Doxorubicin Induced Nephrotoxicity: Protective Effect of Nicotinamide

Introduction. Nephrotoxicity is one of the important side effects of anthracycline antibiotics. The aim of this study was to investigate the effects of nicotinamide (NAD), an antioxidant agent, against nephrotoxicity induced by doxorubicin (DXR). Methods. The rats were divided into control, NAD alone, doxorubicin (20 mg/kg, i.p.) and DXR plus NAD (200 mg/kg, i.p.) groups. At the end of the 10th day, kidney tissues were removed for light microscopy and analysis. The level of tissues' catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), inducible nitric oxide (iNOS) and endothelial nitric oxide (eNOS) activities were determined. Results. The activities of CAT, GPx, and GSH were decreased, and Po was increased in renal tissue of doxorubicin group compared with other groups. The tissue of the doxorubicin group showed some histopathological changes such as glomerular vacuolization and degeneration, adhesion to Bowman's capsule and thickening and untidiness of tubular and glomerular capillary basement membranes. Histopathological examination showed that NAD prevented partly DXR-induced tubular and glomerular damage. Conclusions. Pretreatment with NAD protected renal tissues against DXR-induced nephrotoxicity. Preventive effects of NAD on these renal lesions may be via its antioxidant and anti-inflammatory action

Comparison of active vs. expectant management of the third stage of labor in women with low risk of postpartum hemorrhage: a randomized controlled trial

Objectives: To compare the ‘strictly’ active management protocol in women with low risk of postpartum hemorrhage using the expectant management protocol with respect to changes in hematologic parameters, uterotonics, blood transfusions, or additional interventions. Material and methods: A randomized controlled prospective trial in which 934 singleton parturients enrolled; 654 were randomly assigned to the active and mixed management groups. The primary outcome parameter was the reduction in hemoglobin concentrations due to delivery, and the secondary outcome parameters were changes in hemoglobin of more than 3 g/dL (ΔHb ≥ 3 g/dL), durations of the third stage of labor, need for additional uterotonic agents, blood transfusions, manual removal of the placenta, and surgical evacuation of retained products of conception. Results: The mean postpartum hemoglobin concentration was significantly higher (P = 0.04) in the active management group with a significantly lower reduction (P = 0.03). Falls of hemoglobin levels of more than 3 g/dL (ΔHb ≥ 3g/dL) were less common in the active management group though not significantly (P = 0.32). The mean duration of the third stage of labor was significantly (P < 0.001) shorter in the active management group. There was no significant difference between the two groups with regard to the need for additional uterotonic agents, uterine atony, blood transfusion, manual removal of the placenta, surgical evacuation of retained products of conception, and prolonged third stage of labor. Conclusions: Although active management of the third stage of labor was associated with higher postpartum hemoglobin levels, it did not influence the risk of ‘severe postpartum hemorrhage’ in women with low risk of postpartum hemorrhage

Characteristics of symptoms and symptom change across different heart failure subtypes: a sex-stratified analysis

Aim: To examine sex-stratified differences in the association of left ventricular ejection fraction-based heart failure (HF) subtypes and the characteristics and correlates of self-reported changes in HF symptoms. Methods and Results: We report a secondary data analysis from 528 hospitalised individuals diagnosed with HF characterised by a reduced, mildly reduced, or preserved ejection fraction (HFrEF, HFmrEF, or HFpEF) who completed 12-month follow-up within a multicentre disease management trial. There were 302 men (71.1 ± 11.9 years, 58% with HFrEF) and 226 women (77.1 ± 10.6 years, 49% with HFpEF). The characteristics of self-reported symptoms measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12-month were analysed. At baseline, shortness of breath and fatigue predominated; with key differences according to HF subtypes in bilateral ankle oedema (both sexes), walking problems (women) and depressive symptoms (men). At 12month follow-up, most KCCQ scores had not significantly changed. However, 25% of individuals reported worse symptom. In women, those with HFpEF had worse symptoms than those with HFmrEF/HFrEF (p = 0.025). On an adjusted basis, women (OR 1.78, 95%CI 1.00-3.16 versus men), those with coronary artery disease (OR 2.01, 95%CI 1.21-3.31) and baseline acute pulmonary oedema (OR 1.67, 95%CI 1.02-2.75) were most likely to report worsening symptoms. Among men, worsening symptoms correlated with a history of hypertension (OR 2.16, 95%CI 1.07-4.35) and a non-English-speaking background (OR 2.30, 95%CI 1.02-5.20). Conclusion: We found significant heterogeneity (with potential clinical implications) in the symptomatic characteristics and subsequent symptom trajectory according to the sex and HF subtype of those hospitalised with the syndrome

Naringenin inhibits neointimal hyperplasia following arterial reconstruction with interpositional vein graft

Vessels respond to injury by a healing process that includes the development of neointima. Stenosis secondary to neointima formation is the main cause of failure following arterial reconstructions. Vessel wall homeostasis is regulated by proinflammatory cytokines that affect smooth muscle cell proliferation, growth, migration, and death. We assessed the hypothesis that naringenin, a flavinoid possessing anti-inflammatory, antioxidant, and antiproliferative activities, reduces neointimal hyperplasia (NIH) following vascular injury.Arterial injury was created by interposition grafting of autologous right superficial epigastric vein graft into the right femoral artery (FA) in 48 male Sprague-Dawley rats. Following injury, the rats were divided into 4 groups (n = 12). Two groups were treated with naringenin (100 mg/kg intraperitoneal q daily) for 2 and 4 weeks each while 2 control groups received normal saline for the same durations. For Sham group (n = 10), the FA and vein were isolated without any additional procedure. Rats were killed at the end of treatment regimen in all groups, and FAs were harvested. Thickness of intima was measured in histologic sections, and levels of platelet derived growth factor (PDGF)-BB, TNFα, and Ki67 labeling index (Ki67 LI) were quantified in immunohistochemical analyses to assess the amount of NIH and mechanisms underlying its formation.Although there was no significant difference between the groups at 2 weeks, neointima thickness was lower in the naringenin treated group at 4 weeks (23.7 ± 2.3 vs. 35.6 ± 2.6 μm in control group; P < 0.001). The levels of PDGF-BB, and TNFα were lower in naringenin treated groups at both 2 weeks (PDGF-BB [0.21% ± 0.03% versus 0.39% ± 0.05% in control group, P < 0.001), TNFα (21.2% ± 0.8% vs. 36.1% ± 1.9% in control group, P < 0.001]) and 4 weeks (PDGF-BB [0.25% ± 0.03% vs. 0.57% ± 0.09% in control group, P < 0.001], TNFα [25.5% ± 1.8% vs. 45.0% ± 2.9% in control group, P < 0.001]). Ki67 LI was lower in naringenin treated groups at 2 weeks (13.9% ± 2.8% vs. 18.7% ± 3.7% in control group, P < 0.05), and at 4 weeks (17.5% ± 2.6% vs. 31.1% ± 4.7% in control group, P < 0.001), indicating a lower level of cellular proliferation.Naringenin reduces NIH following arterial reconstruction. This may be mediated by a decrease in PDGF-BB and TNFα levels and the resulting down-regulation of smooth muscle cells' migration and proliferation. Copyright © 2009 by Lippincott Williams & Wilkins

Why are aggregate equity payouts pro-cyclical?

We use two general equilibrium models to explain why changes in the external economic environment result in pro-cyclical aggregate dividend payout behavior. Both models that we consider endogenize low elasticity of investment. The first model incorporates capital adjustment costs, while the second one assumes that risk-averse managers maximize their own objective function rather than shareholder wealth. We show that, while both models generate pro-cyclical aggregate dividends, a feature consistent with the observed business-cycle pattern of payouts from well-diversified portfolios, the second model provides a more likely explanation for this effect. Our findings emphasize the importance of incorporating agency conflicts when considering the relationship between the external economic environment and the financial behavior of businesses

"I should live and finish it": A qualitative inquiry into Turkish women's menopause experience

<p>Abstract</p> <p>Background</p> <p>While bio-medically, menopause could be treated as an illness, from a psychosocial and cultural perspective it could be seen as a "natural" process without requiring medication unless severe symptoms are present.</p> <p>Our objective is to explore the perceptions of Turkish women regarding menopause and Hormone Therapy (HT) to provide health care workers with an insight into the needs and expectations of postmenopausal women.</p> <p>Methods</p> <p>A qualitative inquiry through semi-structured, in-depth interviews was used to explore the study questions. We used a purposive sampling and included an equal number of participants who complained about the climacteric symptoms and those who visited the outpatient department for a problem other than climacteric symptoms but when asked declared that they had been experiencing climacteric symptoms. The interview questions focused on two areas; 1) knowledge, experiences, attitudes and beliefs about menopause and; 2) menopause-related experiences and ways to cope with menopause and perception of HT.</p> <p>Results</p> <p>Most of the participants defined menopause as a natural transition process that one should go through. Cleanliness, maturity, comfort of not having a period and positive changes in health behaviour were the concepts positively attributed to menopause, whereas hot flushes, getting old and difficulties in relationships were the negatives. Osteoporosis was an important concern for most of the participants. To deal with the symptoms, the non-pharmacological options were mostly favoured.</p> <p>Conclusion</p> <p>To our knowledge, this is the first qualitative study which focuses on Turkish women's menopausal experiences. Menopause was thought to be a natural process which was characterised by positive and negative features. Understanding these features and their implications in these women's lives may assist healthcare workers in helping their clients with menopause.</p

Aggregate dividends and consumption smoothing

We show that net equity payouts from the corporate sector play a crucial role in helping individuals manage their consumption path across the business cycle. In particular, we show that, as investors' desire to smooth consumption increases, optimal aggregate dividends become both more volatile and more counter-cyclical to help counterbalance pro-cyclical labor income. These findings are robust to whether or not agency conflicts exist in the economy