Biomedical subjects

T Ziemssen

Publications and source records attributed to T Ziemssen.

5 recordsLinked to original sources

PubMed2006

[Multiple sclerosis. An update with practical guidelines for ophthalmologists].

Multiple sclerosis (MS) is the most frequent chronic inflammatory disease of the central nervous system. Mostly young adults present with a variety of different symptoms due to the multiple localisations of the inflammatory lesions. Up to one-third of MS patients experience symptoms of optic neuritis as the initial symptom. That is the reason why the ophthalmologist often is the first physician contacted by patients later on diagnosed with MS. Today, it is known that there is already a significant irreversible axonal loss in MS patients progressing from the beginning of the disease. Therefore early, diagnosis and application of available therapeutic options are necessary for the patient's benefit. The therapeutic aim in early immunomodulatory treatment is to decrease the number of relapses and to slow down the development of clinical disability. This interdisciplinary overview presents guidelines for the clinical routine: how to assess the individual risk of each patient and how to treat the patient in accordance with current pathogenic, diagnostic and therapeutic knowledge.

Germany↗

PubMed2003

Adult polyglucosan body disease: a postmortem correlation study.

Autopsy of a 50-year-old woman with adult polyglucosan body disease and missense mutations (Arg515His, Arg524Gln) in the glycogen branching enzyme gene (GBE) revealed accumulation of polyglucosan bodies in the heart, brain, and nerve. GBE activity was decreased in the morphologically affected tissues but was normal in unaffected tissues. GBE mRNA transcripts were similar in all tissues and in controls, which confirms the lack of tissue-specific GBE isoforms.

1,4-alpha-Glucan Branching Enzyme↗

PubMed2002

[Treatment of multiple sclerosis with glatiramer acetate. Current aspects of mechanisms of action, pharmacokinetics, adverse effect profile and clinical studies].

Glatiramer acetate (GA, Copaxone), a standardized mixture of synthetic polypeptides, has now been approved also in Germany for the treatment of relapsing-remitting multiple sclerosis (RR-MS). After it had been shown effective in suppression of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), it was evaluated in several clinical studies. In these studies, GA could alter the natural history of MS by both reducing the relapse rate and affecting disability. The clinical therapeutic effect of GA was consistent with the effect on magnetic resonance imaging-defined disease activity and burden in a recent multicenter study. As a daily standard dose, 20 mg of GA is injected subcutaneously. The induction of GA-reactive T-helper 2-like regulatory suppressor cells is thought to be the main mechanism of action. The most common adverse effects are mild injection site reactions. A remarkable but rare adverse effect is the only transient immediate post-injection systemic reaction manifested by flushing, chest tightness, palpitations, and dyspnea. Antibodies to GA which are induced during GA treatment do not interfere with its clinical effects.

Animals↗

PubMed2001

In vitro modulation of steroid 5alpha-reductase activity by phospholipases in epithelium and stroma of human benign prostatic hyperplasia.

Membrane components, such as phospholipids, play an important role in the regulation of prostatic 5alpha-reductase activity. To describe in more detail the impact of such regulation on 5alpha-reductase activity, epithelial and stromal cell homogenates of human BPH were treated with phospholipases to specifically alter the structure of cellular phospholipid components. Phospholipase A(2) (PLA(2)) was used to alter the structure of the nonpolar, hydrophobic region of the membrane bilayer. Various types of phospholipase C (PLC) affect the polar, hydrophilic region of phospholipids. In epithelium and stroma, 5alpha-reductase activity was dose-dependently inhibited by PLA(2) and PLC type III. In epithelium and stroma, the mean IC(50) values of PLA(2) were 9.4 +/- 1.1 and 13.9 +/- 2.6 [U/mg protein +/- SEM], respectively. The mean IC(50) values of PLC type III in epithelium and stroma were 4.5 +/- 1.2 and 1.7 +/- 0.2 [U/mg protein +/- SEM], respectively. In epithelium as well as in stroma, 5alpha-reductase activity was more greatly inhibited by PLC type III than by PLA(2). Both in epithelium and stroma, PLA(2) significantly decreased the V(max) of 5alpha-reductase whereas its K(m) remained unaffected. A similar decrease in V(max) was found with PLC type III in epithelium and stroma. Furthermore, the K(m) of epithelial 5alpha-reductase increased significantly following the addition of PLC type III. The two phospholipases, with their specific substrate affinities and sites of hydrolysis, exhibited significantly different effects on 5alpha-reductase, indicating that 5alpha-reductase activity is not unspecifically affected by modification of the hydrophilic milieu. Rather, 5alpha-reductase activity is specifically modulated by various phospholipids and/or phospholipolysis mediated degradation products. These findings suggest that the structural composition of the lipid environment plays a fundamental role in the post-translational regulation of 5alpha-reductase activity in the epithelium and stroma of human BPH. Thus, changes in membrane phospholipid content seem to be instrumental in the expression of DHT-dependent processes.

Epithelium↗

PubMed2001

Risk-benefit assessment of glatiramer acetate in multiple sclerosis.

Glatiramer acetate, formerly known as copolymer 1, is a mixture of synthetic polypeptides composed of four amino acids. Glatiramer acetate has been shown to be effective in preventing and suppressing experimental autoimmune encephalitis (EAE), the animal model of multiple sclerosis (MS). Therefore it was tested in several clinical studies, where it was found to slow the progression of disability and to reduce the relapse rate and the magnetic resonance imaging (MRI)-defined disease activity and burden in relapsing-remitting MS. As a daily standard dose, 20mg of glatiramer acetate is injected subcutaneously. After injection, glatiramer acetate undergoes rapid degradation to amino acids and shorter peptides; so it is not possible to measure any systemic plasma concentrations or excretion rates. Two major mechanisms have been proposed to explain the effects of glatiramer acetate in EAE and MS: the induction of glatiramer acetate-reactive T helper 2 (Th2)-like regulatory suppressive cells and the interference with T cell activation as an altered peptide ligand. The most common adverse effects were mild injection site reactions (erythema, inflammation and induration). The most remarkable adverse event is the acute and transient immediate postinjection reaction manifested by flushing, chest tightness, palpitations and dyspnoea. Other reported adverse effects are transient chest pain and lymphadenopathy. Antibodies to glatiramer acetate induced during treatment do not interfere with its clinical effects. In several controlled clinical studies, glatiramer acetate has been shown to provide consistent, reproducible clinical benefits in the target population of patients with relapsing-remitting MS. The safety profile and risk-benefit ratio are excellent. Overall, glatiramer acetate is very well tolerated and has an excellent risk-benefit profile in patients with relapsing-remitting MS.

Clinical Trials as Topic↗