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Biomedical subjects

A Ferro

Publications and source records attributed to A Ferro.

At least 19 recordsLinked to original sources

Increased platelet aggregation in vivo in the Zucker Diabetic Fatty rat: differences from the streptozotocin diabetic rat.

BACKGROUND AND PURPOSE: Diabetes mellitus, especially type 2, is associated with increased arterial thrombosis. Our aims were (i) to characterize and compare platelet aggregation in vivo and in vitro in a type 2 diabetes model; and (ii) to determine whether these results differ from those in a type 1 diabetes model. EXPERIMENTAL APPROACH: Platelet aggregation to ADP in lean or obese Zucker Diabetic Fatty (ZDF) rats and in streptozotocin (STZ)-treated or control Wistar rats was measured in vitro, using Born aggregometry, and in vivo, by (111)Indium-labelled pulmonary platelet accumulation. KEY RESULTS: In vivo, ADP responses were higher in obese (type 2 model) than lean ZDF rats. However, in vitro, ADP aggregation did not differ between platelet-rich plasma from ZDF lean or obese rats; nor was any difference seen in ADP responses when platelets from either lean or obese ZDF rats were suspended in plasma from obese or lean ZDF rats, respectively. In vivo, ADP responses were similar in STZ treated (type 1 model) and control rats whereas, in vitro, isolated platelets from STZ diabetic rats were more responsive to ADP aggregation than controls. Platelets from control or STZ-treated rats suspended in plasma from STZ-treated rats exhibited reduced ADP aggregation, compared to when suspended in plasma from control rats. CONCLUSIONS AND IMPLICATIONS: The platelet aggregation results obtained in vitro do not reflect those in vivo, therefore in vitro aggregation data should be interpreted with caution. Moreover, both in vitro and in vivo, different diabetic models exhibit important differences in platelet responsiveness.

Animals↗

UbcH10 expression may be a useful tool in the prognosis of ovarian carcinomas.

The UbcH10 gene codes for a protein that belongs to the ubiquitin-conjugating enzyme family. Previous studies of our group suggest UbcH10 expression as a valid indicator of the proliferative and aggressive status of thyroid carcinomas. Therefore, to better understand the process of ovarian carcinogenesis, and to look for possible tools to be used as prognostic markers in these neoplasias, we decided to extend the analysis of the UbcH10 expression to the ovarian neoplastic disease. We found that the UbcH10 gene was upregulated in some ovarian carcinoma cell lines analysed. Then, immunohistochemical studies demonstrate that UbcH10 expression significantly correlates with the tumor grade and the undifferentiated histotype of the ovarian carcinomas. Furthermore, a significant relationship between UbcH10 expression and overall survival was observed. Finally, the block of UbcH10 protein synthesis by RNA interference inhibited the growth of ovarian carcinoma cell lines, suggesting a role of UbcH10 overexpression in ovarian carcinogenesis. Therefore, all these data taken together suggest the possibility to use UbcH10 detection as a marker for the diagnosis and prognosis of these neoplastic diseases and open the perspective of a therapy of some ovarian carcinomas based on the suppression of the UbcH10 synthesis and/or function.

Carcinoma↗

Beta-adrenergic receptors and nitric oxide generation in the cardiovascular system.

Nitric oxide plays a crucial role in cardiovascular homeostasis, with important vasodilatory, anti-thrombotic and anti-atherogenic properties. Beta-adrenergic receptors (betaARs), present on a wide variety of cardiovascular cells, including vascular endothelial cells, platelets, cardiac myocytes and leukocytes, have long been established as key players in maintaining cardiovascular homeostatic control. During the last few years a wealth of evidence has emerged which directly links stimulation of these cardiovascular betaARs to nitric oxide (NO) generation, suggesting a new and important mechanism of adrenergic control of cardiovascular function. This review explores the cardiovascular cell systems in which this coupling of betaARs and NO occurs, the intracellular signalling and regulatory mechanisms involved and the abnormalities in betaAR-NO oxide coupling found in cardiovascular disease states.

Aging↗

Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy.

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.

Apoptosis↗

Importance of renin in blood pressure regulation and therapeutic potential of renin inhibition.

Despite improvements in its detection and treatment, hypertension remains a significant public health problem worldwide. In recent years, many international hypertension societies and organisations have set increasingly rigorous blood pressure (BP) targets, with the aim of reducing cardiovascular complications, and this has in turn necessitated the use of more antihypertensive medications to reach these targets in individual patients. There is therefore an ongoing need to develop antihypertensive drugs with new mechanisms of action. Renin inhibitors represent a novel class of compounds which offer considerable promise as BP-lowering agents. Here, we review the rationale for renin inhibition as a therapeutic target and examine the preclinical and clinical evidence for the antihypertensive effectiveness of the renin inhibitors.

Antihypertensive Agents↗

Neurohormones and heart failure: the importance of aldosterone.

Heart failure is a major cause of cardiovascular morbidity and mortality and its incidence is on the increase. The pathophysiology of heart failure is multi-factorial but recent studies suggest that aldosterone plays an important and independent role in its progression. Emerging evidence now suggests that aldosterone exerts renal-independent effects. It binds to its mineralocorticoid receptor to produce direct effects on the myocardium and vasculature, leading to damaging processes such as hypertrophy, necrosis, fibrosis and endothelial dysfunction, factors known to contribute to the pathophysiology of heart failure. Mineralocorticoid receptor antagonists have thus emerged as a new paradigm for the treatment of heart failure. The benefits of these agents on both morbidity and mortality when used in patients with chronic symptomatic heart failure have been demonstrated by recent trials.

Adaptation, Physiological↗

Population genetics of wild-type CAG repeats in the Machado-Joseph disease gene in Portugal.

OBJECTIVE: To gain insights on the molecular mechanisms of mutation that led to the emergence of expanded alleles in the MJD gene, by studying the behavior of wild-type alleles and testing the association of its distribution with the representation of the disease. METHODS: The number of CAG motifs in the MJD gene was determined in a representative sample of 1000 unrelated individuals. Associations between the repeat size and the epidemiological representation of MJD were tested. RESULTS: The allelic profile of the total sample was in the normal range (13-41 repeats), with mode (CAG)23. No intermediate alleles were present. Allelic size distribution showed a negative skew. The correlation between the epidemiological representation of MJD in each district and the frequency of small, medium and large normal alleles was not significant. Further correlations performed grouping the districts also failed to produce significant results. CONCLUSIONS: The absence of association between the size of the repeats and the representation of MJD demonstrates that prevalence is not an indirect reflection of the frequency of large normal alleles. Globally the results obtained are in accordance with a model that postulates the occurrence of a few mutations on the basis of most of the MJD cases worldwide.

Ataxin-3↗

The "Green Channel" of the Veneto region as a model for vaccine safety monitoring in Italy.

Modern vaccinology and public health organizations need to satisfy an increased safety demand. Therefore, to improve adverse events following immunization (AEFIs) surveillance systems, some countries have established clinical evaluation centers for AEFI assessment and management of at risk individuals. In the Veneto region of Italy, the Green Channel operates through a counselling service for subjects with prior AEFI or with suspected contraindications to vaccine administration, and a surveillance system of the AEFIs reported in the region. Updated data on 753 consultations and 3023 AEFI analyses are discussed together with the opportunity to include the Green Channel model as part of an international vaccine safety network.

Child↗

Primary reconstruction of anterior neck burns with free flaps.

Comprehensive management of acute neck burns is directed towards a satisfactory aesthetic and functional result. Primary microsurgical burn reconstruction of the anterior neck may offer advantages over the traditional technique of skin grafting and delayed reconstruction. It can be indicated in selected patients, obtaining good aesthetic results, with earlier functional recovery and reducing the number of surgical procedures required.

Burns↗

Current status and future possibilities of nitric oxide-donor drugs: focus on S-nitrosothiols.

Drugs which release nitric oxide (NO) have great therapeutic potential. The organic nitrates and sodium nitroprusside have been used in cardiovascular therapeutics for many years, but several drawbacks limit their usefulness. In this review, we consider novel and potential future developments in NO-donor drugs, and the possible clinical usefulness of such compounds.

Cardiovascular Agents↗

Asymptomatic struma ovarii: a case report.

Struma ovarii is a rare ovarian neoplasm. This tumor is generally benign, although malignant transformation has been reported. The preoperative diagnosis is generally difficult. Thyroid hormones may be produced and in a few cases asymptomatic women may develop definitive clinical hypothyroidism after resection of struma ovarii. We report a case of a 39-year-old woman who underwent laparoscopic resection of an asymptomatic right ovarian mass. The pathologic diagnosis was struma ovarii. The postoperative period was uneventful and her thyroid function remained normal.

Adult↗

Drug treatment of essential hypertension: the case for initial combination therapy.

Essential hypertension is a major cause of cardiovascular morbidity and mortality in the Western world, yet it remains poorly controlled. Single drug-antihypertensive therapy is unsuccessful in up to half of all patients with hypertension; although lack of adherence may account for a proportion of this, there is evidence of considerable variation in the response of different hypertensive patients to different drug classes. A number of algorithms have been proposed in the literature, with a view to predicting an individual's response to different antihypertensive agents. However, even using such algorithms, hypertension control remains problematic, and they are frequently difficult to apply in everyday clinical practice. Initiation of treatment with low-dose combination antihypertensive therapy, using a drug which reduces total body sodium and/or volume in combination with a drug which blocks the renin-angiotensin system, provides an effective and easily applicable means to improve hypertension control in the primary care setting.

Adrenergic beta-Antagonists↗

S-nitrosothiols as nitric oxide-donors: chemistry, biology and possible future therapeutic applications.

In recent years, the gaseous molecule nitric oxide (NO) has been shown to be involved in many important biological events. S-Nitrosothiols are biological substances derived endogenously from NO, and are found in a variety of tissues exhibiting NO-mimetic activity. Fundamental studies on the chemical aspects of S-nitrosothiols have become an integral part of NO research, with a view to further understanding the numerous biological functions both of NO and of S-nitrosothiols themselves. It has often been suggested that S-nitrosothiols represent a means either for the storage or transport of NO, although the evidence for this is sparse. Many S-nitrosothiols have now been synthesized chemically, and at present they show the most promise as clinically useful NO-donor drugs. In this review, we examine in detail the biological functions of S-nitrosothiols, as well as the chemical properties and biomedical applications of these compounds.

Animals↗