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Biomedical subjects

M Fioravanti

Publications and source records attributed to M Fioravanti.

At least 37 records · Page 2Linked to original sources

Variability of interactions between neuroendocrine and immunological functions in physiological aging and dementia of the Alzheimer's type.

A link between neuroendocrine and immunological changes has been suggested in the pathophysiology of dementia of the Alzheimer's type (DAT). Healthy young and old subjects and patients with DAT were recruited to evaluate the chrononeuroendocrine organization of cortisol, GH, and melatonin (MLT) secretions. The study was carried out together with the evaluation of natural killer (NK) cell function: cytotoxic activity (NKCC) and TNF-alpha and IFN-gamma release after exposure to IL-2 (100 U/mL). Moreover, a cerebral morphometric analysis of hippocampus and temporal lobe (MRI) was performed. The activation of hypothalamo-pituitary-adrenal (HPA) axis and the decrease of GH, and MLT nocturnal peaks were associated with normal NKCC and TNF-alpha/IFN-gamma in healthy elderly subjects, whereas in DAT patients the same neuroendocrine changes occurred together with abnormal NKCC (spontaneous and IL-2/IFN-beta-modulated) and with alterations of TNF-alpha/INF-gamma generation from NK. Moreover significant correlations among the increase of NKCC and TNF-alpha and the decrease of cognitive function were found in the DAT group. These correlations were associated with the impairment of nocturnal GH and MLT levels and with the relatively higher serum cortisol concentrations. Moreover, the impairment of cortisol suppression after dexamethasone (1 mg orally at 23:00) was significantly correlated with the increase of spontaneous release of TNF-alpha and with IL-2-modulated NKCC. Finally the imunoneuroendocrine alterations found in DAT were associated with the reduction of cerebral volume in hippocampus and temporal lobes. Taken together these data indicate that the immunoneuroendocrine balance is maintained in physiological aging, whereas NK immune dysregulation in DAT could contribute to altering the neuroendocrine functions and to extend the progression of neurodegeneration and dementia.

Adolescent↗

Menopause and estrogen deficiency as a risk factor in dementing illness: hypothesis on the biological basis.

The positive efficacy of estrogen replacement therapy (ERT) in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD) is a matter of intense debate among clinicians and neuroscientists. The experimental and preliminary clinical evidence supporting the use of ERT are based on epidemiological data and on the study of the effect of estrogens on several aspects of brain homeostasis, including the modulation of neurotransmitters and vascular changes. In spite of numerous data available the mechanisms underlying the putative estrogen effects in neurodegenerative diseases are largely unknown. The aim of this paper is to discuss and elaborate on some of the hypotheses and controversial findings currently present in this field.

Alzheimer Disease↗

Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity.

OBJECTIVES: Insulin-resistance syndrome and hyperinsulinaemia are linked with cardiovascular disease (CVD) in the obese population. In particular, cardiovascular risk is more frequent in central obesity and is associated with microalbuminuria (MA). MA and changes of glomerular permeability to proteins in obesity might be related with renal haemodynamic modifications (that is glomerular hyperfiltration). Since glucagon is physiologically involved in renal haemodynamic regulation, the purpose of this study was to examine whether changes of circulating glucagon levels might haemodynamically induce MA and proteinuria in patients with central obesity. SUBJECTS: Forty normotensive obese out-patients, 22 with central (CO group) and 18 with peripheral (PO group) body fat distribution and 11 healthy subjects. MEASUREMENTS: Serum insulin and glucagon concentrations (fasting and after oral glucose tolerance test (OGTT)) by radio immuno assay (RIA); glomerular filtration rate (GFR, isotopic); total clearances and urinary excretion rates of albumin (AER), IgG (IgGER) and alpha1 microglobulin (computerized immunonephelometry). RESULTS: GFR and insulin concentrations (fasting and during OGTT) were higher in the CO than the PO group. Fasting glucagon concentrations were increased, and not physiologically suppressed during OGTT in patients with CO (fasting, P<0.05; OGTT 60 and 120 min, P<0.001 vs PO group). Moreover, glucagon concentrations were significantly correlated with GFR in the CO group (fasting, r=0.49, P<0.05; 60 min after OGTT, r=0.58, P<0.01); whereas no correlations were found in the PO group. Higher AER (P<0.001), IgGER (P<0.001) and alpha1 microglobulin (P<0.05) urinary concentrations were found in patients with CO than in the PO group. CONCLUSIONS: The increase of serum glucagon concentrations may be associated with the enhancement of GFR in patients with central obesity. Glomerular hyperfiltration might influence the development of MA and of proteinuria by means of a haemodynamic mechanism so contributing to increase the risk of renal microvascular complications and of CVD in central obesity.

Adult↗

Dehydroepiandrosterone sulfate enhances natural killer cell cytotoxicity in humans via locally generated immunoreactive insulin-like growth factor I.

Experimental and clinical investigations suggest the hypothesis that dehydroepiandrosterone sulfate (DHEAS) can positively influence natural killer (NK) immunity via locally produced insulin-like growth factor I (IGF-I) from NK cells. In the present study, the NK cell cytotoxicity (NKCC) and IGF-I levels in the supernatant of NK cells were studied at baseline and after exposure to various molar concentrations of DHEAS (from 10(-5)-10(-8) mol/L x mL/7.75 x 10(6) NK cells) in healthy subjects of young and old age. DHEAS-induced NKCC was also determined after DHEAS coincubation with somatostatin-14 (10-6) mol/L x mL/7.75 x 10(6) NK cells) and with interleukin-2 (IL-2; 100 IU/mL x 7.75 x 10(6) NK cells). NK cells were previously isolated by Ficoll-Hypaque density gradient and then by immunomagnetic procedure; the purity obtained was 97 +/- 1%. NKCC was determined against K562 tumoral targets. We observed that the increase in NKCC after DHEAS exposure was dose dependent and was correlated with the amount of IGF-I released in the supernatant of cultured NK cells. NKCC and IGF-I generation from NK cells were more elevated in healthy elder subjects than in healthy young subjects. The coincubation of DHEAS with somatostatin-14 significantly suppressed NKCC and IGF-I release from NK in both groups, whereas higher NKCC was found after DHEAS plus IL-2 exposure than after incubation with DHEAS alone. Taken together, this study suggests a role for NK-generated IGF-I in the modulation of NKCC by DHEAS in humans. Although DHEAS may contribute to the IL-2-mediated NKCC, its activity on NK cytolytic function can be dependent on a autocrine mechanism (IGF-I-mediated), probably independent of cytokine activation. The higher NKCC response to DHEAS found in old subjects than in younger might counterbalance the age-dependent decline in circulating DHEAS, thus contributing to maintain the pattern of NK immunity during aging.

Adult↗

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↗

Circadian neuroendocrine functions in disorders of eating behavior.

Eating behavior is a complex function determined by regulatory mechanisms characterized by bioperiodic fluctuations. It involves the hypothalamus as well as the related higher centers in the central nervous system (CNS). Many hormones, neurotransmitters and neuropeptides play an important role in the synchronization of food intake. Our study therefore sets out to evaluate the circadian rhythms of several endocrine functions in women with eating disorders, to clarify the pathophysiology of the limbic-hypothalamic system. We measured the circadian rhythms of plasma melatonin, serum cortisol, growth hormone (GH) and prolactin (PRL) in 26 patients with anorexia nervosa (AN), 27 with primary obesity (OB) and 7 with bulimia nervosa (BN). Simultaneous evaluation of different neuroendocrine rhythms in these three groups revealed similar circadian abnormalities, (namely daytime persistence of melatonin secretion in AN and OB, and similar cortisol profile changes in AN and BN), together with evidence of internal desynchronization among the different bioperiodic functions. These findings suggest that some changes of the central pathways involved in the control of eating, mood and endocrine functions are common to dissimilar kinds of eating disorders.

Adult↗

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↗

Biomechanical and hydraulic determinants of tree structure in Scots pine: anatomical characteristics.

The development of anatomical, hydraulic and biomechanical properties in Scots pine (Pinus sylvestris L.) stems aged 7 to 59 years was followed. The hydraulic diameter and length of tracheids increased with age to a maximum at 15 and 35 years, respectively. Number of tracheids per unit of sapwood area decreased with age to a minimum of 500-600 tracheids mm(-2). Variations in specific hydraulic conductivity and Young's modulus of stems were associated with variation in anatomical properties. Over the time sequence considered, hydraulic and mechanical properties were positively related to each other and followed a similar developmental pattern, with no suggestion of a trade-off between the two. For most of the tree's life-cycle, heartwood made only a small contribution to whole-section mechanical stiffness because of its location close to the flexural neutral axis, and because of the presence of juvenile wood.

Journal Article↗

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↗

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↗

The relevance of continuous blood pressure monitoring in examining the relationship of memory efficiency with blood pressure characteristics.

The study of the relationship between hypertension and cognitive decline is characterized by various difficulties of realization and, as a consequence, by incongruent results. One of the reasons for these difficulties may be explained by the occasional method of measurement of blood pressure (once a day). This study presents the results obtained in 27 normotensive and mild hypertensive subjects of both sexes (ages between 20 and 77 years) with a continuous blood pressure monitoring for 24 h. A noninvasive sphygmomanometric technique was used employing a portable recorder programmed to take a measure every 30 min. Both objective and subjective measures of memory, measures of attention efficiency, and IQ were correlated to the blood pressure measures. Continuous monitoring data of blood pressure were analyzed according to a model that included a macroscopic descriptive analysis, a microscopic rhythmometric analysis, and a microscopic integrative analyses where the effects of the interaction between level and duration of excess and the time of the day when the excess eventually appeared were considered. Results evidenced no differences in cognitive efficiency between those subjects identified with the traditional occasional measurement of blood pressure as hypertensives of mild severity and the normal subjects. Cognitive efficiency of our subjects was found correlated, independently from the clinical diagnosis, with the time of peak and with the duration of excess of their blood pressure when the results of the analyses on the continuous monitoring of blood pressure were considered.

Adult↗

Neuroendocrine correlates of the aging brain in humans.

Physiological brain aging is characterized by important biochemical and structural changes and by the unbalance among the different neurotransmitters and neuromodulators. The study of the circadian organization of neuroendocrine functions may be considered a clinically reliable tool to investigate the changes of the CNS and particularly of the limbic-hypothalamic system occurring in aged people. The circadian rhythms of plasma melatonin, ACTH and cortisol and of oral temperature were studied in 16 clinically healthy women aged 66-90 years and in 14 young controls aged 20-30. In addition, the effect of dexamethasone on the plasma cortisol circadian rhythm and the cortisol response to Synacthen pulse intravenous injection were evaluated. All subjects were studied as inpatients, with the same synchronization to the hospital life schedule. When compared with young controls, elderly subjects exhibited a reduction of the mean level and of the amplitude of the circadian rhythm of oral temperature, an increase of the mean level of ACTH and cortisol rhythms and a selective impairment of melatonin nocturnal secretion. Furthermore, elderly subjects showed a reduced sensitivity to the dexamethasone suppression test, by comparison to young controls. These changes were age-related and they may depend either on CNS modification or on alterations of the hormonal metabolic clearance.

Adrenocorticotropic Hormone↗

Forgetting curves in long-term memory: evidence for a multistage model of retention.

An experimental study with 20 normal healthy young adult subjects was performed to evaluate the interaction of type of memory tasks, type of learning modalities, and length of acquisition/recall interval. Four different tasks were employed (serial learning, paired learning, rote learning, and visuolinguistic transfer), some requiring a single trial learning modality others a multitrial learning modality. Acquisition/recall intervals were immediate, intermediate (3 min), and delayed. The experimental design allowed for the comparison of effects from five different delayed recall intervals (2, 8, 12, 24, and 48 hr). Results demonstrated a specific interaction on learning rates due to different ceiling effects for the different types of memory tasks. Forgetting rates, on the other hand, demonstrated a specific effect due to type of memory tasks and learning modalities only for differences between immediate and intermediate recall. These differences remained stable during the longer intervals and were not affected by length of interval. A multistage composition of long-term retention was suggested to explain these results, and a practical indication to build experimental procedures to study memory in the clinical field was evidenced.

Adult↗