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Biomedical subjects

P Cinelli

Publications and source records attributed to P Cinelli.

At least 19 recordsLinked to original sources
PubMed2001

Neuroserpin, a neuroprotective factor in focal ischemic stroke.

Because recent studies have indicated that tissue plasminogen activator (tPA) aggravates neurodegenerative processes in many neural pathologies, we studied whether the endogenous tPA antagonist neuroserpin has a neuroprotective effect in an animal model of focal ischemic stroke. After induction of a focal ischemic stroke in the mouse by occlusion of the middle cerebral artery, we found that microglial cells accumulated in the marginal zone of the infarct are the most important source for both plasminogen activators, tPA and uPA. To investigate the effect of neuroserpin on the size and the histology of the infarct we produced transgenic mice overexpressing neuroserpin approximately sixfold in the nervous system. In the brain of these mice the total tPA activity in the uninjured tissue was strongly reduced. After induction of a focal ischemic stroke in the transgenic mice by a permanent occlusion of the middle cerebral artery (MCA), the infarcts were 30% smaller than in the wild-type mice. Immunohistochemical analyses and in situ hybridization revealed an attenuation of the microglial activation in the reactive zone. Concomitantly, the microglial production of tPA and uPA, as well as the PA-activity in the infarct region was markedly reduced. Thus, our results indicate that neuroserpin reduces microglial activation and, therefore, the PA activity and has a neuroprotective role after focal ischemic stroke.

Animals↗
PubMed2001

Multiple roles of neurotrypsin in tissue morphogenesis and nervous system development suggested by the mRNA expression pattern.

We have mapped the spatio-temporal expression of the multidomain serine protease neurotrypsin in the developing mouse by in situ hybridization. On embryonic day (E) 8, mRNA is detected in giant trophoblast cells, later in embryonic mesenchymal tissues. On E11, expression begins in Schwann cell precursors, olfactory epithelium, trigeminal ganglion, and midbrain. The floor plate shows strong expression on E12. Further prenatal development is characterized by rising neurotrypsin mRNA in sensory ganglia and motor neurons. Staining in cerebral cortex emerges around birth and culminates toward the end of the first week with a complex laminar and areal pattern. Expression in peripheral nerves and nonneural tissues vanishes soon after birth and the adult neuronal distribution is gradually established until weaning age. This developmental expression pattern suggests roles of neurotrypsin in morphogenesis of nonneural tissues, as well as in neural development, in particular in axonal target invasion, synaptogenesis, and Schwann cell differentiation.

Aging↗
PubMed2001

Composite films based on biorelated agro-industrial waste and poly(vinyl alcohol). Preparation and mechanical properties characterization.

As a part of an ongoing project on the production of composite materials based on poly(vinyl alcohol) (PVA) and polymeric materials from renewable resources, the present paper reports on the incorporation of agricultural waste materials as organic fillers in a film matrix based on PVA as continuous phase. In this study lignocellulosic fibers byproducts, derived from sugar cane (SC) and apple (AP) and orange (OR) fruit juice extraction, were cast from PVA aqueous solutions. The effect of fiber type and composition on the relative properties of cast films was evaluated and compared. OR resulted to be suitable for blending in higher amounts by weight than SC and AP. Glycerol and urea were added as plasticizing agents and were observed to be effective in giving flexible films. Additionally, cornstarch was added to further increase the composition of polymers from renewable resources in cost-effective and ecoefficient composite film formulations. The prepared films resulted sensitive to moisture and water. To reduce water sensitivity, hexamethoxymethylmelamine (HMMM) was tested as a cross-linking agent for the present composite formulations. Cross-linked films exhibited significant improvement in water-resistance that can be taken as a tuneable structural feature for customized applications. The mechanical properties of the prepared composite films (elongation at break, tensile strength, Young modulus) were found to be dependent upon the nature and content of the filler and on environmental conditions.

Agriculture↗
PubMed2001

Gelatin-based blends and composites. Morphological and thermal mechanical characterization.

Gelatin, a natural macromolecular proteic material from renewable resources, is widely used in many industrial applications. In this study gelatin scraps, deriving from pharmaceutical capsule productions, were turned into films by casting water solutions or suspensions producing flexible and consistent films. Gelatin was blended with poly(vinyl alcohol), a biodegradable synthetic polymer, in order to improve mechanical properties in the films. Gelatin was blended also with sugar cane bagasse, a lignin cellulosic waste from sugar cane processing. These blends showed good interface adhesion between gelatin and sugar cane fibers and mechanical properties of practical interest for up to 20% of sugar cane content by weight. Glutaraldehyde was used in different amounts as a cross-linking agent increasing elongation at break especially for amount above 1%. Morphology, thermal, thermomechanical, and mechanical properties of the samples were investigated by scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA), and tensile tests, respectively. Cast films presented thermal and mechanical properties, which make them good candidates as biodegradable self-fertilizing mulching films.

Biodegradation, Environmental↗
PubMed1999

Neuronal depolarization enhances the transcription of the neuronal serine protease inhibitor neuroserpin.

Neuroserpin is an axonally secreted neuronal serine protease inhibitor. Based on its inhibitory activity towards tissue plasminogen activator (tPA) and its predominant expression in the cerebral cortex, the hippocampus, and the amygdala, a role for neuroserpin in the regulation of neural plasticity has been suggested. We recently found that neuroserpin mRNA is increased in cultured hippocampal neurons upon depolarization with elevated extracellular KCl. Using luciferase reporter constructs containing segments of the promoter region of the neuroserpin gene, we identified a 200-bp segment near the transcription initiation site that is responsible for both the neuron-specific expression of the neuroserpin gene and the enhanced transcription resulting from depolarization. Nerve growth factor, which alone had no effect on the expression of neuroserpin mRNA in hippocampal neurons, had a marked potentiating effect when supplied in combination with elevated extracellular KCl. In contrast, the transcription factor zif/268 blocked neuroserpin transcription. These results implicate neuroserpin as an activity-regulated modulator of tPA activity at the synapse and provide further support for the occurrence of activity-regulated proteolytic processes at the synapse.

Animals↗
PubMed1998

The axonally secreted serine proteinase inhibitor, neuroserpin, inhibits plasminogen activators and plasmin but not thrombin.

Neuroserpin is an axonally secreted serine proteinase inhibitor that is expressed in neurons during embryogenesis and in the adult nervous system. To identify target proteinases, we used a eucaryotic expression system based on the mouse myeloma cell line J558L and vectors including a promoter from an Ig-kappa-variable region, an Ig-kappa enhancer, and the exon encoding the Ig-kappa constant region (C kappa) and produced recombinant neuroserpin as a wild-type protein or as a fusion protein with C kappa. We investigated the capability of recombinant neuroserpin to form SDS-stable complexes with, and to reduce the amidolytic activity of, a variety of serine proteinases in vitro. Consistent with its primary structure at the reactive site, neuroserpin exhibited inhibitory activity against trypsin-like proteinases. Although neuroserpin bound and inactivated plasminogen activators and plasmin, no interaction was observed with thrombin. A reactive site mutant of neuroserpin neither formed complexes with nor inhibited the amidolytic activity of any of the tested proteinases. Kinetic analysis of the inhibitory activity revealed neuroserpin to be a slow binding inhibitor of plasminogen activators and plasmin. Thus, we postulate that neuroserpin could represent a regulatory element of extracellular proteolytic events in the nervous system mediated by plasminogen activators or plasmin.

Amino Acid Sequence↗
PubMed1997

Expression of neuroserpin, an inhibitor of tissue plasminogen activator, in the developing and adult nervous system of the mouse.

Neuroserpin is a serine protease inhibitor of the serpin family that has been identified as an axonally secreted glycoprotein in neuronal cultures of chicken dorsal root ganglia. To obtain an indication for possible functions of neuroserpin, we analyzed its expression in the developing and the adult CNS of the mouse. In the adult CNS, neuroserpin was most strongly expressed in the neocortex, the hippocampal formation, the olfactory bulb, and the amygdala. In contrast, most thalamic nuclei, the caudate putamen, and the cerebellar granule cells were devoid of neuroserpin mRNA. During embryonic development, neuroserpin mRNA was not detectable in neuroepithelia, but it was expressed in the differentiating fields of most CNS regions concurrent with their appearance. In the cerebellum, the granule cells and a subgroup of Purkinje cells were neuroserpin-positive during postnatal development. As a further step toward the elucidation of neuroserpin function, we performed a study to identify potential target proteases. In vitro, neuroserpin formed SDS-stable complexes and inhibited the amidolytic activity of tissue plasminogen activator, urokinase, and plasmin. In contrast, no complex formation with or inhibition of thrombin was found. Expression pattern and inhibitory specificity implicate neuroserpin as a candidate regulator of plasminogen activators, which have been suggested to participate in the modulation or reorganization of synaptic connections in the adult. During development, neuroserpin may attenuate extracellular proteolysis related to processes such as neuronal migration, axogenesis, or the formation of mature synaptic connections.

Amino Acid Sequence↗
PubMed1997

Implementation of total quality management after reconfiguration of services on a general hospital unit.

In 1992 the New York State Office of Mental Health issued a statewide plan for mental health services to reduce the number of inpatient beds in state-run facilities from approximately 11,000 to between 6,000 and 8,000 by the year 2000. This reduction resulted in at least a 25 percent increase in psychiatric beds at local general hospitals. In 1992 Albany Medical Center Hospital's department of inpatient psychiatry established an interdisciplinary committee to address changes resulting from the reconfiguration of services to chronic mentally ill persons. The committee established procedures to use the principles of total quality management to respond to problems and to continuously improve the therapeutic milieu. The authors describe how these principles were used to create a patient satisfaction survey, to examine and improve part of the hospital admissions procedure, and to review and revise treatment planning documentation. A concurrent review committee reviews patients' records to ensure accuracy of documentation and quality of care.

Chronic Disease↗
PubMed1992

Low incidence of cardiac hypertrophy in essential hypertensives with no retinal changes.

120 subjects, 90 hypertensives and 30 age-matched controls, were evaluated by fundoscopy and echocardiography to assess the degree of target organ involvement. The hypertensive patients were divided into 3 groups (mild, moderate, severe hypertension) according to their diastolic blood pressure levels. No significant difference was demonstrated in left ventricular mass among the 3 groups. Moreover, no relationship was demonstrated between the degree of hypertension and the severity of fundoscopic changes. Our findings indicate that patients with no retinal changes show a low probability of left ventricular hypertrophy and that patients with left ventricular hypertrophy show a high probability of retinal involvement. Our data indicate that fundoscopy is more sensitive than echocardiography in the recognition of the hypertensive disease.

Adult↗
PubMed1991

Ventricular late potentials in the assessment of mitoxantrone cardiotoxicity.

Sixteen female patients underwent signal-averaged electrocardiography and radionuclide angiography for the assessment of the resting left ventricular ejection fraction in the course of chemotherapy with mitoxantrone (MTX) for advanced breast cancer. Nine patients had received prior cardiotoxic treatments. Our findings indicate that patients treated with MTX may develop late potentials.

Adult↗
PubMed1989

Does ergometric stress test induce a procoagulative condition in patients with previous myocardial infarction?

A regularly scheduled physical training program seems to have antithrombotic effects. Moreover, the hemostatic changes occurring in patients with coronary artery disease during acute exercise have not been clearly elucidated. Since stress testing is routinely performed in clinical cardiology, it would be helpful to assess whether patients with coronary artery disease are exposed to acute coronary thrombosis during or soon after sustained physical exercise. This study was designed to evaluate the effect of acute physical exercise (stress test by bicycle ergometer) on blood coagulation in a group of patients with previous myocardial infarction, and to determine whether the antithrombotic therapy commonly administered favorably influences hemostatic equilibrium. Our results suggest that exercise testing is not harmful to patients with previous myocardial infarction in regard to hemostasis and fibrinolysis and that antithrombotic therapy reduces postexercise increase in platelets.

Aged↗
PubMed1989

New indices in the evaluation of clonidine transdermal therapy of hypertension.

Since high blood pressure might be more harmful the higher it is and the more it remains above a determined critical value (140/90 mm Hg - 18.7/12.0 k Pa - in the present study), the hyperbaric impact, a measure of the total load exerted on the arterial walls and the total time during the day when blood pressure is elevated above the critical value, have been evaluated. Ten patients with essential hypertension underwent non-invasive automatic 24-h blood pressure monitoring three times (baseline and after three and seven days from the application on the upper chest of a transdermal self-adhesive patch delivering clonidine). The recorder was programmed to measure blood pressure every 30 min during the day and every 60 min during the night. Significantly lower values of blood pressure, hyperbaric impact and duration of elevated blood pressure have been demonstrated from the third day after the beginning of transdermal therapy.

Administration, Cutaneous↗
PubMed1988

Echocardiographic evaluation of children with and without family history of essential hypertension.

A family history of hypertension is considered a risk factor for developing hypertension. We studied two groups of normotensive children (aged 14 years): one comprising 14 subjects with family history of hypertension, the other comprising 15 subjects without family history of hypertension. Children were comparable with respect to age, weight, height, body surface area, heart rate, and arterial blood pressure. M-mode echocardiography demonstrated higher interventricular septum/posterior wall ratio in progeny of hypertensive subjects. Interestingly, all the parameters evaluated were within the normal limits. Our data suggest that a certain degree of cardiac changes is present in children with positive family history of hypertension, though further studies are needed before considering these findings predictive of future essential hypertension.

Adolescent↗
PubMed1987

Circadian variations of heart rate and premature beats in healthy subjects and in patients with previous myocardial infarction.

Chronobiological analysis of the circadian variations of heart rate, ventricular and atrial ectopies, was carried out on 11 patients with previous myocardial infarction matched with 11 controls. Individual circadian rhythms in heart rate were seen in all the control subjects but only in 6 patients with previous myocardial infarction. The behaviour of the individual circadian rhythms of premature beats was not significantly different between the two groups. A significant group rhythm in ectopies was not demonstrated, nevertheless a trend to higher frequency of arrhythmias during the activity span was detected. These results do not allow to postulate a circadian pattern of arrhythmias common to all the subjects examined. Therefore, the individual circadian behaviour of premature atrial and ventricular beats should be recognized for monitoring antiarrhythmic therapy. A significant group rhythm in heart rate was demonstrated for the two populations studied and linear discriminant analysis showed that the amplitude of this rhythm was significantly lower in patients than in controls. Possibly, myocardial infarction may affect the sinus node function producing a "flattened" range of heart rates during the 24 hours.

Activity Cycles↗
PubMed1987

Echocardiographic assessment of anthracycline cardiotoxicity during different therapeutic regimens.

The use of doxorubicin (Dx) in treating malignancies is limited by a potentially fatal cardiomyopathy. Prevention of this related cardiotoxicity has been attempted either by using doxorubicin analogues such as 4'-epidoxorubicin (4'-EpiDx) or by simultaneous administration of other pharmacological substances. Fifteen patients with breast and lung cancer divided into three groups, treated respectively with Dx alone, Dx and L-carnitine and 4'-EpiDx, were studied to assess the effects of these therapeutic regimens on left ventricular performance. For this purpose the maximum velocities of fibre shortening and lengthening (VcF), obtained by computerized M-Mode echocardiography were used as indices of systolic and diastolic function respectively. Data from patients and from 25 healthy subjects were evaluated by analysis of variance and Tukey test. No significant difference was found in baseline systolic and diastolic VcF values. Significantly lower systolic VcF (p less than 0.05) was shown by patients treated with Dx alone, while diastolic VcF was significantly lower in those treated with 4'-EpiDx after four cycles. Systolic VcF of patients treated with Dx and L-carnitine and with 4'-EpiDx did not significantly differ from controls even after six therapeutic cycles. These data demonstrate that systolic VcF is not affected by 4'-EpiDx or by Dx when administrated with L-carnitine. The reduction of diastolic VcF by 4'-EpiDx and not by Dx could be due to different effects of these drugs on the calcium transport since early isovolumic relaxation depends on an energy-dependent process of calcium removal.

Adult↗
PubMed1986

Evidence of no interobserver variability in M-mode echocardiography.

Left ventricular internal dimensions, septal and posterior wall thickness, aortic root diameter, and left atrial dimensions, were independently measured by two experienced interpreters on 50 consecutive routinely performed M-mode echocardiograms. The purpose of this work was to evaluate the reproducibility of these measurements and to assess if a different "diagnostic effect" could be provided by the two readers. The extent of interobserver variability was calculated and expressed as a percent of the mean. No significant interobserver variability was found for all the measured echocardiographic parameters and the two interpreters gave rise to the same "diagnostic effects." Therefore, the authors suggest following well stated guidelines to provide uniformity in the process of determining the boundaries of the structures to be measured and adjusting the actual measurements by multiplying by a conversion factor (representing the ratio between the number of 1 cm markers and the distance in centimeters between the first and the last marker), as opposed to interpolating between the marks on the recording paper.

Echocardiography↗