Biomedical subjects

C Schwarz

Publications and source records attributed to C Schwarz.

132 records · Page 8Linked to original sources

PubMedDate not supplied

[Beta thalassemia in Germany: molecular genetics and clinical phenotype in immigrant and in the native population].

BACKGROUND: In Germany there are about 300-400 patients with homozygous beta-thalassaemia who immigrated from endemic regions mostly in the Mediterranean. In the non-immigrant population beta-thalassaemia is rare with only single case reports of homozygous patients. Heterozygous beta-thalassaemia, however, is more common and must be considered in the differential diagnosis of hypochromic anemia. PATIENTS AND METHODS: Here, clinical and molecular data of 221 homozygous patients from immigrant families and 256 non-immigrant German heterozygous individuals are presented. RESULTS: Clinically, 87% (n = 192) of the homozygotes are regularly transfused and classified as thalassaemia major (TM). The other 13% (n = 29) are not (regularly) transfused and thus classified as thalassaemia intermedia (TI). There is a wide spectrum of 39 beta-globin gene mutations and even the most common three, IVSI-110G-A, NS 39, and IVSI-6 T-C occur with relatively low frequencies of 28%, 22%, and 9%, respectively. In 17/29 (58%) TI patients "mild" mutations are found that inactivate the affected gene incompletely. In 16/29 (55%) there are mutations that are associated with increased gamma-globin gene activity. alpha-Thalassaemia is rare and only found in 3/29 TI-patients. In the 256 Germans with heterozygous beta-thalassaemia there are 27 different beta-globin gene mutations. The 3 most common are Mediterranean mutations together accounting for 61%. Also-relatively common (5%; n = 13) is an otherwise rare frameshift mutation of codon 83 (FS83 delta G). The other mutations occur in < 10 individuals only. Two mutations described here are novel. One of them affects position-2 of the intron 1 splice acceptor site (IVSI-129 A-G) and the other is a deletion of a single G in codon 15/16 (FS 15/16 delta G). CONCLUSIONS: Taken together, a plausible molecular pathogenesis for the observed phenotype (TM vs. TI) can be identified in most homozygous patients thus allowing for rational counselling of the affected families. In heterozygous Germans beta-thalassaemia has probably been imported from the Mediterranean in about 2/3 of the cases whereas in the remaining 1/3 it has probably originated locally.

Adolescent↗

PubMedDate not supplied

Solid lipid nanoparticles (SLN) for controlled drug delivery. II. Drug incorporation and physicochemical characterization.

Solid lipid nanoparticles (SLN) are a colloidal carrier system for controlled drug delivery. The lipophilic model drugs tetracaine and etomidate were incorporated to study the maximum drug loading, entrapment efficacy, effect of drug incorporation on SLN size, zeta potential (charge) and long-term physical stability. Drug loads of up to 10% could be achieved whilst simultaneously maintaining a physically stable nanoparticle dispersion. Incorporation of drugs showed no or little effect on particle size and zeta potential compared to drug-free SLN. The optimized production parameters previously established for drug-free SLN dispersions can therefore be transferred to drug-loaded systems to facilitate product development.

Anesthetics, Intravenous↗

PubMedDate not supplied

Trioxsalen in the presence of UVA is able to induce nuclear factor kappa B binding activity in HaCaT keratinocytes.

It has been described that treatment of cells with high dose psoralen and UVA induce the production of reactive oxygen species (ROS) leading to DNA damage. Transcription factor nuclear factor kappa B (NFkappaB) plays a crucial role in regulating not only cell growth but also cell differentiation, and ROS seem to be partly involved in these mechanisms. The aim of this research was to find out the effect of a combined treatment with trioxsalen (TMP)/UVA on NFkappaB binding activity in HaCaT keratinocytes. HaCaT keratinocytes were treated with 27 microg/l TMP. This concentration did not affect the proliferation rates, nor was it toxic, as shown by cytotoxicity assays. After treatment with TMP with or without UVA (1 J/cm(2)), NFkappaB binding activity in nuclear protein extracts was measured by electrophoretic mobility shift assays. The effect on cytokines and cytokine receptor genes was investigated using cDNA expression arrays. An inhibitory effect on NFkappaB binding activity was found between 30 and 60 min after TMP supplementation of the culture media. UVA irradiation induced a 2-fold increase in NFkappaB binding activity in TMP supplemented HaCaT keratinocytes compared with the non-irradiated control. In addition, NFkappaB binding activity was higher after UVA irradiation with TMP than in UVA irradiated cells in the absence of TMP. TGF-alpha, IL-1R, IL-2Ralpha, IL-12beta and PDGF expression was induced by UVA. However, all of them except PDGF were inhibited by combined TMP/UVA treatment. Using an inhibitor of NFkappaB activation, we found out that under these conditions, these cytokines or cytokine receptor genes are apparently not regulated by NFkappaB. Our results indicate that a combined TMP/UVA treatment of HaCaT keratinocytes induces NFkappaB binding activity, and that this is a synergistic effect. The investigated cytokines, and cytokine receptor genes do not seem to be NFkappaB regulated; however, TMP shows anti-inflammatory capacities in vitro.

Cell Division↗

PubMedDate not supplied

Effects of UVA and L-ascorbic acid on nuclear factor-kappa B in melanocytes and in HaCaT keratinocytes.

Nuclear factor-kappaB (NFkappaB) is a pleiotropic transcriptional activator, which is a sensitive transcriptional factor for free radicals and activates multiple target genes. UVA is very efficient in inducing free radicals in human skin cells. L-ascorbic acid is regarded as a scavenger of UVA-induced free radicals in human keratinocytes. In epidermis, melanocytes and keratinocytes play an important protective role against skin photodamage. In the present study, we aimed to investigate the role of NFkappaB on photodamage in melanocytes and keratinocytes. Normal human melanocytes (NHM) and HaCaT keratinocytes were treated with UVA (500 mJ/cm(2), 1,000 mJ/cm(2)) and/or L-ascorbic acid (100 microM, 250 microM). NFkappaB binding activity was analysed by electrophoretic mobility shift assay. NFkappaB binding activity was increased by UVA irradiation in HaCaT keratinocytes, but it was not affected in NHM. On the other hand, L-ascorbic acid decreased NFkappaB binding activity both in UVA-irradiated and in non-irradiated NHM. In contrast, NFkappaB binding activity in HaCaT keratinocytes was increased after treatment with L-ascorbic acid. In addition, L-ascorbic acid synergistically induced NFkappaB binding activity with UVA irradiation. The contrary response on NFkappaB binding activity in NHM and HaCaT keratinocytes indicated that the redox regulation might be different on photoprotective action in melanocytes and keratinocytes.

Ascorbic Acid↗

PubMedDate not supplied

Shower PUVA: a novel variant of photochemotherapy. Distribution of photosensitivity and accumulation of trioxsalen in the skin.

Shower PUVA is a new variant of photochemotherapy suitable for therapy of various skin disorders. Psoralen, e.g. trioxsalen-containing water recirculates in a closed shower system and wets the skin continuously. After showering, whole-body UVA irradiation (320-400 nm) is performed. In order to prove the equal distribution of photosensitivity in vivo minimal phototoxic dose (MPD) was determined in different skin areas of healthy individuals. Additionally, we investigated the accumulation of trioxsalen in psoriasis lesions under the conditions described by quantifying psoralen in scales collected after showering. In a randomized study 20 healthy volunteers (skin type I-III) took showers for 5 and 10 min in trioxsalen (0.27 mg/l)-containing water at 37 degrees C. Immediately afterwards, MPD was tested on the inside of the upper arms and on the buttocks by using a polychromator light source (315-400 nm). The applied UVA doses were 0.06-0.75 J/cm(2) with steps of 0.125 J/cm(2). MPD was evaluated after 72 h. Equal distribution of photosensitivity was defined as equal MPD on the insides of the upper arm and the buttocks (+/-0.125 J/cm(2)). Skin scales of 21 patients with psoriasis were collected by scratching after showering with trioxsalen-containing water (0.27 mg/l) for 5 min. For quantification of trioxsalen in the scales HPLC was performed. An equal distribution of photosensitivity was achieved in 70% (14/20) cases after 10-min showering in trioxsalen-containing water. Showering for 5 min only revealed a 30% (6/20) rate of equal distributed photosensitivity. After 10-min shower time MPD was 0.325 J/cm(2) (median; range: 0.06-0.625 J/cm(2)). The average amount of trioxsalen found in the scales was 2.03 ng/mg scales (range: 0.38-7.2 ng/mg). For shower PUVA using trioxsalen, 10 min shower time is recommended to achieve sufficient distribution of photosensitivity on the skin. Clinical efficacy of shower PUVA can be explained by skin accumulation of trioxsalen which enters from the aqueous phase into the upper skin layers in detectable amounts. This is the first report demonstrating the efficacy of shower PUVA which in short shower time allows an uptake of psoralen by the skin.

Adult↗

PubMedDate not supplied

The results of operative treatment of osteochondritis dissecans of the patella.

The course of osteochondritis dissecans (OCD) of the patella and the results of operative treatment are analyzed retrospectively in a review of 31 operatively treated cases in 25 patients. Followup was obtained for 21 cases, with an average of 73 months (range, 15 months to 20 years). These 25 patients were predominantly males, and averaged 18 years of age at the time of surgery. A history of trauma was associated with the lesion in 38% of the cases, and the lesion was bilateral in one out of four patients. The most common presenting complaints were subpatellar pain and swelling. The most common initial physical findings were patellofemoral crepitus and joint effusion. Forty-four operations were performed on 31 knees. The most commonly performed procedures were curettage of the patella and removal of loose bodies, in combination or as part of another procedure. A new patellofemoral rating scale was used to evaluate results. Thirty-eight percent of the knees had a good or excellent result, while 62% had a fair or poor result. Persistent pain with restricted function and residual patellofemoral crepitus were common findings. In general, the patients who come to surgery for OCD of the patella have a guarded prognosis for full recovery of knee function.

Adolescent↗