Factor XI and coagulation. Factor XI inhibitors - antithrombotic perspectives.

Factor XI is a zymogen with an important role in the coagulation cascade. It is activated by FXII, thrombin and or it can be autoactivated. It has a prothrombotic effect after being activated by thrombin, but also through its antifibrinolytic action, stabilizing the formed clot. Hereditary deficiency of FXI causes haemophilia C - a disease manifested by an usually provoked, small to moderate mucosal bleeding. People with severe FXI deficiency have a low risk of thrombotic events. Conversely, increased FXI values have been found to be associated with increased risk of venous thromboembolism and ischemic stroke. Lowering serum FXI levels has become a treatment target for the prevention of thrombotic events. New pharmacological agents - FXI inhibitors - have been investigated in phase II clinical trials, with promising results in terms of efficacy and safety in the prevention of thrombotic events. FXI inhibitors are emerging as new anticoagulant agents with broad indication prospects beyond direct oral anticoagulants and vitamin K antagonists.

Taurine and Its Derivatives: Analysis of the Inhibitory Effect on Platelet Function and Their Antithrombotic Potential.

Taurine is a semi-essential, the most abundant free amino acid in the human body, with a six times higher concentration in platelets than any other amino acid. It is highly beneficial for the organism, has many therapeutic actions, and is currently approved for heart failure treatment in Japan. Taurine has been repeatedly reported to elicit an inhibitory action on platelet activation and aggregation, sustained by in vivo, ex vivo, and in vitro animal and human studies. Taurine showed effectiveness in several pathologies involving thrombotic diathesis, such as diabetes, traumatic brain injury, acute ischemic stroke, and others. As human prospective studies on thrombosis outcome are very difficult to carry out, there is an obvious need to validate existing findings, and bring new compelling data about the mechanisms underlying taurine and derivatives antiplatelet action and their antithrombotic potential. Chloramine derivatives of taurine proved a higher stability and pronounced selectivity for platelet receptors, raising the assumption that they could represent future potential antithrombotic agents. Considering that taurine and its analogues display permissible side effects, along with the need of finding new, alternative antithrombotic drugs with minimal side effects and long-term action, the potential clinical relevance of this fascinating nutrient and its derivatives requires further consideration.

Effects of Exogenous Androgens on Platelet Activity and Their Thrombogenic Potential in Supraphysiological Administration: A Literature Review.

Anabolic androgenic steroids (AAS), simply called "androgens", represent the most widespread drugs used to enhance performance and appearance in a sporting environment. High-dosage and/or long-term AAS administration has been associated frequently with significant alterations in the cardiovascular system, some of these with severe endpoints. The induction of a prothrombotic state is probably the most life-threatening consequence, suggested by numerous case reports in AAS-abusing athletes, and by a considerable number of human and animal studies assessing the influence of exogenous androgens on hemostasis. Despite over fifty years of research, data regarding the thrombogenic potential of exogenous androgens are still scarce. The main reason is the limited possibility of conducting human prospective studies. However, human observational studies conducted in athletes or patients, in vitro human studies, and animal experiments have pointed out that androgens in supraphysiological doses induce enhanced platelet activity and thrombopoiesis, leading to increased platelet aggregation. If this tendency overlaps previously existing coagulation and/or fibrinolysis dysfunctions, it may lead to a thrombotic diathesis, which could explain the multitude of thromboembolic events reported in the AAS-abusing population. The influence of androgen excess on the platelet activity and fluid-coagulant balance remains a subject of debate, urging for supplementary studies in order to clarify the effects on hemostasis, and to provide new compelling evidence for their claimed thrombogenic potential.

Capsaicin and Gut Microbiota in Health and Disease.

Capsaicin is a widespread spice known for its analgesic qualities. Although a comprehensive body of evidence suggests pleiotropic benefits of capsaicin, including anti-inflammatory, antioxidant, anti-proliferative, metabolic, or cardioprotective effects, it is frequently avoided due to reported digestive side-effects. As the gut bacterial profile is strongly linked to diet and capsaicin displays modulatory effects on gut microbiota, a new hypothesis has recently emerged about its possible applicability against widespread pathologies, such as metabolic and inflammatory diseases. The present review explores the capsaicin-microbiota crosstalk and capsaicin effect on dysbiosis, and illustrates the intimate mechanisms that underlie its action in preventing the onset or development of pathologies like obesity, diabetes, or inflammatory bowel diseases. A possible antimicrobial property of capsaicin, mediated by the beneficial alteration of microbiota, is also discussed. However, as data are coming mostly from experimental models, caution is needed in translating these findings to humans.

Real-Time Investigation of Skin Blood Flow Changes Induced by Topical Capsaicin.

Capsaicin induces a localized inflammatory process known as neurogenic inflammation upon its topical administration on the skin, due to the release of various neuropeptides from the cutaneous sensory nerve endings. In this study, we investigated real-time skin blood flow changes that occur in neurogenic inflammation induced by topical capsaicin by means of in vivo reflectance confocal microscopy. 27 healthy subjects (15 women and 12 men, mean age ± Standard Deviation: 22.62±4.47) were administered topical capsaicin solution (Capsaicin group) or immersion oil (Control group) on the dorsal side of their non-dominant hand. At different time intervals during administration (0, 10, 25, and 40 minutes), cutaneous blood flow was evaluated using reflectance confocal microscopy and compared between the two groups. Blood flow values were higher during topical capsaicin, with significant increase after 25 (P=0.0160, Dunn's multiple comparisons test) and 40 minutes (P=0.0132, Dunn's multiple comparisons test) after its administration when compared with the initial 0 min value. Furthermore, the differences in the blood flow changes between the two groups were significant at 25 min (P=0.0182, Dunn's multiple comparisons test) and 40 min (P=0.0296, Dunn's multiple comparisons test) after capsaicin administration. Reflectance confocal microscopy allows in vivo, real-time evaluation of cutaneous blood flow changes within the capsaicin-induced inflammation, and this method might serve as a research model to test neurovascular reactivity.

ECoG spectrum changes at different xenon-isoflurane anaesthesia depths.

BACKGROUND AND AIMS: The purpose of this study is to assess the frontal and parietal ECoG spectrum (gamma range) changes during isoflurane and combined xenon-isoflurane anaesthesia in rats. METHODS: Experiments were carried out on four adult male Sprague-Dawley rats (250-300 g). The anaesthesia was induced with isoflurane and maintained with isoflurane and a xenon-isoflurane mixture. The rats were maintained at two different anaesthetic depths: light (isoflurane anaesthesia) and deep (isoflurane and xenon-isoflurane anaesthesia). The frontal and the parietal cortical activity was assessed by computing the median frequency, spectral edge frequency and functional connectivity between these two areas during light and deep anaesthesia. RESULTS: We noticed a decrease in cortical connectivity under deep isoflurane anaesthesia and an increase in connectivity under deep xenon-isoflurane anaesthesia. Moreover, during xenon-isoflurane anaesthesia, a trend of regularity of electro-cortical activity was present compared with isoflurane anaesthesia. CONCLUSIONS: Xenon-isoflurane deep anaesthesia demonstrated a series of specific ECoG features regarding frontoparietal functional connectivity (gamma range connectivity increase) and regularity of the electrocortical activity compared with isoflurane anaesthesia.

Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC.

Retroperitoneal Functioning Paraganglioma--A Rare Case of Secondary Diabetes.

INTRODUCTION: Paragangliomas are rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia, which can derive from either parasympathetic or sympathetic paraganglia and are closely related to pheochromocytomas. CASE REPORT: We present the case of a young male patient of 37 years old, who was admitted for hypertensive crisis and palpitations. His medical history included medically controlled type 2 diabetes mellitus, (diagnosed 10 months ago), Hepatitis A. Hormonal evaluation revealed elevated urinary metanephrines and normetanephrines, with mainly increased normetanephrines (2330 ug/24 h). Plasmatic metanephrins were in normal range, but levels of plasmatic normetanephrins were elevated (952 pg/ml). The assessment of pituitary and aldosterone-renin axis values were within normal limits. Abdominal computed tomography showed left adrenal nodular lesion on the external arm, bilobulated, size 32/33 mm with maximum axial and cranio-caudal diameter of approx. 45 cm, suggestive of a benign lesion, keeping the cleavage plane to vecinatate structures. Left adrenalectomy was performed by laparoscopic approach. We mention that immediately after induction of anesthesia were recorded blood pressures of 298/143 mmHg. Histopathologic and immunohistochemical examination diagnose paraganglioma, without invasion of adjacent tissues. The patient evolution was favorable, with the remission of the symptoms and normalization of hormonal markers. It is imperative to note the remission of diabetes in the postoperative period. DISCUSSION: This is the case of a young patient with functional retroperitoneal paraganglioma, who presented with symptoms of pheochromocytoma. Compared to pheochromocytomas, paragangliomas are rarely symptomatic and functional. Association with diabetes is even more rare. Specialized investigations allowed the proper diagnosis and the therapeutic approach above was the result of a multidisciplinary cooperation.

Reflectance confocal microscopy and dermoscopy for in vivo, non-invasive skin imaging of superficial basal cell carcinoma.

Superficial basal cell carcinoma (sBCC) is the second most frequent histological type of basal cell carcinoma (BCC), usually requiring a skin biopsy to confirm the diagnosis. It usually appears on the upper trunk and shoulders as erythematous and squamous lesions. Although it has a slow growth and seldom metastasizes, early diagnosis and management are of crucial importance in preventing local invasion and subsequent disfigurement. Dermoscopy is nowadays an indispensable tool for the dermatologist when evaluating skin tumors. Reflectance confocal microscopy (RCM) is a novel imaging technique that allows the non-invasive, in vivo quasi-microscopic morphological and dynamic assessment of superficial skin tumors. Moreover, it offers the advantage of performing infinite repeatable determinations to monitor disease progression and non-surgical treatment for sBCC. Herein, we present three lesions of sBCC evaluated using in vivo and non-invasive imaging techniques, emphasizing the usefulness of combining RCM with dermoscopy for increasing the diagnostic accuracy of sBCC.

Influence of chronic administration of anabolic androgenic steroids and taurine on haemostasis profile in rats: a thrombelastographic study.

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone with thrombogenic potential in high doses and long-term administration. Taurine, a widely distributed amino-sulfonic acid, is known for its beneficial effects in hypercoagulable states. In order to assess the impact of chronic administration of high doses of AAS and taurine upon haemostasis process in rats, 40 male Wistar rats were divided into four equal groups: control group (group C) - no treatment; androgen group (group A) - received 10 mg/kg per week of nandrolone decanoate (DECA); taurine (group T) - received oral supplementation of 2% taurine in drinking water; androgen and taurine group (group AT) - concomitant administration of DECA and taurine. After 12 weeks, blood samples were collected and haemostasis parameters were assessed with the thrombelastographic (TEG) analysis system: reaction time, clot kinetics (K, α), final clot strength, coagulation index and the clot lysis (Ly30). Nandrolone significantly decreased reaction time in group A compared with control (P<0.001), whereas taurine significantly increase reaction time (P=0.01), and this effect was maintained in group AT compared with group A (P=0.009). Similar differences between groups have been recorded for the clot kinetics parameters K, α. The final clot strength and coagulation index were significantly increased in group A versus group C (P=0.04, respectively P<0.001), but not in group AT versus group C (P>0.05). There were no differences in clot lysis, as shown by Ly30. Nandrolone produces an accelerated clot development and an increased clot firmness in Wistar rats. Taurine association ensures a protective effect against this hypercoagulable state, partially restoring the altered parameters of the coagulation profile.