vitamin-k-semiquinone-radical and Fibrosis

Treatment of splanchnic vein thrombosis (SVT) is a clinical challenge due to heterogeneity of clinical presentations, increased bleeding risk, and lack of evidences from clinical trials. We performed an international registry to describe current treatment strategies and factors associated with therapeutic decisions in a large prospective cohort of unselected SVT patients. A total of 613 patients were enrolled (mean age 53.1 years, standard deviation ± 14.8); 62.6% males; the majority (468 patients) had portal vein thrombosis. Most common risk factors included cirrhosis (27.8%), solid cancer (22.3%), and intra-abdominal inflammation/infection (11.7%); in 27.4% of patients, SVT was idiopathic. During the acute phase, 470 (76.7%) patients received anticoagulant drugs, 136 patients (22.2%) remained untreated. Incidental diagnosis, single vein thrombosis, gastrointestinal bleeding, thrombocytopenia, cancer, and cirrhosis were significantly associated with no anticoagulant treatment. Decision to start patients on vitamin K antagonists after an initial course of parenteral anticoagulation was significantly associated with younger age, symptomatic onset, multiple veins involvement, and unprovoked thrombosis. Although a nonnegligible proportion of SVT patients did not receive anticoagulant treatment, the majority received the same therapies recommended for patients with usual sites thrombosis, with some differences driven by the site of thrombosis and the pathogenesis of the disease.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Female; Fibrinolytic Agents; Fibrosis; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Registries; Retrospective Studies; Risk Factors; Splanchnic Circulation; Venous Thrombosis; Vitamin K

Pseudoxanthoma elasticum (PXE), caused by ABCC6/MRP6 mutation, is a heritable multisystem disorder in humans. The progressive clinical manifestations of PXE are accompanied by ectopic mineralization in various connective tissues. However, the pathomechanisms underlying the PXE multisystem disorder remains obscure, and effective treatment is currently available. In this study, we generated zebrafish

Topics: Animals; ATP-Binding Cassette Transporters; Calcinosis; Eye; Fibrosis; Genetic Predisposition to Disease; Mutation; Myocardium; Vitamin K; Zebrafish; Zebrafish Proteins

There is an ongoing need for additional interventions in idiopathic pulmonary fibrosis (IPF) as antifibrotic drugs currently available only inhibit and do not stall disease progression. Vitamin K is a co-factor for the activation of coagulation factors. However, it is also required to activate proteins with functions outside of the coagulation cascade, such as matrix Gla protein (MGP), a defender against soft tissue calcification. Vitamin K antagonists are anticoagulants that are, for unknown reasons, associated with increased mortality in IPF. Areas covered: We advance the hypothesis that modulation of vitamin K-dependent MGP activation in IPF patients by either vitamin K antagonism or administration may result in acceleration and deceleration of fibrosis progression, respectively. Furthermore, shortfall in vitamin K could be suspected in IPF based on the high prevalence of certain co-morbidities, such as vascular calcification and lung cancer. Expert commentary: We hypothesize that vitamin K status is reduced in IPF patients. This, in combination with studies suggesting that vitamin K may play a role in lung fibrosis pathogenesis, would provide a rationale for conducting a clinical trial assessing the potential mitigating effects of vitamin K administration on progression of lung fibrosis, prevention of co-morbidities and mortality in IPF.

Topics: Antifibrinolytic Agents; Calcium-Binding Proteins; Dietary Supplements; Disease Progression; Extracellular Matrix Proteins; Fibrosis; Humans; Idiopathic Pulmonary Fibrosis; Lung Neoplasms; Matrix Gla Protein; Vascular Calcification; Vitamin K

Extrahepatic biliary atresia (EHBA) is a rare disease characterized by progressive and obliterative cholangiopathy in infants and is one of the major causes of secondary vitamin K deficiency bleeding (VKDB) due to cholestasis-induced fat malabsorption. Breast feeding increases the tendency of bleeding in EHBA patients because breast milk contains low amounts of vitamin K. A 2-month-old female infant unexpectedly died, with symptoms of vomiting and jaundice prior to death. She had been born by uncomplicated vaginal delivery and exhibited normal growth and development with breastfeeding. There was no history of trauma. She received vitamin K prophylaxis orally. In an emergency hospital, a CT scan showed a right intracranial hematoma and mass effect with midline shift to the left. In the postmortem examination, severe atresia was observed in the whole extrahepatic bile duct. Histologically, cholestasis, periductal fibrosis, and distorted bile ductules were noted. The gallbladder was not identified. A subdural hematoma and cerebellar tonsillar herniation were found; however, no traumatic injury in any part of the body was observed. Together, these findings suggest that the subdural hemorrhage was caused by secondary vitamin K deficiency resulting from a combination of cholestasis-induced fat malabsorption and breastfeeding. Subdural hemorrhage by secondary VKDB sometimes occurs even when vitamin K prophylaxis is continued. This case demonstrated that intrinsic factors, such as secondary VKDB (e.g., EHBA, neonatal hepatitis, chronic diarrhea), should also be considered in infant autopsy cases presenting with subdural hemorrhage.

Topics: Bile Ducts, Extrahepatic; Biliary Atresia; Cholestasis, Extrahepatic; Encephalocele; Female; Fibrosis; Forensic Pathology; Hematoma, Subdural; Humans; Infant; Liver Cirrhosis; Vitamin K; Vitamin K Deficiency; Vitamins

The morphological changes in rat facial muscles were evaluated after permanent denervation and were compared with findings after immediate reinnervation. Thirty rats underwent transection of the left and right facial nerves immediately followed by hypoglossal-facial nerve anastomosis on the right side (muscular reinnervation) and removal of 8-10 mm of the facial plexus on the left side (permanent muscular denervation). Levator labii muscle samples of both sides were collected sequentially at 2, 6, 7, 10, 20, and 24 weeks after surgery and submitted to routine histological and enzyme histochemical staining procedures. In normal levator labii muscles a typical "chessboard" pattern was found, with type I fibers being smaller than type II fibers. These latter fibers also were more prevalent than the type I fibers. Among the type II fiber subtypes, the type IIB fibers were larger and more frequent. Two weeks after surgery, there were no differences between denervated facial muscles and those undergoing reinnervation. Both showed atrophic myofibers among normal-sized fibers and slight fibrosis. Those muscles denervated for more than 2 weeks displayed increasing fiber atrophy with frequent loss of typability, as well as proliferation of connective tissue and fat cells in perimysial and endomysial sites. After denervation for 20 weeks only a few atrophic fibers were found in wide areas of fibrosis and fat cells. Following nerve anastomosis the reinnervated levator labii muscle showed much less fiber atrophy. Regrowth to normal fiber diameters was found with only a few atrophic myofibers 10 weeks after anastomosis although a moderate fibrosis predominated at perimysial sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphatases; Anastomosis, Surgical; Animals; Atrophy; Connective Tissue; Facial Muscles; Facial Nerve; Female; Fibrosis; Glycerophosphates; Histocytochemistry; Hypoglossal Nerve; Muscle Denervation; Myofibrils; NADH Tetrazolium Reductase; Nerve Transfer; Rats; Rats, Wistar; Regeneration; Vitamin K