Die Phosphatasen der Darmschleimhaut

Zusammenfassung Die Aktivität der alkalischen und sauren Phosphatase in verschiedenen Darmabschnitten wurde bei verschiedenen Altersklassen der Maus untersucht. Säuglingsmäuse bis zum Alter von 12 Tagen zeigen im Dünndarm ein von allen andern Altersstufen signifikant verschiedenes Verhalten der alkalischen Phosphatase. In der folgenden Lebensperiode bis zum 21.–24. Tag nähert sich die Aktivität der alkalischen Phosphatase in ihrer Verteilung zwischen kardianahen und coecumnahen Darmabschnitten den Verhältnissen beim ausgewachsenen Tier an. Die Aktivität der sauren Phosphatase weist gegenüber der alkalischen geringere Schwankungen auf, doch bestehen auch hier deutliche Altersunterschiede. Im Dickdarm bleibt die Aktivität der alkalischen und sauren Phosphatase während des Wachstums unverändert.Die Befunde sind mit der funktionellen Differenzierung der verschiedenen Darmabschnitte beim heranwachsenden Tier in Zusammenhang zu bringen. Parallelen zur Entwicklung des Menschen werden zur Diskussion gestellt.     

Influence of subchronic administration of oestrone-3-O-sulphamate on oestrone sulphatase activity in liver, spleen and white blood cells of ovariectomized rats

Inhibition of oestrone sulphatase followed by oestrogen removal from tumour cells may be a new form of endocrine therapy of breast cancer in women. We investigated the inhibitory effect of the subchronic administration of oestrone-3-O-sulphamate (EMATE), a steroid sulphatase inhibitor, to ovariectomized rats, to evaluate this method for testing new nonsteroidal inhibitors. EMATE in DMSO was administered both orally and subcutaneously (s.c.) for 7 days at doses of 0.5 and 2.5 mg/kg. In addition the rats were injected s.c. with 0.5 mg oestrone sulphate/kg 26 and 2 h before decapitation under ether anaesthesia. Oestrone sulphatase activity (ESA) was measured radiometrically using [3H]oestrone sulphate as substrate for desulphuration in white blood cells, liver homogenate, microsomes and spleen homogenate. ESA in liver microsomes was found to be nearly 40 times higher than in white blood cells while in spleen ESA was nearly half of that found in liver homogenates and white blood cells. ESA can be inhibited by EMATE down to 50-1.5% of control activity depending on the dose and administration route. The inhibition was in the order, liver homogenate < spleen < liver microsomes < white blood cells, and was more pronounced after s.c. administration of the inhibitor than after oral administration. Ovariectomy was found to be not necessary for oestrone sulphatase-inhibiting studies. Two sequential s.c. injections of oestrone sulphate enhanced the enzyme activities significantly in liver and white blood cells, but not in spleen. In conclusion, white blood cells and liver microsomes of intact female rats can be used for ESA-inhibiting studies. Sulphate-conjugated oestrone can induce oestrone sulphatase in vivo in liver and white blood cells thereby enhancing oestrogen supply in the peripheral organs.     

Analysis of mdm2 and p53 Gene Alterations in Glioblastomas and its Correlation with Clinical Factors

Malignant gliomas are the most frequent primary brain tumors. Recent studies defined several genetic markers, which might characterize molecular-biological subsets of glioblastomas with probably prognostic implications. To elucidate the involvement of murine-double-minute (mdm)2 gene amplifications and mutations of the tumor suppressor gene p53 in the tumorigenesis of malignant gliomas we analyzed a series of 75 glioblastomas. The p53 mutations occur in one-third of glioblastomas, mdm2 amplifications were found in 13% of cases. Our analysis revealed a hot spot in the p53 gene locus in codon 156, the same point mutation was detected in 4 tumor samples. None of the mdm2 amplified tumors had p53 mutations, supporting the hypothesis, that mdm2 amplifications are alternative mechanisms for p53 inactivation. Patients with p53 mutated tumors were significantly younger characterized by a mean age of 44 years. Additionally association with longer overall survival could be detected for this subgroup of patients. In our study, survival estimation revealed a significant correlation of mdm2 gene amplification with shorter survival time, and support the hypothesis, that mdm2 oncogene activation appears to occur late in tumor progression and may be characteristic as negative prognostic marker.     

Is there an association between alcohol intake or smoking and small bowel adenocarcinoma? Results from a European multi-center case–control study

Objective:To discover whether tobacco smoking and intake of different types of alcoholic drinks are associated with small bowel adenocarcinoma (SBA). Methods:A population-based European multi-center case–control study was conducted from 1995 to 1997. Results:After a histological review using uniform diagnostic criteria, 47 (33%) of the 142 identified cases of SBA were excluded due to reclassification as either tumors of the papilla of Vater (n = 22), stromal tumors, or metastases; 95 cases were accepted for study. In all, 70 cases of SBA together with 2070 controls matched by age, sex, and region were interviewed. A high intake (more than 24 g alcohol per day) of beer or spirits was associated with SBA, an odds ratio (OR) of 3.5 and 95% confidence intervals (CI) of 1.5–8.0 and 3.4 (95% CI 1.3–9.2), respectively). There was no association with wine intake or total alcohol intake. Tobacco smoking was probably unrelated to SBA. Conclusions:A high intake of beer or spirits seems to be a risk factor for SBA. Since this association was not seen for wine drinkers, protective components of wine may counterbalance a carcinogenic effect of alcohol on the small bowel. Alternatively, the result may be confounded by other factors, e.g. dietary factors.     

Relationship of non-LDL-bound apo(a), urinary apo(a) fragments and plasma Lp(a) in patients with impaired renal function.

BACKGROUND: Plasma lipoprotein (a) [Lp(a)] has been shown to be a risk factor for atherosclerosis in numerous studies. However, the catabolism of this lipoprotein is not very clear. We and others have shown that Lp(a) is excreted into urine in the form of fragments. Lp(a) has also been shown to exist in a low-density non-lipoprotein (LDL)-bound form. Since Lp(a) is increased in all forms of kidney disease with reduced excretory kidney function and decreased excretion of apo(a) fragments could be partially responsible for this increase, we investigated the relationship of non-LDL-bound apo(a), urinary apo(a) fragments and plasma Lp(a) in patients with impaired renal function. METHODS: Plasma Lp(a), non-LDL-bound apo(a) and urinary apo(a) fragments were measured in 55 kidney disease patients (28 males and 27 females) and matched controls. RESULTS: Plasma Lp(a) and non-LDL-bound apo(a) were increased in patients, whereas urinary apo(a) was decreased, especially in patients with a creatinine clearance < 70 ml/min. There was a significant correlation between plasma Lp(a) and non-LDL-bound apo(a) in patients and controls. CONCLUSION: We conclude that decreased urinary apo(a) excretion could be one possible mechanism of increased plasma Lp(a) and non-LDL-bound apo(a) in patients with decreased kidney function.     

Validation of QGS and 4D-MSPECT for quantification of left ventricular volumes and ejection fraction from gated 18F-FDG PET: comparison with cardiac MRI.

The aim of this study was to validate Quantitative Gated SPECT (QGS) and 4D-MSPECT for assessing left ventricular end-diastolic and systolic volumes (EDV and ESV, respectively) and left ventricular ejection fraction (LVEF) from gated (18)F-FDG PET. METHODS: Forty-four patients with severe coronary artery disease were examined with gated (18)F-FDG PET (8 gates per cardiac cycle). EDV, ESV, and LVEF were calculated from gated (18)F-FDG PET using QGS and 4D-MSPECT. Within 2 d (median), cardiovascular cine MRI (cMRI) (20 gates per cardiac cycle) was done as a reference. RESULTS: QGS failed to accurately detect myocardial borders in 1 patient; 4D-MSPECT, in 2 patients. For the remaining 42 patients, correlation between the results of gated (18)F-FDG PET and cMRI was high for EDV (R = 0.94 for QGS and 0.94 for 4D-MSPECT), ESV (R = 0.95 for QGS and 0.95 for 4D-MSPECT), and LVEF (R = 0.94 for QGS and 0.90 for 4D-MSPECT). QGS significantly (P < 0.0001) underestimated LVEF, whereas no other parameter differed significantly between gated (18)F-FDG PET and cMRI for either algorithm. CONCLUSION: Despite small systematic differences that, among other aspects, limit interchangeability, agreement between gated (18)F-FDG PET and cMRI is good across a wide range of clinically relevant volumes and LVEF values assessed by QGS and 4D-MSPECT.     

Desflurane Preconditioning Induces Time-dependent Activation of Protein Kinase C Epsilon and Extracellular Signal-regulated Kinase 1 and 2 in the Rat Heart In Vivo

Background: Activation of protein kinase C epsilon (PKC-[epsilon]) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) are important for cardioprotection by preconditioning. The present study investigated the time dependency of PKC-[epsilon] and ERK1/2 activation during desflurane-induced preconditioning in the rat heart.

Methods: Anesthetized rats were subjected to regional myocardial ischemia and reperfusion, and infarct size was measured by triphenyltetrazoliumchloride staining (percentage of area at risk). In three groups, desflurane-induced preconditioning was induced by two 5-min periods of desflurane inhalation (1 minimal alveolar concentration), interspersed with two 10-min periods of washout. Three groups did not undergo desflurane-induced preconditioning. The rats received 0.9% saline, the PKC blocker calphostin C, or the ERK1/2 inhibitor PD98059 with or without desflurane preconditioning (each group, n = 7). Additional hearts were excised at four different time points with or without PKC or ERK1/2 blockade: without further treatment, after the first or the second period of desflurane-induced preconditioning, or at the end of the last washout phase (each time point, n = 4). Phosphorylated cytosolic PKC-[epsilon] and ERK1/2, and membrane translocation of PKC-[epsilon] were determined by Western blot analysis (average light intensity).

Results: Desflurane significantly reduced infarct size from 57.2 +/- 4.7% in controls to 35.2 +/- 16.7% (desflurane-induced preconditioning, mean +/- SD, P < 0.05). Both calphostin C and PD98059 abolished this effect (58.8 +/- 13.2% and 64.2 +/- 15.4% respectively, both P < 0.05 versus desflurane-induced preconditioning). Cytosolic phosphorylated PKC-[epsilon] reached its maximum after the second desflurane-induced preconditioning and returned to baseline after the last washout period. Both calphostin C and PD98059 inhibited PKC-[epsilon] activation. ERK1/2 phosphorylation reached its maximum after the first desflurane-induced preconditioning and returned to baseline after the last washout period. Calphostin C had no effect on ERK1/2 phosphorylation.     

Fortbildung Coloproctology Obstipation—Wie helfe ich dem Patienten?

Eine 73-jährige Patientin stellt sich wiederholt mit kolikartigen abdominellen Schmerzen in der Praxis vor. Die Lokalisation der Schmerzen sei sehr wechselnd. Zusätzlich berichtet die Patientin über eine erhebliche Blähungsneigung und zeitweise Umfangszunahme des Leibes. Die Beschwerden treten ausschließlich tagsüber auf, der Nachtschlaf werde durch diese Beschwerden nicht beeinflusst. Das Körpergewicht sei in den letzten Monaten konstant gewesen. Auf genaues Nachfragen gibt die Patientin weiterhin an, dass sie etwa zwei bis drei Stuhlentleerungen pro Woche habe. Der Stuhl sei überwiegend sehr hart, und die Darmentleerung bereite immer große Schwierigkeiten. Manchmal habe sie das Gefühl, dass der Darm nach dem Stuhlgang nicht vollständig entleert sei. Außer einem ACE-Hemmer zur Therapie eines seit langer Zeit bekannten arteriellen Hypertonus besteht keine Dauermedikation.In der zu Beginn geschilderten Kasuistik wird das klassische Bild einer chronischen Obstipation beschrieben. Abgegrenzt werden muss das Krankheitsbild von einer Defäkationsstörung, die bei einer Frau in diesem Alter als Folge eines inneren Rektumprolapses vorliegen könnte. Funktionsproktoskopie und Defäkographie sind wesentliche diagnostische Maßnahmen, die zu einer Klärung führen können. Bei der weiteren Vorgehensweise muss nun geklärt werden, ob Alarmsymptome bestehen, die eine weitere diagnostische Abklärung notwendig machen. Ist dies nicht der Fall, kann auf eine aufwendige Diagnostik verzichtet werden. Bevor therapeutische Maßnahmen eingeleitet werden, muss mittels einer detaillierten Anamnese nach möglichen Ursachen gesucht werden. Es ist insbesondere wichtig, Obstipationen als Nebenwirkung einer medikamentösen Therapie aufzudecken, da in diesen Fällen vor einer medikamentösen Therapie der Obstipation geklärt werden sollte, ob die obstipierenden Medikamente reduziert oder abgesetzt werden können. Im nächsten Schritt sollten ein Diabetes mellitus und eine Hypothyreose ausgeschlossen werden. Finden sich keine Hinweise für eine chronische Obstipation als Folge einer medikamentösen Therapie oder metabolischer Störungen, kann eine radiologische Bestimmung der Kolontransitzeit die Diagnose eines verlangsamten Kolontransits bestätigen. Zur Therapie der chronischen Obstipation stehen mehrere Medikamentengruppen zur Verfügung. Bevorzugt sollten gegenwärtig insbesondere bei älteren Menschen synthetische Osmotika eingesetzt werden. Unabhängig von Alarmsymptomen ist der Patientin jedoch eine Dickdarmkrebsprävention entsprechend den aktuellen Richtlinien zu empfehlen, falls diese bislang nicht konsequent durchgeführt worden ist.     

Pyrethroids used indoors--immune status of humans exposed to pyrethroids following a pest control operation--a one year follow-up study.

A multiparametric analysis of immune components was performed in blood and serum of 61 voluntary persons before and after (1 day, 3 days, 4-6 months, 10-12 months) a professional pest control operation (PCO) using pyrethroids. Following parameters were included in the study (1) immunological parameters of the humoral defence, i.e. immunoglobulins of the classes A, G, M and E, complement components C3c and C4, acute phase proteins such as acid alpha 1-glycoprotein, haptoglobin, C-reactive protein; (2) mediators and receptors of immunity, i.e. neopterin, soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor (sTNF RII); (3) immunological markers of the cellular defence, i.e. white blood cell counts and lymphocyte (sub)populations such as total lymphocytes (CD2), mature lymphocytes (CD3), T-helper/inducer cells (CD4), T-suppressor/cytotoxic cells (CD8), B-cells (CD20), natural killer cells (CD56), as well as the ratio of CD4/CD8. The medians of all investigated immune components found before and for all time intervals after pyrethroid application were within the reference interval with respect to the total collective. Within this physiological range the investigated parameters showed a trend to lower values predominantly during the early phase (1 and 3 days) after PCO, partially being significant. Significant decreases were no more present in the late phase (6 to 12 month) after PCO indicating reversibility. Atopics did not differ in the immune response after PCO as compared to non-atopics. Obtained results suggest a modulation of immune components after a correct performed PCO within the physiological range towards lower values during the first days. However these immune changes are considered to be subtle and underlying compensatory mechanisms of immunoregulation.