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Biomedical subjects

Dominik M Alscher

Publications and source records attributed to Dominik M Alscher.

8 recordsLinked to original sources
PubMed2005

Induction of metallothionein in proximal tubular cells by zinc and its potential as an endogenous antioxidant.

BACKGROUND: This study was undertaken to gain further insights into the expression of metallothionein (MT) in kidney, to define the necessary dosage of a metal (zinc) to achieve induction of MT and to evaluate the antioxidative potential of MT in comparison to other more common antioxidative therapeutics, like N-acetyl-L-cysteine (NAC), and endogenous molecules, like glutathione. METHODS: MT was measured in renal specimens from cadaver kidneys from patients with chronic diseases (n = 76) and controls (n = 21) by immunohistochemistry. In addition, induction experiments were performed in cell cultures of proximal tubular cells (LCC-PK1) and MT measured on the RNA and protein level (immunohistochemistry, Western and dot blotting). Antioxidative potential of MT was compared to NAC and glutathione. RESULTS: MT was restricted to tubular cells with no differences between controls and patients. Zn caused a dose-dependent increase of MT on the RNA as well as on the protein level (RNA (ratio MT/histone 3.3): control 0.34 +/- 0.12; Zn 17 microM 0.65 +/- 0.26; Zn 35 microM 1.25 +/- 0.43 (p < 0.05), Zn 52 microM 1.35 +/- 0.46 (p < 0.05), and protein: 5.8-fold increase from 47 +/- 13 mg/g total protein (n = 6) to 272 +/- 140 mg/g total protein (n = 6)). The antioxidative effect of MT was equal to NAC and glutathione. CONCLUSIONS: Induction of renal MT by zinc is easily achievable and might be an interesting therapeutic and preventive tool against oxidative stress.

Adult↗
PubMed2004

Osteoarthritis of the knee--clinical assessments and inflammatory markers.

OBJECTIVE: The present cross sectional study was performed to test the hypothesis that in osteoarthritis (OA) of the knee severity of this disease is related to local levels of inflammatory metabolites and their corresponding enzymes. METHODS: From 41 patients with OA of the knee (age range 45-79 years) undergoing arthroscopy blood, synovial fluid (SF) and synovial membrane (SM) were collected. Clinical conditions were primarily assessed by the WOMAC-index and radiographic grading (K&L-grade). Concentrations of PGE(2), TxB(2)and NO(2/3)and that of IL-6, IL-1 alpha, IL-1 beta, TNF alpha, COX-2 and iNOS were determined in SF and SM, respectively. RESULTS: With advancing age K&L-grade and COX-2 in SM increased significantly (P=0.005 and P=0.01, respectively). TNF alpha and IL-1 alpha were not detectable in SM samples. Apart from a correlation between PGE(2)and WOMAC-index (r=0.36, P=0.035) no significant relationships could be found between the various inflammatory parameters and any of the assessed clinical signs. CONCLUSIONS: Apparently no direct relationships exist between the measured markers of inflammation (e.g. PGE(2), NO(2/3)) or the involved enzymes (e.g. COX-2, iNOS) and the severity of OA of the knee. The degenerative condition of this disease might be due to the more local, mainly mechanical injury with little systemic upset. However, further longitudinal studies are needed to clarify whether the assessed biochemical markers could serve as predictors for the progression of OA.

Age Factors↗
PubMed2003

Apoptosis of mesothelial cells caused by unphysiological characteristics of peritoneal dialysis fluids.

There is an ongoing debate as to which peritoneal dialysis fluids (PDFs) provide the best preservation of peritoneal cells. To investigate this topic further, we measured apoptosis and necrosis of cultured mesothelial cells (MCs) after exposure to different single unphysiological features of PDFs and PDFs for whole. MCs were incubated in buffers containing plasticizers, high osmolarity by sodium chloride, low pH, and high glucose for 0.5, 4, and 24 h. The same procedure was repeated with different PDFs. Apoptosis and necrosis were measured by FACS-analysis (annexin-FITC and propidium iodide). We found that plasticizers were clearly able to induce apoptosis after 24 h (18 +/- 4%). The same result was observed with high osmolarity by sodium chloride (17 +/- 5%), but not for high glucose (9 +/- 8%). All fluids with low pH (5.2) caused severe and almost complete necrosis (after 4 and 24 h). Incubation in neutral, two-compartment PDFs (glucose 4.25%) without plasticizers for 4 h showed no significant necrosis (3%), but after 24 h apoptosis was detectable in 10 +/- 9% and necrosis in 29 +/- 8% of MCs. In conclusion, after improving PDFs and introducing neutral fluids, further attention should be drawn to inducers of apoptosis. Apoptosis can be detected quite early (24 h) and is caused by plasticizers and high osmolarity.

Cells, Cultured↗
PubMed2000

Naltrexone does not relieve uremic pruritus: results of a randomized, double-blind, placebo-controlled crossover study.

Improvement of uremic pruritus was reported under short-term administration of the mu-receptor antagonists naltrexone and naloxone. The aim of the present study was to confirm the efficacy and safety of the oral mu-receptor antagonist naltrexone during a 4-wk treatment period in patients on hemodialysis and peritoneal dialysis. A placebo-controlled, double-blind crossover study of uremic patients with persistent, treatment-resistant pruritus was performed. Of 422 patients screened between December 1997 and June 1998, 93 suffered from pruritus and 23 were eligible for the study. Patients were started either with a 4-wk naltrexone sequence (50 mg/d) or matched placebo. This was followed by a 7-d washout, and patients continued with a 4-wk sequence of the alternate medication. Pruritus intensity was scored daily by a visual analogue scale (VAS) and weekly by a detailed score assessing scratching activity, distribution of pruritus, and frequency of pruritus-related sleep disturbance. Sixteen of 23 patients completed the study. During the naltrexone period, pruritus decreased by 29.2% (95% confidence interval [CI], 18.7 to 39.6) on the VAS and by 17.6% (95% CI, 4.2 to 31.1) on the detailed score. In comparison, pruritus decreased by 16.9% (95% CI, 6.8 to 26.9) on the VAS and by 22.3% (95% CI, 9.3 to 35.2) on the detailed score during the placebo period. The difference between the naltrexone and the placebo treatment period was not statistically significant. Nine of 23 patients complained of gastrointestinal disturbances during the naltrexone period compared with only one of 23 patients during the placebo period (P < 0.05). These results show that treatment of uremic pruritus with naltrexone is ineffective. In addition, a high incidence of adverse effects was observed during treatment with naltrexone.

Administration, Oral↗
PubMedDate not supplied

Metallothionein and dendritic cells in skin of end-stage renal disease patients not on dialysis, or on hemodialysis or peritoneal dialysis.

OBJECTIVE: Renal failure leads to a variety of defects in immune function. The skin, as a major player in the immune system network, also exhibits multiple derangements. The pathogenesis of these defects and derangements are poorly understood; therefore, we studied immune competent cells, dermal dendrocytes (DC), and a special proinflammatory protein, metallothionein (MT), in the skin of these patients. DESIGN: 22 patients with end-stage renal disease (ESRD) but not on dialysis, 18 patients on hemodialysis (HD), 14 patients on peritoneal dialysis (PD), and 35 healthy controls were included in the study. Immunohistochemical staining of skin biopsies for DC and MT was performed with the following antibodies: for DC, antibody against factor XIIIa; and for MT, Dako-MT, E9 (Dako, Carpinteria, California, USA). Measurements were made by counting stained DC per square millimeter, and by optical density (OD) for MT (mean SEM). RESULTS: Metallothionein was increased in the skin of HD (OD 0.42 +/- 0.05, p < 0.01) and PD patients (OD 0.33 +/- 0.04, p < 0.05) compared to controls (OD 0.23 +/- 0.02) and ESRD patients not on dialysis (OD 0.22 +/- 0.05). In contrast, numbers of DC were reduced in patients on PD compared to controls (59 +/- 13 vs 96 +/- 59 DC/mm2, p < 0.01) and increased in patients with ESRD prior to dialysis (141 +/- 13 DC/mm2, p < 0.05). Patients on HD were in-between (105 +/- 20 DC/mm2), with a significant difference versus patients on PD (p < 0.05). CONCLUSIONS: Our data show that the mode of dialysis influences the number of antigen-presenting cells in the dermis. However, in both dialysis modes, a proinflammatory immune status of the skin (MT) was present and, therefore, other regulatory elements for dermal dendrocytes apart from proinflammation exist.

Adult↗