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It is widely acknowledged that cultured myoblasts can not differentiate at very low density. Here we analyzed the mechanism through which cell density influences myogenic differentiation in vitro. By comparing the behavior of C2C12 myoblasts at opposite cell densities, we found that, when cells are sparse, failure to undergo terminal differentiation is independent from cell cycle control and reflects the lack of p27Kip1 and MyoD in proliferating myoblasts. We show that inhibition of p27Kip1 expression impairs C2C12 cell differentiation at high density, while exogenous p27Kip1 allows low-density cultured C2C12 cells to enter the differentiative program by regulating MyoD levels in undifferentiated myoblasts. We also demonstrate that the early induction of p27Kip1 is a critical step of the N-cadherin-dependent signaling involved in myogenesis. Overall, our data support an active role of p27Kip1 in the decision of myoblasts to commit to terminal differentiation, distinct from the regulation of cell proliferation, and identify a pathway that, reasonably, operates in vivo during myogenesis and might be part of the phenomenon known as "community effect".

Atherosclerosis is a chronic inflammatory process due to the endothelial reaction to stress risk factors, only some of which are known. Clinical and experimental observations have suggested that several infectious agents are involved in this process. These agents, particularly the germ Chlamydia pneumoniae, and their relationship to the atheromata are described. Two hypotheses concerning how these infectious agents act are suggested. Both hypotheses are based on the capacity of these agents to induce the production, by endothelial cells, of the so-called heat shock protein (HSP), one of whose characteristics is to provoke an immune system reaction: 1) induction of a cross immune reaction, due to "molecular mimicry", between the HSP of infectious origin and the one that is produced by the endothelium as a consequence of stress due to the risk factors; 2) infection of the endothelial cells, followed by the synthesis and exposure on their surface of the HSP and activation of innate immune surveillance. Numerous experimental studies have been performed and are still being performed with the aim of verifying the efficacy of antibiotic treatment in preventing or reducing the rate of acute cardiovascular events. The results are still inconclusive. Probably, to be effective, treatment should be started at an earlier age. Prevention through vaccination against the involved microorganisms and the consequent induction of immune tolerance toward the HSP is also being investigated. As the mechanisms of action of infectious agents are further clarified, effective therapeutic and preventive measures could be taken with important clinical spin-offs.

The authors describe a case of suicide by a single shot to the head from the latest type of captive bolt pistol (which has lateral instead of frontal gas outlets), with the aim of finding criteria to identify correctly the lesions caused by this type of weapon correctly and to distinguish them from those caused by typical firearms.

A 35-year-old woman was admitted to our hospital with the following complaints, headache, sweating, anxiety, dizziness, nausea, vomiting and severe hypertension. The technical images (abdominal CT, scintigraphic octreotide scan and renal arteriography) revealed the presence of a left adrenal pheochromocytoma and stenosis of the renal artery. Ten days following adrenalectomy, watery diarrhea appeared. The long-acting somatostatin analogue octreotide (LAR, 30 mg/month, i.m.), was started, and after 2 weeks diarrhea decreased and gradually disappeared. In conclusion, we were confronted with an unusual case of pheochromocytoma associated with renal artery stenosis and the appearance of watery diarrhea some days after surgical treatment. Treatment with octreotide brought about the remission of diarrhea in this patient., (Copyright 2002 S. Karger AG, Basel)

1. The gamma-aminobutyric acid (GABA)-ergic system, which is functionally altered in obese (fa/fa) Zucker rats, plays an important role in controlling energy balance within the central nervous system. 2. GABA receptors seem to be involved in the dysfunction of the hypothalamic energy homeostasis-controlling mechanisms in these animals due to a genetically-induced defect of the leptin-neuropeptide Y system. 3. To shed further light on the possible role played by the GABA system in the pathogenesis of this rat model, two benzodiazepine (BDZ) receptor agonists (diazepam and clonazepam) and one BDZ antagonist (flumazenil) were administered intraperitoneally in obese and lean Zucker rats. 4. Body weight gain was reduced by the BDZ agonists in both phenotypes, and one receptor-agonist (diazepam) lowered insulin concentration in obese rats. In GABA-antagonist-treated obese rats, the daily amount of body weight gain and food intake acquired an oscillatory rhythm similar to that of normal rodents. 5. By demonstrating the role of BDZ receptors, these findings may help clarify the pathophysiology of obesity and insulin resistance in fatty Zucker rats.

Two cases of neuroleptic malignant syndrome are reported. Although affecting chiefly psychiatric patients, this rare, polymorphic disease should be well-known to internists, general practitioners, and emergency staff because of its high risk of fatality. Our patients, who presented without some of the main symptoms, fell in the category of incomplete variants of the syndrome, the most difficult to recognize. In both patients, computerized tomography carried out at the outset of symptoms, evidenced signs of cerebral edema, a datum never before reported. The symptomatic polymorphism, pathogenesis, differential diagnosis, and therapy of this disease are illustrated and discussed.

The origin of the insulin resistance syndrome which, mostly through its cardiovascular implications, is characterized by a high incidence of death, is still practically unknown. Energy and glucose homeostasis are under the control of CNS centers and the neurotransmitter GABA modulates the activity of these centers. Alteration of the biochemical structure of GABA receptors is suggested as an interpretation of the origin of the syndrome.

As it's well known from the clinic, human syndromes depending on pituitary GH, ACTH and PRL secreting tumors are associated with alteration of glucose homeostasis. There is an hypothetical but convincing explanation for this, based on a number of concrete observations and experiments. The main mechanism for glucose intolerance or overt diabetes is related to insulin-resistance. The increased concentration of the three hormones would alter the action of insulin on its target cells at binding and (mainly) post-binding level. Besides recent researches indicate that the hypothalamus may play an important role in the pathogenesis of at least some cases of pituitary adenomas and, directly or indirectly, of the glucose homeostasis derangement.

Tissue polypeptide antigen (TPA) has been detected by immunocytochemical assay on urine cytological samples from 28 asymptomatic patients, who previously had a histological diagnosis of papillary transitional cell carcinoma (PTCT) of the urinary bladder (UB), in order to evaluate its role in follow-up controls. TPA staining intensity (SI) in urothelial cells was evaluated to improve the diagnostic accuracy of cytology. Differentiated tumor cells were strongly stained for TPA, heavier than normal urothelial cells. Undifferentiated neoplastic cells were less stained for TPA with a wide range of SI. TPA detection revealed positive cytology in 21 (75%) of the considered cases. The accuracy of our cytological findings compared with both routine examinations and subsequent histopathological diagnosis was of 95.2%. Follow-up urinary cytology limits could be reduced by TPA searching in differentiated tumor cells, deriving from low-grade neoplasms.

Four cases (belonging to two different families) of Wolfram's syndrome (WS), a rare congenital disease characterized in its complete form by insulin-dependent diabetes mellitus, optic atrophy, diabetes insipidus, deafness, and dilation of the urinary tracts are presented, and a review of the literature is included. Three of four patients are characterized by HLA-DR2 haplotype, which is rare in IDDM. The neurodegenerative nature of some symptoms and the possible pathogenesis of diabetes mellitus connected with it are discussed.

The authors have examined some electrophysiologic data in two couples of siblings with Wolfram's syndrome and in the unaffected sister of one of the couples. The results confirment the involvement of some neurologic structures and show up how the Evocated Potentials can disclose a damage in the a.m. structures even lacking clinical features.