Regulation of human basophil activation; the role of Na+ and Ca2+ in IL-3-induced potentiation of IgE-mediated histamine release from human basophils.

The release of mediators from human basophils is strongly enhanced by IL-3. However, the signalling pathways of IL-3 are poorly defined in these cells. Since external Ca2+ and Na+ play important regulating roles in histamine release, the possibility that these cations could be involved in the potentiation by IL-3 of the anti-IgE-induced histamine release from human basophils was considered, and it was observed that: (i) IL-3 dramatically decreased the external Ca2+ requirement for IgE-mediated histamine release. However, histamine release from IL-3-treated basophils became only partially independent of external Ca2+, since addition of EGTA in the external medium abolished the effect of IL-3; (ii) decreasing Na+ influx by lowering external Na+ concentration in isosmotic medium inhibited the potentiating effect of IL-3 on IgE-mediated release; (iii) amiloride, an inhibitor of Na+/Ca2+ and Na+/H+ exchanges, and its derivative, benzamil, more specific for Na+/Ca2+ exchanges, inhibited the release potentiated by IL-3. In contrast, the amiloride derivative 5-(N,N-dimethyl)-amiloride, more specific for Na+/H+ exchanges, slightly increased the IL-3-enhanced release. Thus, the decreased requirement for external Ca2+ and the dependence on external Na+, taken with the effect of the Na+/Ca2+ exchange inhibitors, suggest that Na+/Ca2+ exchanges are involved in the IL-3-induced enhancement of IgE-mediated human basophil histamine release.     

Requirement of IL-5 for induction of autoimmune hemolytic anemia in anti-red blood cell autoantibody transgenic mice

IL-5, IL-10 and lipopolysaccharide (LPS) are known to activateB-1 cells in vivo in normal mice and anti-red blood cell autoantibodytransgenic mice (HL mice). To assess the exact role of IL-5in proliferation and activation of peritoneal B-1 cells, weanalyzed IL-5 receptor chain-deficient HL (IL-5R^–/–x HL) mice generated by the cross between IL-5R^–/–and HL mice. In IL-5R^–/– x HL mice, Ig-producingB-1 cells in the peritoneal cavity were negligible, althoughthe total number of B-1 cells in the peritoneal cavity wereas many as 30% of that in HL mice. Moreover, LPS- or IL-10-induceddifferentiation of B-1 cells into antibody-producing cells wasseverely impaired in IL-5R^–/– x HL mice. We alsoused in vivo 5-bromo-2'-deoxyuridine labeling to estimate theproliferation of B-1 cells in IL-5R^–/– mice. Theabsence of IL-5R did not affect spontaneous proliferation ofperitoneal B-1 cells. However, induced proliferation of peritorealB-1 cells by oral administration of LPS was markedly impairedin IL-5R^–/– mice. These results suggest that IL-5is required for activation-associated proliferation of B-1 cellsbut not for their spontaneous proliferation and support theidea that IL-5 plays an important role on the induction of autoantibodyproduction from B-1 cells.     

Constitutive Secretion of Interleukin-6 by Human Decidual Stromal Cells in Culture. Regulatory Effect of Progesterone

PROBLEM : Although several studies have demonstrated that decidual stromal cells (DSC) can secrete cytokines in culture, none of these studies documented the purity of the cultures. Since other cells of the decidua, such as macrophages and epithelial cells, also produce cytokines, it is important to ensure purity of the culture so that cytokine production can be ascribed with confidence to DSC. METHOD : DSC from early human pregnancies were highly purified and maintained in culture. Basal secretion by these cells of IL-6, together with other cytokines considered critical for pregnancy (IL-1β, TNFα and IFNγ), was measured with immunological techniques. RESULTS : We found that DSC in culture produce insignificant quantities of IL-1β, TNFá and IFNΓ, but appreciable amounts of IL-6. The production of this later cytokine was, however, inhibited by the effect of progesterone. CONCLUSIONS : Basal production of IL-6 by DSC may be involved in physiological functions at the maternal-fetal interface. Nevertheless, the secretion of this cytokine is regulated by progesterone, probably to prevent excessive production of this cytokine from triggering an inflammatory response that might compromise pregnancy.     

Cross-regulatory role of interferon-gamma (IFN-gamma), IL-4 and IL-10 in schistosome egg granuloma formation: in vivo regulation of Th activity and inflammation.

This study examined the relationship of IL-4, IL-10 and IFN-gamma with regard to the local granuloma (GR) and draining lymph node (LN) response to Schistosoma mansoni eggs. Synchronized GR were induced in naive and schistosome-infected mice at the vigorous (8 weeks) and late chronic (20 weeks) stages. In LN cultures, IL-10 and IFN production peaked on day 4 and was greatest for 8 week-infected mice. All GR cultures contained IFN, but compared with naive mice IL-10 production was accelerated at 8 weeks and abrogated at 20 weeks, consistent with expansion and abatement of Th2 activity. Cytokine neutralization was performed in egg-challenged, naive mice that were adoptively sensitized with lymphoid cells from 8 week-infected donors. GR size, GR macrophage tumour necrosis factor (TNF) production and egg antigen-elicited IL-2, IL-4, IL-5, IL-10 and IFN were examined on day 4 of GR formation. Anti-IFN augmented GR area by 40%, increased local IL-4 and IL-10, but decreased IFN and TNF production. In corresponding LN cultures, IFN decreased by about 50%, while IL-2, IL-4, IL-10 and IL-5 increased by nearly two-, four-, five- and six-fold, respectively. Anti-IL-10 did not affect GR size or GR cytokines, but abrogated GR area by 40%, along with a reduction in local IL-4 and TNF production. In LN, IL-4 depletion reduced IL-4 and IL-5 by 60-70% and increased IFN levels. These results support the notion of a cross-regulatory network in which IFN inhibits Th2 and IL-10 inhibits Th1 cells. IL-4 fosters Th2 cells differentiation in LN, but also performs a critical recruitment function in the eosinophil-rich schistosome egg-induced GR, whereas IFN contributes to enhanced GR macrophage function.     

Anastomotic insufficiency in small bowel surgery —incidence and treatment

Summary In the period 1977–1981 234 small bowel anastomoses were constructed in 143 patients. Eight anastomoses showed leakage (3.4%) and from nine anastomoses a fistula developed (3.8%): a total rate of disturbed healing of small bowel anastomoses (7.3%). In the presence of intra-abdominal infection this rate was 14.8%, in the absence of infection 0.8%. The results of treatment with oversewing and with resection and immediate anastomosis were disappointing. Better results were obtained by dismantling of the anastomosis, establishment of a split-enterostomy and reestablishment of continuity in a second stage. Mortality was 3/17 (18%). The literature is reviewed.

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Insuffizienz von Dünndarmanastomosen — Ineidenz und Therapie

Zusammenfassung In dem Zeitraum 1977–1981 wurden bei 143 Patienten 234 Dünndarmanastomosen angelegt. Acht Anastomosen zeigten eine Nahtleckage (3,4%), bei neun entwickelte sich eine Fistel (3,8%): die Gesamthäufigkeit von Wundheilungsstörungen bei Dünndarmanastomosen war 7,3%. Bei gleichzeitigem Vorliegen intraabdominaler Infektionen betrug die Häufigkeit 14,8%, ohne diese 0,8%. Die Resultate einer Therapie durch Übernähung oder Resektion mit sofort anschließender Reanastomosierung waren enttäuschend. Befriedigendere Ergebnisse wurden durch Aufheben der Anastomosen, Anlage einer split enterostomy unter Wiederherstellung der Kontinuität in einer zweiten Sitzung erzielt. Die Mortalität betrug 3/17 (18%). Ein Literaturüberblick wird gegeben.

     

Alpha-adrenoceptors, 5-hydroxytryptamine receptors and the action of dihydroergotamine in human venous preparations obtained during saphenectomy procedures for varicose veins

Summary Changes in tension were monitored isometrically on spiral strips from human saphenous veins obtained during surgical removal of varicose veins. Concentration-response curves for noradrenaline and 5-hydroxytryptamine (5-HT) were established by cumulative administrations, curves for dihydroergotamine were constructed from the mean responses to single concentrations. The use of the antagonists prazosin, yohimbine and pizotifen provided evidence for the existence of both postjunctional ₁- and ₂-adrenoceptors and for the existence of 5-HT receptors. The venoconstrictor effects of dihydroergotamine were unchanged by prazosin. Yohimbine antagonized both dihydroergotamine and 5-HT at about 60 times higher concentrations than required against noradrenaline whereas pizotifen inhibited responses to both dihydroergotamine and 5-HT at about 100 times lower concentrations than those to noradrenaline.These new results are in contrast to conclusions drawn from animal studies and do not support the suggestion that in man the venoconstrictor activity of dihydroergotamine is mediated through stimulation of -adrenoceptors. The present results strongly suggest that in human saphenous veins the constrictor activity of dihydroergotamine is mediated at least in part through stimulation of 5-HT receptors.     

Relative Validity of MijnEetmeter: A Food Diary App for Self-Monitoring of Dietary Intake

This study aimed to evaluate the relative validity of intake of energy, nutrients and food groups assessed with MijnEetmeter food diary as compared to 24-h dietary recalls, and if this differed between experienced and new users. One hundred men and women aged 18–70 y participated, of whom 47 had prior experience with the tool. Participants kept MijnEetmeter on three days. Trained dietitians called them three times for a 24-h dietary recall interview, once recalling food consumption on the same day as the food recording in MijnEetmeter. Systematic differences and correlations were assessed, and Bland–Altman plots were created; both for 3-day mean intakes and for intakes on the same day. Relative to 24-h dietary recalls, MijnEetmeter underestimated consumption of drinks, added fat, cereal products, and potatoes. Relative underestimation was observed for energy intake (6%) and about half of the nutrients. Experienced MijnEetmeter users underestimated intake the least. For intake of energy and six key nutrients, correlations between 3-day mean intakes were above 0.7 except for sodium intake. In conclusion, MijnEetmeter moderately underestimates intakes of energy and some nutrients and food groups. To improve the self-monitoring of dietary intake, it is recommended that the users record food consumption for several days and that the apps probes for easily forgotten foods and drinks.     

纳催离和苯那普利治疗高血压合并糖尿病动态血压及微白蛋白尿的比较研究

探讨纳催离（吲哒帕胺）治疗高血压（HP）合并Ⅱ型糖尿病（NIDDM）病人降压效应及对微量白蛋白（mAlb)尿的影响,并与苯那普利（洛丁）的疗效相比较,对HP合并NIDDM病人46例给予催离以及44例给予苯那普利治疗6个月,进行用药前后24h动态血压（ABPM）及尿mAlb测定,结果显示：与对照组及自身对照相比,纳催离与苯那普利治疗后,ABPM指标及尿mAlb均显著改善（P＜0．05或P＜0．01）,而两药之间疗效对比无差异,上述结果提示,纳催离治疗HP合并NIDDM病人与苯那普利效果一样,明显降低血压的同时,还兼有降低mAlb的作用。     

高血压病患者血压40例昼夜模式分析

目的 探讨高血压病患者的血压昼夜模式,为临床治疗提供依据。方法 按WHO标准选40例高血压病人,用美国罗京公司产2420－2020型动态血压仪连续观察血压24h,结束后使用该机器配置的计算机回放进行分析,观察24h昼夜间平均收缩压、舒张压及标准差,观察血压负荷及血压模式。统计方法采用t检验。结果 构型组昼夜平均收缩压、舒张压、血压变异均值昼＞夜（P＜0．05）;收缩压和舒张压负荷昼＝夜,差异无显著性（P＞0．05）;非构型组平均收缩压、舒张压及血压变异昼夜差异无显著性（P＞0．05）,但收缩压与舒张压负荷夜间明显高于日间,差异有显著性（P＜0．01）。结论 血压昼夜变化受交感神经与肾素血管紧张素系统等双重作用有关。     

Is the Parkland formula still the best method for determining the fluid resuscitation volume in adults for the first 24 hours after injury? — A retrospective analysis of burn patients in Germany

BackgroundR Rapid fluid resuscitation is a crucial therapy during the treatment of patients with extensive burns. In 1968, the Parkland Formula was introduced for the calculation of the estimated volume of the resuscitation fluid. Since then, different methods for the calculation of fluid resuscitation volume have been developed. We aimed to evaluate if the Parkland formula is still the most effective method for fluid resuscitation volume calculation in burn patients.MethodsIn the period between January 2015 and January 2019, data from 569 patients over 16 years old with burns of more than 20% total body surface area (TBSA) and at least 15% TBSA full thickness burns were entered in the German burn registry. The patients were divided into 5 groups (0, +1, ?1, +2, ?2) according to the volume of the resuscitation fluid they received. Group 0 patients received the amount of fluid calculated according to the Parkland formula (n = 83). The 4 other groups received reduced (-1, -2) or increased (+1, +2) fluid volumes in comparison to the value obtained by the Parkland formula.ResultsPatients in Group 0 presented a significantly lower mortality in the first week (4.5%) compared to groups –2 (16.7%) and group +2 (19.5%) (p = 0.021). Furthermore, the mean number of operations in group +2 (5.81) was higher than in group ?2 (3.81). Surviving patients from group +2 presented a longer hospital stay (68.1 days) compared to the other groups. Additionally, the logistic regression analysis showed a higher survival of patients in groups ?2 and ?1 (regression coefficients ?0.11 and ?0.086; Odds Ratio 0.896 and 0.918; 95% Confidence Interval (CI) 0,411–1.951 and 0.42–2.004).ConclusionIn this retrospective study, register based analysis a restrictive fluid regime was associated with a higher survival compared to the liberal Parkland guided fluid regime.