Antihypertensive mechanisms of chronic captopril or N-acetylcysteine treatment in L-NAME hypertensive rats.

Hypertension due to chronic inhibition of NO synthase (NOS) by Nomega-nitro-L-arginine methyl ester (L-NAME) administration is characterized by both impaired NO-dependent vasodilation and enhanced sympathetic vasoconstriction. The aim of our study was to evaluate changes in the participation of major vasoactive systems in L-NAME-treated rats which were subjected to simultaneous antihypertensive (captopril) or antioxidant (N-acetylcysteine, NAC) treatment. Three-month-old Wistar males treated with L-NAME (60 mg/kg/day) for 5 weeks were compared to rats in which L-NAME treatment was combined with simultaneous chronic administration of captopril or NAC. Basal blood pressure (BP) and its acute responses to consecutive i.v. injections of captopril (10 mg/kg), pentolinium (5 mg/kg), L-NAME (30 mg/kg), tetraethylammonium (TEA, 16 mg/kg) and nitroprusside (NP, 20 microg/kg) were determined in conscious rats at the end of the study. The development of L-NAME hypertension was prevented by captopril treatment, whereas NAC treatment caused only a moderate BP reduction. Captopril treatment normalized the sympathetic BP component and significantly reduced residual BP (measured at full NP-induced vasodilation). In contrast, chronic NAC treatment did not modify the sympathetic BP component or residual BP, but significantly enhanced NO-dependent vasodilation. Neither captopril nor NAC treatment influenced the compensatory increase of TEA-sensitive vasodilation mediated by endothelium-derived hyperpolarizing factor in L-NAME-treated rats. Chronic captopril treatment prevented L-NAME hypertension by lowering of sympathetic tone, whereas chronic NAC treatment attenuated L-NAME hypertension by reduction in the vasodilator deficit due to enhanced NO-dependent vasodilation.     

Transjugular intrahepatic cavoportal shunt for Budd–Chiari syndrome

Budd–Chiari syndrome (BCS) is characterized by obstruction of the hepatic venous outflow tract. Therapeutic options for BCS are limited. We report a case of a 21-year-old woman with protein S and C deficiency with gross ascites. Treatment with transjugular intrahepatic portosystemic shunt (TIPS) was attempted, which revealed occluded hepatic veins, so transcaval TIPS was performed. No serious procedure-related complication occurred. After successful shunt creation, the patient's symptoms subsided and she was discharged and followed up for 6 months.     

Resolving the composite trait of hypertension into its pharmacogenetic determinants by acute pharmacological modulation of blood pressure regulatory systems

Acute pharmacogenetic analysis was carried out in an intercross F2 population derived from Prague hypertensive-hypertriglyceridemic and Lewis rats. Quantitative trait loci (QTL) mapping was performed for baseline blood pressure (BP) and for BP after blockade of the renin-angiotensin system by losartan, of the sympathetic nervous system (SNS) by pentolinium, and of the nitric oxide system by N(G)-nitro- L-arginine methyl ester. Two significant loci for baseline BP were found on chromosome (Chr) 3 (logarithm of likelihood, LOD, 3.8) and Chr 5 (LOD 3.6), and one suggestive locus on Chr 1 (LOD 2.7). The QTL on Chr 3 persisted after treatment with the three agents while the QTL on Chr 5 and Chr 1 disappeared after pentolinium administration. This suggests independence of the locus on Chr 3 from each acute BP regulatory system examined, whereas the loci on Chr 5 and Chr 1 appeared to be controlled mainly by the SNS. Although not apparent at baseline, a significant locus appeared on Chr 8 (LOD 7.0) after blockade of the SNS, and NO system blockade led to the appearance of a new QTL on Chr 1 (LOD 3.6), indicating the contribution of the inhibited systems to these loci. Pharmacogenetic dissection of the BP trait is a powerful tool to unravel the underlying physiological mechanisms of QTL affecting baseline BP and to identify specific QTL for the response to drugs. This pharmocogenetic approach enabled us to determine the main causative acute BP regulatory systems and should lead to better selection of suitable antihypertensive drugs for individual patients.     

The Effect of Omega-3 Fatty Acids on Thromboxane,Brain-Derived Neurotrophic Factor,Homocysteine, and Vitamin D in Depressive Children and Adolescents: Randomized Controlled Trial

In the DEPOXIN project, we have found that a high ratio of omega-6/omega-3 fatty acids (FA) is associated with worsening of depressive symptoms in children and adolescents with depressive disorder (DD) and that the 12-week omega-3 FA supplementation modulates DD symptoms. Here we present our results of the secondary outcomes: the levels of thromboxane (TXB), brain-derived neurotrophic factor (BDNF), homocysteine (HCy) and vitamin D. Fifty-eight patients were randomized into two arms. One group received a fish oil emulsion enriched with omega-3 FA, and the other received a sunflower oil emulsion containing omega-6 FA, for 12 weeks. Depressive symptoms were evaluated, using the Child’s Depressive Inventory (CDI). The patients with DD had elevated TXB levels and decreased vitamin D levels, as compared to healthy controls. Both CDI and omega-6/omega-3 ratio correlated positively with TXB and negatively with BDNF at baseline. Compared to the omega-6 FA group, the supplementation with omega-3 FA for 12 weeks significantly reduced plasma TXB (p = 0.024) and increased BDNF (p = 0.011) levels. No changes in HCy and vitamin D were observed. Our results demonstrate the possible role of TXB and BDNF in the pathophysiology of DD and the benefits of omega-3 FA supplementation. The study was registered with the ISRCTN registry (ISRCTN81655012).     

The timing of drain removal—empiricism or science?

Surgical drains are commonly used in plastic surgery. Drains are subsequently removed at arbitrary volumes depending on local protocols. The rational for when to remove a drain has not been scientifically determined. We compared removal of drains at ≤30?ml/24?h vs. ≤50?ml/24?h for 158 wounds, in 90 patients. Postoperative complications, length of hospital stay and resulting cost–benefit were considered. Prospective data were collected for two consecutive similar cohorts of patients undergoing abdominoplasty, bilateral breast reduction and breast augmentation. In the first cohort, drains were removed when drainage was ≤30?ml/24?h and the second cohort when ≤50?ml/24?h. Demographics, days of drainage, surgeon grade and duration of postoperative hospital stay were recorded. Patient records were then analysed and complications recorded, including haematoma, infection, seroma, wound breakdown and fat necrosis. The median postoperative stay for all three operations for both drainage cohorts was similar with no statistically significant difference; however, the drainage time in breast augmentation was significantly less in the <50?ml/24?h group. There were no significant differences in outcome measures between the patients undergoing abdominoplasty, breast reduction or breast augmentation. Drain removal at ≤50 vs. ≤30?ml/24?h did not result in an increase in postoperative morbidity or adverse outcome in any of the three different operation types.     

An Update on the Status of Potent Inhibitors of Metallo-β-Lactamases

The production of metallo-β-lactamases is the most important strategy by which pathogenic bacteria become resistant to currently known β-lactam antibiotics. The emergence of these enzymes is particularly concerning for the future treatment of bacterial infections. There are no clinically available drugs capable of inhibiting any of the metallo-β-lactamases, so there is an urgent need to find such inhibitors. In this review, an up-to-date status of the inhibitors investigated for the inhibition of metallo-β-lactamases has been given so that this rich source of structural information of presently known metallo-β-lactamases could be helpful in generating a broad-spectrum potent inhibitor of metallo-β-lactamases.     

Conjoint bicondylar Hoffa fracture in an adult

Conjoint bicondylar Hoffa fracture is an extremely rare injury. Only one case has been reported previously in the pediatric age group. We describe this injury in a 17-year-old male who presented following a fall with direct impact on his semiflexed right knee. Plain radiographs were inadequate to define the exact pattern of injury. Computed tomographic (CT) scans demonstrated the coronal fracture involving both the femoral condyles which were joined by a bridge of intact bone. The patient was treated with open reduction and internal fixation using swashbuckler (modified anterior) approach. Union occurred within 3 months and at final followup (at 18 months) the patient had a good clinical outcome. The possible mechanism of injury is discussed.     

Self-reported risk factors related to the most frequent musculoskeletal complaints among Czech dentists

The purpose of the study was to describe the occurrence of the most common complaints related to MSDs in Czech dentists and to assess the risk factors affecting them. A questionnaire survey of 581 Czech dentists (the response rate 72.6%) was conducted in 2011. The questionnaire ascertained general information about the respondents, their work habits and environment along with the occurrence of musculoskeletal disorders. The respondents filled out the questionnaires during the educational events organized by the Czech Dental Chamber. At least mild difficulties associated with the motoric system were reported by 96.9% of the respondents, with 66.3% of respondents reporting moderate or major difficulties. Back and neck pain followed by shoulder pain and headache were the most common complaints in our sample. According to our data: age, gender, length of practice, a history of serious MSDs, the occurrence of MSDs in blood relatives, the perception of work as psychologically demanding, and especially a perceived moderate/bad general health were significantly associated with the four most common musculoskeletal complaints. Some of the factors were found as protective. This study suggests that MSDs represent a significant burden for Czech dentists and further research is needed to elucidate this issue.