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Biomedical subjects

Wolfgang Kühnel

Publications and source records attributed to Wolfgang Kühnel.

9 recordsLinked to original sources

The xenoestrogen bisphenol A in the Hershberger assay: androgen receptor regulation and morphometrical reactions indicate no major effects.

We evaluated androgen-like effects of bisphenol A (BPA) using orchiectomized Wistar rats. Animals were treated p.o. either with vehicle or with 3, 50, 200, 500 mg/kgbw/day BPA (n=13) for 7 days. One group was treated s.c. with 1mg/kgbw/day testosterone propionate (TP). Flutamide (FL) (3mg/kgbw/day, p.o.) was used to antagonize androgen effects of the suprapharmacological dose (500 mg/kgbw/day) of BPA. Androgen-like effects of BPA on prostates and seminal vesicles were assessed by the Hershberger assay, densitometric analysis of androgen receptor (AR) immunoreactivity, cell proliferation-index and a morphometric analysis. Absolute weights of prostates and seminal vesicles were not increased by BPA, whereas the relative weights were increased at higher doses of BPA, most likely due to a decrease in body weight. Staining intensity for AR immunoreactivity was increased at low but not at higher doses of BPA in comparison to the orchiectomized rats. BPA at all doses tested did not cause an increase of the cell proliferation-index. Epithelial height and glandular luminal area were increased by low doses of BPA, whereas higher doses caused a decrease of these parameters. The data provide evidence that BPA does not exert major androgenic effects.

Animals↗

Features of the peritoneal covering of the lesser pelvis with special reference to stomata regions.

Occasional reports describe various aspects of the fine morphology of the pelvic peritoneum, but its complete organ characteristics remain undefined. The peritoneal covering of the urinary bladder, rectum, uterus, uterine tube, ovary, broad ligament (BL) and testis in Wistar rats was examined by means of transmission and scanning electron microscopy (TEM, SEM). Unusually complicated relief and stomata between the cubic mesothelial cells characterized the surface of the BL. Deep, parallel furrows separated the wide longitudinal folds over the entire length of the uterine tube. The uterus and the ovary formed less numerous, shallow or extremely deep crypt-like invaginations, as well as serous villus-like or papilla-like evaginations. The flat cells were the predominant cell type over the BL, while the cubic mesothelium was the basic covering of the organs. Most of the cubic cells were located in the invagination of the submesothelial layer (SML). Such cells formed an almost smooth surface over the urinary bladder or formed larger areas of the rectum and the testis surfaces. Numerous microvilli, ciliae, round evaginations and complex lamellar bodies characterized their apical plasmalemma. In conclusion, the mesothelial heterogeneity is a stable feature of the lesser pelvis peritoneum, confirmed by TEM and SEM. The cubic mesothelium characterizes the organ peritoneum, while the BL plays the role of the parietal sheet, involving lymphatic units in the SML. The different types of contacts between the mesothelio-endothelial cells, large lymphatic vessels and occasional stomata are the usual components of the lymphatic units in norm, visible by TEM. Images of stomata, seen by SEM, demonstrate oval-shaped deep channel-like gaps surrounded by cubic mesothelium. The last data extend the evidence on stomata regions, which resemble the diaphragmatic ones. Clusters of cells (macrophages, mastocytes and Lymphocytes), small vessels (blood or lymphatic) and nerve fibers (unmyelinated and rare myelinated) form highly specialized complexes in the SML of the ovary, the uterus and the testis.

Animals↗

[Micro anatomy of the cavernous sinus].

PURPOSE: The surgical anatomy of the human cavernous sinus has been described by several authors. A clearer understanding of the anatomy of the cavernous sinus has resulted in an increased interest in surgical approaches to this region. Regarding the anatomical concept of the cavernous sinus previous descriptions should be revised. METHODS: In our study, 35 skull-base blocks including both cavernous sinuses were investigated. RESULTS: There is considerable reason that the lateral wall of the cavernous sinus is covered by a "medial temporal dura layer" attached to the leptomeningeal pockets of the cranial nerves III-V1+2. There is no significant constance of the internal carotid artery within the cavernous sinus. All cranial nerves adjacent to or traversing the cavernous sinus are embedded within a leptomeningeal sheath similar to a pocket. The abducent nerve traverses a venous space, which should be named "petroclival venous confluence" rather than Dorello's canal. The extremely variable cavernous space is covered by a one-layer cell line. There is no evidence of any venous-plexus structure. Fibrose bands (trabecle) are present in different numbers.

Carotid Arteries↗

Morphological changes in experimental postischemic rat kidney. A pilot study.

The aim of our study was to investigate the changes in the early stages (at weeks 2 and 4) of experimental acute renal failure after short-time ischemia-reperfusion (I/R) compared with the impact of Losartan. Twenty male Wistar rats were divided into three groups: sham-operated rats (2 weeks), I/R groups (2 and 4 weeks); I/R and Losartan-treated groups (2 and 4 weeks). I/R was produced in adult rats by clamping the left kidney renal artery and renal vein for 40 min. The angiotensin II receptor antagonist Losartan was added to the drinking water (40 mg/l), and treatment was started on the first day after the I/R. Body weight, systolic blood pressure (SBP) and 24 h urine amount was measured every week. Urine amount and SBP was higher in I/R groups compared to sham-operated rats. Early stage acute renal disease was characterized by focal segmental glomerulosclerosis (FSGS) and interstitial fibrosis (IF) at weeks 2 and 4 after I/R. In the Losartan group, 2 weeks after the surgery, FSGS, IF and mesangial cell proliferation was decreased, but at week 4 these parameters showed a tendency to increase. Marked changes take place in tubular epithelial cells, especially in I/R groups. Angiotensin II receptor blocker AT1RA Losartan in the small dose (40 mg/l) had no effect on hypertension and urine excretion in the experimental I/R model. A pilot study revealed that tubular basement membrane thickness is markedly increased after I/R.

Animals↗

Androgen-dependent morphology of prostates and seminal vesicles in the Hershberger assay: evaluation of immunohistochemical and morphometric parameters.

The aim of this study was to evaluate androgen-like effects using immunohistochemical and morphometric methods. Therefore, orchiectomized Wistar rats (n > or = 13) were treated s.c. with 1 mg/kg bw/day testosterone propionate (TP) for 7 days and compared to orchiectomized rats without TP substitution (OX) and to an untreated intact control group. Sections obtained from prostates and seminal vesicles were stained with polyclonal and monoclonal antibodies against the androgen receptor (AR) and assessed densitometrically (intensity of the immunoreaction) and morphometrically (epithelial height, luminal area). TP caused an enhancement of staining intensity and an increase in organ weights, epithelial height and luminal area. The use of proliferation markers (PCNA, MIB-5) showed also a highly significant increase of immunoreactive cells in TP-substituted orchiectomized rats compared with the OX group. Based on the present data, the densitometric analysis of AR-immunoreactivity as well as the assessment of proliferation markers, epithelial height and luminal area proved to be sensitive parameters for the evaluation of androgen effects on prostates and seminal vesicles. In further studies these parameters will be used to test several industrial xenooestrogens as well as phytooestrogens on their possible androgenic capacity.

Androgens↗

Low-dose radiation modifies the progression of chronic renal failure.

Previous studies have indicated that the application of low dose radiation to an arterial ligation has the potential to subsequently reduce or eliminate restenosis caused by smooth muscle cell proliferation. Sufficient kidney irradiation causes a radiation nephropathy and often leads to renal failure. In order to evaluate the effect of low-dose irradiation on the kidney we hypothesized that this particular therapy modifies renal injury in rats with renal ablation and subsequently slows the rate of the progression. For further clarification of the effect of irradiation at low doses, we determined proliferating cell nuclear antigen (PCNA) and monocyte chemoattractant protein-1 (MCP-1) expression in remnant kidneys after low-dose radiation. Adult Wistar rats (n = 10) were studied during the two weeks after renal ablation. The left kidney was irradiated 24 hours after an operation in anaesthetised animals with 3 Grey in a single dose. Ablated rats without irradiation (n = 9) served as nephrectomized animals group. Rats without surgery and without radiation (n = 10) served as healthy controls. Renal damage was assessed using the following parameters: urine protein excretion rate (UprotV, mg/day), awake systolic blood pressure (SBP, mm Hg), serum creatinine (SCr, micromol/l). The indirect immunofluorescence method was used for the detection of PCNA and MCP-1 expression. Glomerular and tubular immunostaining was scored semiquantitatively. Numerous PCNA positive cells and MCP-1 expression were present in the glomerulus and tubulointerstitium in nephrectomized rat kidneys. Low-dose radiation application was associated with a significant reduction in PCNA and low MCP-1 expression. This study shows that the application of low-dose irradiation has the potential to modify the progression of chronic renal failure in rats.

Animals↗

Correlated expression of inducible nitric oxide synthase and P53, Bax in benign and malignant diseased gallbladder.

Our goal has been to investigate the expression and correlated significance of inducible nitric oxide synthase (iNOS) and P53, Bax in benign and malignant gallbladder diseases. We detected the expression of iNOS, P53 and Bax in the gallbladder wall by SP immunohistochemistry in 16 cases of chronic cholecystitis, 11 cases of chronic cholecystitis with adenomyoma and 24 cases of gallbladder adenocarcinoma. The percentage of positively marked tumor cells was counted under microscope and the intensity of immunoreactivity was graded. SPSS10.0 statistical software was applied for statistical analysis. In this study, we found that: (1) Both benign and malignant diseased gallbladder wall expressed iNOS and Bax. Compared to benign diseased gallbladders, their expression in adenocarcinoma was decreased (p < 0.05), P53 was expressed strongly only in nuclei of adenocarcinoma cells of some cases. (2) In benign and malignant diseased gallbladders, iNOS expression was related positively to Bax (p < 0.01), the expression of P53 and Bax had a negative relationship (p < 0.01). The results suggested that both chronic cholecystitis and chronic cholecystitis with adenomyoma carry the risk of becoming malignant, especially the latter. NO is an important mediated molecule in cancer, there are intimate relationships between gallbladder cancer and apoptosis.

Acute Disease↗

Macroscopical anatomy of the so-called "rotator interval". A cadaver study on 19 shoulder joints.

The triangular capsular space between the insertion tendons of the Mm. supraspinatus and subscapularis--the "rotator interval", can be divided into lateral, medio-superior and medio-inferior parts. The lateral part of the capsule is strengthened by the "Lig. semicirculare humeri" and the anterior fibres of the M. supraspinatus tendon. The Ligg. coracohumerale and "coracoglenoidale" are the macroscopical elements of the medio-superior part. The medio-inferior part of the "rotator interval" is reinforced by the Ligg. glenohumeralia superius et medium. The key ligament of the "rotator interval" is the "Lig. semicirculare humeri". Laterally it ensures the insertion of the anterior fibres of the M. supraspinatus tendon above the Lig. transversum humeri and on the Tubercula majus et minus. Medially it is the place of attachment of the Lig. coracohumerale and oblique fibres of the Lig. glenohumerale superius. The "rotator interval" is not a weak capsular region but a complex network of macroscopically recognizable tendinous and ligamentous structures.

Cadaver↗

Preferential topography of proteins regulating vascularization and apoptosis in a MX1 xenotransplant after treatment with hypoxia, hyperthermia, ifosfamide, and irradiation.

The MX1 xenotransplant growing in nude mice was used as a model for estrogen- and progesterone-receptor-negative breast cancer. The effects of different therapeutic regimens-combinations of hyperthermia, chemotherapy, and irradiation-on the expression of proteins playing a role in tumor vascularization and apoptosis were investigated. Additionally, MX-1 tumors were exposed to hypoxia to investigate changes in protein expression related to angiogenesis. This is of particular importance with respect to antiangiogenic therapies that may be combined with the treatments mentioned before. Endothelial and adhesion factors, extracellular matrix (ECM) factors, apoptosis-regulating factors, and neuronal factors were examined by immunohistochemical techniques. Concerning vascularization, the most prominent changes were seen in the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which increased strongly after hypoxia. The other cytokines, adhesion and ECM molecules, were either little affected or unaffected by the therapy. At the ultrastructural level, the walls of the tumor vessels are of the sinusoidal type, possessing many fenestrations. With regard to the second focus of this investigation, apoptosis, tumor cells again exerted the strongest differences after hypoxia where c-myc was clearly enhanced, whereas the effects on p53, bcl-2, and CD95 were extremely weak or not detectable. Furthermore, the neurotransmitter somatostatin, a possible "external" regulator of apoptosis, did not show treatment-related changes. In summary, it was shown that 1) within the group of apoptosis-regulating proteins c-myc was particularly affected by hypoxia, indicating a possible role for an activation-induced pathway of apoptosis in this context; 2) minor changes seen after treatment combined with hyperthermia point to a more acute vascular reaction (=dilatation), causing an increase of tissue pO2 rather than angiogenesis; and 3) the concentrations of the angiogenic factors VEGF and bFGF rose strongly under hypoxia, thereby possibly exerting counterproductive effects to antiangiogenic therapy but not to thermochemotherapy or irradiation. This supports the concept of a combined antiangiogenic, hyperthermia, chemo- and irradiation therapy.

Animals↗