的结果,其中扩散是主要作用。     

The Clinical Significance of Serum Apoptotic Cytokeratin 18 Neoepitope M30 (CK-18 M30) and Matrix Metalloproteinase 2 (MMP-2) Levels in Chronic Hepatitis B Patients with Cirrhosis

Background

Serum apoptotic cytokeratine 18 neoepitope M30 (CK-18 M30) and matrix metalloproteinase 2 (MMP-2) have been popular markers for detecting liver fibrosis in recent years. CK-18 is a major intermediate filament protein in liver cells and one of the most prominent substrates of caspases during hepatocyte apoptosis. MMP-2 plays an important role in tissue remodeling and repairing processes during physiological and pathological states.

Objectives

The objective of this study was to investigate the significance of CK-18 M30 and MMP-2 levels for clinical use in patients with chronic hepatitis B (CHB), as well as their sensitivity in determining cirrhotic patients.

Patients and Methods

This study included 189 CHB patients and 51 healthy controls. A modified Knodell scoring system was used to determine the fibrosis level in chronic hepatitis B patients. CK-18 M30 levels were determined with an M30-Apoptosense ELISA assay. MMP-2 levels were determined with the ELISA assay.

Results

The study group consisted of 132 (69.8%) males and 57 (30.2%) females, and the control group consisted of 25 males (49.0%) and 26 females (51%). Patients’ CK-18 M30 levels were higher than values of the control group (308 [1–762] vs. 168 [67–287], P=0.001). Serum MMP-2 levels were found to be statistically higher in the patient group with respect to the controls (3.0 [1.1–6.8] vs. 2.0 [1.2–3.4], P=0.001). The highest serum CK-18 M30 and MMP-2 levels were measured in patients with cirrhosis. Serum apoptotic CK-18 M30 levels positively correlated with advanced age, fibrosis stage, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (P= 0.001, 0.033, 0.001, and 0.001, respectively). Serum MMP-2 levels positively correlated with fibrosis stage, serum ALT, and AST levels (P= 0.001, 0.001, and 0.001, respectively).

Conclusions

Our study indicated that CK-18 M30 and MMP-2 levels were higher in CHB patients compared to healthy controls and they were in association with significant hepatic fibrosis, especially cirrhosis.     

Pregnancy outcomes in women with heart disease

Aim

To evaluate the maternal and fetal outcome of pregnancies complicated by cardiac disease in a developing country.

Methods

A retrospective analysis was carried out of 144 pregnancies in women with cardiac disease who delivered in our unit between 1997 and 2006. Perinatal and maternal outcomes were interpreted according to the type of the heart disease and status of the patient according to the New York Heart Association (NYHA) classification.

Results

The rates of rheumatic and congenital heart disease were 87.5 and 12.5%, respectively. The distribution of the patients according to the NYHA functional classification were 55.6, 36.1 and 8.3% for NYHA classes I, II and III–IV, respectively. There was no maternal mortality. Maternal morbidity was observed in 16 (11.1%) cases. Six perinatal mortalities (4.2%) occurred in this series. There were no significant difference in birth weight, gestational age at delivery and perinatal morbidity between the NYHA stage I–II and stage III–IV groups (P > 0.05), whereas maternal morbidity and cesarean delivery rates were significantly higher in the NYHA stage III–IV group (P < 0.001).

Conclusion

Rheumatic heart disease with pregnancy is still predominant in Turkey. Most of the patients were in a good functional group. Maternal morbidity strongly correlates with maternal cardiac classification.     

The relationship between the helicobacter pylori seropositivity with systemic and local oxidative status and hyperemesis gravidarum: a pilot study

Objectives: The aim of study was to determine the helicobacter pylori (HP) seropositivity and oxidative parameters in serum and saliva of pregnant women with poor oral hygiene and hyperemesis gravidarum (HG).

Methods: A case-control study was conducted involving 50 pregnant women in their first trimester of pregnancy. Twenty-five subjects had a diagnosis of HG, and remaining 25 were healthy pregnant women who served as control subjects were included. The groups were adjusted for age, parity and gestational week. All patients were subjected to the measurement of total oxidant status (TOS) and total antioxidant status in serum and saliva. Also HP seropositivity was investigated.

Results: Serum TAS and TOS values were similar, although oxidative burden in saliva of women with HG were significantly higher than controls. HP seropositivity was found to be 24% in women with HG and 4% of controls.

Conclusions: Our results suggest that significantly increased oxidative burden and slightly decreased antioxidative capacity of saliva may be involved in the pathogenesis of HG and this condition may be the result of HP infection which was found to be significantly more common in women with poor oral hygiene and HG.