The role of nitric oxide in the pathogenesis of systemic and splanchnic vasodilation in cirrhotic rats before and after the onset of ascites.

BACKGROUND: The role of nitric oxide (NO) in the pathogenesis of splanchnic arterial vasodilation in cirrhosis has been recently debated by some experimental studies. AIMS: We investigated the role of NO in the pathogenesis of the splanchnic arterial vasodilation along the course of CCl(4)-induced experimental cirrhosis. METHODS: We analyzed the effect on mean arterial pressure (MAP), cardiac output (CO), total peripheral resistance (TPR), and resistance in the superior mesenteric artery (RSMA), before and after the administration of a unspecific NO synthase (NOS) inhibitor (Nomega-nitro-L-arginine-methyl-ester, L-NAME) and a specific NOS2 inhibitor (L-N-(1-iminoethyl)-lysine, L-NIL) to cirrhotic rats with and without ascites, and to control rats. NOS2 and NOS3 protein expression was also assessed in systemic and splanchnic arteries of these animals. RESULTS: L-NAME in cirrhotic rats markedly improved MAP, and TPR and decreased CO regardless of whether they had ascites or not. L-NIL did not produce any significant effect on systemic haemodynamics in control and cirrhotic rats. NOS3 overexpression in the aorta of cirrhotic animals paralleled the progression of the liver disease. L-NAME increased RSMA in cirrhotic rats, but this effect was much less intense in rats with ascites. L-NIL had an effect only on RSMA in rats with ascites, which was of a similar extent to that produced by L-NAME. Western blot experiment showed a faint overexpression of NOS3 in the mesenteric artery of cirrhotic rats with and without ascites and a clear induction of NOS2 only in the mesenteric artery of rats with ascites. Conclusions: These results indicate that NO contributes significantly to the pathogenesis of arterial splanchnic circulation in the early stages of experimental cirrhosis but has only a minor role in its maintenance after the development of ascites. Furthermore, the expression of the different NOS isoforms varies along the course of the liver disease.     

Cell apoptosis and granulomatous lung diseases

Apoptosis, also known as activation-induced cell death or programmed cell death, is an active suicide mechanism that is involved in normal tissue turnover during embryogenesis and adult life. There are many examples of apoptosis in the immune system, including programmed cell death of T cells during negative intrathymic selection of the TCR repertoire and, in the postthymic phase, death of responsive T cells upon specific activation of the TCR/CD3 complex. Induction of apoptosis assures rapid disappearance of the immune response upon antigenic clearance, avoiding the metabolic costs involved in sustaining a large number of effector cells. The knowledge that failure of immune cells to die is the cause of a number of immune-mediated disorders has opened intriguing new avenues of exploration into the pathogenetic events leading to the accumulation of immunoinflammatory cells at sites of ongoing inflammation in granulomatous disorders, including granulomas initiated by infectious agents, such as Mycobacterium tuberculosis, or in sarcoidosis. In this paper we review recent results obtained in experimental animal models and patients with immune granuloma suggesting that the positive induction by ligands binding to membrane receptors or the induction or loss of intracellular suppressor signals regulates immunoregulatory mechanisms that drive the progressive development of the granulomatous structure. The great advances in understanding how mechanisms for the activation or downregulation of apoptosis have a pathogenetic role in the outcome of granulomatous disorders are also briefly considered.     

Role of insulin-like growth factor-I in primary osteoporosis: a correlative study

Osteoporosis is characterized by impairment of bone mass and deterioration of bone microscopic structure, resulting in increased bone fragility and susceptibility to fracture. Recent reports have indicated that reduced plasma levels of IGF-I are associated with osteoporosis in both males and females. Moreover, there is accumulating clinical evidence that treatment with GH or IGF-I has beneficial effects on bone mass and bone remodeling in men with idiopathic osteoporosis, in the elderly and in hypopituitary patients. As correlative studies on IGF-I, IGF-BP3 and bone mass in the elderly are lacking, we studied the relationships between serum IGF-I, IGF-BP3, bone mineral density (BMD), body mass index (BMI), calciotropic hormones and age in 102 premenopausal and postmenopausal women. Our study indicates that the reduction of the anabolic processes mediated by IGF-I may account for the slow and progressive loss of bone mass that take place after the age of 40-50 years. In addition, nutritional caloric or proteic deficit may add to the effects of GH, age and other factors in decreasing IGF-I synthesis and therefore further contribute to the development of primary osteoporosis.     

Generating proper names: A case of selective inability

This paper reports the study of a brain-injured patient with a selective inability to generate various types of proper names. Auditory and reading comprehension for the same category were both fairly intact. As in other similar cases the deficit is believed to be at the level of the output lexicon, which would therefore be presumed to be categorically organised. The question considered is why certain lexical categories are selectively impaired or preserved. A single answer is difficult to find and may be impossible to obtain since there appears to be nothing in common among these categories. As far as proper names are concerned a distinction between them and common names that may justify independent processing is to be found in the thoughts of some modern philosophers. According to them the function of proper names, unlike common names, is simply to refer to the object so named and not to describe them by any property.     

Severe acute hepatitis B in a treatment‐naïve patient with antiviral drug resistant mutations in the polymerase gene

This is a case of 62 years old Caucasian treatment‐naïve patient who developed a severe acute hepatitis B infection soon after a trip to Thailand. The infection was due to genotype C HBV which was found to be resistant to lamivudine and telbivudine. The patient was treated with tenofovir resulting in complete suppression of viral replication and complete clinical and laboratory remission of acute hepatitis. Later the patient also developed seroconversion of HBeAg to anti‐HBe and of HBsAg to anti‐HBs. This case demonstrates that mutations of HBV polymerase associated with lamivudine, telbivudine, and adefovir resistance can be present also in untreated patients with severe acute hepatitis B. This suggests that in the clinical context, which represents a life threatening condition, a baseline resistance‐testing should be an additional marker in the diagnostic evaluation process. Finally, this case report seems to support the use of tenofovir for the immediate treatment of severe acute hepatitis B. J. Med. Virol. 85:210–213, 2013. © 2012 Wiley Periodicals, Inc.     

Nerve ultrasound in hereditary transthyretin amyloidosis: red flags and possible progression biomarkers

Journal of Neurology - Diagnostic delay of hereditary transthyretin amyloidosis (ATTRv, v for variant) prevents timely treatment and, therefore, concurs to the mortality of the disease. The aim of...     

Beyond physiotherapy and pharmacological treatment for fibromyalgia syndrome: tailored tACS as a new therapeutic tool

European Archives of Psychiatry and Clinical Neuroscience - Fibromyalgia syndrome (FMS) is a complex pain disorder, characterized by diffuse pain and cognitive disturbances. Abnormal cortical...