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Biomedical subjects

F Capani

Publications and source records attributed to F Capani.

At least 19 recordsLinked to original sources
PubMed2003

A high-score Mediterranean dietary pattern is associated with a reduced risk of peripheral arterial disease in Italian patients with Type 2 diabetes.

BACKGROUND: The 'Mediterranean diet' is considered to exert protective effects on cardiovascular disease, although a wide range of dietary patterns exists among subjects living even in the same Mediterranean country. OBJECTIVE: To investigate the association between specific dietary patterns and peripheral arterial disease (PAD) in Italian Type 2 diabetes patients. DESIGN: From a cohort of 944 patients with Type 2 diabetes, 144 patients with PAD were selected, and matched for age and sex with 288 Type 2 diabetic control patients without macrovascular complications. A dietary score was elaborated from a semiquantitative food frequency questionnaire. The higher the final score, the healthier the eating habit. RESULTS: In multivariate analysis, a higher score was independently associated with a significant reduction in PAD risk [odds ratio (OR) = 0.44; 95% confidence interval (CI) 0.24, 0.83]. Diabetes duration (OR > 15 years = 2.49; 95% CI 1.45, 4.25), hypertension (OR = 2.12; 95% CI 1.31, 3.45) and butter consumption (OR = 2.6; 95% CI 1.15, 3.68) were also significantly associated with PAD. The dietary score significantly improved the predictive value of models based on duration of diabetes and hypertension. (LSR = 2.19, DF = 7, P < 0.001). The effect of a high dietary score on the risk of PAD was independent of diabetes duration and hypertension. CONCLUSION: In Italian Type 2 diabetics, a higher dietary score has a protective role against PAD. The use of butter increases the risk of PAD even in patients regularly consuming olive oil. Dietary advice may be helpful for the prevention of PAD in diabetics even in populations traditionally accustomed to a Mediterranean dietary habit.

Aged↗
PubMed2002

Anti-ENA antibodies in patients with chronic hepatitis C virus infection.

The aim of the study was to assess the prevalence of anti-extractable nuclear antigen (ENA) antibodies in patients with chronic HCV infection. We studied 69 consecutive patients with chronic hepatitis C, 59 control subjects with non-HCV liver diseases, and 22 control subjects with extrahepatic, non-immune-mediated, chronic diseases. Thirty-two (46.3%) of 69 patients with HCV infection had anti-ENA antibodies: 16 (23.1%) showed anti-SSA antibodies and 14 (20.2%) had anti-SSB antibodies. Four of the patients with HCV infection suffered from sicca syndrome and three of them had also anti ENA antibodies. The prevalence of anti-ENA antibodies was significantly higher in the anti-HCV subjects compared with both control groups. Twenty-six of 44 HCV-antibodies-positive females had anti-ENA antibodies, compared with 6 of 25 males, showing a sex related difference. In conclusion, our results outline a specific role of HCV infection in the induction of anti-ENA antibodies. Female sex seems a predisposing condition.

Antibodies↗
PubMed2002

Counting dendritic spines in brain tissue slices by image correlation spectroscopy analysis.

Growth of new micrometre sized projections called dendritic spines in neurones has been linked to the encoding of long-term memories in vertebrates. Numerous studies have been carried out at both the light and electron microscopy level to quantify dendritic spine densities in brain tissue in laboratory animals. Currently, such efforts using light microscopy have relied on manual counting of spines in confocal or two-photon optical slice images of tissue containing fluorescently labelled spines. This manual approach can be slow and tedious, especially for samples with high spine densities. We introduce an alternative way of performing spine counting that uses an applied image intensity threshold followed by spatial image correlation spectroscopy (ICS) analysis. We investigated the effect of particle sizes above the diffraction limit on the autocorrelation analysis as well as the influence of background fluorescence. Our results show that, for well labelled cerebellar tissue samples imaged with a signal-to-noise ratio of 5 or greater, ICS-based spine counts can be conducted with the same 15-20% precision as manual counting, but much more rapidly.

Animals↗
PubMed2001

Filamentous actin is concentrated in specific subpopulations of neuronal and glial structures in rat central nervous system.

This paper is the second in a series of studies on the light and electron microscopic distribution of filamentous actin (F-actin) in the rat central nervous system (CNS) using phalloidin tagged with the fluorophore eosin followed by fluorescence photooxidation. A previous report described the selective localization of high concentrations of F-actin in subpopulations of dendritic spines in hippocampus, cerebellum and neostriatum. Dendritic spines were the most intensely stained structures in the CNS, but several other structures were notable for their consistent staining for F-actin. Although the majority of cell bodies, axons and large dendrites were unlabeled, mossy fibers and Schaffer collaterals in the hippocampal formation, basket cell axons in the cerebellar pinceau, and granule cell dendrites in the glomeruli of the cerebellar cortex routinely showed strong F-actin labeling. Staining was observed in all three glial cell types. Labeling was consistently observed in the astrocytic processes surrounding the Purkinje cell soma and primary dendrite. Intense but sporadic staining was observed in the perinodal glia of the Node of Ranvier. A few examples of labeled oligodendrocyte processes were also seen in the neostriatum. Labeling was observed in microglia in every brain region examined, although the labeling was present in the lumen of the endoplasmic reticulum and the nuclear membrane, leading to questions about its specificity. Perycites apposed to the blood vessels also showed very consistent labeling. Our results suggest that selected structures in the adult CNS in addition to dendritic spines are enriched in F-actin.

Actins↗
PubMed2001

Changes in reactive oxygen species (ROS) production in rat brain during global perinatal asphyxia: an ESR study.

A large body of evidence suggests that the production of reactive oxygen species (ROS) can play an important role in ischemic neuronal injury. However any studies has been performed in hypoxic conditions. In the present experiments we studied using electron spin resonance (ESR) techniques the ROS release in neostriatum of newborn rats subjected to acute perinatal asphyxia (PA) followed by various periods of reoxygenation. Pregnant rats' uteri still containing foetuses were taken out and subjected to PA by immersion in a 37 degrees C water bath during the following periods of time: 5, 10, 15, 19 and 20 min. After performing PA, animals were recovered and ROS measured after 0, 5, 15, 30 or 60 min of reoxygenation. Then, pups were sacrificed, their neostriatum removed and homogenised with N-tert.-butyl-alpha-phenylnitrone (PBN) and diethylenetriamine-pentacetic acid (DPTA) in phosphate-buffered saline (PBS) and the formed complexes were extracted with ethyl acetate an analysed using an X-band ESR spectrometer. A significant release of ROS was detected at 19 and 20 min of PA after 5 min of reoxygenation. These data provide strong evidence that ROS could be involved in neuronal damage during PA.

Animals↗
PubMed2001

Selective localization of high concentrations of F-actin in subpopulations of dendritic spines in rat central nervous system: a three-dimensional electron microscopic study.

Dendritic spines differ considerably in their size, shape, and internal organization between brain regions. We examined the actin cytoskeleton in dendritic spines in hippocampus (areas CA1, CA3, and dentate gyrus), neostriatum, and cerebellum at both light and electron microscopic levels by using a novel high-resolution photoconversion method based in the high affinity of phalloidin for filamentous (F)-actin. In all brain regions, labeling was strongest in the heads of dendritic spines, diminishing in the spine neck. The number of labeled spines varied by region. Compared with the cerebellar molecular layer and area CA3, where nearly every dendritic spine was labeled, less than half the spines were labeled in CA1, dentate gyrus, and neostriatum. Serial section reconstructions of spines in these areas indicated that phalloidin labeling was restricted to the largest and most morphologically diverse dendritic spines. The resolution of the photoconversion technique allowed us to examine the localization and organization of actin filaments in the spine. The most intense staining for actin was found in the postsynaptic density and associated with the spines internal membrane system. In mushroom-shaped spines, F-actin staining was particularly strong between the lamellae of the spine apparatus. Three-dimensional reconstruction of labeled spines by using electron tomography showed that the labeled dense material was in continuity with the postsynaptic density. These results highlight differences in the actin cytoskeleton between different spine populations and provide novel information on the organization of the actin cytoskeleton in vivo.

Actins↗
PubMed2001

Acute hyperglycemia and acute hyperinsulinemia decrease plasma fibrinolytic activity and increase plasminogen activator inhibitor type 1 in the rat.

Decreased plasma fibrinolysis may contribute to accelerated atherothrombosis in diabetes. To observe whether hyperglycemia and hyperinsulinemia, common findings in type 2 diabetes, acutely affect plasma fibrinolysis in vivo, we evaluated plasma fibrinolysis (lysis of fibrin plates, free PAI-1 activity and t-PA activity) in the rat after a hyperglycemic euinsulinemic clamp (n=8), an euglycemic hyperinsulinemic clamp (n=7) or a saline infusion (n=15). Plasma fibrinolytic activity was sharply reduced after both the hyperglycemic and hyperinsulinemic clamps as compared to the respective controls (mean lysis areas on the fibrin plate, 139+/-21 vs. 323+/-30 mm2, p<0.001; 78+/-27 vs. 312+/-27 mm2 p<0.001, respectively). Plasma PAI-1 activity was greater after both hyperglycemic and hyperinsulinemic clamps as compared to saline infusion (6.6+/-2.6 vs. 1.6+/-0.6 IU/ml, p<0.001; 26+/-4 vs. 1.3+/-0.7 IU/ml, p<0.0001, respectively). Plasma t-PA activity was significantly reduced both after the hyperglycemic (0.36+/-0.15 vs. 2.17+/-0.18 IU/ml in controls, p<0.001) and the hyperinsulinemic (0.3+/-0.1 vs. 2.3+/-0.3 IU/ml in control, p<0.001) clamps. These data show that in vivo both acute hyperglycemia and acute hyperinsulinemia can decrease plasma fibrinolytic potential and that this is due to increased plasma PAI-1 and decreased free t-PA activities.

Animals↗
PubMed2001

Plasminogen activator inhibitor type 1 is increased in the arterial wall of type II diabetic subjects.

Plasma plasminogen activator inhibitor type 1 (PAI-1) increases in diabetes, and this might contribute to decreased fibrinolysis and accelerated atherosclerosis. Increased PAI-1 levels in the vessel wall could decrease local fibrinolysis and elevate thrombus formation and the unfavorable evolution of atherosclerotic plaques. High glucose increases PAI-1 synthesis in arterial wall cells in culture, and aortic wall PAI-1 levels have been found to be elevated in diabetic animals. However, arterial wall PAI-1 levels have not been investigated in diabetic subjects. Therefore, the aim of this study was to determine the effect of diabetes on PAI-1 levels in the arterial wall. Blood samples and small tissue specimens from the mammary artery were obtained from 11 diabetic and 10 nondiabetic subjects who underwent coronary artery bypass graft surgery. PAI-1 antigen localization in the arterial wall was obtained by immunohistochemistry and was read by laser scanning confocal microscopy; plasma fibrinolytic activity was measured by lysis of fibrin plates; and PAI-1 activity was assessed by a chromogenic method. PAI-1-related immunofluorescence was increased in the arterial wall of diabetic patients, whereas plasma fibrinolysis was reduced. These data provide evidence that diabetes is associated with increased PAI-1 in the arterial wall. This might be an important factor for increased cardiovascular risk and unfavorable plaque evolution in diabetes.

Aged↗
PubMed2001

Phalloidin-eosin followed by photo-oxidation: a novel method for localizing F-actin at the light and electron microscopic levels.

We describe a novel high-resolution method to detect F-actin at the light and electron microscopic levels through the use of the actin-binding protein phalloidin conjugated to the fluorophore eosin, followed by photo-oxidation of diaminobenzidine. This method possesses several key advantages over antibody-based labeling and structural methods. First, phalloidin binding to F-actin can tolerate relatively high concentrations of glutaraldehyde (up to 1%) in the primary fixative, resulting in good ultrastructural preservation. Second, because both eosin and phalloidin are relatively small molecules, considerable penetration of reagents into aldehyde-fixed tissue was obtained without any permeabilization steps, allowing 3D reconstructions at the electron microscopic level. By employing a secondary fixation with tannic acid combined with low pH osmication, conditions known to stabilize actin filaments during preparation for electron microscopy, we were able to visualize individual actin filaments in some structures. Finally, we show that fluorescent phalloidin can be directly injected into neurons to label actin-rich structures such as dendritic spines. These results suggest that the fluorescent phalloidin is an excellent tool for the study of actin networks at high resolution.

Actins↗
PubMed2001

The relationship between physicians' self-reported target fasting blood glucose levels and metabolic control in type 2 diabetes. The QuED Study Group--quality of care and outcomes in type 2 diabetes.

OBJECTIVE: To investigate the relationship between beliefs of physicians relative to intensive metabolic control in type 2 diabetes and levels of HbA1c obtained in a sample of their patients. RESEARCH DESIGN AND METHODS: Physicians' beliefs were investigated through a questionnaire sent to a sample of self-selected clinicians participating in a nationwide initiative aimed at assessing the relationship between the quality of care delivered to patients with type 2 diabetes and their outcomes. At the same time, physicians were asked to collect clinical data on a random sample of their patients, stratified by age (<65 vs. > or = 65 years). Mean HbA1c levels in the study population were thus evaluated according to target fasting blood glucose (FBG) used by their physicians. RESULTS: Of 456 physicians, 342 (75%) returned the questionnaire. Among the responders, 200 diabetologists and 99 general practitioners (GPs) recruited 3,297 patients; 2,003 of whom were always followed by the same physician and 1,294 of whom were seen by different physicians in the same structure on different occasions. Only 14% of the respondents used target FBG levels < or = 6.1 mmol/l, whereas 38% pursued values >7.8 mmol/l, with no statistically significant difference between diabetologists and GPs. The analysis of the relationship between FBG targets and metabolic control, restricted to those patients always seen by the same physician, showed a strong linear association, with mean HbA1c values of 7.0 +/- 1.6 for patients in the charge of physicians pursuing FBG levels < or = 6.1 mmol/l and 7.8 +/- 1.8 for those followed by physicians who used target values >7.8 mmol/l. After adjusting for patients' and physicians' characteristics, the risk of having HbA1c values > 7.0% was highly correlated with physicians' beliefs. Patients followed by different physicians in the same unit showed a risk of inadequate metabolic control similar to that of patients followed by physicians adopting a nonaggressive policy. CONCLUSIONS: Doctors adopt extremely heterogeneous target FBG levels in patients with type 2 diabetes, which in turn represent an important independent predictor of metabolic control. To improve patient outcomes, physicians-centered educational activities aimed at increasing the awareness of the potential benefits of a tight metabolic control in patients with type 2 diabetes are urgently needed.

Aged↗
PubMed2000

Interaction between the G1057D variant of IRS-2 and overweight in the pathogenesis of type 2 diabetes.

The insulin receptor substrate-2 (IRS-2) is a major insulin signalling molecule. IRS-2 inactivation in mice induces a form of diabetes characterized by peripheral insulin resistance and reduced beta cell mass. We tested the hypothesis that a common non-conservative amino acid substitution of IRS-2 (G1057D) might interact with overweight in the pathogenesis of type 2 diabetes. The variant was genotyped in 193 Italian patients with type 2 diabetes and 206 control subjects. In the absence of overweight, the risk of type 2 diabetes decreased according to the dosage of the D1057 allele (odds ratio for GD genotype 0.46 [95% CI 0.25-0.86]; DD genotype 0.18 [0.04-0.68]; P for trend = 0.0012). Conversely, the interaction between overweight and genotype increased the risk of type 2 diabetes according to the dosage of the D1057 allele (odds ratio for GD genotype 2.50 [1.11-5.65]; DD genotype 5.74 [1.11-29. 78]; P for trend = 0.0047). Among controls, fasting C-peptide levels, after adjustment for plasma glucose, were inversely related to the dosage of the D1057 allele (P = 0.020). This finding suggested that carriers of the D1057 allele may have higher insulin sensitivity and supported the protective effect of this allele. Conversely, among overweight patients there was a parallel increase in fasting plasma glucose (P for trend = 0.037) and fasting C-peptide according to the dosage of the D1057 allele, suggesting that higher insulin resistance and relative beta cell failure contributed to the increased risk of type 2 diabetes in overweight carriers of this allele. These data provide evidence for a strong association between type 2 diabetes and the G1057D common genetic variant of IRS-2, which appears to be protective against type 2 diabetes in a codominant fashion. Overweight appears to modify the effect of this polymorphism toward a higher risk of type 2 diabetes. Carriers of this polymorphism may represent an elective target for prevention of type 2 diabetes through preventing or treating excessive weight.

Adult↗
PubMed2000

Relationship between patient practice-oriented knowledge and metabolic control in intensively treated Type 1 diabetic patients: results of the validation of the Knowledge and Practices Diabetes Questionnaire.

AIMS: To validate a newly developed questionnaire for the measurement of patients' knowledge and practices, with particular attention to its ability in predicting HbA1c levels. RESEARCH DESIGN AND METHODS: The Knowledge and Practices Diabetes Questionnaire (KPDQ) is a questionnaire composed of two scales, investigating patient knowledge and practices. Twenty-two questions, 12 dealing with patients' knowledge and 10 relative to patients' practices, were initially identified. Factor analysis and reliability analysis were used to validate the questionnaire. The ability of the two scales in predicting metabolic control was then evaluated. The questionnaire was administered to a population of Type 1 diabetic subjects intensively treated and regularly attending the diabetes outpatient clinic of Pescara General Hospital. The mean of all HbA1c measurements performed after patients were taken in charge by the clinic was used as an indicator of metabolic control. RESULTS: Out of 133 Type 1 patients identified, 77 (58 %) filled in the questionnaire. Respondents had a mean age (+/- SD) of 37 +/- 13 years and a mean diabetes duration of 13 +/- 9 years. The application of factor and reliability analyses led to the definition of two final scales composed of 10 (Knowledge Score, KS) and 5 items (Practice Score, PS), respectively. Item-scale correlation was > or = 0.40 for all the items investigated. Cronbach's alpha coefficient exceeded the value of 0.70 for both scales. The mean number of HbA1c determinations during a median period of observation of 4 years was of 11 +/- 5. The mean HbA1c value for the whole population was of 7.0% +/- 1.4, while the proportion of patients with values < or = 7.0% was of 57%. After adjusting for clinical and patient-related characteristics, the KS was the only independent predictor of metabolic control. Patients in the lowest quartile of the KS showed a more than 20-fold increased risk of having mean HbA1c values > or = 7.0% as opposed to those in the highest quartile (odds ratio, OR=23.3;p=0.009). No association emerged between metabolic control and PS. CONCLUSIONS: The KPDQ presents excellent psychometric properties. The KS also shows a very impressive association with the mean HbA1c values over a period of 4 years. These findings are particularly remarkable in that many studies have failed in documenting such a relationship. The KS can thus be considered as a quick and efficient screening tool to be used in an ambulatory setting to monitor the level of practice-oriented knowledge of patients with Type 1 diabetes as well as to identify those subjects who need individualized educational interventions.

Adult↗
PubMed1999

In vivo formation of 8-iso-prostaglandin f2alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation.

BACKGROUND: Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F2-isoprostane 8-iso-prostaglandin (PG)F2alpha, a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation. METHODS AND RESULTS: Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF2alpha and 11-dehydro-thromboxane B2 (TXM), an in vivo index of platelet activation. Sixty-two had non-insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF2alpha in this setting. Urinary 8-iso-PGF2alpha excretion was significantly higher (P=0.0001) in NIDDM patients (419+/-208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208+/-92; 41 to 433). Urinary 8-iso-PGF2alpha was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF2alpha excretion was also significantly (P=0. 0001) higher in IDDM patients (400+/-146; 183 to 702) than in control subjects (197+/-69; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF2alpha (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P=0.0001) reduction in 8-iso-PGF2alpha and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF2alpha was unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion. CONCLUSIONS: We conclude that DM is associated with increased formation of F2-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.

Adult↗
PubMed1999

Atrial natriuretic peptide effect on NADPH-diaphorase in rat intestinal tract.

Histochemical reaction of NADPH-diaphorase (NOS-NADPH-d) was used to identify NO synthesis. A 30-min 0.1 microg microg/kg/min ANP infusion led to about a 10% and 35% increase in small and large intestine enterocytes stain respectively. This increase was abolished by a bolus of 1 mg/kg L-NAME before ANP infusion in small intestine, and partially abolished it in colon. Incubation of small and large intestine with 0.5 microM ANP increased stain at about 20%. In both tissues the preincubation with 0.1 mM L-NAME abolished the ANP effect. Incubation with 0.1 mM 8-Br-cGMP enhanced staining about 70% and 30% in small and large intestine respectively. Our results show that ANP enhances NOS-NADPH-d activity, suggesting that ANP stimulates NO synthase in enterocytes by L-arginine-NO pathway. 8-Br-cGMP mimicked the effect of ANP described above. Therefore, the guanylate cyclase-coupled natriuretic receptors, NPR-A and NPR-B, probably mediate this ANP effect.

Animals↗
PubMed1998

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↗