The legacy of Václav Trnka: modern medical education in Slovakia and Hungary in the eighteenth century.

A fresh start of higher medical education in Slovakia and Hungary is closely related to Trnava (Nagyszombat). The University of Trnava had originally been established in 1635 but the Faculty of Medicine was added only later, in 1769, when the name of the university was also changed to Royal Hungarian University of Sciences. A fresh graduate, Václav Trnka from Krovice (1739-1791), was appointed as head of the Department of Anatomy. He was not only an anatomist, but a real polymath of the second half of the eighteenth century practicing medicine as well as becoming the Dean, then the Rector of the University. He has lived and acted within several countries of Central Europe, or rather, the Austrio-Hungarian monarchy during the reign of Empress Maria Theresia, then her son Joseph II. Born in Bohemia (now Czech Republic), studied and graduated in Austria, then finally was appointed as the first Professor of Anatomy of a newly established medical faculty in Upper Hungary (now Slovakia). In 1777, the university was moved first to Buda, then to Pest (now parts of the capital of Hungary), and the Faculty of Medicine was not separated from the rest of the faculties before the end of the Second World War. Following several institutional and name changes, this Medical Faculty is considered as the foundation of the present Semmelweis University. Trnka was a proliferous author, publishing more than 20 monographs covering various branches of clinical medicine, however, no anatomical work may be connected to his activity. And as a typical intellectual of the era, he was a keen and talented musician composing several canons.

Inhibitory Effects of Diclofenac on Steroid Glucuronidation In Vivo Do Not Affect Hair-Based Doping Tests for Stanozolol.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3'-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair, which holds considerable advantages over urinalysis for anti-doping tests.

CT Images Are Noninferior to Anatomic Specimens in Teaching Cardiac Anatomy-A Randomized Quantitative Study.

PURPOSE: The new generation's learning habits demand reforms in the methods by which we teach anatomy. Medical imaging techniques such as CT may offer a solution to help the understanding of complex anatomic structures. Our objective was to assess the noninferiority of using radiologic images in teaching anatomy as opposed to prosections or lecture slides. METHODS: Seventy-three first-year medical students were assigned to three experimental groups taught using different approaches: lecture slides (LG), prosections (PG), or radiology images (RG). All three groups received a 2-hour presentation on cardiac anatomy. Three days after the lectures, the participants were subjected to a gross anatomic "pin test" followed by a written theoretical examination to evaluate their knowledge of cardiac anatomy. RESULTS: We found a significant difference between the three groups regarding their gross anatomic examination scores (LG: 8.1 ± 4.1, PG: 10.6 ± 3.3, RG: 8.5 ± 3.4, P = .03; Tukey's honest significant difference: P(LG-PG) = .04, P(PG-RG) = .08, P(LG-RG) = .94), whereas no significant difference was apparent regarding their written theoretical examination scores (LG: 16.6 ± 4.2, PG: 18.6 ± 3.5, RG: 18.3 ± 3.0, P = .13). CONCLUSIONS: Concerning gross anatomic knowledge, groups taught using prosections or radiologic images showed no significant difference. Demonstrative materials do not seem to significantly affect the theoretical knowledge of the students. The use of medical imaging techniques could represent a valuable contribution toward teaching anatomy.

Multiple amygdaloid divisions of arcopallium send convergent projections to the nucleus accumbens and neighboring subpallial amygdala regions in the domestic chicken: a selective pathway tracing and reconstruction study.

Retrograde tracing with choleratoxin B, injected into the nucleus accumbens (Ac) and bed nucleus of stria terminalis, lateral part (BSTL), yielded labeled perikarya in a ring-shaped area of arcopallium, including dorsal and hilar subdivisions, with a wedge-shaped node of dense accumulation in the amygdalopiriform area (APir). Also, the position of source neurons for this arcopallio-subpallial pathway was verified by anterograde tracing. Three subregions of arcopallium (amygdalopiriform, dorsal, hilar) were injected with dextran (10 kDa), and fibers and terminal fields were detected in Ac, BSTL and extended amygdala (EA). Most abundant projections to Ac arose from APir. The study enabled precise description of the main output fiber streams: the dorsal stream follows the dorsal border of arcopallium and, continuing in the ventral amygdalofugal tract, it traverses the EA and the BSTL before reaching the Ac. The ventral stream of fibers enters the EA along the ventral subpallial border and terminates in the basal nucleus and ventral pallidum. The course of the pathway was reconstructed in 3D. Retrogradely labeled arcopallial neurons were devoid of DARPP-32. DARPP-32 was present in the Ac but not the BSTL. No colocalization between the calcium binding proteins calbindin, parvalbumin and calretinin, and retrogradely labeled neurons was detected, despite a considerable territorial overlap. This finding further supports the excitatory nature of the arcopallial-accumbens pathway. Conjoint and convergent amygdalar input to EA, including BSTL, as well as to Ac subregions likely transmits fear and aggression related signals to both viscerolimbic (EA) and learned reward- and motivation-related (Ac) ventrobasal forebrain regions.

Expression of Vascular Endothelial Growth Factor Has a Regulatory Role in Gingival Venules in Experimental Diabetes.

BACKGROUND: In the present study, the possible localization and role of vascular endothelial growth factor receptor type 2 (VEGFR2) in the regulation of gingival venules in a rat model of experimental diabetes are examined. METHODS: Six weeks after streptozotocin premedication, Wistar male rats presenting blood sugar levels >20 mmol/L were selected for investigation. The VEGFR2 antagonist ZM323881 [5-((7-benzyloxyquinazolin-4-yl)amino)-4-fluoro-2-methylphenol-hydrochloride] (20 µg/mL) was dripped onto the gingiva between the mandibular incisors. Changes in diameter of the selected gingival venule were measured by vital microscopy combined with digital photography at specified times. Immunohistochemical staining was used to localize VEGFR2. For controls, the same protocol was used on animals with normal blood sugar levels and healthy gingiva. RESULTS: There was a significant difference between the baseline venule diameter of the diabetic and the control groups (47 ± 1 and 28 ± 2 µm, respectively). After 15, 30, and 60 minutes of local application of ZM323881, significant vasoconstriction was observed in the venules of diabetic rats compared with the baseline (81.4% ± 4.6%, 81.8% ± 4.4%, and 80.6% ± 5.1%, respectively). The control group showed no change in the venule diameter. The immunohistochemical analysis showed significantly increased VEGFR2 expression in the mast cells along the venules in the diabetic group, whereas mast cells were rarely found in the control group. CONCLUSIONS: The findings suggest that VEGF expression is increased in gingiva in experimentally induced diabetes. After VEGFR2 activation, the mast cell-derived vasodilatory and inflammatory mediators may contribute markedly to the concomitant changes in the microcirculation.

Determination of stanozolol and 3'-hydroxystanozolol in rat hair, urine and serum using liquid chromatography tandem mass spectrometry.

BACKGROUND: Anabolic androgenic steroids, such as stanozolol, are typically misused by athletes during preparation for competition. Out-of-competition testing presents a unique challenge in the current anti-doping detection system owing to logistic reasons. Analysing hair for the presence of a prohibited drug offers a feasible solution for covering the wider window in out-of-competition testing. To assist in vivo studies aiming to establish a relationship between drug levels detected in hair, urine and blood, sensitive methods for the determination of stanozolol and its major metabolite 3'-hydroxystanozolol were developed in pigmented hair, urine and serum, using brown Norway rats as a model system and liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: For method development, spiked drug free rat hair, blood and urine samples were used. The newly developed method was then applied to hair, urine and serum samples from five brown Norway rats after treatment (intraperitoneal) with stanozolol for six consecutive days at 5.0 mg/kg/day. The assay for each matrix was linear within the quantification range with determination coefficient (r2) values above 0.995. The respective assay was capable of detecting 0.125 pg/mg stanozolol and 0.25 pg/mg 3'-hydroxystanozolol with 50 mg hair; 0.063 ng/mL stanozolol and 0.125 ng/mL 3'-hydroxystanozolol with 100 µL of urine or serum. The accuracy, precision and extraction recoveries of the assays were satisfactory for the detection of both compounds in all three matrices. The average concentrations of stanozolol and 3'-hydroxystanozolol, were as follows: hair = 70.18 ± 22.32 pg/mg and 13.01 ± 3.43 pg/mg; urine = 4.34 ± 6.54 ng/mL and 9.39 ± 7.42 ng/mL; serum = 7.75 ± 3.58 ng/mL and 7.16 ± 1.97 ng/mL, respectively. CONCLUSIONS: The developed methods are sensitive, specific and reproducible for the determination of stanozolol and 3'-hydroxystanozolol in rat hair, urine and serum. These methods can be used for in vivo studies further investigating stanozolol metabolism, but also could be extended for doping testing. Owing to the complementary nature of these tests, with urine and serum giving information on recent drug use and hair providing retrospective information on habitual use, it is suggested that blood or urine tests could accompany hair analysis and thus avoid false doping results.

Potentially harmful advantage to athletes: a putative connection between UGT2B17 gene deletion polymorphism and renal disorders with prolonged use of anabolic androgenic steroids.

BACKGROUND AND OBJECTIVE: With prolonged use of anabolic androgenic steroids (AAS), occasional incidents of renal disorders have been observed. Independently, it has also been established that there are considerable inter-individual and inter-ethnic differences, in particular with reference to the uridine diphosphate-glucuronosyltransferase 2B17 (UGT2B17) gene, in metabolising these compounds. This report postulates the association of deletion polymorphism in the UGT2B17 gene with the occurrence of renal disorders on chronic exposure to AAS. PRESENTATION OF THE HYPOTHESIS: The major deactivation and elimination pathway of AASs is through glucuronide conjugation, chiefly catalyzed by the UGT2B17 enzyme, followed by excretion in urine. Excretion of steroids is affected in individuals with a deletion mutation in the UGT2B17 gene. We hypothesize that UGT2B17 deficient individuals are more vulnerable to developing renal disorders with prolonged use of AAS owing to increases in body mass index and possible direct toxic effects of steroids on the kidneys. Elevated serum levels of biologically active steroids due to inadequate elimination can lead to prolonged muscle build up. An increase in body mass index may cause renal injuries due to sustained elevated glomerular pressure and flow rate. TESTING THE HYPOTHESIS: In the absence of controlled clinical trials in humans, observational studies can be carried out. Real time PCR with allelic discrimination should be employed to examine the prevalence of different UGT2B17 genotypes in patients with impaired renal function and AAS abuse. In individuals with the UGT2B17 deletion polymorphism, blood tests, biofluid analyses, urinalysis, and hair analyses following the administration of an anabolic steroid can be used to determine the fate of the substance once in the body. IMPLICATIONS OF THE HYPOTHESIS: If the hypothesis is upheld, anabolic steroid users with a deletion mutation in the UGT2B17 gene may be exposed to an increased risk of developing renal disorders. In the current detecting - sanctioning anti-doping system, athletes motivated by the potential to evade detection owing to their unique genetic make-up could subject themselves to a serious health consequence. More research on AAS metabolism in the presence of UGT2B17 gene deletion is required. Benefit - harm evaluations in therapeutic use of anabolic steroids should also consider this potential link between UGT2B17 gene deletion polymorphism and renal disorders.

Venodilatory effect of vascular endothelial growth factor on rat gingiva.

BACKGROUND: Endothelial cell proliferation, angiogenesis, and increased vascular permeability are among the effects of vascular endothelial growth factor (VEGF) in various organs. However, the effects of VEGF on gingival hemodynamics, especially on venules, have not been thoroughly investigated. This study investigated the acute circulatory effects of VEGF on rat gingival venules. METHODS: Fifty-six anesthetized rats were divided into five study groups; each rat received 10 microl of experimental solution dripped onto the lower interincisal gingiva. The groups included: 1) saline control (after the experiment, gingiva was excised for VEGF receptor 2 [VEGFR2] immunohistochemistry); 2) VEGF (0.1, 1, 10, or 50 microg/ml); 3) VEGF2 receptor antagonist 5-((7-benzyloxyquinazolin-4-yl)amino)-4-fluoro-2-methyl-phenol-hydrochloride (ZM323881; 20 microg/ml); 4) ZM323881 (20 microg/ml) followed by VEGF application (50 microg/ml after 15 minutes); and 5) VEGF (10 microg/ml), these rats were premedicated with nitric oxide (NO) synthase blocker (N(G)-nitro-L-arginine-methyl-ester [L-NAME]; 1 mg/ml in drinking water) for 1 week before the experiment. Changes in gingival superficial venule diameter were measured by vital microscopy prior to and 1, 5, 15, 30, and 60 minutes after the administration of the experimental solutions. RESULTS: VEGF dose-dependently increased the venular diameter compared to saline. ZM323881 alone did not cause any alteration. Premedication with ZM323881 or L-NAME decreased the dilatory effects of VEGF. VEGFR2 immunohistochemical labeling was observed in the wall of the venules. CONCLUSIONS: There is no remarkable VEGF production under physiologic circumstances in rat gingiva, but VEGF is able to increase gingival blood flow through the activation of VEGF2 receptors. Furthermore, NO release may contribute to VEGF's vasodilatory effect.

Efferent connections of septal nuclei of the domestic chick (Gallus domesticus): an anterograde pathway tracing study with a bearing on functional circuits.

Small iontophoretic injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin were placed in different subregions of the septum of domestic chicks. The main targets of septal projections comprised the ipsi- and contralateral septal nuclei, including the nucleus of the diagonal band, basal ganglia, including the ventral paleostriatum, lobus parolfactorius, nucleus accumbens, and olfactory tubercle, archistriatum, piriform cortex, and anterior neostriatum. Further diencephalic and mesencephalic septal projections were observed in the ipsilateral preoptic region, hypothalamus (the main regions of afferentation comprising the lateral hypothalamic nuclei, ventromedial, paraventricular and periventricular nuclei, and the mammillary region), dorsal thalamus, medial habenular and subhabenular nuclei, midbrain central gray, and ventral tegmental area. Contralateral projections were also encountered in the septal nuclei, ventral paleostriatum, periventricular and anteromedial hypothalamic nuclei, suprachiasmatic nucleus, and the lateral hypothalamic area. Avian septal efferents are largely similar to those of mammals, the main differences being a relatively modest hippocampal projection arising mainly from the nucleus of the diagonal band (as confirmed by a specific experiment with the retrograde pathway tracer True blue), the lack of interpeduncular projection, and a greater contingent of amygdalar efferents arising from the lateral septum rather than the nucleus of the diagonal band. This pattern of connectivity is likely to reflect an important role of the avian septal nuclei in the coordination of limbic circuits and the integration of a wide variety of information sources modulating the appropriate behavioral responses: attention and arousal level, memory formation, hormonally mediated behaviors, and their affective components (such as ingestive, reproductive, and parental behaviors), social interaction, locomotor modulation, and circadian rhythm.