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Background: Adhesion of monocytes triggers apoptosis, cytotoxicity, cytokine release, and later proliferation of cultured human mesangial cells (HMC). In the search for transmembrane signals transducing the interaction of HMC adhesion molecules with leukocyte counterreceptors, we measured variations of cytosolic Ca(2+) ([Ca(2+)](i)) in HMC and monocytes of the U937 cell line during 6-h co-cultures., Methods: Monolayer cultures of HMC and suspensions of U937 cells were loaded with the fluoroprobe fura 2-AM and subsequently co-cultured for 6 h while separately monitoring by microfluorometry the Ca(2+)-dependent 500 nm fluorescent emission of each cell line at fixed intervals upon excitation at 340/380 nm., Results: U937 and peripheral blood monocyte adhesion was followed in HMC by a slow, progressive rise of [Ca(2+)](i) from basal levels of 96+/-9 nM to 339+/-54 at 60 min and 439+/-44 nM at 3 h. The [Ca(2+)](i) elevation reached a steady state thereafter, while parallel monolayers incubated with control media maintained resting levels throughout the co-culture with stable fluoroprobe retention. Receptor sensitivity to vasoconstrictor agents, including compounds not released by monocytes, such as angiotensin II, was rapidly downregulated in HMC co-cultured with U937 cells. No [Ca(2+)](i) changes could be elicited by the octapeptide or by the TxA(2) analogue, U-46619, as early as 30 min after exposure to U937 cells. No [Ca(2+)](i) changes were observed in U937 cells throughout the co-culture. Conditioned media from monocytes and from co-cultured HMC+U937 cells had no effect on [Ca(2+)](i) of HMC. Ca(2+) entry leading to fura 2 saturation was still inducible by Ca(2+) ionophores, such as ionomycin and 4-Br-A23187, which also inhibited the responses to vasoconstrictors. Ca(2+)-free solutions prevented the [Ca(2+)](i) rise as well as subsequent receptor inactivation, implicating Ca(2+) influx through store-operated Ca(2+) channels (SOC), a major pathway for Ca(2+) entry in these cultured cells. Ca(2+) influx was confirmed by Mn(2+)-quenching of fura 2., Conclusions: In HMC, early changes in [Ca(2+)](i) signal for monocyte adhesion in a co-culture model of glomerular inflammation. This signalling mechanism may mediate the functional responses elicited in glomerular cells by leukocytes, including downregulation of receptors for vasoactive agents.

Liver fibrosis is the end result of an imbalance between synthesis and degradation of extracellular matrix proteins of the liver. The extracellular matrix of the liver is complex. It comprises multiple components of three major types of macromolecules: proteins, glycoproteins and proteoglycans. The normal liver contains limited amounts of extracellular matrix composed of elastin, fibronectin, collagen, proteoglycans and other macromolecules. These molecules have specific structure-function properties. In the liver they provide a structural framework and modulate tissue repair. The fibrogenesis is a reaction to liver injury, it leads to marked impairment of hepatic sinusoidal blood flow and ultimately to cirrhosis associated with portal hypertension and hepatocyte dysfunction. The process of fibrosis is the result from complex interactions between extracellular matrix macromolecules, hepatic cells, cytokines and growth factors, that activate the stellate cells of the liver to induce the synthesis of extracellular matrix components that deposit into the local extracellular matrix and to produce the inhibitor of metalloproteinase. The end result of these activities is an imbalance in the synthesis/degradation homeostasis of the liver, that is, liver fibrosis.

Serum levels of some extracellular matrix components increased in different liver diseases are studied. Hyaluronic acid (HA) and amino-terminal propeptide of type III procollagen (PNIIIP) have been the most extensively studied serum components. In particular, serum levels of PNIIIP seem to be mainly correlated with histological activity in chronic hepatitis. Considering the close pathophysiological relationship between histological activity and fibrogenesis, it is possible to consider PNIIIP as a marker of fibrogenesis. Thus, serum PNIIIP could be a useful tool for monitoring the therapeutic response in patients with chronic hepatitis in treatment with antifibrogenetic and antifibrotic agents. Like PNIIIP, serum HA concentrations increase in patients with liver fibrosis. There is evidence that serum levels of HA are more strongly correlated with histological grades of liver fibrosis than serum PNIIIP. This suggests that serum HA may be preferable for discriminating patients with cirrhosis from those without cirrhosis. There are other extracellular matrix components and a combination of several serum markers could increase their diagnostic value, but further studies are needed to confirm this.

Purpose: To evaluate long-term results of hypocaloric dietetic treatment in patients with essential obesity., Patients and Methods: The study was carried out in 1,479 woman and 320 men. Body weight was evaluated at 3 months and at 1, 2 and 3 years., Results: The best results in short term reduction of weight excess were found in obesity due to sedentariness or arisen after operation or emotional stress. It has been also observed that the percentage of subjects loosing weight decreased after the first year of treatment, while the percentage of subjects gaining body weight., Conclusions: Long term hypocaloric dietetic treatment in subjects with low or moderate essential obesity should primarily be aimed preventing further gain in body weight.

We have investigated 2672 obese subjects (2324 females and 348 males); of these, the following two groups were considered: obese subjects with or without thyroid disease. Subjects were stratified according to age, sex, and BMI. The prevalence of thyroid disease was correlated to age, sex and BMI increased body weight. Our data showed that 22% of patients affected by essential obesity and not resident in area of iodine deficiency is affected by thyroid diseases which are not diagnosed (18%). In the obese subjects, presence of goiter is more frequent than in the normal weight subjects and affects mainly adult males. Chronic thyroiditis is typical of females (9:1 female:male ratio) with no difference between normo and overweight subjects. Prevalence of single nodule in the obese is similar to the normal weight subjects, it is more frequent in adults and in subjects with medium size obesity. However, occurrence of carcinoma (8%) in single nodules appears higher in the overweight (5-6%) as compared to the normal weight subjects.

The treatment of chronic liver disease represents still now an open problem in medicine. The first objective of therapy has to be the causal agent removal; however, there are many cases (viral infections, autoimmunity, genetic disease) in which it is not possible to reach this issue; in these situations the secondary objective of the therapy is to inhibit the hepatic fibrogenesis, in attempt of easing or blocking the transformation of chronic liver disease in cirrhosis. The aim of this work is to review the various compounds which showed an antifibrotic activity, using a simple classification model, allowing a fast setting of different compounds. These last, on the basis of their main action, can be divided into two main groups: drugs with direct action, which interfere with collagen metabolism (for instance interferons, glucocorticoids, prolyl 4-hydroxylase inhibitors, cyclosporin A, colchicine, D-penicillamine, phosphatidylcholine and so on) and drugs with indirect action, that decrease the inflammatory stimuli, capable of stirring up the fibrogenetic hepatic process (S-adenosylmethionine, malotilate, ursodeoxycholic acid, ribavirin and so on). There are drugs that have both mechanisms of action, without the prevalence of one or other mechanism (prostaglandins).

Background: The presence of nodules in the thyroid gland is the most frequent cause of endocrinopathy. The prevalence of thyroid nodules in the United States is estimated to be between 3-10%, whereas the prevalence of thyroid nodules in European adult population is estimated to be between 4-10%. At our Clinic of Obesity, the presence of nodules in the thyroid gland of obese patients is often found, incidentally, for this reason, we decide to investigate the prevalence of this pathology in obese patients and to quatify the number of times in which the presence of nodules had not been previously diagnosed., Methods: 3248 obese patients were examined during in the last six years (1991-1996); of these patients 747 were affected by obesity and thyropathy; of these 747 we took into consideration only those with a cold single nodule and correlated the presence of the nodule with BMI, sex and age., Results and Conclusions: The prevalence of a cold single nodule in the obese patients was 31%, of which 83% has not been previously diagnosed. Of cold nodules 8% was represented by carcinoma. The carcinoma appeared more often in females than in males (3:1). The incidence of cold nodules was more frequent in adults and in mild-medium obesity.