Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice.

Chronic liver diseases are multifactorial and the need to develop effective therapies is high. Recent studies have shown the potential of ameliorating liver disease progression through protection of the liver endothelium. Polyamine spermidine (SPD) is a caloric restriction mimetic with autophagy-enhancing properties capable of prolonging lifespan and with a proven beneficial effect in cardiovascular disease in mice and humans.

Impact of lifestyle interventions targeting physical exercise and caloric intake on cirrhosis regression in rats.

In patients, advanced cirrhosis only regresses partially once the etiological agent is withdrawn. Animal models for advanced cirrhosis regression are missing. Lifestyle interventions (LIs) have been shown to improve steatosis, inflammation, fibrosis, and portal pressure (PP) in liver disease.

Autoimmune biomarkers in porto-sinusoidal vascular disease: Potential role in its diagnosis and pathophysiology.

Background And Aims: Porto-sinusoidal vascular disease (PSVD) is a rare disease that requires excluding cirrhosis and other causes of portal hypertension for its diagnosis because it lacks a specific diagnostical test. Although it has been occasionally associated with autoimmune diseases, the pathophysiology of PSVD remains unknown. The aim of this study was to evaluate the potential role of autoimmunity in the pathophysiology and diagnosis of PSVD.

The Endothelium as a Driver of Liver Fibrosis and Regeneration.

Liver fibrosis is a common feature of sustained liver injury and represents a major public health problem worldwide. Fibrosis is an active research field and discoveries in the last years have contributed to the development of new antifibrotic drugs, although none of them have been approved yet. Liver sinusoidal endothelial cells (LSEC) are highly specialized endothelial cells localized at the interface between the blood and other liver cell types.

Aging Influences Hepatic Microvascular Biology and Liver Fibrosis in Advanced Chronic Liver Disease.

Advanced chronic liver disease (aCLD) represents a major public health concern. aCLD is more prevalent and severe in the elderly, carrying a higher risk of decompensation. We aimed at understanding how aging may impact on the pathophysiology of aCLD in aged rats and humans and secondly, at evaluating simvastatin as a therapeutic option in aged animals.

Simvastatin Prevents Progression of Acute on Chronic Liver Failure in Rats With Cirrhosis and Portal Hypertension.

Background & Aims: Cirrhosis and its clinical consequences can be aggravated by bacterial infections, ultimately leading to the development of acute on chronic liver failure (ACLF), characterized by acute decompensation, organ failure, and high mortality within 28 days. Little is known about cellular and molecular mechanisms of ACLF in patients with cirrhosis, so no therapeutic options are available. We developed a sepsis-associated preclinical model of ACLF to facilitate studies of pathogenesis and evaluate the protective effects of simvastatin.

Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

Background & Aims: In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension.

The anticoagulant rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells.

Unlabelled: In cirrhosis, increased intrahepatic vascular resistance (IHVR) is the primary factor for portal hypertension (PH) development. Hepatic stellate cells (HSCs) play a major role increasing IHVR because, when activated, they are contractile and promote fibrogenesis. Protease-activated receptors (PARs) can activate HSCs through thrombin and factor Xa, which are known PAR agonists, and cause microthrombosis in liver microcirculation.

Enoxaparin reduces hepatic vascular resistance and portal pressure in cirrhotic rats.

Background & Aims: Increased hepatic vascular resistance due to fibrosis and elevated hepatic vascular tone is the primary factor in the development of portal hypertension. Heparin may decrease fibrosis by inhibiting intrahepatic microthrombosis and thrombin-mediated hepatic stellate cell activation. In addition, heparin enhances eNOS activity, which may reduce hepatic vascular tone.

Metformin reduces hepatic resistance and portal pressure in cirrhotic rats.

Increased hepatic vascular resistance is the primary factor in the development of portal hypertension. Metformin ameliorates vascular cells function in several vascular beds. Our study was aimed at evaluating the effects, and the underlying mechanisms, of metformin on hepatic and systemic hemodynamics in cirrhotic rats and its possible interaction with the effects of propranolol (Prop), the current standard treatment for portal hypertension.

Preoperative platelet count and postoperative blood loss in patients undergoing hip surgery: an inverse correlation.

In a previous study we tried to assess the clinical usefulness of platelet count (PlC) to confirm whether postoperative pulmonary embolism could be suspected early. Unexpectedly, the 19 patients who subsequently developed pulmonary embolism had significantly lower mean PlC levels even before surgery. In an attempt to discover whether the preoperative PlC levels were associated with a different incidence of postoperative blood loss, we decided to retrospectively study the relationship between preoperative PlC levels and the consequences of blood loss.

Platelet count, antiplatelet therapy and pulmonary embolism--a prospective study in patients with hip surgery.

Pulmonary embolism (PE) is a serious complication following hip surgery. Trials of antiplatelet thromboprophylaxis indicated a substantial reduction in PE rate, and we prospectively studied the effect of a combination of low-dose heparin and two different antiplatelets. Furthermore, our experience in previous studies suggested that platelet count (PC) levels could be useful to reliably suspect PE at a very early stage, and we prospectively tried to confirm our previous findings.

Pulmonary embolism in patients with upper extremity DVT associated to venous central lines--a prospective study.

We performed a prospective study in 86 consecutive patients with central vein catheter-related deep venous thrombosis (DVT) of the upper extremity, to evaluate the prevalence of pulmonary embolism (PE), and to identify clinical variables that would increase the likelihood of developing PE in an individual patient. Since upper-extremity DVT was established, all patients received intravenous heparin therapy. Then, a ventilation-perfusion lung scan was obtained within 24 h of DVT diagnosis, whether respiratory symptoms were present or not.

Recurrent pulmonary embolism in patients treated because of acute venous thromboembolism: a prospective study.

Objective: To evaluate the risk of pulmonary embolism (PE) despite adequate heparin therapy in a large series of patients with acute deep venous thrombosis and/or pulmonary embolism.

Design: Prospective study.

Setting: University Hospital Germans Trias i Pujol, Badalona, Spain.

Comparison of subcutaneous unfractionated heparin with a low molecular weight heparin (Fragmin) in patients with venous thromboembolism and contraindications to coumarin.

Intravenous heparin followed by oral anticoagulant therapy (e. g. with coumarin) is still the most widely used treatment for deep venous thromboembolism.

Platelet count in acute pulmonary embolism: its relationship to recurrences.

We have prospectively studied a large series of patients with acute venous thromboembolism, trying to correlate pulmonary embolism (PE) recurrences to a number of clinical variables, and platelet count behavior. A baseline lung scan was obtained initially in every patient. Repeated chest X-ray and lung scans were obtained routinely 8 days after heparin onset.

Venographic assessment of deep vein thrombosis and risk of developing post-thrombotic syndrome: a prospective study.

It is well known that patients with deep vein thrombosis (DVT) constitute a risk group for development of pulmonary embolism. However, the relation of DVT and the extent thereof with the subsequent sequelae (post-thrombotic syndrome) are insufficiently investigated. We have prospectively studied a series of consecutive patients admitted because of DVT on lower limbs, trying to correlate venographic findings during acute DVT with post-thrombotic (PTS) symptoms that develop later.

Platelet count and venous thromboembolism. A useful test for suspected pulmonary embolism.

We have previously reported that patients with deep vein thrombosis (DVT) and scintigraphic evidence of pulmonary embolism (PE) had a fall in platelet count, as compared with their levels before thrombosis had developed. Otherwise, no changes were found in DVT patients without embolism. We recently conducted a prospective study with a larger series of patients and studied platelet count behavior in 189 consecutive patients with acute venous thromboembolism (VTE) in whom a baseline blood cell count was available (obtained before thromboembolism developed).

[Deep venous thrombosis of the upper limb. A prospective study of the central venous catheter as an etiologic factor and clinical and subclinical incidence of pulmonary thromboembolism].

The thrombogenicity presented in different types of endovenous catheters and their anomalies are the cause of the development of pulmonary thromboembolism (PTE) in some patients, secondary to deep venous thrombosis (DVT) of the upper limbs. Presentation of a study made on the incidence of PTE in patients with prior history of DVT of the upper limbs. Of the 30 cases of DVT of the upper limbs studied, 20 were directly attributed to catheters.

Upper-extremity deep venous thrombosis and pulmonary embolism. A prospective study.

We prospectively evaluated the prevalence of pulmonary embolism (PE) in 30 consecutive patients with proved deep venous thrombosis (DVT) of the upper extremity. Ten patients (seven male and three female; mean age, 43 years) had primary DVT, and 20 patients (14 male and six female; mean age, 52 years) had catheter-related DVT. Ventilation-perfusion lung scans were routinely performed at the time of hospital admission to all but one patient (one patient was critically ill, and he died four days after DVT diagnosis because of massive PE).

Occult cancer in patients with deep venous thrombosis. A systematic approach.

The authors prospectively studied 113 consecutive patients with deep venous thrombosis of the lower extremities to determine the most appropriate workup study for searching for a hidden cancer. After a careful physical examination, the following routine tests were performed: erythrocyte sedimentation rate (ESR), whole blood counts, biochemistry, carcinoembryonic antigen (CEA) levels, chest radiograph, upper gastrointestinal endoscopy, abdominal ultrasound and computed tomography (CT) scan. If a malignant lesion was suspected, further appropriate studies were performed.

Occlusive arterial disease as a form of presentation of homocystinuria.

Homocystinuria was first described in 1962. The disease affects several systems including the eyes, skeletal and nervous and vascular systems. We present the case of a 28-year old woman who presented with a severe occlusive arteriopathy.