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Biomedical subjects

M Masini

Publications and source records attributed to M Masini.

At least 19 recordsLinked to original sources
PubMed2007

Gliclazide protects human islet beta-cells from apoptosis induced by intermittent high glucose.

BACKGROUND: Decreased beta-cell mass, mainly due to apoptosis, is crucial for the development and progression of type 2 diabetes. Chronic exposure to high glucose levels is a probable underlying mechanism, whereas the role of oral anti-diabetic agents (sulphonylureas in particular) is still unsettled. METHODS: To directly investigate more on such issues, we prepared isolated human islets, which were then cultured for 5 days in continuous normal glucose concentration (NG, 5.5 mmol/L) or normal and high (HG, 16.7 mmol/L) glucose levels (alternating every 24 h), with or without the addition of therapeutical concentration (10 micromol L) of gliclazide or glibenclamide. RESULTS: Intermittent high glucose caused a significant decrease of glucose-stimulated insulin secretion, which was not further affected by either sulphonylurea. Apoptosis, as assessed by electron microscopy, was also significantly increased by alternating high glucose exposure, which was accompanied by altered mitochondria morphology and density volume, and increased concentrations of nitrotyrosine, a marker of oxidative stress. Gliclazide, but not glibenclamide, was able to significantly reduce high glucose induced apoptosis, mitochondrial alterations, and nitrotyrosine concentration increase. CONCLUSION: Therefore, gliclazide protected human beta-cells from apoptosis induced by intermittent high glucose, and this effect was likely to be due, at least in part, to the anti-oxidant properties of the molecule.

Antioxidants↗
PubMed2006

[The cardiac natriuretic peptides].

Cardiac natriuretic peptides (including ANP, BNP, CNP and urodilatin) constitute a family of peptide hormones and neurotransmitters, sharing similar chemical structure (characterized by a cysteine bridge) and biological function. ANP and BNP are cardiac hormones because they are principally produced and secreted by cardiomyocytes. CNP is principally produced and secreted by endothelial cells, while urodilatin only by renal tubular cells. Natriuretic peptides share a direct diuretic, natriuretic and vasodilator effect and an inhibitory action on ventricular myocyte contraction as well as on remodeling, restenosis and other inflammatory processes of myocardium and smooth muscle cells. Cardiac natriuretic peptides share their biological action by means of specific receptors (NPR), which are present into the cell membranes of target tissues. Three different subtypes of NPRs have been so far identified in mammalian tissues. NPR-A and NPR-B are generally considered to mediate all known biological actions throughout the guanylate cyclase (GC) intracellular domain, while the third member of the natriuretic peptide receptor family, the NPR-C receptor, has not a GC domain. It is generally thought that the NPR-C is not linked to GC and so serves as a clearance receptor. Natriuretic peptides constitute a family sharing both endocrine. paracrine and autocrine actions and neurotransmitter and immuno-modulator functions. Therefore, it can be hypothesized that the cardiac natriuretic peptide system is closely related with other regulatory systems in a biological hierarchical networks.

Atrial Natriuretic Factor↗
PubMed2005

Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients.

AIMS/HYPOTHESIS: Little information is available on the insulin release properties of pancreatic islets isolated from type 2 diabetic subjects. Since mitochondria represent the site where important metabolites that regulate insulin secretion are generated, we studied insulin release as well as mitochondrial function and morphology directly in pancreatic islets isolated from type 2 diabetic patients. METHODS: Islets were prepared by collagenase digestion and density gradient purification, and insulin secretion in response to glucose and arginine was assessed by the batch incubation method. Adenine nucleotides, mitochondrial membrane potential, the expression of UCP-2, complex I and complex V of the respiratory chain, and nitrotyrosine levels were evaluated and correlated with insulin secretion. RESULTS: Compared to control islets, diabetic islets showed reduced insulin secretion in response to glucose, and this defect was associated with lower ATP levels, a lower ATP/ADP ratio and impaired hyperpolarization of the mitochondrial membrane. Increased protein expression of UCP-2, complex I and complex V of the respiratory chain, and a higher level of nitrotyrosine were also found in type 2 diabetic islets. Morphology studies showed that control and diabetic beta cells had a similar number of mitochondria; however, mitochondrial density volume was significantly higher in type 2 diabetic beta cells. CONCLUSIONS/INTERPRETATION: In pancreatic beta cells from type 2 diabetic subjects, the impaired secretory response to glucose is associated with a marked alteration of mitochondrial function and morphology. In particular, UCP-2 expression is increased (probably due to a condition of fuel overload), which leads to lower ATP, decreased ATP/ADP ratio, with consequent reduction of insulin release.

Adenine Nucleotides↗
PubMed2005

Anatomical description of the facet joint innervation and its implication in the treatment of recurrent back pain.

AIM: Many techniques are used in the back pain treatment, standing out the facet denervation as a therapeutic option for pain that originates in the facet joints. It's known that the facet joint is an abundant area of nocireceptor innervation, although the distribution and the location of the involved branches have not being well demonstrated. A good comprehension about the affected innervation is very important to get an effective treatment. Purpose of study was to describe innervation of the lumbar facet joints, potentially used in the diagnosis and treatment of painful pictures of the lumbar region by facet syndrome. STUDY DESIGN: anatomical study of nerve roots distribution of the facet joint 3 human corpses. The determination of the neurotomy s point was carried out by direct visualization and the radiological study in human parts. METHODS: Three anatomical pieces of the human lumbar spine were dissected. In those 3 pieces, the facet joint innervation distribution was studied thoroughly using surgical microscope and microsurgical technique. In one of the pieces the needles positioning was first made to test through the radiological study the possible application of the precise denervation in low back pain treatment. RESULTS: The L1 to L4 segments, each dorsal branch of root emits a medial branch that emerges from intertransversal ligament. This branch crosses the superior margin of the medial termination of transverse process, passing through the root of the superior articulate process. Each branch innerves the anterior region of the inferior facet and the inferior portion of articulation which one spins around. The L5 dorsal branch was larger than the superior branches. It emerges dorsally and in the inferior region on top of the sacrum wing. This nerve is in the bone fissure of the junction between the wing and the posterior region of the sacrum articular process. Near the inferior portion of the articular process, the nerve ramifies itself in lateral and medial branch. The medial branch comes back around the inferior portion of the lumbar-sacrum articulation that it innervates. CONCLUSIONS: We didn't note great variations in the anatomy from L1 do L4. The L5 segment has a different distribution of the branches that should be considered when we do a percutaneous denervation procedure. The approach of the needle must touch the transverse process and feels the resistance of the articular joint . The determination of the neurotomy s point tends to become more precise denervation procedure.

Back Pain↗
PubMed2001

The incremental prognostic value of pharmacological stress echo over exercise electrocardiography in women with chest pain of unknown origin.

AIMS: The value of exercise electrocardiography in evaluating women with suspected coronary artery disease is limited. Conversely, stress echocardiography is effective for both diagnostic and prognostic purposes in females. The purpose of the study was to determine the relative prognostic value of exercise electrocardiography and pharmacological stress echocardiography in a cohort of women with chest pain of unknown origin, in order to verify whether criteria could be established for the daily non-invasive evaluation of such a low-risk profile population. METHODS AND RESULTS: Exercise electrocardiography and pharmacological stress echocardiography (171 dipyridamole, 73 dobutamine) were performed in 244 women (age 60+/-10 years) with chest pain and known coronary artery disease. A positive result of exercise electrocardiography (ST-segment shift > or =1 mm at 80 ms after the J point) was detected in 95 patients; a positive result of stress echocardiography (new regional wall motion abnormalities) was observed in 33 patients. During follow-up (36+/-18 months), two deaths, five infarctions, seven unstable anginas, and 11 coronary revascularizations occurred. Using Cox analysis, the positive result of stress echocardiography (odds ratio=40.1) alone, was independently related to hard cardiac events (death, infarction). With spontaneous cardiac events (death, infarction, and unstable angina) as end-points, the multivariate prognostic predictors were a positive result of stress echocardiography (odds ratio=37.0), a family history of coronary artery disease (odds ratio=4.1), typical chest pain (odds ratio=3.7), and a positive exercise electrocardiography result with a rate-pressure product < or =20 000 (odds ratio=3.5). By adopting an interactive stepwise procedure, the prognostic value of stress echocardiography was incremental to that of clinical and exercise electrocardiography data. Nevertheless, the negative result of exercise electrocardiography and pharmacological stress predicted a very high and comparable (P=ns) 24-month survival rate when both hard and spontaneous cardiac events were taken as end-points. CONCLUSIONS: In women with chest pain, stress echocardiography is a strong and independent prognostic indicator, incremental to that shown by exercise electrocardiography. However, the two tests have a similar high negative predictive value in this population. Therefore, exercise electrocardiography has to be considered the initial approach and the only test when the result is negative, whereas stress echocardiography is warranted in selected conditions, including those in women with uninterpretable electrocardiograms, those unable to exercise maximally, and those with an ambiguous or ischaemic response to exercise electrocardiography.

Aged↗
PubMed2001

Th2 cytokines have a partial, direct protective effect on the function and survival of isolated human islets exposed to combined proinflammatory and Th1 cytokines.

Studies in rodents have suggested that Th2 and Th3 cytokines can be effective in reducing proinflammatory and Th1 cytokine-induced islet damage. Whether this is the case with human islets and might be due to a direct action of Th2 and Th3 cytokines is not known. In the present study, we evaluated whether Th2 (500 U/ml IL-4 plus 100 U/ml IL-10) or Th3 (5 ng/ml TGF-1beta) cytokines may prevent the derangements induced on isolated human islets by prolonged (12 or 72 h) exposure to combined proinflammatory (50 U/ml IL-1beta, 1000 U/ml TNF alpha) and Th1 (1000 U/ml interferon gamma) cytokines. Compared with control islets, cells preincubated for 12 or 72 h with proinflammatory and Th1 cytokines showed a significant decrease of glucose-stimulated insulin secretion and a significant increase of nitrites production. The addition of IL-4 plus IL-10 or TGF-1beta in the medium prevented these cytostatic effects in the 12-h incubation experiments, but not after the 72-h exposure period. IL-1beta, interferon gamma, and TNF alpha caused no major change in either islet cell survival or Bcl-2 and Bax mRNA expression after a 12-h incubation; however, a marked increase in the amount of dead cells, with a major decrease of Bcl-2 mRNA expression, was observed after 72 h. The presence of Th2, but not of Th3, cytokines significantly reduced beta-cell death, without any major effect on Bcl-2 and Bax mRNA expression. These results suggest that Th2 and (at lower extent) Th3 cytokines may have a partial, direct protective effect on isolated human islets exposed to the cytostatic and cytotoxic action of proinflammatory and Th1 cytokines.

Glucose↗
PubMed2000

[The evaluation of the appropriateness of instrumental exams in cardiology. The case of echocardiography].

BACKGROUND: The aim of this study was to evaluate the appropriateness and utility rates of echocardiograms performed in 309 patients in an outpatient clinical setting. METHODS: Data were collected by means of a questionnaire filled in by the cardiologists who performed the examinations. Appropriateness was evaluated according to international guidelines and scored as class I: appropriate, class II: doubtful appropriateness, class III: inappropriate; the exam was deemed useful if it was able to influence the clinical decision-making; normalcy rate was also checked. The relationship between both the referring physicians and motivation of the exam and its appropriateness, and the relationship between appropriateness and both the normalcy rate and utility of the exam were assessed. RESULTS: An echocardiogram was requested by the cardiologist in 46% of patients; the more common reasons for the exam were arterial hypertension (26%), cardiac murmur (18%), palpitations (15%), and known coronary artery disease (10%). The echocardiogram was appropriate (class I) in 25% of patients, doubtfully appropriate (class II) in 39% of patients and inappropriate (class III) in 36% of patients. The appropriateness rate between the cardiologists was similar to that of other prescribing clinicians (p = NS). The highest class III rate was found in patients with hypertension, while the highest class I rate was found in patients with a cardiac murmur (p < 0.01). Normalcy rate was lower in class I than in class II and III exams (p < 0.001). The utility rate was higher in class I (76%) than in class II (13%) and III (< 1%) exams (p < 0.01). CONCLUSIONS: International guidelines can be used effectively and safely to identify (not to prescribe) the useless echocardiograms.

Chi-Square Distribution↗
PubMed1999

The clinical impact of dynamic intraventricular obstruction during dobutamine stress echocardiography.

We selected 73 consecutive patients without myocardial-infarction, hypertrophic cardiomyopathy or hypertension complaining of effort chest discomfort/dyspnoea, and/or reporting exercise ischaemic ECG changes, and submitted them to simultaneous dobutamine stress echocardiography (DSE) and 99mTc tetrofosmin SPECT (T SPECT) and to coronary angiography to evaluate the clinical impact of intraventricular obstruction (IVO) during dobutamine infusion. Sixteen patients (22%, 7 males, mean age+/-SD 63+/-8 years, group 1) developed IVO (mean CW Doppler velocity+/-SD: 3.8+/-1.0 m/s) and 57 (41 males, mean age+/-SD 63+/-10 years, group 2) did not. The two groups had similar incidence of angina and ischaemic ECG changes at exercise tolerance test. DSE did not demonstrate wall motion abnormalities in any group 1 patient while T SPECT showed a perfusion defect in the only one with coronary artery disease (CAD). DSE reproduced symptoms in a higher percentage of patients with than without IVO, while there was no statistical difference in the reproduction of ischaemic ECG changes, despite CAD prevalence was much lower in group 1. Group 1 patients remained asymptomatic on beta-blockers at 12-month follow-up. Dobutamine-induced IVO, by reproducing symptoms, suggests that IVO plays a role in the clinical setting in patients without CAD complaining of unexplained reduced effort tolerance who should undergo DSE.

Adult↗
PubMed1999

The age-related accumulation of protein carbonyl in rat liver correlates with the age-related decline in liver proteolytic activities.

Increases of protein carbonyl in animal tissues have been associated with the aging process. So far, the accumulation of oxidized proteins, highly susceptible to proteolysis, has been attributed to age-related changes in proteasomal alkaline proteases. Carbonyl in protein was monitored in six different tissues of male Sprague-Dawley rats fed ad libitum up to the age of 27 months, and of 24 and 27-month-old rats subjected to anti-aging diet restriction (every-other-day feeding ad libitum). Alkaline protease activities and liver lysosomal proteolysis were studied. The levels of protein carbonyl were significantly different in different tissues, and quite stable throughout life; accumulation was restricted to liver tissue very late in life, between ages 24 and 27 months; was fully prevented by diet restriction; was not accompanied by any diet-restriction-sensitive decline of alkaline protease activity; and was accompanied by a dramatic age-related decline in lysosomal proteolysis that was partially prevented by anti-aging diet restriction. No correlation was found between levels of alkaline protease activity and levels of protein carbonyl in the different tissues from younger animals. It is concluded that the process of autophagy, a well-known mechanism for cell maintenance, may deserve more interest in aging studies.

Aging↗
PubMed1999

Anomalous "VVI" pacing of a dual chamber pacemaker when programmed in DDI(R) mode.

We describe the case of a dual chamber rate responsive pacemaker (Relay, model 294-03, Intermedics, Angleton, TX, USA) implanted in a 68-year-old male for sick sinus syndrome, which was not working properly when programmed in the DDIR mode, thus determining occasionally a sort of "VVI" pacing. However, the pacemaker performed well when programmed in the DDDR mode. We discovered that this was not a malfunction of a single device but rather a general behavior of this family of Intermedics dual chamber pacemakers (also not rate responsive), caused by a software problem.

Aged↗
PubMed1999

Insufficient adaptive capability of pancreatic endocrine function in dexamethasone-treated ageing rats.

This study was aimed at exploring the capability of the pancreatic endocrine adaptive mechanisms of ageing Sprague-Dawley rats to counteract the metabolic challenge induced by the prolonged administration of dexamethasone (DEX) (0.13 mg/kg per day for 13 days). DEX treatment induced peripheral insulin resistance in 3-, 18- and 26-month-old rats, as indicated by the significant and persistent rise of plasma insulin levels in each age group (plasma insulin in 3-, 18- and 26-month-old rats from basal values of 4.3+/-0.8, 4.7+/-0.5 and 5.6+/-1.0 ng/ml (means+/-s.e.m.) respectively, rose to 11.9+/-1.7, 29.1+/-5.5 and 27.9+/-2.7 ng/ml respectively, after 9 days of administration). However, plasma glucose concentrations remained unchanged during the treatment in young rats, whereas they increased up to frankly diabetic levels in most 18-month-old and in all 26-month-old animals after a few days of DEX administration. Plasma free fatty acid concentrations increased 2-fold in 3- and 26-month-old rats and 4-fold in 18-month-old rats and could possibly be involved in the glucocorticoid-induced enhancement in insulin resistance, although they showed no significant correlation with glycaemic values. Incubation of pancreatic islets obtained from treated rats showed that DEX administration increased the insulin responsiveness of islets from not only younger but also older donors. However, in the islets of ageing rats, which already showed an age-dependent impairment of the sensitivity to glucose and other secretagogues, this enhancing effect was clearly attenuated with respect to the younger counterpart. Furthermore, DEX treatment depressed significantly the priming effect of glucose in islets isolated from all the three age groups. In conclusion, our results show that ageing rats are unable to counteract effectively a prolonged hyperglycaemic challenge as such induced by DEX administration. This homeostatic defect can be ascribed to the age-dependent failure of the endocrine pancreas to provide enough insulin to overcome the aggravation of an antecedent state of increased peripheral insulin resistance.

Aging↗
PubMed1999

[Variation in the evoked ventricular potentials after the implantation of an endocardiac catheter; the correlation with stimulation thresholds].

BACKGROUND: The drop in T wave amplitude of the ventricular pace-evoked response (VER) is a well-recognized and reliable mean of detecting localized conditions of myocardial hypoxia. In patients who undergo pacemaker implantation, the post-implant change at the electrode-tissue interface consists of an early inflammatory reaction. The aim of this study was to establish whether the extent of the inflammatory reaction following an endocardial lead can be assessed by the changes in the T wave amplitude of VER. METHODS: Modifications in VER amplitude and the correlation between these changes and pacing threshold time-course were evaluated in 30 patients receiving an endocardial catheter. Telemetered endocardial recordings of T wave amplitude and pacing thresholds were measured at the time of implant and after 1, 2, 3, 7, 14 and 30 days. RESULTS: A biphasic time-course was observed for T wave, characterized by reduction in amplitude of 48% (p < 0.005) from baseline at day 3 and subsequent increment up to 84% (p = ns) of the baseline value at day 30. By using a linear regression analysis, a significant correlation between T wave changes and increment in pacing threshold was found (r = 0.81; p < 0.002). A higher pacing threshold increment was observed in patients having a decrease in VER amplitude > or = 1 mV at 3rd in comparison with patients with a decrease in VER amplitude < 1 mV (1.1 +/- 0.4 vs 0.2 +/- 0.2 V; p < 0.001). CONCLUSIONS: VER recordings during the first days after endocardial lead implantation may be a valuable means of assessing the extent of the inflammatory reaction developing at the electrode-tissue interface. This method may be useful for early identification of patients at risk of increases in pacing threshold and for evaluation of the biocompatibility of different leads.

Aged↗
PubMed1998

Age-dependent accumulation of dolichol in rat liver: is tissue dolichol a biomarker of aging?

Dolichols are long hydrophobic molecules broadly distributed in all tissues and cellular membranes of eukariotic cells. Dolichol affects membrane structure and fluidity, membrane-associated protein activities, and membrane sensitivity to oxidative stress. Reports have shown that dolichols exhibit a remarkable (6- to 30-fold) age-related increase in the tissues of adult and mature rats and of old flies, mice, and humans. In our longitudinal study, the age-related accumulation of dolichol was monitored in the liver tissue of male Sprague Dawley rats fed ad libitum up to age of 27 months. In addition 24-month-old rats subjected to different regimens of anti-aging diet restriction (40% calorie restriction or every-other-day feeding ad libitum) were tested. A parallel study of the accumulation of carbonyl in liver protein (a proposed biomarker of aging) was made. In addition, the age-related decline of liver autophagy/proteolysis was studied in isolated liver cells, in view of the essential role of this function in liver membrane maintenance. Results show that an age-dependent accumulation of dolichol can be observed in the liver of the rats fed ad libitum but not in the liver of 24-month-old food-restricted rats, that accumulation of dolichol precedes the accumulation of altered liver proteins, and that dolichol accumulation is accompanied by a decline in liver autophagy. It is concluded that dolichol accumulation satisfies the proposed primary and secondary applicable criteria and the desirable features required to be qualified as a biomarker of aging.

Aging↗
PubMed1997

Experimental determination of the effect of progressive sharp-angle spinal deformity on the spinal cord.

Neurological deficit is a serious though not well-known complication associated with spinal deformity. Sharp-angle kyphosis may be congenital, traumatic, degenerative, infectious, or iatrogenic in origin. Many kyphotic deformities are underestimated, thus leading to severe neurological deficit. In order to determine exactly what procedures of angulation the patients should undergo to stabilize the spine, which are major operations, the authors analyzed in an experimental model the effects of progressive sharp angulation on the anatomy of spinal canal and cord. We found that sharp anterior angulation of 50 degrees causes anterior-posterior stenosis and the dura will touch the spinal cord. At 90 degrees of angulation, the spinal cord will be squeezed and the pressure in the canal will be double what it was initially, probably leading to ischemia. The experimental confirmation (determination) of these angulations allows the physician in charge to define early in the treatment program when a surgical stabilization procedure should be included, before the angulation causes any neurological damage.

Humans↗
PubMed1996

Activated pyrolytic carbon tip pacing leads: an alternative to steroid-eluting pacing leads?

Pyrolytic carbon technology is known for its excellent mechanical properties and electrical conductivity; it is particularly biocompatible and does not require high production costs. The Sorin S100/4 lead is a ventricular passive fixation lead with a hemispherical electrode surface area of 4 mm2; the stimulating tip is made of a graphite core coated by a thin activated pyrolytic carbon layer. We evaluated the acute and medium-term performance of the unipolar version of this lead in 65 patients. At implantation, pacing threshold (at 0.5 ms) was 0.26 +/- 0.08 V; pacing impedance (at 5 V and 0.5 ms) was 537 +/- 94 omega and R wave amplitude was 15.0 +/- 5.5 mV. No lead related complications (dislodgment, perforation, exit block, etc.) occurred in any patient; one patient presented with a wire fracture after 26 months, due to subclavian crush syndrome. Follow-up procedures were performed at 1 week, and 2-, 10-, 18-, and 30-months postimplant. Since the leads were connected to pacemakers from different manufacturers, either voltage or duration thresholds were measured. In approximately two thirds of the patients, with an output of 2.5 V, a mean duration threshold of 0.16 +/- 0.13 ms at 1 week, 0.12 +/- 0.08 ms at 2 months, 0.11 +/- 0.06 ms at 10 months, 0.09 +/- 0.06 ms at 18 months, and 0.07 +/- 0.03 ms at 30 months, was measured. In the remaining one-third of the patients, a comparable voltage threshold trend was measured. The mean pacing impedance showed a transient drop at 1 week, and then increased to a plateau of about 600 omega reached after 10 months. No sensing defect occurred in any patient. Our data show good acute and intermediate-term results of the S100/4 lead; the early rise in threshold was remarkably blunted. Activated pyrolytic carbon tip leads might therefore be considered as a possible, inexpensive alternative to steroid-eluting leads.

Aged↗