Nitrite Anion Therapy Protects Against Chronic Ischemic Tissue Injury in db/db Diabetic Mice in a NO/VEGF-Dependent Manner

Nitrite anion has been demonstrated to be a prodrug of nitric oxide (NO) with positive effects on tissue ischemia/reperfusion injury, cytoprotection, and vasodilation. However, effects of nitrite anion therapy for ischemic tissue vascular remodeling during diabetes remain unknown. We examined whether sodium nitrite therapy altered ischemic revascularization in BKS-Lepr^db/db mice subjected to permanent unilateral femoral artery ligation. Sodium nitrite therapy completely restored ischemic hind limb blood flow compared with nitrate or PBS therapy. Importantly, delayed nitrite therapy 5 days after ischemia restored ischemic limb blood flow in aged diabetic mice. Restoration of blood flow was associated with increases in ischemic tissue angiogenesis activity and cell proliferation. Moreover, nitrite but not nitrate therapy significantly prevented ischemia-mediated tissue necrosis in aged mice. Nitrite therapy significantly increased ischemic tissue vascular endothelial growth factor (VEGF) protein expression that was essential for nitrite-mediated reperfusion of ischemic hind limbs. Nitrite significantly increased ischemic tissue NO bioavailability along with concomitant reduction of superoxide formation. Lastly, nitrite treatment also significantly stimulated hypoxic endothelial cell proliferation and migration in the presence of high glucose in an NO/VEGF-dependent manner. These results demonstrate that nitrite therapy effectively stimulates ischemic tissue vascular remodeling in the setting of metabolic dysfunction that may be clinically useful.     

Involvement of vH+‐ATPase in synaptic vesicle swelling

Secretory vesicle swelling is central to cell secretion, but the underlying mechanism of vesicle swelling, particularly synaptic vesicles, is not completely understood. The G_αi3‐PLA2‐mediated involvement of water channel AQP‐1 in the regulation of secretory vesicle swelling in exocrine pancreas and the G_αo‐mediated AQP‐6 involvement in synaptic vesicle swelling in neurons have previously been reported. Furthermore, the role of vH⁺‐ATPase in neurotransmitter transport into synaptic vesicles has also been shown. Using nanometer‐scale precision measurements of isolated synaptic vesicles, the present study reports for the first time the involvement of vH⁺‐ATPase in GTP‐G_αo‐mediated synaptic vesicle swelling. Results from this study demonstrate that the GTP‐G_αo‐mediated vesicle swelling is vH⁺‐ATPase dependent and pH sensitive. Zeta potential measurements of isolated synaptic vesicles further demonstrate a bafilomycin‐sensitive vesicle acidification, following the GTP‐G_αo‐induced swelling stimulus. Water channels are bidirectional and the vH⁺‐ATPase inhibitor bafilomycin decreases both the volume of isolated synaptic vesicles and GTP‐mastoparan stimulated swelling, suggesting that vH⁺‐ATPase is upstream of AQP‐6, in the pathway leading from G_αo‐stimulated swelling of synaptic vesicles. Vesicle acidification is therefore a prerequisite for AQP‐6‐mediated gating of water into synaptic vesicles. © 2009 Wiley‐Liss, Inc.     

Adhesive small bowel obstruction (ASBO) in children--role of conservative management

Adhesive small bowel obstruction (ASBO) is an annoying postoperative complication. Though the diagnosis can be made easily, the role of conservative management in children is controversial. Hence a study was conducted to determine the role of conservative management, and to identify the factors that can predict / influence the outcome of conservative treatment in children with ASBO. Children admitted with ASBO from 1980 to 2002 (22 year period) formed the material for this study. The data was analyzed with respect to the influence of age at the time of presentation, primary disease for which original laparotomy was done, time interval between the primary surgery and the development of ASBO and the number of laparotomies prior to the development of ASBO on the outcome of conservative management. There were 74 episodes of ASBO in 69 children (Five children had two episodes). Out of 74 episodes, 5 episodes (6.75%) needed immediate laparotomy for suspected gangrene. All others were managed conservatively. Of the 69 episodes managed conservatively, 36 responded to conservative treatment (2-5 days) while 33 required subsequent surgical intervention, with 11 of them requiring bowel resection (two for gangrene and 9 for bowel damage during adhesiolysis) and in the rest 22 cases adhesiolysis. A substantial number of children with ASBO respond well to conservative treatment. Majority of the children developed ASBO within three months after the primary laparotomy. Children below the age of one year (at the time of presentation with ASBO) responded poorly to the conservative management. Children who had primary surgery for Hirschsprung's disease and intussusception also appeared to have responded poorly to conservative management, but statistically not significant. Time interval between the primary surgery and the number of laparotomies before the child developed ASBO did not influence the outcome of conservative management.     

Cranial magnetic resonance imaging of Wolfram (DIDMOAD) syndrome

Wolfram syndrome is a rare neurodegenerative disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD). A wide spectrum of abnormalities of the central nervous system, urinary tract and endocrine glands is also observed. We report cranial MRI findings in a 32-year-old female patient with Wolfram syndrome. In addition to the classical features, including absence of the normal high signal of the neurohypophysis, atrophy of visual pathways, the brainstem, cerebellum and cerebral cortex, we observed bilateral hyperintensity on proton density- and T2- weighted images related to the optic radiations in the periventricular white matter of the temporal and parieto-occipital lobes, which may reflect gliosis pathologically.     

Biomechanics of the head for Olympic boxer punches to the face

Objective: The biomechanics of the head for punches to the jaw and the risk of head injury from translational and rotational acceleration were studied. Results: Punch force averaged 3427 (standard deviation (SD) 811) N, hand velocity 9.14 (SD 2.06) m/s, and effective punch mass 2.9 (SD 2.0) kg. Punch force was higher for the heavier weight classes, due primarily to a higher effective mass of the punch. Jaw load was 876 (SD 288) N. The peak translational acceleration was 58 (SD 13) g, rotational acceleration was 6343 (SD 1789) rad/s², and neck shear was 994 (SD 318) N. Conclusions: Olympic boxers deliver straight punches with high impact velocity and energy transfer. The severity of the punch increases with weight class.