Search

In spite of tremendous scientific effort, the mechanisms underlying multiple sclerosis (MS) still remain to be elucidated. The prevalent pathogenetic concept adheres to the assumption of a strict hierarchical sequence of the triad inflammation, demyelination and axonal damage. However, recent studies have provided evidence that axonal pathology can occur independently of inflammation and demyelination. The present article critically re-evaluates the traditional paradigm of MS pathology. Potential cellular, humoral and metabolic mechanisms of axonal pathology are delineated and the development of isolated axonal damage is assessed. A better understanding of the pathological processes underlying MS is likely to result in an improvement of current therapeutic strategies. These should not only target the inflammatory, but also the neurodegenerative component of the disease.

In spite of keen clinical and neuroscientific interest, the aetiology and immunopathology of multiple sclerosis (MS) remain to be elucidated. The present work seeks to give insight into the important, but thus far underestimated contribution of B cells to the disease. Emphasis will be placed on the role of B cells as producers of autoantibodies and as antigen presenting cells. In addition, the development of ectopic B cell follicles in the CNS and their potential correlation with the course of the disease and MS severity will be discussed. Finally, regulatory functions of a B cell-dependent immunopathology should be mentioned. A better understanding of the complex pathomechanisms of MS will allow for therapeutic options that are causative. Potential targets of a B cell-oriented therapy will be delineated in the following review. We hereby aim at triggering a critical re-evaluation of traditional paradigms assigned to MS, appreciating the importance of B cells in the disease.

Zusammenfassung Gegenstand und Ziel: Für die Therapie von orthopädischen Erkrankungen wie Sehnenläsionen werden mesenchymale Stammzellen therapeutisch genutzt. Da den Pferden vor der Stammzelltherapie routinemäßig nichtsteroidale Antiphlogistika (NSAID) verabreicht werden, war es das Ziel dieser Studie zu untersuchen, wie sich diese Substanzen unter Zellkulturbedingungen auf die mesenchymalen Stammzellen hinsichtlich Vitalität, Proliferation und Differenzierung auswirken. Mate - rial und Methoden: Nach Inkubation der mesenchymalen Stamm - zellen (MSC) mit den NSAID Flunixin, Phenylbutazon und Meloxicam wurden Vitalität, Proliferationsrate und Wachstum der MSC geprüft. Durch Kultivierung der MSC in Medien für die adipogene, chondrogene und osteogene Differenzierung wurde mittels histologischer Nachweismethoden auch der Einfluss der NSAID auf die Differenzierungskapazität beurteilt. Ergebnisse: Von den in therapeutisch relevanten Konzentrationen eingesetzten NSAID konnte ausschließlich Flunixin eine Verlängerung der Generationszeit und damit eine Verminderung der Proliferationsrate induzieren. Darüber hinaus wurde insbesondere durch Flunixin und Metacam das osteogene Differenzierungspotenzial inhibiert, während die adipogene und die chondrogene Differenzierung durch alle drei NSAIDs unbeeinflusst blieb.Schlussfolgerung: Die hier verwendeten NSAID haben abgesehen von Flunixin keinen negativen Einfluss auf Vitalität und Proliferation. Die osteogene Differenzierung der Stammzellen unterliegt großen Schwankungen, was frühere Daten bestätigt. Klinische Relevanz: Die Auswahl der in der Pferdepraxis üblicherweise verwendeten NSAID muss in Zusammenhang mit einer Stammzelltherapie kritisch hinterfragt werden. Von einer Vorbehandlung mit Flunixin ist eher abzusehen.

Human synovial membrane was studied by light- and electronmicroscope and histomorphometrically. Areas of distinct structures are seen. The surface structure fold that is mainly seen in the areaolar and adipose synovial membrane type, seemed to be the prime structure for the synovial turn over. Villi have fenestrated capillaries and they are covered of A- and AB-synoviocytes. Villi are regarded as the synovia production areas. The fibrous type of the synovial membrane is mostly smooth surfaced and seemed to be an ordinary fibrous connective tissue. The B-synoviocyte is discussed as fibrocyte.

In spite of tremendous scientific effort, the mechanisms underlying multiple sclerosis (MS) still remain to be elucidated. The prevalent pathogenetic concept adheres to the assumption of a strict hierarchical sequence of the triad inflammation, demyelination and axonal damage. However, recent studies have provided evidence that axonal pathology can occur independently of inflammation and demyelination. The present article critically re-evaluates the traditional paradigm of MS pathology. Potential cellular, humoral and metabolic mechanisms of axonal pathology are delineated and the development of isolated axonal damage is assessed. A better understanding of the pathological processes underlying MS is likely to result in an improvement of current therapeutic strategies. These should not only target the inflammatory, but also the neurodegenerative component of the disease.

In spite of keen clinical and neuroscientific interest, the aetiology and immunopathology of multiple sclerosis (MS) remain to be elucidated. The present work seeks to give insight into the important, but thus far underestimated contribution of B cells to the disease. Emphasis will be placed on the role of B cells as producers of autoantibodies and as antigen presenting cells. In addition, the development of ectopic B cell follicles in the CNS and their potential correlation with the course of the disease and MS severity will be discussed. Finally, regulatory functions of a B cell-dependent immunopathology should be mentioned. A better understanding of the complex pathomechanisms of MS will allow for therapeutic options that are causative. Potential targets of a B cell-oriented therapy will be delineated in the following review. We hereby aim at triggering a critical re-evaluation of traditional paradigms assigned to MS, appreciating the importance of B cells in the disease.

Es gibt Hinweise darauf, dass epikardiales Fett (Epi) ahnliche Eigenschaften wie abdominales Fett aufweist und in der Lage ist, pro-inflammatorische Zytokine und Fettsauren in die koronare Strombahn freizusetzen. Damit ware eine ahnlich direkte Interaktion zwischen Epi und dem Herz als Zielorgan moglich, wie sie fur das abdominale Fett und die Leber diskutiert wird. Unsere Hypothese geht deshalb davon aus, dass Diabetes Typ 2 und andere Insulin-resistenten Zustande das Muster und die Menge der Sekretionsprodukte (Zytokine, Fettsauren) des Epi modifizieren und dadurch zur Entwicklung von Insulinresistenz im Herzen, zur kardialen Dysfunktion und zum im Diabetes erhohten kardialen Risiko beitragen. Ein geeignetes experimentelles Modell um die spezifischen Wechselwirkungen zwischen Epi und dem Herzen zu untersuchen, wurde bisher nicht beschrieben. Bekannt ist aber, dass es im Meerschweinchen ahnlich wie bei Mensch und Affe zur Anreicherung von Epi in Abhangigkeit von Ernahrung und Alter kommt. Um die Eignung des Meerschweinchenherzens als Model zu untersuchen, wurden in einem ersten Ansatz die Freisetzung und Synthese von Zytokinen durch Epi im Vergleich zu subkutanem Fett (Sc) mit einer Array Technik untersucht. Beide Gewebe synthetisieren ein breites Spektrum an pro- und anti-inflammatorischen Zytokinen (>50). Im Epi uberwiegen Leptin, Eotaxin 3, Fraktalkalin, BDNF, IL1a, MDC, IGFBP1, 2 und 4, FAS, TIMP 2, Adiponektin, Angiopoietin 2, GCSF und bFGF. Abhangig vom Alter und der Menge an EPi wird nicht nur eine vermehrte Freisetzung von Zytokinen beobachtet, sondern das Spektrum der sezernierten Zytokine verschiebt sich pro-inflammatorisch. Morphologisch liegt ein hoher Anteil von Epi dem Myokard auf; ein wesentlicher Anteil durchzieht aber auch die epikardialen Muskelschichten, die dadurch eine aufgelockerte Schichtung erfahren. Zusatzlich akkumuliert ein erheblicher Teil entlang der grosen Gefase und an der Herzspitze. Mit der Zunahme an Epi sind das flachenartige Auftreten von perivaskularem und interstitiellem Kollagen und die vermehrte Ablagerung von Grundsubstanz (Vorstufe zur Kollagenablagerung) assoziiert. Die Muskelzelle und die Zellen des parasympathischen Nervensystems erscheinen demgegenuber unauffallig. Die morphologischen Veranderungen legen nahe, dass es in Abhangigkeit von der Menge an Epi zur Beeintrachtigung der myokardialen Struktur kommt und Defekte der diastolischen Dysfunktion und beim venosen Abfluss auftreten. Trotz der morphologischen Unauffalligkeit weist der Herzmuskel biochemisch charakteristische Auffalligkeiten auf: mit zunehmendem Epi und Alter werden die 12-Lipoxygenase, Calreticulin, der Glucosetransporter 4 sowie PPARa down-reguliert. Diese Veranderungen stellen erste Hinweise auf die Entwicklung von Storungen des Glucosestoffwechsels und der Calcium-Homoostase dar.

BACKGROUND: Myocardial edema is a common finding in congestive heart failure, transplant rejection, and cardiomyopathy. Although pathological alterations in the lymphatic morphology are part of the underlying disease, knowledge on these changes is limited. However, lymphatic morphology may be investigated by immunohistochemical staining for fms-like tyrosine 4 kinase (flt-4), which is specific for lymphatic endothelium in adult tissue. METHODS: We used myocardial tissue of ventricular out flow tract taken from five human semilunar valves harvested as allografts but unsuitable for implantation for analysis, performing immunohistochemical staining for flt-4 with a commercially available antibody. Lymphatic morphometry was completed according Gundersen method. RESULTS: Immunohistochemical staining for flt-4 resulted in successful labeling of lymph capillaries in adult human myocardium. Lymph capillary density was calculated as 50.7 +/- 12.5 per mm2 and average diameter was 3.7 +/- 0.7 microm. Conclusions. Lymph capillary morphology in human myocardium may be successfully determined by immunohistochemical staining for flt-4. Tissue samples as small as myocardial biopsies may be used for analysis. Using this method, morphological changes in myocardial lymphatics may be investigated in various cardiovascular diseases.

The aim of this investigation was to assess new information concerning the capacity of transplanted embryonic stem cell (ESC)-derived neuronal cells to migrate into host brain and to evaluate these cells as a possible source for cell replacement therapy in neurodegenerative disorders such as Parkinson's disease (PD).The authors investigated the ability of ESC-derived neural precursor cells to migrate and differentiate in a host striatum by using a D3-derived ESC clone that was transfected stably with a chicken beta-actin cytomegalovirus enhancer-driven green fluorescent protein (GFP)-labeled construct. This procedure allowed easy monitoring of all transplanted cells because of the green fluorescent labeling of donor cells. This approach also afforded easy estimation of cell integration and simultaneous observation of the entire transplanted cell population in relation to immunocytochemically identified neuronal and glial differentiation. After selection of nestin-positive neural precursor cells in a synthetic medium, they were implanted into the striatum of male adult Wistar rats. Their integration was analyzed on morphological studies performed 3 days to 4 weeks posttransplantation.The investigators found that after transplantation, a subpopulation of GFP-labeled cells differentiated into various neural morphological types that were positive for the mouse-specific Thy-1 antigen, which is known be expressed on neurons, as well as being positive for the astroglial marker glial fibrillary acidic protein. Moreover, GFP-expressing cells that were negative for either of these markers remained close to the injection site, presumably representing other derivatives of the neural lineage. Together, these findings contribute to basic research regarding future transplantation strategies in neurodegenerative diseases such as PD.

BACKGROUND Concomitant application of anabolic-androgenic steroids and physical exercise can induce cardiac hypertrophy. These experiments investigate the still unknown response of the cardiac myocytes and capillaries to the combined influence of various anabolic steroids and muscular exercise. METHODS Female SPF-NMRI mice were divided into the following groups: a) sedentary control, b) exercise (treadmill running); c) sedentary receiving Dianabol; d) exercise + Dianabol; e) exercise + Oral-Turinabol. After 3 and 6 weeks the left ventricular papillary muscles were studied morphometrically. Evaluated variables: minimal myocyte diameter, number of capillaries around a single myocyte, capillary density and intercapillary distance. RESULTS Only the anabolic steroids + exercise groups showed a mild myocyte hypertrophy. In contrast, only exercise alone caused a significant increase of the capillary density after both experimental periods; e.g. capillary density after 6 weeks (capillaries/mm2, mean values +/- standard deviation, p < 0.05): control (4,272 +/- 287), exercise (5411 +/- 755), dianabol (4,004 +/- 333), dianabol + exercise (4,076 +/- 403), oral-turinabol + exercise (4,053 +/- 306). Moreover, unlike all other regimens, only exercise alone shortened the intercapillary distance. Finally, exercise without drugs induced the greatest increase in the number of capillaries around a single myocyte. CONCLUSIONS Anabolic steroids combined with exercise: 1) induce mild hypertrophy of the cardiac myocytes, 2) impair the cardiac microvascular adaptation to physical conditioning. The microvascular impairment may cause a detrimental alteration of the myocardial oxygen supply, especially during muscular exercise.

Nitric oxide (NO) can play an important role in the regulation of vascular tone and neurotransmission, as well as in non-specific immunoreactions and inflammation in a variety of tissues. Increased quantities of nitric oxide in respired air can be measured during inflammatory processes. However, the exact role and precise sources of NO under physiological and pathophysiological conditions within the airways remain to be defined. Three isoforms of NO-synthases can be distinguished: two constitutive (neuronal and endothelial) Ca(2+)-dependent cNOS and one inducible Ca(2+)-independent iNOS (NOS II). Constitutive NOS (NOS I and III) release a basal amount of NO under physiological conditions. The inducible form once expressed can catalyse the generation of large quantities of NO. Many kinds of cells, such as macrophages, neutrophils, endothelium and smooth muscle cells, are capable of expressing NOS II. Since all isoforms of NO-synthase seem to be present in nasal tissues and the expression of iNOS under inflammatory conditions seems to be responsible for excessive production of NO, the distribution of NOS-isoforms (especially NOS II) in normal and inflammatory nasal tissue, as well as the exact requirements for expression of iNOS remain to be proven. Non-inflamed fresh human nasal mucosa from the middle turbinate was compared immuno-histologically with nasal mucosa having the typical findings of chronic polypoid rhinosinusitis (i.e., polypoid middle turbinates and polyps of the middle nasal duct). In order to gain more information about the mechanisms of acute inflammation, non-inflamed vital turbinates were incubated in vitro with the proinflammatory substances bacterial lipopolysaccharides (LPS) and tumor necrosis-factor (TNF) for 30, 60, 90, 120, 180 and 240 min. Subsequent to exposure to NADPH-diaphorase and immunostaining with specific antibodies to each NOS-isoform, clearly increased or initiated expressions of inducible NOS (iNOS) in blood vessels, glands, macrophages and epithelium of chronically inflamed and LPS-incubated nasal tissue became apparent in comparison to the non-inflamed controls. In contrast, NOS III/NOS I seemed to be not affected. The onset of immunohistochemically recognizable NOS II expression was observed after 90 min incubation with of LPS/TNF-alpha. Polypoid tissue showed a strong increase in submucosal thickness and a high infiltration of iNOS-positive leukocytes (granulocytes and macrophages) compared to the LPS-incubated non-inflamed specimens. These findings implicate NOS II generated nitric oxide as a key agent for causing swelling, secretion and obstruction in patients with acute and chronic polypoid or allergic rhinitis. These findings also suggest that molecular NO has to be considered in the pathophysiology of chronic polypoid rhinosinusitis.

It has recently been suggested that, in addition to nitric oxide (NO), carbon monoxide (CO) is an important gaseous messenger which might be involved in vertebrate olfactory transduction because its effects include activation of guanylyl cyclase and the formation of cGMP. As there is no information regarding the presence of heme oxygenase-2 -- the constitutive isoform of the heme oxygenase system -- in olfactory neurons of non-rodent species, we have investigated the distribution pattern of heme oxygenase-2 in the olfactory epithelium of the bovine, a representative of macrosmatics. Localization of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity of the olfactory epithelium was compared with heme oxygenase-2 and NO synthase (NOS) immunoreactivities in order to obtain possible hints at functional significance. NADPH-d activity was particularly intense in apical dendrites of receptor neurons. It was also found in Bowman glands and intraepithelial duct cells. Less intense, discrete NADPH-d activity was present also at intermediate and basal levels of the olfactory epithelium, corresponding to the layer of receptor neuron somata and basal cells. While heme oxygenase-2 activity mainly occurred in neuronal perikarya, a very intense NOS immunoreactivity, exclusively for the inducible isoform, was detected in the apical dendrites. Ultrastructurally, NADPH-d histochemistry showed distinct labelling of membranes, in particular of endoplasmic reticulum, mitochondria and nucleus. The coincident localization of the moderate NADPH-d activity and heme oxygenase-2 immunoreactivity in receptor cell perikarya suggest a functional association between NADPH-cytochrome P450 reductase and heme oxygenase-2. In contrast, dendritic localization of NADPH-d activity is topically and possibly functionally related to the presence of the inducible isoform of NOS. The results suggest that both CO and NO may be generated in bovine receptor neurons and thus involved in odorant stimulation. Based on immunocytochemical localization of synthesizing enzymes, NO might be regarded as a direct regulator of transduction related processes while CO might act as a modulator of the initial signal.

In this study, the effect of endotoxin on the guinea pig cochlea has been examined electrophysiologically and immunohistochemically. Bacterial lipopolysaccharide (LPS, 5 mg/ml, 0.2 ml) was injected into the middle ear trans-tympanically. The electrocochleograms were measured before, immediately upon, and 3, 6 and 12 h after the injection continuously with an electrode inserted into the facial canal. After each measurement, some of the animals were killed with an intracardiac perfusion of fixative, temporal bones were removed and were immunohistochemically examined for inducible nitric oxide synthase (iNOS/NOS II). On serial paraffin section, iNOS could be detected first after 3 h in the lateral wall, the supporting cells of the organ of Corti and in cells of the spiral ganglion and was observed up to 12 h. After the injection of LPS, the threshold of compound action potential became significantly worse after 12 h in the LPS group. These changes became evident first at higher frequency (8 kHz). These results suggest that iNOS-generated NO is involved in the cochlea dysfunction under inflammatory conditions.

Based on the idea of differentiation-related changes in the glycosylation pattern of neurons, the expression of two cell surface oligosaccharide epitopes, N-acetyl-lactosamine (NALA), and its sulpho-glucuronyl derivative (HNK-1), was studied, by immunohistochemistry and Western blot experiments, in the developing chick retina beginning on day 2 of incubation (E2) until day 18 post-hatching. NALA was detectable on neuroepithelial cells as soon as the primary optic vesicles formed, and this pattern continued until E3. During subsequent retinal development NALA expression became progressively restricted in concert with the appearance of postmitotic neurons as revealed by neurite outgrowth, and with the formation of synaptic contacts until it disappeared at the end of the incubation period. The pattern of NALA expression was the inverse of HNK-1 which was detected for the first time at E3 on postmitotic ganglion cells accumulating at the vitreal surface. The number of HNK-1+ cells steadily increased until around E10, when the entire neural epithelium was labelled. Synchronously to synaptogenesis, most neurons lost their HNK-1 immunoreactivity. At the time of hatching the adult-like pattern was found, characterised by subpopulations of labelled horizontal, bipolar, amacrine, and ganglion cells. Immunoblot experiments demonstrated transient NALA glycosylation of protein bands, partially identical in their apparent molecular weight to those proteins with HNK-1 glycosylation. The observed temporospatial changes in the glycosylation patterns of distinct proteins during retinal development suggest NALA as a suitable marker for neuronal proliferation, and HNK-1 for differentiation and establishment of final synaptic configuration.

Based on in vitro studies, nitric oxide (NO) is reported to be involved in initial neuronal differentiation. In order to compare this finding with the situation in vivo, we have looked for the expression of the three NO synthase isoforms in the developing mouse vestibulocochlear system. From these isoforms only the inducible NOS II is expressed during inner ear development. Examination of a series of embryonic and early postnatal animals, up to postnatal day 6, reveals a maturation-dependent, monophasic expression of this isoform. Initial expression is observed by day 10 of gestation in nerve cells of the vestibolocochlear ganglion and on their fibres. By day 14 of gestation, these afferent fibres penetrate the epithelium of the prospective receptor fields making contact with early, differentiating immunoreactive cochlear hair cells and receptor cells of the macula and crista ampullaris. This receptor-cell-derived immunoreactivity vanished in differentiated sensory hair cells by postnatal day 6, when both the constitutive isoforms and subsequent activated members of the down stream second messenger cascade (guanylate cyclase/cGMP) of the adult mouse were not then detectable. The strict phasic expression of NOS-II, independent of the second messenger system mentioned above, implies that there is a unique role for the inducible NOS isoform in nerve cell differentiation, independent of the NO/guanylate cyclase/cGMP pathway.

Because earlier studies indicate that the choroid close to the ora serrata may have unique anatomic features such as wandering cells, blood vessels in Bruch's membrane, and accumulated pigment in the retinal pigment epithelium (RPE), the morphology of the normal human eye at the ora serrata region was investigated.Specimens from the ora serrata region of two normal human eyes (male donors, 48 and 52 years old) were investigated by light and electron microscope. Specimens from all quadrants were studied in one eye.The elastic layer of Bruch's membrane extended as far as 15 microm into the peripheral choroid; capillaries were included between the elastin layer and the RPE. Nasally, from the anterior end to 2 mm posterior of the ora serrata, the RPE cells contained more melanin than did those in the adjacent posterior region. Melanin granules in the RPE cells close to the ora either formed large clusters or appeared unusually small because of fragmentation. A unique, fine lamellar, membranous material with a fingerprint-like structure was found between the basal folds of the RPE. This material is also found within the extracellular matrix of the choroid and in association with red blood cells.The morphology of Bruch's membrane is varied near the ora serrata because capillaries and wandering cells are present in its outer collagenous layer. Unique, fine lamellar, fingerprint-like structures are extruded from the RPE and are removed from the eye together with red blood cells. Capillaries within the inner collagenous region of Bruch's membrane at the ora serrata may not necessarily represent a pathologic response but may be a normal characteristic of thick regions of Bruch's membrane.

Nitric oxide (NO) is suggested as an important mediator for the regulation of biological processes. In the present study we tried to determine histochemically and immunohistochemically the localization and distribution of the constitutive NO-synthase Isoforms (bNOS and eNOS) of 14 normal non-obstructive and 12 hyperplastic obstructive human prostates. Differentiated nitrinergic innervation was shown for the prostate glands, fibromuscular stroma and blood vessels by NADPH-diaphorase staining and immunohistochemically with specific NOS antibodies. In the specimens with benign prostatic hyperplasia nitrinergic innervation seems to be distinctly reduced. The vascular distribution of NOS provides evidence for segmental differentiation of NO-mediated vascular regulation. The NADPH-diaphorase reaction was not confirmed immunohistochemically by the specific NOS antibody in the glandular epithelium. The distribution of NO synthase shows the importance of nitric oxide in the regulation of smooth muscle tone, blood flow and secretory function in the normal and hyperplastic human prostate.

An endogenous NO-release which exceeds the basal endogenous NO-release has a regulatory effect on capillary microvasculature in isolatedly perfused rat hearts. The basal NO-release in contrast has no effect on capillaries. The functional findings are corresponding to the endothelial distribution of NOS in coronary vessels, which displays a lack of NOS in capillary endothelium. An increase of coronary flow by exogenously administered NO-donors does not necessarily lead to a dilation of capillary microvasculature. Local differences in the release of unstable NO by SNP and GTN are responsible for variations in effects. We can conclude: NO influences the dilation of the capillary microvasculature independently of flow regulation.

The permeability influencing effect of nitric oxide was studied by means of an isolated perfused mesentery preparation in combination with a intravital/fluorescence microscopic set up. As a fluorescent marker served FITC-dextran mol wt 70,000 daltons. Tissue treatment was performed by application of NO-donors like SNP or GTN. Additionally the effects of bradykinin, L-nitroarginine or the combination of both were tested in regard to a permeability modulation. The results point out that NO-donors did not enhance microvascular permeability, whereas the permeability increasing effect of bradykinin is mediated by an NO-independent pathway.

Ultrastructural differences between ganglia of the plexus submucosus internus (Meissner; PSI) and plexus submucosus externus (Schabadasch; PSE) are described. Comparison revealed a different glia index (ratio glia per neuron) between the PSE (3:1) and the PSI (1:1), the arrangement of PSI neurons in compartments and the appearance of broad membrane-to-membrane appositions inside the compartments of the PSI. Structural and immunohistochemical differences between the two plexuses are discussed. In general, PSE neurons show a wider variety in size and shape than most of the PSI neurons.

Epidemiological data reviewed suggest that diabetes itself increases the cardiac risk of diabetics (types I and II), independently from the development of coronary heart disease and in addition to other risk factors (hypertension, hypercholesterolemia, hypertriglyceridemia, smoking and others), presumably by a specific myocardial disease called "diabetic cardiopathy", or according to the recommendations of the WHO, "diabetic heart muscle disease." Disturbances of the left and right ventricular function as well as the autonomic function of the heart can be understood as signs of this specific cardiopathy. The pathophysiological mechanisms underlying this disease are not yet fully known; however, recent evidence is presented that diabetes leads to a facet of metabolic dysfunctions regarding glucose and energy metabolism, calcium homeostasis and the expression of specific proteins that diminish the ability of the heart to respond to increased workload and increase the vulnerability of the heart in diabetes. Since preliminary experimental data indicate that inhibitors of the angiotensin-converting enzyme can protect the heart in diabetes, it is intriguing to suggest that increased release of angiotensin II plays a significant role in the change from reduced adaptability to irreversible damage of the heart in diabetes.

In a comparative study the influence of periodontal disease on the autonomous nerve-system of human attached gingiva was analysed ultrastructurally in 20 gingiva specimens. The test group was formed by 10 patients with adult periodontitis (AP) and compared with 10 patients with clinically healthy gingiva. The specimens were prepared for ultrastructural evaluation. The autonomous nerve fibres near the epithelium, in the connective tissue, and at the blood vessels were qualified and quantified by means of electron microscopy. In the test group clear signs of neuropathy of the autonomous nerve system like lysis of axoplasm, evagination of axons from their Schwann's sheaths, de- and regeneration pistons and reduction of axons were found. The possible pathogenic significance of this neuropathy of the autonomous nerve system in periodontal disease is discussed.

Human synovial membrane was studied by light- and electronmicroscope and histomorphometrically. Areas of distinct structures are seen. The surface structure fold that is mainly seen in the areaolar and adipose synovial membrane type, seemed to be the prime structure for the synovial turn over. Villi have fenestrated capillaries and they are covered of A- and AB-synoviocytes. Villi are regarded as the synovia production areas. The fibrous type of the synovial membrane is mostly smooth surfaced and seemed to be an ordinary fibrous connective tissue. The B-synoviocyte is discussed as fibrocyte.

The innervation of the rabbit maxillary sinus mucosa has been studied with histochemical techniques, using the glyoxylic acid-induced fluorescence for the demonstration of catecholamines and the acetylcholinesterase method. A dense acetylcholinesterase-positive nerve plexus can be demonstrated around the secretory end-pieces, the efferent ducts, the blood vessels in the lamina propria, and rarely but regularly in the ciliated epithelium. A doubtless identification of these nerve fibres to be cholinergic does not seem possible. The adrenergic innervation is lacking within the epithelium, but can be seen near the muscle layers around blood vessels and in the lamina propria. An additional sympathetic control of the glandular activity is not excluded.

In the atrioventricular system (AVS) consisting of the compact node, the penetrating bundle and the branching bundles of about 250 bovine hearts there were made several studies: 1. In quickly removed and fixed specimens (distal AV-node, penetrating bundle) determination of a metabolic state with respect to glycogen, glucose, lactate, ATP, ADP, AMP, creatinephosphate, total creatine, gluc-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, dihydroxyacetonphosphate and pyruvate. 2. Determination of glycogen contents and glygolytic activity in AVS and its parts for ischemic times up to three hours. 3. The determination of metabolic contents in samples of connective tissue in atrium and ventricle of bovine hearts. The AV-nodes are poor in glycogen comparable with glycogen content of central nervous system and other ganglia. Penetrating bundles of Hiss and branching bundle belong after liver to the glycogen richest parenchyma of animal tissues. Even after ischemia of 3 h only a part of glycogen was recovered as lactate. The greater part of glycogen must be considered as a structural element of Hiss bundle and branching bundles of the ventricles.

Electron micrographs of cat aortic bodies were submitted to point-counting analysis to determine the volume/volume densities (vv%) of general tissue components. Paraganglia, enclosed by a perineural sheath (endoneural paraganglia), exhibit a significantly higher density of specific tissue elements (type-I cells, type-II cells, nerves) than those which covered by fibroblasts (exoneural paraganglia). Additional criteria which allowed distinction of these types of aortic bodies were not evident in this study. On average, type-I cells occupied 27.8 vv% if related to the entire organ, or 35.6 w% if related to the blood vessel-free space. Comparing our data with those reported for the carotid body, we found an about twofold amount of type-I cells within aortic bodies. The relevance of this finding is discussed with respect to the known different electrophysiological properties of carotid and aortic body arterial chemoreceptors.

In the rat SCG two types of paraganglionic cells have been identified immunohistochemically in a ratio of about 5% DBH-positive to 95% DBH-negative cells. Measurements of CAs in SIF cell clusters separated from principal neurons with the microlaser and using the technique of quantitative mass fragmentography disclosed the presence of E within paraganglionic cells, thus confirming the proposal that, besides DA, E also is stored in most cells. Following immobilization of adult rats, the majority of SIF cells revealed a time-dependent loss of formaldehyde-induced fluorescence intensity that could be ultrastructurally correlated with an increasing degranulation of small granule-containing perikarya, presumed to store DA and E. Similar results were obtained in type I cells of the rat carotid body and adrenal medullary cells, thus suggesting a mutual endocrine function. An additional interneuronal mode of modulation is assumed, since degranulated cells are capable of displaying efferent synaptic contact with postganglionic neurons. A minor cell population, storing granular vesicles similar to those in the NE-containing cells of the adrenal medulla, did not respond with degranulation to functional strain of the vegetative nervous system. Our results strongly corroborate the hypothesis that a functional dualism exists: Most paraganglionic cells can act as an interneuron and as an endocrine cell.

Electron micrographs of cat aortic bodies were submitted to point-counting analysis to determine the volume/volume densities (vv%) of general tissue components. Paraganglia, enclosed by a perineural sheath (endoneural paraganglia), exhibit a significantly higher density of specific tissue elements (type-I cells, type-II cells, nerves) than those which covered by fibroblasts (exoneural paraganglia). Additional criteria which allowed distinction of these types of aortic bodies were not evident in this study. On average, type-I cells occupied 27.8 vv% if related to the entire organ, or 35.6 vv% if related to the blood vessel-free space. Comparing our data with those reported for the carotid body, we found an about twofold amount of type-I cells within aortic bodies. The relevance of this finding is discussed with respect to the known different electrophysiological properties of carotid and aortic body arterial chemoreceptors.

Der aktive Bewegungsapparat, d. h. die Muskulatur, das Binde- und Stutzgewebe [12,18,21,25,26,29] sowie die Herzmuskulatur [3,4,5,10] sind in der Vergangenheit haufig Untersuchungsobjekte gewesen, um den Einflus der Steroidhormone auf Gewebestrukturen aufzuzeigen. Obwohl die Wirkung von Testosteronderivaten und anabolen Steroiden auf die Steigerung der zellularen Aktivitat seit langem bekannt sind [13,14,15,16,22,23], ist es um so erstaunlicher, das bisher keine Arbeit vorliegt, die die Wirkung von korperlicher Belastung und zusatzlicher Steroidhormonapplikation auf das vegetative Nervengewebe beschreibt.

The baroreceptor endings of the sinus nerve extend into the region of the external media, to the media-adventitia border, and into the adventitia of the wall of the carotid sinus. The size of the receptors, tightly filled with mitochondria, varies between 600 and 5,700 nm in diameter. The endings are accompanied by densely structured Schwann's cells, come into contact with the muscular-elastic system or are surrounded by the collagenous material of the vessel wall. This functional junction makes the reception of the tension in the vessel wall possible. Glycogen granules could be demonstrated in some axon endings. In kittens and older cats, numerous receptors were regularly found with various degrees of structural change: homogeneous and lamellar transformation of mitochondria, lamellar aggregates, lysis of axoplasm matrix, irregularities of tubules and vesicles. These modifications may be evaluated as the morphological expression of degeneration and regeneration processes. Physiological detrition is considered to be the cause for this.

In the dog, pressosensitive endings of the sinus nerve extend along the border between the adventitia and media of the carotid sinus wall. The axon endings, containing a great number of mitochondria, can be divided into small (600–2,000 nm) and large (6,000–8,000 nm) end swellings. In the terminal region the pressosensitive fibers are surrounded by ramified and highly structured Schwann “terminal cells”. The topographic location in relation to elastic and collagenous tissue indicates a functional relation between vascular wall and the activity of receptor tissue. A functional connection between receptors and efferent nerve endings in the immediate surroundings has been discussed in this report. Several axon endings contain variable amounts of glycogen which is regarded as an indication for the inactive metabolic state of the ending. Axonal swellings demonstrate considerable modification in structure, such as loss of structural integrity in mitochondria, the formation of lamellar fields, vesicular irregularities and disintegration of axoplasm, all of which are considered as the morphological expression of “wearing out”, degeneration and possibly regeneration.