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The aim of this study was to evaluate the efficacy of acarbose, an inhibitor of alpha-glucosidase, on glycemic control in elderly overweight type 2 diabetic patients poorly controlled by oral hypoglycemic agents (OHA) or insulin. Our study included 22 overweight patients, 60-75-years-old, treated with OHA and/or insulin who, after a period of 4 weeks of controlled diet, showed a poor metabolic control. They were divided into two groups: Group I (nine patients) on OHA treatment; Group II (13 patients) undergoing treatment with insulin alone or in combination with OHA. Acarbose was administered to all the patients (100 mg three times a day at meal times) for 6 months in addition to their previous treatment. The addition of acarbose caused a significant reduction in both groups with regard to fasting glycemia (after 3 and 6 months, respectively, 20.7 and 21.9%, P

To gain further insights into the immunopharmacological mode of action of the immunosuppressant antibiotic deoxyspergualin (DSP), its effects were evaluated in murine lethal endo- and exotoxemia. These are two cytokine-mediated macrophage and T cell dependent immunoinflammatory conditions that can be induced in D-Galactosamine (D-Gal) presensitized mice by the injections with either LPS or SEB, respectively. The results show that prophylactic treatment with DSP (2.5 or 5 mg/kg bd.wt. 48, 24 and 2 h prior to challenge) neither improved the rate of survival, nor influenced the massive increase in the blood levels of tumor necrosis factor-alpha which followed the challenge with LPS or SEB. In sharp contrast, these clinical and seroimmunological events were both markedly counteracted by prophylactic treatment with sodium fusidate, another immunosuppressive agent used as control.

Patients with chronic heart failure have elevated levels of proinflammatory cytokines; however, the mechanism for their increased expression and the site of their production are unknown.Twenty-two patients with heart failure, New York Heart Association functional class II to IV, underwent hemodynamic evaluation and echocardiographic study. Blood samples for cytokine evaluation were performed in the ascending aorta, coronary sinus, inferior vena cava, and hepatic vein. Levels of tumor necrosis factor-alpha (TNF-alpha), its soluble receptors sTNF-RI and sTNF-RII, interleukin-6 (IL-6), IL-6 soluble receptor, soluble gp130, interleukin-2 soluble receptor, and soluble Fas were measured with enzyme-linked immunosorbent assay kits.IL-6 concentrations were higher in class IV patients than in class III patients, which in turn were higher than those in class II. TNF-alpha, sTNF-RI, and sTNF-RII were higher in class IV patients than in class III and II patients. Significant correlations were found between IL-6 concentrations and left ventricular end-systolic volume (r = 0.64; P.001), pulmonary wedge pressure (r = 0.56; P.01), and left ventricular ejection fraction (r = -0.56; P.01). No correlation was found between TNF-alpha and its soluble receptors and left ventricular volumes or hemodynamic measures. Finally, no difference in cytokine concentrations was found among the different sample sites.Among inflammatory cytokines, IL-6 concentrations better reflect the hemodynamic derangement in patients with heart failure. No cardiac or gut production of cytokines occurs in patients with mild to severe heart failure.

In human adult hematopoiesis, the TAL-1 gene is up- and down-modulated in erythropoiesis and granulopoiesis, respectively [G. L. Condorelli et al., Blood, 86: 164-175, 19951. Here, it is shown that, in a hematopoietic progenitor cell (HPC) unilineage differentiation culture, tal-1 is induced and then expressed, in a sustained manner, in the megakaryopoietic lineage, whereas it is barely or not detected in the monocytopoietic series. We have investigated the role of enforced tal-1 expression by retroviral transfer into HPCs [erythroid burst-forming units and megakaryocytic and granulomonocytic colony-forming units (CFUs)], primitive HPCs (high proliferative potential colony-forming cells), and putative hematopoietic stem cells (HSCs), assayed as long-term culture initiating cells. TAL-1 overexpression induces an increase of erythroid burst-forming unit colony number and size and megakaryocytic CFU colony number and an inhibition of granulomonocytic CFU and granulocytic CFU (CFU-G) but not monocytic CFU colony number; conversely, TAL-1 mutants with defective heterodimerizing or DNA-binding domains do not exert these effects at a significant level. Although it does not affect long-term culture initiating cells, exogenous TAL-1 causes a significant proliferative stimulus on primary and secondary high proliferative potential colony-forming cells. In conclusion, exogenous tal-1 exerts differential and stage- and lineage-specific effects on the HPC/HSC differentiation/proliferation gene programs. Thus, it induces a stimulatory effect at the level of erythroid and megakaryocytic HPCs, while exerting a selective proliferative action on downstream erythropoiesis. Furthermore, it induces differential effects on the myeloid series: the partial blockade of CFU-G differentiation is possibly linked to the sharp down-modulation of endogenous TAL-1 expression at the level of the CFU-G-to-granulopoietic precursor differentiation step; in contrast, no significant effect is observed on monocytic CFU colony formation. Finally, the stimulatory effect on primitive HPCs but not putative stem cells suggests subtle differences in the effects exerted by tal-1 overexpression on primitive HPC/HSC subsets in adult life.

The TAL-1 gene specifies for a basic domain-helix-loop-helix protein, which is involved in the control of normal hematopoiesis. In human pathology, the TAL-1 gene product is expressed in a high percentage of T-cell acute lymphoblastic leukemias in the pediatric age range; however, it has not been established whether the expression has a causal role in oncogenesis. In this report, we describe the phenotype of mouse transgenic lines obtained by inducing tal-1 protein expression in lymphoid tissues using the LCK promoter. The survival rate of tal-1 transgenic animals was much lower as compared with control mice. Histopathological analysis revealed lymphomas of T-cell type, often comprising a minor B-cell component. Some mice showed marked splenic lymphocyte depletion. Primary lymphocyte cultures showed partial independence from exogenous growth stimuli and increased resistance to low-serum apoptosis. To further unravel the tal-1 oncogenic potential, a strain of tal-1 transgenic mice was crossbred with p53-/- mice; the survival rate in these animals was reduced by more than one-half when compared with that of tal-1 mice, and histopathological analysis revealed exclusively T-cell lymphomas. These data indicate that TAL-1, expressed in T cells, is per se a potent oncogene, which may exert a key leukemogenetic role in the majority of T-cell acute lymphoblastic leukemias.

The treatment of NIDDM patients with secondary failure to sulfonylureas is still a debated problem. In this study we compared in NIDDM patients with secondary failure to glyburide, the effect of adding a single, low-dose bed time either NPH or ultralent insulin injection (0.15-0.2 U/kg) to the previously ineffective sulfonylurea treatment. Both NPH and ultralent insulin therapy have been demonstrated to be effective in ameliorating metabolic control in NIDDM patients with secondary failure to sulfonylureas. However, the addition of bed-time ultralent insulin caused a greater and significant decrease in post prandial plasma glucose. In contrast, the average fasting plasma glucose decrease was significantly greater after NPH insulin administration. These results indicate that in NIDDM patients with secondary failure to glyburide bed-time ultralent insulin administration is a better tool to improve the post prandial plasma glucose.

Mossbauer parameters for hexacoordinate iron(II) complexes of the type [Fe(N-N)n(CNMe)m](ClO4)2 (m = 6, 4, 2 or 0; n = 0, 1, 2 or 3; N−N = 2,′ -bipyridine or 1,10-phenanthroline) have been determined. Treatment by a point-charge model including distortions has been carried out in order to rationalize the quadrupole splittings. A computer program has been developed to handle variable geometry systems.

1. Die obere Abklemmung bewirkt, indem sie die Reizleitung im oberen sino-aurikularen Bundel unterbricht, entweder ein erniedrigtes Potential oder eine Umkehrung der P-Zacke.

Die AA. haben die Untersuchung der 1958 schon beschriebenen (L. Condorelli-Atti del XX Congresso della Soc. It. di Cardiologia, Rimini 1958) peripheren Atmungsrezeptoren weiter vertieft. Die Resultate der vorliegenden Untersuchung konnen so zusammengefast werden: Die chemische Reizung durch Injektion von KCN-Losung in die Arterien der Extremitaten bewirkt auser dem kardiovaskularen Reflex (Tachykardie und Blutdrucksteigerung), der schon vonHeger, Spallitta undConsiglio und vonPagano beschrieben wurde, einen Atmungsreflex, bestehend aus Atemfrequenzzunahme mit Zunahme der Tiefe der Atmung. Dieser Reflex ist in seiner Qualitat verschieden von demjenigen, der auf die Reizung mit KCN der Chemorezeptoren des Karotissinus und der kardio-aortischen Zone erfolgt. Zum Unterschied zu den Chemorezeptoren des Sinus carotideus sprechen die Atmungsrezeptoren der peripheren Gefase nicht auf Lobelin und nur wenig auf Nikotin an; ihre Reizbarkeit wird nicht durch Beatmung mit 100% igem O2 beeintrachtigt. Die Nerven, die die Impulse der peripheren Gefasrezeptoren zum Zentrum fuhren, verlaufen in den gemischten somatischen Nerven. Der Sitz der Rezeptoren befindet sich in den letzten Aufzweigungen der Arteriolen. Aus dem bis jetzt gesammelten Material scheinen sich diese Rezeptoren nur in den Arteriolen der Muskulatur zu befinden.

Die vorliegenden Forschungen zeigen, das die Arteriolen von Leber, Pankreas, Magen, Dunndarm und Dickdarm, Nieren und Hirn, ahnlich wie Venen, Endokard des Vorhofs und des rechten Ventrikels sowie Lungenarterien nicht mit sensitiven und KCN-reizbaren Endigungen ausgestattet sind.

Die in den unteren Gliedmasen beim Ubergang von der Horizontallage zur Aufrechtstellung entstehende endoarterielle Druckerhohung lost in den Arterien grosen und mittleren Kalibers eine „Tonusreaktion” aus.

Der in einem Muskelarterienbereich durch bruske Injektion von 20–30 cm3 defibriniertem Blut oder isotonischer NaCl- oder Glukoselosung hervorgerufene Widderstos, erzeugt nicht immer eine fluchtige kardiovaskulare und respiratorische Wirkung, ahnlich derjenigen, die durch die Reizwirkung von Kaliumsalzen ausgelost wird. Die “Veratrinisierung” eines Muskelarterienbereichs erhoht die Sensibilitat der Rezeptoren der Muskelarteriolen fur langere Zeit gegenuber der durch die bruske endoarterielle Injektion von defibriniertem Blut erzeugte mechanische Wirkung des Widderstoses. Die vorherige Injektion von Kalziumsalzlosungen im gleichen Gebiet hebt die Sensibilitat der Rezeptoren der Muskelarteriolen gegenuber der mechanischen Reizwirkung auf, selbst nach einer Sensibilisierung des Gebietes mittels Veratrin. Daraus wird gefolgert, das die mechanische Reizwirkung durch den Widderstos auf die Rezeptoren der Muskelarteriolen eine Folgeerscheinung der ortlichen Freisetzung von Klonen ist.

Die vorliegenden Versuche zeigen, das die mit KCN gereizten peripheren Gefasrezeptoren ihren Sitz in der Intima der Muskelarteriolen haben. Ferner wird festgestellt, das die Elektrostimulierung des Hauptendes der sensitiven Hautnerven weder einen kardiovaskularen noch einen respiratorischen Effekt auslost, dagegen eine solche des Zentralstumpfes der Muskelnerven sowohl einen kardiovaskularen (Hypertension und Tachykardie) als auch einen respiratorischen Effekt (Tachypnoe) hat, ahnlich dem durch KCN-Injektion in die arteriellen Muskelgefase erzielten. Schlieslich wird zugegeben, das die afferenten Bahnen der spezifischen Sensibilitat der Muskelarteriolen in den durch die Muskelnerven verlaufenden Fasern γ und δ dargestellt sind und das die afferenten Bahnen zum Teil einen gekreuzten, zum Teil einen direkten intramedullaren Verlauf haben.

1.Die Abklemmung des Bachmannschen Bundels bewirkt in vielen Fallen einerseits eine Anderung des Vorhof-Elektrokardiogramms, die entweder in einer Abnahme der Hohe der P-Zacke oder in einer vollkommenen Spaltung der Zacke besteht, und fuhrt andererseits zu einer zeitlichen Verzogerung der Kontraktionen des linken Vorhofs. Es ist nicht mit Sicherheit zu entscheiden, ob die nach der Unterbindung desBachmannschen Bundels auftretenden Storungen die Folgen der Abklemmung der Muskelfasern oder des mit den Fasern verlaufenden Gefases seien.

Aus den Untersuchungen der Verfasser kann geschlossen werden, das die Muskelarteriolen, deren Chemorezeptoren empfindlich sind gegen CN−, K+ und Zitronensaure-Ionen, mit Histamin, Azetylcholin, Nikotin und Pepton nicht reizbar sind. Die Untersuchungen zeigen ebenfalls, das Natriumfluorid und Monojodessigsaure eine inhibierende Wirkung auf die Reizung mit Cyanid und Zitronensaure-Ionen ausuben, wahrend sie die Reizwirkung mit Kalium-Ionen nicht beeinflussen wurden.

In order to evaluate the function of the hypothalamic-pituitary-prolactin axis in "adolescent gynaecomastia" (AG), sulpiride was administered to 7 normal boys and 7 boys with AG. The maximum increase in serum prolactin (PRL) above the mean baseline level (Δmax) was used as index of response. The sulpiride induced a greater PRL release in boys with gynaecomastia than in the controls. Our data indicate that boys with gynaecomastia may have a greater pituitary prolactin pool. The results also illustrate the usefulness of specific neurotrophic agents such as sulpiride as important tools for evaluating the function of the hypothalamic-pituitary-PRL axis.