Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage

Nitric oxide (NO.) is thought to protect against the damaging effects of myocardial ischemia-reperfusion injury, whereas xanthine oxidoreductase (XOR) normally causes damage through the generation of reactive oxygen species. In the heart, inorganic nitrite (NO(2)(-)) has the potential to act as an endogenous store of NO., liberated specifically during ischemia. Using a detection method that we developed, we report that under ischemic conditions both rat and human homogenized myocardium and the isolated perfused rat heart (Langendorff preparation) generate NO. from NO(2)(-) in a reaction that depends on XOR activity. Functional studies of rat hearts in the Langendorff apparatus showed that nitrite (10 and 100 microM) reduced infarct size from 47.3 +/- 2.8% (mean percent of control +/- SEM) to 17.9 +/- 4.2% and 17.4 +/- 1.0%, respectively (P < 0.001), and was associated with comparable improvements in recovery of left ventricular function. This protective effect was completely blocked by the NO. scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (carboxy-PTIO). In summary, the generation of NO. from NO(2)(-), by XOR, protects the myocardium from ischemia-reperfusion injury. Hence, if XOR is presented with NO(2)(-) as an alternative substrate, the resultant effects of its activity may be protective, by means of its production of NO. , rather than damaging.     

Primary pituitary tubercular abscess mimicking as pituitary adenoma

Tubercular abscess of the pituitary fossa is rare and may lead to diagnostic uncertainty in a patient with absence of tuberculosis elsewhere in the body. We present a rare case report of a young lady who presented with sellar and suprasellar cystic mass. She was diagnosed as a case of pituitary macroadenoma and was intraoperatively found to harbor pus in the lesion. She did not have any symptoms of infection. The case underlines the importance of considering such a possibility in the differential diagnosis of cystic sellar lesions and further diagnostic tests should be done for confirmation and treatment of this rare and potential life threatening illness.     

Medical management of pheochromocytoma: Role of the endocrinologist

Pheochromocytoma is a rare tumor arising from chromaffin cells in adrenal medulla or other paraganglia in the body, which may be associated with many genetic syndromes and mutation. The role of endocrinologist is in biochemical diagnosis of suspected cases; its anatomic and functional localization with the help of imaging like CT, MRI, and nuclear scanning; preoperative control of hypertension; and postoperative follow-up of cases that have undergone surgical resection. Familial and genetic screening of cases and their family is important to detect occult cases. Endocrinologist will also play a role in cases with malignant pheochromocytoma in assessment of metastasis, control, chemoradiotherapy, and follow-up.     

Influence of the site of human gallbladder xenograft (Mz-ChA-1) on angiogenesis at the distant site

We reported that orthotopic xenograft of human gallbladder cancer (Mz-ChA-2) produced a greater amount of endogenous angiogenic inhibitory factors, however, only TGFbeta1 suppressed angiogenesis and tumor growth at the distant site (intracranium). The aim of this study was to confirm the validity of our previous findings that the site of the primary tumor would influence the angiogenesis in the distant site in a different xenograft of human gallbladder cancer (Mz-ChA-1). The growth rates, histology of the ectopic (flank) and orthotopic (gallbladder) xenografts, the plasma level of TGFbeta1, micro-circulation and angiogenesis in the distant site (intracranium) were estimated by size-measurement, hematoxylin and eosin staining, ELISA, intravital fluorescence microscopic observation and cranial window gel assay for angiogenesis. All experiments were performed in severe combined immunodeficient (SCID) mice. Orthotopic tumors grew faster and were less necrotic than ectopic tumors. Angiogenesis, vessel diameters, vessel density and leukocyte-rolling count in the distant site were significantly decreased in orthotopic tumor-bearing mice compared to those in either ectopic or no tumor-bearing mice. The plasma level of TGFbeta1 was significantly elevated in mice bearing orthotopic tumor as compared with ectopic and no tumor-bearing mice. Angiogenesis at the distant site was inhibited by the orthotopic xenograft of Mz-ChA-1 by the greatest amount of TGFbeta1 production. The results of the present study together with our previous study imply that the primary tumor microenvironment is conducive to the angiogenesis at a distant site by the production of the endogenous angiogenesis inhibitor TGFbeta1.     

Peritumor lymphatics induced by vascular endothelial growth factor-C exhibit abnormal function

Vascular endothelial growth factor (VEGF)-C is known to induce hyperplasia in normal murine lymphatics and in peritumor lymphatics. Here, we examine the function of these hyperplastic peritumor lymphatics. Microlymphangiography of B16F10 melanomas growing in the murine dorsal skinfold chamber showed that the number of functional, draining lymphatics in the peritumor tissue of VEGF-C-overexpressing tumors was significantly greater than that in mock-transduced tumors (9.5 +/- 1.0 versus 6.3 +/- 0.4; n = 6; P < 0.05). Forty percent of functional lymphatics associated with VEGF-C-overexpressing tumors contained proliferating lymphatic endothelial cells. Surprisingly, these new, functional lymphatic vessels displayed a retrograde draining pattern, which indicates possible dysfunction of the intraluminal valves of these vessels.     

Autonomic alterations and endothelial dysfunction in pediatric obstructive sleep apnea

The cardiovascular consequences of obstructive sleep apnea syndrome (OSAS) in children have started to emerge over the last decade. It is clear that the respiratory and sleep alterations that characterize this relatively prevalent condition induce substantial alterations in autonomic nervous system control, ultimately generating high sympathetic outflow and reactivity that reflect an imbalance between sympatho-excitatory and vagal inhibitory inputs. In addition to these important consequences, the constitutive elements of OSAS also elicit a rather extensive activation of systemic inflammatory pathways that in turn pose substantial risk to the integrity and functional homeostasis of the endothelial network. The complex interactions between the multiple injury-associated pathways recruited by OSAS are further compounded by the potential release of angiogenic factors and by the mobilization and homing of progenitor cells that have the potential to repair and restore the OSAS-disrupted vascular function. Improved characterization of the mechanisms involved in every one of these processes and identification of the determinants of susceptibility in pediatric populations along with the interactions with obesity will clearly modify our approaches to OSAS in the future.     

Periodic electroencephalogram discharges in a case of Lafora body disease: An unusual finding

Lafora body disease (LBD) is a form of progressive myoclonic epilepsy, characterized by seizures, myoclonic jerks, cognitive decline, ataxia, and intracellular polyglucosan inclusion bodies (Lafora bodies) in the neurons, heart, skeletal muscle, liver, and sweat gland duct cells. Electroencephalogram (EEG) findings in LBD may include multiple spikes and wave discharges, photosensitivity, multifocal epileptiform discharges, and progressive slowing in background activity. Periodicity in epileptiform discharges has not been frequently depicted in LBD. We herein report an unusual case of LBD who showed generalized periodic epileptiform discharges in EEG.     

Disclosure of the HIV infection status in children

Objective  

To determine the perception of caregivers about the disclosure of the diagnosis of HIV infection in children.