Die Wirkungen von Eserin, Cholin und Glucose auf die Synthese und die Freisetzung von Acetylcholin im Darm

Zusammenfassung Die Wirkungen von Eserin, Cholin und Glucose auf die Freisetzung und die Synthese von Acetylcholin (ACh) wurden im isolierten Dünndarm des Meerschweinchens durch Bestimmungen des ACh-Gehaltes des Gewebes und der ACh-Freisetzung in die Badelösung untersucht.In Lösungen, die Eserin, Cholin und Glucose enthielten, nahm der ACh-Gehalt des Gewebes zu, und es erfolgte eine Freisetzung von ACh in die Badelösung. Die Zunahme des ACh-Gehaltes des Gewebes, welche nur in Eserin-haltigen Lösungen auftrat, konnte auf intracelluläre Anhäufung von ACh zurückgeführt werden.ACh wurde auch in Cholin-freien Lösungen synthetisiert, doch war die ACh-Synthese geringer als in Gegenwart von Cholin. Aus der ACh-Synthese in Cholinfreier Lösung und dem Anteil des Nervengewebes am Darmvolumen wurde die Cholinkonzentration im Nervengewebe berechnet. Es zeigte sich, daß die intracelluläre Cholinkonzentration viel größer als die Cholinkonzentration im Plasma war. Die Cholinaufnahme in das Nervengewebe scheint deshalb in vivo durch aktiven Transport zu erfolgen.Bei Fehlen von Glucose trat keine Synthese von ACh auf, die Freisetzung von ACh hingegen war etwa doppelt so groß wie in Glucose-haltiger Lösung. Die Erhöhung der ACh-Freisetzung nach Glucose-Entzug könnte eine Anzahl der Symptome des hypoglykämischen Schockes erklären.

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Summary The effects of eserine, choline, and glucose on the liberation and the synthesis of acetylcholine (ACh) were studied in the guinea pig's small intestine by measuring the ACh content of the tissue and the amount of ACh liberated in the bath.Incubation in solutions containing eserine, choline, and glucose caused an increase in the ACh content of the tissue and the liberation of ACh. The increase in tissue content, which was only found when eserine was present, appears to result from intracellular accumulation of ACh.ACh was also synthezised in choline free solution, but the amounts were smaller than in the presence of choline. Estimation of the choline concentration in the nervous tissue, from the ACh synthesis in choline free solution and the amount of nervous tissue in the intestine, shows that the choline concentration in nerve is much higher than in plasma. It is suggested that uptake of choline in vivo necessitates an active transport process.No synthesis of ACh was found in the absence of glucose; the liberation of ACh was increased and occured entirely on account of the initial ACh content. The increase in ACh liberation after glucose withdrawal might explain some symptoms of hypoglycemic shock.

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Mit 4 Textabbildungen

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

The influence of obesity on the frequency and distribution of medication

Obesity is a serious health problem in industrialized countries and is associated with a significant increase in total health care costs. Only few data are available about the costs of drug therapies in patients with an increased body weight treated under clinical routine procedures. Such data could support efforts to intensify obesity prevention and treatment programmes in order to reduce comorbidities and costs. We have evaluated body mass index (BMI), diagnosis, and medication in 3360 outpatients (2175 women and 1185 men; mean age: 56.7 +/- 17.5 years). All patients underwent physical examinations, including BMI determination, and provided a detailed record concerning medication. In 1809 patients, the percentage of body fat content was measured with a bioimpedance method (OMRON BF 302 body fat monitor). Continuous variables were compared using the t-test or Wilcoxon U-test. Frequency distributions were compared using chi-squared tests. With respect to BMI, most of the patients (n = 1793; 53 %) were overweight or obese, 1349 (40 %) showed a normal BMI and 218 (7 %) a low BMI. The majority of cardiovascular (61 %), rheumatological (61.1 %) and metabolic (60.4 %) medication was administered to overweight and obese patients. Parallel findings could be obtained by analysing the percentage of body fat and the frequency of medication. Overall, 82.5 % of all medication was given to patients with a body fat content >20 %. Our results support the importance of weight-reduction programmes in order to prevent an overall increase in the costs of medication as a consequence of overweight and obesity.     

Phantoms for texture analysis of MR images. Long-term and multi-center study

The application of texture analysis (TA) in magnetic resonance imaging (MRI) requires the availability of texture phantoms for use in the standardization of in vivo measurements. The aims of our study were (a) to develop a new type of phantoms suitable for MRI and TA and test their long-term stability; (b) to optimize the choice of texture parameters describing the phantoms; (c) to compare different MR imagers according to texture parameters in a multi-center study. A long-term study performed at 4.7 T proved that the developed phantom based on polystyrene spheres and an agar gel solution is stable at least 12 months. This phantom, with nodular patterns, was found useful for the modeling of structural differences. The comparison of TA parameters at 4.7 and 7 T proved that the same parameters can be used for the separation of structures. The proposed algorithm of the selection of TA parameters shows that there exists a part of texture parameters which can be measured with high reproducibility (1-3%); on the other hand, their absolute values can differ by more than 30% if the textures differ. Results obtained from the multi-center study of whole body MR imagers show the wide variation in the misclassification rates at the different sites and point out the importance of the set up of MR sequences.     

A new method to bind allergens for the measurement of specific IgE antibodies

BACKGROUND: Detection of allergen-specific IgE antibodies in patients' sera plays a key role for the diagnosis of IgE-mediated allergy. If no validated test system is available, diagnostic tools must be developed, usually by coupling or binding the allergens to a solid phase. Streptavidin ImmunoCAP is a new solid phase for binding of allergens which can be used in the Pharmacia CAP system. OBJECTIVE: It was the aim of this study to assess the diagnostic validity of Streptavidin ImmunoCAP. METHODS: Biotinylation and allergen concentration for binding to Streptavidin ImmunoCAP were optimized and IgE obtained with natural rubber latex, obeche wood, wheat and rye flour Streptavidin ImmunoCAP were compared with the results of ImmunoCAP and Enzyme Allergo-Sorbent Test (EAST) using sera from patients complaining of workplace-related respiratory symptoms. RESULTS: While the relation of biotin-label and protein was critical (best results were obtained with a 5- fold molar excess), labelled protein for coupling to streptavidin ImmunoCAP was applicable in a wide concentration range. On average, IgE values with streptavidin ImmunoCAP were as high as with ImmunoCAP but considerably higher than values obtained by EAST. CONCLUSION: Streptavidin ImmunoCAP is a valuable tool for sensitive and specific measurement of IgE binding to new allergens superior to cellulose disk-based methods.     

Glomerular Hypertrophy in Offspring of Subtotally Nephrectomized Ewes

We have shown that fetuses whose mothers underwent subtotal nephrectomy (STNx) before pregnancy had high urine flow rates and sodium excretions, but lower hematocrits, plasma chloride, and plasma renin levels compared with controls. To see if these functional differences in utero persist after birth and are the result of altered renal development, we studied 8 lambs born to STNx mothers (STNxL) and 10 controls (ConL) in the second week of life. These lambs were of similar body weights, nose–rump lengths and abdominal girths. Their kidney weights were not different (ConL 36.1 ± 1.9 vs. STNxL 39.8 ± 3.3 g), nor were kidney dimensions or glomerular number (ConL 423,520 ± 22,194 vs. STNxL 429,530 ± 27,471 glomeruli). However, STNxL had 30% larger glomerular volumes (both mean and total, P < 0.01) and there was a positive relationship between total glomerular volume and urinary protein excretion (P < 0.05) in STNxL. Despite this change in glomerular morphology, glomerular filtration rate, tubular function, urine flow, and sodium excretion rates were not different between STNxL and ConL, nor were plasma electrolytes, osmolality, and plasma renin levels. Thus while many of the functional differences seen in late gestation were not present at 1–2 weeks after birth, the alteration in glomerular size and its relationship to protein excretion suggests that exposure to this altered intrauterine environment may predispose offspring of mothers with renal dysfunction to renal disease in adult life. Anat Rec, 291:318–324, 2008. © 2008 Wiley‐Liss, Inc.     

Regulation of human natural killer (NK) cell function: Induction of killing of an NK-resistant renal carcinoma cell line

Natural killer (NK)-like activity against a renal carcinoma cell line, Cur, was assessed. There was no spontaneous killing of Cur cells by human peripheral blood mononuclear cells in 4-hr assays. Cur killing was observed in 18-hr assays, but the magnitude of killing was variable and always markedly less than that against K562. Cur killing was mediated by a nonadherent, nonphagocytic lymphocyte, the activity of which could be modulated both positively and negatively by monocytes or their products. Preincubation of effectors with monocyte supernatant, interleukin 1 (IL-1), -interferon (IFN), or interleukin 2 (IL-2) greatly increased the magnitude of Cur killing and accelerated the kinetics of lysis. The addition of prostaglandin E₂ (PGE₂) duringin vitro activation of NK by IL-2 profoundly inhibited subsequent Cur lysis, whereas only minimal inhibition of K562 lysis was noted. However, following activation with IL-2, lysis of Cur targets was less sensitive to the inhibitory effects of PGE₂. Removal of Leu 11b(+), OKM1(+), orl-leucylleucine methyl ester-sensitive cells markedly decreased both Cur and K562 lysis. Moreover, CD16(+) cells purified with the fluorescence-activated cell sorter were found to mediate Cur killing. Whereas Cur and K562 lysis is mediated by phenotypically similar effector cells, the present studies demonstrate that the cytotoxic functions defined by the ability to lyse these two targets differ in response to a variety of immunoregulatory stimuli.     

Visualisation of the extent of damage in a rat spinal cord injury model using MR microsopy of the water diffusion tensor

Magnetic Resonance Diffusion Tensor Imaging (DTI) of the control and traumatic injured spinal cord of a rat in vitro is reported. Experiments were performed on excised spinal cords from 10 Wistar rats, using a home-built 6.4 T MR microscope. MRI and histopathological results were compared. Presented results show that DTI of the spinal cord, perfused with formalin 10 minutes after the injury, can detect changes in water diffusion in white matter (WM) and in gray matter (GM), in areas extending well beyond the region of direct impact. Histology of neurons of the GM shows changes that can be attributed to ischemia. This is in agreement with the observed decrease of diffusion in the injured regions, which may be attributed to the cytotoxic edema due to ischemia. However, the diffusion changes in highly anisotropic WM seem to be caused by a direct action of mechanical force of impact, which significantly distorts the nerve fibers.     

Hippocampal metabolic abnormalities in mild cognitive impairment and Alzheimer's disease

Mild cognitive impairment (MCI) defines a group of otherwise healthy elderly subjects with a markedly elevated risk of developing Alzheimer's disease (AD). In the search for biomarkers of MCI, we assessed whether MCI shares neurochemical abnormalities with AD in areas affected early in the course of the disease. As a secondary study aim, we tested to what extent neurochemical findings reflect neuropsychological deficits. Proton spectroscopy was performed in 19 MCI patients, 18 AD patients and 22 age and gender matched controls (CON) within the parietal gray and white matter (PWM and PGM) and the hippocampus (HIP). The cognitive test battery used included measures compiled by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The N-acetyl-aspartate to creatine ratio (NAA/Cr) was significantly reduced in the HIP of MCI and AD compared with CON (p < 0.05). Only AD patients showed parietal abnormalities, namely significantly elevated myoinositol (mI/Cr and mI/NAA) in PGM, reduced NAA/Cr and elevated mI/NAA in PWM. MCI subjects were significantly impaired in categorical verbal fluency (VF) (p < 0.001) and delayed verbal recall (DVR) (p < 0.001). VF was positively correlated with hippocampal NAA/Cr (p < 0.05) and parietal mI/NAA (p < 0.05). In summary, this study demonstrates shared neurobiological hippocampal abnormalities in MCI and AD, whereas parietal lobe neurochemical profiles and functions were normal in MCI. Thus, biological evidence is provided that MCI represents a precursor stage of AD. Moreover, multivoxel 1H MRS may enable an objective staging of the neurodegenerative process underlying the age-dependent cognitive deficits eventually leading to dementia.     

How to perform high ultrasound examination of skin involvement among patients with systemic sclerosis – proposition of a unified protocol

IntroductionA fast and cheap method of skin assessment in systemic sclerosis (SSc) is an area of extensive research. Established in 1979, the Rodnan skin score is a palpation-based method used among clinicians. This method has some limitations, such as: examiner’s skills, subjective results, and no standardization. In the last few years researchers have been exploring ultrasound-based techniques as a possible tool for skin assessment among patients with SSc. The aim of the study is to develop a protocol of elastography-based skin imaging evaluation among patients with SSc.Material and methodsReview of the literature and own experience.ResultsProposition of elastography-based skin imaging protocol among patients with SSc.ConclusionsThe authors present a potential protocol of ultrasound-based examination of skin involvement among patients with SSc.     

Protroca: A Noninterventional Study on Prophylactic Lipegfilgrastim against Chemotherapy-Induced Neutropenia in Nonselected Breast Cancer Patients

BackgroundProtroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT).Patients and MethodsOf the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed.ResultsNine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in <15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim.ConclusionsApplication of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer.