Sympathetic-mediated hypertension of awake juvenile rats submitted to chronic intermittent hypoxia is not linked to baroreflex dysfunction

In the present study, we evaluated the mechanisms underpinning the hypertension observed in freely moving juvenile rats submitted to chronic intermittent hypoxia (CIH). Male juvenile Wistar rats (20-21 days old) were submitted to CIH (6% O(2) for 40 s every 9 min, 8 h day(-1)) for 10 days while control rats were maintained in normoxia. Prior to CIH, baseline systolic arterial pressure (SAP), measured indirectly, was similar between groups (86 +/- 1 versus 87 +/- 1 mmHg). After exposure to CIH, SAP recorded directly was higher in the CIH (n = 28) than in the control group (n = 29; 131 +/- 3 versus 115 +/- 2 mmHg, P < 0.05). This higher SAP of CIH rats presented an augmented power of oscillatory components at low (10.05 +/- 0.91 versus 5.02 +/- 0.63 mmHg(2), P < 0.05) and high (respiratory-related) frequencies (12.42 +/- 2.46 versus 3.28 +/- 0.61 mmHg(2), P < 0.05) in comparison with control animals. In addition, rats exposed to CIH also exhibited an increased cardiac baroreflex gain (-3.11 +/- 0.08 versus -2.1 +/- 0.10 beats min(-1) mmHg(-1), P < 0.0001), associated with a shift to the right of the operating point, in comparison with control rats. Administration of hexamethonium (ganglionic blocker, i.v.), injected after losartan (angiotensin II type 1 receptor antagonist) and [beta-mercapto-beta,beta-cyclopenta-methylenepropionyl(1), O-Me-Tyr(2), Arg(8)]-vasopressin (vasopressin type 1a receptor antagonist), produced a larger depressor response in the CIH (n = 8) than in the control group (n = 9; -49 +/- 2 versus -39 +/- 2 mmHg, P < 0.05). Fifteen days after the cessation of exposure to CIH, the mean arterial pressure of CIH rats returned to normal levels. The data indicate that the sympathetic-mediated hypertension observed in conscious juvenile rats exposed to CIH is not secondary to a reduction in cardiac baroreflex gain and exhibits a higher respiratory modulation, indicating that an enhanced respiratory-sympathetic coupling seems to be the major factor contributing to hypertension in rats exposed to CIH.

Use of the frontal assessment battery in evaluating executive dysfunction in patients with Huntington`s disease

The frontal assessment battery (FAB) is a bedside cognitive scale designed to measure executive functions. Huntington`s disease (HD) is a neurodegenerative disorder characterized by motor, behavioral, and cognitive dysfunction. The aim of this study was to check the validity of the FAB for the evaluation of cognitive impairment in patients with HD. Forty-one patients diagnosed with HD and 53 healthy controls matched by education, sex and age were evaluated with a validated Brazilian version of the UHDRS, the VFT, the SDMT, the SIT, the MMSE, and the FAB. The diagnosis of HD was made by DNA analysis. FAB scores were lower in patients than in the controls (p < 0.001) and had significant correlations with the VFT (r = 0.79; p < 0.05), the SDMT (r = 0.80; p < 0.05), the SIT (r = 0.72; p < 0.05), the MMSE (r = 0.83; p < 0.05), the FCS (r = 0.79; p < 0.05) and the motor section of the UHDRS (r = -0.80; p < 0.05). The FAB differentiated between HD patients in the initial and later stages of the disease. The one-year longitudinal evaluation revealed a global trend toward a worsening in the second score of the FAB. The results demonstrate that the FAB presents good internal consistency and also convergent and discriminative validity; therefore it is a useful scale to assess executive functions and to evaluate cognitive impairment in patients with HD.

Disruption of sarcolemmal dystrophin and beta-dystroglycan may be a potential mechanism for myocardial dysfunction in severe sepsis

Evidence from our laboratory has shown alterations in myocardial structure in severe sepsis/septic shock. The morphological alterations are heralded by sarcolemmal damage, characterized by increased plasma membrane permeability caused by oxidative damage to lipids and proteins. The critical importance of the dystrophin-glycoprotein complex (DGC) in maintaining sarcolemmal stability led us to hypothesize that loss of dystrophin and associated glycoproteins could be involved in early increased sarcolemmal permeability in experimentally induced septic cardiomyopathy. Male C57Bl/6 mice were subjected to sham operation and moderate (MSI) or severe (SSI) septic injury induced by cecal ligation and puncture (CLP). Using western blot and immunofluorescence, a downregulation of dystrophin and beta-dystroglycan expression in both severe and moderate injury could be observed in septic hearts. The immunofluorescent and protein amount expressions of laminin-alpha 2 were similar in SSI and sham-operated hearts. Consonantly, the evaluation of plasma membrane permeability by intracellular albumin staining provided evidence of severe injury of the sarcolemma in SSI hearts, whereas antioxidant treatment significantly attenuated the loss of sarcolemmal dystrophin expression and the increased membrane permeability. This study offers novel and mechanistic data to clarify subcellular events in the pathogenesis of cardiac dysfunction in severe sepsis. The main finding was that severe sepsis leads to a marked reduction in membrane localization of dystrophin and beta-dystroglycan in septic cardiomyocytes, a process that may constitute a structural basis of sepsis-induced cardiac depression. In addition, increased sarcolemmal permeability suggests functional impairment of the DGC complex in cardiac myofibers. In vivo observation that antioxidant treatment significantly abrogated the loss of dystrophin expression and plasma membrane increased permeability supports the hypothesis that oxidative damage may mediate the loss of dystrophin and beta-dystroglycan in septic mice. These abnormal parameters emerge as therapeutic targets and their modulation may provide beneficial effects on future cardiovascular outcomes and mortality in sepsis. Laboratory Investigation (2010) 90, 531-542; doi: 10.1038/labinvest.2010.3; published online 8 February 2010

Sexual Dysfunction Treatment in a Patient With Mullerian Agenesy Submitted to Neovaginoplasty: A Case Report

Vagina agenesis is a rare entity. Mayer-Rokitansky-Kuster-Hauser syndrome is the most significant cause of vagina agenesis, whereas the second most common cause is complete androgen syndrome. Surgical treatment can propitiate a vaginal reconstruction, but sexual function depends on several factors that affect sexual performance. Many reports focus on the intraoperative and postoperative results and only describe the global approach to these patients, but reports focusing on the management of these patients to enable them to have a normal sexual life are lacking. This case report highlights a multidisciplinary treatment for this kind of morbidity and emphasizes the necessity of incorporating careful attention to sexual health in the treatment of these patients so that they may achieve a good therapeutic response, resulting in a pleasurable sexual life and a good quality of living.

Chronic Ethanol Consumption Induces Cavernosal Smooth Muscle Dysfunction in Rats

OBJECTIVES To investigate the effects of chronic ethanol consumption on nitric oxide (NO)-mediated relaxation in rat cavernosal smooth muscle (CSM). METHODS Male wistar rats were divided into 2 groups: control and ethanol. CSM obtained from both groups were mounted in organ chambers for measurement of isometric tension. Contraction of the strips was induced by electrical field stimulation (EFS, 1-32 Hertz) and phenylephrine. We also evaluated the effect of ethanol consumption on the relaxation induced by acetylcholine (0.01-1000 mu mol L(-1)), sodium nitroprusside (SNP, 0.01-1000 mu mol L(-1)), or EFS (1-32 Hz) in strips precontracted with phenylephrine (10 mu mol L(-1)). Blood ethanol, serum testosterone levels, and basal nitrate generation were determined. Immunoexpression of endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) was also accessed. RESULTS Ethanol intake for 4 weeks significantly increased noradrenergic nerve-mediated contractions of CSM in response to EFS. The endothelium-dependent relaxation induced by acetylcholine decreased after the ethanol treatment. Ethanol consumption decreased serum testosterone levels but did not affect the nitrate levels on rat CSM. The mRNA and protein levels for eNOS and iNOS receptors were increased in CSM from ethanol-treated rats. CONCLUSIONS Ethanol consumption reduces endothelium-dependent relaxation induced by acetylcholine, but does not affect SNP or EFS-induced relaxation, suggesting that ethanol disrupts the endothelial function. Despite the overexpression of eNOS and iNOS in ethanol-treated rats, the impaired relaxation induced by acetylcholine may suggest that chronic ethanol consumption induces endothelial dysfunction. UROLOGY 74: 1250-1256, 2009. (C) 2009 Published by Elsevier Inc.

Diabetes and Vascular Disease: Basic Concepts of Nitric Oxide Physiology, Endothelial Dysfunction, Oxidative Stress and Therapeutic Possibilities

The vascular manifestations associated with diabetes mellitus (DM) result from the dysfunction of several vascular physiology components mainly involving the endothelium, vascular smooth muscle and platelets. It is also known that hyperglycemia-induced oxidative stress plays a role in the development of this dysfunction. This review considers the basic physiology of the endothelium, especially related to the synthesis and function of nitric oxide. We also discuss the pathophysiology of vascular disease associated with DM. This includes the role of hyperglycemia in the induction of oxidative stress and the role of advanced glycation end-products. We also consider therapeutic strategies.

Factors that prevent or assist the integration of assistive technology into the workplace for people with spinal cord injuries: Perspectives of the users and their employers and co-workers

Examined the barriers faced by people with Spinal Cord Injuries (SCI) when integrating their Assistive Technology (AT) into the workplace, as well as factors that contribute to successful integration. In-depth interviews were taken with 5 men (aged 37-50 yrs) with SCI, 3 of their employers and 2 co-workers. Results indicate that in addition to the barriers previously outlined in the literature related to funding the technology, time delays, information availability, training and maintenance, other issues were highlighted. Implications for service providers are considered in relation to these barriers and the factors that prompted successful integration. The author discusses limitations of the study and makes recommendations for future research. (PsycINFO Database Record (c) 2007 APA, all rights reserved)

Role of the spinal cord heme oxygenase-carbon monoxide-cGMP pathway in the nociceptive response of rats

The aim of the present study was to investigate the role of the spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase (sGC)-cGMP pathway in nociceptive response of rats to the formalin experimental nociceptive model. Animals were handled and adapted to the experimental environment for a few days before the formalin test was applied. For the formalin test 50 mu l of a 1% formalin solution was injected subcutaneously in the dorsal surface of the right hind paw. Following injections, animals were observed for I h and flinching behavior was measured as the nociceptive response. Thirty min before the test, rats were pretreated with intrathecal injections with the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is known to induce the HO pathway. Control animals were treated with vehicles. We observed a significant increase in nociceptive response of rats treated with ZnDPBG, and a drastic reduction of flinching nociceptive behavioral response in the heme-lysinate treated animals. Furthermore, the HO pathway seems to act via cGMP, since methylene blue (a sGC inhibitor) prevented the reduction of flinching nociceptive behavioral response caused by heme-lysinate. These findings strongly indicate that the HO pathway plays a spinal antinociceptive role during the formalin test, acting via cGMP. (C) 2007 Elsevier B.V. All rights reserved.

Pyrrolidine dithiocarbamate down-regulates vascular matrix metalloproteinases and ameliorates vascular dysfunction and remodelling in renovascular hypertension

BACKGROUND AND PURPOSE Mounting evidence implicates matrix metalloproteinase (MMP) in the vascular dysfunction and remodelling associated with hypertension. We tested the hypothesis that treatment with pyrrolidine dithiocarbamate (PDTC), which interferes with NF-kappa B-induced MMPs gene transcription, could exert antihypertensive effects, prevent MMP-2 and MMP-9 up-regulation, and protect against the functional alterations and vascular remodelling of two-kidney, one clip (2K1C) hypertension. EXPERIMENTAL APPROACH Sham-operated or hypertensive rats were treated with vehicle or PDTC (100 mg.Kg(-1).day(-1)) by gavage for 8 weeks. Systolic blood pressure (SBP) was monitored weekly. Aortic rings were isolated to assess endothelium-dependent relaxations. Quantitative morphometry of structural alterations of the aortic wall was carried out in haematoxylin/eosin sections. Formation of vascular reactive oxygen species (ROS), and inducible (i) NOS and phosphorylated-p65 NF-kappa B subunit expression were measured in the aortas. MMP-2 and MMP-9 aortic levels and gelatinolytic activity were determined by gelatin and in situ zymography and by immunofluorescence. KEY RESULTS Treatment with PDTC attenuated the increases in SBP and prevented the endothelial dysfunction associated with 2K1C hypertension. Moreover, PDTC reversed the vascular aortic remodelling, the increases in aortic ROS levels and in iNOS and phosphorylated-p65 NF-kappa B expression found in 2K1C rats. These effects were associated with attenuation of 2K1C up-regulation of aortic MMP-2 and MMP-9 levels and gelatinolytic activity. CONCLUSION AND IMPLICATIONS These findings suggest that PDTC down-regulates vascular MMPs and ameliorates vascular dysfunction and remodelling in renovascular hypertension, thus providing evidence supporting the suggestion that PDTC is probably a good candidate to be used to treat hypertension.

Developmental changes of gene expression after spinal cord injury in neonatal opossums

Changes in gene expression have been measured 24 h after injury to mammalian spinal cords that can and cannot regenerate In opossums there is a critical period of development when regeneration stops being possible at 9 days postnatal cervical spinal cords regenerate, at 12 days they do not By the use of marsupial cDNA microarrays we detected 158 genes that respond differentially to injury at the two ages critical for regeneration For selected candidates additional measurements were made by real time PCR and sites of their expression were shown by immunostaining Candidate genes have been classified so as to select those that promote or prevent regeneration Up regulated by injury at 8 days and/or down regulated by injury at 13 days were genes known to promote growth, such as Mitogen activated protein kinase kinase 1 or transcripton factor TCF7L2 By contrast, at 13 days up regulation occurred of Inhibitory molecules including annexins ephrins and genes related to apoptosis and neurodegeneranve diseases Certain genes such as calmodulin 1 and NOGO changed expression similarly in animals that could and could not regenerate without any additional changes in response to injury These findings confirmed and extended changes of gene expression found in earlier screens on 9 and 12 day preparations without lesions and provide a comprehensive list of genes that serve as a basis for testing how identified molecules singly or in combination, promote and prevent central nervous system regeneration (C) 2010 Elsevier B V All rights reserved

A simple, inexpensive and easily reproducible model of spinal cord injury in mice: Morphological and functional assessment

Spinal cord injury (SCI) causes motor and sensory deficits that impair functional performance, and significantly impacts life expectancy and quality. Animal models provide a good opportunity to test therapeutic strategies in vivo. C57BL/6 mice were subjected to laminectomy at T9 and compression with a vascular clip (30 g force, 1 min). Two groups were analyzed: injured group (SCI, n = 33) and laminectomy only (Sham, n = 15). Locomotor behavior (Basso mouse scale-BMS and global mobility) was assessed weekly. Morphological analyses were performed by LM and EM. The Sham group did not show any morphofunctional alteration. All SCI animals showed flaccid paralysis 24 h after injury. with subsequent improvement. The BMS score of the SCI group improved until the intermediate phase (2.037 +/- 1.198): the Sham animals maintained the highest BMS score (8.981 +/- 0.056). p < 0.001 during the entire time. The locomotor speed was slower in the SCI animals (5.581 +/- 0.871) than in the Sham animals (15.80 +/- 1.166), p < 0.001. Morphological analysis of the SCI group showed, in the acute phase, edema, hemorrhage, multiple cavities, fiber degeneration, cell death and demyelination. In the chronic phase we observed glial scarring, neuron death, and remyelination of spared axons by oligodendrocytes and Schwann cells. In conclusion, we established a simple, reliable, and inexpensive clip compression model in mice, with functional and morphological reproducibility and good validity. The availability of producing reliable injuries with appropriate outcome measures represents great potential for studies involving cellular mechanisms of primary injury and repair after traumatic SCI. (C) 2008 Elsevier B.V. All rights reserved.

Lercanidipine decreases vascular matrix metalloproteinase-2 activity and protects against vascular dysfunction in diabetic rats

Abnormal matrix metalloproteinases (MMPs) activity causes cardiovascular diseases. Because hyperglycemia increase MMPs activities through increased oxidative stress. we hypothesized that antioxidant effects produced by lercanidipine could attenuate the increases in MMP-2 expression/activity in diabetic rats. Control and diabetic (alloxan-induced diabetes) rats received lercanidipine 2.5 mg/kg/day (or tap water) starting three weeks after alloxan (or vehicle) injections. Blood pressure was monitored weekly. After six weeks of treatment, vascular reactivity and structural changes were assessed in aortic rings. MMP-2 levels were determined by gelatin zymography, and MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined by fluorimetry. Lercanidipine produced antihypertensive effects (201 +/- 5 vs. 163 +/- 7 mm Hg in diabetic rats untreated and treated with lercaniclipine, respectively; P < 0.01) and reversed the impairment in endothelium-dependent vasorelaxation in diabetic rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of diabetic rats (both P < 0.001). Lercandipine attenuated the increases in oxidative stress and in MMP-2 (both P < 0.05). While diabetes induced no major structural changes, it caused a 16-fold increase in the ratio of MMP-2/TIMP-2 mRNA expression, which was completely reversed by lercanidipine (both P < 0.001). These results show that antioxidant and beneficial vascular effects produced by lercanidipine in diabetic rats are associated with reversion of the imbalance in vascular MMP-2MMP-2 expression. (C) 2008 Published by Elsevier B.V.

Syndromes with salivary dysfunction predispose to tooth wear: case reports of congenital dysfunction of major salivary glands, Prader-Willi, congenital rubella, and Sjogren's syndromes.

Four cases-of congenital dysfunction of the major salivary glands as well as of Prader-Willi, congenital rubella, and Sjogren's syndromes-were identified in a series of 500 patients referred for excessive tooth wear. Although there was evidence of consumption of highly acidic drinks, some occlusal parafunction, and unacceptable toothbrushing habits, salivary dysfunction was the salient factor predisposing a patient to tooth wear in these syndromal cases. The 500 subjects have been characterized either as having medical conditions and medications that predispose them to xerostomia or lifestyles in which workplace- and sports-related dehydration lead to reduced salivary flow. Normal salivation, by buffering capacity, clearance by swallowing, pellicle formation, and capacity for remineralization of demineralized enamel, protects the teeth from extrinsic and intrinsic acids that initiate dental erosion. Thus, the syndromes, unrelated in many respects, underline the importance of normal salivation in the protection of teeth against tooth wear by erosion, attrition, and abrasion.