Superoxide does not mediate the acute vasoconstrictor effects of angiotensin II: a study in human and porcine arteries

OBJECTIVE: To investigate whether superoxide mediates angiotensin (Ang) II-induced vasoconstriction. METHODS: Human coronary arteries (HCAs), porcine femoral arteries (PFA) and porcine coronary arteries (PCAs) were mounted in organ baths and concentration-response curves to Ang II, the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) and the NAD(P)H oxidase substrate NADH were constructed in the absence and presence of superoxide inhibiting and activating drugs. Extracellular superoxide was measured using cytochrome c reduction. RESULTS: Ang II constricted both HCAs and PFAs. In HCAs, the NAD(P)H inhibitors diphenyleneiodonium (DPI) and apocynin, and the xanthine oxidase (XO) inhibitor allopurinol, but not the superoxide dismutase (SOD) mimetic tempol or the SOD inhibitor diethyldithiocarbamate (DETCA), reduced this constriction. Catalase potentiated Ang II in HCAs, indicating a vasodilator role for H2O2. DPI, tempol and SOD did not affect Ang II in PFAs. DPI, apocynin and allopurinol relaxed preconstricted HCAs. Although the relaxant effects of the NO donor SNAP in PCAs was reduced by DETCA, indicating that superoxide-induced constrictions depend on NO inactivation, the apocynin-induced relaxations were NO independent. Moreover, NADH relaxed all vessels, and this effect was blocked by KCl but not DPI or NO removal. Xanthine plus XO also relaxed HCAs and PCAs. Incubation of human or porcine arteries with Ang II or NADH did not result in detectable increases of extracellular superoxide within 1 h. CONCLUSIONS: Acute vasoconstriction by Ang II is not mediated via superoxide generated through NAD(P)H oxidase and/or XO activation. Such activation, if occurring, rather results in the generation of the vasodilator H2O2.     

Development of the principal nucleus trigeminal lemniscal projections in the mouse

The principal sensory (PrV) nucleus‐based trigeminal lemniscus conveys whisker‐specific neural patterns to the ventroposteromedial (VPM) nucleus of the thalamus and subsequently to the primary somatosensory cortex. Here we examined the perinatal development of this pathway with carbocyanine dye labeling in embryonic and early postnatal mouse brains. We developed a novel preparation in which the embryonic hindbrain and the diencephalon are flattened out, allowing a birds‐eye view of the PrV lemniscus in its entirety. For postnatal brains we used another novel approach by sectioning the brain along an empirically determined oblique horizontal angle, again preserving the trigeminothalamic pathway. PrV neurons are born along the hindbrain ventricular zone and migrate radially for a short distance to coalesce into a nucleus adjacent to the ascending trigeminal tract. During migration of the spindle‐shaped cell bodies, slender axonal processes grow along the opposite direction towards the floor plate. As early as embryonic day (E) 11, pioneering axons tipped with large growth cones cross the ventral midline and immediately make a right angle turn. By E13 many PrV axons form fascicles crossing the midline and follow a rostral course. PrV axons reach the midbrain by E15 and the thalamus by E17. While the target recognition and invasion occurs prenatally, organization of PrV axon terminals into whisker‐specific rows and patches takes place during the first 4 postnatal (P) days. Initially diffuse and exuberant projections in the VPM at P1 coalesce into row and whisker specific terminal zones by P4. J. Comp. Neurol. 521:299–311, 2013. © 2012 Wiley Periodicals, Inc.     

How to improve the management of chest pain: hospitalists and use of prediction rules

BACKGROUND: Three percent of patients with acute myocardial infarction are still missed despite the excess number of admissions with chest pain. The purpose of this study was to review the characteristics of patients who were admitted with chest pain, to evaluate the appropriateness of admissions and the outcomes. We also discuss whether use of a prediction rule could have made a difference in the management of these cases. METHODS: We performed retrospective chart review on all patients admitted to the hospitalist service with a diagnosis of chest pain. Each patient was risk stratified using Diamond and Forrester algorithm for probability of coronary artery disease (CAD), retrospectively. Results were analyzed using chi2 test or exact test and Student's t test. RESULTS: Of 260 patients admitted with chest pain to the hospitalist service, only 24 (9.2%) received the final diagnosis of acute coronary syndrome (ACS). The patients in the ACS group were older and more likely to be male and to have a history of hyperlipidemia, CAD, peripheral vascular disease, cerebrovascular disease and percutaneous coronary intervention (PCI). Of 34 patients who underwent cardiac catheterization, 20 (58.8%) had occlusive CAD and 14 of them received PCI. Risk stratification of patients, retrospectively, revealed 28.3% of the total patient population was high risk, while 6.6% of them were low risk. The number of ACS cases was highest in the high risk group, while none was detected in the low risk group. CONCLUSIONS: Our study demonstrated that using a prediction rule could have prevented about 6% of the chest pain admissions. Therefore, the use of risk stratification methods should be encouraged to decrease cost and improve efficiency of care.     

Assessment on self-care,mobility and social function of children with spina bifida in Turkey

The aim of the study was to investigate the functional performance in children with spina bifida, using the Pediatric Evaluation of Disability Inventory(PEDI) to look into capacity of twenty-eight children with spina bifida with lesions at different levels in different dimensions of selfcare, mobility and social function. Mean age of the patients was 3.5 ± 2.3(1–10) years. In the muscle test carried out, 13 patients(44.8%) had no movements including pelvic elevation in lower extremity muscles and they were at level 5. Sixteen patients(54%) were non-ambulatory according to the Hoofer ambulation classification. Raw and scale scores in the self-care, mobility and social function domains both in the functional skill scale and in the caregiver scale were found to be lower compared to the data of the normal population. A statistically significant correlation was observed in the self-care values of the Functional Skills Scales and the Caregiver Assistance Scale measurements, which was positive for age and negative for Functional Ambulation Scale and muscle test(P 0.05). A positive relation was found between the Functional Skills Scales-mobility area and age while a negative relation was observed between Functional Ambulation Scale and muscle test(P 0.005). A negative relation was also found between Caregiver Assistance Scale-mobility and Functional Ambulation Scale and muscle test(P 0.005). In our study, the functional performance of the children was found to be low. Low-level lesions, encouraging muscular strength and independence in mobility are all very important factors for functional independence.     

Vesiculopustular Eruption in Neonatal Transient Myeloproliferative Disorder

Transient myeloproliferative disorder (TMD) typically presents with pancytopenia, hepatosplenomegaly, and immature circulating white blood cells, and affects approximately 10 % of neonates with Down syndrome. The authors report a neonate with Down syndrome who developed acute widespread pustular eruptions as a sign of TMD. The white blood cell counts on the first day of life were markedly elevated, with blasts seen on examination of the peripheral blood smear. And the patient was noted to have a few erythematous papules and pustules especially on the face. On the following days pathergy positive crusted papules and pustules were increased and spread to trunk and extremities. Skin biopsy specimens showed pustular dermatitis, with subcorneal vesiculopustules and perivascular inflammation in superficial dermis. These lesions improved parallel with the hematologic improvement within two weeks. The authors aim to alert clinicians about this uncommon cause of vesiculopustular eruption with the present illustrative case and review the literature.     

Bradykinin potentiation by ACE inhibitors: a matter of metabolism

1. Studies in isolated cells overexpressing ACE and bradykinin type 2 (B(2)) receptors suggest that ACE inhibitors potentiate bradykinin by inhibiting B(2) receptor desensitization, via a mechanism involving protein kinase C (PKC) and phosphatases. Here we investigated, in intact porcine coronary arteries, endothelial ACE/B(2) receptor 'crosstalk' as well as bradykinin potentiation through neutral endopeptidase (NEP) inhibition. 2. NEP inhibition with phosphoramidon did not affect the bradykinin concentration-response curve (CRC), nor did combined NEP/ACE inhibition with omapatrilat exert a further leftward shift on top of the approximately 10 fold leftward shift of the bradykinin CRC observed with ACE inhibition alone. 3. In arteries that, following repeated exposure to 0.1 microM bradykinin, no longer responded to bradykinin ('desensitized' arteries), the ACE inhibitors quinaprilat and angiotensin-(1-7) both induced complete relaxation, without affecting the organ bath fluid levels of bradykinin. This phenomenon was unaffected by inhibition of PKC or phosphatases (with calphostin C and okadaic acid, respectively). 4. When using bradykinin analogues that were either completely or largely ACE-resistant ([Phe(8)psi(CH(2)-NH)Arg(9)]-bradykinin and [deltaPhe(5)]-bradykinin, respectively), the ACE inhibitor-induced shift of the bradykinin CRC was absent, and its ability to reverse desensitization was absent or significantly reduced, respectively. Caveolar disruption with filipin did not affect the quinaprilat-induced effects. Filipin did however reduce the bradykinin-induced relaxation by approximately 25-30%, thereby confirming that B(2) receptor-endothelial NO synthase (eNOS) interaction occurs in caveolae. 5. In conclusion, in porcine arteries, in contrast to transfected cells, bradykinin potentiation by ACE inhibitors is a metabolic process, that can only be explained on the basis of ACE-B(2) receptor co-localization on the endothelial cell membrane. NEP does not appear to affect the bradykinin levels in close proximity to B(2) receptors, and the ACE inhibitor-induced bradykinin potentiation precedes B(2) receptor coupling to eNOS in caveolae.     

A reevaluation of the structures accepted to represent the postnatal gubernaculum

INTRODUCTION: The structure called the residual gubernaculum (G) has been evaluated to define its origin. MATERIALS AND METHODS: Girls operated for inguinal hernia (n = 7) and boys operated for undescended testis (n = 12), inguinal hernia (n = 7), hydrocele of the cord (n = 1), and ectopic (n = 1) and entrapped (n = 1) testes were evaluated. Attachments of the structures coursing distally from the sacs were identified, and they were removed en block. Three samples, first from the distal part of the sac with the beginning of the fibrous structure, second from the midportion, and third from the most distal part, were prepared and stained with hematoxylin-eosin, trichrome and elastic van Gieson. Histologic structures within the samples were determined and compared with Mann-Whitney U test. RESULTS AND CONCLUSIONS: Structures called the residual G differed from the walls of accompanying sacs by only the absence of mesothelial lining. Therefore, the structure called the residual G in boys with an undescended testis and the round ligament in girls actually represent the obliterated processus vaginalis.     

Prevalence of Chlamydia pneumoniae specific antibodies in different clinical situations and healthy subjects in Izmir, Turkey

Serological markers for Chlamydia pneumoniae were investigated by using the microimmunofluorescence (MIF) test in various age and patient groups in a specific area in Turkey. IgG seropositivity to C. pneumoniae was 64.3% and 18.7% in healthy adults and children, respectively. The highest positivity rate (77%) was in the 15–19 age group. Among the groups investigated, serological findings revealed a possible etiological association between C. pneumoniae and the clinical condition in the groups with acute myocardial infarction, atypical pneumoniae and chronic obstructive pulmonary disease.