Dual regulation of the Na+/H(+)-exchange in rat peritoneal mast cells: role of protein kinase C and calcium on pHi regulation and histamine release

1. The purpose of this study was to compare the actions of phorbol 12-myristate 13-acetate (PMA) and ionomycin on Na+/H+ exchange activation and histamine release to that of compound 48/80 in order to study the possible relationship between pHi and secretion of histamine in rat peritoneal mast cells. 2. Resting pHi in mast cells suspended in a bicarbonate-free physiological salt solution amounted to 6.73 +/- 0.05 (mean +/- s.d., n = 52). 3. PMA (20 nM) induced a substantial but rather slow increase in pHi. This response was very sensitive to inhibition by staurosporine, very sensitive to inhibition by 5-(N,N-hexamethylene)amiloride (HMA), insensitive to the absence of extracellular calcium (without EGTA), and sensitive to partial depletion of intracellular calcium with EGTA. 4. Ionomycin (1 microM) induced a biphasic change in pHi that was sensitive to inhibition by HMA, insensitive to staurosporine. In the absence of extracellular calcium using EGTA, the biphasic response disappeared, leaving only a slow, and diminished change in pHi. 5. The effects of ionomycin and PMA on pHi were additive. 6. Addition of the secretagogue compound 48/80 (1 microgram ml-1) increased pHi, substantially, delta pHi amounting to 0.29 +/- 0.05 pH-units (n = 4). The biphasic pHi-response was insensitive to the absence of extracellular calcium (without EGTA). The initial fast response in pHi was, however, inhibited by HMA, not staurosporine. 7. The finding that staurosporine and HMA each inhibited approximately half of the compound 48/80-induced pHi-response, whereas both inhibitors completely abolished the compound 48/80-induced pHi-response seems to indicate that two independent pathways for the activation of the Na+/H+ exchange were stimulated by compound 48/80. 8. The histamine release induced via both PKC activation (using PMA) and calcium (using ionomycin) were much larger than the sum of each activation pathway, whereas in the absence of extracellular calcium using EGTA, the histamine release in response to PMA and ionomycin was completely abolished. 9. The compound 48/80-induced histamine release was partially sensitive to inhibition by HMA (approximately 30% inhibition) and partially sensitive to inhibition by staurosporine (approximately 50% inhibition). Preincubation with staurosporine and HMA before stimulation with compound 48/80 showed the same degree of inhibition as observed after staurosporine alone, even though this combination of drugs completely inhibited the pHi-response. Furthermore, compound 48/80-induced histamine release was not dependent on the presence of extracellular calcium (with and without EGTA). 10. In spite of the similarities in second messenger pathways for pHi regulation and histamine release, it is, however, not very likely that these two processes are directly related. It is, however, possible, that an increase in pHi plays a permissive, rather than an essential role for histamine release in rat peritoneal mast cells. This hypothesis was supported by the finding that preincubation with the Na+/H+ exchange-inhibitor HMA inhibited 30% of the compound 48/80-induced histamine secretion.     

Complementary feeding: a global perspective

BACKGROUND AND HYPOTHESIS: Antiarrhythmic drugs are widely used for treatment of atrial fibrillation (AF) and restoration of sinus rhythm. This prospective, randomized, and controlled study compared the efficiency and safety of propafenone versus procainamide for the treatment of acute AF. METHODS: In all, 117 patients (55 women, 62 men, mean age 64.2 +/- 13 years, median 63 years) who presented with AF were included in the study. Exclusion criteria were signs or symptoms of heart failure on physical examination, recent myocardial infarction or cardiac surgery, cardiogenic shock, or hypotension. Forty-one patients spontaneously recovered sinus rhythm; the remaining 76 patients were randomized to receive propafenone or procainamide. Propafenone was given at a dose of 2 mg/kg body weight intravenously (i.v.) over 30 min. Patients randomized to receive procainamide received a bolus of 100 mg i.v. administered every 5 min up to a maximum dose of 1 g. The clinical characteristics of the two groups were comparable. RESULTS: The number of patients who recovered sinus rhythm after the treatment was larger in the procainamide-treated group (Group 1) (69.5%) than in the propafenone-treated group (Group 2) (48.7%); p < 0.05. The time required for cardioversion was significantly lower in Group 1 (mean 4.1 +/- 1.3 h), than in Group 2 patients (mean 7.3 +/- 2.6 h) (p < 0.01). CONCLUSION: In the present study, procainamide was more effective than propafenone for the treatment of AF of short duration.     

Prostatic cancer men under age 65. Occurrence and need for study

Based on information from the nationwide Danish Cancer Registry, the development in prostate cancer incidence among Danish men under 65 years is reviewed. Changes in incidence rate, clinical stage and the number of possible candidates for radical treatment are discussed.     

Transport of paraquat by isolated renal proximal tubular segments from rabbits

In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH concentrations were determined in basal conditions and after an oral glucose tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose concentrations were also evaluated. The results were compared with those obtained in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients, respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L). SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per min). Data indicate that chronic uremia induces a loss of SRIH secretory cell responsiveness to glucose. A possible effect of impaired SRIH secretion on glucose metabolism in CRF is discussed.     

Traumatic knee luxation

This report is based on two case stories. Traumatic knee dislocation is a rare but serious event. There is extensive damage to the ligaments of the knee, but the vascular lesions, with an incidence of approximately 29% are of primary concern. Signs of ischaemia indicate arteriography or exploration, and if the vascular lesion is repaired within eight hours, the majority can avoid amputation. Complicating fractures, ligament lesions and nerve lesions have secondary priority to arterial lesions. A combination of surgical ligament-repair/reconstruction and intensive rehabilitation seems the most promising.     

Geophagy, iron status and anaemia among pregnant women on the coast of Kenya

OBJECTIVE: To report a case of methemoglobinemia in a patient receiving dapsone for prophylaxis of Pneumocystis carinii pneumonia (PCP). CASE SUMMARY: A 69-year-old white woman was hospitalized to rule out sepsis. Two years prior to this admission, the patient received an orthotopic liver transplant after which she required hemodialysis three times weekly. Because of intolerance to trimethoprim/ sulfamethoxazole and aerosolized pentamidine, she was prescribed dapsone therapy on hospital day 13, that was continued for 11 days. On hospital day 45 the patient received a cadaveric kidney transplant, and dialysis treatments were scheduled only as needed. One week after the transplant, dapsone therapy was resumed. Nine days into this course of dapsone, the patient developed dyspnea and oxygen desaturation of unknown etiology. The patient was evaluated for and diagnosed with methemoglobinemia. She received two doses of intravenous methylene blue and one dose of oral activated charcoal due to fluctuating methemoglobin concentrations. DISCUSSION: The elimination of dapsone is not completely understood. Several case reports of dapsone-induced methemoglobinemia are present in the literature. Most have occurred in patients who have accidentally or deliberately overdosed. Cases of methemoglobinemia in patients receiving therapeutic doses of dapsone are discussed. CONCLUSIONS: The growing numbers of immunosuppressed patients due to transplantation of HIV may result in increased dapsone use for the prevention of PCP. Clinicians should be aware of the adverse effects associated with dapsone therapy, and patients with dyspnea and hypoxemia of unclear etiology should be evaluated for methemoglobinemia.     

The use of a stereological method to estimate the volume of Schistosoma mansoni granulomas: the effect of zinc deficiency

Kidney xenotransplantation is not yet a realistic clinical treatment modality. However, during the last decades more than 30 kidneys from other species have been transplanted into humans; some of the kidneys sustained some function up to 60 days. Recent progress in genetic engineering has raised the possibility to create large transgenic animals which express human complement regulatory proteins (CRP). Since early complement activation is believed to be the main triggering event for xenograft destruction, complement regulation by species-specific CRP should avoid hyperacute rejection in transspecies transplantation. The perfusion of hDAF-transgenic pig kidneys with human blood was not associated with the morphological signs of hyperacute rejection when compared to non-transgenic control organs. Specific immunohistology could demonstrate that the transgene was sufficient to regulate complement activation beyond C3 despite the endothelial deposition of xenoantibodies. In the future, these organs could be further optimized and ultimately tested in a clinical pilot protocol under appropriate immunosuppression.     

Changing monopolies and European oil supplies: the shifting balance of economic and political power in the world oil market

Monopoly now dominates the world oil market. Its effects are often unexpected, and forecasting is more difficult than under competition. The authors of this article illustrate the need to forecast not only the impacts of supply and demand, but also the control over supply by a group of countries whose interests are not always uniform, depending on political as well as economic factors.     

Phase-type models of channel-holding times in cellular communication systems

In this paper, we derive the distribution of the channel-holding time when both cell-residence and call-holding times are phase-type distributed. Furthermore, the distribution of the number of handovers, the conditional channel-holding time distributions, and the channel-holding time when cell residence times are correlated are derived. All distributions are of phase type, making them very general and flexible. The channel-holding times are of importance in performance evaluation and simulation of cellular mobile communication systems.