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Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 109 records · Page 6Linked to original sources

Effects of zinc histidine and zinc sulfate on natural human keratinocytes.

BACKGROUND: Zinc salts are widely used as food supplements and medicinal mineral supplementation. Zinc deficiency is associated with impaired skin conditions. The influence of zinc on skin functionality has been proven in clinical investigations. OBJECTIVE: Within the following study comparative in vitro experiments were performed to study the influence of zinc sulfate (ZnSO(4)) and zinc histidine (Zn(His)(2)) on the physiology of cultured natural human keratinocytes. METHOD: Proliferation of natural human keratinocytes was quantitatively assessed by measurement of 5-bromo-2-deoxyuridine (BrdU) incorporation against an oligomeric procyanidin as positive control. Differentiation was determined by monitoring involucrin formation. Cell viability and cytotoxicity were assessed by dimethylthiazolyldiphenyltetrazolium bromide (MTT) testing and quantification of lactate dehydrogenase. RESULTS: Neither keratin synthesis as a late marker of cell differentiation nor mitochondrial cell activity were influenced by either zinc compound. The synthesis of involucrin, an early marker of differentiation, was significantly increased by both zinc salts, ZnSO(4) being the more potent stimulator. Both zinc salts significantly increased cell proliferation, with the histidine complex being more potent. Effects were in the range of the positive control. Necrotic cell toxicity decreased significantly when Zn(His)(2) was added to the cells. CONCLUSION: Under in vitro conditions Zn(His)(2) is a strong proliferation inductor of keratinocytes with a better tolerability and a lower induction of differentiation behavior than ZnSO(4).

Cell Differentiation↗

No peri- and postnatal effects on calves born after transfer of in vitro produced embryos vitrified by the open pulled straw (OPS) method.

The general objective of this study was to perform follow-up studies including selected peri- and postnatal characteristics on calves born after transfer of in vitro produced (IVP) embryos vitrified by the 'Open Pulled Straw' (OPS) method. An overall pregnancy rate of 16% after transfer of the OPS-vitrified IVP embryos was achieved and resulted in birth of 9 calves, with 11 AI calves serving as controls. There were no immediate or long-term effects on these calves with respect to birth weight, gestation length, perinatal mortality, growth rate, disease susceptibility and reproductive performance.

Animals↗

Moving-table MR angiography of the peripheral runoff vessels: comparison of body coil and dedicated phased array coil systems.

OBJECTIVE: The aim of our study was to compare the signal-to-noise ratio and the diagnostic accuracy of moving-table MR angiography of the peripheral arteries with body coil and dedicated phased array coil systems. SUBJECTS AND METHODS: Forty patients were examined with digital subtraction angiography and moving-table MR angiography with a 1.5-T MR imaging system either with a body coil (n = 20) or with a dedicated phased array coil (n = 20). The timing of contrast material was performed with real-time MR fluoroscopy. RESULTS: For the iliac artery, upper leg, and lower leg, the mean values for signal-to-noise ratios were 56, 51, and 17, respectively, for the body coil, and 54, 74, and 64, respectively, for the dedicated phased array coil. For the body coil, sensitivity and specificity in identifying stenosis greater than 50% and occlusions were 100% and 96%, respectively, for the iliac arteries, and 100% and 96%, respectively, for the upper leg. For the dedicated phased array coil, sensitivity and specificity for stenosis greater than 50% and occlusions were 100% and 96%, respectively, for the iliac arteries, and 100% and 98%, respectively, for the upper leg. Sensitivity and specificity were inferior for the body coil (88% and 85%) compared with the dedicated phased array coil (100% and 96%) in the lower leg. A significant difference of the mean values of contrast-to-noise ratio was found before and after subtraction for the dedicated phased array coil and body-coil techniques (Student's t test, p < 0.01). CONCLUSION: In comparison with the body coil, the dedicated peripheral phased array surface coil system improves signal-to-noise ratio for the upper and lower leg and diagnostic accuracy in the lower leg.

Adult↗

[Prevention, screening and therapy of thyroid diseases and their cost-effectiveness].

Cost-effectiveness analyses focused on benign thyroid diseases are under-represented in the literature. The calculation of costs per additionally gained life year is difficult: The benefit of prevention is shifted into the distant future. The influence of an untreated subclinical thyroid disease on life expectancy can only be demonstrated by a long-term follow-up and by epidemiological databases. Iodine supplementation and programs for the prevention of tobacco smoking (primary prevention) are very cost-effective. Smoking increases the risk both of multinodular goiter and of Graves' disease. Screening programs (secondary prevention) are discussed for the laboratory parameters thyrotropin (TSH), calcium and calcitonin. TSH testing seems to be very cost-effective for epidemiological considerations in a certain lifespan (newborn, pregnancy, postpartal, older persons, hospitalisation due to acute diseases) and in persons with previously elevated TPO-antibodies or TSH-values >2 mU/l, but dedicated cost-effectiveness analyses are lacking. On the other hand, the cost-effectiveness of a routine TSH testing beyond the age of 35 years has been shown by a high-quality decision analysis. Therapeutic strategies (tertiary prevention) aim at the avoidance of complications (atrial fibrillation, myocardial infarction, death for cardiac reasons) and of iatrogenic complications. Examples of a tertiary prevention are: firstly the definitive therapy of Graves' disease in patients who have an increased risk of relapse after antithyroid drugs (ATD), secondly the radioiodine therapy for subclinical hyperthyroidism and the radioiodine therapy of large goiters in older patients or in patients suffering from a relevant comorbidity. Cost-effectiveness analyses for different therapeutic strategies of Graves' disease were published using a lifelong time-horizon. The ablative radioiodine dose-regime is cost-effective as a first line therapy if the risk of relapse after ATD exceeds 60%.

Cost-Benefit Analysis↗

A novel form of constitutively active farnesylated Akt1 prevents mammary epithelial cells from anoikis and suppresses chemotherapy-induced apoptosis.

Protein kinase B/Akt has been described as a central mediator of anti-apoptotic signals transduced by the PI3 kinase. Although the role of Akt in the suppression of apoptosis is well elucidated, a potential function of Akt in tumorigenesis and chemoresistance is less intensively documented. In this study, we describe the construction of a novel form of constitutively active Akt1, which relies on the deletion of its pleckstrin homology domain and the insertion of a C-terminal farnesylation sequence. Stable cell lines were generated with MCF10A mammary epithelial cells and A549 human NSCLC cells expressing constitutively active Akt1. Enigneered MCF10A cells were rendered resistant towards apoptosis resulting from loss of cellular substrate attachment (anoikis). We investigated the chemosensitivity of A549 cells expressing farnesylated Akt vs control cells. A profoundly decreased sensitivity towards Mitoxantrone and cisplatin was observed in cells expressing farnesylated Akt. No significant difference in sensitivity however was observed upon treatment with cell cycle specific chemotherapeutic agents like paclitaxel. Our data suggest, that Akt is a central mediator in the suppression of anoikis and modulation of chemotherapy-induced apoptosis. Therefore it represents a promising target for small molecule inhibitors to shift the apoptotic threshold in cancer cells after treatment with standard chemotherapy.

Anoikis↗

Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters.

In the present study, we addressed the question of a putative relevance of Rho proteins in tumour progression by analysing their expression on protein and mRNA level in breast tumours. We show that the level of RhoA, RhoB, Rac1 and Cdc42 protein is largely enhanced in all tumour samples analysed (n=15) as compared to normal tissues originating from the same individual. The same is true for (32)P-ADP-ribosylation of Rho proteins which is catalysed by Clostridium botulinum exoenzyme C3. Also the amount of Rho-GDI and ERK2 as well as the level of overall (32)P-GTP binding activity was tumour-specific elevated, yet to a lower extent than Rho proteins. Although the amount of Rho proteins was enhanced in tumours, most of them did not show changes in rho mRNA expression as compared to the corresponding normal tissue. Thus, elevated gene expression seems not to be the underlying mechanism of tumour-specific overexpression of Rho proteins. Sequence analysis of RhoA, RhoB, RhoC and Rac1 failed to detect any mutations in both the GTP-binding site and effector binding region. By analysing >50 tumour samples, the amount of RhoA-like proteins (i.e. RhoA, B, C), but not of Rac1, was found to significantly increase with histological grade and proliferation index. Rho protein expression was neither related to p53 nor to HER-2/neu oncogene status. Expression of rho mRNAs did not show a significant increase with histological grade. Overall the data show that (1) Rho proteins are overexpressed in breast tumours (2) overexpression is not regulated on the mRNA level (3) the expression level of RhoA-like proteins correlates with malignancy and (4) Rho proteins are not altered by mutation in breast tumours.

ADP Ribose Transferases↗

[Acute aortic syndrome. A thoracic emergency--unfortunately with a large selection of symptoms].

Acute aortic arch syndrome is a medical emergency associated with a high mortality rate. In view of the great variation in symptomatology, this condition can readily be overlooked. A carefully obtained history (pain!), a thorough physical examination (differences in pulse and blood pressure) may be suspicious for acute aortic arch syndrome, which today can be reliably and rapidly diagnosed by noninvasive imaging (CT, TEE). Confirmation of the suspected diagnosis must be followed by further intensive medical surveillance (Stanford B) or, in the event of involvement of the ascending aorta or aortic arch (Stanford A), referral without delay to a cardiosurgical center. Apart from a further shortening of the time lapse between diagnosis establishment and emergency surgery, new therapeutic (e.g. stenting) and surgical procedures may improve the prognosis of the syndrome. Maybe new diagnostic tools (monoclonal antibodies against aortic myosin and radio-immunoscintigraphy) will help to recognize the aortic syndrome more rapidly.

Acute Disease↗

Deuterium-deuterium fusion dynamics in low-density molecular-cluster jets irradiated by intense ultrafast laser pulses.

Following the interaction of superintense, short pulse lasers and plasmas, ions can be accelerated to velocities sufficient to drive nuclear fusion reactions, in particular, by the process of Coulomb explosion of clusters [T. Ditmire, Nature (London) 398, 491 (1999)]]. We show here how short bursts of neutrons can be produced using a jet of low-density deuterated methane clusters. Ion velocity distributions were simultaneously measured by a Thomson parabola mass spectrometer, demonstrating deuteron energies up to 120 keV. We show that, in such conditions, nuclear fusion will occur not only in the hot plasma core, but also in the cold outer region by collision processes.

Journal Article↗

How practical are recommendations for dietary control in phenylketonuria?

In patients with phenylketonuria, blood phenylalanine concentration during childhood is the major determinant of cognitive outcome. Guidelines provide age-related recommendations for treatment. To ascertain the extent to which these aims are achievable, we audited results from four centres for the years 1994-2000. The median proportion of samples with phenylalanine concentrations above those recommended was less than 30% for those younger than age 10 years but almost 80% for those aged 15 years and older. Similarly, the median frequency of blood sampling, expressed as a proportion of that recommended, was more than 80% for patients younger than 10 years but less than 50% by age 15 years. Our results indicate the difficulty of maintaining control in phenylketonuria, especially in older rather than younger children.

Adolescent↗

[Atherosclerotic renal artery stenosis].

Only patients with the typical symptoms of a stenosis of the renal artery should be submitted to a screening examination. In elderly patients with suspected atherosclerotic stenosis of the renal artery, color-coded duplex ultrasonography is the diagnostic method of choice. If visualization proves to be poor, and in particular when accessory renal arteries are present, magnetic resonance angiography may be considered. If there is significant stenosis of the renal artery, and if a positive effect on renal function or blood pressure control is to be expected, percutaneous transluminal angioplasty with implantation of a stent is the treatment of first choice. In the case of patients with additional aortic pathology, operative revascularization must be considered.

Aged↗

Decoration lattices of colloids adsorbed on stripe-patterned substrates.

The equilibrium structure of decoration lattices composed of colloidal particles adsorbed on periodic stripe-patterned substrates is calculated as a function of the stripe width and separation and for different interparticle interactions. Due to a competition of length scales, a wealth of different stable decoration lattices occurs such as triangular, quadratic, rhombic, kitelike, and sheared honeycomb lattices, triangular slices as well as triangle superlattices. This is of relevance for constructing templates that enforce crystal growth of unusual solid structures.

Journal Article↗

Macromolecule absorption and cortisol secretion in newborn calves derived from in vitro produced embryos.

Earlier reports indicate that calves derived from in vitro produced (IVP) embryos are more susceptible to neonatal disease than calves produced after artificial insemination (AI) or natural mating. The aims of the present study were to investigate whether calves born after IVP embryos show an altered macromolecule absorption (immunoglobulin G (IgG) and porcine serum albumin (PSA)) compared with AI calves and whether the macromolecule absorption could be related to the degree of acidosis or to the cortisol secretion around birth. Hence, IgG and PSA absorption in control AI calves (n=7) was compared with that in two groups of IVP calves (IVP-defined: SOFaa embryo culture with polyvinyl alcohol, n=6; IVP-serum: SOFaa embryo culture with serum and co-culture, n=8). The calves were fed colostrum (40ml/kg) at 2, 6 and 12h after birth. At 24h after birth, both AI and IVP calves had achieved a level of plasma IgG sufficient to provide passive immunization (>15mg/ml). When the values were adjusted for the varying colostral IgG contents and the degree of acidosis, the IVP-defined calves had significantly lower peak plasma IgG concentrations than the AI calves at 18-24h after birth (P<0.04). However, when the macromolecule marker (PSA), was fed to all calves at 2 and 12h after birth the resulting plasma PSA levels were significantly lower in the AI calves compared with the IVP calves during the whole observation period (P<0.0001). Calves with a moderate neonatal acidosis (mean pH<7.2 during the first 30min after birth) had reduced peak plasma IgG concentration at 18-24h after birth (P<0.02) compared to calves without acidosis. The basal and ACTH-stimulated cortisol levels were lower in the newborn IVP-defined calves than in the AI calves (P<0.05) and the IVP-serum calves (P<0.002). Cortisol levels shortly after birth correlated positively with birth weight (r=0.60, P<0.0001) and with gestation length (r=0.34, P<0.04). Since, the IVP calves absorbed sufficient amounts of IgG from colostrum to acquire sufficient passive immunity, we conclude that the lower viability described in IVP offspring probably is not caused by an impaired passive immunization. IVP-defined calves had significantly lower absorption efficiency of IgG compared with AI calves, whereas absorption of a non-Ig macromolecule (PSA) was higher for IVP than AI calves. This might indicate a more selective absorption in AI calves in favor of IgG. Acidosis around birth affected immunoglobulin absorption negatively. IVP-defined calves had significantly lower cortisol levels the first 3h after birth and during an ACTH-challenge and a lower IgG absorption efficiency, which might indicate a mild degree of organ dysmaturity in these calves.

Absorption↗

New modified single chained glycolipids. Part 1: synthesis of deoxy and partially O-methylated glycolipids with or without a sulfur containing spacer.

A way to synthesize neoglycolipids with high yields and anomeric purity is described. Starting point of the synthesis strategy is the glycosylation of allyl alcohol with definite steric orientation. Introduction of the hydrophobic moiety was achieved by photoaddition of n-hexadecanethiol and 3-mercaptopropionic acid followed by amidation with n-hexadecylamine, respectively. In order to investigate the influence of different carbohydrate headgroups in the physicochemical behavior of the general glycolipid, especially the orientation of the alkyl chain, a range of neoglycolipids was synthesized. Beside the differences in the configuration between unfunctionalized glycopyranoses like D-glucose, D-galactose and D-mannose, a number of deoxy and partially O-methylated sugar derivatives was prepared. The divergences concerning the different carbohydrate headgroups and the hydrophobic moiety, respectively, can be compared to relatively simple structured glycolipids with hexadecyl residue and without spacer function.

Glycolipids↗

Hepatic function during xenon anesthesia in pigs.

BACKGROUND: Inhalation anesthetics decrease liver perfusion and oxygen consumption by changing the distribution pattern of perfusion between the hepatic artery and the portal vein and by direct effects on liver cells. The effects of xenon on liver perfusion and function have been not investigated until now. METHODS: Fourteen pigs were randomly assigned to two groups to receive either 73-78% xenon or 75% nitrogen in oxygen with additional supplementation of pentobarbital and buprenorphine. Microspheres were used to determine the arterial perfusion of the liver and splanchnic organs. Oxygen contents were measured by catheterization of the portal and a liver vein. Lactate and glucose plasma concentrations were measured in hepatic, mixed venous and arterial blood. Alanine aminotransferase (ALT) and lactate dehydrogenase (LOH) plasma concentrations were measured in arterial blood. Urea production rates were calculated to assess hepatic metabolic function. RESULTS: Significant higher oxygen contents were found in the liver venous blood during xenon anesthesia. No differences were found in any other investigated parameters. CONCLUSION: Higher oxygen content in liver venous blood observed during xenon anesthesia was not induced by changes in hepatic perfusion distribution or by an impairment of liver metabolic capacity. However, it can be explained by similar results known from inhalation anesthesia. Additionally, the effect can be caused by the reduction of plasma catecholamine concentrations during xenon anesthesia.

Adjuvants, Anesthesia↗

Effect of xenon on cerebral autoregulation in pigs.

There are little data on the effect of anaesthetic concentrations of xenon on cerebral pressure autoregulation. In this study, we have investigated the effect of 79% xenon inhalation on cerebral pressure autoregulation and CO2 response in pigs. Ten pigs were randomly allocated to receive xenon 79% or halothane anaesthesia, respectively, in a crossover designed study. Halothane was used to validate the experimental set-up. Transcranial Doppler was performed to determine the mean flow velocities in the middle cerebral artery (vMCA) during defined cerebral perfusion pressures and during normo-, hyper- and hypoventilation. The results showed that the inhalation of 79% xenon preserved cerebral autoregulation during conditions of normo-, hyper- and hypoventilation and at different cerebral perfusion pressures in pigs. These results suggest that with the inhalation of xenon, in the highest concentration suitable for a safe clinical use, cerebral autoregulation is preserved.

Anesthetics, Inhalation↗

Maternal regulation of the hypothalamic-pituitary-adrenal axis in the 20-day-old rat: consequences of laboratory weaning.

There is a large body of evidence that the development of the hypothalamic-pituitary-adrenal (HPA) system in the rat is under maternal regulation. One method used to study the influence of the dam-pup interaction in neonates and weanlings is the separation of mother and litter for 24 h. Previous studies showed that, even at the time of weaning, maternal deprivation results in a dysregulation of the HPA axis at multiple levels. However, the maternal deprivation paradigm usually includes deprivation of food and water, and it was not clear to which extent the observed effects are due to either maternal cues or dehydration and fasting. The primary purpose of the present study was to determine the role of fasting and/or maternal separation on the HPA axis at the time of weaning. Pups at 20 days after parturition are capable of self-feeding and no longer require tactile stimulation to induce eliminative functions. The results indicated that 24 h of fasting led to increased basal levels and further increases in stress induced corticosterone secretion. Fasting also appeared to contribute to the down regulation of basal glucocorticoid receptor mRNA in the hippocampus. In contrast, abrupt weaning irrespective of fasting or dehydration resulted in a suppressed adrenocorticotropin hormone response to an injection of isotonic saline. Although there was an effect of maternal separation on corticotropin-releasing factor mRNA in the paraventricular nucleus, this effect was further exacerbated by the absence of food. Finally, all rats that were separated from their dams showed more efficient negative-feedback. Thus, different aspects of the HPA system appear to respond differentially to either the absence of food or the absence of the mother or both.

Adrenocorticotropic Hormone↗