Lactulose Works in the Large Bowel: But How Does It Improve Hepatic Encephalopathy in a Patient Without a Large Bowel?

Introduction: Lactulose is a non-absorbable disaccharide which acts in the large bowel, and is commonly used in the treatment of hepatic encephalopathy. We present an interesting case of altered mental status due to hepatic encephalopathy successfully managed with lactulose in a patient with history of total colectomy. Case Description/Methods: A 67-year-old male with non-alcoholic cirrhosis and inflammatory bowel disease (IBD) post total proctocolectomy with a continent ileostomy known as a Kock-pouch (K-pouch) presented to the hospital with flu like symptoms and altered mental status. He was subsequently found to be positive for COVID-19. At the time of initial evaluation, the patient was obtunded with an elevated ammonia level of 91 umol/L. Colorectal surgery was consulted as the patient was not able to empty his K-pouch. Recently, he complained of inability to catheterize and with bleeding from the stoma. Initial catheterization with a Water's tube yielded 400 cc of effluent. Nasogastric tube was placed through which he was receiving lactulose 30 mg q8 hours. The patient's mental status improved within 24 hours. The patient ultimately underwent flexible pouchoscopy with endoscopic dilation and placement of a 22 French mushroom catheter for decompression of the K-pouch. Discussion(s): Lactulose is a non-absorbable disaccharide composed of galactose and fructose. The small intestine does not have the enzymes required to breakdown lactulose so it reaches the large bowel in its original form. In the large bowel, it is metabolized by colonic bacteria into monosaccharides and then to volatile fatty acids, hydrogen and methane. Lactulose decreases both the production and absorption of ammonia mainly through the presence of gut bacteria. The question arises as to how lactulose decreased ammonia levels in this patient without a large bowel. One proposed mechanism is the translocation of bacteria normally found in the large bowel to the small intestine. Small Intestinal Bacterial Overgrowth (SIBO), is a condition causing an increased number of bacteria in the small intestine. Patients with IBD and structural abnormalities are at increased risk of developing SIBO. Lactulose is commonly used in the diagnosis through the administration of lactulose and subsequent measurements of hydrogen and methane gas in expired air. This condition, in our patient with history of ulcerative colitis and colectomy, is a proposed mechanism of the efficacy of lactulose in the treatment of hepatic encephalopathy.

A Case of Iga Vasculitis That Developed Gross Hematuria and Lower-Limb Purpura Following Covid-19 Vaccines

Introduction: There have been some reports on flare-ups of kidney diseases following COVID-19 vaccines such as IgA nephropathy and minimal change disease. However, there have been few reports on those of IgA vasculitis following the vaccines yet. We report a case of IgA vasculitis with a flare-up of gross hematuria and lower-limb purpura following Moderna COVID-19 vaccines. Method(s): The patient is a 16-year-old female with no previous history of abnormal results of urinalyses before April in 2021. She had developed microscopic hematuria, proteinuria and purpura on both of her lower limbs that emerged and then disappeared repeatedly since then. She received Moderna COVID-19 vaccines in August and September in 2021, both of which were followed by gross hematuria lasting for around 10 days. The lower-limb purpura reemerged at the same time as the hematuria. Microscopic hematuria of around 30-49 RBC/HPF, glomerular hematuria of moderate degree and urine protein-to-creatinine ratio (UPCR) of around 0.8 g/gCr had continuously been detected. Skin and kidney biopsies were performed in December in 2021 and in February in 2022 respectively. Result(s): The skin tissue showed formation of leukocytoclastic vasculitis, and the kidney tissue showed that of cellular and fibrocellular crescents and endocapillary hypercellularity. Immunofluorescence staining of both tissues showed deposition of galactose-deficient IgA1(Gd-IgA1) and C3, and she was diagnosed as IgA vasculitis. She received steroid pulse therapy followed by tonsillectomy. The lower-limb purpura has disappeared after she received three courses of the steroid pulse therapy, but microscopic hematuria and UPCR of around 0.8 g/gCr have still continued. Conclusion(s): IgA vasculitis is leukocytoclastic vasculitis characterized by deposition of Gd-IgA1 on microvessel walls in skin and on glomerular capillaries in kidneys. The detailed mechanism of IgA vasculitis has not been fully elucidated yet. Gross hematuria following an upper respiratory infection is considered as a characteristic clinical symptom of IgA vasculitis as well as IgA nephropathy. Post-vaccination gross hematuria of patients with IgA nephropathy has been reported, and it is believed that innate immunity is related to its mechanism. Moderna COVID-19 vaccines, which the patient received, are mRNA vaccines. We estimate that exposure to the mRNA vaccine triggered excess glomerular deposition of Gd-IgA1-containing immune complexes and subsequent gross hematuria by overactivation of innate immunity such as Toll-like receptors that detect RNA. This case suggests that such immune activation by a mRNA vaccine might be related not only to the mechanism of IgA nephropathy but also to that of IgA vasculitis. No conflict of interestCopyright © 2023

Newly-diagnosed immunoglobulin A nephropathy with increased plasma galactose-deficient-IgA1 antibody associated with mRNA COVID-19 vaccination: a case report.

Newly-diagnosed or relapses of immunoglobulin A nephropathy (IgAN) have been associated with COVID-19 vaccination in the literature. Most reported cases were mild clinical diseases characterized by microscopic haematuria and do not require dialysis treatment. This current case report describes a 55-year-old male patient that presented to the emergency department with acute kidney injury after receiving the first dose of the mRNA-1273 COVID-19 vaccine. After admission, his renal function deteriorated rapidly, and then he developed uraemic encephalopathy. He underwent emergency haemodialysis with a rapid improvement in his mental status. Renal biopsy showed newly-diagnosed IgA nephropathy along with markedly elevated plasma level of galactose-deficient-IgA1 (Gd-IgA1) antibody. The patient did not receive immunosuppressive treatment and is now dialysis-free. Immune activation is considered an essential factor in developing or exacerbating IgAN following COVID-19 vaccination. This current case report demonstrates that elevated Gd-IgA1 antibody may be the potential mechanistic link between COVID-19 vaccination and IgAN.

Alterations in heparan sulfate proteoglycan synthesis and sulfation and the impact on vascular endothelial function.

The glycocalyx attached to the apical surface of vascular endothelial cells is a rich network of proteoglycans, glycosaminoglycans, and glycoproteins with instrumental roles in vascular homeostasis. Given their molecular complexity and ability to interact with the intra- and extracellular environment, heparan sulfate proteoglycans uniquely contribute to the glycocalyx's role in regulating endothelial permeability, mechanosignaling, and ligand recognition by cognate cell surface receptors. Much attention has recently been devoted to the enzymatic shedding of heparan sulfate proteoglycans from the endothelial glycocalyx and its impact on vascular function. However, other molecular modifications to heparan sulfate proteoglycans are possible and may have equal or complementary clinical significance. In this narrative review, we focus on putative mechanisms driving non-proteolytic changes in heparan sulfate proteoglycan expression and alterations in the sulfation of heparan sulfate side chains within the endothelial glycocalyx. We then discuss how these specific changes to the endothelial glycocalyx impact endothelial cell function and highlight therapeutic strategies to target or potentially reverse these pathologic changes.

The Meat of the Matter: Understanding and Managing Alpha-Gal Syndrome.

Alpha-gal syndrome is an unconventional food allergy, characterized by IgE-mediated hypersensitivity responses to the glycan galactose-alpha-1,3-galactose (alpha-gal) and not to a food-protein. In this review, we discuss how alpha-gal syndrome reframes our current conception of the mechanisms of pathogenesis of food allergy. The development of alpha-gal IgE is associated with tick bites though the possibility of other parasites promoting sensitization to alpha-gal remains. We review the immune cell populations involved in the sensitization and effector phases of alpha-gal syndrome and describe the current understanding of why allergic responses to ingested alpha-gal can be delayed by several hours. We review the foundation of management in alpha-gal syndrome, namely avoidance, but also discuss the use of antihistamines, mast cell stabilizers, and the emerging role of complementary and alternative therapies, biological products, and oral immunotherapy in the management of this condition. Alpha-gal syndrome influences the safety and tolerability of medications and medical devices containing or derived from mammalian products and impacts quality of life well beyond food choices.

Metabolic engineering in food crops to enhance ascorbic acid production: crop biofortification perspectives for human health.

Ascorbic acid (AsA) also known as vitamin C is considered as an essential micronutrient in the diet of humans. The human body is unable to synthesize AsA, thus solely dependent on exogenous sources to accomplish the nutritional requirement. AsA plays a crucial role in different physiological aspects of human health like bone formation, iron absorption, maintenance and development of connective tissues, conversion of cholesterol to bile acid and production of serotonin. It carries antioxidant properties and is involved in curing various clinical disorders such as scurvy, viral infection, neurodegenerative diseases, cardiovascular diseases, anemia, and diabetes. It also plays a significant role in COVID-19 prevention and recovery by improving the oxygen index and enhancing the production of natural killer cells and T-lymphocytes. In plants, AsA plays important role in floral induction, seed germination, senescence, ROS regulation and photosynthesis. AsA is an essential counterpart of the antioxidant system and helps to defend the plants against abiotic and biotic stresses. Surprisingly, the deficiencies of AsA are spreading in both developed and developing countries. The amount of AsA in the major food crops such as wheat, rice, maize, and other raw natural plant foods is inadequate to fulfill its dietary requirements. Hence, the biofortification of AsA in staple crops would be feasible and cost-effective means of delivering AsA to populations that may have limited access to diverse diets and other interventions. In this review, we endeavor to provide information on the role of AsA in plants and human health, and also perused various biotechnological and agronomical approaches for elevating AsA content in food crops.

Rescue of Infectious Sindbis Virus by Yeast Spheroplast-Mammalian Cell Fusion.

Sindbis virus (SINV), a positive-sense single stranded RNA virus that causes mild symptoms in humans, is transmitted by mosquito bites. SINV reverse genetics have many implications, not only in understanding alphavirus transmission, replication cycle, and virus-host interactions, but also in biotechnology and biomedical applications. The rescue of SINV infectious particles is usually achieved by transfecting susceptible cells (BHK-21) with SINV-infectious mRNA genomes generated from cDNA constructed via in vitro translation (IVT). That procedure is time consuming, costly, and relies heavily on reagent quality. Here, we constructed a novel infectious SINV cDNA construct that expresses its genomic RNA in yeast cells controlled by galactose induction. Using spheroplasts made from this yeast, we established a robust polyethylene glycol-mediated yeast: BHK-21 fusion protocol to rescue infectious SINV particles. Our approach is timesaving and utilizes common lab reagents for SINV rescue. It could be a useful tool for the rescue of large single strand RNA viruses, such as SARS-CoV-2.