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Biomedical subjects

Mario Di Napoli

Publications and source records attributed to Mario Di Napoli.

At least 19 recordsLinked to original sources
PubMed2006

Predicting mortality in spontaneous intracerebral hemorrhage: can modification to original score improve the prediction?

BACKGROUND AND PURPOSE: A clinical grading scale for intracerebral hemorrhage (ICH), formally ICH score, was recently developed showing to predict 30-day mortality in a simple and reliable manner. The aim of the present study was to validate the original ICH (oICH) score in an independent cohort of patients from a developing country assessing 30-day mortality and 6-month functional outcome and whether its modifications can improve prediction. METHODS: Consecutive patients admitted with acute ICH between January 1, 2003, and July 31, 2004, were prospectively included. oICH score was applied and 2 modified ICH (mICH) scores were created with the same variables, except localization, of the oICH score but with different cutoff values. Outcome was assessed as 30-day mortality and 6-month good outcome (Glasgow Outcome Scale [GOS] 4 to 5). RESULTS: A total of 153 patients were included during study period. Thirty-day mortality rate was 34.6% (n=53), and 59 patients (38.6%) had good functional outcome (GOS 4 to 5) at 6 months. The oICH and mICH scores predicted mortality equally well. According to Youden's index (J), the oICH score was a reliable predictor for mortality (J=0.59) but less reliable for predicting good outcome (J=0.54). The mICH scores were equal in predicting mortality but better for predicting good outcome than the oICH score (J=0.60). CONCLUSIONS: oICH score also confirms its validity in a socially and culturally different population. Modifications of oICH do not improve its 30-day mortality prediction but improve its ability to predict good functional outcome at 6 months.

Aged↗
PubMed2006

Systemic inflammation, blood pressure, and stroke outcome.

Hypertension is the most important modifiable risk factor for ischemic stroke, and antihypertensive treatment is of paramount importance to reduce the incidence of stroke mortality and morbidity. The significance and best management of hypertension during the first hours after stroke onset, however, are still matters of debate. Cerebral ischemia results in a complex inflammatory cascade; inflammatory mechanisms are also important participants in the pathophysiology of hypertension. There has been a convergence of evidence that is important to consider in managing systemic blood pressure after stroke to ensure an optimal outcome. The identification of useful markers will allow progress in our ability to treat blood pressure in the acute phase of a stroke. The determination of levels of C-reactive protein, an acute-phase inflammation marker, may help to guide our approach in the management of blood pressure in acute ischemic stroke. Whether this target will be useful in the development of risk prediction strategies or therapies for the treatment of stroke in humans is far from clear.

Acute Disease↗
PubMed2006

[Present insights in the cerebral small vessel disease physiopathology: the role of C-reactive protein].

The mechanisms underlying the pathogenesis of cerebral small vessel disease (SVD) are incompletely understood, although it represents a large burden upon healthcare and social service. New experimental and clinical data suggest that inflammatory reactions may play a crucial role in both the initiation and progression of SVD. Inflammatory processes could be involved in the pathogenesis of SVD, and particularly in the development of white matter lesions and leukoaraiosis. These new data regarding the possible effects of inflammatory reactions in SVD may be of more than just academic interest. It may be that adding evaluation of inflammatory markers, such as C-reactive protein, to conventional risk factors will allow more appropriate preventive and therapeutic interventions.

Biomarkers↗
PubMed2005

Evaluation of C-reactive protein measurement for assessing the risk and prognosis in ischemic stroke: a statement for health care professionals from the CRP Pooling Project members.

BACKGROUND AND PURPOSE: Several studies have shown, in different populations, that modest elevation of plasma C-reactive protein (CRP) in the range seen in apparently healthy individuals is a strong predictor of future vascular events. Elevated plasma CRP concentrations are also associated with an increased risk of cerebrovascular events and an increased risk of fatal and nonfatal cardiovascular events in ischemic stroke patients. These epidemiological and clinical observations suggest that determination of plasma CRP concentrations could be used as an adjunct for risk assessment in primary and secondary prevention of cerebrovascular disease and be of prognostic value. The aim of this review is to summarize the evidence for CRP as an independent predictor of cerebrovascular events in at-risk individuals and ischemic stroke patients and to consider its usefulness in evaluating prognosis after stroke. SUMMARY OF REVIEW: CRP fulfils most of the requirements of a new risk and prognostic predictor, but several issues await further confirmation and clarification before this marker can be included in the routine evaluation of stroke patients and subjects at risk for cerebrovascular disease. Potentially important associations have been established between elevated plasma CRP concentrations and increased efficacy of established therapies, particularly lipid-lowering therapy with statins. CONCLUSIONS: At present, there is not sufficient evidence to recommend measurement of CRP in the routine evaluation of cerebrovascular disease risk in primary prevention, because there is insufficient evidence as to whether early detection, or intervention based on detection, improves health outcomes, although shared risk of cardiovascular disease indicates this may be of value. In secondary prevention of stroke, elevated CRP adds to existing prognostic markers, but it remains to be established whether specific therapeutic options can be derived from this.

Aged↗
PubMed2005

Inflammation, blood pressure, and stroke: an opportunity to target primary prevention?

Promising findings suggest that systemic inflammation and neuroinflammation are central features in cerebrovascular disease. Inflammatory mechanisms are also important participants in the pathophysiology of hypertension. Markers of inflammation have been shown to be upregulated in different forms of cerebrovascular disease, and to correlate with vascular risk. The inhibitor nuclear factor-kB/nuclear factor-kB system is considered a major intracellular inflammatory pathway, mediating most of the vascular inflammatory responses. Increasing evidence indicates that hypertension, through the vasoactive peptides angiotensin and endothelin-1, promotes and accelerates the atherosclerotic process via inflammatory mechanisms. Proinflammatory properties of angiotensin II have been demonstrated. The identification of useful markers of inflammation, of new therapeutic targets to interfere with these mechanisms, and the evaluation of the efficacy of anti-inflammatory treatments will allow progress in our ability to combat cerebrovascular disease and the complications of hypertension. Whether these targets will be useful in the development of risk prediction strategies or therapies for the treatment of stroke in humans is far from clear.

Biomarkers↗
PubMed2005

M-40403 Metaphore Pharmaceuticals.

Metaphore Pharmaceuticals Inc. is developing M-40403, a superoxide dismutase mimetic, for the potential treatment of pain, dermatological disease and inflammation. The company is also investigating the compound for its potential in the treatment for the side effects associated with chemotherapy and radiation therapy.

Analgesics↗
PubMed2005

The ubiquitin-proteasome system as a drug target in cerebrovascular disease: therapeutic potential of proteasome inhibitors.

Proteasomes are large, multi-catalytic protease complexes that are found in the cytosol and in the nucleus of eukaryotic cells with a central role in cellular protein turnover. The ubiquitin-proteasome system (UPS) is the predominant non-lysosomal protein degradation pathway that ensures the viability, proliferation and signaling of eukaryotic organisms. Overwhelming data exist implicating a critical role for the UPS in cerebral ischemic injury. Ischemic and hypoxic trauma, and their associated oxidative, nitrosylative and energetic stress, underlie neurodegeneration following stroke, and evoke a discreet set of transcriptional events which have a complex and interdependent relationship with proteasomal function. Rapid elimination of denatured, misfolded and damaged proteins by the proteasome becomes a critical determinant of cell fate. Proof-of-principle has been obtained from animal models of cerebral ischemia, in which proteasome inhibitors reduce neuronal and astrocytic degeneration, cortical infarct volume, infarct neutrophil infiltration. and nuclear factor kappaB immunoreactivity. This neuroprotective efficacy has also been observed when proteasome inhibitors have been used 6 h after ischemic insult. Strategies aimed at effecting long-lasting changes in proteasomal function are not recommended, given the growing body of evidence implicating long-term proteasomal dysfunction in chronic neurodegenerative disease. These effects are likely due to the fact that the UPS is also essential for cellular growth, metabolism and repair, and untoward effects of proteasomal inhibition indicate that the development of short-lived proteasome inhibitors, or compounds which can spatially and temporally regulate the UPS, is a desirable clinical target. Studies in animal models indicate that the use of specific proteasome inhibitors may be beneficial in treating a host of acute neurological disorders, including ischemic stroke.

Animals↗
PubMed2004

Ubiquitin-proteasome system and proteasome inhibition: new strategies in stroke therapy.

BACKGROUND AND PURPOSE: Proteasomes are large multicatalytic proteinase complexes that are found in the cytosol and in the nucleus of eukaryotic cells with a central role in cellular protein turnover. The ubiquitin-proteasome system (UPS) has a central role in the selective degradation of intracellular proteins. Among the key proteins whose levels are modulated by the proteasome are those involved in the control of inflammatory processes, cell cycle regulation, and gene expression. There are now overwhelming data suggesting that the UPS contributes to cerebral ischemic injury. SUMMARY OF REVIEW: Proteasome inhibition is a potential treatment option for stroke. Thus far, proof of principle has been obtained from studies in several animal models of cerebral ischemia. Treatment with proteasome inhibitors reduces effectively neuronal and astrocytic degeneration, cortical infarct volume, infarct neutrophil infiltration, and NF-kappaB immunoreactivity with an extension of the neuroprotective effect at least 6 hours after ischemic insult. However, it is clear that the UPS represents a central pathway for the processing and metabolism of multiple proteins with critical roles in cellular function. To avoid eliciting significant side effects associated with complete inhibition of the proteasome and the possible immunosuppressive effects from persistent suppression of NF-kappaB activation, it is critical that we understand how to partially and temporally attenuate proteasome function to elicit the desired therapeutic effect before any large-scale use in humans. CONCLUSIONS: This review highlights the most recent advances in our knowledge on UPS, as well as the early experience of using proteasome inhibition strategies to treat acute stroke.

Adenosine Triphosphate↗
PubMed2004

Clinical application of C-reactive protein in stroke prevention: bright and dark sides of the moon.

In different study populations, several studies have shown that modest C-reactive protein elevation, in the range of apparently healthy individuals, is a strong predictor of future vascular events. Willcox and colleagues summarize the epidemiological and clinical observations that have led to the enthusiastic suggestion that determination of serum C-reactive protein levels could also be used as an adjunct for risk assessment in primary and secondary prevention of cerebrovascular disease. Currently, high-sensitivity C-reactive protein assays as a screening test to ascertain individuals at risk of cerebrovascular disease does not provide an accurate determination of the risk of stroke likelihood, and adequate evidence that early detection improves health outcomes and that an early intervention is likely to have a beneficial impact. High-sensitivity C-reactive protein assays as a screening test, only provide inadequate evidence to be considered as an effective cerebrovascular screening test, especially in the elderly.

Biomarkers↗
PubMed2004

Benefits of statins in cerebrovascular disease.

Although elevated cholesterol levels have been associated with coronary heart disease, the evidence for a role of cholesterol in stroke is less well defined. Epidemiological studies indicate that high lipid levels are linked with an increase in ischemic stroke, while low lipid levels may increase the risk of hemorrhagic stroke. Lipid lowering with statins reduces the incidence of ischemic stroke without increasing the frequency of hemorrhagic stroke. The benefits of statins on stroke may be due to a combination of mechanisms. Statins lower cholesterol levels and reduce the progression of atherosclerotic plaque formation in carotid arteries, and the incidence of emboli from cardiac, aortic and carotid sites. Furthermore, statins may produce cholesterol-independent effects such as improving cerebral blood flow and reducing inflammation and oxidative stress, which could limit the size of an ischemic lesion. Statins offer potential benefits for reducing the incidence and improving the prognosis of stroke.

Clinical Trials as Topic↗
PubMed2003

Angiotensin-converting enzyme inhibitor use is associated with reduced plasma concentration of C-reactive protein in patients with first-ever ischemic stroke.

BACKGROUND AND PURPOSE: High levels of C-reactive protein (CRP) are associated with an increased risk of future cardiovascular events in ischemic stroke. It has been hypothesized that the benefit of angiotensin-converting enzyme (ACE) inhibitors in patients at high vascular risk may also result from their anti-inflammatory action. Data evaluating this hypothesis are limited in ischemic stroke. METHODS: We conducted a prospective observational study in 507 patients with first-ever ischemic stroke to analyze the effect of ACE inhibitor treatment at the time of stroke onset on CRP levels within the first 24 hours and the relationship to outcome. Risk estimates were calculated according to Cox regression analysis controlled for blood pressure (BP) levels, clinical and neuroradiological confounding variables, and log-normalized CRP levels at entry. RESULTS: ACE inhibitor treatment was associated with lower (2.6-fold; P<0.0001) median CRP levels and with a reduced 2-year cardiovascular risk (hazard ratio, 0.39; 95% CI, 0.29 to 0.53; P<0.0001) compared with a different BP-lowering regimen. The relationship between ACE inhibitor status and log-normalized CRP levels remained significant (P<0.0001) after we controlled for important confounding variables and concomitant treatments. The reduced risk was also evident in multivariable analysis when ACE inhibitor treatment was controlled for BP, associated risk factors, neuroradiological findings, and concomitant treatments (hazard ratio, 0.43; 95% CI, 0.30 to 0.62; P<0.0001). This risk reduction was greatly attenuated and not more significant when log-normalized CRP levels were included (hazard ratio, 0.67; 95% CI, 0.43 to 1.04; P=0.0721) in the model. CONCLUSIONS: Concomitant treatment with ACE inhibitor at the time of an acute stroke is associated with lower inflammatory response and better long-term outcomes, apparently apart from the effects on BP.

Aged↗
PubMed2003

Association between blood pressure and C-reactive protein levels in acute ischemic stroke.

Among patients with acute stroke, high blood pressure (BP) and higher levels of circulating C-reactive protein (CRP) at the entry are often associated with poor outcome, although the reason is unclear. If the link between BP and stroke outcome is indeed mediated by inflammatory response, one would expect to see positive associations between BP and CRP. In a prospective observational stroke data bank involving 535 first-ever ischemic stroke patients, we studied the association between BP and baseline concentrations of CRP within 24 hours after stroke onset. The association between BP components and the odds of having an elevated CRP level (> or =1.5 mg/dL) was assessed by logistic regression analysis. An increase in systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), or pulse pressure (PP) was significantly associated with an increase in the odds of having an elevated CRP level, independent of other associated study factors. For each 10 mm Hg increase in SBP, DBP, MAP, or PP, the odds of having a high CRP level increased by 72% (P<0.0001), 10% (P<0.0001), 21% (P<0.0001), and 10% (P<0.0001), respectively. When the same model was rerun, adjusting for all considered BP components, only SBP significantly increased the odds of an elevated CRP level by 77% (P<0.0001). Increased SBP was significantly associated with elevated levels of circulating CRP in ischemic stroke patients. These findings support a possible role of acute hypertension after stroke as an inflammatory stimulus contributing to ischemic brain inflammation.

Acute Disease↗