Alprostadil

Abstract

This study aimed to investigate the regulation of chloride channels in proliferative vitreoretinopathy (PVR) both in vitro and in vivo using a rabbit model and to explore the underlying mechanism.

Abstract

Chronic constipation reduces quality of life and imposes a significant economic burden. The introduction of novel agents in Japan has expanded treatment options. This study aimed to establish a cost-effective treatment strategy, considering clinical utility and patient satisfaction.

Abstract

Chronic idiopathic constipation (CIC) is a common disorder associated with socioeconomic burden. The aim of this study was to quantify the socioeconomic burden of CIC, including non-traditional value elements, and to compare the cost-effectiveness of 3 treatments for CIC with unique mechanisms of action: elobixibat 10 mg, linaclotide 0.5 mg, and lubiprostone 48 μg.

Abstract

Nephronophthisis (NPHP) is a recessive tubulointerstitial nephropathy and a leading genetic cause of kidney failure in children and young adults. The most common genetic cause is a homozygous deletion of NPHP1, which encodes nephrocystin-1, a protein essential for primary cilium structure and cell junctions. Using personalized medicine and deep phenotyping, we investigated a family with three siblings carrying a homozygous NPHP1 deletion. We compared kidney biopsy tissue and human urine-derived renal epithelial cells (hURECs) from these individuals. Bulk RNA-seq on patient hURECs revealed altered expression in EGFR signalling, extracellular components and adherens junctions, which is consistent with the known roles for nephrocystin-1. Treatment with alprostadil, a proposed NPHP therapy, increased ciliation but worsened ciliary elongation. By contrast, the EGFR kinase inhibitor AG556 rescued of ciliary length and morphology. Transcriptional profiling post-treatment showed AG556 reversed the disease signature more effectively that alprostadil. These findings suggest that EGFR inhibition might offer a more promising therapeutic strategy for NPHP1-associated renal ciliopathy, warranting further testing in in vivo models before clinical application.

Abstract

Chronic constipation is one of the most common digestive diseases encountered in clinical practice. Constipation manifests as a variety of symptoms, such as infrequent bowel movements, hard stools, feeling of incomplete evacuation, straining at defecation, a sense of anorectal blockage during defecation, and use of digital maneuvers to assist defecation. During the diagnosis of chronic constipation, the Bristol Stool Form Scale, colonoscopy, and a digital rectal examination are useful for objective symptom evaluation and differential diagnosis of secondary constipation. Physiological tests for functional constipation have complementary roles. They are recommended for patients who have failed to respond to treatment with available laxatives and those who are strongly suspected of having a defecatory disorder. As new evidence on diagnosing and managing functional constipation emerged, the need to revise the previous guideline was suggested. Therefore, these evidence-based guidelines have proposed recommendations developed using a systematic review and meta-analysis of the treatment options available for functional constipation. The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding management. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding managing functional constipation.

Abstract

Irritable bowel syndrome with predominant constipation (IBS-C) is a functional gastrointestinal disorder characterized by abdominal pain with chronic constipation and abdominal bloating, which could significantly impair the quality of life of patients and bring substantial socio-economic burdens. Pharmacology treatment is central to managing patients with IBS-C, aiming to alleviate symptoms and improve patient treatment outcomes. Guanylate cyclase-C agonists (linaclotide and plecanatide) enhance intestinal fluid secretion and motility, normalize bowel movements, and reduce abdominal pain. Na+/H+ exchanger inhibitors (e.g., tenapanor) decrease sodium absorption, increase fluid secretion, and alleviate visceral pain. Lubiprostone activates the chloride channels to facilitate bowel movements, while polyethylene glycol laxatives regulate osmotic pressure to improve stool consistency and ease defecation. Highly selective 5-HT4 agonists, such as prucalopride, accelerate gastrointestinal and colonic transit and improve stool frequency and consistency without increasing the cardiovascular risks raised in earlier agents such as tegaserod. Neuromodulators, including selective serotonin reuptake inhibitors and tricyclic antidepressants, help manage visceral hypersensitivity and chronic abdominal pain in selected patients. These pharmacology agents have shown efficacy and safety in clinical studies, but drug availability, adverse effects, and variable patient responses are still challenging. Effective strategies to manage IBS-C require a personalized approach, considering the patient's symptom profile, treatment goals, and safety concerns.

Abstract

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are common functional intestinal disorders which impact all age groups, yet there is limited comparative evidence on the economic benefits of treatment of these conditions on the elderly. We assessed differences in healthcare resource utilization (HCRU) and total costs of care among Medicare-insured patients initiating linaclotide, lubiprostone, or plecanatide after 1 year.