Prevalence of gastrointestinal symptoms in patients with cannabis abuse presenting to the emergency room

Introduction: Cannabis is a common recreational drug among young adults that is used to induce euphoria, promote relaxation and enhance appetite. There is a recognized correlation between cannabis abuse and cyclic episodes of nausea, vomiting, and abdominal pain (cannabinoid hyperemesis syndrome). However, the contribution of such symptoms to emergency room visits and hospital admissions is not known. Methods: A one-year, retrospective study was conducted on patients who presented to the emergency department and were later admitted at Abington Hospital-Jefferson Health with confirmed cannabis use (positive urine drug screen). Aim/Goal: Our primary outcome was to understand the prevalence of gastrointestinal symptoms in this patient population. We also studied other indices including other recreational drug use, the level of care, and comorbid psychological illnesses. Results: A total of 100 patients were included in the study, 60% were male, 30.3% were admitted with a primary diagnosis of gastrointestinal symptoms (e.g., nausea, vomiting and abdominal pain or cannabinoid hyperemesis), 26.3% with neurological symptoms (i.e., altered mental status, loss of consciousness (LOC) and/or seizures), 23.2% with trauma (i.e., fall or car accident), and 6.1% with cardiac issues. 34% of our patients had no past medical history. Over 50% had at least one psychiatric illness and 38.7% were taking at least one or more antipsychotic medications. Subgroup analysis of our population admitted with GI symptoms (n=30) revealed 47% males, 36% active smokers (vs 34% in total population), 33% admit to alcohol use (vs 40% in total), 10% positive for opiates (vs 18% in total), 6.7% positive for cocaine (vs 8% in total), and 16% are on prescribed narcotics (vs 20.2% total). 27 % of these patients were placed on GMF with tele or higher level of care such as MICU, SICU, or PCU (vs 51% total) and 13.3% received echocardiogram (vs 21.2% total). Interesting results were observed when stratifying patients based on age and type of controlled substance abuse. Marijuana, opiates, and benzodiazepines or barbiturates users were more prevalent in patients 27-36 yrs. of age, with 30%, 33%, and 50%, respectively. While, cocaine, hallucinogens, and amphetamines or methamphetamines users were more prevalent in those aged 26 yrs. or younger, with 37.5%, 100%, and 66%, respectively. Conclusion: GI symptoms represent an important presenting feature in patients with cannabis abuse likely more than any other presenting features. However, patients with predominant GI symptoms might require lower level of care and less cardiac workup. Additional studies are required to elucidate the significance of GI symptoms in this population of patients further

A Role for XIST in the Regulation of Inflammatory Response by Female Cells

Biological sex influences inflammatory response [1]. There is a greater incidence of acute inflammation in men, and chronic inflammation in women. X-inactive specific transcript (XIST) is a long noncoding RNA (lncRNA) crucial for equalizing expression of X-linked genes between females and males. Xist was upregulated in animal and cellular models of acute inflammation. Our in vitro and in vivo experiments and studies from patients with complex regional pain syndrome (CRPS) show that miR-34a could play a role in regulating XIST under inflammation directly and through the regulation of Yin-Yang 1 (YY1). We observed changes in subcellular localization of Xist in J774A.1 female macrophages and an upregulation of Xist RNA in the cytoplasm after inflammatory stimulus. There was a reciprocal regulation between Xist and pro-inflammatory cytokines involving the NF-[kappa]B pathway. Under acute inflammation, Xist associates with NF-[kappa]B in the cytoplasm and inhibits its nuclear migration, thereby reducing acute inflammatory response. Transfection of male THP-1 cells with a 5 kb fragment of the 5' XIST significantly reduced IL-6 expression, NF-[kappa]B activation and migration into the nucleus. Adoptive transfer of splenocytes overexpressing Xist reduced acute paw swelling in male mice induced by complete Freund's adjuvant (CFA). These findings suggest that XIST can have a protective anti-inflammatory effect in females that can contribute to sex-specific differences underlying acute inflammatory response. Thus, XIST can have a role beyond X chromosome inactivation, in the cytoplasm. We propose that the aberrant role of XIST could contribute to the predominance of chronic pain and autoimmune disorders in women and warrants further investigations into the dual role of XIST under acute and chronic inflammation.Ph.D., Pharmacology and Physiology -- Drexel University, 201

Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells

Exosome-mediated signaling is important in mediating the inflammatory response. To exert their biological or pathophysiological functions in the recipient cells, exosomes deliver a diverse array of biomacromolecules including long and short coding and non-coding RNAs, proteins, and lipids. Exosomes secreted by antigen-presenting cells can confer therapeutic benefits by attenuating or stimulating the immune response. Exosomes play a crucial role in carrying and presenting functional major histocompatibility peptide complexes to modulate antigen-specific T cell responses. Exosomes from Dendritic Cells (DCs) can activate T and B cells and have been explored for their immunostimulatory properties in cancer therapy. The immunosuppressive properties of exosomes derived from macrophages and DCs can reduce inflammation in animal models for several inflammatory disorders. This review focuses on the protective role of exosomes in attenuating inflammation or augmenting immune response, emphasizing studies on exosomes derived from DCs and macrophages

Sledování utužení půdy na daném pozemku

In the thesis is discussed problem with soil compaction in the agriculture in the Czech Republic, causing of aspects of this phenomenon as well as a method suppressing this phenomenon and prevent its. In this work are also mentioned machinery and equipment and their possibilities editing to reduce the compression of the soil. There are also the results of field measurements, which were carried out during the season on land that has been processed by different technology in several of its parts and other measurements carried out occasionally in the Czech Republic to observe the state of soil compaction

Hsa-miR-605 regulates the proinflammatory chemokine CXCL5 in complex regional pain syndrome

Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by inflammation and debilitating pain. CRPS patients with pain refractory to more conventional analgesics can be treated with subanesthetic doses of ketamine. Our previous studies found that poor responders to ketamine had a 22-fold downregulation of the miRNA hsa-miR-605 in blood prior to ketamine treatment. Hence, we sought to investigate the functional significance of miR-605 downregulation and its impact on target gene expression, as investigating target mRNAs of differentially expressed miRNAs can provide important insights on aberrant gene expression that may contribute to disease etiology. Using a bioinformatics prediction, we identified that miR-605 can target the proinflammatory chemokine CXCL5, which plays a role in leukocyte recruitment and activation. We hypothesized that downregulation of miR-605 in poor responders to ketamine could increase CXCL5 expression and thereby contribute to inflammation in these patients. We confirmed that miR-605 regulates CXCL5 by using a miRNA mimic and inhibitor in human primary endothelial cells. Inhibition of miR-605 increased CXCL5 secretion and migration of human monocytic cells, thereby demonstrating a functional impact of miR-605 on chemotaxis. Additionally, CXCL5 mRNA was upregulated in whole blood from poor responders to ketamine, and CXCL5 protein was increased in plasma from CRPS patients. Thus, our studies suggest that miR-605 regulation of CXCL5 can regulate inflammation

Exosome microRNA signatures in patients with complex regional pain syndrome undergoing plasma exchange

Abstract Background Therapeutic plasma exchange (PE) or plasmapheresis is an extracorporeal procedure employed to treat immunological disorders. Exosomes, nanosized vesicles of endosomal origin, mediate intercellular communication by transferring cargo proteins and nucleic acids and regulate many pathophysiological processes. Exosomal miRNAs are potential biomarkers due to their stability and dysregulation in diseases including complex regional pain syndrome (CRPS), a chronic pain disorder with persistent inflammation. A previous study showed that a subset of CRPS patients responded to PE. Methods As a proof-of-concept, we investigated the PE-induced exosomal miRNA changes in six CRPS patients. Plasma cytokine levels were measured by HPLC and correlated with miRNA expression. Luciferase assay following co-transfection of HEK293 cells with target 3′UTR constructs and miRNA mimics was used to evaluate miRNA mediated gene regulation of target mRNA. Transient transfection of THP-1 cells with miRNA mimics followed by estimation of target gene and protein expression was used to validate the findings. Results Comparison of miRNAs in exosomes from the serum of three responders and three poor-responders showed that 17 miRNAs differed significantly before and after therapy. Of these, poor responders had lower exosomal hsa-miR-338-5p. We show that miR-338-5p can bind to the interleukin 6 (IL-6) 3′ untranslated region and can regulate IL-6 mRNA and protein levels in vitro. PE resulted in a significant reduction of IL-6 in CRPS patients. Conclusions We propose that lower pretreatment levels of miR-338-5p in poor responders are linked to IL-6 levels and inflammation in CRPS. Our data suggests the feasibility of exploring exosomal miRNAs as a strategy in patient stratification for maximizing therapeutic outcome of PE