[Vascular disease and asymptomatic diabetic patients].
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Diabetic Angiopathies↗
Biomedical subjects
F Capani
Publications and source records attributed to F Capani.
Remission of psoriatic arthritis after porto-caval anastomosis in a patient with primary biliary cirrhosis.
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Arthritis, Psoriatic↗
A novel mutation (V191G) in a German-British type 1 Gaucher disease patient. Mutations in brief no. 131. Online.
Gaucher disease results from mutations in the glucocerebrosidase gene located on human chromosome 1q21. Three clinical forms of Gaucher disease have been described: type 1, nonneuropathic; type 2, acute neuropathic; and type 3, subacute neuropathic. We have identified a novel mutation in a German-British patient with type 1 Gaucher disease which results in V191G of the glucocerebrosidase polypeptide. Because the mutation abolishes a HphI cleavage site, its presence was confirmed by HphI RFLP analysis of PCR-amplified genomic DNA. In the second allele of the patient, the mutation identified was g.5841A G(N370S). Sequence analysis of the remainder of the coding region of the gene as well as the exon-intron boundaries showed identity to normal controls. Because mutation N370S has so far been found only in type 1 Gaucher disease and postulated to result in mild clinical presentation, and since the clinical course of this patient has been relatively mild with minimal skeletal involvement, we speculate that the V191G/N370S genotype may also result in good prognosis.
Chromosomes, Human, Pair 1↗
Ultrastructural changes in nitric oxide synthase immunoreactivity in the brain of rats subjected to perinatal asphyxia: neuroprotective effects of cold treatment.
Striatal and cortical neurons containing nitric oxide synthase (NOS) were studied in adult rats subjected to different periods of perinatal asphyxia (PA) using immunohistochemistry at both light microscopy (LM) and electron microscopy (EM). Another group was subjected to PA + hypothermia to study its neuroprotective effect. Quantitative image analysis was performed on the striatum and neocortex in order to count the number of immunoreactive neurons and to compare the pattern of staining between the different groups. Six-month-old rats that suffered subsevere and severe PA demonstrated, at LM, cytomegaly of the striatal and neocortical neurons containing NOS. Control and hypothermic neurons were more weakly immunostained than PA neurons. Subsevere and severe asphyctic rats showed an important neuronal loss that was reduced by hypothermic treatment. The PA group disclosed, at EM, dense electronic bodies distributed in terminals surrounding synaptic vesicles and in dendrites. Non-NOS-containing neurons showed signs of degeneration, such as dark cytoplasm and shrunken nuclei. Surrounding the blood vessels, we observed a clear edema. The immunolabeling in hypothermic rats resembled that observed in controls. These data suggest that subsevere and severe PA induces chronic changes in the neuronal content of NOS in the striatum and neocortex. Degeneration observed in neurons surrounding cytomegalic NOS-containing cells may be due to the excess of NO in their environment. Moreover, the chronic alterations produced by PA seem to be prevented by hypothermia.
Animals↗
The nitric oxide synthase expression of rat cortical and hippocampal neurons changes after early lead exposure.
The effect of lead exposure in nitric oxide synthase containing neurons (nNOS) within rat cortex and hippocampus was studied. Lead administration (1 g% lead acetate in drinking water) was commenced prior to mating and continued until 30 postnatal (PN) days. Immunohistochemical studies using antibody to nNOS showed, after lead treatment at PN21-PN30, a reduction in neuronal size and optical density (OD) of nNOS+ cells. In both regions, non-pyramidal immunoreactive neurons exhibited smaller soma size and less developed dendrites. A significant difference in cell areas and OD of lead exposed versus control rats and no variation in the number of nNOS+ neurons was seen. Morphological modifications after early lead exposure, induced nNOS reduction in NOS expressing neurons thereby interfering in NO synthesis.
Animals↗
Short-term changes in NADPH-diaphorase reactivity in rat brain following perinatal asphyxia. Neuroprotective effects of cold treatment.
Perinatal asphyxia (PA) produces changes in nitric oxide synthase (NOS) activity in neuronal and endothelial cells of the striatum and neocortex. The changes were examined using a histochemical NADPH-diaphorase (NADPH-d) staining method. Newborn rats were exposed to severe PA at 37 degrees C and other groups were subjected to severe PA under hypothermic condition (15 degrees C) for 20 or 100 min, respectively. Quantitative image analysis was performed on the striatum and neocortex in order to count cell number of reactive neurons and to compare the pattern of staining between the different groups of animals. Severe asphyctic pups showed an important neuronal loss in striatum and neocortex that was reduced by hypothermia. NADPH-d(+) neurons with reactive processes were found in the lateral zone of the striatum and neocortex in asphyctic pups. Controls and hypothermic striatum showed rounded cells without reactive process, while no cells were stained in cortex. There was also an increase in NADPH-d activity in endothelial cells in severe asphyctic pups in striatum and neocortex vs control and hypothermically treated animals. Our data evidenced that an inappropriate activation of NOS in neuronal and endothelial cells induced by PA is related to neuronal injury. Hypothermia inhibits neuronal injury and may be a valuable neuroprotective agent.
Animals↗
Long term changes in NADPH-diaphorase reactivity in striatal and cortical neurons following experimental perinatal asphyxia: neuroprotective effects of hypothermia.
Nitric oxide (NO) is known to be involved in the neuropathological mechanisms triggered by excitatory aminoacids. NO(+) neurons in the brain may be detected histochemically by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemical technique, as the latter readily labels NO synthase in the central nervous system (CNS). NADPH-d stained striatal and cortical sections were studied in 6-month-old male Sprague-Dawley rats exposed to perinatal asphyxia (PA) at 37 degrees C, as well as in animals subjected to PA plus hypothermia treatment at 15 degrees C. Quantitative image analysis was performed to compare the staining pattern in the various groups. NADPH-d(+) neurons in striatum and cortex from subsevere and severe asphyctic animals showed a significant increase in soma size and in dendritic processes versus controls and hypothermia-treated rats. These findings indicate that chronic NO changes are involved in postischemic striatal and cortical alterations induced by PA that may be prevented by hypothermia.
Animals↗
A re-evaluation of glycohaemoglobin standardisation: the Italian experience with 119 laboratories and 12 methods.
The effect of calibration on glycohaemoglobin results was investigated in 119 laboratories where glycohaemoglobin (HbA1c) percentages were determined in triplicate in two samples and in two calibrators. The materials were human lyophilized haemolysates home-prepared with a novel protocol. The HbA1c content was assigned to calibrators using 4 HPLC methods with the data obtained from 11 laboratories. Intra-laboratory variation was low, although in 14 out of 119 laboratories CV values greater than 3.5% were reported. Calibration decreased inter-method variation from 16.3% to 5.6%, and from 15.3% to 4.2% for samples with low and high HbA1c content, respectively. Calibration decreased overall inter-laboratory variation from 18.7% to 7.4%, and from 17.2% to 5.4%. The calibrated results obtained with all methods, including Abbott IMx and Vision, were comparable.
Calibration↗
Prenatal and postnatal lead exposure induces 70 kDa heat shock protein in young rat brain prior to changes in astrocyte cytoskeleton.
In previous studies we found that chronic postnatal (PN) lead exposure [1 g% (w/v)] induced astroglial hypertrophy in rat hippocampus. Since astrocytic responses change upon the stage during which exposure occurs, astroglial reactions in cerebral cortex and hippocampus of young animals were studied and compared when exposure began during development. Lead-treatment started 90 days prior to mating, and was maintained during gestation and after birth up to PN160. Alterations observed from PN21 to PN140 were assessed by antibodies to the 70kDa heat shock proteins (hsp), glial fibrillary acidic protein (GFAP) and vimentin (VIM) using immunohistochemistry, transmission electron microscopy (TEM), and computer assisted image analysis. The induction of hsp was seen from PN21 to PN45 in non-pyramidal neurons and astrocytes, and at the same time, astroglial swelling was noticed. After PN45 the resolution of this edema coincided with an increase of gliofilaments and GFAP and VIM immunoreaction (PN60-PN90). Recovery of VIM expression persisted after PN120 in the hilus; meanwhile, lipofuscin-like bodies appeared in neurons and astrocytes. Lead exposure during rapid brain growth induced hsp after weaning in neurons and astrocytes prior to astrocyte cytoskeletal changes. Astroglial and neuronal alterations could modify complex neuron-glia interactions, disturbing brain function in consequence.
Animals↗
Association of coagulation factor VArg506Gln mutation with non-insulin-dependent diabetes mellitus.
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Aged↗
Deletion of Gly723 in the insulin receptor substrate-1 of a patient with noninsulin-dependent diabetes mellitus.
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Amino Acid Sequence↗
Glucose and insulin independently reduce the fibrinolytic potential of human vascular smooth muscle cells in culture.
Hyperglycaemia and hyperinsulinaemia have both been related to accelerated atherosclerosis in non-insulin-dependent diabetes mellitus (NIDDM). Plasma fibrinolytic potential is reduced in NIDDM and it is known that glucose and insulin can modulate plasminogen activator inhibitor (PAI-1) and tissue-plasminogen activator (t-PA) secretion and can therefore regulate local fibrinolysis. Vascular smooth muscle cells (vSMC) play an important role in the development of atherosclerotic lesions; however, the role of insulin and glucose in regulating PAI-1 and t-PA production in vSMC is presently not known. Therefore, we cultured arterial vSMC explanted from human umbilical cords and exposed them to increasing concentrations of glucose (5, 12, 20, 27, 35 mmol/l) or insulin (0.1, 0.5, 1, 10 nmol/l) in a serum free medium. After 24 h, PAI-1 and t-PA antigens and activity were evaluated in the culture medium; in cells exposed to 20 mmol/l glucose and to 0.5 nmol/l insulin PAI-1 gene expression was also evaluated. An increase in PAI-1 antigen was observed at each glucose concentration (by 138, 169, 251 and 357% as compared to 5 mmol/l glucose) which was paralleled by an increase in PAI-1 activity. t-PA concentration was also increased by glucose but its activity was sharply reduced. An increase in PAI-1 antigen was detected at each insulin level (by 121, 128, 156 and 300% as compared to no insulin). PAI-1 activity was slightly increased at the lowest insulin concentrations but markedly increased by 10 nmol/l insulin. t-PA antigen was also increased by insulin; however, its activity was markedly reduced at each concentration. As compared to control cells, PAI-1 mRNA was increased by 2.5 and 2.0 fold by 20 mmol/l glucose and 0.5 nmol/l insulin, respectively. We conclude that in human vSMC both glucose and insulin can affect the fibrinolytic balance so as to reduce fibrinolytic potential. This might contribute to decreased local fibrinolysis and thereby might accelerate the atherothrombotic process in NIDDM subjects.
Antibodies, Monoclonal↗
A comprehensive assessment of the avoidability of long-term complications of diabetes. A case-control study. SID-AMD Italian Study Group for the Implementation of the St. Vincent Declaration.
OBJECTIVE: To identify and quantify risk factors for the development of long-term diabetic complications (i.e., critical limb ischemia, amputation, chronic renal failure [creatinine > 3 mg/dl], dialysis treatment, proliferative retinopathy, blindness), with particular emphasis on those variables that, being related to quality of care, can be considered avoidable. RESEARCH DESIGN AND METHODS: We designed a case-control study that enrolled 886 patients with long-term diabetic complications and 1,888 control subjects without complications from 35 diabetic outpatient clinics and 49 general practitioners offices during a 6-month period. Selected socioeconomic, pathophysiologic, self-care, health care, and lifestyle information were collected for all patients. RESULTS: A logistic regression analysis showed that several factors are related to the development of major diabetic complications. Among patient characteristics, male sex (odds ratio [OR] = 1.8, 95% CI 1.4-2.3) and age (OR = 1.7, 95% Cl 1.2-2.4 for patients between 50 and 69 years of age as opposed to those younger than 50 years of age) were associated with an increased risk of complication. Among clinical variables, the type and the duration of diabetes were the most important predictors of diabetic complications. The presence of hypertension was also associated with the development of diabetic complications, particularly when it was poorly controlled by treatment (OR = 3.1, 95% CI 2.3-4.3). Patients who needed help to reach a health care facility and those who did not regularly attend such a facility were at higher risk of developing complications (OR = 1.5, 95% CI 1.2-1.9; OR = 1.7, 95% CI 1.3-2.2, respectively). Educational aspects were also related to the outcome: patients who did not receive any kind of educational intervention had an increased risk of developing complications (OR = 4.1, 95% CI 1.7-9.7), while self-management of insulin therapy had a protective effect (OR = 0.6, 95% CI 0.5-0.8). The summary attributable risk related to avoidable risk factors (i.e., uncontrolled hypertension, poor compliance with visit scheduling, inadequate diabetes education, no self-management of insulin treatment) was 0.39. CONCLUSIONS: Our data suggest that, by removing avoidable risk factors, the number of diabetic complications considered could be reduced by more than one-third. The case-control methodology represents an efficient way of monitoring clinical practice and relating it to important outcomes. It can be of help for policy makers in identifying the more effective strategies and in tailoring specific interventions aimed at improving the quality of the care delivered to diabetic patients.
Adult↗
Unilateral enucleation induces an increase of 160 kd neurofilament in lateral geniculate nuclei synapses.
Ultrastructural synaptic changes of retinal origin in the pars dorsalis lateral geniculate nuclei (dLGN) after enucleation have been studied in this laboratory, showing a filamentous hypertrophy with maximal expression at 4-6 days post-lesion in monkeys (Pecci Saavedra et al., 1970, 1971). The aim of this work was to elucidate the nature of the newly formed filament in dLGN in post-enucleated rats. Male Wistar rats were fixed with 4% paraformaldehyde plus 0.25% glutaraldehyde in 0.1M phosphate buffer, through the abdominal aorta after 3, 5, and 7 days postenucleation. Sections obtained were incubated with antibodies to the phosphorylated portion of the 160 Kd neurofilaments (1:3000) and anti-GFAP (1:25000). There was an increase in 160 Kd neurofilament staining in axons and degenerating nerve endings in dLGN, as well as a typical astroglial immunostained reaction. Our results show that the newly formed neurofilaments after deafferentation are of the 160 Kd type, commonly present in normal axons.
Animals↗
Striatal cytomegalic neurons containing nitric oxide are associated with experimental perinatal asphyxia: implication of cold treatment.
Neuropathological mechanisms triggered by excitatory aminoacids are known to involve nitric oxide (NO). Neurons containing NO are histochemically reactive to nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), which labels NO synthase in CNS. Sprague-Dawley male rats subjected to perinatal asphyxia (PA) at 37 degrees C, and PA plus 15 degrees C hypothermia were evaluated when 6 months old by NADPH-d histochemical reaction. Computarized image analysis was used for quantification of stained sections. NADPH-d neurons in striatum from subsevere and severe PA showed a significant increment in soma size and dendritic process length versus control and hypothermic treated rats. Post-ischemic damage neurons are therefore involved in NO changes induced by PA that may be prevented by hypothermia treatment.
Analysis of Variance↗
Prolonged lead exposure modifies astrocyte cytoskeletal proteins in the rat brain.
The time-course and the regional astrocyte responses were studied during 15 months of continuous lead-exposure. Rat pups were exposed from postnatal day 1 (P1 group) and day 7 (P7 group) through the maternal milk, (1g% lead acetate solution in the drinking water). Following weaning lead-exposed offspring were treated during 15 months. Immunohistochemical staining for glial fibrillar acidic protein (GFAP) and vimentin were used to evaluate astrocyte response. In coincidence with previous results, after 2-3 months of treatment, we observed in both groups a transient increase of GFAP immunoreactivity in hippocampal and cerebellar astrocytes (first stage). After 4-12 months (second stage), the hypertrophy declined to near control levels despite the persistence of high blood lead-levels; meanwhile, lipofuscin-like bodies appeared in neuronal and glial cells. After one year of treatment, the immunostaining of homologous sections showed an increase of GFAP reactivity and the presence of vimentin + cells in the upper and the lower limb, and in the hilus of the fascia dentata. GFAP and vimentin astrocytic response extended to the adjacent cerebral cortex after 14 months. Although both cells showed a similar aspect, vimentin + cells showed a smaller area and a restricted arrangement. However, in the cerebellum the hypertrophy of vimentin positive astrocyte and Bergmann fibers was confined to the white matter as observed in the first stage. Astrocyte alterations, the recovery of vimentin expression and the appearance of lipofuscin-like bodies induced by prolonged lead-exposure suggest modifications in neuronal microenvironment, and might accelerate age-dependent changes in CNS.
Analysis of Variance↗
Reproducibility of ultrasound measurement of pancreatic size with new advanced high-resolution dynamic image scanners.
The reproducibility of ultrasound measurements of the pancreas was investigated in 10 healthy volunteers. All subjects underwent three different evaluations, each consisting of three ultrasound examinations, at 8:00 after overnight fasting, at 12:00 after a solid, standard meal, and at 14:00. The longitudinal and anteroposterior (AP) diameters of the head, body, and tail, as well as the total areas of the gland, were measured in longitudinal and axial scans. Significant differences were observed in the head and body longitudinal diameters measured at 12:00 and in the tail AP diameter at 14:00. We conclude that ultrasonography of the pancreas should be performed in the morning with patients in the fasting state. In these conditions, the reliability of ultrasound measurements of the gland appears to be the highest.
Adult↗
Limitations in the use of [2-14C]acetate for measuring gluconeogenesis in vivo.
This study was undertaken to test two assumptions critical for use of [2-14C]acetate to measure gluconeogenesis in vivo. For the assumption that incorporation into glucose of products of [14C]acetate metabolism does not affect the distribution of label within the glucose molecule, we infused [2-14C]acetate in 17 healthy subjects and [3-14C]lactate in 10 healthy subjects and compared the ratio of the resultant specific activities of plasma glucose carbons 1, 2, 5, 6, and 3, 4 obtained with each tracer. The ratio obtained with [2-14C]acetate (2.99 +/- 0.07) was significantly different from the ratio obtained with [3-14C]lactate, (3.82 +/- 0.2, P < 0.01). Because the model predicts that these ratios should be identical, these results indicate that either the model is incorrect or that metabolism of [14C]acetate to other compounds affects the distribution of the label within the glucose molecule. To test the assumption that plasma 3-OH-butyrate specific activity approximates the specific activity of hepatic intramitochondrial acetyl CoA, we compared the ratio of specific activities of plasma glucose and 3-OH-butyrate obtained in 7 healthy subjects infused with [2-14C]acetate and [2-14C]octanoate. The ratio obtained with [2-14C]acetate (0.18 +/- 0.03) was significantly different from that obtained with [2-14C]octanoate, (0.10 +/- 0.02), P < 0.001. These results suggest compartmentalization of acetyl CoA within liver mitochondria and indicate that plasma 3-OH-butyrate specific activity may not necessarily approximate intramitochondrial acetyl CoA specific activity during [2-14C]acetate infusion. We conclude that assumptions critical for use of [2-14C]acetate to measure gluconeogenesis in vivo are not valid.
3-Hydroxybutyric Acid↗