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Luigi Bergamaschini

Publications and source records attributed to Luigi Bergamaschini.

12 recordsLinked to original sources
PubMed2006

Selective inhibition of plasma kallikrein protects brain from reperfusion injury.

We have studied the effect of DX-88, a selective recombinant inhibitor of human plasma kallikrein, in transient or permanent focal brain ischemia (with or without reperfusion, respectively) induced in C57BL/6 mice. Twenty-four hours after transient ischemia, DX-88 administered at the beginning of ischemia (pre) induced a dose-dependent reduction of ischemic volume that, at the dose of 30 microg/mouse, reached 49% of the volume of saline-treated mice. At the same dose, DX-88 was also able to reduce brain swelling to 32%. Mice treated with DX-88 pre had significantly lower general and focal deficit score. Fluoro-Jade staining, a marker for neuronal degeneration, showed that DX-88-treated mice had a reduction in the number of degenerating cells, compared with saline-treated mice. Seven days after transient ischemia, the DX-88 protective effect was still present. When the inhibitor was injected at the end of ischemia (post), it was still able to reduce ischemic volume, brain swelling, and neurological deficits. DX-88 efficacy was lost when the inhibitor was given 30 min after the beginning of reperfusion (1 h post) or when reperfusion was not present (permanent occlusion model). This study shows that DX-88 has a strong neuroprotective effect in the early phases of brain ischemia preventing reperfusion injury and indicates that inhibition of plasma kallikrein may be a useful tool in the strategy aimed at reducing the detrimental effects linked to reperfusion.

Animals↗
PubMed2006

Mild cognitive impairment subtypes and vascular dementia in community-dwelling elderly people: a 3-year follow-up study.

OBJECTIVES: To investigate whether mild cognitive impairment (MCI) with multiple impaired cognitive domains (mcd-MCI) is a prodromal manifestation of vascular dementia (VaD). DESIGN: Prospective cohort study. SETTING: Geriatric unit of the Ospedale Maggiore Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy. PARTICIPANTS: Four hundred community-dwelling subjects aged 65 and older who came freely to the geriatric unit as part of a comprehensive geriatric assessment program were evaluated for memory impairment or other cognitive disorders. Subjects with MCI were kept under observation for 3 years. MEASUREMENTS: Subjects with MCI were studied by applying a standardized clinical evaluation and a conducting a computed tomography brain scan. Cognitive performance was assessed using the Mini-Mental State Examination, the Clock Drawing Test, and a comprehensive battery of neuropsychological tests. Cardiovascular comorbidity was assessed on the basis of medical history and using electrocardiography, echocardiography, and carotid color Doppler ultrasound. RESULTS: MCI was found in 65 of the 400 community-dwelling subjects; 31 were classified with amnestic MCI (a-MCI) and 34 with mcd-MCI. A dysexecutive syndrome characterized people with mcd-MCI, who had significantly more vascular comorbidity and signs of vascular disease on brain imaging as well as a higher prevalence of extra pyramidal features, mood disorders, and behavioral symptoms than people with a-MCI. Twenty of the 65 subjects with MCI (31%) progressed to dementia within 3 years of follow-up: 11 subjects with Alzheimer's disease (AD) and nine with VaD. All patients who evolved to AD had been classified with a-MCI at baseline, whereas all patients who evolved to subcortical VaD had been classified with mcd-MCI at baseline. CONCLUSION: All subjects who converted to subcortical VaD had been classified with mcd-MCI, suggesting that mcd-MCI might be an early stage of subcortical VaD.

Aged↗
PubMed2005

[The arterial pulse: from oblivious to revival?].

It seems reasonable to suppose that there is some relationship between the fanciful descriptions of arterial pulse dating back to ancient times and the more sophisticated data stemming from the technological advances of recent years. The clinical evidence derived from "the flowing blood" has always been associated with diseases of the heart and vessels and indeed of apparently unrelated organs, as well as with emotional states. Centuries before the Christian era, Chinese and Indian doctors seat great store by the study of the pulse which was described in imaginative terms and considered a clue to a person's character and illnesses. This subject was just as important to Greeks and Romans: to mention just one famous name Galeno, who wrote extensively about pulses. Up to the 18th century many European Universities had chairs entitled: "De pulsibus et urines" and from this time onwards sphygmic doctrine gained an ever-growing space in the scientific literature in the attempt to establish diagnostic and prognostic connections (often rather whimsical ones) between different kinds of pulses and so-called "crises of cerebral, thoracic and abdominal organs". Between the mid 18th century and the end of the 19th century the study of pulses was mainly focused on identifying arrhythmias and valvular defects even though we still find descriptions of "alternating" and "paradoxical" pulses accompanied by somewhat ambiguous explanations. From the second half of the 20th century the possibility of measuring the pulse wave velocity and the "augmentation index" has led to remarkable advances in epidemiological studies of cardiovascular diseases. This work would like to draw the readers' attention to the relevance a simple semeiological practice such as the examination of the pulse still has in the clinical approach to a patient even in these modern times.

Cardiology↗
PubMed2004

Peripheral treatment with enoxaparin, a low molecular weight heparin, reduces plaques and beta-amyloid accumulation in a mouse model of Alzheimer's disease.

We investigated the effect of long-term, peripheral treatment with enoxaparin, a low molecular weight heparin, in transgenic mice overexpressing human amyloid precursor protein(751). Enoxaparin (6 IU per mouse intraperitoneally, three times a week for 6 months) significantly lowered the number and the area occupied by cortical beta-amyloid deposits and the total beta-amyloid (1-40) cortical concentration. Immunocytochemical analysis of glial fibrillary acid protein-positive cells showed that enoxaparin markedly reduced the number of activated astrocytes surrounding beta-amyloid deposits. In vitro, the drug dose-dependently attenuated the toxic effect of beta-amyloid on neuronal cells. Enoxaparin dose-dependently reduced the ability of beta-amyloid to activate complement and contact systems, two powerful effectors of inflammatory response in AD brain. By reducing the beta-amyloid load and cytotoxicity and proinflammatory activity, enoxaparin offers promise as a tool for slowing the progression of Alzheimer's disease.

Alzheimer Disease↗
PubMed2004

Angioedema associated with angiotensin-converting enzyme inhibitor use: outcome after switching to a different treatment.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are associated with angioedema episodes that are potentially life-threatening. Few data are available on the outcome of patients reporting this adverse effect when they are switched to another drug. Scattered reports of angioedema associated with angiotensin II receptor blocker (ARB) use question the safety of using these drugs in patients with ACE inhibitor-related angioedema. We describe 64 consecutive patients with ACE inhibitor-related angioedema, the outcome after discontinuing this treatment, and the safety of using ARBs. METHODS: Retrospective analysis of 64 consecutive patients (January 1993 to June 2002) presenting with angioedema onset while receiving treatment with an ACE inhibitor. RESULTS: Patients were recommended to stop ACE inhibitor use, substituting it upon advice of the physician. Fifty-four patients were available for follow-up (median follow-up, 11 months; range, 1-80 months): 26 had switched to an ARB, 14 to a calcium antagonist, and 14 to other antihypertensive drugs. Angioedema disappeared or drastically reduced upon withdrawal of the ACE inhibitor in 46 patients (85%). For the remaining 8 patients, angioedema was due to a cause other than ACE inhibitor use in 2; angioedema persisted independent of the treatment and without apparent cause (idiopathic angioedema) in 4; angioedema persisted after switching to an ARB and disappeared upon its withdrawal in 2. CONCLUSIONS: Stopping ACE inhibitor use without further assessments is a successful measure in the large majority of patients developing angioedema while taking this drug. Only a small percentage of patients with ACE inhibitor-related angioedema continue with this symptom when switched to an ARB.

Aged↗
PubMed2004

The powerful neuroprotective action of C1-inhibitor on brain ischemia-reperfusion injury does not require C1q.

C1-inhibitor (C1-INH) is a major regulator of the complement classical pathway. Besides this action, it may also inhibit other related inflammatory systems. We have studied the effect of C1-INH in C57BL/6 mice with focal transient brain ischemia induced by 30 minutes of occlusion of the middle cerebral artery. C1-INH induced a dose-dependent reduction of ischemic volume that, with the dose of 15 U/mouse, reached 10.8% of the volume of saline-treated mice. Four days after ischemia the treated mice had significantly lower general and focal neurological deficit scores. Fluoro-Jade staining, a marker for neuronal degeneration, showed that C1-INH-treated mice had a lower number of degenerating cells. Leukocyte infiltration, as assessed by CD45 immunostaining, was also markedly decreased. We then investigated the response to ischemia in C1q(-/-) mice. There was a slight, nonsignificant decrease in infarct volume in C1q(-/-) mice (reduction to 72.3%) compared to wild types. Administration of C1-INH to these mice was still able to reduce the ischemic volume to 31.4%. The study shows that C1-INH has a strong neuroprotective effect on brain ischemia/reperfusion injury and that its action is independent from C1q-mediated activation of classical pathway.

Animals↗
PubMed2004

[Does a "senile heart" actually exist?].

The study of the aging heart raised for a long time difficulties in distinguishing the age-related physiological processes from the associated pathological changes. In recent years, however, several obscure or controversial items have been clarified through a wide use of imaging techniques such as echocardiography, positron emission tomography, and of molecular biology. The general notion of remodeling has been extended to include the arterial capacitance vessels, and the emerging concept of "ventricular-arterial coupling" has yielded a rational explanation for some structural and functional changes of the aging heart. Particular attention has been paid to the left ventricular diastolic dysfunction, while the new data have generally confirmed the old ones regarding the preserved systolic performance at rest. The aging of the heart should anyhow be considered in the context of the "cardiopulmonary unit" and by the light of the new acquisitions on the loss of skeletal muscle mass and strength (sarcopenia).

Aged↗
PubMed2003

[Pulmonary circulation in the history of medicine].

The history of medicine is frequently equivocal, fanciful and contradictory because of the interlacing with philosophy, theology and astronomy. However, old achievements, that were completely forgotten, are frequently rediscovered and hailed as new. Although widely dispersed in the centuries, we believe that a continual progress in the knowledge of pulmonary circulation is present in the works of the ancient scientists. For instance, Galen's statements that heart and lung act together and that they contribute to the preservation of body heat may anticipate the modern ideas of the metabolism and of heart-lung unit.

Cardiology↗
PubMedDate not supplied

C1-inhibitor protects against brain ischemia-reperfusion injury via inhibition of cell recruitment and inflammation.

Previous studies demonstrated that C1-inhibitor (C1-INH), a complement and contact-kinin systems inhibitor, is neuroprotective in cerebral ischemia. To investigate the mechanism of this action, we evaluated the expression of neurodegeneration and inflammation-related factors in mice subjected to 2-h ischemia and 2 or 46 h reperfusion. C1-INH significantly dampened the mRNA expression of the adhesion molecules P-selectin and ICAM-1 induced by the ischemic insult. It significantly decreased the pro-inflammatory cytokine (TNF alpha, IL-18) and increased the protective cytokine (IL-6, IL-10) gene expression. C1-INH treatment prevented the decrease of NFH gene, a marker of cellular integrity and counteracted the increase of pro-caspase 3, an apoptosis index. Furthermore, C1-INH markedly inhibited the activation and/or recruitment of microglia/macrophage, as shown by immunohistochemistry. In conclusion, C1-INH exerts an anti-inflammatory and anti-apoptotic action on ischemia-reperfusion injury. Our present and past data support a major effect of C1-INH on cell recruitment from the vasculature to the ischemic site.

Animals↗
PubMedDate not supplied

Heparin attenuates cytotoxic and inflammatory activity of Alzheimer amyloid-beta in vitro.

Amyloid-beta protein (Abeta) is implicated in the pathogenesis of Alzheimer's disease because of its neurotoxicity and the ability to trigger local inflammation. Compounds that interact with the amino acids of the N-terminal region or interfere with aggregation can reduce the Abeta biologic activity. We evaluated the effect of heparin on Abeta (1-42) neurotoxicity and on its ability to activate complement and contact system. On differentiated PC12 cells, a reliable model of neuronal cells, heparin at the doses of 10 and 20 microg/ml significantly counteracted Abeta cytotoxicity as assessed by measuring MTT conversion. We then explored the effect of heparin on Abeta (1-42)-induced complement and contact system activation. Abeta (1-42) was incubated with heparin in presence of normal plasma as the source of complement and contact system factors. Heparin reduced, in a dose-dependent manner, complement and contact system activation, assessed by measuring the degree of C4 and high molecular weight kininogen cleavage. The present data show that heparin can attenuate neurotoxic and pro-inflammatory activity of Abeta and suggest that this drug could represent a new strategy to reduce the progressive neurodegeneration in AD.

Amyloid beta-Peptides↗