Aescin and troxerutin as a successful combination for the treatment of inner ear perfusion disturbances.

A fixed combination of aescin and troxerutin has been developed for treating inner ear perfusion problems of different aetiology. The efficacy of this combination is tested versus pentoxyfyllin in a randomized clinical study as group comparison with 34 patients for each group. The improvement of hearing after 40-44 days of treatment is determined as end point of treatment. Hearing was measured by threshold, whereby a difference of more than 10dB is judged as a significant improvement. After the treatment with the combination of aescin and troxerutin hearing is significantly improved, in 23 of 34 patients the threshold is changed more than 10dB, which is checked by sign-test with p<0.05. With pentoxyfyllin hearing is also improved, although to a lesser degree. Both drugs are well tolerated, major adverse drug effects are not observed with either treatment.

The blood supply of the growth plate and the epiphysis: a comparative scanning electron microscopy and histological experimental study in growing sheep.

The blood supply of the growth plate has been described in the late 50s and early 60s, and there was controversial discussion about the existence of transphyseal vessels. The vascular supply of growth plate and epiphysis of the proximal tibia was reinvestigated using a modern technique, the Mercox-perfusion method, in six sheep aged 6-24 weeks. A comparison was made among pure perfusion specimens, the corrosion casts, and histological sections. The metaphyseal, epiphyseal, and perichondral blood supply systems were confirmed. However, there was evidence of regular transphyseal anastomoses between the metaphyseal and epiphyseal system. Based on the histological arrangement of the blood vessels, the arterial blood flow would appear to be from the metaphysis to the epiphysis. The existence of transphyseal arterial vessels originating metaphyseally and seen both in cast preparations and histological sections was added to the present description of the blood supply of the growth plate. Age-related differences in the vascularization of the growth plate were not found in this study.

Granin proteins (chromogranin A and secretogranin II C23-3 and C26-3) in the endocrine pancreas of reptiles.

The endocrine pancreas of four reptile species belonging to the turtles, lizards and snakes was investigated immunohistochemically for the occurrence and cellular distribution of chromogranin A (CgA) and of two synthetic secretonin II (SgII)-peptides (C23-3 and C26-3). CgA-immunoreactivity was found only in the turtle pancreas, whereas that for SGIIC23-3 appeared both in the turtle and snake. None of the species studied displayed immunoreactivity for SgIIC26-3. The two detected granins showed different distributions in relation to the endocrine cell types. Conspicuous variations of the immunostaining density for either granin in the same endocrine cell population and even complete lack of the immunoreaction were recorded. The findings suggest that, despite the restricted presence in the endocrine pancreas of the reptiles investigated, the granins are relatively well conserved during phylogeny; they do not confirm, however, the previously accepted usefulness of the granin protein family as common markers of neuroendocrine cells.

Endotracheal placement of balloon-expanded stents: an experimental study in rabbits.

The authors implanted balloon-expanded stents in the trachea of 10 rabbits for 1 day to 6 months. Follow-up included chest radiography, clinical examination, light microscopy, and scanning electron microscopy. Pneumothorax occurred in two cases after placement, marked stridor due to mucus plugging in all cases, signs of infection in three cases (two of which developed into pneumonitis), compression of the upper stent end in two cases, and moderate to severe mucus plugging in all cases. Microscopically, none of the stents was completely covered with epithelium even at 6 months. The high rate of complications may be a result of the rigid construction, which does not allow tracheal movement or adaptation of the stent shape to the shape of the trachea.

Overexpression of vascular endothelial growth factor in the avian embryo induces hypervascularization and increased vascular permeability without alterations of embryonic pattern formation.

Vascular endothelial growth factor (VEGF)--also known as vascular permeability factor--has been implicated in the regulation of blood vessel formation, i.e., vasculogenesis and angiogenesis. High amounts of VEGF mRNA and protein have been detected during embryonic and tumor angiogenesis, but it remained unclear whether the level of VEGF correlated with the extent of vascularization in a given organ or tissue. We examined the role of VEGF and the high affinity, signal-transducing VEGF receptor-2 (flk-1) in the avian embryo. In a gain of function transgene-like approach the retroviral expression vector RCAS was used to increase the level of quail VEGF during critical periods of avian limb bud growth and morphogenesis. In contrast to basic fibroblast growth factor, which recently was demonstrated to induce morphogenetic alterations when overexpressed in this system, overexpression of VEGF in the limb bud exclusively resulted in hypervascularization as reflected by an increase in vascular density. However, cartilage expressing the construct was not vascularized prematurely. Thus hypervascularization was probably due to the augmentation of the VEGF signaling mechanism in a permissive environment. In addition to hypervascularization, vascular permeability was dramatically increased, leading to local and in some cases to general edema. This is the first indication of a link between the functions of VEGF as a vascular growth factor and as a permeability factor. VEGF receptor-2 (flk-1) was found to be upregulated only in those areas where VEGF was overexpressed. This implies a positive feedback system of the VEGF receptor on its own synthesis and would provide a basis for a paracrine system in which ligand concentration is critical for the extent of tissue vascularization. Our results show that the VEGF/VEGF-receptor system is specific and sufficient for the formation of new blood vessels. They also have implications for somatic gene therapy of diseases which are characterized by a lack of blood vessels such as chronic ischemic diseases of heart and brain.

Improvement of cardiac performance and metabolism in long-term diabetes mellitus after treatment with insulin [see comment].

Rat hearts induced diabetic by administration of streptozotocin were investigated after 8 months using the isolated perfused working rat heart model at a physiological workload of approximately 45 min. They are hemodynamically characterized by a significantly reduced cardiac output (p < 0.001) and metabolically by a 49% reduction in glucose utilization (p < 0.001), mainly caused by reduced glucose uptake (p < 0.001) and an increased lactate and pyruvate production (p < 0.001), associated with a reduction of oxygen consumption by 44% (p < 0.001). Both lead to reduced ATP and CP myocardial tissue levels (p < 0.001). Similar results with respect to cardiac performance and metabolism are observed already after 2 months of diabetes. Treating these rats after 2 months of diabetes with insulin for 6 months, cardiac output (ns), cardiac metabolism (ns), oxygen uptake (ns) as well as ATP and CP levels (ns) are restored, indicating that normalization of cardiac function in this model depends mainly on the restored cardiac metabolism. These findings were associated with changes in the angioarchitecture as demonstrated.

Angioarchitecture in the heart of rats with streptozotocin-induced diabetes mellitus.

The effects of chronic streptozotozin-induced diabetes mellitus on the angioarchitecture of the heart in male Wistar rats were studied with the use of cast preparations and scanning electron microscopy. The following results were obtained in normal rats. Epicardial arteries branch obliquely and run parallel to the outer surface of the heart. Arterioles emerging from these arteries run in different directions. They show a fold-like structure equipped with a prearteriole sphincter. The capillaries in the myocardium form a net-like architecture with many H-like and Y-like anastomoses. Venous capillaries run directly into small veins at right angles while venules converge to form small veins at acute angles. In rats which have been suffering from diabetes mellitus for 8 months the capillary system appears less systematically arranged. The venous system generally exhibits dilatations. Dilatations were also seen along capillaries at short distances. In rats which had had untreated diabetes mellitus for 2 months and then 6 months of insulin treatment, a dilatation of the whole venous system was seen, but there were no significant changes in the capillary system.

[Perorally insertable endotracheal stents made from NiTi memory alloy--an experimental animal study]. / Peroral einführbare endotracheale Stützgerüste aus der Memory-Legierung NiTi--Tierexperimentelle Studie.

NiTi prostheses were perorally inserted in 12 rabbits. The spiral prostheses were overgrown by normal tracheal epithelium over time. No adverse effects due to impairment of the mucociliary clearance and no chondromalacia occurred. We conclude that perorally insertable prostheses made of the shape-memory alloy NiTi may be used as endotracheal or endobronchial prostheses.

Microvasculature of the principal islets in the scorpion fish, Myoxocephalus scorpius.

Since precise information with respect to the microvasculature of the teleost pancreas is lacking, analysis of the so-called principal islets (Brockmann bodies) was performed in Myoxocephalus scorpius with the use of methacrylate resin for the production of cast preparations. Stereoanalytical observations indicate that the circulatory pattern in the juxtasplenic pancreatic islets depends on nutritive and functional factors. Corkscrew-like arteries end in capillaries, and back flow is directed via sinuses into efferent vessels displaying nodular and valve-like structures.

Angioarchitecture of the pancreas of the cat. Light-, scanning- and transmission electron microscopy.

By the use of scanning- and transmission electron microscopy, the possible sources of errors in interpretation of the microcirculation of the pancreas can be reduced in comparison to the classical India-ink injection method. Sphincter-like structures in the capillary wall of the cat pancreas are established by pericytes. These sphincters encircle the junctional zones between the endocrine and exocrine capillaries. They are assumed to be regulatory structures of blood flow and to regulate indirectly hormone secretion according to demand.

Vascular pattern in the pancreas of the cat.

The pathways of microcirculation in the pancreas of the cat were investigated by scanning electron microscopy of Mercox preparations of the vascular bed. A portal system from islet to exocrine vessels as well as a direct arterial flow to the exocrine pancreas have been observed. Sphincters appear to exist in portal capillaries at the border between the endocrine and exocrine portions of the pancreas. Islets possess an independent venous drainage.

Cell types of the endocrine pancreas in the shark Scyliorhinus stellaris as revealed by correlative light and electron microscopy.

In the pancreas of Scyliorhinus stellaris large islets are usually found around small ducts, the inner surface of which is covered by elongated epithelial cells; thus the endocrine cells are never exposed directly to the lumen of the duct. Sometimes, single islet cells or small groups of endocrine elements are also incorporated into acini. Using correlative light and electron microscopy, eight islet cell types were identified: Only B-cells (type I) display a positive reaction with pseudoisocyanin and aldehyde-fuchsin staining. This cell type contains numerous small secretory granules (diameter 280 nm). Type II- and III-cells possess large granules stainable with orange G and azocarmine and show strong luminescence with dark-field microscopy. Type II-cells have spherical (diameter 700 nm), type III-cells spherical to elongated granules (diameter 450 x 750 nm). Type II-cells are possibly analogous to A-cells, while type III-cells resemble mammalian enterochromaffin cells. Type IV-cells contain granules (diameter 540 nm) of high electron density showing a positive reaction to the Hellman-Hellerström silver impregnation and a negative reaction to Grimelius' silver impregnation; they are most probably analogous to D-cells of other species. Type V-cells exhibit smaller granules (diameter 250 x 500 nm), oval to elongated in shape. Type VI-cells contain small spherical granules (diameter 310 nm). Type VII-cells possess two kinds of large granules interspersed in the cytoplasm; one type is spherical and electron dense (diameter 650 nm), the other spherical and less electron dense (diameter 900 nm). Type VIII-cells have small granules curved in shape and show moderate electron density (diameter 100 nm). Grimelius-positive secretory granules were not only found in cell types II and III, but also in types V, VI, and VII. B-cells (type I) and the cell types II to IV were the most frequent cells; types V to VII occurred occasionally, whereas type VIII-cells were very rare.