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Biomedical subjects

M Locatelli

Publications and source records attributed to M Locatelli.

At least 55 records · Page 3Linked to original sources

Differential effects of selective beta-adrenergic blockade on insulin sensitivity and release in control subjects and in patients with angina and normal coronary arteries (syndrome X).

AIMS: Betablockers are very effective in patients with angina and angiographically smooth coronary arteries (syndrome X), but may exacerbate the state of insulin resistance that is known to be present in such patients. The aim of the study was to evaluate the effects of short-term treatment with atenolol on carbohydrate metabolism in syndrome X patients, as compared to normal subjects. METHODS AND RESULTS: Seventeen patients (15 females, 55 +/- 8 years, BMI 23.4 +/- 2.7 kg/m2) and 11 controls (5 females, 50 +/- 7 years, BMI 23.1 +/- 2.0 kg/m2) were studied twice by an intravenous glucose tolerance test (IVGTT, 0.5 g/kg) after ten days of both placebo and atenolol (100 mg o.d.), given in random order. Metabolic indices measuring glucose effectiveness and insulin sensitivity were derived from minimal model analysis of the glucose and insulin profiles measured during the IVGTT. Indices of first- and second-phase insulin release were also calculated from the IVGTT insulin response. Atenolol had different metabolic effects on normal subjects and syndrome X patients. Despite the fact that the drug was found to be effective in relieving symptoms of chest pain, it induced a significant (p < 0.05) worsening of insulin resistance in syndrome X patients. No such effect was observed in control subjects. On the other hand, atenolol produced a marked reduction (40%, p < 0.05) of first-phase insulin release in control subjects, but no significant change of the same index in syndrome X patients. CONCLUSION: These results show that betablockers are very effective for controlling symptoms and improving quality of life in syndrome X patients. However, they appear to further impair the ability to dispose glucose. Long-term studies on the net effects of beta-blockade administration for the treatment of such patients are warranted.

Administration, Oral↗

Circadian secretory pattern of growth hormone, insulin-like growth factor type I, cortisol, adrenocorticotropic hormone, thyroid-stimulating hormone, and prolactin during HIV infection.

The circadian rhythms of plasma growth hormone (GH), insulin-like growth factor type I (IGF-I), cortisol, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and prolactin (PRL) were evaluated in 13 HIV-seropositive patients (8 males and 5 females; mean age [+/-SD], 30 +/- 5 years), classified as CDC C2. Sixteen clinically healthy subjects (9 males and 7 females; mean age [+/-SD], 32 +/- 8 years) were chosen as control group. Samples were taken every 4 hr from 04:00 to 20:00 and every 2 hr from 20:00 to 04:00. Plasma GH was evaluated by IRMA procedure, plasma IGF-I by RIA (after separation of soluble IGF-I from IGF-I-binding proteins, using acid-ethanol extraction), plasma cortisol by a solid-phase RIA, plasma ACTH by double-antibody RIA, and serum TSH and serum PRL by a solid-phase two-site fluoroimmunometric assay. Rhythmometric data were analyzed by single and population mean cosinor analysis; the comparison of the parameters of the rhythm between patients and controls was carried out by the mesor test and the amplitude-acrophase Hotelling test. Alterations of the circadian pattern of GH, IGF-I, cortisol, ACTH, TSH, and PRL were demonstrated in HIV-seropositive patients. In fact, the circadian profiles of these hormones were clearly flattened and no statistically significant 24-hr rhythm was detectable (with the exception of cortisol). These results are consistent with the hypothesis that alterations of the circadian temporal structure may already be present in HIV-seropositive patients without wasting and infectious complications.

Adrenocorticotropic Hormone↗

Retrospective analysis of long-term hemorheologic effects of pentoxifylline in diabetic patients with angiopathic complications.

Blood rheology alterations have often been reported in diabetic patients and may be associated with an increased risk for diabetic vascular disease. In this light a hemorheologic approach with pentoxifylline has been suggested in diabetic patients with hemorheological changes in order to improve the hemorheology approach and to evaluate the long-term effects of this treatment on the other clinical and metabolic variables. The study concerned a 10-year retrospective analysis of diabetic patients with hemorheologic alterations and angiopathic complications. Pentoxifylline (Trental 400) significantly reduced blood and plasma viscosity (at high and low shear-rates), fibrinogen and erythrocyte aggregation, and increased erythrocyte filterability throughout the study. The improvement of the hemorheologic pattern was obtained independently of the variation in glycometabolic control and body weight changes, whereas concomitant reductions of arterial blood pressure levels and of urinary excretion of albumin and total proteins was observed during the treatment. Pentoxifylline might therefore be successfully employed for long-term periods in the treatment of hemorheologic disorders in diabetic patients without effects on the metabolic pattern.

Adult↗

Hyperviscosity and microproteinuria in central obesity: relevance to cardiovascular risk.

OBJECTIVES: To investigate the role of blood rheology changes in the occurrence of glomerular proteinuria in obese patients with central fat distribution. SUBJECTS: Fifty-nine obese out-patients (31 with central and 28 with peripheral body fat distribution) and 24 healthy subjects. MEASUREMENTS: Blood and plasma viscosity (Rotational viscometer CV100 HAAKE), erythrocyte deformability (whole-blood filtration time), fibrinogen (nephelometry), urinary excretion rates of albumin, IgG, transferrin and IgA (nephelometry). RESULTS: Higher blood viscosity (at low and high shear-rates), plasma viscosity, fibrinogen, erythrocyte aggregability and lower erythrocyte deformability were found in patients with central obesity than in patients with peripheral obesity (P < 0.01) and in healthy subjects (P < 0.001). Furthermore an increased urinary excretion rate of albumin (P < 0.001), IgG (P < 0.001), transferrin (P < 0.01) and IgA (P < 0.05) was found in patients with central obesity than in the other two groups. Blood hyperviscosity (at shear-rate 1 s-1 and 1/200 ratio) significantly correlated with the amount of urinary excretion of proteins independently of the other clinical and metabolic variables. CONCLUSIONS: The data demonstrated haemorheologic disorders related to pathologic proteinuria in patients with central obesity. The interaction between these two components may increase the risk of widespread cardiovascular disease.

Adult↗

Changes in endocrine circadian rhythms as markers of physiological and pathological brain aging.

We studied the circadian rhythm of plasma melatonin, growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), and cortisol in 52 mentally healthy old subjects, 35 old demented patients, and 22 clinically healthy young controls. When compared to young controls, the circadian profile of plasma melatonin of old subjects, both demented or not, was clearly flattened, particularly during the night. The selective impairment of nocturnal melatonin secretion was significantly related to both the age and the severity of mental impairment (Mini Mental State Examination [MMSE] score). The PRL and GH circadian profiles were similar in the three groups during the day, but a significant lowering of the values recorded during the night occurred with aging. The impairment of the nocturnal secretion was related to the subjects' age and, for the GH secretory pattern only, also to the MMSE score. The ACTH circadian profile was similar in the three groups studied, even when old subjects exhibited higher ACTH levels throughout the 24 h cycle, compared to young controls. Significantly higher cortisol values at evening- and nighttime occurred in elderly subjects and particularly in the demented group. Both the mean levels and the nadir values of plasma cortisol were positively related to age and negatively to MMSE score. In order to verify the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to the steroid feedback, the circadian profile of plasma cortisol was evaluated also after dexamethasone (DXM) administration (1 mg at 23:00 h); the sensitivity of the HPA axis was significantly impaired in old subjects and particularly in the demented ones. These findings suggest that the neuroendocrine alterations already present in physiological aging, due to both anatomical damages and unbalanced central neurotransmitters, are enhanced in senile dementia.

Adrenocorticotropic Hormone↗

Nephelometry in the clinical assessment of glomerular proteinuria and tubular function in diabetic nephropathy.

Urinary excretion rate and total clearances of albumin, IgG, IgA and alpha 1-microglobulin, together with selectivity index and proteinuria, were determined by computerized nephelometry in 187 IDDM and NIDDM diabetic out-patients and in 39 healthy subjects in order to perform a prompt clinical assessment of diabetic nephropathy. Significant correlations between nephelometric and RIA procedures were demonstrated for the urinary excretion of albumin (p < 0.001) and total IgG (p < 0.001) in diabetic patients and healthy subjects. Nephelometry allowed us to classify diabetic patients in different stages of nephropathy: non nephropathic, normoalbuminuric with hyperfiltration, with incipient (microalbuminuric) and overt nephropathy (macroalbuminuric). Thirty consecutive subjects were analyzed within 1 h from the beginning of the procedure. A normal tubular function was demonstrated in non nephropathic, hyperfiltering and in 34% of microalbuminuric diabetic patients. On the contrary, in 66% of microalbuminuric and in 93% of macroalbuminuric patients alpha 1-microglobulin urinary levels were found above the upper normal limit. Urinary excretion of IgA was significantly increased only in macroalbuminuric diabetic patients (p < 0.001); this marker might therefore characterise the stage of overt nephropathy. Computerized nephelometry can be considered as a prompt, reproducible and high sensitive approach in the clinical evaluation of proteinuria and tubular function in diabetic renal disease.

Adult↗

Temporal lobe electroencephalogram power modifications during olfactory stimulation in HIV-infected patients.

Evidence derived from studies concerning brain metabolism and brain electrical activity suggests that temporal lobe functioning is impaired in the course of HIV infection. To test the hypothesis of temporal lobe dysfunction in HIV infection, we utilized computerized electroencephalogram (EEG) analysis to evaluate temporal lobe EEG power modifications induced by olfactory stimulation in 10 HIV-infected patients as compared with 10 seronegative control subjects. Our findings show that HIV-infected patients respond to olfactory stimulation with an increase in temporal lobe slow electrical activity (theta EEG power), whereas control subjects show a decrease in the same activity. The theta EEG power increase during olfactory stimulation in HIV-infected patients can be interpreted as a paradoxical response of the deep temporal regions to specific procedures, supporting the hypothesis of temporal lobe dysfunction in HIV infection.

Adult↗

EEG power modifications in obsessive-compulsive disorder during olfactory stimulation.

Temporal lobe electroencephalogram (EEG) activity was quantitatively analyzed in obsessive-compulsive disorder (OCD) when subjects are at rest and during a temporal lobe activating procedure, i.e., olfactory stimulation. At rest with eyes closed, delta-1 and alpha-2 power differences were evident in OCD patients as compared with normal controls. During olfactory stimulation, differences between patients and normal groups were detectable in the slower beta frequencies: Normal subjects showed a power increase, whereas OCD patients showed no modification or slight decrease. Our results support previous findings of temporal lobe EEG abnormalities in OCD patients with an abnormal pattern of response to a temporal lobe activating procedure.

Adult↗

Determination of amisulpride, a new benzamide derivative, in human plasma and urine by liquid-liquid extraction or solid-phase extraction in combination with high-performance liquid chromatography and fluorescence detection. application to pharmacokinetics.

Amisulpride (SOLIAN) belongs to the benzamide series and shows antischizophrenic and antidepressant (anti-dysthymic) properties in man. Two methods suitable for pharmacokinetic investigations are proposed for the determination of amisulpride in human plasma. For the liquid-liquid extraction (LLE) based method, the plasma, added with the internal standard (an amisulpride analogue) is alkalinised with NaOH and extracted with a diethyl ether-chloroform mixture. The organic phase is removed, evaporated to dryness and redissolved in an acidic phosphate-acetonitrile mixture that, after a back-washing step with n-hexane, is injected onto the HPLC column (C18 BDS type) connected with a fluorimetric detector. The second method is based on an automatic solid-phase extraction (SPE) performed on an ASPEC device. The plasma sample, diluted with a pH 9 borate buffer, is loaded onto a disposable SPE C18 100-mg column. The analytes of interest (amisulpride and internal standard), after two washing steps with different solvents, are recovered in pure methanol; after evaporation to dryness, the residue is dissolved in an acidic phosphate buffer and injected onto the chromatographic apparatus already described. The limit of quantitation (LOQ) is 0.5 ng ml-1 for both methods; a linear correlation between concentrations and detector response has been demonstrated in the range 0.5-640 ng ml-1 for LLE, which is the most used method; for SPE methods, less used, linearity has been assessed in the plasma range of 0.5-160 ng ml-1.

Amisulpride↗

Chrono-neuroendocrine markers of the aging brain.

The study of the neuroendocrine changes occurring in aging may give information about the CNS functions, and also explain the impaired plasticity of the aged organism. In 16 elderly women and in 14 young controls, the circadian rhythms of plasma melatonin, GH, PRL, ACTH and cortisol, and of oral temperature were simultaneously studied. The plasma cortisol circadian rhythm was also evaluated after DXM administration (1 mg orally at 23:00). The circadian profile of all the bioperiodic functions evaluated was clearly flattened in elderly subjects, and an impairment of the hormonal nocturnal secretion of GH, PRL and melatonin was apparent in elderly subjects when compared to young controls. The plasma ACTH levels throughout the 24-hour cycle were significantly higher in elderly than in young subjects. The cortisol circadian profile exhibited significantly higher values in the evening- and night-time in elderly subjects, compared to young controls; the cortisol nadir values were significantly age-related. A reduction of the sensitivity to DXM inhibition occurred in the elderly group. Both the selective impairment of nocturnal melatonin secretion, and the reduction of hypothalamo-pituitary-adrenal (HPA) sensitivity to steroid feed-back might be considered as markers of aging brain. The neuroendocrine alterations of physiological aging may be ascribable to both the structural and neurochemical changes occurring in the CNS.

Adrenocorticotropic Hormone↗

In vivo evaluation of timing, degree, and distribution of bacterial translocation following experimental small bowel transplantation.

These studies were designed to evaluate the correlation between morphologic and functional changes after heterotopic auxiliary small bowel isograft with systemic venous drainage and two ostomies in 20 Lewis rats. Morphologic damage of the graft was scored by full-thickness biopsies before surgery and 1, 3, 5, and 7 days after transplant. Functional evaluation of the graft was done, at the same time points, by urinary excretion of lactulose and mannitol injected in the proximal ostomy. The intestinal permeability was also studied by injecting Escherichia coli labeled with indium-111 oxine in the proximal ostomy. Translocation of radiolabeled bacteria was quantitated in extraintestinal tissues by radionuclide counts and number of viable organisms and in vivo by scintigraphic imaging. One day after transplant, significant graft damage (score 17.2 +/- 4.2) was observed when compared with the pretransplant value (7.3 +/- 2.6). The degree of tissue injury was similar on days 3 (15.8 +/- 3.5) and 5 (16.1 +/- 3.9) after transplant and remained high on day 7 (11.8 +/- 2.8). The lactulose to mannitol ratio showed a significantly increased permeability on day 1 (17.5) versus pretransplant values (2.6), remained high on day 3 (8.6), and returned to normal values on day 5 (2.8). Translocation of bacteria to distant organs, as measured by both radionuclide counts and number of viable organisms, was strikingly enhanced on day 1 after transplantation, compared with control animals, but returned to the pretransplant value on day 3. A good qualitative and quantitative correlation was observed between radionuclide counts in the extraintestinal organs and in vivo images obtained by scintigraphic scanning. In conclusion, in this model, timing and degree of bacterial translocation do not seem to correlate well, with the exception of the acute post-transplantation phase, with morphologic and permeability changes of the graft. Evaluation of translocation by scintigraphic imaging appears a suitable approach to study in vivo the kinetics and distribution of this process.

Animals↗

Determination of diltiazem and its main metabolites in human plasma by automated solid-phase extraction and high-performance liquid chromatography: a new method overcoming instability of the compounds and interference problems.

An automated sample preparation method, based on solid-phase extraction (SPE) was developed on an ASPEC-Gilson device and combined with HPLC for the determination of diltiazem and three of its metabolites in human plasma (N-desacetylmonodesmethyldiltiazem, N-monodesmethyldiltiazem, O-desacetyldiltiazem). A 1-ml volume of plasma is diluted with 0.5 ml of 0.1 M ammonium dihydrogen phosphate and the sample is automatically loaded onto a SPE silica (C18) column (100 mg); the column is flushed with two different solvents, then eluted with 0.5 ml of a 0.1 M ammonium dihydrogen phosphate-acetonitrile mixture (20:80, v/v) containing 0.06% of triethylamine. The eluate is evaporated to dryness and the residue reconstituted with a suitable solvent and injected onto a C8 silica column connected to a UV detector (lambda = 238 nm). This method overcomes problems caused by the partial instability of diltiazem and metabolites in human plasma during analysis. There is no chromatographic interference from endogenous compounds. The limits of quantitation (LOQ) are 2.5 and 2 ng ml-1 for diltiazem and the metabolites in human plasma, respectively. Linearity between concentrations and detector response for diltiazem and metabolites ranged from 10-200 and 5-100 ng ml-1 in human plasma, respectively. The method has been validated.

Acetylation↗

Memory functions and temporal-limbic morphology in schizophrenia.

Several psychopathological and morphological studies support the hypothesis of temporal-limbic involvement in the pathophysiology of schizophrenia. In the present study, magnetic resonance imaging was used to evaluate the areas of the temporal lobes and related structures in 18 schizophrenic patients and 18 normal control subjects who were homogeneous for sex and age. The Wechsler Memory Scale was used to assess the memory functions of all subjects. Although the MRI data did not reveal any significant differences between the two groups, the Wechsler Memory Scale indices of memory functions showed significant differences between the schizophrenic patients and the control subjects.

Adult↗

EEG power modifications in panic disorder during a temporolimbic activation task: relationships with temporal lobe clinical symptomatology.

Computerized EEG activity derived from the temporal lobes was investigated in normal subjects and panic disorder patients with and without depersonalization and/or derealization, in a resting condition and during an odor stimulation task. Panic patients without depersonalization or derealization showed an increase of fast and a decrease of slow activities independent of odor stimulation. Panic patients with depersonalization and/or derealization showed an increase of slow activity and bilateral lack of responsiveness in the fast alpha frequency band during odor stimulation. Findings suggest there are different EEG patterns in the temporal regions of the two different groups of panic patients during rest and activating conditions.

Adult↗

Factor analysis and computerized EEG: preliminary data on schizophrenic patients.

Factor Analysis can extract salient features from EEG data and reduce redundancy of multi-channel computerized EEG data. A 16-channel computerized frequency analysis of background brain electrical activity during 3 functional conditions (eyes closed, eyes open and hyperventilation) was carried out in two groups, fifty healthy subjects and twenty-three schizophrenics. The power log-transformed relative values of normal subjects and schizophrenic patients were submitted to Factor Analysis and the resulting factor scores were compared. Schizophrenics showed EEG abnormalities in delta 2, theta 1 and alpha 2 bands for the first factor, accounting for the eyes closed condition, and in theta 2 and beta 2 bands for the second factor, accounting for the eyes open condition. This preliminary study demonstrates the utility of Factor Analysis in managing and comparing computerized EEG data.

Adult↗