In vivo effects of caffeic acid phenethyl ester on myocardial ischemia-reperfusion injury and apoptotic changes in rats

Ischemia/reperfusion (I/R) has been reported to induce apoptotic cellular death in myocardium. This study tested the hypothesis that caffeic acid phenethyl ester (CAPE), one of the active components of propolis, may ameliorate myocardial apoptosis and oxidative myocardial injury. Wistar rats were divided into 4 groups: (i) sham operated, (ii) I/R, (iii) I/R+CAPE, and (iv) I/R+glutathione (GSH). CAPE (10 micromol/kg) was infused iv 10 min before occlusion of the left anterior descending coronary artery (30 min) followed by reperfusion (120 min). GSH (5 mg/kg) was infused iv after the occlusion and immediately before reperfusion. The TdT-mediated in situ nick end-labeling (TUNEL) method was used to evaluate apoptotic activity. I/R resulted in myocardial apoptosis, alterations of antioxidant status, elevation of serum creatine kinase (CK) and aspartate aminotransferase (AST) activities, evidence of lipid peroxidation, and elevated nitric oxide levels, compared to the sham-operation group. No apoptotic cells were found in the myocardial tissue of sham-operated rats. The TUNEL-positive myocardial cells averaged 60%, 30%, and 40% in the I/R, I/R+CAPE, and I/R+GSH groups, respectively. This study demonstrates that pretreatment with CAPE provides cardio-protection from I/R injury. The I/R+CAPE group showed reduced apoptosis, attenuated NO production, elevated myocardial superoxide dismutase (SOD) activity, and diminished serum CK and AST activities, compared to the I/R group.     

Determinants and consequences of sexual networks as they affect the spread of sexually transmitted infections

Because pathogens spread only within the unique context of a sexual union between people when one person is infectious, the other is susceptible to new infection, and condoms are not used to prevent transmission, the epidemiological study of sexually transmitted infections (STIs) is particularly challenging. Social network analysis entails the study of ties among people and how the structure and quality of such ties affect individuals and overall group dynamics. Although ascertaining complete sexual networks is difficult, application of this approach has provided unique insights into the spread of STIs that traditional individual-based epidemiological methods do not capture. This article provides a brief background on the design and assessments of studies of social networks, to illustrate how these methods have been applied to understanding the distribution of STIs, to inform the development of interventions for STI control.     

Failure to detect hepatitis B virus in vitreous by polymerase chain reaction

PURPOSE: To assay the vitreous of asymptomatic hepatitis B virus (HBV) carriers for the presence of HBV DNA using polymerase chain reaction (PCR). METHODS: Vitreous and serum specimens were collected from 13 carriers of HBV. The presence of HBV DNA was investigated by using PCR and Digene's Hybrid Capture System. The presence of hepatitis B surface antigen (HBsAg) in vitreous was also investigated by using the enzyme immunoassay (EIA). RESULTS: The serum was positive for HBV DNA in3 of the 13 asymptomatic carriers using PCR. Vitreous samples of all the patients, including 3 patients who were positive for HBV DNA in serum, were negative for HBV DNA with PCR and were negative for HBsAg with EIA. CONCLUSION: There is no evidence of HBV in the vitreous of asymptomatic HBV carriers.     

Design and synthesis of tri-ring P3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin K

We have prepared a series of achiral aminoacetonitriles, bearing tri-ring benzamide moieties and an aminocyclohexanecarboxylate residue at P2. This combination of binding elements resulted in sub-250 pM, reversible, selective, and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of bovine bone). The best compound in this series, 39n (CRA-013783/L-006235), was orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen breakdown products were reduced by up to 76% dose-dependently. Plasma concentrations of 39n above the bone resorption IC50 after 24 h indicated a correlation between functional cellular and in vivo assays. Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.     

Effects of pars plana vitrectomy on retrobulbar haemodynamics in diabetic retinopathy

BACKGROUND: The purpose of the present study was to determine the effects of pars plana vitrectomy on retrobulbar haemodynamics in patients with proliferative diabetic retinopathy (PDR). METHODS: Colour Doppler imaging was used for measurement of blood flow velocities and resistive index of the ophthalmic artery (OA), posterior ciliary arteries (PCA) and central retinal artery (CRA) in 14 eyes of 14 patients with PDR before pars plana vitrectomy and at the 1 and 6 months after operation. The patients were also treated by laser photocoagulation before or during surgery. Twenty age- and sex-matched healthy subjects were used as control group. RESULTS: Mean peak systolic velocity and the end diastolic velocity of the CRA in the patients with PDR were lower and the mean resistive index was higher than in those of the control group (P < 0.05). The mean end diastolic velocity of OA in the patients was lower and the mean resistive index was higher than in the control group (P < 0.05). The peak systolic velocity of the OA and the end diastolic velocity of the CRA were significantly increased (P = 0.043 and P = 0.018, respectively) and the mean resistive index of the CRA was significantly decreased after pars plana vitrectomy (P = 0.043). No significant changes were detected among preoperative and postoperative values of peak systolic velocity, end diastolic velocity, and resistive index of the PCA and the mean velocity of the central retinal vein (P > 0.05). CONCLUSIONS: The blood flow velocities of OA and CRA are decreased but the resistive index is increased significantly in patients with PDR. Pars plana vitrectomy in patients with PDR may decrease resistive index and improve blood flow in the CRA.     

Comparing the efficacy of nebulizer recombinant human DNase and hypertonic saline as monotherapy and combined treatment in the treatment of persistent atelectasis in mechanically ventilated newborns

Background: The purpose of the present study was to compare the cost‐effectiveness and efficacy of nebulizer recombinant human DNase (rhDNase) and hypertonic saline (HS) as monotherapy and combined treatment in neonatal atelectasis. Methods: Eighty‐seven newborns with persistent atelectasis who did not respond to traditional treatment were studied retrospectively. Group 1 did not receive nebulizer drugs; Group 2 received 7%HS; Group 3 received rhDNase; and Group 4 received both 7%HS and rhDNase. Subjects' chest X‐ray scores, partial pressure of CO₂, respiratory rate, fraction of inspired oxygen (FiO₂) peak inspiratory pressure, atelectasis healing rate, median duration of nebulizer treatment and costs were compared. Results: Percentages of improvement in atelectasis on Day 3 of treatment in Group 1, Group 2, Group 3 and Group 4 were 27, 70, 81 and 95%, respectively, while median duration of treatment was 8.1, 3.3, 2.9 and 2.4 days, respectively. Comparison of chest X‐ray scores, partial pressure of CO₂, respiratory rate, FiO₂ and peak inspiratory pressure values before and 48 h after treatment did not yield a significant difference for the control group (P > 0.05), while a marked improvement was observed in other groups for all parameters (P < 0.05). The most distinct improvement was in Group 4, followed by Group 3. Conclusions: Although both the combined treatment with HS and rhDNase and their monotherapies are effective in the treatment of persistent atelectasis in newborns receiving mechanical ventilation, their combined use produces higher efficacy. The efficacy of rhDNase is superior to monotherapy with HS. Use of these two treatments concomitantly reduces the cost. To the best of our knowledge, the present study is the first to use HS alone or in combination with rhDNase in newborn patients.     

Fucoidin, a neutrophil rolling inhibitor, reduces damage in a rat electrical burn injury model

Background

Electrical injuries induce progressive tissue loss caused by free oxygen radicals released from neutrophil aggregates. Fucoidin, a potent inhibitor of L-selectin function, reduces the aggregation of neutrophils. The aim of this study was to evaluate the effect of fucoidin on tissue damage in rat electrical burn injury model.

Methods

Forty-two male Wistar albino rats (250–300 g) were divided into 3 groups (Group A (n = 6), control group without electrical burn injury; Groups B (n = 18) and C (n = 18), electrical burn injury groups without and with fucoidin therapy, respectively). Three separate analyses were performed at different time points on 6 out of 18 mice from Group B and C at each time point. Biochemistry (myeloperoxidase and malondialdehyde levels) and histopathology (number of neutrophils) of the skin and muscle biopsies at 1st hour; tissue edema (ratio of wet weight/dry weight of extremities) at 24th hour; and necrotic areas at 7th day after electrical injury were evaluated. The electrical burn was induced by exposing rats to 220 V AC between their left upper extremity and right lower extremity for 10 s. Fucoidin was administered as 25 mg/kg intravenous bolus injection at 15 min after electrical burn injury.

Results

Myeloperoxidase and malondialdehyde levels, number of neutrophils, tissue edema, and necrotic area were significantly less in fucoidin-applied rats than the group without fucoidin therapy.

Conclusions

Fucoidin inhibits tissue damage induced by electrical burn injury in rats by reducing necrotic area, edema and number of neutrophils.     

The effect of dialytic modalities on clinical outcomes in ESRD patients with familial Mediterranean fever

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease seen primarily in Sephardic Jews, Turks, and Armenians. The disease manifests as recurrent attacks of fever and serositis. The most important complication of FMF is the development of renal failure due to AA type amyloidosis. There has not been extensive experience with renal replacement therapy in FMF amyloidosis. Nevertheless, there may be a concern about the possibility of higher rates of morbidity and mortality in amyloidotic patients maintained on chronic hemodialysis. Moreover, there is not enough experience regarding patients on chronic peritoneal dialysis. As a result, the best treatment modality of end-stage renal disease (ESRD) in these circumstances still remains unclear. This study aimed to compare the effect of hemodialysis and peritoneal dialysis modalities on clinical outcomes in ESRD patients associated with FMF amyloidosis. METHODS: Forty FMF patients with ESRD due to amyloidosis were retrospectively analyzed. All 40 patients were on renal replacement therapy, 20 on hemodialysis (HD), 20 on peritoneal dialysis (PD). Peritoneal solute transport rates, weekly mean creatinine clearance, and daily mean ultrafiltration (UF) of the patients on chronic peritoneal dialysis were evaluated. Weekly dialysis durations, dialysis membrane properties, Kt/V values, interdialytic weight gains, and frequency of hypotension during dialysis were evaluated on hemodialysis patients. All of the patients were examined according to their demographic characteristics, laboratory results, duration time on dialysis, erythropoietin requirements, frequencies of infectious complications requiring hospitalization, and the two renal replacement modalities mentioned above were compared in terms of these parameters. RESULTS: Serum albumin levels of the patients with FMF amyloidosis who were maintained on peritoneal dialysis treatment were lower (2.87 vs 3.45) and the frequency of infections of the same group was higher (4.2 vs 0.5) than the patients with ESRD secondary to other diseases in the CAPD group. CONCLUSIONS: This retrospective analysis showed that peritoneal dialysis may have some disadvantages in amyloidotic patients. Due to the high frequency of hypoalbuminemia and infectious complications seen in this group, peritoneal dialysis is widely accepted as an alternative choice of treatment when hemodialysis is not appropriate.