Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes.

Oxidative stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a cellular adaptive response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative stress and cellular stress response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic cellular stress response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P<0.05 and P<0.01) in diabetic patients were higher than in normal subjects, while sirtuin-1 and sirtuin-2 protein was significantly decreased (p<0.05). In conclusion, patients affected by type 2 diabetes are under condition of systemic oxidative stress and, although the relevance of downregulation in sirtuin signal has to be fully understood, however induction of HSPs and thioredoxin protein system represent a maintained response in counteracting systemic pro-oxidant status. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

Redox regulation of cellular stress response in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease with characteristic foci of inflammatory demyelination in the brain, spinal cord, and optic nerves. Recent studies have demonstrated not only that axonal damage and neuronal loss are significant pathologic components of MS, but that this neuronal damage is thought to cause the permanent neurologic disability often seen in MS patients. Emerging finding suggests that altered redox homeostasis and increased oxidative stress, primarily implicated in the pathogenesis of MS, are a trigger for activation of a brain stress response. Relevant to maintenance of redox homeostasis, integrated mechanisms controlled by vitagenes operate in brain in preserving neuronal survival during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. In the present study we assess stress response mechanisms in the CSF, plasma and lymphocytes of control patients compared to MS patients. We found that the levels of vitagenes Hsp72, Hsc70, HO-1, as well as oxidative stress markers carbonyls and hydroxynonenals were significantly higher in the blood and CSF of MS patients than in control patients. In addition, an increased expression of Trx and sirtuin 1, together with a decrease in the expression of TrxR were observed. Our data strongly support a pivotal role for redox homeostasis disruption in the pathogenesis of MS and, consistently with the notion that new therapies that prevent neurodegeneration through nonimmunomodulatory mechanisms can have a tremendous potential to work synergistically with current MS therapies, unravel important targets for new cytoprotective strategies.

[Efficacy of dutasteride, alfuzosin or both on Quality of Life in patients with prostatic hyperplasia and BOO.A two-year spontaneous, observational, self-controlled study].

Three homogeneous groups of patients suffering from benign prostatic hypertrophy (BPH) were evaluated by means of a two-year observational study, in order to assess and compare their Quality of Life (QoL) under the following different medical treatments. Group 1: alfuzosin alone, Group 2: alfuzosin and dutasteride, Group 3: dutasteride alone. QoL was evaluated by validated indexes, such as the IPSS and the QoL-Vas. Although different in entity and timing, as expected, all the three groups showed an improvement. The best and quickest results were detected in the drug association of Group 2. Significant decrease in volume was detected in the dutasteride groups (2 and 3) but not in group 1 (alfuzosin alone), where a quick relief of LUTS was detected, due to its wellknown alphalytic action. Our results suggest that dutasteride alone does not result in a rapid decrease in LUTS, whereas it can help to manage the reduction of the prostate volume. A combination therapy seems therefore to be recommended to obtain LUTS relief both in the short and long term results.

[Blind traumas of the scrotum: three case reports].

The blind traumas of the scrotum are an uncommon event; references, iconography and descriptions of the clinical development of scrotal syndromes are poor. The scrotum and the didimal or funicular structures are often involved in different conditions. The authors are reporting on three interesting cases (for patients' age, mechanism of traumatism and anatomic damage), gathered from a series of 12 cases of blind traumas of the scrotum, observed during 2 years (2005-2006). They include the iconography related to each single case, and emphasize the uncertain role of ultrasonography with color Doppler for a correct diagnosis. The clinical evolution and the long-term damage to gonad functionality are presented.

[Primary hyperoxaluria and pregnancy]. / L'iperossaluria primaria e gravidanza.

A rare case of pregnancy in a patient with primary hyperoxaluria type 1 is reported offering a clinical contribution for the prognostic study of a natural event such as the pregnancy on these patients. It is underlined how epicriticity of the hepatorenal system is remarkably altered during the last weeks of pregnancy with a great increase of calciuria and proteinuria with a risk of life for the patient and the newborn. In fact, during the 36rd week a caesarean section was performed due to gestosis. Moreover, the deterioration of kidney functionality doesn't decrease during post partum. Therefore, it would be advisable inform these patients about the risk of pregnancy.

Disorders of micturition in neurological patients. A clinical study of 786 patients.

Our aim was to evaluate the utility and effectiveness of a study protocol for neurological involvement in neurological disorders. We studied a sample of 786 patients with neurological disorders followed by the Neurological Department of Catania University and applied to them a four-step diagnostic protocol. Fifty-six per cent of the sample showed urological functional abnormalities; only 78 patients (9.9%) presented with an organic urological disease. Among the vesicosphincteric dysfunctions, bladder hyperreflexia was the most common pattern with remarkable differences between diseases. The present study demonstrated the utility of a standardized urological protocol in the screening and detection of neurological involvement in neurological diseases. Our protocol showed good specificity and reasonable low costs.