Inhibition of the Cl-/NaCO3- anion exchanger by xipamide in human red blood cells.

The mechanism of action of classical loop diuretics of the 2- or 3-amino-5-sulfamoylbenzoic acid and (aryloxy)acetic acid families involves competition with chloride for a common site on the (Na+, K+, 2Cl-) co-transport system. However this is not the mechanism of action of some high-ceiling diuretics like muzolimine, MK 473, xipamide, indapamide and clopamide, which are not carboxylic acids. We evaluated three of these latter diuretics (xipamide, muzolimine and clopamide) for their inhibitory effects on five ion transport systems in human red blood cells: (i) Cl(-)-dependent (Na+, K+) co-transport, (ii) (NaCO3-/Cl-) anion exchanger, (iii) (Cl-, K+) co-transport, (iv) Na+, K+ pump and (v) Na+: Li+ counter-transport; and on one ion channel the Ca2+-dependent, K+ channel. All erythrocyte transport pathways were resistant to the three diuretics studied (IC50 of 10(-3) M or higher) with one remarkable exception, the (NaCO3-/Cl-) anion exchanger. This transport system was inhibited by xipamide (IC50 of 2.5 +/- 0.4 X 10(-5) M, mean +/- S.D. of five experiments) and less potently by muzolimine (IC50 of 1.1 +/- 0.3 X 10(-4) M, mean +/- S.D. of three experiments). Clopamide only inhibited the anion exchanger at high concentrations (IC50 of about 10(-3) M). Xipamide, the most potent diuretic in this test, was at least one order of magnitude more active than furosemide, ethacrynic acid, hydrochlorothiazide and amiloride. Inhibition of the anion carrier could be involved in the diuretic action (inhibition of CO2-stimulated NaCl absorption in the TAL) and/or in the antihypertensive action (inhibition of net NaCO3- influx and secondarily of Ca2+ influx through Na+: Ca2+ exchange in vascular smooth muscle cells of xipamide).

[Beneficial effects of xipamide on pH and Ca2+ ions of cardiac cells]. / Effets bénéfiques du xipamide sur le pH et le Ca2+ des cardiocytes.

We have shown that xipamide is the only antihypertensive agent able to selectively inhibit the anion exchanger (AE), a transport system translocating (i) chloride and bicarbonate (thus participating to internal pH), but also (ii) Na+ as NaCO3-(which could explain the natriuretic effect of xipamide). On the other hand, Ollivier (Val de Grâce, Paris) has shown that xipamide exerts a beneficial action on heart by favoring left ventricular relaxation in essential hypertensive patients exhibiting cardiac hypertrophy. In order to understand this clinical effect, we have studied the effect of xipamide on pH and cytosolic free calcium in cultured Rat cardiocytes (H9c2 line). pHi was measured at equilibrium using 14C-DMO and cytosolic free calcium was measured spectrofluorimetrically with Fura2 (Shimadzu RF 5000). 1) The presence of bicarbonate induced a 0.39 +/- 0.14 (mean +/- SD; n = 3) alkalinization; final pHi was 7.08 +/- 0.15 (n = 8). Nor 20 microM DIDS (specific AE inhibitor), neither 50 microM xipamide were able to modify this result. This suggests that the alkalinization is not due to the anion exchanger. 2) After preincubation in the presence of 0.5 microM DIDS, we observed a 0.35 +/- 0.21 acidification (n = 4). Conversely, 0.5 microM xipamide induced a 0.22 +/- 0.16 alkalinization (n = 4). 3) Xipamide (0.5-500 microM) increased the internal K/Na ratio (at 0.5 microM, delta = 3.1 +/- 0.2; n = 3); this was mainly due to internal K+ increase.(ABSTRACT TRUNCATED AT 250 WORDS)

[Idiopathic nephrotic syndrome and food hypersensitivity. Value of an exclusion diet]. / Syndrome néphrotique idiopathique et hypersensibilité alimentaire. Valeur des régimes d'éviction.

A case of idiopathic nephrotic syndrome (INS) evolving since more than 7 years with 4 successive corticosensitive relapses is reported. At the time of a 5th relapse corticosteroid treatment was refused by the parents and evolution went on without any spontaneous tendency to remission. Three months later, allergy tests detected various sensitizations, especially for food allergens. An antiallergic treatment including dietary exclusions induced a complete and durable remission. Five similar cases are reported. These facts, compared to data from the literature, indicate the possible role of food hypersensitivity in INS. Its mechanism has been discussed; the possible part of a lymphocyte activation has been emphasized.

Appearance of specific antibody-bearing cells in human bronchial mucosa after local immunization with bacterial vaccine.

The immune response to local in vivo inhalation of a lysed bacteria vaccine was assessed in surgical specimens of main-stem bronchi from patients who had undergone pneumectomy for cancer. The patient population included 22 subjects; 11 of these received the aerosol vaccine twice a day for 10 days prior to surgery, while the remaining 11 patients were used as controls and were not immunized. The submucous glands of immunized subjects showed significantly more cells than did those of the controls, i.e., 62 +/- 8 versus 37 +/- 7, respectively (P less than 0.05). The following five antigens were chosen for study by fluorescence assay: Streptococcus pneumoniae types II and III, Haemophilus influenzae, Streptococcus sp. strain D19, and Klebsiella pneumoniae. An immunization-dependent correlation was found between immunoglobulin A, immunoglobulin A-bearing cells, and specific antibody-bearing cells on the one hand and three of the five antigens (S. pneumoniae types II and III and Streptococcus sp. strain D19) on the other hand. This is the first time that a relationship has been established between bacterial immunization of the lower respiratory tract and local immunoglobulin production in humans.

[Lymphadenopathy caused by hemophagocytic sinus histiocytosis (Destombes-Rosai-Dorfman syndrome). Immunologic and histopathologic study of a new case]. / Lymphadénopathie par histiocytose sinusale hémophagocytaire (syndrome de Destombes-Rosai-Dorfman). Etude immunologique et histo-pathologique d'un nouveau cas

The case reported is one of lymphadenopathy due to haemophagocytic sinusal histiocytosis which had progressed for more than 10 years before resulting in death at the age of 58 years. In this advanced form, all superficial and deep nodes were involved. In addition to histiocytic hyperplasia, with haemophagocytosis and lipid overload, there was plasmocytic hyperplasia, i.e. B-lymphocytes, with polyclonal hypergamma-globulinaemia and an increase in the levels of many antibodies, in particular against rubella and the Epstein-Barr virus. The aetiopathological significance is discussed, in particular the role of an infection due to the EB virus.