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Biomedical subjects

T Krieg

Publications and source records attributed to T Krieg.

299 records · Page 17Linked to original sources
PubMed1976

[Accident in treatment of porphyria cutanea tarda by chloroquine (Resochin) (author's transl)].

About a 65-year old patient with the typical clinical and biochemical characteristics of porphyria cutanea tarda (Pct) is reported. After treatment with Resochin in an erroneously high dosage (1.250 mg instead of 125 mg) an acute crisis set in with a triple increase of porphyrin excretion, fever, tachycardia, hypertension and joint-discomfort. Despite the rise in excretion of total porphyrines in urine to approximately 18.00 mcg/l there was no change in the amount of the porphyrin precursors (ALA, PBG). The pattern of the porphyrin-metabolites (URO-, HEPTA,- HEXA-, PENTA-, COPRO-porphyrin)-expressed in rel.%-does not change during the excessive rise of porphyrin excretion. The duration Resochin-therapy could obviously not be shortened by an initial too high dosage of chloroquine. The mechanism of action of chloroquine in Pct is not clear. It is discussed that a change in the permeability of the liver mitochondria leads to a continuously increased excretion of porphyrin and to an exhaustion of the hepatic porphyrin pool.

Aminolevulinic Acid↗
PubMedDate not supplied

In vitro reconstituted skin as a tool for biology, pharmacology and therapy: a review.

Various culture procedures, suitable to maintain the differentiated phenotype of various types of cells in vitro, have been devised during the past decade. These culture systems use macromolecular components extracted from extracellular matrixes or synthetic polymers which provide cells with a three-dimensional, spatially structured support. Substantial information has come from the use of collagen lattices. Many types of cells, of mesenchymal or other origin, are able to organize collagen fibrils in these models and to form a connective tissue-like structure. Prerequisites for this process are active function of the cytoskeleton and the expression of alpha(2)beta(1) integrin collagen receptors. Interaction of cells with such a matrix has profound effects on morphologic status, proliferation, cellular metabolism, and state of differentiation. The in vitro procedures reviewed and described in this article offer the possibility to combine different types of cells to approximate the in vivo environment and to investigate such physiologic processes as cell-cell and cell-matrix interactions which are otherwise not easily accessible. In pathologic conditions of the skin, these models have proven to be useful tools in investigating diseases relating to impaired recognition of extracellular matrix structures or alterations of cytoskeletal assembly. In pharmacologic and toxicologic studies, activity of drugs and potentially useful therapeutic substances has been evaluated. The use of cells and matrix components derived from skin has lead to refined systems which could be adapted and extended to other organs in an attempt to better understand pathophysiologic mechanisms.

Journal Article↗
PubMedDate not supplied

Localization of platelet-derived growth factor receptor subunit expression in chronic venous leg ulcers.

Cellular responses to platelet-derived growth factor, which affects all phases of the wound healing process, are dependent on the interaction of the growth factor with its cell surface receptors. Recently, we have shown that the platelet-derived growth factor-receptor was not expressed in uninjured human skin. In acute human wounds healing by secondary intention, both platelet-derived growth factor-receptor subunits were coordinately expressed, whereas no expression was found after reepithelialization at day 47. Even though impaired wound healing may be due to uncoordinated expression or the failure to express platelet-derived growth factor-receptor subunits, little is known regarding their expression in chronic ulcers. We studied the localization of platelet-derived growth factor-receptor expression in chronic venous leg ulcers of 15 patients with a median age of 73 years. Cryostat sections of biopsy specimens were immunostained with the use of antibodies against the alpha- and the beta-platelet-derived growth factor subunits. RNA was extracted from biopsy specimens and subjected to Northern blot analysis with the use of oligolabeled complementary DNA for the platelet-derived growth factor-receptor. Platelet-derived growth factor-receptor alpha- and beta-subunit expression was found in fibroblast-like cells within the wound bed and in cells beneath the epidermis of the wound edge. Platelet-derived growth factor-receptor beta-subunit expression was detected in endothelial cells of the vessels, in the granulation tissue, and the wound edge, whereas platelet-derived growth factor-receptor alpha-subunit was not expressed in endothelial cells of the uninjured skin. This finding suggests that the platelet-derived growth factor alpha-subunit may be involved in vessel formation during tissue repair. Both platelet-derived growth factor-receptor subunits were expressed at the messenger RNA level indicating that the synthesis is at least partly regulated at a pretranslational level. As the cellular responsiveness to growth factors depends on their specific receptors, our finding that both platelet-derived growth factor-receptor subunits are expressed in chronic venous ulcers substantiates the concept of therapeutic trials with recombinant platelet-derived growth factor.

Journal Article↗
PubMedDate not supplied

Particle-mediated gene therapy of wounds.

Gene therapy is becoming a reality, and it is a particularly attractive approach for wound healing, because the wound site is often exposed, the treatment and condition should be transient, and gene products such as growth factors and cytokines suffer from problems with bioavailability and stability. Among the techniques for gene delivery to the wound site, particle-mediated bombardment with a device called the gene gun has become an important developmental tool. This instrument has been used in numerous examples of wound gene therapy with growth factors or their receptors in the last decade. Among the advantages of particle-mediated bombardment are ease and speed of preparation of the delivery vehicle, the stability of the DNA preparation, the absence of (viral) antigens, the ability to target the projectiles to different tissue depths and areas, and the rapid shedding of both particles and DNA if they are targeted to the epidermis. Clinical application of the technology remains limited by the relatively low efficiency of the method, the potential tissue damage created by impact of the particles, and the coverage area. The gene gun can also be used to facilitate the discovery and validation of gene products as wound healing agents.

Drug Carriers↗
PubMedDate not supplied

Stevens-Johnson syndrome-like exanthema secondary to methotrexate histologically simulating acute graft-versus-host disease.

A 61 year old male patient suffering from psoriasis vulgaris developed a severe skin reaction with toxic myelosuppression three days after administration of 20 mg methotrexate (MTX) p.o. per week and concomitant 100 mg acetylic salicylic acid (ASA) per day. The skin lesions simulated Stevens-Johnson syndrome with ulcerations of the oral mucosa and erythema multiforme-like target lesions. The histology of the epidermis resembled an acute graft-versus-host reaction. The increased toxic effect of MTX on keratinocytes in our patient was most likely caused by a lowered plasma binding capacity and reduced renal excretion of MTX due to concomitant administration of ASA. Thus in the treatment of severe forms of psoriasis with MTX, the combined administration of drugs aggravating MTX toxicity, particularly of ASA, should be carefully considered, due to the increased toxicity and risk of severe skin reactions.

Diagnosis, Differential↗
PubMedDate not supplied

Antibodies against terminal galactosyl (alpha 1-3) galactose epitopes in systemic sclerosis (scleroderma).

Sera from 224 patients with systemic sclerosis (scleroderma) were analyzed for circulating antibodies against an antigenic determinant characterized by two molecules of galactose in alpha 1-3 linkage. About 45% of the patients were found to have values above the normal range. The mean antibody level was significantly higher than that found in normal subjects (p less than 0.001) or in patients with primary Raynaud's phenomenon who were included as controls. The mean level of anti-Gal antibodies correlated with the degree of skin and internal organ involvement, as well as with the presence of progression or inflammation. Furthermore, when patients with early onset disease were analyzed, high levels of anti-Gal antibodies were present in the subgroups characterized by evidence of progression or inflammation, whereas patients with stable disease did not differ from the controls. We conclude that humoral immunity against Gal alpha 1-3 Gal is an early feature of scleroderma, may be important for its pathogenesis, and may provide a more sensitive tool to detect disease activity.

Adolescent↗
PubMedDate not supplied

Regulation of connective tissue homeostasis in the skin by mechanical forces.

Mechanical forces come in a variety of different forms and act on many more tissues than the obvious vascular and musculo-skeletal systems. Next to soluble mediators, they have caught our attention as potent regulatory parameters in modifying the metabolism and phenotype of cells. This paper concentrates on the response of the skin to tensile forces and describes the adaptive phenotype of fibroblasts residing in the dermal connective tissue. Work from a number of different groups suggests that tension induces in these cells many biological properties which have been found in pathological conditions, e.g. in fibrotic skin lesions. Mechanical tension can therefore be regarded as an additional important regulatory parameter, which we would like to better understand with respect to mechanosensing cellular structures and specific or shared signaling pathways.

Biomechanical Phenomena↗
PubMedDate not supplied

Localized and systemic forms of scleroderma in adults and children .

Systemic sclerosis (SSc) presents a great deal of variability in the extent and severity of skin and internal organ involvement. The diagnostic and prognostic significance of autoantibodies in SSc is undisputed and the patient's autoantibody profile represents a fundamental tool for clinicians. Scleroderma is a rare condition in children. Unlike adults, localized scleroderma is more frequent than the systemic sclerosis, nevertheless it represents a disabling condition. In both conditions, no validated outcome measures and proven effective treatment is available to date.Raynaud's phenomenon (RP) is one the most common and significant clinical symptoms of SSc and therefore in patients with RP a capillaroscopic analysis should be carried out as soon as possible. The actual and select advantage of the early nailfold videocapillaroscopic (NVC) analysis is to distinguish between the primary RP and the secondary RP and to allow the early detection of SSc.

Adult↗