The NO donor DETA-NONOate reversibly activates an inward current in neurones and is not mediated by the released nitric oxide

Background and purpose:

It has been previously shown that high levels of nitric oxide (NO), from NO donors, kill neurones, but the mechanisms are unclear.

Experimental approach:

The effects of NO donors on the electrical properties of rat cultured cerebellar granule cells (CGC neurones) were investigated using the whole-cell patch-clamp technique.

Key results:

The NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate or NOC-18) caused a rapid, persistent, but fully reversible inward current that was associated with an increase in baseline noise and was concentration dependent (100 µM–10 mM). The response to 3 mM DETA-NONOate was completely inhibited by 1 mM gadolinium, but not by NO scavengers (1 mM haemoglobin or 1 mM PTIO) or glutamate receptor antagonists (10 µM MK-801 or 60 µM CNQX). Application of decomposed 3 mM DETA-NONOate or 3 mM nitrite had no effect. In contrast, the NO donor S-nitrosoglutathione (GSNO) caused a rapid, persistent, but fully reversible outward current that was also concentration dependent (1–10 mM). The 3 mM GSNO response was unaltered by NO scavengers, glutamate antagonists or gadolinium, but was mimicked by decomposed 3 mM GSNO and 3 mM oxidized glutathione.

Conclusions and implications:

These results suggest that DETA-NONOate directly activates cation-selective channels, causing an inward current in CGCs. In contrast, GSNO causes an outward current in these cells. Some of the effects of these NO donors are independent of NO, and thus caution is required in interpreting results when using high concentrations of these compounds.     

A study of computed tomography scan and magnetic resonance imaging findings in pseudohypoparathyroidism

We report three children with pseudohypoparathyroidism aged 13-16 years who presented with seizures and tetany. CT scan revealed striatopallidal calcification in two. MRI revealed wide-spread involvement showing T1 hyperintensity in striatopallidodentate distribution in all three and midbrain in one patient. T2 and FLAIR images were normal. T1 hyperintensity could represent early stage of calcification in whom MRI is more sensitive.     

Erythrocyte plasma membrane redox system in human aging

Eukaryotic cells display a plasma membrane redox system (PMRS) that transfers electrons from intracellular substrates to extracellular electron acceptors. The physiologic importance of PMRS is still not fully understood. The authors have carried out studies to determine the activity of PMRS in human erythrocytes as a function of age and correlate the activity with total plasma antioxidant capacity in an effort to understand the role of PMRS in human aging. The study was carried out on 80 normal healthy subjects of both genders between the ages of 18 and 85 years. The activity of erythrocyte PMRS was estimated by following the reduction of ferricyanide. The total antioxidant capacity of the plasma was estimated in terms of Ferric Reducing Ability of Plasma (FRAP) values. A significant (p < 0.0001) positive correlation (r = 0.7797) is observed between PMRS activity of erythrocytes and human age. There is an age-dependent decrease in total plasma antioxidant capacity measured in terms of FRAP values. A highly significant correlation is observed between PMRS activity and plasma FRAP values. The authors hypothesize that the increased PMRS in erythrocytes during aging may be a protective mechanism of the system for efficient extracellular DHA reduction and ascorbate recycling under condition of increased oxidative stress.     

Gloves as a teaching tool in vascular surgery

Training and practice are essential aspects of keeping surgical skills sharp. We present a technique where we use latex gloves as a reliable, easily available, inexpensive tool to train surgeons in vascular surgery.     

Therapy with un-engineered naïve rat umbilical cord matrix stem cells markedly inhibits growth of murine lung adenocarcinoma

Background  

Lung cancer remains the leading cause of cancer-related mortality despite continuous efforts to find effective treatments. Data from the American Cancer Society indicate that while the overall incidence of lung cancer is declining, it continues to rise in women. Stem cell-based therapy has been an emerging strategy to treat various diseases. The purpose of this paper is to determine the efficacy of an intrinsic anti-cancer effect of rat umbilical cord matrix stem cells (UCMSCs) on lung cancer.     

Evaluation of anti-ulcerogenic and ulcer-healing properties of Ocimum sanctum Linn

Ocimum sanctum (OS) is known to possess various therapeutic properties. We evaluated its anti-ulcerogenic activity in cold restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models in Sprague-Dawley rats, histamine-induced duodenal (HST) ulcer in guinea pigs, and ulcer-healing activity, in acetic acid-induced (AC) chronic ulcer model. We found that OS, decreased the incidence of ulcers and also enhanced the healing of ulcers. OS at a dose of 100 mg/kg was found to be effective in CRU (65.07%), ASP (63.49%), AL (53.87%), PL (62.06%), and HST (61.76%) induced ulcer models and significantly reduced free, total acidity and peptic activity by 72.58, 58.63, 57.6%, respectively, and increased mucin secretion by 34.61%. Additionally, OS completely healed the ulcers within 20 days of treatment in AC. We observed that anti-ulcer effect of OS may be due to its cytoprotective effect rather than antisecretory activity. Conclusively, OS was found to possess potent anti-ulcerogenic as well as ulcer-healing properties and could act as a potent therapeutic agent against peptic ulcer disease.     

One-stage Fowler-Stephens orchidopexy for impalpable undescended testis

Background The Fowler-Stephens orchidopexy (FSO) is a well-described treatment for high maldescended testes where the limiting factor for successful placement in the scrotum is short testicular vessels. The operation involves division of these vessels. The testicular blood supply is then dependent on collaterals from the vasal artery. Aims To assess the long-term outcome of patients who underwent this procedure in our institution. Methods The medical records of 20 patients who underwent 22 FSO from 1978 to 1999 by one urologist (HB) were reviewed. Outcome was assessed in terms of testicular position and size. Results Age at operation ranged from 2 to 14 years (mean 5.8 years). All patients had a one-stage FSO and in two of them the procedure was bilateral. In five patients, FSO was preceded by a diagnostic laparoscopy. Mean follow up was 22 months (range 0–121 months). Overall, results were considered good in 18 of 22 testes (82%). Conclusion Our results for the one-stage FSO are comparable with other procedures for the management of high maldescended testis.     

Isoniazid associated,painful, bilateral gynaecomastia

Gynaecomastia is a rarely reported adverse drug reaction due to isoniazid therapy. We describe a 25-year-old, human immunodeficiency virus (HIV)--negative man, who was started on antituberculosis treatment (ATT) with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) in the combination RHZE for the first two months and RH there on. After four months, while receiving RH, he developed painful bilateral gynaecomastia. ATT had to be stopped because of this adverse drug reaction. Gynaecomastia, however, persisted even after three months of cessation of therapy. A year later, the patient reported complete disappearance of pain and swelling, although right breast continued to appear larger than the left.