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Biomedical subjects

M A Zocco

Publications and source records attributed to M A Zocco.

25 records · Page 2Linked to original sources
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Human cordonal stem cell intraperitoneal injection can represent a rescue therapy after an acute hepatic damage in immunocompetent rats.

BACKGROUND AND AIM: Tissue homeostasis and turnover require reserve stem proliferating cells. Several studies performed on immunodeficient animals have suggested a degree of plasticity by the hematopoietic stem cell compartment that may represent source for liver regeneration. We sought to explore the hepatic differentiation potential of hematopoietic stem cells from human cord blood, after toxic liver damage induced by allyl-alcohol in immunocompetent rats. MATERIALS AND METHODS: Wistar rats were divided into groups (A) allyl-alcohol intraperitoneal injection with hematopoietic stem cell intraperitoneal infusion at 1 day and sacrifice 3 days later; (B) stem cell injection and sacrifice 3 days later; (C) allyl-alcohol infusion and sacrifice 4 days later; and (D) sacrifice without any treatment. Livers, spleens, and bone marrows were analysed for human stem cells using flow-cytometry; livers were also tested by histology and immunohistochemistry to study the pattern of hepatic regeneration after damage and human stem cell conversion into hepatocyte-like cells, respectively. RESULTS: Flow-cytometry revealed selective recruitment of human hematopoietic stem cells by damaged livers (group A) compared with control group B. In addition, liver damage was reduced in animals treated with stem cells. Immunohistochemistry demonstrated that human stem cells could convert hepatic cells. CONCLUSIONS: Our study demonstrated that hematopoietic stem cells selectively recruited by injured livers can contribute to hepatic regeneration after acute toxic damage in immunocompetent recipients.

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Idiopathic chronic constipation: pathophysiology, diagnosis and treatment.

Constipation is one of the most common disease in Western countries. Its prevalence is widely variable (5-30%), depending on criteria utilized for diagnosis. Usually constipated patients have mild-moderate symptoms and are self-treated. Only patients that do not benefit from simple therapy (dietary supplementation of fiber and water, laxatives) need examinations such as blood tests, colonoscopy, radiography with bario-enemas, intestinal transit time and manometry. These tests are able to differentiate idiopathic from secondary constipation. Idiopathic chronic constipation is a collective term that involves different functional disorders. More specific investigations (oro-cecal transit time, manometry, electromyography) allow one to distinguish between two different patterns of idiopathic chronic constipation (slow transit constipation and pelvic floor disease) and to utilize the appropriate treatment of disease. The aims of this paper are to review the recent world literature on chronic constipation and to propose a diagnostic and a therapeutic flow chart for this disorder.

Chronic Disease↗
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13C-breath tests in the study of mitochondrial liver function.

Breath tests for "dynamic" liver function evaluation have been proposed several years ago. A variety of carbon-labelled breath tests for the assessment of mitochondrial, microsomal and cytosolic liver function have been described with the aim to increase data on liver disease staging, prognosis, and response to therapy. In the last years a great interest is developed about the use of breath test for liver mitochondrial function evaluation since it results impaired in a wide range of liver diseases either of genetic or acquired origin. In these cases mitochondrial oxidative metabolism of some substrates, as far as recovery of the hepatic energy state after a metabolic insult, results impaired because of the disfunction of the electron transport chain and/or ATP synthesis. Ketoisocaproic acid and methionine are the best studied carbon-labelled substrates for the investigation of mitochondrial functional damages related to structural alterations that occur in many liver diseases. Although these tests are simple, cost-effective and safe, to date there is still not general approval for their usefulness in clinical settings since they should fulfill several requirements to overcome the drawbacks of traditional quantitative tests. On the other hand, this field is relatively young and further studies are needed in order to assess the suitable substrate for the evaluation of the complex mitochondrial metabolism both in healthy subjects and in patients with liver disease.

Breath Tests↗
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13C-breath tests in the study of microsomal liver function.

Conventional liver tests can be used to estimate a mixture of injury and function but none of these may be regarded as a reliable marker either to quantify functional hepatic reserve or to reflect life-threatening complications of acute and chronic liver diseases. To overcome this limit, many dynamic tests have been developed in order to evaluate the "hepatic functional mass". Among these tests we can include breath tests with 13C-labeled substrates undergoing different metabolic pathways. As concerning the evaluation of microsomal function, two main categories of breath tests have been developed based on the limiting step in the different substrates metabolism. The first group include aminopyrine, caffeine and diazepam, all substrates with a metabolism independent from hepatic blood flow and dependent almost exclusively from the enzymatic activity of different cytochromes P450. The other group is composed of substrates with flow dependent metabolism like methacetin, phenacetin, erythromycin. The aim of this review is to describe the clinical applications of microsomal liver breath tests in different hepatic diseases.

Acetamides↗
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Hepatic steatosis and vascular disease.

Nonalcoholic fatty liver disease (NAFLD) refers to a wide picture of liver damage, ranging from steatosis to steatohepatitis, fibrosis and cirrhosis. The epidemiological studies demonstrated an association of NAFLD with obesity, type 2 diabetes and hyperlipidemia. Under this light the metabolic syndrome (MS), including NAFLD, obesity, central fat distribution, diabetes, dyslipidemia, hypertension and atherosclerotic cardiovascular disease (CVD) can be considered the link to explain the presence of vascular diseases in patients with NAFLD. In NHANES III, the authors demonstrated that the presence of MS was associated with increased risk of myocardial infarction, stroke or both. In a prospective study on 1209 Finnish middle-aged men without CVD or diabetes at baseline, Lakka showed that MS per se is associated with an increased risk of CVD and all-cause mortality. Finally the Atherosclerosis Risk in Communities (ARIC) confirmed that subjects with MS were 2 times more likely to have prevalent coronary heart disease. From a pathophysiological point of view, growing evidences implicate the oxidative stress as the unifying mechanism for many CVD risk factors. Under this light there is emerging evidence suggesting that there is a significant increase in vascular oxidative stress in patients with MS, with the presence of endothelial dysfunction in the early stage of the syndrome. Indeed, the inflammation process evidentiated in these patients is initiated at the endothelial level, stressing the key role of this active and dynamic tissue in the pathophysiological pathways. Under this light the endothelium can be considered as the last effector of a multi-syndrome and the main target of all the future studies focused on the underlying mechamisms of this complex network. Because of the potential serious public health impact, the comprehension of these patophysiological pathways will be crucial to design new preventive measures and therapeutic strategies.

Animals↗
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From stem cell to solid organ. Bone marrow, peripheral blood or umbilical cord blood as favorable source?

Adult stem cells (ASC) have becoming a great domain of research by their promising interest for the regenerative medicine. For some years, the number of publications has been increasing, displaying the potential of ASC to differentiate in all tissue-lineages, challenging the previous dogma that ASC were restricted to give rise only to specific cells from their tissue of origin. Among the diversity of ASC, hematopoietic stem cells (HSC) have been the most studied and their use in the clinical setting is largely documented. Commonly, HSC have been harvested from the bone marrow, but for some years, two others sources, the peripheral blood and the umbilical cord blood have been introduced. All these HSC posses their own molecular characteristics and degree of maturity and represent a more or less good candidate to participate in the cellular-based tissue regeneration. We have reviewed the different parameters allowing to define which subset could be the more favorable such as the accessibility to the pool of HSC; the quantity of available cells; the tolerability of host-engraftment and the capacity of the cells to home correctly to the required site of damaged. Besides, recently, the molecular profiling of HSC has allowed identifying which subset posses the more promising characteristics.

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