International medical students--a survey of perceived challenges and established support services at medical faculties.

INTRODUCTION: Medical students with a non-German background face several challenges during their studies. Besides support given by foreign student offices further specific projects for international students have been developed and are offered by medical faculties. However, so far, neither a systematic survey of the faculties' perceived problems nor of the offered support exists. METHOD: All study deaneries of medical faculties in Germany were contacted between April and October 2013 and asked for their participation in a telephone interview. Interview partners were asked about 1.) The percentage of non-German students at the medical faculty; 2.) The perceived difficulties and problems of foreign students; 3.) The offers for non-German students; and 4.) The specification of further possibilities of support. Given information was noted, frequencies counted and results interpreted via frequency analysis. RESULTS: Only 39% of the medical faculties could give detailed information about the percentage of non-German students. They reported an average share of 3.9% of students with an EU migration background and 4.9% with a non-EU background. Most frequently cited offers are student conducted tutorials, language courses and tandem-programs. The most frequently reported problem by far is the perceived lack of language skills of foreign students at the beginning of their studies. Suggested solutions are mainly the development of tutorials and the improvement of German medical terminology. DISCUSSION: Offers of support provided by medical faculties for foreign students vary greatly in type and extent. Support offered is seen to be insufficient in coping with the needs of the international students in many cases. Hence, a better coverage of international students as well as further research efforts to the specific needs and the effectiveness of applied interventions seem to be essential.

Examination performances of German and international medical students in the preclinical studying-term--a descriptive study.

INTRODUCTION: Medical students with a migration background face several specific problems during their studies. International surveys show first indications that this group of students performs worse in written, oral or practical exams. However, so far, nothing is known about the performance of international students in written pre-clinical tests as well as in pre-clinical State Examinations for German-speaking countries. METHOD: A descriptive, retrospective analysis of the exam performances of medical students in the pre-clinical part of their studies was conducted at the Faculty of Medicine of Heidelberg in for the year 2012. Performance in written tests of the final exams in the second (N=276), third (N=292) and fourth semester (N=285) were compared between German students, students from EU countries and students from non-EU countries. Same comparison was drawn for the performance in the oral exam of the First State Examination in the period from 2009 - 2012 (N=1137). RESULTS: German students performed significantly better than students with a non-EU migration background both in all written exams and in the oral State Examination (all p<.05). The performance of students with an EU migration background was significantly better than that of students with a non-EU background in the written exam at the end of the third and fourth semester (p<.05). Furthermore, German students completed the oral exam of the First State Examination significantly earlier than students with a non-EU migration background (<.01). DISCUSSION: Due to its poorer performance in written and oral examinations and its simultaneously longer duration of study, the group of non-German medical students with a country of origin outside of the European Union has to be seen as a high-risk group among students with a migration background. For this group, there is an urgent need for early support to prepare for written and oral examinations.

Correlation between local glucose transporter densities and local 3-O-methylglucose transport in rat brain.

The present study addresses the question whether local glucose transport kinetics are correlated with local glucose transporter densities in the brain. In 47 brain structures the local rate constants for 3-O-[(14)C]methylglucose (3-O-MG) transport, K(1) and k(2,) were quantified, and local glucose Glut1 and Glut3 transporter densities were determined by immuno-autoradiographic methods. Statistically significant correlations were found between the rate constants for glucose transport and the transporter densities. The correlations were tighter for Glut1 than for Glut3. Inasmuch as 3-O-MG is transported by the same transporter as glucose, these results indicate that the local densities of glucose transporters determine local glucose transport rates in the brain.

Brain glucose transporters: relationship to local energy demand.

Glucose, the major fuel in the brain, is transported across the cell membranes by facilitated diffusion mediated by glucose transporter proteins. Essentially two types of glucose transporters are localized in the membranes of brain endothelial cells, astrocytes, and neurons. Their densities are well adjusted to changes in local energy demand.

Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain.

Monocarboxylate transporter (MCT1) levels in brains of adult Long-Evans rats on a high-fat (ketogenic) diet were investigated using light and electron microscopic immunocytochemical methods. Rats given the ketogenic diet (91% fat and 9% protein) for up to 6 weeks had increased levels of the monocarboxylate transporter MCT1 (and of the glucose transporter GLUT1) in brain endothelial cells and neuropil compared to rats on a standard diet. In ketonemic rats, electron microscopic immunogold methods revealed an 8-fold greater MCT1 labeling in the brain endothelial cells at 4 weeks. Abluminal endothelial membranes were twice as heavily labeled as luminal membranes. In controls, luminal and abluminal labeling was not significantly different. The endothelial cytoplasmic compartment was sparsely labeled (<8% of total endothelial labeling) in all brains. Neuropil MCT1 staining was more intense throughout the brain in ketonemic rats, especially in neuropil of the molecular layer of the cerebellum, as revealed by avidin-biotin immunocytochemistry. This study demonstrates that adult rats retain the capacity to upregulate brain MCT1 levels. Furthermore, their brains react to a diet that increases monocarboxylate levels in the blood by enhancing their capability to take up both monocarboxylates (MCT1 upregulation) and glucose (GLUT1 upregulation). This may have important implications for delivery of fuel to the brain under stressful and pathological conditions, such as epilepsy and GLUT1 deficiency syndrome.

Expression of large amino acid transporter LAT1 in rat brain endothelium.

The expression of the large amino acid transporter, LAT1, was investigated in brain of adult Long-Evans rats. The LAT1 transcript was readily detected in brain microvessels and choroid plexus by reverse transcription polymerase chain reaction analysis using three different gene specific primer pairs. A polyclonal affinity purified antibody against the N-terminus of LAT1 was generated in chickens and used in immunoblot and immunocytochemical analyses of brain tissue sections of adult rats. On immunoblots, the antibody detected a peptide-inhibitable 45 kDa band in a rat brain microvessel membrane preparation. It also identified the same protein band in membrane preparations of different brain structures, as well as in heart and testis, whereas the protein was absent or only faintly detectable in muscle, kidney, and liver. In brain sections, the antibody intensely labeled the luminal and abluminal membranes of brain microvessel endothelial cells in all brain areas examined including cerebral cortex, cerebellum, hippocampus, and in gray and white matter regions. These results suggest that LAT1 is involved in transcellular transport and may play an important role in large, neutral amino acid transfer across the blood-brain barrier.

Increased cerebral glucose utilization and decreased glucose transporter Glut1 during chronic hyperglycemia in rat brain.

Whereas acute hyperglycemia has been shown to result in an unchanged local cerebral glucose utilization (LCGU) the changes of LCGU during chronic hyperglycemia are a matter of dispute. The present study had three aims: (1) To compare the effects of acute and chronic hyperglycemia on LCGU and to investigate in vivo the lactate level as a potential indicator of glycolytic flux. (2) To investigate local changes in brain Glut1 and/or Glut3 glucose transporter densities during chronic hyperglycemia. (3) To analyze the relationship between LCGU and local Glut densities during chronic hyperglycemia. To induce chronic hyperglycemia in rats steptozotocin was given i.p. and experiments were performed 3 weeks later. LCGU was measured by the 2-[14C]deoxyglucose method and intraparenchymal lactate concentration by MR-spectroscopy. Local densities of the glucose transport proteins were determined by immunoautoradiographic methods. During chronic hyperglycemia weighted average of LCGU increased by 13.9% whereas it remained unchanged during acute hyperglycemia. The cerebral lactate/choline ratio was increased by 143% during chronic hyperglycemia. The average density of glucose transporters Glut1 decreased by 7.5%. Local densities of Glut1 were decreased in 12 of 28 brain structures. Glut3 remained unchanged. Positive correlations were found between LCGU and local Glut densities during control conditions and during chronic hyperglycemia. It was concluded that (1) Chronic, but not acute hyperglycemia is followed by an increased LCGU. (2) The capacity to transport glucose is decreased during chronic hyperglycemia. (3) Increased LCGU and decreased densities of Glut1 are matched on a local level.

Brain water content, glucose transporter densities and glucose utilization after 3 days of water deprivation in the rat.

After 3 days of water deprivation, the following parameters were measured in rats: (i) brain water content (apparent diffusion coefficient); (ii) local cerebral glucose utilization (LCGU) ([14C]deoxyglucose method) and (iii) densities of glucose transporters Glut1 and Glut3 (immunoautoradiography). The results show that brain water content is maintained after water deprivation. Densities of glucose transporters Glut1 and Glut3 increased in parallel to increased LCGU in some of the osmoregulatory structures indicating a long-term local adaptation of glucose transporters to LCGU.

Increase in glucose transporter densities of Glut3 and decrease of glucose utilization in rat brain after one week of hypoglycemia.

The present study addresses the question whether a chronic decrease of plasma glucose concentration for 1 week induces a global or local increase in glucose transporter densities Glut1 and Glut3 in the brain. To induce chronic hypoglycemia insulin was infused into rats by osmotic minipumps for 1 week resulting in a mean plasma glucose concentration of 3.1+/-0.5 mmol/l (control group: 8.1+/-0.5 mmol/l). Global and local densities of Glut1 and Glut3 glucose transporters were measured by immunoautoradiographic methods. The mean density of glucose transporters Glut1 remained unchanged, whereas the mean density of Glut3 increased slightly, although significantly. To determine whether the increased density of Glut3 is related to a change in glucose metabolism, the local cerebral metabolic rate of glucose (lCMR(glc)) was quantified by the 2-deoxyglucose method. Mean glucose utilization was decreased by 15%. Local analysis of transporter densities (Glut1 and Glut3) and glucose utilization showed a significant correlation between local glucose transporter densities (Glut1 and Glut3) and lCMR(glc) during hypoglycemia as already previously observed during normoglycemia. It is concluded that 1 week of hypoglycemia is a stimulus for the induction of additional glucose transporters Glut3 in the brain. These additional neuronal glucose transporters may support the maintenance of glucose utilization which is not completely maintained under these conditions.

Local transport kinetics of glucose during acute and chronic nicotine infusion in rat brains.

Acute and chronic infusion of nicotine is known to result in a distinct increase in local cerebral glucose utilization (LCGU) in several brain structures. The present study addresses the question whether this increase in LCGU is paralleled by a local change in glucose transport in rat brain. Nicotine was infused either acutely for 3 hours or chronically by osmotic minipumps for one week. Local rate constants for glucose transport were measured in brain cryosections using the 3-O-[14C]methylglucose method. Local rate constants K1 and k2 were lower in part of the brain structures during acute (-10% to -20%) and in nearly all structures during chronic (-39% to -41%) nicotine. The finding of a decreased glucose transport during chronic nicotine was confirmed by additional experiments of 3-O-[14C]methylglucose transfer in an epithelial cell culture. It is concluded that acute and chronic nicotine infusion results in decreased glucose transport although LCGU is either unchanged or increased.

Decreased glucose transporter densities, rate constants and glucose utilization in visual structures of rat brain during chronic visual deprivation.

The question was investigated whether local changes in glucose transporter densities and transport kinetics can occur when local cerebral glucose utilization (LCGU) is decreased in some brain structures. Unilateral visual deprivation was induced by monocular enucleation in 25 rats. After 1 week, the contralateral structures of the visual system were analyzed for (1) densities of glucose transporters Glut1 and Glut3 (immunoautoradiography), (2) LCGU (2-[14C]deoxyglucose method) and (3) local rate constants (3-O[14C]methylglucose method). The ipsilateral structures served as controls. During chronic visual deprivation Glut1 and Glut3 densities, LCGU and rate constants were significantly decreased in some structures of the visual system and remained unchanged in others. These results indicate a moderate degree of downregulation of glucose transporters, LCGU and rate constants in the visual system during visual deprivation.

Autoradiographic determination of local cerebral blood flow and local cerebral glucose utilization during chemical stimulation of the nucleus tractus solitarii of anesthetized rats.

This study was conducted to determine whether the decrease in cerebral blood flow (CBF) observed during chemical stimulation of the nucleus tractus solitarius (NTS) can be explained by a decrease in cerebral metabolism. In anesthetized (urethane and chloralose), paralyzed and artificially ventilated rats, neurons in the NTS were chemically stimulated by microinjection of L-glutamate. Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were quantified in 43 brain structures by quantitative autoradiographic techniques using [14C]iodoantipyrine and 2-[14C]deoxyglucose, respectively. During chemical stimulation of the NTS (n = 6), LCBF decreased significantly in 32 of the 43 structures investigated when compared to either a control group with artificial cerebrospinal fluid injection (n = 6), or a controlled hemorrhage group (n = 5). In the controlled hemorrhage group, blood pressure was decreased to a degree comparable to that induced by microinjection of L-glutamate into the NTS. Mean blood flow of all structures investigated was significantly (P < 0.01) lower in the stimulation group than that in the control group and in the hemorrhage group. No significant differences in LCGU were observed between the three investigated groups in all structures examined except for an increase in LCGU in the chemically stimulated NTS site. It is concluded that the decrease in LCBF measured in most brain structures during chemical stimulation of the NTS is not caused by a decrease in LCGU in these structures and may therefore be explained by neurogenic influences on brain vessels.

Increase of glucose transporter densities (Glut1 and Glut3) during chronic administration of nicotine in rat brain.

Chronic infusion of nicotine is known to result in a distinct pattern of increases in local cerebral glucose utilization (LCGU). The present study addresses the question whether this increase in LCGU is paralleled by (1) a local increase in Glut1 and/or Glut3 glucose transporter densities and (2) a local increase in capillary density in the brain. Nicotine was infused by osmotic minipumps for one week. In cryosections of rat brains local densities of Glut1 (vascular) and Glut3 (neuronal) glucose transporters were measured by immunoautoradiographic methods whereas local capillary densities were determined by an immunofluorescent method. Densities of glucose transporters Glut1 and Glut3 were increased in 12 of the 27 structures investigated. Glut1 was elevated in four additional structures and Glut3 in two more structures. Comparison of the changes in transporter densities with the changes of LCGU measured in a previous study during chronic nicotine infusion showed that LCGU was also elevated in most of these structures. In contrast, capillary density remained unchanged in all structures investigated. It is concluded that one week of nicotine infusion is sufficient to raise the densities of Glut1 and Glut3 glucose transporters predominantly in those structures in which LCGU is elevated. The unchanged capillary density under these conditions indicates an increased density of Glut1 transporters per capillary.

Parallel changes of blood flow and heterogeneity of capillary plasma perfusion in rat brains during hypocapnia.

Plasma perfusion patterns were investigated in brain capillaries during decreased cerebral blood flow induced by hyperventilation. Anesthetized rats were decapitated 3-4 s after being given an intravenous bolus injection of Evans blue dye. the measured steep increase of the arterial dye concentration at this moment ensures that different capillary plasma transit times are reflected in different intracapillary dye concentrations. The observed heterogeneity of capillary plasma transit time was expressed as the coefficient of variation (means +/- SD) of the intracapillary dye concentrations. For comparison, cerebral blood flow was determined at comparable PCO2 values in a second experimental group. At arterial PCO2 values between 40 and 25 mmHg, the cerebral blood flow and the coefficient of variation of the intracapillary dye concentration decreased with decreasing PCO2, whereas at PCO2 values <25 mmHg cerebral blood flow and coefficient of variation did not correlate with the arterial PCO2. However, it cannot be excluded that the coefficient of variation of the intracapillary dye concentration increases between 25 and 14 mmHg and decreases between 14 and 10 mmHg. It is concluded that the reduction of cerebral blood flow measured during moderate hypocapnia is paralleled by a decreased heterogeneity of the brain capillary perfusion. During severe hypocapnia this relationship is lost, indicating a potential disturbance of the cerebral microcirculation.

Autoradiographic analysis of the regional distribution of Glut3 glucose transporters in the rat brain.

Glut3 is a glucose transporter protein which facilitates the transport of glucose across the neuronal membranes. The local distribution of Glut3 in the brain is not well known. The present study had the aim to verify the local distribution of Glut3 in the brain and to compare it with the local glucose utilization. A polyclonal antibody directed against the C-terminal peptide sequence of Glut3 was applied to cryosections of rat brains. A secondary antibody was added which had been coupled to 35S. Using autoradiography and radioactive standards, 17 cerebral structures were investigated. The results show moderate differences of Glut3 density in the structures investigated ranging from -23% to +41% of the mean density. The pineal gland was an exception with a density 66% lower than mean. Local cerebral glucose utilization (LCGU) was analyzed in identical brain structures by application of the quantitative autoradiographic 2-deoxyglucose method to conscious rats. The range of LCGU was from -59% to +55% of the mean. No correlation was found between the moderately heterogeneous Glut3 transporter density and the strongly heterogeneous local cerebral glucose utilization. The results show that the local density of Glut3 glucose transporter protein does not reflect the local level of glucose utilization in the brain.

The importance of baroreceptor afferents for the decrease in brain glucose utilization during stimulation of the rostroventrolateral medulla of the rat.

The rostroventrolateral medulla (RVLM) is the main integration center for the regulation of the sympathetic outflow. The present study had the aim of investigating the effects of stimulation of the RVLM on the glucose utilization of the brain. Local cerebral glucose utilization (LCGU) can be regarded as an indicator of the brain functional activity. In anesthetized (chloralose-urethan), paralyzed (pancuronium) and ventilated rats, the medulla was exposed by a ventral craniotomy. The RVLM was stimulated by microinjection of 100 nl of 0.5 M sodium glutamate (n = 6). The effective stimulation was verified by the increase in arterial blood pressure. In a control group (n = 7), an identical volume of saline was injected into the RVLM. Local cerebral glucose utilization was measured in both groups using the 2-[14C]deoxyglucose method. The results showed a significant decrease in LCGU in the stimulated group in 33 of 39 brain structures examined. In order to investigate whether the decrease in brain glucose utilization is secondary to the stimulation of baroreceptor afferents by the increase in arterial blood pressure the carotid sinus nerves and both vagal nerves were cut. In this denervated group (n = 5) the decrease in LCGU was abolished in all brain structures although blood pressure was increased to a degree comparable to the innervated group. It is concluded that cerebral glucose metabolism is decreased during stimulation of the RVLM and that this decrease is secondary to the activation of baroreceptor afferents by the increase in blood pressure.

Intracerebroventricular injection of streptozotocin induces discrete local changes in cerebral glucose utilization in rats.

The purpose of the present study was to investigate whether or not cerebral glucose utilization is changed locally after damage of the neuronal insulin receptor by means of intracerebroventricular (icv) streptozotocin (STZ) administered in a subdiabetogenic dosage (1.5 mg/kg bw.). STZ was administered at the start of the study, and 2 and 21 days later bilaterally into the cerebral ventricles in rats of a mean age of 18 months. The local distribution of cerebral glucose utilization was analyzed in conscious rats on the 42nd day after the first STZ injection using the quantitative (14C)-2-deoxyglucose method. Of the 35 brain structures investigated from autoradiograms of brain sections, 17 showed a reduction in glucose utilization. Decreases in glucose utilization were observed in the frontal, parietal, sensory motor, auditory and entorhinal cortex and in all hippocampal subfields. In contrast, glucose utilization was increased in two white matter structures. The decrease in cerebral glucose utilization observed in cortical and hippocampal areas in the present study may correspond to changes in morphobiological parameters which have been found in patients with Alzheimer's disease. The present data are in accordance with the hypothesis that an impairment in the control of neuronal glucose metabolism at the insulin receptor site may exist in sporadic dementia of Alzheimer type (DAT), and can be studied by the icv STZ animal model.

Changes in brain capillary diameter during hypocapnia and hypercapnia.

Since changes in the surface area of capillaries may be relevant to capillary exchange, the distensibility of brain capillaries was investigated. Brain capillary diameters were measured after perfusion fixation of brain tissue at a constant perfusion pressure during hypo- or hypercapnia. Sections were embedded, stained, and analyzed by light microscopy. The results showed significant differences in mean capillary diameter between the hypocapnic and the hypercapnic group. In the eight brain structures analyzed, capillary diameters were always larger in the hypercapnic group. Mean capillary diameter was 4.93 +/- 0.29 microns in the hypocapnic group and 5.91 +/- 0.10 microns in the hypercapnic group (means +/- SD). We conclude that brain capillaries exhibit a moderate degree of distensibility. Variations in the precapillary pressure of microvessels may therefore influence both capillary flow and capillary surface area.

[Ultrasound of incidental tumors of the adrenal gland and endocrine hypertension]. / Sonographische Inzidentalome der Nebenniere und endokrine Hypertonie.

We report on a retrospective analysis of 1,500 hypertensive patients who underwent a sonographic examination of the abdomen. 8 'incidentalomas' of the adrenal gland (0.6%) were thereby found. Endocrinological analysis showed that only 1 of the incidentalomas was active (pheochromocytoma). The other tumors had no endocrine activity. On the other side, 7 patients without any sonographic abnormality had hyperaldosteronism, 1 patient suffered from an adrenomedullary hyperplasia. Those patients had been thought to have endocrine hypertension from clinical suspicion. We conclude that a thorough sonographic examination of the adrenal area is an important part of the diagnostic workup in hypertensive patients, although most of the incidentally discovered tumors are endocrinologically inactive. Adrenocortical and adrenomedullary hyperplasias and adrenocortical adenomas are detected clinically while they are still not visible by ultrasound.