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Bergamo, Italy

The Mario Negri Institute for Pharmacological Research is a nonprofit research institute dedicated to clinical and biomedical research. It was made possible by a special bequest of Milan philanthropist it:Mario Negri . It was founded in 1961 although it started working in Milan from 1st Feb 1963. There are branches of the institute in Bergamo, Ranica , and at Santa Maria Imbaro, near Chieti.Founder and director from 1961 is prof. it:Silvio Garattini. Wikipedia.

Beghi E.,Mario Negri Institute for Pharmacological Research | Hesdorffer D.,Columbia University
Epilepsia | Year: 2014

The incidence, prevalence, and mortality of epilepsy vary across countries with different economies. Differences can be explained by methodological problems, premature mortality, seizure remission, socioeconomic factors, and stigma. Diagnostic misclassification - one possible explanation - may result from inclusion of patients with acute symptomatic or isolated unprovoked seizures. Other sources of bias include age and ethnic origin of the target population, definitions of epilepsy, retrospective versus prospective ascertainment, sources of cases, and experienced and perceived stigma. Premature mortality is an issue in low-income countries (LICs), where treatment gap, brain infections, and traumatic brain injuries are more common than in high-income countries (HICs). Death rates may reflect untreated continued seizures or inclusion of acute symptomatic seizures. Lack of compliance with antiepileptic drugs has been associated with increased risk for death, increased hospital admissions, motor vehicle accidents, and fractures in poor communities. Epilepsy is a self-remitting clinical condition in up to 50% of cases. Studies in untreated individuals from LICs have shown that the proportion of remissions overlaps that of countries where patients receive treatment. When the identification of patients is based on spontaneous reports (e.g., door-to-door surveys), patients in remission may be less likely to disclose the disease for fear of stigmatization with no concurrent benefits. This might lead to underascertainment of cases when assessing the lifetime prevalence of epilepsy. In LICs, the proportion of people living in poverty is greater than in HICs. Poverty is associated with risk factors for epilepsy, risk for developing epilepsy, and increased mortality. The high incidence and prevalence of epilepsy found in LICs is also observed in low income individuals from HICs. Epileptogenic conditions are associated with an increased mortality. This may partly explain the difference between incidence and lifetime prevalence of epilepsy in LICs. Poverty within LICs and HICs could be a preventable cause of mortality in epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. © Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Ruggenenti P.,Mario Negri Institute for Pharmacological Research
Nature reviews. Nephrology | Year: 2010

Angiotensin II and other components of the renin-angiotensin-aldosterone system (RAAS) have a central role in the pathogenesis and progression of diabetic renal disease. A study in patients with type 1 diabetes and overt nephropathy found that RAAS inhibition with angiotensin-converting-enzyme (ACE) inhibitors was associated with a reduced risk of progression to end-stage renal disease and mortality compared with non-RAAS-inhibiting drugs. Blood-pressure control was similar between groups and proteinuria reduction was responsible for a large part of the renoprotective and cardioprotective effect. ACE inhibitors can also prevent microalbuminuria in patients with type 2 diabetes who are hypertensive and normoalbuminuric; in addition, ACE inhibitors are cardioprotective even in the early stages of diabetic renal disease. Angiotensin-II-receptor blockers (ARBs) are renoprotective (but not cardioprotective) in patients with type 2 diabetes and overt nephropathy or microalbuminuria. Studies have evaluated the renoprotective effect of other RAAS inhibitors, such as aldosterone antagonists and renin inhibitors, administered either alone or in combination with ACE inhibitors or ARBs. An important task for the future will be identifying which combination of agents achieves the best renoprotection (and cardioprotection) at the lowest cost. Such findings will have major implications, particularly in settings where money and facilities are limited and in settings where renal replacement therapy is not available and the prevention of kidney failure is life saving.

Beghi E.,Mario Negri Institute for Pharmacological Research
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration | Year: 2013

Since the observation of several deaths from amyotrophic lateral sclerosis (ALS) among Italian professional soccer players, an association between ALS and soccer has been postulated, supported by high rates of morbidity and mortality risks in large cohorts of professionals. Several factors may explain this. A history of repeated (head) injuries is reported more frequently by ALS patients than by individuals with other clinical conditions. An association between exercise and ALS has also been suggested, but results in animals and humans are conflicting. Some clinical and experimental observations suggest a relation between ALS and use of substances such as non-steroidal anti-inflammatory agents, and dietary supplements including branched-chain amino acids. Although Italian soccer players may be at higher risk of ALS than players in other countries, and higher than expected disease frequency seems soccer-specific, increased attention by the Italian lay press is an explanation that cannot be excluded. However, growing evidence points to the possibility that soccer players with ALS are susceptible individuals who develop the disease in response to combinations of environmental factors. Only cohort and case-control studies carried out with the same design in different European countries can provide a definite answer to this suspected but still unconfirmed association. © 2013 Informa Healthcare.

Cravedi P.,Mario Negri Institute for Pharmacological Research
Advances in Experimental Medicine and Biology | Year: 2010

Transplantation of pancreatic islets is considered a therapeutic option for patients with type 1 diabetes mellitus who have life-threatening hypoglycaemic episodes. After the procedure, a decrease in the frequency and severity of hypoglycaemic episodes and sustained graft function as indicated by detectable levels of C-peptide can be seen in the majority of patients. However, true insulin independence, if achieved, usually lasts for at most a few years. Apart from the low insulin independence rates, reasons for concern regarding this procedure are the side effects of the immunosuppressive therapy, allo-immunization, and the high costs. Moreover, whether islet transplantation prevents the progression of diabetic microand macrovascular complications is largely unknown. Areas of current research include the development of less toxic immunosuppressive regimens, the control of the inflammatory reaction immediately after transplantation, the identification of the optimal anatomical site for islet infusion, and the possibility to encapsulate transplanted islets to protect them from the allo-immune response. At present, pancreatic islet transplantation is still an experimental procedure, which is only indicated for a highly selected group of type 1 diabetic patients with life-threatening hypoglycaemic episodes. © Springer Science+Business Media B.V. 2010.

Vezzani A.,Mario Negri Institute for Pharmacological Research
Epilepsy Currents | Year: 2014

The possibility that inflammatory processes in the brain contribute to the etiopathogenesis of seizures and the establishment of a chronic epileptic focus is increasingly recognized as a result of supportive evidence in experimental models and in the clinical setting. Prototypical inflammatory cytokines (such as IL-1beta) and "danger signals" (such as HMGB1 and S100beta) are overexpressed in human and experimental epileptogenic tissue, prominently by glia. Neurons and endothelial cells of the blood-brain barrier contribute to inflammatory processes. All these cell types also express receptors for inflammatory mediators, suggesting that inflammatory molecules in the brain exert both autocrine and paracrine activation of intracellular signaling cascades; thus, they may act as soluble mediators of cell communication in diseased tissue. In experimental models, seizures also trigger brain inflammation in the absence of cell loss; in human epileptogenic tissue, the type of neuropathology associated with chronic seizures contributes to determine the type of cells expressing the inflammatory mediators, and the extent to which inflammation occurs. Inflammatory molecules, such as IL-1beta and HMGB1, have proconvulsant activity in various seizure models, most likely by decreasing seizure threshold via functional interactions with classical neurotransmitter systems. These findings reveal novel glioneuronal communications in epileptic tissue that highlight potential new targets for therapeutic intervention.

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