神经生长因子对小鼠突触体内Ca^2＋水平的调节作用

观察了多次海马内微注射ＮＧＦ对小鼠突触体内游离钙水平的影响，并在离体情况下观察ＮＧＦ对ＥＧＴＡ和ＣａＣｌ２分别造成突触体内低钙和高钙状态的调节作用。结果如下：（１）在体实验表明，一定剂量的ＮＧＦ可显著降低老年小鼠海马突触体内游离钙水平（Ｐ＜００５）；（２）离体实验表明，当突触体游离钙水平降低时，适当剂量的ＮＧＦ具有升高游离钙水平的作用；而突触体内游离钙水平升高时，则ＮＧＦ有降低游离钙水平的作用。提示ＮＧＦ对游离钙水平的双向调节作用可能是ＮＧＦ改善老年性记忆衰退的作用机制。     

Effect of barucainide on left ventricular ejection fraction in patients with ventricular cardiac arrhythmias]

We studied the effect of barucainide, an investigational class lb antiarrhythmic drug, on ventricular arrhythmias and left-ventricular ejection fraction in 10 patients with frequent and complex ventricular arrhythmias (Lown grade 4a/4b). The study was conducted as a single-blind and placebo-controlled trial. With placebo, mean frequency of ventricular arrhythmias was 6238 VPB/24 h, 510 couplets/24 h, and 24 salvos/24 h. Mean left-ventricular ejection fraction was 37.6%, ranging from 18% to 58%. Therapy with barucainide (300-400 mg/day) resulted in a significant reduction of ventricular arrhythmias in 7 of 10 patients; in one patient barucainide had a clear proarrhythmic effect. Over all, left-ventricular ejection fraction (37.6% +/- 12% with placebo vs 36.1% +/- 11% with barucainide) was not significantly altered. In one patient, however, it was depressed by more than 5%; one patient complained of shortness of breath during exercise. None of the four patients with an initial ejection fraction below 35% showed a drop of ejection fraction during therapy with barucainide. The only main adverse effect was a small, but significant (p less than 0.005) rise of serum-kreatinine (1.13 +/- 0.26 vs 1.39 +/- 0.38 mg%) in all patients. We conclude that barucainide has a good antiarrhythmic effect and is usually well tolerated in patients with markedly depressed left-ventricular function. The mechanism causing the rise of serum-kreatinin, however, needs to be clarified in further studies.     

The Na(+)-H+ exchanger is stimulated and cell volume increased in lymphocytes from patients with essential hypertension.

A stimulation of the Na(+)-H+ exchanger has been shown in platelets of hypertensive man and lymphocytes of spontaneously hypertensive rats. In the present paper, human mononuclear leukocytes (HML) were investigated in 12 patients with essential hypertension with regard to the activity of the Na(+)-H+ exchanger and HML volume. The swelling of HML in isotonic sodium propionate was determined using a Coulter Channelyzer. Compared with matched normotensives, the cell volume of HML in a physiological buffer was significantly increased in essential hypertension (P less than 0.05). The amiloride-inhibitable rate of cell swelling in isotonic sodium propionate was also increased in HML from hypertensives. Amiloride (400 mumol/l) abolished the difference in cell volume within 1 min. These data show a functional swelling of HML in essential hypertension, probably due to an activation of the Na(+)-H+ exchanger. If also representative of smooth muscle cells, these findings could explain hypertensive vessel wall hypertrophy, in part, as functional cell swelling.     

Treatment with the antigranulocyte monoclonal antibody RB6-8C5 impairs resistance of mice to gastrointestinal infection with Listeria monocytogenes.

Treatment with the antigranulocyte monoclonal antibody (MAb) RB6-8C5 increased the severity of infection in mice intragastrically inoculated with Listeria monocytogenes. Most MAb RB6-8C5-treated mice died when inoculated intragastrically with as few as 4 x 10(4) L. monocytogenes bacteria, whereas most control mice survived intragastric inoculation with 4 x 10(8) L. monocytogenes bacteria. The increased severity of infection in MAb RB6-8C5-treated mice appeared to result from listerial multiplication in the spleen and liver rather than from local proliferation in the intestinal tract or mesenteric lymph nodes.     

Altered calcium metabolism in red blood cells of hypertensives: Persistent marker or sequel of essential hypertension?

Summary The characteristics of the increased calcium (Ca) influx observed in metabolically depleted red blood cells (RBCs) of hypertensive patients were investigated. Twenty-four normotensives, 16 untreated essential hypertensives, and 10 essential hypertensives under sufficient blood pressure control by 50–100 mg/day atenolol were studied. Free intracellular concentrations of Ca, sodium (Na), and potassium (K) were assessed using ion-selective electrodes in freeze-thawed RBCs, which were metabolically depleted by 30 mM desoxy-glucose at 37°C for 48 h. In the treated hypertensives values for Ca and K at 24 and 48 h were not different from values for the normotensives, whereas elevated Ca was found in RBCs of untreated hypertensives. Na in treated hypertensives was significantly increased at 0 and 48 h, thus, being similar to values for untreated hypertensives. Additionally, RBCs of six normals were stressed in a glass/teflon potter. Before metabolic depletion electrolytes were not affected by this procedure, while Ca at 24 and 48 h of metabolic depletion increased to significantly higher values for the hypertensive patients as compared to the controls. These results suggest that the altered Ca metabolism in the RBCs of hypertensives may reflect a secondary phenomenon due to the mechanical damage to RBCs by the elevated blood pressure.     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Analysis of the OspE determinants involved in binding of factor H and OspE-targeting antibodies elicited during Borrelia burgdorferi infection in mice

Immune evasion by Lyme spirochetes is a multifactorial process involving numerous mechanisms. The OspE protein family undergoes antigenic variation during infection and binds factor H (fH) and possibly FHL-1/reconectin. In Borrelia burgdorferi B31MI, the OspE family consists of three paralogs: BBL39 (ErpA), BBP38, and BBN38 (ErpP). BBL39 and BBP38 are identical and therefore are referred to here as BBL39. The goals of this study were to assess the specificity of the antibody (Ab) response to the OspE paralogs and to identify the domains or determinants of OspE that are required for the binding of fH and OspE-targeting Abs that develop during infection. Here we demonstrate that at least some of the anti-OspE Abs produced during infection are paralog specific and that Ab binding requires conformational determinants whose formation requires both the N- and C-terminal domains of OspE. The binding of fH to OspE was also found to be dependent on conformational determinants. It is also demonstrated here that all of the OspE paralogs expressed by B. burgdorferi B31MI are capable of binding fH. The binding of fH to members of the OspF protein family was also assessed. In contrast to an earlier report, no binding of BBO39 or BBR42 to human fH was detected. Lastly, a series of competitive binding enzyme-linked immunosorbent assay analyses, designed to determine if fH and infection serum Abs bind to the same sites on OspE, revealed that these ligands interact with different regions of OspE.     

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors

The molecular mechanisms involved in luteolysis are still unclear in the primate. This study aimed to investigate the effect of induced luteolysis on the ovarian luteinizing hormone (LH) receptor and the steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset monkey. Luteolysis was induced in the mid-luteal phase either directly by systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal using systemic gonadotrophin releasing hormone antagonist (GnRHant) treatment. The LH receptor was studied by isotopic mRNA in-situ hybridization and in-situ ligand binding and 3beta-HSD expression was studied using isotopic mRNA in-situ hybridization and immunohistochemistry. Induced luteolysis was associated with a reduction in the expression of LH receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a reduction in the LH receptor (P < 0.05) and 3beta-HSD protein concentrations within 24 h. There were no differences in the findings whether luteolysis was induced with PGF2alpha or GnRHant. This study shows that disparate mechanisms to induce luteolysis in the primate result in an identical rapid loss of the LH receptor and 3beta-HSD. In conclusion, induced luteolysis leads to rapid loss of the steroidogenic pathway in luteal cells.      

Medikamentöse Therapie tachykarder Herzrhythmusstörungen

Zusammenfassung Tachykarde Herzrhythmusstörungen lassen sich im wesentlichen auf eine Störung der Erregungsbildung — Fokusgenese — oder der Erregungsleitung — begünstigend für eine Kreiserregung —, zurückführen. Antiarrhythmika wirken diesen beiden entscheidenden Störungen entgegen. Auf Grund ihrer Hauptwirkung auf das Aktionspotential isolierter Herzmuskelzellen in therapeutischen Dosen lassen sich die Antiarrhythmika in 4 Gruppen einteilen. Beim Menschen läßt die schwerpunktmäßige Beeinflussung der Erregungsleitung in den verschiedenen Anteilen des Erregungsleitungssystems Anwendungsschwerpunkte begründen und Nebenwirkungen voraussagen. Die Antiarrhythmikawirkung auf die elektrophysiologischen Vorgänge am kranken menschlichen Herzen sind bisher noch unzureichend untersucht, so daß für die klinische Therapie letztlich die Empirie, d.h. die systematische therapeutische Anwendung entscheidet. Für die wichtigsten Antiarrhythmika haben sich so bevorzugte Indikationen ergeben. Unter bestimmten Voraussetzungen ist in der Klinik aber auch eine pathogenetisch differenzierende Therapie möglich, wenn auf Grund der bekannten spezifischen Wirkung eines Antiarrhythmikums ein Rückschluß auf die Pathogenese möglich wird; so u.a. beim Ansprechen auf Kalziumantagonisten, Typ Verapamil, die offenbar spezifisch auf sogenannte slow response Aktionspotentiale wirken. Vorbestehende TU-Abnormitäten im EKG weisen auf eine inhomogene Repolarisation als prädisponierenden Faktor für ventrikuläre Tachykardien durch Kreiserregung hin. Beim akuten Herzinfarkt kommt es zu wechselnden elektrophysiologischen Voraussetzungen für die Entstehung von Herzrhythmusstörungen, die eine therapeutische Beeinflussung durch ein einziges Antiarrhythmikum unwahrscheinlich erscheinen lassen. In der Hospitalphase ist eine ausreichend dosierte prophylaktische Gabe von Lidokain sinnvoll, in der prähospitalen Phase ohne Überwachungsmöglichkeit jedoch von zweifelhaftem Wert. Die prophylaktische Gabe von Betarezeptorenblockern kann in der posthospitalen Nachbehandlungsphase das Risiko des plötzlichen Herztodes um 50% senken. Auch bei anderen Risikopatienten mit ventrikulären Herzrhythmusstörungen ist eine konsequente antiarrhythmische Behandlung notwendig.