[Evaluation of the interleukin 1 production by adherent cells in patients with diabetes type II]. / Evaluación de la producción de interluequina 1 por células adherentes en pacientes con diabetes tipo II.

We have studied the comitogenic activity of IL 1 produced by cultures of mononuclear adherent cells obtained from Diabetes Mellitus (DM) type II or non insulin dependent diabetic patients. This activity was measured by the incorporation of 3H Thymidine into cultures of C3H/HeJ mice thymocytes in the presence of phytohemagglutinin (PHA). We have observed that IL 1 from patients with DM type II did not produce a synergistic effect with PHA, since the lymphoproliferation levels were similar to those obtained in the absence of this lectin. This lack of comitogenic activity (P less than 0.001) in relation to the response obtained with IL 1 from normal subjects plus PHA, could be due to the release of one or several soluble substances capable of blocking glycosylated receptors to mitogens or of impairing the cellular activation process.

Evaluacion de la producion de interleuquina 1 por celulas adherentes en pacientes con diabetes tipo II / Production of interleukin 1 by adherent cells in patients with Diabetes Mellitus type II

Se evaluó la actividad comitogénica de la interleuquina 1 producida en cultivos de células adherentes mononucleares de pacientes con diabetes mellitus (DM) tipo II o insulino no dependente. Dicha actividad fue medida por la incorporación de timidina en cultivos de timocitos de ratones (C3H/Hej, en presencia de fitohemaglutinina (PHA). Se observó que los sobrenadantes de los cultivos de células adherentes de los pacientes con DM tipo II no produjeron efecto sinergista con la PHA, obteniéndose niveles de linfoproliferación semejantes a los obtenidos en ausencia de dicha lectina. Esta falta de efecto comitogénico (p < 0,001) con respecto a la respuesta obtenida con la interleuquina 1 de sujetos normales más PHA, podría deberse a la liberación de algún/os factor/es solubles que podieron interferir con los receptores glicosilados para mitógenos o con los procesos de activación celular

Evaluación de la producción de interluequina 1 por células adherentes en pacientes con diabetes tipo II. / [Evaluation of the interleukin 1 production by adherent cells in patients with diabetes type II]

We have studied the comitogenic activity of IL 1 produced by cultures of mononuclear adherent cells obtained from Diabetes Mellitus (DM) type II or non insulin dependent diabetic patients. This activity was measured by the incorporation of 3H Thymidine into cultures of C3H/HeJ mice thymocytes in the presence of phytohemagglutinin (PHA). We have observed that IL 1 from patients with DM type II did not produce a synergistic effect with PHA, since the lymphoproliferation levels were similar to those obtained in the absence of this lectin. This lack of comitogenic activity (P less than 0.001) in relation to the response obtained with IL 1 from normal subjects plus PHA, could be due to the release of one or several soluble substances capable of blocking glycosylated receptors to mitogens or of impairing the cellular activation process.

Evaluacion de la producion de interleuquina 1 por celulas adherentes en pacientes con diabetes tipo II / Production of interleukin 1 by adherent cells in patients with Diabetes Mellitus type II

Se evaluó la actividad comitogénica de la interleuquina 1 producida en cultivos de células adherentes mononucleares de pacientes con diabetes mellitus (DM) tipo II o insulino no dependente. Dicha actividad fue medida por la incorporación de timidina en cultivos de timocitos de ratones (C3H/Hej, en presencia de fitohemaglutinina (PHA). Se observó que los sobrenadantes de los cultivos de células adherentes de los pacientes con DM tipo II no produjeron efecto sinergista con la PHA, obteniéndose niveles de linfoproliferación semejantes a los obtenidos en ausencia de dicha lectina. Esta falta de efecto comitogénico (p < 0,001) con respecto a la respuesta obtenida con la interleuquina 1 de sujetos normales más PHA, podría deberse a la liberación de algún/os factor/es solubles que podieron interferir con los receptores glicosilados para mitógenos o con los procesos de activación celular (AU)

Some characteristics of neutrophils from diabetic patients and their relation to the levels of circulating immune complexes.

In the present work we studied different characteristics of neutrophils from diabetic patients and their relation to the levels of circulating immune complexes (CIC). Twenty-five insulin-dependent (IDD) and 25 non-insulin-dependent diabetic (NIDD) patients were evaluated. Each group was then subdivided according to the presence or absence of microvascular complications (MC). We found that the chemiluminescence (CL) emitted by opsonized zymosan (Zop) stimulated neutrophils in IDD and NIDD patients was significantly increased when compared to healthy subjects (p less than 0.01 and p less than 0.02, respectively). The CL values were correlated to CIC levels and both parameters were related to the presence of MC. On the other hand, the percentage of neutrophils capable of reducing nitroblue tetrazolium was diminished in the two groups of diabetic patients (p less than 0.05 for IDD and p less than 0.01 for NIDD). The percentage of neutrophils with functional C3b receptors was normal in diabetic patients; however, the proportion of phagocytic cells through Fc receptors was significantly decreased in both types of patients (p less than 0.05 and p less than 0.01 for IDD and NIDD, respectively). Furthermore, the number of granulocytes with immune complexes (IC) bound to their cell surface was increased in diabetics. We suggest that the increase of CIC level may produce an increase in IC binding to the neutrophil membrane. These IC could block the Fc receptors, diminish phagocytic capacity and, simultaneously, stimulate the release of toxic oxygen products, thus contributing to produce tissue damage.

Evaluation of neutrophil activity and circulating immune complexes levels in diabetic patients.

We have studied chemiluminescence produced by neutrophils stimulated by opsonized zymosan in insulin dependent (IDD) and non insulin dependent (NIDD) diabetic patients. Chemiluminescence was evaluated as the integral and maximum peak, total time and time to maximum peak of the response curve to opsonized zymosan. These values were then compared with circulating immune complexes (CIC) and glucose levels. Both IDD and NIDD patients had significantly higher values of chemiluminescence and CIC than normal controls. We also observed that patients who had the highest values of CIC and chemiluminescence levels were the ones with clinical microvascular complications.

Circulating immune complexes and B lymphocytes in diabetic patients with and without microangiopathy.

Circulating immune complexes (CIC) were evaluated in 57 diabetic patients: 28 were insulin-dependent (IDD) and 29 were non insulin-dependent (NIDD) subdivided according to the presence or absence of microangiopathy. The following techniques were used: 1) binding to human red blood cells through C3b complement fraction and posterior radioimmunoassay with 125I labeled anti human IgG (HRBC RIA test); and 2) CIC precipitation with 3.5% polyethylenglycol (PEG test). The percentage of circulating B lymphocytes was evaluated simultaneously in the same patients, using a) direct immunofluorescence techniques (surface IgC cells) and b) cells with complement C3b fraction receptors (EAC rosettes). Twenty normal donors were studied simultaneously as controls. Our results showed that CIC levels were significantly higher in both groups of patients when compared to normal controls. Values for IDD and NIDD were 48.55 +/- 5.97 and 34.68 +/- 3.08 microgram/ml, respectively, for HRBC RIA test and 0.53 +/- 0.07 and 0.41 +/- 0.04 O.D., respectively, for PEG test, while control values were 26.63 +/- 2.12 microgram/ml for HRBC RIA test and 0.26 +/- 0.03 O.D. for PEG test. IDD patients with microangiopathy presented higher CIC levels as measured by HRBC RIA test than IDD without microvascular complications, while no difference was found within the NIDD group. An increase in the proportion of cells bearing surface IgG was observed in IDD and NIDD patients when compared to controls. By contrast, no difference was observed when EAC rosettes-forming cells were evaluated.

Comparative study of bezafibrate and fenofibrate in patients with primary hyperlipoproteinaemia.

A study was carried out in 40 patients with primary hyperlipoproteinaemia to compare the efficacy and tolerance of bezafibrate and fenofibrate, combined with a dietary regimen, in reducing lipid levels. Patients were allocated at random to receive treatment for 4 months with either 600 mg bezafibrate or 300 mg fenofibrate per day. Efficacy of treatment was assessed from measurement before and after treatment of the levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and blood glucose. Tolerance was monitored by monthly clinical examinations and routine investigation of blood chemistry and urinalysis before and after treatment. The results indicated that bezafibrate was a more effective normolipaemic agent than fenofibrate. Whilst both drugs reduced triglyceride levels significantly, only in the bezafibrate group were they decreased to within the risk-free range. Bezafibrate also produced a significant decrease in total cholesterol and LDL-cholesterol to near the risk-free level and an increase in HDL-cholesterol. With fenofibrate, total cholesterol and LDL-cholesterol levels remained within the range necessitating treatment and HDL-cholesterol showed little if any change. Although there were decreases in alkaline phosphatase and significant decreases in gamma-glutamyl transpeptidase levels in both groups after treatment, there was a tendency for SGPT, SGOT, total bilirubin and direct bilirubin levels to increase after fenofibrate but to decrease after bezafibrate.

Circulating immune complexes and B lymphocytes in diabetic patients with and without microangiopathy.

Circulating immune complexes (CIC) were evaluated in 57 diabetic patients: 28 were insulin-dependent (IDD) and 29 were non insulin-dependent (NIDD) subdivided according to the presence or absence of microangiopathy. The following techniques were used: 1) binding to human red blood cells through C3b complement fraction and posterior radioimmunoassay with 125I labeled anti human IgG (HRBC RIA test); and 2) CIC precipitation with 3.5

polyethylenglycol (PEG test). The percentage of circulating B lymphocytes was evaluated simultaneously in the same patients, using a) direct immunofluorescence techniques (surface IgC cells) and b) cells with complement C3b fraction receptors (EAC rosettes). Twenty normal donors were studied simultaneously as controls. Our results showed that CIC levels were significantly higher in both groups of patients when compared to normal controls. Values for IDD and NIDD were 48.55 +/- 5.97 and 34.68 +/- 3.08 microgram/ml, respectively, for HRBC RIA test and 0.53 +/- 0.07 and 0.41 +/- 0.04 O.D., respectively, for PEG test, while control values were 26.63 +/- 2.12 microgram/ml for HRBC RIA test and 0.26 +/- 0.03 O.D. for PEG test. IDD patients with microangiopathy presented higher CIC levels as measured by HRBC RIA test than IDD without microvascular complications, while no difference was found within the NIDD group. An increase in the proportion of cells bearing surface IgG was observed in IDD and NIDD patients when compared to controls. By contrast, no difference was observed when EAC rosettes-forming cells were evaluated.

Circulating immune complexes and peripheral B lymphocytes in non insulin dependent diabetic patients.

Serum circulating immune complexes (CIC) were measured in 27 patients with non insulin dependent diabetes (NIDD). This was done by measuring the degree of binding to human red blood cells by the C3b complement fraction. At the same time, the percentage of B lymphocytes in peripheral blood was evaluated by means of the direct immunofluorescence technique for surface IgG and EAC rosettes for cells with receptors to C3b complement fraction. Twenty normal control subjects were simultaneously studied by the same methodology. An increase in serum CIC was observed in NIDD patients, as compared to healthy subjects. Values were 35.8 +/- 3.2 and 25.6 +/- 2.1 micrograms/ml, respectively. The percentage of cells with surface IgG was 10.2 +/- 0.8 in diabetic patients; this value was significantly higher than that found in the control group (6.0 +/- 0.8). No significant quantitative difference in the percentage of EAC binding cells was found between NIDD patients and the control group. When NIDD patients were divided into two groups, those with and those without microvascular complications, neither differences in CIC levels nor in the percentage of B lymphocytes were found. Nor any correlation could be found between the highest individual CIC levels and the highest percentage of lymphocytes with surface IgG. These data show an increase of CIC levels and of cells with surface IgG in NIDD patients who had not received insulin at least not in a constant or prolonged therapy. This could allow us to suspect the existence of antigen-antibody complexes different to insulin-antiinsulin CIC found in insulin dependent diabetes.

Circulating immune complexes and peripheral B lymphocytes in non insulin dependent diabetic patients.

Serum circulating immune complexes (CIC) were measured in 27 patients with non insulin dependent diabetes (NIDD). This was done by measuring the degree of binding to human red blood cells by the C3b complement fraction. At the same time, the percentage of B lymphocytes in peripheral blood was evaluated by means of the direct immunofluorescence technique for surface IgG and EAC rosettes for cells with receptors to C3b complement fraction. Twenty normal control subjects were simultaneously studied by the same methodology. An increase in serum CIC was observed in NIDD patients, as compared to healthy subjects. Values were 35.8 +/- 3.2 and 25.6 +/- 2.1 micrograms/ml, respectively. The percentage of cells with surface IgG was 10.2 +/- 0.8 in diabetic patients; this value was significantly higher than that found in the control group (6.0 +/- 0.8). No significant quantitative difference in the percentage of EAC binding cells was found between NIDD patients and the control group. When NIDD patients were divided into two groups, those with and those without microvascular complications, neither differences in CIC levels nor in the percentage of B lymphocytes were found. Nor any correlation could be found between the highest individual CIC levels and the highest percentage of lymphocytes with surface IgG. These data show an increase of CIC levels and of cells with surface IgG in NIDD patients who had not received insulin at least not in a constant or prolonged therapy. This could allow us to suspect the existence of antigen-antibody complexes different to insulin-antiinsulin CIC found in insulin dependent diabetes.