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Biomedical subjects

M Negri

Publications and source records attributed to M Negri.

At least 91 records · Page 5Linked to original sources

Inhibition of protein non-enzymic glycation induced by Bendazac.

Enhanced non-enzymic glycation of proteins has been suggested to play a role in the pathogenesis of diabetic microangiopathy. Thus pharmacological inhibition of this reaction could be envisaged to delay the development of late diabetic complications. In the present study we have investigated the effect of a new compound, 1-Benzylindazole-3-oxyacetic acid, Bendazac (BDZ) on the in vitro glycation of soluble proteins (albumin and fibrinogen) and isolated glomerular basement membrane (GBM). The data obtained indicate that BDZ is capable of reducing significantly the glycation of albumin and fibrinogen (p less than 0.001). When present in concentrations usually found in patients undergoing therapy (40-80 micrograms/ml), an inhibitory effect on soluble proteins was also observed. Inhibition of glycation of GBM was found only in the presence of the active metabolite (5 hydroxy BDZ) and at high glucose concentrations. These results suggest that BDZ could interfere with protein non-enzymic glycation and its use in patients with diabetes may be then taken into consideration to evaluate the effect on late diabetic complications.

Animals↗

Primary adenocarcinoma of the appendix: report of five cases and review of the literature.

Five patients with primary adenocarcinoma of the appendix are reported. All patients presented with symptoms resembling those of acute appendicitis or periappendicular abscess. In none of them was malignancy suspected prior to operation. It is advisable that every patient above 50 years of age presenting with symptoms of appendicitis undergo laparotomy, thus enabling a better exploration of the cecal region. If an appendiceal mass is present and frozen section shows malignancy, a right hemicolectomy should be performed. The prognosis of adenocarcinoma of the appendix is dismal as most patients present with an advanced stage of the disease.

Adenocarcinoma↗

Increased serum aldosterone in diabetic pregnancy.

Serum levels of aldosterone and cortisol were measured by radioimmunoassay in 15 patients with gestational diabetes, in 18 patients with Type 1 (insulin-dependent) diabetes, in 36 pregnant control women and in 10 non-pregnant control women. All subjects, on habitual sodium and potassium intake, were sampled in a supine position at 09.00 hours. Pregnant women were examined twice, during gestational week 32-34 and at delivery. Serum levels of aldosterone and cortisol were also measured in the umbilical cord blood of newborn babies of these diabetic and non-diabetic mothers. Serum levels of aldosterone in both gestational and Type 1 pregnant diabetic women were found to be consistently above the reference values of non-diabetic pregnant women. Abnormal serum levels of aldosterone were also observed in newborn infants of diabetic mothers. In contrast, serum levels of cortisol were not increased.

Adult↗

Reduced HDL2 levels in myocardial infarction patients without risk factors for atherosclerosis.

Out of a total of 170 patients with a first myocardial infarction, aged below 65 years, consecutively admitted to the Coronary Care Unit of a large urban hospital, only 14 did not present with any risk factor(s) for atherosclerosis (smoking, hypertension, diabetes and obesity). None of these 14 patients showed significant hyperlipidemia. Compared to a control series of normal individuals of the same age (50.0 +/- 5.8 years for males and 61.6 +/- 3.0 years for females), they showed a significant reduction of high-density lipoprotein (HDL)-cholesterol and of apolipoprotein A-I (respectively -18.2 and -9.5%). However, the most striking abnormality was a 30% decrease of the HDL2 mass and of HDL2 cholesterol; both HDL2 and HDL3 had a reduced cholesteryl ester content in the patients. Reduced HDL2 mass and cholesterol levels in plasma, accompanied by significant alterations in HDL subfraction composition, are consistent with a defective cholesterol esterification in HDL. HDL2 deficiency may be a primary alteration in myocardial infarction patients without other significant risk factors.

Arteriosclerosis↗

Labelling of interleukin-2 (IL-2) with 123-iodine with retention of its capacity to bind to activated lymphocytes.

Human recombinant interleukin-2 (IL-2) was labelled with Iodine-123 using modified Bolton and Hunter method. Separation from free iodine was performed by gel filtration chromatography using a Sephadex G10 column. HPLC analysis of labelled IL-2 showed that 98% of TCA precipitable radioactivity eluted in a single peak. The immunoreactivity of 123I-labelled IL-2 was determined by divert binding using the Fluorescence Activated Cell Sorter (FACS) and by receptor binding assay of IL-2 to activated lymphocytes. To demonstrate in vivo binding to activated lymphocytes, 123I-labelled IL-2 was injected intravenously into a newly diagnosed diabetic BB/Wistar rat. Higher radioactivity was detected in the pancreas and in the lymph nodes of the BB/W rat compared to a normal rat. These preliminary data show that 123I-labelled IL-2 retains its immunoreactivity and capacity to bind to activated lymphocytes both in vitro and in vivo and may be used for in vivo localization of lymphocytic infiltration in Type 1 diabetes.

Animals↗

Normalization of the CD4/CD8 lymphocyte ratio and increased B lymphocytes in long standing diabetic patients following therapy with thymopentin.

A double blind study with thymopentin (TP5) and placebo was performed in 49 patients affected by Type 1 and Type 2 diabetes of long duration characterized by a reduction of the CD4/CD8 (helper/suppressor) lymphocyte ratio. TP5 (50 mg) was administered subcutaneously 3 times weekly for 1 month. Total peripheral lymphocytes and functionally different cell subsets were measured throughout the course of the study. Data showed a statistically significant increase of the CD4/CD8 lymphocyte ratio (p less than 0.02) and of the percentage of B lymphocytes (p less than 0.001) only in the TP5 receiving group. No side effects were observed during the study and patients remained well controlled. These results suggests that TP5 may be administered safely to diabetic patients and by improving impaired cell mediated immune parameters TP5 may contribute to prevent the development of infections in these patients.

Adult↗

Sensitive immunoenzymatic assay for urinary immunoglobulin subclasses of different pH: its significance in diabetic patients.

In search of a marker for monitoring the progression of diabetic nephropathy from the stage of charge- to that of size-selectivity loss, attention has been focused on the evaluation of immunoglobulin G (IgG) subclasses in the urine. We have developed a new sensitive enzyme immunoassay for the quantitation of urinary IgG1 and IgG4. Mouse monoclonal antibodies specific for each subclass were bound to microtitre wells precoated with rabbit anti-mouse immunoglobulin antibody. IgG1 and IgG4 of standard preparations (or of samples to be tested) were revealed using peroxidase-conjugated rabbit anti-human IgG. The procedure was carried out at 4 degrees C. This method can detect about 2 ng/ml of IgG4 and 20 ng/ml of IgG1. The monoclonal antibodies used were shown to be highly subclass-specific. IgG1 and IgG4 have a similar molecular weight but a different pH (about 9 and 4.6 respectively); a change in their ratio in the urine of diabetic patients may indicate a progressive deterioration of kidney function at the stage of incipient diabetic nephropathy.

Diabetic Neuropathies↗

In vivo determination of cell mediated immune response in diabetic patients using a multiple intradermal antigen dispenser.

The in vivo cell mediated immune response using a multiple intradermal antigen dispenser (Multitest) was evaluated in 99 diabetic patients (24 Type I and 75 Type II) and in 50 age matched normal subjects. Seven different antigens (tetanus, diphteria, streptococcus, tubercoline, candida, trichophyton, proteus and a glycerine control) were applied in the forearm and the induration for the antigens tested was measured 48 hours later. A score was calculated adding the arithmetic means obtained with each single antigen. Overall we did not find major differences between diabetic patients and controls except Type I patients of shorter duration (less than 5 years) having a reduced response (p less than 0.05) and both Type I and Type II patients showing an elevated response to candida antigen (p less than 0.001). No correlation was found between the intradermal response and metabolic control. As the intradermal test is a model for delayed type of hypersensitivity, these data suggest that the in vivo lymphocyte to lymphocyte cooperation in patients with long standing diabetes is not impaired.

Adult↗

Selective operative cholangiography.

This is a study of 505 patients who underwent surgical treatment of the gallbladder. Of this group, 343 were operated upon without operative cholangiography with an incidence of retained stones of 0.03 per cent. One hundred and ten underwent operative cholangiography according to five indications. These are: stones in the common duct on ultrasound or roentgenography; obstructive jaundice; dilation of the common duct greater than 1.2 centimeters; previous cholangitis, and preoperative pancreatitis. The advantages of selective operative cholangiography versus routine cholangiography are discussed in detail. We concluded that the selective operative cholangiography should be the preferred procedure.

Cholangiography↗

[Risk factors in acute myocardial infarct and cerebral ischemic disease].

Ten risk factors (RF) were sought and compared in 100 patients with acute myocardial infarct (MI) and 50 with cerebrovascular disease (CVD) on their first admission. No other diseases were present. Only 3 subjects were free of the RF. At least three RF were noted in 71 MI (71%) and 32 CVD (64%), and four or more in 51 (51%) and 22 (44%) respectively. The most commonly observed in both groups were: high total: HDL cholesterol ratio, cigarette smoking, hypertriglyceridaemia, arterial hypertension, hyperuricaemia Total blood cholesterol was more frequently above normal in MI (52%) than CVD (28%). The difference between the means was significant (p less than 0.01). No significant differences, on the other hand, were noted for the other RF. These findings suggest that the definition of RF for MI and CVD patients is both practicable and important in the secondary prevention of these two diseases. They also show that their atherosclerotic risk profile is substantially the same.

Adult↗