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Biomedical subjects

H Strobel

Publications and source records attributed to H Strobel.

At least 19 recordsLinked to original sources
PubMed2005

[Lavasept as an alternative to PVP-iodine as a preoperative antiseptic in ophthalmic surgery. Randomized, controlled, prospective double-blind trial].

BACKGROUND: To reduce the risk of endophthalmitis PVP-iodine is typically used preoperatively. Since iodine is contraindicated in patients with a specific allergic history or severe thyroid disorder we studied the effect of Lavasept, which contains Polyhexanid as an antiseptic alternative. PATIENTS AND METHODS: In a randomized controlled double-blind trial 3 drops of 0.2% Lavasept, 1.25% PVP-iodine or Ringer's solution were applied preoperatively to 67 patients, which have had a minimum of 5 colony forming units (cfu's) in the conjunctival swap. The effectiveness and tolerability were measured. RESULTS: After application of Lavasept or PVP-iodine, the number of cfu was statistically significantly reduced. Lavasept reduced the number of bacterial colonies significantly better than PVP-iodine (p=0.05). All test solutions were equally well tolerated. CONCLUSION: The use af Lavasept is safe, well tolerated and reduces the microbiological contamination of the conjunctival fornix effectively. lt provides a more effective reduction of the cfu's than PVP-iodine 1.25% and this effect tends to be prolonged. Lavasept is a good alternative option in ophthalmology for preoperative antisepsis.

Anti-Infective Agents, Local↗
PubMed2004

[Polyhexamethylbiguanid (PHMB) as preoperative antiseptic for cataract surgery].

BACKGROUND: We examined the efficacy and tolerability of Lavasept (polyhexamethylenbiguanid or PHMB)-an iodine-free antiseptic-in comparison to polyvinylpyrolidon iodine and Ringer's solution, as an alternative preoperative antiseptic. PATIENTS AND METHODS: In a randomized controlled double-blind trial 3 drops of Lavasept, 1.25%, PVP-iodine or Ringer's solution were applied preoperatively in 29 patients. The number of colony forming units (cfu) grown from conjunctival smears and conjunctival hyperaemia, corneal epitheliopathy and ocular surface pain were assessed preoperatively, intraoperatively and 1 day postoperatively. RESULTS: Despite intraoperative application of PVP-iodine, 40% of patients receiving Ringers solution still presented with more than 5 colony forming units (cfu) at the end of the procedure, while all patients that had additional preoperative Lavasept or PVP-iodine achieved relative sterility with less than 5 cfu (p < 0.05). While the effect of Lavasept lasted until the next day, conjunctival microbial colonisation recurred in eyes treated with PVP-iodine. As expected conjunctival hyperaemia and corneal epitheliopathy increased significantly postoperatively but no differences were observed between the 3 solutions tested. CONCLUSION: The preoperative application of Lavasept reduces the conjunctival flora safely and effectively. The microbicidal efficacy is equal to PVP-iodine, but potentially longer lasting. No signs of local or systemic intolerability were observed. Lavasept may be used as a potential alternative preoperative antiseptic and is suitable for iodine-intolerant patients.

Adult↗
PubMed2003

[Malaria surveillance in Germany 2000/2001--results and experience with a new reporting system].

In Germany, malaria is one of the most frequently imported infectious diseases. In January 2001, the newly implemented Infektionsschutzgesetz (Law for Protection Against Infectious Diseases) brought some important changes in surveillance case notification procedures. After one year, experience shows that the changes did not affect the continuity and representative nature of malaria reporting in Germany. In the years 2000 and 2001, 836 and 1,040 malaria cases, respectively, were reported. In both years, most of the patients were between 30 and 49 years old. 82 % of the infections had been acquired in Africa, and 11 % in Asia. The predominant parasite species was P. falciparum (70 %), followed by P. vivax (12 % in 2000, and 16 % in 2001, respectively). The majority of infections occurred among tourists, fewer in immigrants or business travellers. About two thirds of all patients had not taken any chemoprophylactics. Compared to previous years a decrease in the number of fatal cases was observed (1998: 21, 1999: 18, 2000: 8, 2001: 8). To ameliorate the situation of imported malaria intensified prevention activities are necessary, including efforts to improve choice and compliance of chemoprophylaxis and to facilitate timely diagnosis and treatment.

Adolescent↗
PubMed2001

Structural basis for pterin antagonism in nitric-oxide synthase. Development of novel 4-oxo-pteridine antagonists of (6R)-5,6,7,8-tetrahydrobiopterin.

Pathological nitric oxide (NO) generation in sepsis, inflammation, and stroke may be therapeutically controlled by inhibiting NO synthases (NOS). Here we targeted the (6R)-5,6,7,8-tetrahydro-l-biopterin (H(4)Bip)-binding site of NOS, which, upon cofactor binding, maximally increases enzyme activity and NO production from substrate l-arginine. The first generation of H(4)Bip-based NOS inhibitors employed a 4-amino pharmacophore of H(4)Bip analogous to antifolates such as methotrexate. We developed a novel series of 4-oxo-pteridine derivatives that were screened for inhibition against neuronal NOS (NOS-I) and a structure-activity relationship was determined. To understand the structural basis for pterin antagonism, selected derivatives were docked into the NOS pterin binding cavity. Using a reduced 4-oxo-pteridine scaffold, derivatives with certain modifications such as electron-rich aromatic phenyl or benzoyl groups at the 5- and 6-positions, were discovered to markedly inhibit NOS-I, possibly due to hydrophobic and electrostatic interactions with Phe(462) and Ser(104), respectively, within the pterin binding pocket. One of the most effective 4-oxo compounds and, for comparisons an active 4-amino derivative, were then co-crystallized with the endothelial NOS (NOS-III) oxygenase domain and this structure solved to confirm the hypothetical binding modes. Collectively, these findings suggest (i) that, unlike the antifolate principle, the 4-amino substituent is not essential for developing pterin-based NOS inhibitors and (ii), provide a steric and electrostatic basis for their rational design.

Animals↗
PubMed2001

High-performance liquid chromatographic method with electrochemical detection for the analysis of O6-methylguanine.

An improved system consisting of a combination of high-performance liquid chromatographic methods with electrochemical detection for the separation and analysis of the DNA adduct O6-methylguanine (O6MG) has been developed. This adduct is produced by the interaction of methylating agents with DNA and induces mispairing in the DNA of the target cells. A good separation of modified from unmodified bases is first achieved with an HPLC system using a Partisil 10 SCX column and a salt gradient. A second HPLC step with electrochemical detection and a C18 column is used for farther separation and quantitation of O6-methylguanine. This method shows a linear response up to 15 pg of 06MG tested. The lowest amount detected was 0.5 pg of O6MG and is highly reproducible. This method is useful to study DNA damage as a product of cellular metabolism and its effects on the process of carcinogenesis.

Antineoplastic Agents↗
PubMed2001

[Malaria incidence in Germany 1998/99--results of single case studies of the Robert Koch Institute].

Malaria is a common imported infectious disease in Germany. A total of 931 cases of malaria were reported in Germany in 1999 (1998: 1,008 cases). Most of the infected patients were 24-45 years of age. Eighty per cent of the cases acquired infection in Africa, in Asia (8.5%) and in Central and South America (5%). Plasmodium falciparum accounted for the largest number of cases (80%) followed by Plasmodium vivax (12%). In 1999 60% of all malaria cases were Germans. Most of them travelled for holidays or study purposes. 20 deaths, all attributed to falciparum malaria, were notified in 1999, most of them (19) were German citizens. In 1999 61% of the patients had not taken chemoprophylaxis at all while travelling abroad. Improving prophylactic measures is the only way to reduce the incidence of malaria cases in Germany.

Adolescent↗
PubMed2001

Rec (formerly Corf) function requires interaction with a complex, folded RNA structure within its responsive element rather than binding to a discrete specific binding site.

It was recently reported that the human endogenous retrovirus HTDV/HERV-K encodes the regulatory protein Rec (formerly designated Corf), which is functionally equivalent to the nuclear export adapter proteins Rev of human immunodeficiency virus and Rex of human T-cell leukemia virus. We have demonstrated that the Rec protein interacts with a characteristic 429-nucleotide RNA element, the Rec-responsive element (RcRE), present in the 3' long terminal repeat of HTDV/HERV-K transcripts. In analogy to the Rev and Rex proteins, which have distinct RNA binding sites in their responsive elements, we have proposed that Rec may also have a defined binding site in the RcRE. In this report, we demonstrate that not every HTDV/HERV-K copy present in the human genome contains an active RcRE, and we characterize mutations that abrogate Rec function. In addition, we demonstrate that Rec function requires binding to a complex, folded RNA structure rather than binding to a discrete specific binding site, in contrast to Rev and Rex and their homologous responsive elements. We define four stem-loop structures in the RcRE that are essential for Rec function. Finally, we demonstrate that both Rev and Rex can mediate nuclear export through the RcRE but that their binding sites are different from each other and from that of Rec.

Base Sequence↗
PubMed2001

Role of cytochrome P450 in DNA damage produced by treatment of colon cells with 1,2-dimethylhydrazine.

Human colon cells (LS174T) were treated with the model colon carcinogen 1,2-dimethylhydrazine (DMH) to determine the production of O(6)-methylguanine DNA adducts. Three known P450 inducers (benzanthracene, pyrazole and phenobarbital) were used to produce different P450 environments in each group of cells prior to treatment with DMH. An increased level of DNA damage of different degrees above uninduced levels was observed in all treated groups. Inhibition of the natural protection systems (glutathione and O(6)-methyltransferase) were also included in the study. Glutathione apparently is not of significant protection against DMH damage in colon cells challenged with DMH. In contrast methyltransferase does exert a protective role in this type of cells by reducing the extent of DNA O(6)-methylguanine adduct formation in colon cells following induction of different panels of cytochrome P450 isoforms.

1,2-Dimethylhydrazine↗
PubMed1999

Inhibition of neuronal nitric oxide synthase by 4-amino pteridine derivatives: structure-activity relationship of antagonists of (6R)-5,6,7,8-tetrahydrobiopterin cofactor.

The family of nitric oxide synthases (NOS) catalyzes the conversion of L-arginine to L-citrulline and nitric oxide (NO), an important cellular messenger molecule which has been implicated in the pathophysiology of septic shock and inflammatory and neurodegenerative disease states. NOS can be maximally activated by the ubiquitous cofactor, (6R)-5,6,7,8-tetrahydrobiopterin (H(4)Bip), and antagonists of H(4)Bip may be of therapeutic importance to inhibit pathologically high NO formation. The 4-amino substituted analogue of H(4)Bip was reported to be a potent NOS inhibitor. Therefore, we developed a series of novel 4-amino pteridine derivatives, anti-pterins, to pharmacologically target the neuronal isoform of nitric oxide synthase (NOS-I). To functionally characterize the pterin/anti-pterin interaction and establish a structure-activity relationship (SAR), we systematically altered the substituents in the 2-, 4-, 5-, 6-, and 7-position of the pteridine nucleus. Varying the substitution pattern in the 2-, 5-, and 7-position resulted in no significant inhibitory effect on enzyme activity. In contrast, bulky substituents in the 6-position, such as phenyl, markedly increased the inhibitory potency of the reduced 4-amino-5,6,7,8-tetrahydropteridines, possibly as a consequence of hydrophobic interactions within NOS-I. However, this was not the case for the aromatic 4-amino pteridines. Interestingly, chemical modification of the 4-amino substituent by dialkyl/diaralkylation together with 6-arylation of the aromatic 2,4-diamino pteridine resulted in potent and efficacious inhibitors of NOS-I, suggesting possible hydrophilic and hydrophobic interactions within NOS-I. This SAR agrees with (a) the recently published crystal structure of the oxygenase domain of the inducible NOS isoform (NOS-II) and (b) the comparative molecular field analysis of selected NOS-I inhibitors, which resulted in a 3D-QSAR model of the pterin binding site interactions. Further optimization should be possible when the full length structure of NOS-I becomes available.

Animals↗
PubMed1999

Release of nitric oxide from endothelial cells stimulated by YC-1, an activator of soluble guanylyl cyclase.

1 In this study we examined the endothelium-dependent effect of YC-1 - a benzyl indazole derivative which directly activates soluble guanylyl cyclase (sGC) - on vascular relaxation and nitric oxide (NO) and guanosine-3',5'-cyclic monophosphate (cyclic GMP) in endothelial cells. 2 In preconstricted rat aortic rings with intact endothelium, YC-1 produced a concentration-dependent relaxation. However, the concentration response curve was shifted rightward to higher concentrations of YC-1, when (i) the aortas were pre-treated with L-NG-nitroarginine methylester (L-NAME) or (ii) the endothelium was removed. 3 Incubation of bovine aortic endothelial cells (BAEC) with YC-1 produced a concentration-dependent NO synthesis and release as assessed using a porphyrinic microsensor. Pre-incubating cells with L-NAME or with 8-bromo-cyclic GMP decreased this effect indicating that the YC-1 stimulation of NO synthesis is due to an activation of nitric oxide synthase, but not to an elevation of cyclic GMP. No direct effect of YC-1 on recombinant endothelial constitutive NO synthase activity was observed. 4 The YC-1 stimulated NO release was reduced by 90%, when extracellular free calcium was diminished. 5 In human umbilical vein endothelial cells (HUVEC), YC-1 stimulated intracellular cyclic GMP production in a concentration- and time-dependent manner. Stimulation of cyclic GMP was greater with a maximum concentration of YC-1 compared to calcium ionophore A23187. Similar effects were observed in BAEC and rat microvascular coronary endothelial cells (RMCEC). 6 When HUVEC and RMCEC were pre-treated with L-NG-nitroarginine (L-NOARG), the maximum YC-1 stimulated cyclic GMP increase was reduced by >/=50%. 7 These results indicate, that beside being a direct activator of sGC, YC-1 stimulates a NO-synthesis and release in endothelial cells which is independent of elevation of cyclic GMP but strictly dependent on extracellular calcium. The underlying mechanism needs to be determined further.

Animals↗
PubMed1999

Heterotrimerization of PII-like signalling proteins: implications for PII-mediated signal transduction systems.

PII-like signalling molecules are trimeric proteins composed of 12-13 kDa polypeptides encoded by the glnB gene family. Heterologous expression of a cyanobacterial glnB gene in Escherichia coli leads to an inactivation of E. coli's own PII signalling system. In the present work, we show that this effect is caused by the formation of functionally inactive heterotrimers between the cyanobacterial glnB gene product and the E. coli PII paralogues GlnB and GlnK. This led to the discovery that GlnK and GlnB of E. coli also form heterotrimers with each other. The influence of the oligomerization partner on the function of the single subunit was studied using heterotrimerization with the Synechococcus PII protein. Uridylylation of GlnB and GlnK was less efficient but still possible within these heterotrimers. In contrast, the ability of GlnB-UMP to stimulate the adenylyl-removing activity of GlnE (glutamine synthetase adenylyltransferase/removase) was almost completely abolished, confirming that rapid deadenylylation of glutamine synthetase upon nitrogen stepdown requires functional homotrimeric GlnB protein. Remarkably, however, rapid adenylylation of glutamine synthetase upon exposing nitrogen-starved cells to ammonium was shown to occur in the absence of a functional GlnB/GlnK signalling system as efficiently as in its presence.

Adenosine Monophosphate↗
PubMed1998

Identification of cytochrome P450s in human glioma cell line.

Five different isoforms of cytochrome P450 including 1A1, 1A2, 2E1, 2A and 2B6 have been identified in human glioma Hs 683 cell line using RT-PCR reaction. These isoforms belong to four distinct subfamilies. The effect of benzanthracene (Ba) as inducer was tested on the mRNA level of cytochrome P450 1A1. Northern blot analysis clearly showed an induction response from these cells to Ba in a proportion that is comparable to the induction seen in rat glioma cells.

Aryl Hydrocarbon Hydroxylases↗
PubMed1991

Caloric restriction affects liver microsomal monooxygenases differentially in aging male rats.

Caloric restriction (CR) extends life span and retards the onset of physiological changes and pathologies associated with aging, but the underlying mechanisms remain unresolved. This study demonstrates that CR postpones the documented age-related declines in and/or enhances the activity and microsomal concentration of several liver monooxygenases in male rats, i.e., NADPH cytochrome P-450 reductase, total cytochromes P-450. However, the relative concentration of cytochrome P-450b+C did not exhibit statistically significant changes, whereas another isozyme, the male specific P-450h, declined significantly in both ad libitum-fed and CR rats as a function of increasing age. While CR appears to retard age-associated changes in certain liver enzymes, this effect is by no means universal. The hepatic monooxygenases constitute a well-characterized enzyme system in which to examine the perturbation of the aging process by CR.

Aging↗
PubMed1988

Purification and characterization of liver cytochrome P-446 isolated from protein energy malnourished rats.

A liver cytochrome P-450 isozyme has been purified to homogeneity from protein-energy malnourished rats induced with beta-naphthoflavone (beta-NF). The purification steps included chromatography on DEAE-Sephadex-A-25, DEAE-cellulose (DE-53), hydroxylapatite (HA) and carboxymethyl-sephadex (CM) columns. The reduced carbon monoxide difference and absolute spectra showed a Soret peak at 446.5 nm. The wavelength maxima for the oxidized and reduced spectra were at 416 and 408 nm, respectively. Cytochrome P-446 appears to have a predominantly low spin ferric iron, migrates as a single band of molecular weight 56,000 in sodium dodecyl sulfate polyacrylamide gels and has a specific content of 14 nmol/mg of protein. P-446 oxidized various substrates at different rates in a reconstituted system with NADPH-cytochrome P-450 reductase and dilauroyl-phosphatidylcholine. In this system turnover rates for benzo[alpha]pyrene, testosterone and benzphetamine oxidation were: 81.10; 1.85 and 1.42 nmoles product/min/nmol P-446 respectively. While NH2 terminal amino acid sequence analysis of 18 of the first 20 residues suggests that the cytochrome P-446 isolated from malnourished rats is identical with form c, the catalytic activities suggest that this isozyme may be a more effective or efficient catalyst for some substrates.

Animals↗
PubMed1982

Experimental chemotherapy with N'N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) in autochthonous neurogenic tumors of the rat transplacentally induced by ethylnitrosourea.

Autochthonous neurogenic tumors of the rat induced by transplacental application of ethylnitrosourea were used for the first time to study their suitability as tumor models for experimental chemotherapy. Of 189 transplacentally treated rats, 87% developed neurogenic tumors. After the initial clinical diagnosis of a neurogenic tumor, additional malignant tumors often occurred. The mean number of neurogenic tumors from 62 untreated control rats increased from 1.0 per rat at the time of randomization to 1.2 as revealed by autopsy and 1.5 tumors by histological examinations. Out of all neurogenic tumors, tumors of the brain were observed in 31%, tumors of cranial nerves in 36% (90% tumors of trigeminal nerve), tumors of spinal cord in 21%, and tumors of peripheral nerves in 10%. The median survival time until natural death of 62 control rats was 228 days. Rats with tumors of peripheral nerves lived shortest, followed by rats with tumors of cranial nerves, tumors of the spinal cord, and brain tumors. Brain tumors were mainly astrocytomas and oligodendrogliomas. The survival time of untreated rats from randomization to natural death was longest for those with brain tumors, followed by tumors of peripheral nerves, cranial nerves, and tumors of the spinal cord. There was great variation in survival time from a few days to more than 6 months. To study the responsiveness to chemotherapy, 62 rats received BCNU as a single intravenous dose of 9 and later 10 mg/kg. Sixty-two untreated control rats had a median survival time of 36 days (95% confidence interval 26-52 days), the treated rats 43.5 days (26-62 days). The difference was not statistically significant. BCNU produced a remission or a no change of neurologic symptoms in 60% (37 out of 62) in comparison to 39% (24 out of 62) in the control group (p less than 0.05). The advantages and disadvantages of the present models are discussed. Due to methodical problems and the marginal response to BCNU, autochthonous neurogenic tumors of the rat are not suitable as models for chemotherapeutic studies.

Animals↗