Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.     

Impact of medication therapy management on pharmacotherapy safety in an intensive care unit

Background Drug-related problems are mostly preventable or predictable circumstances that may impact on health outcomes. Clinical pharmacy activities such as medication therapy management can identify and solve these problems, with potential to improve medication safety and effectiveness. Objective To evaluate ability of medication therapy management service to detect drug-related problems and prevent adverse drug events. This study also aimed to assess the risk factors for drugrelated problem occurrence. Setting Medical intensive care unit of a public tertiary hospital in Brazil. Methods Patients were evaluated by a clinical pharmacist, who provided medication therapy management service. Detected drug-related problems were categorized according to the Pharmaceutical Care Network Europe methodology and analyzed in multinomial regression to identify risk factors. Main outcome measure Potential risk factors for drug-related problem occurrence. Results The proposed medication therapy management service allowed detection of 170 drug-related problems that had potential to reach patients causing harm and other 50 unavoidable adverse events. Drug-related problems identified were more often associated with antibacterial use, caused by improper combinations or inadequate drug dosage. These problems required interventions that were accepted by the multidisciplinary team, resulting in more than 85% adherence and total problem solving. Main risk factors identified were previous diagnosis of kidney injury (OR?=?8.38), use of midazolam (OR?=?7.96), furosemide (OR?=?5.87) and vancomycin (OR?=?4.82). Conclusion Medication therapy management proved to be an effective method not only for drug-related problem detection, but also for adverse drug event prevention, contributing to improve patient safety.

     

HLA markers in familial Lichen Sclerosus

Background: Lichen sclerosus (LS) has been identified with increased frequency in families,often associated with HLA markers, mainly DQ7. A genetic co‐etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti‐thyroid peroxidase autoantibodies (anti‐TPO), a hallmark of autoimmune thyroid diseases. Patients and Methods: In 3 families affected by LS, we verified their HLA markers, and identified previously undiagnosed cases of LS and autoimmune disorders. 30 individuals were examined with history, skin biopsy, HLA class I and II typing by PCR‐SSP, and measurement of anti‐TPO, free thyroxine and thyroidstimulating hormones (TSH) levels. Results: There were 8 cases of LS, 50 % of them anti‐TPO+. Autoimmune disorders were found in 40 % (total) and in 87.5 % of those affected. Most common HLA markers were B*15, B*57, CW*03, CW*07, CW*18, DRB1*04, DRB1*07, DRB4*. The three latter have been previously associated with LS. Conclusion: New cases of LS and autoimmune disorders can be detected in first degree relatives of patients with LS. The presence of anti‐TPO antibodies strongly suggests autoimmune thyroiditis. There is intra‐familial association between the haplotype HLA‐B*15 ‐DRB1*04 ‐DRB4* and anti‐TPO,emphasizing their link with thyroiditis. New familial approaches might help to make clear the pathogenesis of LS and its association with autoimmune diseases.     

Leishmania identification by PCR of Giemsa-stained lesion imprint slides stored for up to 36 years

This study examined the ability of PCR to amplify Leishmania DNA, stored on Giemsa-stained slides, from American cutaneous leishmaniasis (ACL) patients. In total, 475 slides stored for up to 36 years were obtained from an outpatient clinic in a Brazilian ACL-endemic region, and Leishmania DNA was amplified from 395 (83.2%) of the DNA samples using primers specific for the minicircle kinetoplast DNA. Restriction fragment length polymorphism analysis of these amplicons demonstrated that Leishmania (Viannia) braziliensis was the only species present in these samples. The results demonstrated that archived Giemsa-stained slides can provide a Leishmania DNA source for performing clinical and epidemiological studies of leishmaniasis.