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Biomedical subjects

D Lubach

Publications and source records attributed to D Lubach.

At least 19 recordsLinked to original sources
PubMed1999

Suramin blocks hepatitis C binding to human hepatoma cells in vitro.

It was demonstrated recently that the binding of dengue virus to its target cell receptor could be effectively blocked by both heparin and by the polysulphonate pharmaceutical, Suramin [Chen et al. (1997) Nature Medicine 3:866-871]. Because both dengue and hepatitis C virus (HCV) belong to the Flaviviridae and because the HCV envelope is predicted to possess a heparin-binding motif, we tested heparin, Suramin, and a number of other polyanionic compounds for their ability to block HCV binding in vitro. The compounds, at concentrations ranging from 0.5 to 5,000 microg/ml, were tested using the human hepatoma cell line HepG2 cultured under conditions designed to enhance hepatocyte differentiation. Cells were harvested at 2 weeks postinoculation and HCV-RNA was quantified by means of a chemiluminescent reverse transcription polymerase chain reaction (PCR) assay. Suramin was found to be capable of blocking HCV binding in this system at a concentration similar to that reported to be effective against dengue virus. Removal of the viral envelope by treatment with chloroform also prevented HCV infection. Neither chondroitin sulphate nor the Suramin analogue CPD14 were able to block HCV under these conditions.

Carcinoma, Hepatocellular↗
PubMed1997

Classification of Sneddon's syndrome.

BACKGROUND: The combination of generalized broken ("racemose") livedo and cerebrovascular accidents is referred to as "Sneddon's syndrome". Although several pathogenetic factors have been suggested the aetiology of Sneddon's syndrome is unknown. Furthermore, considerable variability of patient characteristics gives rise to the question whether "Sneddon's syndrome" denotes a homogeneous disease entity at all. We hypothesized that the diagnosis "Sneddon's syndrome" can be broken down into different subgroups according to possible aetiologic factors. PATIENTS AND METHODS: Thirty-two patients with the combination of generalized broken livedo and cerebrovascular accidents were evaluated by clinical examination, routine diagnostic procedures, MRI of the brain, echocardiography, vascular ultrasound, immunologic and haemostaseologic testing. Patient groups were formed, depending on (1) whether or not an additional feature with a possibly aetiologic role for Sneddon's syndrome was present, and (2) which kind of feature it was. RESULTS: In 16 out of 32 patients, diagnostic features with an implication for the pathogenesis of Sneddon's syndrome could be identified. An autoimmune disorder was diagnosed in six patients. A thrombophilic state was detected in six patients. Three patients had preexisting atherosclerosis. One patient suffered from an embolizing atrial myxoma. Extent and kind of cerebral pathology differed between patient groups as did the kind of cardiac involvement. CONCLUSION: Sneddon's syndrome is not a homogeneous disease entity. Patients should be classified as "primary Sneddon's syndrome" if no aetiologic factor can be detected. On clinical grounds, this from differs from several varieties of "secondary Sneddon's syndrome" which occurs mainly as part of an autoimmune disorder or in a thrombophilic state.

Adult↗
PubMed1996

Neuropsychological deficits in patients with Sneddon's syndrome.

The results of a neurological, neuropsychological and MRI study of the brain in 21 patients (aged 18-59 years) with Sneddon's syndrome are reported. The predominant findings were marked neuropsychological deficits in two-thirds of the patients. While sensorimotor deficits after stroke in these patients had a good prognosis, neuropsychological deficits persisted. Of the 21 patients, 14 were incapable of gainful employment, 10 because of severe cognitive dysfunction.

Adult↗
PubMed1996

Recent findings on the angioarchitecture of the lymph vessel system of human skin.

The regional distribution of initial (i.e. most peripheral) lymph vessels of the human skin is unknown. New methods permit a precise systematic determination of the density of initial lymph vessels in every region of the dermis. Based on 202 skin specimens, it was possible to investigate the density of the lymph vessels of the skin derived from head, neck, upper arm, forearm, upper and lower leg. In all regions there seem to be a uniform structured dense subpapillary network and a wide meshed deep dermal network. The lymph vessels are at their most dense in the skin of the head.

Anthropometry↗
PubMed1995

Skin atrophy induced by initial continuous topical application of clobetasol followed by intermittent application.

BACKGROUND: The most frequent side effect of a long-term topical corticosteroid therapy is skin atrophy. To avoid or to reduce atrophy often an initial continuous application is followed by an intermittent maintenance therapy. OBJECTIVE: In this study we measured the skin thickness before and after the two-phase application schedule with the superpotent topical steroid clobetasol propionate (CP). For 16 days CP samples were applied twice daily on the test areas of 12 volunteers (phase 1). Then CP was applied to the same skin areas in accordance with the following timing: every 5th day, every 7th day, every 10th day, every 14th day (phase 2). Phase 2 lasted for 45 days. During the entire period of the study the skin thickness was measured regularly by the skin compression and thickness method as described previously. RESULTS: It could be seen that in phase 1 the skin became about 15% thinner. In phase 2 the steroid-induced skin thinning was approximately the same when CP was applied every 5th or 7th day. The skin thickness reached a more or less normal level when CP was applied every 10th day. After the 14th day a completely normal level was found. By measuring the skin thickness every day it was further shown that the skin thinning process lasted for 3 days when CP was applied once only. CONCLUSION: These results demonstrate that skin thinning must be expected by an intermittent maintenance therapy applied at relatively short intervals. The longer the intervals, the weaker the skin thinning. Moreover, these investigations showed that the skin thinning effect after a single CP application persists for nearly 3 days.

Administration, Topical↗
PubMed1993

The isolated perfused bovine udder as an in vitro model of percutaneous drug absorption. Skin viability and percutaneous absorption of dexamethasone, benzoyl peroxide, and etofenamate.

Using udders from slaughtered cows as a new in vitro model of percutaneous drug absorption, the tissue viability and the percutaneous absorption of dexamethasone, benzoyl peroxide, and etofenamate were studied. The organ was perfused with gassed tyrode solution for up to 6 hr. As shown by measurement of glucose consumption, lactate production, lactate dehydrogenase activity, and pH in the perfusate, the tissue was viable over a 6-hr period. This was confirmed by a histological examination. Determination of the udder skin-fold thickness demonstrated that no edema developed within the perfusion period. A maximum skin penetration of dexamethasone was found after administration of dexamethasone dissolved in acetone with dimethyl sulfoxide, followed by ointment with salicylic acid, ointment without salicylic acid, and acetone solution. Experiments with benzoyl peroxide and etofenamate demonstrated that the perfused udder skin was capable of metabolizing drugs in vitro. In conclusion, the isolated perfused bovine udder is a new in vitro model, which maintains bovine udder skin with an isolated vasculature in a viable state. Using this in vitro model, we note it is possible to compare the dermal penetration, metabolism, and absorption of substances after topical administration of different drug formulations.

Animals↗
PubMed1992

Localization of fibronectin in the initial lymphatics and blood vessels of normal human skin: an immunoelectron microscopic investigation.

The initial lymphatics of the human skin do not possess a basal lamina, but a subendothelial fibrous network, of which we do not know the biochemical and immunohistological composition. We investigated the wall of blood vessels and initial lymphatics in normal human skin for the presence of fibronectin by immunoelectron microscopy. We found discontinuous linear subendothelial diaminobenzidine (DAB) reaction products in both blood vessels and lymphatics. In addition fibronectin could be found at the anchoring fibrils of the initial lymphatics.

Adult↗
PubMed1992

Ultrastructural studies on the invasion of melanomas in initial lymphatics of human skin.

The way in which melanoma cells invade the initial lymphatics of the skin was investigated in this study. Samples of sixty melanomas were examined by transmission electron microscopy. Tumor cells invading lymph vessels were demonstrated in 20 specimens. In most cases the melanomas penetrated the subendothelial space as single cells. These fused with the endothelial cytoplasmic membrane and subsequently destroyed the endothelial wall.

Humans↗
PubMed1992

Effects of the phthalazinone azelastine on epidermal metabolism after mechanical skin irritation.

In female NMRI mice, the phthalazinone azelastine was administered orally once daily over 7 days. The drug influenced the epidermal thymidine triphosphate and amino acid incorporation rates at doses between 1 and 5 mg/kg. In control mice, an epidermal hyperproliferation induced by abrasion of superficial epidermal layers was characterized by enhanced prostaglandin and leukotriene concentrations in epidermal homogenate, an increase in thymidine triphosphate and amino acid incorporation and an increase in epidermal thickness. In mice treated with 1 mg/kg azelastine HCl, this epidermal reaction was changed. Compared to controls, the increase in leukotriene concentration was diminished, and that of prostaglandins was enhanced. The incorporation of thymidine triphosphate and of amino acids as well as the epidermal thickness and the ratio cell count/epidermal thickness were increased in irritated skin of azelastine-treated mice. In conclusion, azelastine influences the epidermal metabolism in irritated and unirritated skin. Therefore, a beneficial role of this phthalazinone in the treatment of psoriasis and related skin disorders seems to be possible.

Administration, Oral↗
PubMed1992

Steroid-induced dermal thinning: discontinuous application of clobetasol-17-propionate ointment.

The skin thinning effect of discontinuous topical clobetasol-17-propionate applications was tested in human volunteers. Application frequencies were daily (1/0), every third day (1/2), every fifth day (1/4), every seventh day (1/6) and every ninth day (1/8). Clobetasol-17-propionate was administered topically under occlusion for 1 h. The treatment period was 41 days. There were no differences of the skin thinning effect of daily and 1/2 administration. The skin thinning effect of 1/4, 1/6 and 1/8 was smaller but also significant compared to controls. The curves demonstrating skin thinning effects initially were dropping off and reached a plateau within about 2 weeks. After finishing application, skin thickness normalized within 2 weeks. Because of these findings, a treatment interval of 3 days is discussed as therapeutically efficient.

Administration, Topical↗
PubMed1992

Wet working conditions increase brittleness of nails, but do not cause it.

The incidence of brittle nails is higher in women than in men. Repeatedly a suspected cause for the higher incidence of brittle nails in women is the frequent exposure to water. This study was aimed at clarifying whether wet working conditions increase the incidence of brittle nails in women and men in a similar degree. We determined the incidence of brittle nails in 511 persons in professions that involve frequent hand contact with water. The data were compared to those of a large, non-selected control group. 50% of the female probands showed the sign of brittle nails (control group: 30.4%, p less than 0.05). Only 13.5% of the male test persons of this study had brittle nails; the difference to the control group (13.2%) was not significant. It is discussed that in women the bridges between nail corneocytes are possibly weaker than in males as a constitutional characteristic. Accordingly, frequent alternating periods of hydration and drying increase the incidence of brittle nails particularly in women.

Adolescent↗
PubMed1992

[Effect of etretinate on the activity of intestinal disaccharidases].

The retinoid etretinate influences the proliferation and differentiation of epithelial cells. Therefore, the activity of disaccharidases maltase and sucrase was measured in duodenum and jejunum after oral retinoid application to female mice. The enzymes are localized in the brush border of differentiating mucosal cells. The etretinate dose ranged from 0.1 to 1 mg/kg. The treatment with etretinate induced a decrease of the duodenal and jejunal disaccharidase activity. A correlation between the influence in intestinal enzyme activity and undesired gastrointestinal side effects which were described by GOLD et al. (1988) is supposed.

Animals↗
PubMed1991

Sneddon's syndrome and pregnancy; a case report.

The diagnostic and therapeutic problems posed by Sneddon's syndrome are discussed with reference to the case of a 31-year-old pregnant woman. This patient developed episodes of cerebral ischemia with multiple neurological deficits in the 24th week of pregnancy. The symptoms were associated with the dermatological signs of livedo racemosa. Delivery by Cesarean section in the 36th week of pregnancy resulted in marked improvement of the neurological signs and symptoms.

Adult↗
PubMed1991

Histological demonstration of initial lymphatics in human skin: comparison between different extension techniques.

Initial lymphatic vessels (IL) are difficult to demonstrate histologically in excised normal skin, as they are usually completely collapsed. In this report three different methods (vacuum extension, large traction extension, and small traction extension) are described by which human skin specimens can be mechanically extended. After extension specimens were Epon enbedded and the IL counted and their diameters measured. The greatest number of lymphatic vessels was found in specimens extended by vacuum, and the smallest number in small specimens extended by traction. The highest density of lymphatic vessels was found 50-300 microns below the epidermis. Our data reveal that vacuum extension is useful for investigating questions concerning the topography of IL, whereas preparations extended by traction are more suitable for obtaining information about single lymphatic vessels.

Adult↗
PubMed1991

Demonstration of initial lymphatics in excised human skin using an extension technique and dye injection.

Using a newly developed technique (extension technique) we succeeded in presenting dermal lymph vessel networks by subepidermal injection of an aqueous Berlin blue solution in excised human skin. Of 94 skin specimens taken from the safety margin of excised melanomas it was possible to demonstrate 32 networks and 14 single dermal lymph vessels. The networks can be documented by macroscopic photographs. Acetic fixation enables us to produce transparent preparations suitable for investigations with a stereo-microscope. The technique described here for macroscopically demonstrating dermal lymph vessels makes it possible to investigate systemically structural variations of lymph vessel networks in human skin.

Acetates↗
PubMed1991

Incorporation of tritiated thymidine, leucine and histidine in murine tail epidermis after skin irritation (histoautoradiography).

Thymidine incorporation into epidermal DNA as well as leucine and histidine incorporation into epidermal protein were studied by histoautoradiography in female mice tail epidermis. Prior to in vitro incubation of skin samples with labelled precursors, tail skin was irritated mechanically by rubbing with fine sand paper, chemically by repeated topical administration of n-hexadecane and by feeding an essential fatty acid deficient diet. After these skin irritations, an increased thymidine labelling index and skin thickening were found. Leucine was shown to be incorporated into protein predominantly in basal epidermal cell layers, while histidine was incorporated predominantly in the granular layer. Especially after mechanical skin irritation, this difference was obvious.

Alkanes↗
PubMed1991

Inhibition of n-hexadecane-induced epidermal hyperplasia due to systemically administered ciclosporin.

Epidermal hyperplasia was induced in hairless mice (hr/hr) by topical n-hexadecane treatment of tail and back skin. Following this skin irritation, a granular layer developed in interfollicular regions of the tail epidermis. An increase of ornithine decarboxylase activity, of thymidine triphosphate incorporation into DNA and of amino acid incorporation into protein was found. Shown histologically and by measurement of the called biochemical parameters, ciclosporin (cyclosporin A, CAS 59865-13-3; pretreatment with 30 mg/kg b.w. per day subcutaneously for 7 days) inhibited the development of epidermal hyperplasia in back and tail epidermis.

Alkanes↗