Alteration of beta-cell constitutive NO synthase activity is involved in the abnormal insulin response to arginine in a new rat model of type 2 diabetes.

We have previously obtained a new type 2 diabetic syndrome in adult rats given streptozotocin and nicotinamide, characterized by reduced beta-cell mass, partially preserved insulin response to glucose and tolbutamide and excessive responsiveness to arginine. We have also established that the neuronal isoform of constitutive NO synthase (nNOS) is expressed in beta-cells and modulates insulin secretion. In this study, we explored the kinetics of glucose- and arginine-stimulated insulin release in perifused isolated islets as well as the effect of N-omega-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, to get insight into the possible mechanisms responsible for the arginine hypersensitivity observed in vitro in this and other models of type 2 diabetes. A reduced first phase and a blunted second phase of insulin secretion were observed upon glucose stimulation of diabetic islets, confirming previous data in the isolated perfused rat pancreas. Exposure of diabetic islets to 10 mM arginine, in the presence of 2.8 mM glucose, elicited a remarkable monophasic increment in insulin release, which peaked at 639 +/- 31 pg/islet/min as compared to 49 +/- 18 pg/islet/min in control islets (P << 0.01). The addition of L-NAME to control islets markedly enhanced the insulin response to arginine, as expected from the documented inhibitory effect exerted by nNOS activity in normal beta-cells, whereas it did not further modify the insulin secretion in diabetic islets, thus implying the occurrence of a defective nNOS activity in these islets. A reduced expression of nNOS mRNA was found in the majority but not in all diabetic islet preparations and therefore cannot totally account for the absence of L-NAME effect, that might also be ascribed to post-transcriptional mechanisms impairing nNOS catalytic activity. In conclusion, our results provide for the first time evidence that functional abnormalities of type 2 experimental diabetes, such as the insulin hyper-responsiveness to arginine, could be due to an impairment of nNOS expression and/or activity in beta-cells.

[Rheumatological manifestations following hepatitis B vaccination. A report of 2 clinical cases]. / Manifestazioni reumatologiche dopo vaccinazione contro l'epatite B. Descrizione di due casi clinici.

In the literature there are a few occasional case reports of rheumatic manifestations following vaccination. The link between vaccination and musculoskeletal complaints was established on the grounds of the chronological succession between the two events. The occurrence of an individual genetic predisposition has been stressed many times. With regard to immunopathological mechanisms, it has been proposed the vaccination as a trigger of a very autoimmune disease or an immune complex-induced disease. In this paper we describe two females who underwent vaccination against hepatitis B virus. One complained of polyarticular pain that, even if self-limiting, was accompanied by the positivity of RA-test and Waaler-Rose reaction; the other showed migratory arthritis, urticaria and oedema of the glottis and the upper lip, all successfully treated with a short course of corticosteroids. We think these reports are of interest at the time when vaccination against hepatitis B virus is becoming a mass practice.

[Current views on the pathogenesis and therapy of ankylosing spondylitis]. / Orientamenti attuali in tema di patogenesi e terapia della spondilite anchilosante.

Ankylosing spondylitis is a frequent and disabling inflammatory chronic disease, that affects mainly young men. In this paper the authors reviewed the pathogenetic mechanism and pharmacological and physical treatment. Nowadays the pathogenesis of ankylosing spondylitis is considered similar to that of reactive arthritis. The management of each patient should take into account the different aspects of the disease; therefore it should be individually designed.