207 research outputs found

    Medical Implications of the Relationships among Protein Denaturation, Necrosis and Inflammation: An Intriguing Story

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    This story deals with the role of protein denaturation in inflammation. The starting point was the description of the necrotizing action of inflammatory proteins, followed by the discovery of the antidenaturant action of NSAIDs (nonsteroidal anti-inflammatory drugs). Hence, the idea is that the antidenaturant action accounted for the action of NSAIDs. This hypothesis was dropped following the discovery of the antiprostaglandin action of NSAIDs, which shifted the focus to the arachidonic acid cascade. It was revived by assuming that protein denaturation is a process in its own, suitable for separate medical treatment. This approach led to bendazac and bindarit, the first selective antidenaturant drugs. This experience shows that protein denaturation has two main pathological sequelae. The first concerns the so-called primary (innate) inflammation. The second sequela concerns the so-called secondary (acquired) inflammation. Natural antidenaturant agents represent a promising alternative to the synthetics bendazac and bindarit. Within this framework, tendinitis finds a separate but significant place

    Toxicity testing in environmental monitoring: The role of enzymatic biosensors

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    Biological toxicity testing is a rapidly expanding field involving numerous bioanalytical techniques. The enzymatic biosensors are valuable screening tools to identify pollutants and/or toxic agents in the environment and/or in food matrices, thus representing a valid alternative to animal testing in analytical toxicology. Inhibition based biosensors here presented have been proved to represent alternative assays for the toxicity evaluation of warfare agents and endocrine disrupting chemicals as well as algal toxins (phycotoxins) in the contamined sea foods (mainly clams and other mollusks). Results obtained by inhibition studies performed by means of several enzymatic biosensors indicate the reliability of the proposed method and the possibility to extend such an experimental approach to other toxicants as a simple, rapid and cheap biotest, to be used easily also "on the spot"

    Collagen Involvement in Health, Disease, and Medicine

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    This chapter discusses the physiologic, metabolic, and clinical aspects of collagen, including the role of nutritional factors in a new nosographic entity, called “extended collagen carential disease.” Except water and possibly fats, carbohydrates, and other structural proteins, perhaps there is more collagen in the mammalian body than anything else. Moreover, collagen participates in almost all of the body functions, adjusting its structure constantly in response to changes in environment, development, growth, and external clues. Collagens found in bones and nails are different from collagens found in body fluids and other biological structures, such as basement membrane, skin, tendons, muscles, and hair. The ubiquity of collagen functions accounts for its phylogenetic ubiquity, involving any tissue, organ, and apparatus. This is shown by the so-called “collagen carential disease,” involving nails, hair, osteoarticular and gastrointestinal systems. For instance, the Ehlers-Danlos syndrome describes another group of genetic collagen disorders, affecting the collagen processing and structure. Some of them are inherited in an autosomal dominant manner, while others emerge in the absence of essential nutritional factors. It is the case of Vitamin C, which plays a critical role in the maintenance of a normal mature collagen network. Hence, the idea of an “extended collagen carential disease,” applicable to the absence of essential nutritional factors

    Evaluation of oxidative stress effects on different macromolecules in adult growth hormone deficiency

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    Adult growth hormone deficiency (GHD) is being increasingly recognized to cause premature mortality exacerbated by oxidative stress. A case-control observational study has been performed with the primary objective of evaluating new parameters of oxidative stress and macromolecular damage in adult GHD subjects: serum nitrotryptophan; Total Antioxidant Capacity expressed as LAG time; urinary hexanoil-lysine; urinary dityrosine and urinary 8-OH-deoxyguanosine. GHD was diagnosed using Growth Hormone-Releasing Hormone 50\u3bcg iv+arginine 0,5 g/Kg test, with a peak GH response <9 \u3bcg /L when BMI was <30 kg/m2 or <4 \u3bcg/L when BMI was >30 kg/m2. Patients affected by adult GHD were divided into three groups, total GHD (n = 26), partial GHD (n = 25), and controls (n = 29). Total Antioxidant Capacity, metabolic and hormonal parameters have been determined in separate plasma samples; nitrotryptophan in serum samples; hexanoil-lysine, dityrosine, 8-OH-deoxyguanosine in urine samples. Assessment of hexanoil-lysine exhibited a trend to increase in comparing total GHD vs partial and controls, although not significant. Values of 8-OH-deoxyguanosine did not significantly differ among the three groups. Significant lower levels of dityrosine in partial GHD vs total and controls were found. No significant difference in nitrotriptophan serum levels was found, while significantly greater values of Total Antioxidant Capacity were showed in total and partial GHD vs controls. Thus, our result confirm that oxidative stress is increased both in partial and total adult GHD. The lack of compensation by antioxidants in total GHD may be connected to the complications associated to this rare disorder

    Circulating irisin levels in heart failure with preserved or reduced ejection fraction: A pilot study

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    Irisin, a recently discovered myokine, has been considered a prognostic factor in several cardiovascular diseases. Nevertheless, no data are available on the role of irisin in patients with heart failure (HF), both with preserved (HFpEF) or reduced (HFrEF) ejection fraction. We have therefore evaluated the circulating irisin levels in HFpEF and HFrEF patients, correlating them with metabolic parameters and total antioxidant capacity (TAC), as index of oxidative stress. Irisin was significantly higher in HFpEF than in HFrEF patients (7.72 \ub1 0.76 vs 2.77 \ub1 0.77 ng/ml, respectively). An inverse correlation between irisin and TAC was found in HFpEF, but not in HFrEF. Conversely, no correlation was present with HOMA index. These data support the hypothesis that a different pathophysiological mechanism is involved in the two HF subtypes, and oxidative stress modulates irisin secretion

    Anabolic Hormone Deficiencies in Heart Failure with Reduced or Preserved Ejection Fraction and Correlation with Plasma Total Antioxidant Capacity

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    While anabolic hormone deficit is a common finding in heart failure with reduced ejection fraction (HFrEF), few data are available in heart failure with preserved ejection fraction (HFpEF). Methods. Blood samples were collected for metabolic (total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glucose) and hormonal (IGF-1, DHEA-S, TSH, fT3, fT4, and T) determination, comparing 30 patients with HFpEF and 20 patients with HFrEF. Total antioxidant capacity was evaluated by using the spectrophotometric method using the latency time in the appearance of the radical species of a chromogen (LAG, sec) as a parameter proportional to antioxidant content of the sample. Echocardiographic parameters were also assessed in the two groups. Results. A high prevalence of testosterone (32% in HFrEF and 72% in HFpEF, ) and DHEA-S deficiencies was observed in HFpEF patients. Echocardiographic parameters did not correlate with hormone values. A significant direct correlation between T (r2\u2009=\u20090.25, ) and DHEA-S (r2\u2009=\u20090.19, ) with LAG was observed only in HFpEF. Conclusion. Anabolic hormone deficiency is clearly shown in HFpEF, as already known in HFrEF. Although longitudinal studies are required to confirm the prognostic value of this observation, our data suggest different mechanisms in modulating antioxidants in the two conditions, with possible therapeutic implications

    Standard Model Confronting New Results for epsilon'/epsilon

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    We analyze the CP violating ratio \epe=epsilon'/epsilon in the Standard Model in view of the new KTeV results. We review the present status of the most important non-perturbative parameters B_6, B_8, B_K and of the strange quark mass m_s. We also briefly discuss the issues of final state interactions and renormalization scheme dependence. Updating the values of the CKM parameters, of m_t and Lambda (MSbar) and using Gaussian errors for the experimental input and flat distributions for the theoretical parameters we find \epe substantially below the NA31 and KTeV data: \epe= (7.7^{+6.0}_{-3.5}) 10^{-4} and \epe= (5.2^{+4.6}_{-2.7}) 10^{-4} in the NDR and HV renormalization schemes respectively. A simple scanning of all input parameters gives on the other hand 1.05 10^{-4} < \epe < 28.8 10^{-4} and 0.26 10^{-4} < \epe < 22.0 10^{-4} respectively. Analyzing the dependence on various parameters we find that only for extreme values of B_6, B_8 and m_s and suitable values of CKM parameters and Lambda(MSbar), the ratio \epe can be made consistent with data. We analyze the impact of these data on the lower bounds for Im(V_{td}V_{ts}^*), Br(K_L to pi^0 nu barnu), Br(K_L to pi^0e^+e^-)_{dir} and on tan(beta) in the Two Higgs Doublet Model II.Comment: main latex-file, 4 figures and related latex files, 47 page
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