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Biomedical subjects

G Goerz

Publications and source records attributed to G Goerz.

At least 37 records · Page 2Linked to original sources
PubMed1997

Ex vivo application of delta-aminolevulinic acid induces high and specific porphyrin levels in human skin tumors: possible basis for selective photodynamic therapy.

In photodynamic therapy with topically applied delta-aminolevulinic acid porphyrins are acting as photosensitizers. The profile of porphyrin metabolites in normal or in neoplastic skin after administration of delta-aminolevulinic acid has not been determined in detail yet. Thus, to study porphyrin biosynthesis in human skin an organ culture model was developed. Explant pieces of normal skin, keratoacanthoma, and basal cell carcinoma were incubated with 1 mM delta-aminolevulinic acid for 36 h. Levels of delta-aminolevulinic acid, porphyrins and porphyrin metabolites were measured in tissues and supernatants. After incubation with delta-aminolevulinic acid, higher porphyrin levels were demonstrated in tumors as compared to normal skin. In supernatants, most of formed porphyrins, preferentially highly carboxylated porphyrin metabolites, were measured. The pattern of synthesized porphyrins differed between normal and neoplastic skin explants. In tissues of basal cell carcinomas protoporphyrin was preferentially shown and tissues of keratoacanthomas were characterized by a predominance of coproporphyrin as compared to normal skin. The results show that explant cultures offer an easy approach to examine the porphyrin biosynthesis of various tissues. The tumor-specific delta-aminolevulinic acid metabolism indicates additional porphyrin metabolites such as coproporphyrin apart from protoporphyrin as effective photosensitizers and may offer a novel approach to tumor-selective photodynamic damage.

Aminolevulinic Acid↗
PubMed1997

Influence of indoles (melatonin, serotonin and tryptophan) on the porphyrin metabolism in vitro.

We examined the influence of melatonin, serotonin and tryptophan on the basal and delta-aminolevulinic acid (ALA)-induced porphyrin content in HaCaT, SKMel-23 and HepG2 cells. ALA-preincubated and ALA-free cells were fed with medium containing 1 mM melatonin, serotonin or tryptophan. After 24 h the porphyrin content in the cells and in the culture medium was measured. In the three cell lines the inbucation with 1 mM ALA over 24 h increased the porphyrin concentration in all cell lines in different degrees: HepG2 > SKMel-23 > HaCaT cells. In HepG2 cells, neither melatonin, serotonin nor tryptophan influenced ALA-induced porphyrin concentrations significantly, but all three indoles depressed the porphyrin levels in SKMel-23 and HaCaT cells. The indoles may decrease the ALA uptake in HaCat or SKMel-23 cells. Another mechanism could be the inhibition of enzymes converting ALA into porphyrins.

5-Aminolevulinate Synthetase↗
PubMed1997

Porphyrins preferentially accumulate in a melanoma following intravenous injection of 5-aminolevulinic acid.

Systemically, as opposed to topically, administered 5-aminolevulinic acid (ALA) is of increasing interest for photodynamic therapy (PDT) because of more selective and more homogeneous accumulation of porphyrins in neoplastic tissues. This study investigates the profile and the time course of porphyrin metabolites in various tissues following intravenous injection of ALA (0.5 g/kg body weight) into hamsters bearing an amelanotic melanoma (A-Mel-3). ALA injection led to maximum levels of ALA and porphyrins in erythrocytes after 45 min. In tissues, maximum porphyrin levels were detected after 45 min (tumor), 4 h (skin, kidney), and 24 h (liver). Sixfold higher porphyrin levels were observed in tumors as compared to surrounding normal skin at 45 min. Predominant porphyrin metabolites were protoporphyrin (tumor, skin, liver, kidney), coproporphyrin (tumor) and highly carboxylated porphyrins (tumor, skin, kidney). These data suggest optimum efficacy of light irradiation in systemic PDT with ALA within the first two hours after injection. Tumor-specific ALA metabolism yields protoporphyrin and coproporphyrin as the prevailing porphyrin metabolites.

Aminolevulinic Acid↗
PubMed1997

Effects of clonidine in a primed rat model of acute hepatic porphyria.

Acute hepatic porphyrias can be induced by several drugs and acute attacks of porphyrias are often associated with severe hypertension. Therefore it is important to know if an antihypertensive drug used has porphyrogenic potency or not. As previously demonstrated in normal rats the alpha-receptor blocker clonidine (CAS 4205-90-7) has no significant influence on the porphyrin metabolism. Pretreatment of rats with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or allyl-isopropyl-acetamide (AIA) induces hepatic delta-aminolaevulinic acid synthase (ALA-S) and increases the urinary excretion of porphyrin precursors (ALA and PBG) comparable to the latent phase of acute hepatic porphyrias in humans. Clonidine did not induce hepatic ALA-S or urinary excretion of ALA or PBG in normal as well as in DDC or AIA pretreated rats. Moreover the induction of P4501A1 (7-ethoxyresorufin-O-deethylase) by DDC was abolished by simultaneous application of clonidine. From these findings one can probably conclude that clonidine is a safe drug in human acute hepatic porphyria.

5-Aminolevulinate Synthetase↗
PubMed1996

Influence of topical photodynamic therapy with 5-aminolevulinic acid on porphyrin metabolism.

Photodynamic therapy (PDT) with topically applied 5-aminolaevulinic acid (5-ALA) is increasingly used for treating tumours. The efficacy of topical PDT is limited to superficial and initial tumours. The topically applied doses of 5-ALA vary from 0.02 to 7.0 g per session according to the type of lesion. There are no studies on the influence of topically applied 5-ALA on the systemic accumulation of porphyrins or porphyrin precursors. A group of 20 patients with actinic keratoses (AK) and basal cell carcinomas (BCC) were treated by topical PDT with 5-ALA. Prior to and 6 and 24 h after PDT, 5-ALA and total porphyrin concentrations were determined in red blood cells and plasma, respectively. In addition, before and after 5-ALA treatment, 24-h urine samples were collected and porphyrins and porphyrin precursors were measured. There was no significant alteration in porphyrin metabolism. In some patients, a slight but insignificant increase in erythrocyte and plasma porphyrins was found 6 h after 5-ALA PDT. This investigation confirms clearly the safety of this treatment modality and demonstrates that 5-ALA application (up to 7 g) in the course of PDT has no influence on the concentrations of porphyrins and porphyrin precursors measured in various compartments.

Administration, Topical↗
PubMed1996

[Case report of jellyfish injury].

We are presenting a 47-year-old woman who was stung by jellyfish while bathing in the sea of Thailand. Immediately after the injury she developed sharp pain and urticarial erythema of the skin of the knees accompanied by muscle cramps of the entire body. After a few days a toxic contact dermatitis with edematous swelling and ulcerations developed, which did not respond to topical antibiotics or corticosteroids. Three weeks later the patient presented with a disseminated urticarial eruption, which at first responded well to topical treatment and systemic corticosteroids. Over the next few weeks, however, a relapse of the eruption and the ulcerations occurred. Raised titres of IgG and IgM antibodies against different jellyfish from the Indian and Pacific Ocean were detected in the patient's serum by the enzyme-linked immunosorbent assay. Antibodies against bees (class 1) and wasps (class 4) were found by the radioallergosorbent test. The clinical features and the immunological findings led to the diagnosis of toxic and allergic contact dermatitis to jellyfish venom. First aid and secondary treatment of jellyfish injuries are suggested.

Adrenal Cortex Hormones↗
PubMed1996

[Photodynamic therapy and breast-plasty of a extensive superficial trunk skin basalioma of the breast. An effective combination therapy with photodynamic diagnosis].

We treated a large superficial basal cell carcinoma (ca. 10 x 6 cm) on the right breast in a 48-year old woman with photodynamic therapy (PDT). Fractionated PDT was performed by topical application of delta-aminolevulinic acid (delta-ALA, 20%) with subsequent red light (570-750 nm; 180 J/ cm2) in three sessions. Nearly total remission of the tumor resulted; however, a few residual neoplastic islands partly infiltrating the nipple-areola complex could be detected by photodynamic diagnosis (PDD). These fluorescent areas were marked, excised, and the defect was closed by a rotation advancement flap. Total excision of the tumor was verified histologically. By combining PDT and surgery, this large tumor was treated with excellent cosmetic results. This case demonstrates the efficiency of topical PDT with adjunctive plastic surgery controlled by PDD even in large tumors.

Administration, Topical↗
PubMed1996

Influence of UVA and UVB irradiation on hepatic and cutaneous P450 isoenzymes.

The influence of UVA and UVB irradiation of the skin for 1, 2 and 4 weeks on the activities of the hepatic and cutaneous P450 isoenzymes was investigated in female Wistar rats before and after systemic administration of hexachlorobenzene (HCB), a well-known porphyrogenic agent, which additionally induces P450 1A1 and P450 1A2 isoenzymes. UVA and UVB irradiation of the skin of controls and HCB-treated animals did not influence porphyrin metabolism. In the nonporphyric rats hepatic EROD (P450 1A1) activity was induced by UVB, but the activity of ADM (P450 2B) and EMDM (P450 3A) was either minimally or not affected. In the HCB-treated (porphyric) rats UVA and UVB irradiation resulted in a significant depression of HCB-induced EROD in the liver and in the skin. In both the nonporphyric and the porphyric rats UVA and UVB irradiation had no effect on hepatic ADM activity. In the liver of the nonporphyric animals EMDM activity remained unchanged after UVA and UVB irradiation, whereas in the HCB-treated animals the activity of this enzyme was increased. Finally, after UVA and UVB irradiation cutaneous EMDM activity was increased in the controls, whereas the HCB-induced increase of this enzyme in porphyric animals was decreased. In addition long-term (28 days) UVB irradiation decreased hepatic GSH content significantly in normal and porphyric rats. These experimental findings cannot be directly extrapolated to humans; however, they suggest that exposure of human skin to UV radiation may result in alterations in the activity of cutaneous hepatic and other extracutaneous P450 isoenzymes.

Aminopyrine N-Demethylase↗
PubMed1996

Beta-carotene serum levels in patients with erythropoietic protoporphyria on treatment with the synthetic all-trans isomer or a natural isomeric mixture of beta-carotene.

The all-trans-beta-carotene serum level of patients suffering from erythropoietic protoporphyria increases substantially during continuous treatment with beta-carotene (either with the synthetic all-trans compound or with beta-carotene from a natural source consisting of a cis-trans isomeric mixture). On continuous daily ingestion, the beta-carotene serum level rose from day 0 to day 30, and no further increase was observed between day 30 and day 150. Slightly lower beta-carotene steady state serum levels were observed with the natural isomeric mixture than with synthetic beta-carotene. Higher levels of 13-cis-beta-carotene, in some cases up to 10% of the total beta-carotene, were detected after ingestion of the synthetic compound. The level of 9-cis-beta-carotene was below or close to the limit of quantification in all samples, even when the isomeric mixture containing high amounts of 9-cis-beta-carotene was applied.

Administration, Oral↗
PubMed1996

Photosensitization of uroporphyrin augments the ultraviolet A-induced synthesis of matrix metalloproteinases in human dermal fibroblasts.

Porphyria cutanea tarda is characterized by severe connective tissue damage in sun-exposed skin. The regulated synthesis and degradation of the extracellular matrix by various matrix metalloproteinases (MMPs) determine its amount and composition within the skin. In this study, we therefore asked whether long-wave ultraviolet irradiation (340-450 nm) in conjunction with uroporphyrin I could modulate the synthesis of MMPs with substrate specificities for dermal (collagens I, III, V; proteoglycans) and basement membrane components (collagens IV, VII; fibronectin; laminin) and whether synthesis of the counteracting tissue inhibitor of metalloproteinases is also affected. After irradiation of uroporphyrin-pretreated fibroblasts, specific mRNAs of MMP-1 and MMP-3 increased concomitantly up to 2.7-fold compared with ultraviolet-irradiated cells and up to 10-fold compared with mock-irradiated or uroporphyrin I-treated controls. In contrast, mRNA levels of tissue inhibitor of metalloproteinases remained unaltered. Similar results were obtained by immunoprecipitation. Gelatin and casein zymography revealed increased proteolytic activity of MMP-2 and MMP-3 in blister fluids of patients with porphyria cutanea tarda, indicating that similar events may occur in vivo. Using deuterium oxide as enhancer and sodium azide as quencher of singlet oxygen, we could increase or reduce MMP synthesis, suggesting that singlet oxygen is the major intermediate in the upregulation of MMPs after irradiation of uroporphyrin-pretreated fibroblasts. Taken together, our results show that ultraviolet irradiation alone, and to a greater extent in conjunction with uroporphyrin I, results in an unbalanced synthesis of MMPs that may contribute to the destruction of the dermis and basement membrane, leading to blistering and accelerated photoaging in porphyria cutanea tarda patients.

Body Fluids↗
PubMed1996

Erythropoietic protoporphyria and terminal hepatic failure.

We report on a 44-year-old patient with erythropoietic protoporphyria who could effectively control his photosensitivity for 22 years with oral carotinoids. The clinical course of his disorder was complicated by liver involvement, initially expressed as marginally raised serum transaminase levels for several years. Terminal hepatic failure with fatal outcome developed 22 years after manifestation of his liver function abnormalities. Hepatic involvement represents an inconstant and unpredictable feature of erythropoietic protoporphyria, determining the prognosis of an otherwise clinically benign disorder.

Adult↗
PubMed1996

Brittle and sparse hair with normal cystine content caused by methionine deficiency?

The unusual case of an 8-year-old girl with a hair disorder is presented, characterized by brittle, short and sparse hair. On polarizing microscopy the latter reveals a "tiger tail" pattern, whereas severe cuticular defects are detected on scanning electron microscopy. The patient's hair has a normal cystine content but is completely devoid of methionine and reveals distinct changes of its visoelastic parameters. It is presently unknown whether the lack of methionine may be implicated in the pathogenesis of this hair disorder, which to the best of our knowledge has not been previously described.

Child↗
PubMed1996

[Pruritus].

Explore the source record for details and available documents.

Antipruritics↗
PubMed1996

Ferrochelatase activities in patients with erythropoietic protoporphyria and their families.

Ferrochelatase, estimated as zinc chelatase, was measured in the lymphocytes of 30 patients with erythropoietic protoporphyria (EPP), in 35 first- or second-degree relatives of patients with EPP, and in 50 healthy controls. In 30 EPP patients the zinc chelatase level (mean +/- standard deviation, SD) was 0.45 +/- 0.10 nmol of zinc protoporphyrin per hour per milligram of protein, in 14 EPP carriers the zinc chelatase level (mean +/- SD) was 0.42 +/- 0.09 and in 50 healthy controls the zinc chelatase level (mean +/- SD) was 0.84 +/- 0.27. All patients with EPP were also demonstrated to have an elevated protoporphyrin level in their red blood cells: the erythrocyte protoporphyrin levels were as follows EPP patients (mean +/- SD) 1300 +/- 758 nmol protoporphyrin/dl, EPP carriers (mean +/- SD) 60 +/- 24, and healthy controls (mean +/- SD) 50 +/- 25 (P < 0.001 for EPP patients compared to controls and EPP carriers). The families of 12 out of 15 EPP patients were examined with respect to the mode of inheritance of the disorder. Of 35 relatives, 14 were carriers of EPP, as characterized by reduced zinc chelatase activity in lymphocytes and by a normal protoporphyrin level in red blood cells. None of the 14 EPP carriers had presented with clinical symptoms of EPP. The mod of inheritance was autosomal dominant in seven of the 12 examined families, and autosomal recessive in two. In two families only one parent could be investigated, but we nevertheless concluded that the inheritance was autosomal dominant. Inheritance in one EPP family could not be elucidated as both parents showed normal zinc chelatase levels and did not demonstrate abnormal erythrocyte protoporphyrin levels.

Female↗
PubMed1995

[Low dosage cyclosporin A therapy in pyoderma gangrenosum. Experiences with 6 patients].

Pyoderma gangraenosum can cause great therapeutic problems. High dosed corticosteroids are the treatment of choice. However, recalcitrant pyoderma gangraenosum or side effects from corticosteroid treatment may require therapeutic alternatives. Pyoderma gangraenosum responds excellently to treatment with cyclosporine A. Because of side effects and drug interactions, the patients must be selected and carefully and closely monitored. Six patients with pyoderma gangraenosum, unresponsive to various topical and systemic therapies, were treated with oral cyclosporine A at mean daily doses of approximately 3 mg/kg. Marked improvement of the skin lesions and complete healing occurred in all patients over a period of 3-6 months. Only one patient suffered a relapse after discontinuation of the treatment. No severe irreversible side effects occurred. The results show that low-dose cyclosporine A treatment can be considered a first-line treatment of pyoderma gangraenosum.

Adult↗
PubMed1995

Schönlein-Henoch purpura associated with gastric Helicobacter pylori infection.

Schönlein-Henoch purpura is characterized by palpable purpura, colicky abdominal pain, gastrointestinal hemorrhage, arthralgias, and renal involvement. Bacterial and viral infections, as well as drugs and diseases associated with immune complexes, are thought to be responsible. We describe the case of a 21-year-old woman with Schönlein-Henoch purpura and chronic active gastritis with erosions. Helicobacter pylori was found in gastric mucosa using the newly introduced, nontoxic, noninvasive 13C-urea breath test; infection was confirmed by gastric mucosal biopsy. After eradication of H. pylori with omeprazole and amoxicillin, the skin changes, gastric complaints, and proteinuria disappeared. Ten months later, Schönlein-Henoch purpura recurred. H. pylori was again detected. After therapy, H. pylori was eradicated and the clinical manifestations faded. To our knowledge, H. pylori has not previously been described as a cause of Schönlein-Henoch purpura.

Adult↗
PubMed1995

Testing the porphyrinogenicity of propofol in a primed rat model.

We evaluated the porphyrinogenicity of propofol in a rat model. After a pilot study had been conducted to determine an optimal dose, 48 fasting male Sprague-Dawley rats were allocated randomly to six groups. The animals in groups 1-3 received saline i.p. In groups 4-6, the animals were given allylisopropylacetamide (AIA). Twelve hours later, animals in groups 1 and 4 received saline, groups 2 and 5 were given propofol 150 mg kg-1 i.p., followed by 75 mg kg-1 3 h later, and groups 3 and 6 received phenobarbitone 50 mg kg-1 i.p. and 25 mg kg-1 i.p. The animals were anaesthetized and killed 3 h after the second drug bolus and we measured the concentration of cytochrome P450, total porphyrin content and the activity of delta-aminolaevulinic acid synthase (ALAS) in the liver. Urinary delta-aminolaevulinic acid (ALA) and porphobilinogen (PBG) concentrations were measured. Analysis of variance and the t test with Bonferroni's correction were used to compare data. The hepatic cytochrome P450 concentration in the non-primed groups varied from 28.1 to 31.1 nmol g-1; administration of AIA decreased this to 20.1-20.9 nmol g-1. Total hepatic porphyrins were between 0.78 and 1.22 nmol g-1 in the non-primed groups and between 2.71 and 3.54 nmol g-1 in the AIA-primed groups. Hepatic ALAS activity was 29.2 and 35.5 nmol h-1 g-1 in groups 1 and 2. In the primed saline group, ALAS activity was measured at 134.5 nmol h-1 g-1.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Aminolevulinate Synthetase↗