Impact of SCN10A Polymorphism on Abdominal Pain Perception and Visceral Hypoalgesia in Crohn's Disease and Ulcerative Colitis.

Introduction: Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970, A1073V; 1073 val/val ) related to Na v 1.8, a voltage-gated sodium channel preferentially expressed on nociceptors.

Does a single oral administration of amiloride affect spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults?

Preclinical models indicate that amiloride (AMD) reduces baroreflex sensitivity and perturbs homeostatic blood pressure (BP) regulation. However, it remains unclear whether these findings translate to humans. This study investigated whether oral administration of AMD reduces spontaneous cardiac and sympathetic baroreflex sensitivity and perturbs BP regulation in healthy young humans.

Insights into the voltage-gated sodium channel, Na1.8, and its role in visceral pain perception.

Pain is a major issue in healthcare throughout the world. It remains one of the major clinical issues of our time because it is a common sequela of numerous conditions, has a tremendous impact on individual quality of life, and is one of the top drivers of cost in medicine, due to its influence on healthcare expenditures and lost productivity in those affected by it. Patients and healthcare providers remain desperate to find new, safer and more effective analgesics.

Heterologous expression of the human wild-type and variant Na 1.8 (A1073V) in rat sensory neurons.

Background: Silent inflammatory bowel disease (IBD) is a condition in which individuals with the active disease experience minor to no pain. Voltage-gated Na (Na ) channels expressed in sensory neurons play a major role in pain perception. Previously, we reported that a Na 1.

Dissimilar effects of stereoisomers and racemic hydroxychloroquine on Ca oscillations in human induced pluripotent stem cell-derived cardiomyocytes.

All currently employed pharmaceutical formulations of hydroxychloroquine (HCQ) sulfate are a racemate, consisting of equal parts mixture of two stereoisomers: R(-)HCQ and S(+)HCQ sulfates. The aims of the current study were first, to obtain and characterize pure HCQ enantiomers. The separation and purification of free base HCQ enantiomers from the racemate form were performed using semi-preparative chiral high-performance liquid chromatography.

A 10-mg dose of amiloride increases time to failure during blood-flow-restricted plantar flexion in healthy adults without influencing blood pressure.

Amiloride has been shown to inhibit acid-sensing ion channels (ASICs), which contribute to ischemia-related muscle pain during exercise. The purpose of this study was to determine if a single oral dose of amiloride would improve exercise tolerance and attenuate blood pressure during blood-flow-restricted (BFR) exercise in healthy adults. Ten subjects (4 females) performed isometric plantar flexion exercise with BFR (30% maximal voluntary contraction) after ingesting either a 10-mg dose of amiloride or a volume-matched placebo (random order).

Manifestations of renal involvement in sarcoidosis - case series.

Unlabelled: Renal involvement is observed in 30% of sarcoidosis cases, but the exact occurrence is unknown, and the current numbers are estimated to be underestimated. The most common manifestation of renal sarcoidosis is interstitial nephritis, but other presentations are also possible, with specific histopathological and laboratory findings. Glomerulopathies, nephrocalcinosis and nephrolithiasis are among the most commonly seen types of renal involvement.

Adult Renal Transplantation in a Patient 28 Years after Heart Transplantation as a Neonate for Hypoplastic Left Heart Syndrome.

We present a case of kidney transplantation in a 28-year-old patient who received a heart transplant at 7 weeks of age due to hypoplastic left heart syndrome. The patient's renal insufficiency was the result of chronic immunosuppression and hypertension. The almost 28-year-old graft demonstrated very good function.

Renal Protective Effect of Everolimus in Liver Transplantation: A Prospective Randomized Open-Label Trial.

Unlabelled: Renal dysfunction is associated with poor long-term outcomes after liver transplantation. We examined the renal sparing effect of everolimus (EVR) compared to standard calcineurin inhibitor (CNI) immunosuppression with direct measurements of renal function over 24 months.

Methods: This was a prospective, randomized, open-label trial comparing EVR and mycophenolic acid (MPA) with CNI and MPA immunosuppression.

Non-secretory multiple myeloma in a patient with chronic kidney disease.

Unlabelled: Multiple myeloma (MM) ) is a malignant plasma cell disorder from the group of monoclonal gammopathies. One of the most frequent diagnostic findings is the M-spike in serum protein electrophoresis (SPEP), which is notably absent in a rare non-secretory subtype of this disease.

A Case Report: A case report describes a 55-year old woman with a history of chronic kidney disease (CKD) in stage 3, proteinuria, asthma and Graves' disease.

Impact of the Na1.8 variant, A1073V, on post-sigmoidectomy pain and electrophysiological function in rat sympathetic neurons.

Na1.8 channels play a crucial role in regulating the action potential in nociceptive neurons. A single nucleotide polymorphism in the human Na1.

Sporadic Erythromelalgia Associated with a Homozygous Carrier of Common Missense Polymorphism in SCN9A Gene Coding for NaV1.7 Voltage-gated Sodium Channel.

A 68-year-old female with a history of sporadic type and presumably secondary erythromelalgia with chronic intractable pain presented for foot surgery. The procedure was performed with combined general anesthesia and regional anesthesia consisting of the placement of a popliteal pain catheter for postoperative pain management. Subsequent whole-genome sequencing revealed that the patient was a homozygous carrier of the common missense mutation in the SCN9A gene coding for voltage-gated sodium channel (NaV1.

Increased burden of rare deleterious variants of the KCNQ1 gene in patients with large‑vessel ischemic stroke.

The impact of rare and damaging variants in genes associated with platelet function in large‑vessel ischemic stroke (LVIS) remains unknown. The aim of this study was to investigate the contribution of some of these variants to the genetic susceptibility to LVIS in Polish patients using a deep re‑sequencing of 54 selected genes, coding for proteins associated with altered platelet function. Targeted pooled re‑sequencing (Illumina HiSeq 2500) was performed on genomic DNA of 500 cases (patients with history of clinically proven diagnosis of LVIS) and 500 age‑, smoking status‑, and sex‑matched controls (no history of any type of stroke), and from the same population as patients with LVIS.

Perioperative thrombotic complications associated with pediatric liver transplantation: a UNOS database evaluation.

Background: This retrospective UNOS database evaluation analyzes the prevalence of preoperative portal vein thromboses (PVT), and postoperative thromboses leading to graft failure in pediatric patients undergoing liver transplantation (LT).

Methods: The evaluation was performed in three age groups: I (0-5), II (6-11), III (12-18) years old. Factors predictive of pre- and postoperative thromboses were analyzed.

Pharmacogenomics of analgesics in anesthesia practice: A current update of literature.

The field of pharmacogenomics seeks to understand how an individual's unique gene sequence can affect their response to certain drugs. It is particularly relevant in anesthesia when the interindividual response to pain medication is essential. Codeine and tramadol are prodrugs metabolized by CYP2D6, polymorphisms of which can cause dangerous or even fatal levels of their metabolites, or decrease the level of metabolites to decrease their analgesic effect.

African Americans have a lower prevalence of portal vein thrombosis at the time of liver transplantation.

Background: Perioperative vascular thrombotic events in patients undergoing liver transplantation (LT) are associated with significant morbidity and mortality.

Methods: In this retrospective UNOS database analysis, we evaluated the prevalence of portal vein thrombosis (PVT) and factors contributing to PVT development in different ethnic groups.

Results: Of the 47 953 LT performed between 2002 and 2015, we identified 3642 cases of PVT.

Analysis of Common Single Nucleotide Polymorphisms in Complex Regional Pain Syndrome: Genome Wide Association Study Approach and Pooled DNA Strategy.

Objective: The objective of this study was to use a genome-wide association (GWAS) approach and pooled DNA strategy to search for new genomic loci associated with complex regional pain syndrome (CRPS).

Design: The study cohort consisted of 230 patients with established diagnosis of CRPS. The control group consisted of 230 age- and gender-matched subjects without chronic pain.

New single-nucleotide polymorphisms associated with differences in platelet reactivity and their influence on survival in patients with type 2 diabetes treated with acetylsalicylic acid: an observational study.

Aims: Genetic polymorphisms may contribute to platelet reactivity in diabetic patients; however, the information on their influence on long-term antiplatelet therapy is lacking. Our aim was to evaluate the role of previously described genetic variants and platelet reactivity on risk of all-cause mortality and cardiovascular events.

Methods: Blood samples were obtained from 303 Caucasian patients.

Massive Fulminant Thrombosis During Liver Transplantation in a Patient With a Previously Unknown Antithrombin Pathway Mutation.

We describe a case of fulminant intraoperative thrombosis during deceased donor liver transplantation. Despite significant medical bleeding, the patient suddenly developed diffuse thrombosis in all chambers of the heart and pulmonary vasculature resulting in intraoperative death. The patient's postmortem genetic analysis demonstrated a deleterious missense mutation in a coagulation pathway gene, SERPINC1, which codes for antithrombin III.

Common genetic variants in platelet surface receptors and its association with ischemic stroke.

Ischemic stroke has been named one of the leading causes of death worldwide. Whereas numerous biological mechanisms and molecules were found to be associated with stroke, platelets are particularly contributive to its pathogenesis. Recent data indicate considerable variability in platelet phenotype which accounts for differences in platelet surface receptor function, count and reactivity.

Autoimmune conditions are associated with perioperative thrombotic complications in liver transplant recipients: A UNOS database analysis.

Background: End stage liver disease (ESLD) is associated with significant thrombotic complications. In this study, we attempted to determine if patients with ESLD, due to oncologic or autoimmune diseases, are susceptible to thrombosis to a greater extent than patients with ESLD due to other causes.

Methods: In this retrospective study, we analyzed the UNOS database to determine the incidence of thrombotic complications in orthotopic liver transplant (OLT) recipients with autoimmune and oncologic conditions.