Prevalence of elevated liver enzymes in Type 2 diabetes mellitus and its association with the metabolic syndrome.

The occurrence of liver disease and raised liver enzymes is common in Type 2 diabetes, and may be multifactorial in origin. Very few studies are available on the exact prevalence of the phenomenon, however. We carried out an observational point-prevalence study of elevated liver enzymes in eight hospital-based Italian diabetes units. Data of 9621 consecutive Type 2 diabetes patients (males, 52.4%; median age, 65 yr) were analyzed, and alanine and aspartate aminotransferase (ALT, AST) and gamma-glutamyltransferase (GGT) levels were related to body mass index (BMI), metabolic control and the presence of the metabolic syndrome. ALT, AST, and GGT levels exceeding the upper limit of normal were present in 16.0%, 8.8%, 23.1%, respectively, the prevalence being higher in males, increasing with obesity class and poor metabolic control, and decreasing with age. Elevated enzymes were systematically associated with most parameters of the metabolic syndrome. After correction for age, gender, BMI, and differences across centers, elevated triglyceride levels/fibrate treatment [odds ratio (OR), 1.57; 95% confidence interval (CI), 1.34- 1.84] and an enlarged waist circumference (OR, 1.47; 95% CI, 1.17-1.85) were the only parameters independently associated with high ALT. In a separate analysis, the presence of metabolic syndrome (Adult Treatment Panel III criteria) was highly predictive of raised liver enzymes. After exclusion of hepatitis B and C positive cases, tested in 2 centers, the prevalence of raised enzymes decreased by approximately 4%, but the association with the metabolic syndrome did not change significantly. In conclusion, the high prevalence of elevated liver enzymes in Type 2 diabetes is in keeping with the well-demonstrated risk of progressive liver disease. A large amount of diabetes patients may require a thorough clinical, laboratory and histological investigation.

Accelerated elimination from the circulation of homologous aged red blood cells in rats bearing anti-spectrin antibodies.

In order to analyse a possible role of anti-spectrin antibodies in the clearance of aged red blood cells (RBC), a homologous system was employed, whereby a population of aged RBC, obtained by hypertransfusion, was injected into rats bearing a high level of anti-spectrin antibodies, following immunization with spectrin. The aged RBC bound the anti-spectrin antibodies 'in vitro' and were eliminated from circulation in spectrin-treated rats at a faster rate than in control rats with naturally occurring antibodies. The analysis of the clearance curves revealed aged RBC of heterogeneous lifespans: two principal populations of short- and longer-living could be identified. In rats with anti-spectrin antibodies, the survival of the short-living population was further reduced. However, the similar kinetics of elimination of aged RBC in the two groups (with naturally-occurring and induced antibodies, respectively) suggest that anti-spectrin antibodies strengthened the intervention of the naturally-occurring ones. On the basis of these results, we assume that during their aging in circulation, RBC can accumulate surface alterations to make spectrin accessible to antibodies so that, in addition to anti-band 3 antibodies, anti-spectrin antibodies may contribute to their elimination.

Analogs of cord red blood cell membrane components displayed on placenta, amnion and amniotic cells in culture.

Placenta and amnion were analyzed to ascertain the presence of antigens in common with red blood cells (RBC) from cord or fetuses. The expression of distinct antigens displayed on a subpopulation of cord RBC and detected by anticord RBC membrane antibodies was particularly investigated, concomitantly with the presence of transferrin receptors (TR) by employing immunohistochemistry. The placenta showed both cord antigen and TR; on the contrary, amnion--which was labelled by anti-cord RBC membrane antibodies--was not stained by the anti-TR antibody. The results of inhibition and double labelling assays further excluded TR as the relevant antigen in the labelling of both placenta and amnion. The staining of fetal membranes disappeared after absorption of antibodies with cord RBC membranes. These results suggest that the antigens externally expressed on a subpopulation of cord RBC are shared by amnion and placenta.

[A non-fatal Nerium oleander self-poisoning: case report and discussion]. / Intoxication volontaire au laurier rose ; cas clinique et revue de la littérature.

Nerium oleander is potentially lethal plants after ingestion. We report a case of poisoning by these plants. Our patient complained of nausea, vomiting, and diarrhoea. He had bradycardia during first twelve hours. He was discharge after 3 days. All parts of these plants are toxic and contain a variety of cardiac glycosides including oleandrin. In most cases, clinical management of poisoning by N. oleander involves administration of activated charcoal and supportive care. Digoxin specific Fab fragments are an effective treatment.

[Release of antigens into the culture medium by LS fibroblasts in culture]. / Cessione di antigeni al terreno da parte di fibroblasti LS in coltura.

LS fibroblasts cultivated for 1 or more days in unsupplemented Eagle's MEM release antigens into the medium, without showing any evidence of lysis, but on the contrary continuing to proliferate. These antigens give up to three precipitation lines when tested by means of immunodiffusion and immunoelectrophoresis against specific rabbit antisera; one or two of them give identity reactions with antigens obtained by repeatedly washing the fibroblasts with balanced salt solutions. Evidence has been obtained that they are surface components, easily stripped or spontaneously shed by the cells.

[Growth of the Yoshida ascites/hepatoma in co-culture with rat fibroblasts]. / Osservazioni sulla crescita dell'epatoma--ascite di Yoshida in cocoltura con fibroblasti di ratto.

Ascites hepatoma cells (Y) co-cultured with rat fibroblasts (F) in Dulbecco-Eagle's MEM (DMEM) proliferate rapidly in suspension, at a rate consistent with that shown in vivo after intraperitoneal injection; the population doubling time is about 1 day. The log phase of growth may be retained indefinitely, provided fresh medium is supplied regularly and the F monolayer is changed when necessary. The tumorigenicity is preserved. To maintain a high rate of growth the presence of F seems important: in this study, culturing without F in various media at best only sustained slow proliferation rates; this is in keeping with the notion of normal tissue components supplying useful factors to the neoplastic cells. Adding minced polyester surgical thread (Mersilene - M) into the co-cultures slowed down the growth of Y to some extent, yet no evidence has been obtained of toxic compounds released by M.

[Interaction of the 3rd component of complement (C3) with the surface of LS murine fibroblasts]. / Interazione tra terzo componente del complemento (C3) e superficie di fibroblasti LS di topo.

LS fibroblasts grown in suspension culture fix C3 on their surface when they are incubated with human or guinea pig complement as shown by reacting te cells with FITC-labelled anti C3c sera or immunoglobulins. At the same time the lytic activity of complement is lowered and aliquots of C3 are subtracted from the sera following incubation with the cells. EDTA - EGTA experiments and other observations suggest that C3 fixation requires activation, which proceeds via the alternative pathway, in much the same manner as it has been reported for limphoid cells and thymocytes.

[Polyester treatment in rats with a dorsal air pouch: chemotaxis in lavage fluid from the pouch]. / Studio del trattamento con poliestere in ratti portatori di una sacca dorsale d'aria: chemiotassi dei liquidi di lavaggio della sacca.

Minced polyester threads introduced into peritoneal cavity of rats cause a granulomatous inflammation with evidence of macrophage stimulation. Chemotactic agents play an important role in the inflammatory reaction; they are released locally by cells involved in inflammation. In this paper the chemotactic effect of the peritoneal and subcutaneous air pouch fluids from rats bearing the polyester inflammatory process, have been studied on PMN cells "in vitro". The fluids were obtained by washing the cavity of untreated rats or rats injected with polyester, 7 days after the injection. The chemotactic response was assayed by employing modified chemotaxis Boyden chambers (Blind Well Neuro Probe) and polymorphonuclear cells from normal rats. Quantification of the migration was calculated by chemotactic index (A/B) (B = random migration, A = chemotaxis). The results demonstrate that a chemotactic activity is present in peritoneal and subcutaneous air pouch fluids following the inflammatory process. In conclusion the chronic inflammation determines the appearance of chemotactic factors for PMN cells, in the peritoneal cavity and in the air pouch, and the air pouch is a very convenient experimental system with the particular advantage that it permits easy repeated sampling of exudate during the course of an inflammatory response.

[Interference of polyester inflammation on the development of Yoshida ascites hepatoma in the rat]. / Interferenza dell'infiammazione da poliestere con lo sviluppo dell'epatoma-ascite di Yoshida nel ratto.

Minced polyester threads introduced into the peritoneal cavity cause a chronic inflammation with evidence of macrophage and lymphocyte stimulation. In this paper an interference between this kind of inflammation and the growth of Yoshida ascites hepatoma has been shown, which has been found to dependent on the time interval elapsed between the introduction of polyester (Mersilene) minces and injection of the hepatoma cells. Rats were treated intraperitoneally with Mersilene and then divided in to three groups: the first was injected intraperitoneally with hepatoma cells immediately (TM 0), the second after 7 (TM 7) and the third after 14 days (TM 14); rats untreated with polyester and implanted with the same number of hepatoma cells served as controls (NT). While in groups NT and TM 0 a rapid growth of hepatoma cells occurred, together with the accumulation of a considerable volume of ascitic fluid, no tumor growth neither ascite production occurred in groups TM 7 and TM 14; in these animals where several days were allowed to elapse after polyester introduction, the hepatoma cells which had been injected rapidly disappeared and were no more found 48 h after the intraperitoneal injection. It is suggested that the inhibition of the neoplastic growth may be dependent on the activation of macrophages (and possibly NK cells) which accompanies the development of the chronic polyester inflammation.

Regulation of transglutaminase activity by GTP in digitonin permeabilized Yoshida tumor cells.

Yoshida tumor cells contain consistent amounts of type 2 transglutaminase, along with a membrane bound form of the enzyme. Digitonin permeabilized cells retain a large proportion of type 2 TGase and of substrate proteins which are labelled by radioactive putrescine in the presence of calcium. GTP inhibits protein labelling at low calcium concentration by inhibiting type 2 TGase without affecting membrane-bound TGase. These results support the notion that inhibition of type 2 TGase by GTP is physiologically relevant.

[Three cases of coma during parenteral alimentation]. / Trois observations de coma au cours de l'alimentation parentérale.

Three cases of coma occuring during parenteral alimentation are presented. The common factor was that they occurred during the phase of realimentation in patients with severely impaired nutrition. In two cases out of three, the coma marked the beginning of the absolute or relative anabolic period. They were studied clinically, biologically and electrically. In one case only, major hypophosphataemia was discovered (2mg/l). Of the three patients, one only died 4 days after the onset of coma, whilst clinical and biological characteristics had returned to normal.

[Inflammatory reaction to polyester material in the guinea pig. IV. Production and liberation of beta glucuronidase and lactate dehydrogenase by peritoneal macrophages in culture]. / Il processo infiammatorio da materiale poliestere nella cavia. IV. Produzione e liberazione di beta glicuronidasi e di lattato deidrogenasi da parte di macrofagi peritoneali in coltura.

Peritoneal macrophages obtained from guinea pigs intraperitoneally injected with minced polyester threads with saline, and from control animals were cultivated and the activities of the lysosomal enzyme beta-glucuronidase and of the cytoplasmic enzyme lactate dehydrogenase were determined in the cells and in the culture media. The production and particularly the release into the medium of beta-glucuronidase increased in the cultures from the treated animals; the LDH production was also markedly increased, and the enzyme was partly lost into the medium, suggesting that the injection of Mersilene into the guinea pigs markedly induces these enzymes in the phagocytes and at the same time probably increases the leakiness of their cell membrane.

[Inflammatory reaction to polyester material in the guinea pig. V. Semiautomatic determination of peritoneal cell volume]. / Il processo infiammatorio da materiale poliestere nella cavia. V. Determinazione semiautomatica del volume delle cellule peritoneali.

The volume of the peritoneal cells of guinea pigs treated with injections of 1) minced polyester threads (Mersilene), 2) saline, and of untreated animals, has been determined utilizing a Coulter Counter coupled with a pulse height analyzer. The volumetric test on the whole cell population has emphasized a distinctly bimodal distribution, due to the presence of two cellular types picked out as first peak (P 1 degrees) and second peak (P 2 degrees), while the non-adherent cells (CNA) have shown an unimodal distribution. Statistically significant difference in the mean volumes have been found between the P 1 degrees and P 2 degrees cells and between the CNA and P 1 degrees cells. The percentage of CNA in the whole cell population significantly decreases in "Mersilene"-treated guinea pigs.

[Inflammatory reaction to polyester threads in guinea pigs. III. Reduction of Nitroblue tetrazolium by peritoneal macrophages in vitro]. / Il processo infiammatorio da materiale poliestere nella cavia. III. Riduzione in vitro del Nitroblu di tetrazolio da parte dei macrofagi peritoneali.

Peritoneal cells of guinea pigs treated or not by intraperitoneal injection of minced polyester threads have been tested by the NBT test. In phagocytic cells nitroblue tetrazolium (NBT) is reduced to formazan. This is deposited as a dark blue precipitate in the cytoplasm. Changes in reduction capacity have been quantitated by calculation of percentage of macrophages containing formazan deposits, (Tab. 1), and by extraction and photometric evaluation of formazan (Tab. 2). Peritoneal cells incubated with polyester show an increased NBT reduction, which is more apparent with the photometric evaluation. A statistically significant difference in NBT reduction has been found between the peritoneal cells of the guinea pigs treated "in vivo" with polyester and those of the untreated "in vivo" with polyester and those of the untreated animals, whether or not challenged in vitro with polyester threads. These results suggest a change in cell population following polyester treatment.

[Interference of inflammation caused by polyester with the growth of Yoshida ascite hepatoma. IV. Modifications of the sedimentation profile of the hepatoma cells]. / Interferenza dell 'infiammazione da poliestere con la crescita dell'epatoma ascite di Yoshida. IV. Modificazioni del profilo di sedimentazione delle cellule dell'epatoma.

It was previously shown that Yoshida's ascites-hepatoma cells (Y cells) intraperitoneally injected into rats carrying chronic inflammation caused by polyester thread rapidly disappear. In this paper the sedimentation rate in a continuous Percoll gradient at unit gravity (1 g) using the CELSEP apparatus (Sorvall), the mean diameter and volume of the Y cells harvested from the peritoneal cavity of untreated (NT) and polyester-treated (TM) animals were determined at 6-12-18-24 hours after the inoculum. At 6 hours a number of Y cells appeared enlarged both from TM and NT rats, while afterwards, and notably at 18 and 24 hours, their size was decreased and their sedimentation rate was reduced only in TM animals. It seems that the chronic inflammation causes alterations both in the size and in the density of the Y cells and probably one of the mechanisms of their death is through shrinkage and apoptosis.

[Interference of inflammation caused by polyester with the development of Yoshida ascite hepatoma in rats. V. Study of cytotoxicity in vitro]. / Interferenza della infiammazione da poliestere con lo sviluppo dell'epatoma-ascite di Yoshida nel ratto. V. Ricerca di citotossicita' in vitro.

It has been known for some years that rats developing a granulomatous inflammation following the intraperitoneal injection of fragments of a polyester suture thread (Mersilene, M) reject a graft of 10(8) Yoshida's ascites hepatoma cells, which on the contrary rapidly grow in M-uninjected animals, originating an ascites tumor and killing the rats in a few days. In this paper granulomatous (TM) and normal (control, C) small pieces of peritoneum (omentum, mesentery and parietal) have been cultivated for 15 h in Eagle-Dul becco's medium together with 10(5) 51Cr-labelled hepatoma cells: the release of the label, an index of cell lysis, was considerably higher in the TM cultures, suggesting a cytotoxic activity of some components of the granulomas. Differences have been observed in the amount of radioisotope released among the TM cultures, suggesting that the particular composition of the cell population may be relevant to the cytotoxicity versus the hepatoma cells.

[Inflammatory process caused by intraperitoneal injection of polyester in the rat: chemotactic activity in lavage fluid from the cavity]. / Processo infiammatorio da inoculo intraperitoneale di poliestere nel ratto: attivita chemiotattica nei liquidi di lavaggio della cavita.

Minced polyester threads introduced into peritoneal cavity of guinea pigs or rats cause a granulomatous inflammation with evidence of macrophage stimulation. Chemotactic agents play an important role in the inflammatory reaction; they may be exogenous and/or endogenous. These are released locally by the cells involved in inflammation. In this paper the chemotactic effects of the peritoneal fluids from rats bearing the polyester inflammatory process, have been studied on PMN cells "in vitro". The peritoneal cavity fluids were obtained by washing the cavity of untreated rats or rats intraperitoneally injected with polyester, 1, 3, 7, 14 days after the intraperitoneal injection. The chemotactic response was assayed by employing modified chemotaxis Boyden chambers (Blind Well Neuro Probe) and polymorphonuclear leukocytes from normal or treated rats. Quantification of the migration was calculated by chemotactic index (A/B) (B = random migration, A = chemotaxis). The results demonstrated that the peritoneal fluids taken 3 and 7 days after the intraperitoneal polyester injection, elicit an evident chemotaxis response greater than that showed by peritoneal fluids from control rats. It is suggested that chemotactic factors can be produced and released by mononuclear cells involved in the inflammatory process.

[Chemotactic activity of the peritoneal lavage fluid of guinea pigs with inflammatory processes caused by the inoculation of various types of suture thread]. / Attività chemiotattica dei liquidi di lavaggio della cavità peritoneale di cavie con processo infiammatorio da inoculo di vari tipi di fili da sutura.

Minced non adsorbable or adsorbable suture threads introduced into peritoneal cavity of guinea pigs elicit at inflammation with mononuclear and giant cells surrounding suture thread fragments. We studied the presence in the peritoneal cavity of chemotactic factors for PMN cells and we compared the results in relation to the different type of the suture threads used (Dexon, Mersilene, Gore-Tex). The peritoneal cavity was washed, the fluids collected and used as chemotactic agents. The chemotactic response was assayed by employing multiwell chemotaxis chambers (Neuro Probe) and PMNs from normal, non-treated guinea pigs. Quantification of the migration was calculate by chemotactic index (A/B) (B = random migration, A = chemotaxis). The results demonstrate that a chemotactic activity is present in peritoneal fluids following the inflammatory process. This activity is evident at 7th day after Dexon and Mersilene inoculation; using PTFE however, it decreases at 14th d, when the inflammatory process is already developing into healing tissue. In conclusion the chronic inflammation determines the appearance of chemotactic factors for PMN cells; it is suggested that reactive, mononuclear cells, involved in the process, could be responsible for their production and release.

Frog brain expresses a 60 KDa Ca2+ binding protein similar to mammalian calreticulin.

The present report was undertaken in an effort to characterize the nature of Ca2+ binding protein(s) in the central nervous system of less evolved vertebrates. In particular we investigated whether the brain microsomal fraction of Rana esculenta expresses calsequestrin, calreticulin and/or other related Ca2+ binding protein(s). We found that a 60 KDa protein having an NH2-terminal amino acid sequence similar to mammalian calreticulin is the major microsomal Ca2(+)-binding protein.