Effects of nifedipine and indomethacin on cough induced by angiotensin-converting enzyme inhibitors: a double-blind, randomized, cross-over study.

Prostaglandins (PG) have been suggested to play a role in the genesis of cough induced by angiotensin-converting enzyme inhibitors (ACE-I) and that inhibition of PG synthesis can reduce or abolish the incidence of this side effect. Moreover, experimental and clinical data suggest that nifedipine, a dihydropyridine Ca antagonist, can inhibit PG synthesis. Therefore, we wished to determine whether nifedipine can reduce cough induced by ACE-I as compared with indomethacin, a known inhibitor of PG synthesis. Fourteen hypertensive patients who developed cough during captopril chronic therapy randomly received slow-release nifedipine 20 mg twice daily (b.i.d.), indomethacin 50 mg b.i.d., and placebo b.i.d. for 1 week in a double-blind, cross-over design. At the end of each treatment phase, cough was evaluated by a self-administered questionnaire containing an ordinal scale for daily cough intensity and frequency. Indomethacin abolished or markedly reduced cough induced by ACE-I, whereas nifedipine reduced it but to a lesser degree. These findings suggest that PG can play a role in cough caused by ACE-I, and a dihydropyridine Ca antagonist can reduce the occurrence of this side effect.     

Antihypertensive activity and duration of action of dilevalol in hypertensive patients at rest and during exercise. A comparison with captopril

The aim of this study was to compare the effect of dilevalol and captopril on blood pressure and heart rate in hypertensive subjects, both at rest and during bicycle exercise. Thirty mild hypertensive patients (24 men, 6 women), aged 34-55, were studied in a randomized, double-blind, parallel group trial. After a 3-week placebo run-in, patients were randomized to receive either dilevalol (200 mg once daily) or captopril (50 mg twice daily) for 4 weeks. Dilevalol-treated patients whose diastolic blood pressure had not decreased by more than 8 mmHg from baseline (or to less than 95 mmHg) were given 400 mg once daily for a further 2 weeks. Treatment was stopped for all other patients. Blood pressure and heart rate were measured at rest and during bicycle exercise tests 4 ("peak") and 24 hours ("trough") after dosing in the dilevalol group and 4 ("peak") and 12 hours ("trough") after dosing in the captopril group. At the end of the placebo run-in, mean resting blood pressure was 156/102 mmHg in the dilevalol group and 157/103 in the captopril group. Six patients had blood pressure normalization with captopril and 9 with dilevalol 200 mg; a further 2 patients achieved normalized blood pressure levels with dilevalol 400 mg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic ulcerative stomatitis: A comprehensive review and proposal for diagnostic criteria

Chronic ulcerative stomatitis (CUS) is an immune‐mediated disorder characterized by oral erosions and ulcers usually refractory to conventional treatments. The disease often involves middle‐aged and older women with painful lesions sometimes resembling those of erosive oral lichen planus (OLP). The most affected sites are the buccal mucosa, the gingiva and the tongue, but the skin is involved in 22.5% of cases. Histopathologic features in CUS are non‐specific and indistinguishable from those of OLP, with the exception of the presence of a mixed infiltrate composed of lymphocytes and plasma cells. Direct immunofluorescence (DIF) analysis reveals the presence of stratified epithelium‐specific antinuclear antibodies (SES‐ANA) in the lower third of the epithelium. The IgG antibodies detected on DIF are directed against the ?Np63α isoform of p63 expressed in the nuclei of the epithelial basal cells. A distinguishing feature of CUS is the low response to conventional corticosteroid therapy and the good outcome with hydroxychloroquine at the dosage of 200 mg/day or higher dosages. This paper presents a comprehensive review of CUS and is accompanied by a new case report (the 73rd case) and a proposal for updated diagnostic criteria.     

Prognostic value of estimated glomerular filtration rate in hospitalized elderly patients

A multicenter observational study, REPOSI (REgistro POliterapie Società Italiana di Medicina Interna), was conducted to assess the prognostic value of glomerular filtration rate (eGFR) on in-hospital mortality, hospital re-admission and death within 3 months, in a sample of elderly patients (n = 1,363) admitted to 66 internal medicine and geriatric wards. Based on eGFR, calculated by the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, subjects at hospital admission were classified into three groups: group 1 with normal eGFR (≥60 ml/min/1.73 m², reference group), group 2 with moderately reduced eGFR (30–59 ml/min/1.73 m²) and group 3 with severely reduced eGFR (<30 ml/min/1.73 m²). Patients with the lowest eGFR (group 3) on admission were more likely to be older, to have a greater cognitive and functional impairment and a high rate of comorbidities. Multivariable logistic regression analysis showed that severely reduced eGFR at the time of admission was associated with in-hospital mortality (OR 3.00; 95 % CI 1.20–7.39, p = 0.0230), but not with re-hospitalization (OR 0.97; 95 % CI 0.54–1.76, p = 0.9156) or mortality at 3 months after discharge (OR 1.93; 95 % CI 0.92–4.04, p = 0.1582). On the contrary, an increased risk (OR 2.60; 95 % CI 1.13–5.98, p = 0.0813) to die within 3 months after discharge was associated with decreased eGFR measured at the time of discharge. Our study demonstrates that severely reduced eGFRs in elderly patients admitted to hospital are strong predictors of the risk of dying during hospitalization, and that this measurement at the time of discharge helps to predict early death after hospitalization.     

The Lepidopteran endoribonuclease-U domain protein P102 displays dramatically reduced enzymatic activity and forms functional amyloids

Hemocytes of Heliothis virescens (F.) (Lepidoptera, Noctuidae) larvae produce a protein, P102, with a putative endoribonuclease-U domain. In previous works we have shown that P102 is involved in Lepidopteran immune response by forming amyloid fibrils, which catalyze and localize melanin deposition around non-self intruders during encapsulation, preventing harmful systemic spreading. Here we demonstrate that P102 belongs to a new class of proteins that, at least in Lepidoptera, has a diminished endoribonuclease-U activity probably due to the lack of two out of five catalytically essential residues. We show that the P102 homolog from Trichoplusia ni (Lepidoptera, Noctuidae) displays catalytic site residues identical to P102, a residual endoribonuclease-U activity and the ability to form functional amyloids. On the basis of these results as well as sequence and structural analyses, we hypothesize that all the Lepidoptera endoribonuclease-U orthologs with catalytic site residues identical to P102 form a subfamily with similar function.