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Biomedical subjects

M Barbieri

Publications and source records attributed to M Barbieri.

At least 55 records · Page 3Linked to original sources
PubMed2001

Depression of windup of spinal neurons in the neonatal rat spinal cord in vitro by an NK3 tachykinin receptor antagonist.

The effects of the NK3 tachykinin receptor antagonist SR 142801 on synaptic transmission and spike windup induced by trains of stimuli applied to a dorsal root were investigated with intra- and extracellular recording from the neonatal rat spinal cord in vitro. SR 142801 (10 microM) reduced the depolarization (recorded from lumbar ventral roots) induced by senktide (an NK3 agonist) more strongly than the one evoked by substance P methyl ester (SPMeO; an NK1 agonist). Nevertheless, after a long (>2 h) application time, SR 142801 largely depressed the response to SPMeO as well. When NK1 or NK3 receptors were blocked by >50% in the presence of SR 142801, there was also a significant reduction in the cumulative depolarization induced by repeated stimuli to a single dorsal root. This blocking action by SR 142801 was also observed in the presence of the N-methyl-D-aspartate (NMDA) receptor antagonist D-aminophosphonovalerate (APV) and the calcium channel blocker nifedipine. Intracellular data from lumbar motoneurons showed that the spike windup was the first and most sensitive target for the SR 142801 blocking effect. Increasing stimulus strength to dorsal root fibers could partly surmount such a block. SR 142801 per se had no direct action on fast synaptic transmission, membrane potential, or input resistance. These findings indicate that SR 142801 could lead to an early, large reduction in the windup of action potential discharge by motoneurons, suggesting its ability to suppress the reflex component of central sensitization evoked by repeated dorsal root stimuli.

Action Potentials↗
PubMed2001

Inverse association between free insulin-like growth factor-1 and isovolumic relaxation in arterial systemic hypertension.

Several trials have suggested that insulin-like growth factor-1 (IGF-1) may have a pathophysiological role in the development of arterial essential hypertension. To verify the possible association of IGF-1 with left ventricular morphological and functional echocardiographic parameters in hypertension, we studied 40 male patients with newly diagnosed hypertension and 15 normotensive control subjects. Doppler echocardiography was performed and circulating free IGF-1 levels were determined in all subjects. Circulating free IGF-1 levels were higher in hypertensives than in control subjects (P<0.01). A significant inverse correlation was observed between free IGF-1 and isovolumic relaxation time in the overall population (r=-0.37, P<0.01) and in hypertensives (r=-0.57, P<0.0001), whereas this relation disappears in normotensives. These results were confirmed by multivariate analysis. The present study confirms that arterial essential hypertension represents a clinical condition associated with an increased synthesis of IGF-1. The observation of an inverse, independent association between free IGF-1 and isovolumic relaxation time suggests 2 alternative hypotheses: a possible beneficial effect of IGF-1 to diastolic relaxation or a resistance to IGF-1 in hypertension.

Adult↗
PubMed2001

Presence of autoantibodies in the sera of Meniere's disease.

We examined the sera of patients with Meniere's disease for the presence of antibodies against 8 inner ear antigens by enzyme-linked immunosorbent assay (ELISA). One hundred eight patients with Meniere's disease and 28 control subjects were studied. The antibodies against chicken type II collagen, bovine type II collagen, the cyanogen bromide cleaved peptide 11 (CB11) of each, type IX and XI collagens, C-Raf, and tubulin were measured by ELISA. The sensitivity of each antigen was between 37% and 60% individually, and was 91% when all 8 inner ear antigens were combined. These results showed that 91% of Meniere's disease sera have antibody activities to 1 or more of these inner ear antigens. The results suggest that performing ELISA for these 8 inner ear antigens was useful as a diagnostic tool for Meniere's disease. Further study is required for elucidating the role of these antigens in the pathogenesis of Meniere's disease, which might eventually result in better therapy.

Autoantibodies↗
PubMed2001

Oral administration of collagen conjugated with cholera toxin induces tolerance to type II collagen and suppresses chondritis in an animal model of autoimmune ear disease.

B10.RIII (H-2r) mice were orally administered cyanogen bromide peptide 11 (CB11) or cholera toxin B (CTB)-conjugated CB11 to induce tolerance in collagen-induced autoimmune ear disease. Oral administration of a high dosage of CB11 provided partial protection from chondritis. However, administration of a tiny amount of CTB-CB11 conjugate effectively suppressed chondritis. Oral administration of CTB-CB11 conjugate did not alter the stimulation of T cells in vitro or the fine specificities of B cells. The oral administration of CTB-CB11 caused a higher level of type II collagen-specific IgG and its subclass. Interestingly, increases of TH1 cytokine (interferon-gamma) in Peyer's patches and of TH1/TH2 cytokines (interleukin-2 and interleukin-4) in lymph nodes were detected in mice that had been fed CTB-CB11. An increase of CD8+ T cells in the Peyer's patches with a decrease of CD8+ T cells in lymph nodes was seen in mice that had been fed CTB-CB11. These results suggest that protection from chondritis by oral administration of minute amounts of CTB-CB11 conjugate can be achieved by a mechanism distinct from that of conventional oral tolerance induction.

Administration, Oral↗
PubMed2001

The BB-paraoxonase genotype is associated with impaired brachial reactivity after acute hypertriglyceridemia in healthy subjects.

The possible relationship between paraoxonase (PON) gene polymorphism and brachial reactivity in healthy adult subjects in the presence of acute hypertriglyceridemia (HT), as a prooxidant factor, was investigated. In 101 healthy subjects the response to flow- induced vasodilatation was measured before and after Intralipid infusion. In the same subjects the A/B PON polymorphism was detected. The frequency was 0.545 for AA genotype, 0.356 for the AB genotype, and 0.099 for the BB genotype. At baseline all genotype groups had a similar increase in brachial artery diameter and flow. After Intralipid infusion, subjects sharing the BB genotype had a significant decrease vs. baseline values in changes in brachial artery diameter (P for trend < 0.001 vs. the other genotypes), but not in flow. In a subgroup of 55 subjects distributed among the 3 PON genotypes the same study protocol was repeated by buccal nitroglycerine administration to study the endothelium-independent vasodilatation. Again, subjects with the BB genotype had the worse vasodilation (P for trend < 0.001). Furthermore, subjects sharing the BB genotype had the lowest endothelium-independent and -dependent changes in diameter (P for trend < 0.001 vs. the other genotypes) independently of gender ratio, basal plasma triglycerides concentrations, and changes in plasma triglycerides concentrations. In conclusion, our study demonstrates that transient HT decreases vascular reactivity more in subjects with the PON BB genotype than in those with the other PON genotypes.

Adult↗
PubMed2001

Absence of mutations involving the LIM homeobox domain gene LHX9 in 46,XY gonadal agenesis and dysgenesis.

The etiology of most cases of 46,XY gonadal dysgenesis in the absence of extragenital anomalies is not accounted for by mutations in the genes known to date to be involved in sex determination. We have investigated the possibility that mutations in the gene LHX9, whose murine ortholog causes isolated gonadal agenesis when inactivated, might be responsible for gonadal dysgenesis and agenesis in humans. We isolated a human LHX9 complementary DNA (cDNA), mapped the gene to the long arm of human chromosome 1, and determined its genomic structure. We found that LHX9 is highly conserved between species, sharing in particular over 98% amino acid identity. A mutational screen was performed in a sample of patients with a range of gonadal maldevelopment, including bilateral gonadal agenesis in two sisters with an opposite sex karyotype. We did not detect mutations in the open reading frame of LHX9 in the patients studied. However, the extent of between-species structural conservation suggests that LHX9 deserves further consideration as a determinant of gonadal function in humans.

Amino Acid Sequence↗
PubMed2001

Role of free fatty acids on cardiac autonomic nervous system in noninsulin-dependent diabetic patients: effects of metabolic control.

Decreased heart rate variability (HRV) is a risk factor for cardiovascular mortality. Elevated plasma free fatty acid (FFA) levels decrease HRV in healthy subjects. Thus, we investigated the effect of changes in plasma FFA levels on HRV, in non-insulin-dependent diabetes (NIDDM) patients. Thirty NIDDM patients free from diabetic neuropathy volunteered for a study made by two phases. In study A, changes in HRV along a 10% lipid emulsion infusion + heparin (n = 15) or saline infusion (control study; n = 15) were investigated. In study B, all patients (n = 30) underwent further determination of HRV after 3 months of improved metabolic control achieved by intensified insulin treatment. In study A, lipid emulsion infusion increased plasma FFA (P < 0.001) and catecholamine concentrations (P < 0.005), mean arterial blood pressure (P < 0.005), low frequency/high frequency (LF/HF) ratio (P < 0.001). Delta plasma FFA levels correlated with delta LF/HF ratio (r = 0.57; P < 0.02). Along with saline infusion, metabolic and cardiovascular parameters remained unchanged throughout the test. In study B, improved metabolic control lowered fasting plasma glucose (P < 0.005), FFA (P < 0.001), norepinephrine (P < 0.02), epinephrine (P < 0.04), and glycosylated hemoglobin levels (P < 0.001), mean arterial blood pressure(P < 0.05), and LF/HF ratio (P < 0.001). Again percent decline in plasma FFA correlated with the percent change in LF/HF ratio (r = 0.72; P < 0.001). In a multivariate analysis, percent changes in LF/HF ratio were associated with percent changes in plasma FFA independently of gender and percent changes in body mass index, waist/hip ratio, plasma norepinephrine, epinephrine, glycosylated hemoglobin, and daily insulin therapy. Our study demonstrates that changes in plasma FFA levels may have a parallel effect on cardiac sympathetic/parasympathetic nervous system balance in NIDDM patients.

Autonomic Nervous System↗
PubMed2001

[Nursing diagnoses in women attending a family planning service].

The purpose of this study was to identify nursing diagnoses in women enrolled in a family planning program. An instrument of data collection was elaborated according to the Functional Health Patterns. The sample consisted of 100 adult women. Forty-nine nursing diagnoses, of which 9 with a frequency equal or higher to 45.0% were identified. Further studies are still needed in institutions that offer assistance in the area of family planning in order to examine if the nursing diagnoses found in these women can be generalized to the population.

Adult↗
PubMed2001

Oxidative stress and a thrombophilic condition in alcoholics without severe liver disease.

BACKGROUND AND OBJECTIVES: The degree of oxidative stress and its association with a thrombophilic condition, if any, were investigated in alcoholics before the onset of severe liver disease. DESIGN AND METHODS: Reactive oxygen species and total antioxidant capacity were evaluated using two new kinetic spectrophotometric methods in a selected group of 45 consecutive chronic alcohol abusers and 42 apparently healthy moderate drinkers, used as controls. The hemostatic system was explored by detecting the plasma levels of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT) with enzyme-linked immunosorbent assays, while D-dimer plasma levels were measured with a turbidimetric immunoassay. RESULTS: Reactive oxygen species were significantly higher (p<0.001) in heavy drinkers than in controls: 328.1 (143.4-847.2) U.CARR vs 250 (200.7-366.8) U.CARR, respectively. The total antioxidant capacity was similar in chronic alcohol abusers and in moderate drinkers: 360.2 (336.8-374.4) microMol HClO/mL vs 369 (362-378.4) microMol HClO/mL, respectively. All molecular markers of hemostatic system activation were significantly increased in chronic alcohol abusers in comparison with those in moderate drinkers, as follows: TAT: 2.5 (1.4-13) microg/L vs 1.5 (1-4.1) mocrog/L, respectively (p<0.001); F1+2: 1.7 (0.5-5.2) nMol/L vs 0.9 (0.4-1.1) nMol/L, respectively (p<0.01); D-dimer: 235.5 (208-462) ng/mL vs 163.5 (71-233) ng/mL, respectively (p<0.001). INTERPRETATION AND CONCLUSIONS: Our results suggest that oxidative stress and a thrombophilic condition can be observed in heavy drinkers without severe liver disease. The new test available for measuring reactive oxygen species in serum proved to be reliable and useful as an early marker of tissue damage.

Adult↗
PubMed2001

Voltage-dependent antagonist/agonist actions of taurine on Ca(2+)-activated potassium channels of rat skeletal muscle fibers.

Emerging evidence supports the idea that taurine exerts some of its actions through inhibition of inward rectifier K(+) channels, ATP-sensitive K(+) channels, and voltage-dependent K(+) channels. However, to date not much is known about the effects of this sulfonic amino acid on Ca(2+)-activated K(+) (K(Ca(2+))) channels, which are widely expressed in various tissues, including skeletal muscle. In the present work, the effects of taurine on K(Ca(2+)) channels of rat skeletal muscle fibers were investigated using the patch-clamp technique. The application of the amino acid to the internal side of the excised macropatches induced a dose-dependent decrease in the outward K(Ca(2+)) currents recorded at positive membrane potentials in the presence of 8 to 16 microM concentrations of free Ca(2+) ions in the bath with an IC(50) of 31.9. 10(-3) +/- 1 M (slope factor = 1.2) (n = 11 patches). In contrast, at negative membrane potentials taurine caused an enhancement of the muscular inward K(Ca(2+)) currents with a DE(50) (drug concentration needed to enhance the current by 50%) of 46.7. 10(-3) +/- 2 M (slope factor = 1.3) (n = 9 patches). Single channel analysis revealed that this effect was mediated by changes in the reversal potential of the K(Ca(2+)) channel for K(+) ions with no changes in the gating properties or in the sensitivity of the channel to Ca(2+) ions. Taurine also did not affect the single channel conductance. In conclusion, taurine shows a voltage-dependent dualistic action on K(Ca(2+)) channels, being an inhibitor of the channel at positive membrane potentials and an activator at negative membrane potentials.

Animals↗
PubMed2001

[Delayed diagnosis of benign paroxysmal vertigo: economic impact].

Some time has passed since the early 1980's when a group of vestibologists with the same singular passion introduced in Italy the concept of Paroxysmal Positional Vertigo (PPV). Since then great advances have been made, but, despite the energy focused on improving and expanding the knowledge on this common disorder, PPV still frequently goes unrecognized. The direct consequence of delayed diagnosis is prolonged patient discomfort and the execution of useless, costly clinical examinations. Today, in most cases, delayed diagnosis is unjustified. Within the modern concept of health care economics, such delay is costly to the health care provider and has obvious psycho-physical repercussions for the patient who has to undergo a fruitless series of examinations and treatments of all types without reaping any benefits. In this light the Authors have performed a study to identify and quantify the relative costs of the most common errors made in the diagnosis of PPV. For a sample population of 100 patients, the clinical-instrumental tests performed before the disorder was correctly diagnosed were gathered and analyzed. Then the costs for the management of PPV patients diagnosed late were compared with those for patients whose diagnosis was reached early on. The results indicate that for each delay in PPV diagnosis the average cost was Euro 317.66 vs. Euro 64.04 for early diagnosis: a difference of Euro 253.06. The Authors underline how in this brief period of time (March-September 2000) the prescription of excessive testing led to a significant waste of money (Euro 10137.01).

Adult↗
PubMed2000

The human doublesex-related gene, DMRT2, is homologous to a gene involved in somitogenesis and encodes a potential bicistronic transcript.

Intense efforts are currently being pursued to identify autosomal genes associated with 46,XY male-to-female sex reversal. The genes DMRT1 and 2 are located on distal 9p, a region deleted in 46,XY sex-reversed patients. They are considered excellent candidates because of their homology to regulators of sex development in invertebrates. We present the genomic structure of DMRT2, showing that it generates several transcripts with distinct coding potential. In addition to the previously reported 226-amino-acid protein-encoding transcript, we describe other mRNA isoforms that are potentially bicistronic and are predicted to encode an additional 328-amino-acid polypeptide. Finally, a stop codon-containing exon (exon 4) can be skipped by alternative splicing and can generate a transcript that is predicted to encode a fusion protein. The latter shares 58% amino acid identity with a gene recently described in fish, termed terra. Differences in expression pattern exist for DMRT2 mRNA isoforms among the human adult tissues tested, between adult tissues and human embryos, and between DMRT2 and DMRT1 during embryonic development. We failed to detect mutations by sequencing of DMRT2 in a sample of 46,XY female patients. The interesting structure of DMRT2 coupled to preliminary functional studies in fish showing that terra is involved in somitogenesis suggests that validation or exclusion of this gene as a cause of sex reversal will require more in-depth investigations.

Adult↗
PubMed2000

Effects of simvastatin and atorvastatin administration on insulin resistance and respiratory quotient in aged dyslipidemic non-insulin dependent diabetic patients.

One hundred and ninety-five aged (mean age: 67+/-4.8 years), non-insulin dependent diabetic patients underwent a randomised single-blind study for investigating the effect of statin administration on insulin resistance and respiratory quotient. After 4 weeks run-in period, all patients were randomised in three groups: placebo (n=67), simvastatin (10 mg/day) (n=61) and atorvastatin (5 mg/day) (n=67). Each treatment period lasted 8 weeks. At the beginning, after the run-in and at the end of the study, insulin resistance was assessed by homeostasis model assessment (HOMA) index, while respiratory quotient (Rq) was evaluated by indirect calorimetry. Statins versus placebo significantly lowered plasma total, LDL-, HDL-cholesterol and triglyceride concentrations and improved insulin resistance and Rq and metabolic control. Atorvastatin had a greater effect than simvastatin on plasma triglyceride concentration (-26.3+/-3.1 vs. -19.7+/-2.8%, P<0.03), HOMA index (-13.1+/-0.6 vs. -9.1+/-0.9%, P<0.05), Rq (5.9+/-0.4 vs. 3.1+/-0.5%, P<0.05) and glycosylated haemoglobin (-11.2+/-0.3 vs. -7. 1+/-0.4%, P<0.05). In the whole group of subjects (n=195) and at the end of the study, changes in plasma triglyceride concentrations were significantly correlated with the change in the HOMA index (r=0.44, P<0.001) and age and BMI adjusted-Rq (r=-0.32, P<0.005). Multivariate analyses demonstrated that decline in plasma triglyceride concentration was a significant determinant for explaining the effect of statin on insulin resistance and Rq. In conclusion our study demonstrates that statin administration is useful for controlling dyslipidemia in NIDDM patients and for improving the metabolic control. With regard to this latter aim, atorvastatin seems to be more powerful than simvastatin.

Aged↗
PubMed2000

Taurine blocks ATP-sensitive potassium channels of rat skeletal muscle fibres interfering with the sulphonylurea receptor.

Taurine is a sulphonic aminoacid present in high amounts in various tissues including cardiac and skeletal muscles showing different properties such as antioxidative, antimyotonic and anti-schaemic effects. The cellular mechanism of action of taurine is under investigation and appears to involve the interaction of the sulphonic aminoacid with several ion channels. Using the patch-clamp technique we studied the effects of taurine in rat skeletal muscle fibres on ATP-sensitive K(+) channel (K(ATP)) immediately after excision and on channels that underwent rundown. The cytoplasmic application of 20 mM of taurine reduced the K(ATP) current; this effect was reverted by washout of the drug solution. In this experimental condition the IC(50) was 20.1 mM. After rundown, taurine inhibited the K(ATP) current with similar efficacy. Competition experiments showed that taurine shifted the dose-response inhibition curve of glybenclamide to the left on the log-dose axis without significantly affecting those of ATP or Ca(2+) ion. Single channel recording revealed that taurine affects the close state of the channel prolonging it and reducing the bursts duration. Our data indicate that taurine inhibits the muscular K(ATP) channel interfering with the glybenclamide site on the sulphonylurea receptor of the channel or on the site allosterically coupled to it. During ischaemia and hypoxia, the skeletal and heart muscles undergo several changes; for example, the activation of K(ATP) channels and loss of the intracellular taurine content. The depletion of taurine during ischaemia would contribute to the early activation of K(ATP) channels and salvage the intracellular ATP content.

ATP-Binding Cassette Transporters↗
PubMed2000

Effects of insulin on the cardiac autonomic nervous system in insulin-resistant states.

The effects of insulin infusion on cardiac autonomic nervous system (ANS) activity were investigated in healthy subjects (n=15) and in patients with various types of insulin-resistance, such as obese subjects (n=20) and those with hypertension (n=15) or type II (non-insulin-dependent) diabetes (n=22). Healthy subjects and patients underwent euglycaemic hyperinsulinaemic glucose clamp, and cardiac ANS and haemodynamic changes were investigated by continuous recording of heart rate variability by the Holter technique and by venous occlusion plethysmography respectively. At baseline, healthy subjects had the highest values for total spectral power and the low-frequency (LF) component, and the lowest value for the high-frequency (HF) component. In the pooled data (n=72), the fasting plasma insulin concentration was correlated with baseline total spectral power (r=-0.37; P<0.001) and the LF/HF ratio (r=-0. 35; P<0.003). Such correlations were still significant (P<0.01 for both) after adjustment for body fat and mean arterial blood pressure. In a multivariate linear stepwise analysis (n=72), a model including body fat, waist/hip ratio, fasting plasma glucose concentration and insulin-mediated glucose uptake explained 47% of the variability of the change in the LF/HF ratio, with body fat (t=-3.11; P<0.01) and insulin-mediated glucose uptake (t=-3.48; P<0. 008) being significantly and independently associated with insulin-mediated changes in the LF/HF ratio. Insulin infusion reduced the total spectral power and increased the LF/HF ratio in healthy subjects, but not in insulin-resistant patients. In conclusion, our study demonstrates that insulin fails to stimulate cardiac ANS activity in insulin-resistant patients, independently of the causes of insulin resistance.

Analysis of Variance↗
PubMed2000

Effects of glucose ingestion on cardiac autonomic nervous system in healthy centenarians: differences with aged subjects.

BACKGROUND: Spectral analysis of heart rate variability (HRV) investigates the cardiac autonomic nervous system (ANS) activity. In particular, low frequency/high frequency (LF/HF) is considered an index of cardiac sympatho-vagal balance and is stimulated by glucose ingestion in healthy subjects. No studies have evaluated the effect of glucose ingestion on cardiac ANS in centenarians. MATERIALS AND METHODS: In 30 healthy centenarians (HC) and 25 aged subjects (AS) power spectral analysis of HRV was investigated during an oral glucose ingestion. RESULTS: Glucose ingestion rose LF/HF ratio in both groups studied. Such stimulatory effects were restrained to the first 60 min of the study. Independent of age, gender, body mass index (BMI) and fasting plasma norepinephrine and FT3 concentrations, HC had basal total power (1318 +/- 546 vs. 1918 +/- 818 msec2, P < 0.01), lower low frequency (LF) (33 +/- 21 vs. 50 +/- 11 n.u., P < 0. 03), and higher high frequency (HF) (74 +/- 18 vs. 43 +/- 15 n.u., P < 0.05) than AS. Consequently, LF/HF ratio (0.43 +/- 0.07 vs. 0.91 +/- 0.05, P < 0.02) was also lower in HC than in AS. In AS, but not in HC, the baseline LF/HF ratio correlated significantly with BMI (r = 0.48, P < 0.01), waist-hip-ratio (WHR) (r = 0.45, P < 0.02), fasting plasma insulin (r = 0.49, P < 0.01) and norepinephrine (r = 0.57, P < 0.02) concentration. Glucose ingestion was associated with a significant rise in LF/HF ratio in both groups studied but per cent changes in glucose mediated stimulation of LF/HF was lower in HC than in AS. In a control study, water administration did not affect power spectral parameters of HRV. CONCLUSION: Our study demonstrates that basal- and glucose-stimulated LF/HF, an indirect index of cardiac sympatho-vagal balance, are lower in HC than in AS.

Aged↗
PubMed2000

Metabolic age modelling: the lesson from centenarians.

Evolutionary theories of ageing, and data emerging from cellular and molecular biology of ageing, suggested that animals and humans capable of reaching an age close to the extreme limit of the life span should be equipped with a very efficient network of anti-ageing mechanisms. Indeed several evidences have demonstrated that starting from young to very old subjects, ageing is associated with a progressive remodelling. Thus, a new paradigm, the remodelling theory of age, was proposed. This theory, focusing on the human immune system, suggested that immunosenescence is the net result of the continuous adaptation of the body to the deteriorative changes occurring over time. According to this hypothesis, body resources are continuously optimized, and immunosenescence must be considered a very dynamic process including both loss and gain. Whether the metabolic pathways and the endocrine functions are also part of the age remodelling is not investigated. The aim of this review is to focus on the age-related changes in metabolic pathways and endocrine functions and to demonstrate that healthy centenarians (HC) represent the best living example of successful age-remodelling in whom the age remodelling has occurred without problems. In order to design the clinical picture of such successful ageing, anthropometric, endocrine and metabolic characteristics of healthy centenarians (HC), compared with aged subject, have been outlined.

Aged↗