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PLoS Pathogens Jun 2023Abnormal deposition of α-synuclein is a key feature and biomarker of Parkinson's disease. α-Synuclein aggregates can propagate themselves by a prion-like seeding-based...
Abnormal deposition of α-synuclein is a key feature and biomarker of Parkinson's disease. α-Synuclein aggregates can propagate themselves by a prion-like seeding-based mechanism within and between tissues and are hypothesized to move between the intestine and brain. α-Synuclein RT-QuIC seed amplification assays have detected Parkinson's-associated α-synuclein in multiple biospecimens including post-mortem colon samples. Here we show intra vitam detection of seeds in duodenum biopsies from 22/23 Parkinson's patients, but not in 6 healthy controls by RT-QuICR. In contrast, no tau seeding activity was detected in any of the biopsies. Our seed amplifications provide evidence that the upper intestine contains a form(s) of α-synuclein with self-propagating activity. The diagnostic sensitivity and specificity for PD in this biopsy panel were 95.7% and 100% respectively. End-point dilution analysis indicated up to 106 SD50 seeding units per mg of tissue with positivity in two contemporaneous biopsies from individual patients suggesting widespread distribution within the superior and descending parts of duodenum. Our detection of α-synuclein seeding activity in duodenum biopsies of Parkinson's disease patients suggests not only that such analyses may be useful in ante-mortem diagnosis, but also that the duodenum may be a source or a destination for pathological, self-propagating α-synuclein assemblies.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Biopsy; Intestines; Duodenum
PubMed: 37390080
DOI: 10.1371/journal.ppat.1011456 -
The American Journal of Emergency... Feb 2024Acute diverticulitis is a condition commonly seen in the emergency department (ED). Therefore, it is important for emergency medicine clinicians to be aware of the... (Review)
Review
INTRODUCTION
Acute diverticulitis is a condition commonly seen in the emergency department (ED). Therefore, it is important for emergency medicine clinicians to be aware of the current evidence regarding the diagnosis and management of this disease.
OBJECTIVE
This paper evaluates key evidence-based updates concerning acute diverticulitis for the emergency clinician.
DISCUSSION
Diverticulitis is a complication of diverticulosis and most commonly affects the sigmoid and descending colon in Western countries. History and examination can suggest the diagnosis, with abdominal pain and tenderness in the left lower quadrant being the most common symptom and sign, respectively. Change in bowel habits and fever may also occur. Laboratory testing may demonstrate leukocytosis or an elevated C-reactive protein. Imaging options can include computed tomography (CT) of the abdomen and pelvis with intravenous contrast, magnetic resonance imaging (MRI), or ultrasound (US), though most classification systems for diverticulitis incorporate CT findings. While the majority of diverticulitis cases are uncomplicated, complications may affect up to 25% of patients. Treatment of complicated diverticulitis requires antibiotics and surgical consultation. Antibiotics are not required in select patients with uncomplicated diverticulitis. Appropriate patients for supportive care without antibiotics should be well-appearing, have pain adequately controlled, be able to tolerate oral intake, be able to follow up, have no complications, and have no immunocompromise or severe comorbidities.
CONCLUSIONS
An understanding of literature updates can improve the ED care of patients with acute diverticulitis.
Topics: Humans; Diverticulitis, Colonic; Diverticulitis; Colon, Sigmoid; Tomography, X-Ray Computed; Anti-Bacterial Agents
PubMed: 37956503
DOI: 10.1016/j.ajem.2023.10.051 -
Magyar Sebeszet Apr 2024A felnőttkori invaginatiók ritkák, klinikai megjelenésük eltér a gyerekkori formáktól. Klinikumuk igen változatos, gyakran atípusos, jellemző, hogy egy...
A felnőttkori invaginatiók ritkák, klinikai megjelenésük eltér a gyerekkori formáktól. Klinikumuk igen változatos, gyakran atípusos, jellemző, hogy egy klinikai sejtés nyomán gondolni kell az invaginatio lehetőségére. A kiegészítő vizsgálatok közül kiemelkedő szerep jut a computer tomográfiának (CT), ami magas érzékenységgel és fajlagossággal képes kimutatni a béltraktus invaginatióját. Gyógyításuk az esetek legnagyobb részében sebészi, sokszor csak a műtét során lehetséges felismerni a kiváltó okot. Esetismertetésünkben egy rendkívül ritka, felnőttkori, passage-zavart okozó colo-colicus, a bal colonfelet érintő, a colon-flexura lienalis-descendens határra lokalizált invaginatio klinikai jellemzőit, diagnosztikáját és definitív megoldásaként a laparoscoposan asszisztált bal oldali haemicolectomia műtéti megoldását mutatjuk be. Munkánkban összefoglaljuk a felnőttkori invaginatiókra vonatkozó kórélettani fogalmakat, diagnosztikai lehetőségeket, a leggyakoribb kiváltó tényezőket és terápiás lehetőségeket.
Topics: Adult; Humans; Intussusception; Citrus; Colon; Colon, Descending
PubMed: 38564272
DOI: 10.1556/1046.2024.10007 -
European Journal of Pharmacology Sep 2023Capsaicin and allyl isothiocyanate (AITC) activate transient receptor potential (TRP) vanilloid-1 (TRPV1) and TRP ankyrin-1 (TRPA1), respectively. TRPV1 and TRPA1...
Capsaicin and allyl isothiocyanate (AITC) activate transient receptor potential (TRP) vanilloid-1 (TRPV1) and TRP ankyrin-1 (TRPA1), respectively. TRPV1 and TRPA1 expression have been identified in the gastrointestinal (GI) tract. GI mucosal functions remain largely undefined for TRPV1 and TRPA1 with side-dependence and regional differences in signalling unclear. Here we investigated TRPV1- and TRPA1-induced vectorial ion transport as changes in short-circuit current (ΔI), in defined segments of mouse colon mucosa (ascending, transverse and descending) under voltage-clamp conditions in Ussing chambers. Drugs were applied basolaterally (bl) or apically (ap). Capsaicin responses were biphasic, with primary secretory and secondary anti-secretory phases, observed with bl application only, which predominated in descending colon. AITC responses were monophasic and secretory, with ΔI dependent on colonic region (ascending vs. descending) and sidedness (bl vs. ap). Aprepitant (neurokinin-1 (NK1) antagonist, bl) and tetrodotoxin (Na channel blocker, bl) significantly inhibited capsaicin primary responses in descending colon, while GW627368 (EP4 receptor antagonist, bl) and piroxicam (cyclooxygenase inhibitor, bl) inhibited AITC responses in ascending and descending colonic mucosae. Antagonism of the calcitonin gene-related peptide (CGRP) receptor had no effect on mucosal TRPV1 signalling, while tetrodotoxin and antagonists of the 5-hydroxytryptamine-3 and 4 receptors, CGRP receptor, and EP1/2/3 receptors had no effect on mucosal TRPA1 signalling. Our data demonstrates the regional-specificity and side-dependence of colonic TRPV1 and TRPA1 signalling, with involvement of submucosal neurons and mediation by epithelial NK1 receptor activation for TRPV1, and endogenous prostaglandins and EP4 receptor activation for TRPA1 mucosal responses.
Topics: Mice; Animals; Transient Receptor Potential Channels; TRPA1 Cation Channel; Capsaicin; Tetrodotoxin; Colon; Mucous Membrane; TRPV Cation Channels
PubMed: 37394028
DOI: 10.1016/j.ejphar.2023.175897