At least two cortical collecting duct (CCD) intercalated cell populations mediate HCO3- secretion and reabsorption. The present study examined the membrane location of intercalated cell Cl-/base exchange activity and the axial distribution of CCD intercalated cells. CCD were studied using in vitro microperfusion in CO2/HCO3(-)-containing solutions; intracellular pH was measured using 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. The A-type intercalated cell (A cell) and B-type intercalated cell (B cell) were identified functionally by the absence and presence of apical Cl-/HCO3- exchange activity, respectively. When a 0 mM Cl-, 0 mM HCO3- luminal solution was used, removal of Cl- from the peritubular solution caused intracellular alkalinization in all B cells. The alkalinization required neither extracellular Na+ nor changes in membrane potential. Peritubular 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) (10(-4) M) inhibited A cell but not B cell basolateral Cl-/base exchange activity. In comparison to studies performed with a 0 mM Cl- 0 mM HCO3- luminal solution, the use of a 0 mM Cl-, 25 mM HCO3- luminal solution inhibited both the identification and the magnitude of B cell basolateral Cl-/base exchange activity. When CCD from the inner and outer cortex were separately studied, only 7% of outer CCD intercalated cells were A cells, whereas 93% were B cells. In contrast, in the inner CCD, 58% of intercalated cells were A cells and 42% were B cells. Under stop-flow conditions, outer CCD alkalinized the luminal fluid, whereas inner CCD acidified the luminal fluid. These results indicate that all CCD intercalated cells possess basolateral Cl-/base exchange activity; however, A cell and B cell basolateral Cl-/base exchange activity differs, at least in terms of sensitivity to DIDS. Furthermore, there is axial heterogeneity in both intercalated cell type and function.
Objectives The occurrence of immune-related myositis (irM) is increasing, yet there are no therapeutic guidelines. We sought to analyze the current therapeutic strategies of irM and evaluate the outcomes of immune checkpoint inhibitors (ICI) rechallenge. Methods We conducted a nationwide retrospective study between April 2018 and March 2020 including irM without myocardial involvement. Depending on the presence of cutaneous signs or unusual histopathological features, patients were classified into two groups: typical or atypical irM. Therapeutic strategies were analyzed in both groups. The modalities and outcomes of ICI rechallenge were reviewed. Results Among the 20 patients, 16 presented typical irM. Regardless of severity, most typical irM were treated with steroid monotherapy (n = 14/16) and all had a complete response within ≤ 3 weeks. The efficacy of oral steroids for non-severe typical irM (n = 10) was the same with low-dose (≤ 0.5 mg/kg/day) or high-dose (1 mg/kg/day). Severe typical irM were successfully treated with intravenous methylprednisolone. Atypical irM (n = 4) had a less favorable evolution, including one irM-related death, and required heavy immunosuppression. ICI were safely reintroduced in 9 patients presenting a moderate (n = 6) or a severe (n = 3) irM. Conclusion Our data highlight that steroid monotherapy is an effective treatment for typical irM, either with prednisone or with intravenous methylprednisone pulses depending on the severity. The identification of unusual features is important in determining the initial therapeutic strategy. The outcomes of rechallenged patients are in favor of a safe reintroduction of ICI following symptom resolution and CK normalization in moderate and severe forms of irM.
The efficiency of Pygenum africanum treatment was tested on a population where the acid phosphatase activity was shown to be reduced at two successive examinations. The treatment caused an increase in acid phosphatase activity and total protein secretion. However, the fact that the men who had IgA present in their ejaculate reacted more favorably to the treatment shows that Pygenum africanum is more efficient in cases where there is no prostate gland inflammation.
Background Erythema multiforme (EM) is a muco‐cutaneous inflammatory disease mainly triggered by herpes simplex virus (HSV) recurrences. Association of EM and circulating auto‐antibodies against plakins (anti‐PLK‐Abs [EM‐PLK+]) has been reported. However, little is known about this subset of EM. Objectives We aimed to describe the clinical and immunological features and response to treatment of EM‐PLK+. Methods We conducted a retrospective multicentric study of EM‐PLK+ selected from the database of the immunological laboratory of Bichat hospital, Paris, France, from January 2009 to December 2020. Anti‐PLK‐Abs were detected in ≥1 immunological tests: immunofluorescence assay, immunoblotting and/or ELISA. Patients with alternative diagnoses were excluded. Results We included 29 patients (16 women, median age 25 [range 2–58] years). EM‐PLK+ were mostly major (EM with ≥2 mucosal involvements; n = 24, 83%) and relapsing (≥2 flares; n = 23, 79%). Cutaneous lesions were target (n = 13, 54%) and target‐like lesions (n = 9, 38%) with usual topography (acral, n = 19, 79%; limbs, n = 21, 88%). Mucosal lesions affected the mouth (n = 27, 96%) and genitalia (n = 19, 68%), with a median of 2 [range 0–5] mucous membranes. EM‐PLK+ were suspected as certain or possible postherpetic (EM‐HSV) in 19 cases (65.5%); no triggering factors were detected in 9 (31%) patients. Desmoplakin‐I/II Abs were the most frequent anti‐PLK‐Abs (n = 20, 69%); envoplakin and periplakin Abs were detected in 11 and 9 cases. Relapsing EM‐PLK+ (n = 23) were still active (≥1 flare within 6 months) in 13 (57%) patients despite immunosuppressive therapy (n = 8, 62%). Antiviral drugs were ineffective in preventing relapse in 15/16 (94%) EM‐HSV. Conclusion The rationale for anti‐PLK‐Ab detection in EM is not elucidated. More systematic research of anti‐PLK‐Abs is warranted to better understand whether this association reflects humoral immune activity in a subset of EM or is fortuitous, related to an epitope spreading process. However, EM‐PLK+ seems to be associated with major and relapsing subtypes, and difficult‐to‐treat cases.
The inner medullary collecting duct (IMCD) is the final portion of the mammalian renal tubule that is able to significantly regulate systemic acid-base balance. Although the H+ transporters of this segment are relatively well studied, little is known regarding the mechanisms of HCO3- transport. The mechanisms of HCO3- transport in primary cultures of rabbit IMCD were studied using the pH-sensitive dye, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, in CO2/HCO3(-)-containing solutions at 37 degrees C. Removal of Cl- from the extracellular solution caused reversible intracellular alkalinization, demonstrating the presence of Cl-/HCO3- exchange. Alkalinization with Cl- removal was independent of changes in membrane potential, did not require the presence of extracellular Na+, and was inhibited by the disulfonic stilbene, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 10(-4) M). Half-maximal intracellular pH (pHi) recovery with readdition of Cl- to the extracellular solution occurred at a Cl- concentration of 37.4 +/- 5.7 mM. When rabbit IMCD were cultured on permeable support membranes, Cl-/HCO3- exchange activity was found only on the basolateral membrane. However, there was no evidence of band 3 protein immunoreactivity. In contrast, no evidence for Na(+)-(HCO3-)n > 1 cotransport activity was found. Depolarization of IMCD cells by acute increases in extracellular K+ did not alter pHi, nor was Na(+)-dependent, 5-(N-ethyl-N-isopropyl)amiloride-insensitive pHi recovery from an acid load inhibited by DIDS (10(-4) M). Finally, recovery from intracellular alkalosis induced by incubation in 0 mM Cl-, 50 mM HCO3- extracellular solution required Cl- and was independent of Na+. These studies indicate that the major mechanism of HCO3- transport in primary cultures of the rabbit IMCD is via a band 3 protein-negative, Na(+)-independent, basolateral, Cl-/HCO3- exchanger.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.