Lung morphometry and MMP-12 expression in rats treated with intraperitoneal nicotine.

Nicotine, a toxic tobacco component, plays an important role in the development of cardiovascular and lung diseases in smokers. Our objective was to investigate the effects of the intraperitoneal (i.p.) nicotine treatment in lung morphology. Wistar male rats (3-4 months old) were divided in five groups, a control one, and other groups treated with nicotine (1 mg/kg/day) for 8 days and sacrificed after 24, 48, 96, and 192 h. Morphometry was used to estimate the lung alveolar parenchyme and septal elastic fibers changes, and immunohistochemistry was performed to detect macrophage metalloelastase (MMP-12) and quantify vessels by immunolabelling with alpha-smooth muscle cells. Thickening of the alveolar septa was present in all nicotine groups, and associated with mononuclear cell infiltration, angiogenesis, and irregular areas of collapse. After 96 h, rat lungs showed macrophage, expressing MMP-12, that was also present after 192 h of recovery. Pleural and parenchyma inflammation, fibrosis and macrophage were also seen after 192 h. Intraperitoneal nicotine treated rats exhibited an increase of the volume fraction of alveolar parenchyme, a reduction of volume and surface fraction septal elastic fibers, and an increase of the numerical fraction of microvasculature vessels compared to control ones. MMP-12 was detected in groups of macrophages Wistar rats lung exhibited a progressive morphological damage after 192 hours of recovery, after 8 daily doses of 1 mg/kg body weight on i.p. nicotine.     

KMD-3213, a uroselective and long-acting alpha(1a)-adrenoceptor antagonist, tested in a novel rat model.

KMD-3213, an alpha(1a)-adrenoceptor (AR) antagonist, is under development for the treatment of urinary outlet obstruction in patients with benign prostatic hypertrophy. In the present study, we developed a rat model to investigate simply the effects of alpha(1)-AR antagonists on the intraurethral pressure (IUP) response to phenylephrine. Using this model, inhibitory effects of both i.v. and intraduodenally administered KMD-3213 on the IUP response were evaluated and compared to those of other reference compounds, including prazosin and tamsulosin. In addition, the hypotensive effects of these compounds were estimated to evaluate uroselectivity. Intravenously administered alpha(1)-AR antagonists tested, including KMD-3213, potently inhibited the IUP response in a dose-dependent manner. Although the higher doses of those compounds almost completely inhibited the IUP response, yohimbine failed to inhibit the response. When the in vivo potencies of those compounds on IUP response were correlated with their affinities for the human or animal recombinant alpha(1)-AR subtypes, alpha(1a)-AR gave the best correlation. In this model, KMD-3213 had greater uroselectivity than any other compounds examined, by both i.v. and intraduodenal routes. Moreover, 12, 18, and 24 h after the oral administration of KMD-3213, a dose-dependent inhibition of the IUP response was found, whereas the effect of tamsulosin disappeared at 18 h after the oral administration. These data indicate that KMD-3213 is a highly uroselective alpha(1)-AR antagonist with a longer duration of action. In addition, this model is useful for not only estimation of uroselectivity but also some part of the administration, distribution, metabolism, and excretion of many compounds to discover uroselective compounds.     

Immune responses to Aspergillus antigen in IL‐4‐/‐ mice and the effect of eosinophil ablation

BACKGROUND: Exposure to Aspergillus fumigatus allergens results in enhanced total serum IgE and peripheral blood eosinophils in mice. The associated pulmonary inflammation and immunologic responses are comparable to those detected in human allergic bronchopulmonary aspergillosis. Allergen-induced cytokines are thought to regulate the inflammatory and immune responses in these animals. METHODS: In the present study, we exposed C57BL/6 and BALB/c mice to A. fumigatus antigen. Both wild-type and IL-4 knockout phenotypes of animals of both strains were used. Some animals were also treated with anti-IL-5 or anti-IFN-gamma. Total serum IgE, Aspergillus species IgG subclass, peripheral blood eosinophils, and lung histology were studied. RESULTS: The results demonstrate similar lung inflammation in all wild-type and IL-4-/- animals exposed to A. fumigatus antigen. Similarly, in spite of the diverse immune response produced by the anticytokine treatment, no major differences were detected among any of the animal groups studied. CONCLUSIONS: It can be concluded that A. fumigatus exposure in an immunologically unaltered host is predominantly of a Th2 type, and that depletion of the Th2 cytokine leads to a similar lung inflammation but with a characteristic Th1 response, suggesting that the pathogenesis of allergic aspergillosis is the result of multiple induction pathways.     

Anterior Cruciate Ligament Reconstruction with Bone Patellar Tendon Bone Graft through a Mini Arthrotomy

Instability after rupture of anterior cruciate ligament (ACL) may lead to recurrent episodes of giving way, an increased risk of meniscal injury and premature degenerative changes. A total of 25 cases with ACL injuries were evaluated after reconstruction with bone patellar tendon bone graft through a mini-arthrotomy. All patients were male. Maximum number of patients were between 25-30 years of age (40%). The most common modality of injury was contact sports (44%). Most common complaint was instability of knee (100%). Average Lysholm score increased from pre-operative of 47 (27-75) to post-operative of 87 (68-95). Two patients (8%) had retropatellar pain. Moderate to severe graft site tenderness was present in 4 (21%). After an average follow up of one year three months, the results were comparable with the results of arthroscopic reconstruction.Key Words: Anterior cruciate ligament reconstruction, Mini arthrotomy     

Improving Quality and Safety in Maternity Care: The Contribution of Midwife‐Led Care

This article draws on findings from a recent Cochrane systematic review of midwife‐led care and discusses its contribution to the safety and quality of women's care in the domains of safety, effectiveness, woman‐centeredness, and efficiency. According to the Cochrane review, women who received models of midwife‐led care were nearly eight times more likely to be attended at birth by a known midwife, were 21% less likely to experience fetal loss before 24 weeks' gestation, 19% less likely to have regional analgesia, 14% less likely to have instrumental birth, 18% less likely to have an episiotomy, and significantly more likely to have a spontaneous vaginal birth, initiate breastfeeding, and feel in control. In addition to normalizing and humanizing birth, the contribution of midwife‐led care to the quality and safety of health care is substantial. The implications are that policymakers who wish to improve the quality and safety of maternal and infant care, particularly around normalizing and humanizing birth, should consider midwife‐led models of care and how financing of midwife‐led services can support this. Suggestions for future research include exploring why fetal loss is reduced under 24 weeks' gestation in midwife‐led models of care, and ensuring that the effectiveness of midwife‐led models of care on mothers' and infants' health and well‐being are assessed in the longer postpartum period.