Serum biomarkers predictive of cirrhosis in alcoholic liver disease as an alternative to ARFI-SW elastography.

OBJECTIVE: Aspartate aminotransferase to platelet ratio index (APRI) and fibrosis 4 (FIB-4) index are noninvasive biomarkers that evaluate liver stiffness in patients with chronic viral hepatitis and are able to detect advanced hepatic fibrosis and cirrhosis. However, their usefulness in alcoholic liver disease (ALD), when compared with Acoustic Radiation Force Impulse- Shear Wave (ARFI-SW) elastography, is debatable. PATIENTS AND METHODS: We sifted the files of all enrolled patients with ALD that were admitted to our Emergency hospital between January 2019 and December 2020. All patients had undergone ARFI-SW elastography, and APRI and FIB-4 scores were calculated. The performance of APRI and FIB-4 scores in the prediction of cirrhotic patients according to ARFI-SW elastography was evaluated. RESULTS: In total, 120 patients with ALD were evaluated. All of them were male and Caucasian, with a mean age of 55.54±12.4 years. The mean ARFI-SW elastography score was 1.57±0.7 m/s, the median APRI score was 0.68 (0.1-11.6) and the median FIB-4 score was 1.8 (0.2-19.4). Stages of liver fibrosis according to ARFI-SW elastography were evaluated as F0-1 in 21 (10.5%), F2 in 35 (26%), F3 in 52 (17.5%), and F4 in 92 (46%) patients. Based on ARFI-SW elastography fibrosis stage classification, we estimated the optimal APRI and FIB-4 scores to predict the presence of liver cirrhosis (F4) by using ROC curve analysis and the Youden index. The optimal APRI score for F4 patients was calculated as >1.52 [area under the curve (AUC) 0.875, 95% CI 0.809-0.919; p<0.001], giving sensitivity (Se) 81.2%, specificity (Sp) 81.4%, positive predictive value (PPV) 76%, and negative predictive value (NPV) 86.1%. The optimal FIB-4 score for F4 patients was calculated as >2.77 (AUC 0.916, 95% CI 0.814-0.922; p<0.001), giving Se 83.8%, Sp 77%, 81.4 77%, and NPV 84.3%. CONCLUSIONS: APRI and FIB-4 scores can be used as screening tools in ALD for predicting cirrhosis instead of ARFI-SW elastography measurement, which is neither widely available nor an affordable method. Additional prospective studies are required in the future to confirm this finding.

Oxidative stress in androgenetic alopecia.

Rationale:Androgenetic alopecia is not considered a life threatening disease but can have serious impacts on the patient's psychosocial life. Genetic, hormonal, and environmental factors are considered responsible for the presence of androgenetic alopecia. Recent literature reports have proved the presence of inflammation and also of oxidative stress at the level of dermal papilla cells of patients with androgenetic alopecia Objective:We have considered of interest to measure the oxidative stress parameters in the blood of patients with androgenetic alopecia Methods and results:27 patients with androgenetic alopecia and 25 age-matched controls were enrolled in the study. Trolox Equivalent Antioxidant Capacity (TEAC), malondialdehyde (MDA) and total thiols levels were measured on plasma samples. Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activities, and also non protein thiols levels together with TEAC activity were determined on erythrocytes samples No statistically significant changes were observed for TEAC erythrocytes, non-protein thiols, GPx and CAT activities. Significantly decreased (p<0.01) SOD activity was found in patients with androgenetic alopecia. For plasma samples decreased TEAC activity (p<0.001), increased MDA levels (p<0.001) and no change in total thiols concentration were found in patients when compared with the controls. Discussions:Decreased total antioxidant activity and increased MDA levels found in plasma samples of patients with androgenetic alopecia are indicators of oxidative stress presence in these patients. Significantly decreased SOD activity but no change in catalase, glutathione peroxidase, non protein thiols level and total antioxidant activity in erythrocytes are elements which suggest the presence of a compensatory mechanism for SOD dysfunction in red blood cells of patients with androgenetic alopecia. ABBREVIATIONS: AAG = androgenetic alopecia, MDA = malondialdehyde, SOD = superoxide dismutase, CAT = catalase, GPx = glutathione peroxidase, GSH = glutathione, GST = glutathione transferase, SH = thiols, TEAC = trolox equivalent antioxidant capacity, ABTS = 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), CDNB = 1-chloro-2,4-dinitrobenzene.

Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats.

Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme.

Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats

Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme.

Clozapine and risperidone influence on cortisol and estradiol levels in male patients with schizophrenia.

Estrogens role in schizophrenia patients is a subject, which has gained an increased attention from the medical community. Estrogens have been shown to inhibit dopamine actions, improve neuronal regeneration, and overall, have a protective role in the pathology of schizophrenia. The adjunctive estrogen therapy for men is currently under debate. Antipsychotic medication is known to influence the hypothalamo-hypophyseal - gonadal axis by inducing variable degrees of hyperprolactinemia. Several studies have found that some of the atypical antipsychotics lower cortisol levels in patients and also in healthy controls. We have investigated the effects of clozapine and risperidone on estradiol levels in men with schizophrenia. We have also evaluated the levels of prolactin and cortisol, taking into account the possible influence of antipsychotic drugs on both these hormones. Both prolactin and cortisol also have the potential to regulate sexual hormones biosynthesis. Our study found decreased estradiol levels in men with schizophrenia treated with clozapine and risperidone, while prolactin levels were increased only in the risperidone treated group. Cortisol levels are not statistically significant different between groups.

Oxidative stress and alopecia areata.

Alopecia areata (AA) is an inflammatory and autoimmune disease presenting with non-scarring hair loss. The aethiopathogenesis of alopecia areata is unclear and many factors including autoimmunity, genetic predisposition, emotional and environmental stress are thought to play important roles in its development. Antioxidant/ oxidant balance perturbation is a common feature in autoimmune, emotional and environmental stress. Therefore, our paper discusses the implications of oxidative stress in alopecia areata.

Venous versus arterial iron administration in haemodialysis. Influence on erythrocytes antioxidant parameters.

Introduction Intravenous iron administration in patients treated by haemodialysis for end stage renal disease can exacerbate oxidative stress by increasing the level of free redox active iron. A way to reduce the impact of iron on oxidative stress in haemodialysis patients may be the administration of iron through arterial extracorporeal circuit. Objective The aim of our study was to compare the influence of iron route of administration (venous versus arterial extracorporeal circuit infusion) on antioxidant parameters in red blood cells of haemodialysis patients in order to clarify if arterial iron administration can have positive impacts related to iron induced oxidative stress. Method Twenty stable patients on regular haemodialysis treatment were selected for the study. They were investigated in a cross-over design at 3 mid-week HD sessions, one week apart, without iron [HD basal] and with either IV infusion of 100mg iron sucrose over the first 20 minutes of HD session, via venous line [HDvenous], or the same solution infused on the arterial extracorporeal circulation [HDarterial]. Blood samples were drawn at 0 min, 40 min and 270 min. Erythrocytes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activity, non-protein thiol levels and total antioxidant capacity (TEAC) were analysed. Conclusion Haemodialysis significantly decreases the total antioxidant activity in erythrocytes. Iron supplementation, through venous or arterial extracorporeal route has no impact on the total antioxidant activity in red blood cells. Venous iron administration increases GPx activity in erythrocytes suggesting increased lipid peroxidation compared with arterial extracorporeal administration.

Biochemical changes and treatment in glaucoma.

Glaucoma is the second cause of blindness worldwide. This disease is a neurodegenerative disorder characterized by high intraocular pressure, loss of retinal ganglion cells (apoptosis). Even though there is much research done in this field, the results have not yet managed to stop the progression of glaucoma or to heal this pathology. Free oxygen radicals play a major role; they are formed in the aqueous humor and in the vitreous and they produce apoptosis of the neurons in the optic nerve head, degradation of the trabecular meshwork cells. The purpose of the article is to help in trying to understand the physiopathology of glaucoma and the efficacy of its treatments.

Gingival overgrowth as secondary effect of calcium channel blockers administration. A case report.

Gingival overgrowth is, among other things, a side effect of the administration of dihydropyridine antihypertensives, generally associated with irritant factors of marginal periodontium. This case refers to a patient, female, who developed a large gingival enlargement that has a combined etiology: the systemic medication with lercanidipina and the presence of dental bridges, which are incorrectly adjusted to the dental cervix. The treatment for this case, involved a complex local treatment (antimicrobial, surgical, endodontic and prosthetic) and the collaboration with a specialist cardiologist. Maintaining the normal gingival parameters in time depends on the possibility of changing the antihypertensive medication, the accuracy of the new dental bridges and the periodic monitoring of the patient.

Implant surgery in healthy compromised patients-review of literature.

Systemic diseases are of major importance in terms of prosthetic restorations supported by dental implants in healthy compromised patients. Each treatment stage from conception of the treatment plan to the long-term monitoring is under the necessity of the interdisciplinary approach to the underlying disease.

Increase in total antioxidant capacity of plasma despite high levels of oxidative stress in uncomplicated type 2 diabetes mellitus.

OBJECTIVE: Oxidative stress is implicated in the pathophysiology of diabetes mellitus and its chronic complications. The aim of this study was to evaluate plasma antioxidant status in patients with uncomplicated type 2 diabetes, in order to understand the interactions between its components and the diabetic milieu. METHODS: Plasma samples were collected from 15 patients with type 2 diabetes receiving oral antidiabetic agents and from 18 healthy control subjects without diabetes. Glycosylated haemoglobin was measured as an indicator of blood glucose control. Total and residual antioxidant activities were measured. Lipid peroxides were measured as indicators of plasma oxidative stress. Copper and caeruloplasmin were also assayed as possible pro-oxidants. RESULTS: Antioxidant activities, lipid peroxide level, copper concentration and caeruloplasmin activity were significantly increased in the plasma of patients with diabetes compared with control subjects. CONCLUSIONS: The total antioxidant capacity of plasma was increased, despite high levels of oxidative stress, in patients with uncomplicated type 2 diabetes. Increased levels of copper and caeruloplasmin characterized the diabetic milieu, despite an absence of chronic complications.

Can ageing be slowed?: Hormetic and redox perspectives.

Redox metabolism has long been considered to play important roles in aging and the development of age-related diseases. Both dietary and pharmacological manipulations of redox metabolism have been associated with the extension of lifespan. Increasing new evidence s also suggests that the process of aging may derive from imperfect clearance of oxidatively damaged material. The accumulation of this molecular "garbage", relatively indigestible, further hinders cellular functions, induces progressive failure of maintenance and repair and increases the probability of death. One important trend in anti-aging strategy is, therefore, to prevent or even revert the accumulation of these oxidatively altered molecules by stimulating the maintenance and repair systems through hormesis. A promising approach for slowing down ageing and achieving a healthy senescence is represented by repeated exposure to various mild stresses (caloric restriction, moderate exercise, nutritional or pharmacological hormetins). This article reviews the potential therapeutic tools available to date for increasing longevity and obtaining and successful ageing from the redox and hormetic perspective.

Problems concerning diagnosis and treatment of compartment syndromes after lower limb trauma.

Compartment Syndrome (CS) is characterised by an imbalance produced by increased pressure in an inextensible space (called "the Compartment"). Without being specific for orthopaedics, CS has increasing frequency in modern traumatology. Microcirculation disturbances generate the syndrome's self-augmenting physiopathological character. The pathognomonic feature of the clinical panel in CS of the lower limbs is increased consistency of the muscular groups, while peripheral pulse maintainance does not exclude CS. Although positive diagnosis is based on measuring the intra-compartmental pressure, (ICP) clinical suspicion is crucial. The correct treatment is surgical, consisting in early and large decompressive fasciotomy. Without proper treatment, CS endangers not only the vitality of the limb (due to Acute Peripheral Ischemia with onset in microcirculation and centripetal extension), but also the patient's life, thus becoming a life-threatening disorder. The authors underline the importance of correct clinical evaluation and early treatment in order to prevent the serious local and general complications of the CS.

Metastatic malignant melanoma.

Metastatic malignant melanoma is an incurable malignancy with extremely poor prognosis. Patients bearing this diagnosis face a median survival time of approximately 9 months with a probability of surviving 5 years after initial presentation at less than 5%. This is contrasted by the curative nature of surgical resection of early melanoma detected in the skin. To date, no systemic therapy has consistently and predictably impacted the overall survival of patients with metastatic melanoma. However, in recent years, a resurgence of innovative diagnostic and therapeutic developments have broadened our understanding of the natural history of melanoma and identified rational therapeutic targets/strategies that seem poised to significantly change the clinical outcomes in these patients. Herein we review the state-of-the-art in metastatic melanoma diagnostics and therapeutics with particular emphasis on multi-disciplinary clinical management.

The electrocardiographic abnormalities in highly trained athletes compared to the genetic study related to causes of unexpected sudden cardiac death.

BACKGROUND: Electrocardiograms in elite endurance athletes sometimes show bizarre patterns suggestive of inherited channelopathies (Brugada syndrome, long QTc, catecholaminergic polymorphic ventricular tachycardia) and cardiomyopathies (arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy) responsible for unexpected sudden cardiac death. Among other methods, genetic analyses are required for correct diagnosis. OBJECTIVE: To correlate 12-lead electrocardiographic patterns suggestive of inherited channelopathies and cardiomyopathies to specific genetic analyses. DESIGN: Prospective study (2004-2007) of screening 12-lead ECG tracings in standard position and higher intercostal spaces V1 to V3 precordial leads, performed in athletes and normal sedentary subjects aged match. Genetic analyses of subjects with ECG abnormalities suggested inherited channelopathies and cardiomyopathies. SETTING: All cardiologic exams and electrocardiograms were performed at "Prof. Dr. C.C. Iliescu" National Institute of Cardiovascular Diseases (Bucharest, Romania). The genetic studies were done at "Mina Minovici" National Institute of Forensic Medicine (Bucharest, Romania). PARTICIPANTS: 347 elite endurance athletes (seniors--190, juniors--157), mean age of 20; 200 subjects mean age of 21, belonging to the control group of 505 normal sedentary population. RESULTS: Seniors. RSR' (V1 to V3) pattern, in 45 cases (23.68%), 5 of them with questionable Brugada sign (elevated J wave and "coved" ST segment, < 2 mm in one lead, V1. Typically, Brugada 1 sign was found in one case (0.52%) with no SCN5A abnormalities. One athlete (0.52%) had normal ECG and exon1 SCN5A duplication. MRI confirmed three arrhythmic right ventricular cardiomypathy epsilon waves (1.57%), in one case. ST-segment elevation myocardial injury like in V1-V3 precordial leads in 34 athletes (17.89%). Genetic analyses-no gene mutations. Juniors. Upright J wave was found in 43 cases (27.38%). Convex ST segment elevation in V1-V3/V4, in 39 cases (24.84%). Bifid T wave with two distinct peaks was found in 39 cases (24.84%), 5 of them with mild prolonged QTc (0.48"-0.56") and KCN genes mutations. Nine (5.73%) of the elevated ST segment juniors had questionable Brugada sign, two of which with KCN (n=1) and SCN5A (n=1) gene mutations. Ajmaline provocative test was negative in 4 and was refused by 5 subjects. CONCLUSION: Bizarre QRS, ST-T patterns suggestive of abnormal impulse conduction in the right ventricle, including the right outflow tract, associated with prolonged QTc interval in some cases were observed in highly trained endurance athletes. The genetic analyses, negative in most athletes, identified surprising mutations in SCN5A and KCN genes in some cases.

So many options but one choice: the human body prefers alpha-tocopherol. A matter of stereochemistry.

alpha-Tocopherol belongs to the group of vitamin E vitamers. Recent years findings indicate that alpha-tocopherol is more than just a simple fat-soluble anti-oxidant as it was found that it can also regulate gene expression. From all vitamin E vitamers human body preferentially retains alpha-tocopherol, but the reasons for this preference are still elusive. Different studies indicated that human body, through the action of two hepatic proteins, alpha-tocopherol transfer protein (alpha-TTP) and cytochrome P450 4F2 (CYP4F2), is able to make subtle structural differences between different vitamin E forms. This is an example of stereochemistry used as a discrimination factor between molecules with different biological activities.

The oxidative hypothesis of senescence.

The oxidative hypothesis of senescence, since its origin in 1956, has garnered significant evidence and growing support among scientists for the notion that free radicals play an important role in ageing, either as "damaging" molecules or as signaling molecules. Age-increasing oxidative injuries induced by free radicals, higher susceptibility to oxidative stress in short-lived organisms, genetic manipulations that alter both oxidative resistance and longevity and the anti-ageing effect of caloric restriction and intermittent fasting are a few examples of accepted scientific facts that support the oxidative theory of senescence. Though not completely understood due to the complex "network" of redox regulatory systems, the implication of oxidative stress in the ageing process is now well documented. Moreover, it is compatible with other current ageing theories (e.g, those implicating the mitochondrial damage/mitochondrial-lysosomal axis, stress-induced premature senescence, biological "garbage" accumulation, etc). This review is intended to summarize and critically discuss the redox mechanisms involved during the ageing process: sources of oxidant agents in ageing (mitochondrial -electron transport chain, nitric oxide synthase reaction- and non-mitochondrial- Fenton reaction, microsomal cytochrome P450 enzymes, peroxisomal beta -oxidation and respiratory burst of phagocytic cells), antioxidant changes in ageing (enzymatic- superoxide dismutase, glutathione-reductase, glutathion peroxidase, catalase- and non-enzymatic glutathione, ascorbate, urate, bilirubine, melatonin, tocopherols, carotenoids, ubiquinol), alteration of oxidative damage repairing mechanisms and the role of free radicals as signaling molecules in ageing.

Right ventricular functional recovery after acute myocardial infarction: relation with left ventricular function and interventricular septum motion. GISSI-3 echo substudy.

OBJECTIVE: To evaluate the pattern of right ventricular (RV) functional recovery and its relation with left ventricular (LV) function and interventricular septal (IVS) motion in low risk patients after acute myocardial infarction (AMI). DESIGN AND SETTING: Multicentre clinical trial carried out in 47 Italian coronary care units. PATIENTS: 500 patients from the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico) -3 echo substudy, who underwent serial echocardiograms 24-48 hours after symptom onset and at discharge, six weeks, and six months after AMI. RESULTS: Tricuspid annular plane systolic excursion (TAPSE) increased significantly during follow up (mean (SD) 1.79 (0.46) cm at 24-48 hours to 1.92 (0.46) cm at six months, p < 0.001) and the increase was already significant at discharge (1.88 (0.47) cm, p < 0.001). LV ejection fraction (LVEF) was the best correlate of TAPSE at 24-48 hours (r = 0.15, p = 0.001). TAPSE increased significantly in patients both with reduced (< 45%) and with preserved (> or = 45%) LVEF, but the magnitude of increase was higher in patients with lower initial LVEF (p = 0.001). Improvement in IVS wall motion score index (IVS-WMSI) was the only independent predictor of TAPSE changes during follow up (r = -0.12, p = 0.007). CONCLUSIONS: In low risk patients after AMI, RV function recovered throughout six months of follow up and was already significant at discharge. TAPSE was significantly related to LVEF at 24-48 hours. The magnitude of RV functional recovery was higher in patients with lower initial LVEF. RV functional recovery is best related to IVS-WMSI improvement, suggesting that IVS motion has an important role in RV functional improvement in this setting.

Relation between early mitral regurgitation and left ventricular thrombus formation after acute myocardial infarction: results of the GISSI-3 echo substudy.

OBJECTIVE: To evaluate the prevalence and correlates of left ventricular thrombosis in patients with acute myocardial infarction, and whether the occurrence of early mitral regurgitation has a protective effect against the formation of left ventricular thrombus. DESIGN AND SETTING: Multicentre clinical trial carried out in 47 Italian coronary care units. PATIENTS AND METHODS: 757 patients from the GISSI-3 echo substudy population with their first acute myocardial infarct were studied by echocardiography at 24-48 hours from symptom onset (S1), at discharge (S2), at six weeks (S3), and at six months (S4). The diagnosis of left ventricular thrombosis was based on the detection of an echo dense mass with defined margins visible throughout the cardiac cycle in at least two orthogonal views. RESULTS: In 64 patients (8%), left ventricular thrombosis was detected in one or more examinations. Compared with the remaining 693 patients, subjects with left ventricular thrombosis were older (mean (SD) age: 64.6 (13.0) v 59.8 (11.7) years, p < 0.005), and had larger infarcts (extent of wall motion asynergy: 40.9 (11.5)% v 24.9 (14)%, p < 0.001), greater depression of left ventricular ejection fraction at S1 (43.3 (6.9)% v 48.1 (6.8)%, p < 0.001), and greater left ventricular volumes at S1 (end diastolic volume: 87 (22) v 78 (18) ml/m(2), p < 0.001; end systolic volume: 50 (17) v 41 (14) ml/m(2), p < 0.001). The prevalence of moderate to severe mitral regurgitation on colour Doppler at S1 was greater in patients who had left ventricular thrombosis at any time (10.2% v 4.2%, p < 0.05). On stepwise multiple logistic regression analysis the only independent variables related to the presence of left ventricular thrombosis were the extent of wall motion asynergy and anterior site of infarction. CONCLUSIONS: Left ventricular thrombosis is not reduced, and may even be increased, by early moderate to severe mitral regurgitation after acute myocardial infarction. The only independent determinant of left ventricular thrombosis is the extent of the akinetic-dyskinetic area detected on echocardiography between 24-48 hours from symptom onset.