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P Köhler

Publications and source records attributed to P Köhler.

At least 55 records · Page 3Linked to original sources
PubMed1991

The pathways of energy generation in filarial parasites.

It has been commonly accepted that most adult filarial parasites use the glycolytic breakdown of carbohydrates to lactate as a preferred route to supply their energy requirements. Their ability to catabolize glucose by oxygen-dependent pathways is rather limited. An exception to this is the rodent filarial species Litomosoides carinii, which requires a unique type of aerobic glucose metabolism to maintain motor activity and survival. However, the prominent role of carbohydrates as energy substrates for filariids may no longer be tenable. Recent studies have shown that glutamine is a major energy source in filarial worms and that a fully oxidative mitochondrial metabolism can be employed for the utilization of this substrate.

Journal Article↗
PubMed1991

In vitro effects of 2-tert-butyl-benzothiazole derivatives on microfilariae of Litomosoides carinii, Brugia malayi and Acanthocheilonema viteae.

Six 2-tert-butyl-benzothiazole derivatives (2-tert-butyl-6-iso-thiocyanato-5-methyl-benzothiazole CGP 21306); 3-[(2-tert-butyl-5-methyl-benzothiazole-6-yl) aminothiocarbonylthiol] propionic acid (CGP 21835); 2-tert-butyl-5-methyl-6-(N-methyl-piperazinyl-thiocarbonylamino)-b enzothiazole (CGP 21833); 2-tert-butyl-5-methyl-6-(4-dimethylamino-piperid-1-yl-thiocarbo nylamino)- benzothiazole (CGP 26702); CGP 20376, the 5-methoxy analogue to CGP 21835 and CGP 20309, the 5-methoxy analogue to CGP 21833) with known, high filaricidal activity in vivo were tested for in vitro efficacy against microfilariae of L. carinii (Lc), B. malayi (Bm) and A. viteae (Av) in order to study intrinsic antifilarial activities. All drugs affected the motility of the microfilariae of the three species in a species, dose and time dependent fashion. Lc was the most sensitive, Av the most resistant species. CGP 20376 and 21835 were the most effective compounds followed by CGP 21306. Complete immobilization of microfilariae was observed after 20 h in protein-free medium RPMI 1640 at drug concentrations of 0.1 to 10 nmol/ml. Effects were still marked 2 when graded on a 4 (full motility) to 0 (immobile) scale at concentrations of 0.01-0.1 nmol/ml. In the case of the thiourea derivatives CGP 21833, 26702 and 20309 concentrations had to be increased 10-100 fold to obtain similar effects. When proteins were present in the incubation medium (10% foetal calf serum, 100% normal serum) the efficacy of the compounds was reduced, i.e. drug concentrations had to be increased up to 100 fold to produce similar effects as in protein-free medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Antifilarial efficacy in vitro of 2-tert-butyl-benzothiazole derivatives on adult Litomosoides carinii.

Six 2-tert-butyl-benzothiazole derivatives (2-tert-butyl-6-isothiocyanato-5-methyl-benzothiazole (CGP 21306); 3-[(2-tert-butyl-5-methyl-benzothiazole-6-yl)aminothiocar-bonyl thiol] propionic acid (CGP 21835); 2-tert-butyl-5-methyl-6-(N-methyl-piperazinyl-thiocarbonylamino)- benzothiazole(CGP 21833); 2-tert-butyl-5-methyl-6-(4-dimethylamino-piperid-1-yl-thiocarbo nylamino)- benzothiazole (CGP 26702); CGP 20376, the 5-methoxy analogue to CGP 21835 and CGP 20309, the 5-methoxy analogue to CGP 21833) were tested in vitro against adult Litomosoides carinii. When exposed to the drugs in protein-free medium RPMI 1640 drug concentrations of 1 nmol/ml caused complete immobilization of female worms within 4 h (CGP 21306, 21835, 20376) or 20 h (CGP 21833, 26702, 20309). Short term exposure for 1 h had similar effects with CGP 21306, 21835, 21833 and 20376. However, the levels of CGP 26702 and 20309 (both thiourea derivatives) had to be increased to 10 nmol/ml to obtain complete immobilization after short term exposure. Male parasites were more resistant to the drugs than females under these experimental conditions. When the medium was supplemented with 10% foetal calf serum (FCS) the efficacy of all compounds was reduced. The effect of the compounds during permanent and short term exposure on the release of microfilariae was determined over an incubation period of 7 days (medium RPMI 1640/10% FCS). In general only drug concentrations which affected markedly the motility of the worms within 2 days reduced significantly the number of microfilariae released by treated worms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Development of bed potential and occupancy in hospitals of East Germany].

In the former GDR, in-patient treatment had been performed mainly by governmental hospitals. Between 1950 and 1989 the number of hospitals was reduced from 1060 to 539 by closing uneconomic small hospitals or by combining them with bigger ones. During the same period the number of beds decreased from 197,219 to 163,305. Finally, 98.2 bed accommodations existed per 10,000 inhabitants. Information is given on personnel, financing and on the structural status of the hospitals. In-patients discharges of the hospitals were recorded by uniform documentation over about 20 years. It was therefore possible to evaluate in-patient morbidity.

Bed Occupancy↗
PubMed1990

[Early and late results after local streptokinase administration in massive lung embolism].

In a total number of 44 patients with acute massive lung embolism 42 patients survived the acute phase. The treatment was carried out by thrombolysis with streptokinase. The application was performed as near to the thrombus as possible, in several patients after preceding balloon dilatation or also as multiphase treatment using urokinase. We altogether obtained favourable early results concerning the recanalisation got as well as also with regard to the clinical state and the subjective condition, particularly for patients with single acute occurrence and a latency period of less than 72 hours up to the beginning of the treatment. In follow-up examinations of 17 patients after more than 9 months (on an average after 32 months) without exception a good and further on ameliorated condition, respectively, was stated. Under long-term anticoagulation with phenprocoumon no recidivation embolisms appeared. Ergooxytensiometric investigations had as result a clear to extreme hypoxia on exertion as limiting factor for 12 out of 17 patients. Apart from this the majority of the patients a hyperdynamic regulatation of the circulation was to be observed. Therefore the ergooxytensiometry is recommended for the judgment of the result of the treatment as to the demandable exercise tolerance.

Adult↗
PubMed1990

High-pressure glycosylations of unreactive alcohols and the formation of N-glycosyl collidinium salts.

The yields of disaccharide glycosylation products in tetramethylammonium bromide or silver triflate-collidine activated reactions between hindered alcohols and glycosyl halides were not greatly ++affected when a pressure of 15 kbar was applied. The formation of orthoester products was greatly increased under pressure. When orthoester formation was not possible both disaccharides and the related N-glycosyl collidinium salts were found.

Alcohols↗
PubMed1990

The role of amino acids in the energy generating pathways of Litomosoides carinii.

The filarial parasite Litomosoides carinii was able to survive for longer than 15 h in basic filarial medium (BFM) containing either glutamine or alanine as a sole substrate. The filariids were more motile in BFM containing glucose, but even higher motility was recorded in media containing both glucose and glutamine. Incubations under aerobic conditions showed that radiolabelled glutamine was metabolised primarily to CO2. In addition, small amounts of lactate and acetate were excreted in almost equimolar quantities. Incubations where both glutamine and glucose were present demonstrated that the glutamine carbon utilised by the parasite could be completely recovered in the above three end products. The glutamine nitrogen could be recovered in the additional excretory products, alanine and ammonia. The glutamine-dependent viability of L. carinii was affected by known inhibitors of the mitochondrial respiratory chain. Glucose utilisation, and the production of CO2 from this substrate, were greatly stimulated by the presence of glutamine in the external medium. Various carbon balance studies, in conjunction with enzymatic analyses, suggest that in L. carinii, glutamine provides an input of carbon into the tricarboxylic acid (TCA) cycle, probably at the level of alpha-ketoglutarate. This increased availability of Krebs cycle intermediates will stimulate the rate of pyruvate oxidation via acetyl-CoA and the TCA cycle, and thus increase the rate of carbon flux through glycolysis. The energetic advantage associated with the utilisation of the glucose/glutamine substrate couple may explain the worm's enhanced motor activity compared to incubations with glucose as the sole energy source. Alanine was found to be degraded by the filariid to equivalent amounts of lactate, acetate and CO2, indicating a relatively low energetic efficiency. There was no detectable uptake of glutamate. A variety of other amino acids tested were neither metabolised nor able to maintain worm viability in vitro.

Acetates↗
PubMed1990

Osteogenic enhancement of diaphyseal reconstruction. Comparison of bone grafts in the rabbit.

We investigated incorporation of autoclaved autografts in segmental defects of rabbit humeri for comparison with a previous study on similar grafts supplemented with demineralized allogeneic bone matrix (DABM). We also made similar reconstructions with frozen allografts--both DABM and nonsupplemented allografts. Before the animals were killed at 8 months, they underwent scintigraphy, showing that all 28 humeral reconstructions were metabolically active. Faxitrone radiography showed nonunion in three of nine with autoclaved autografts and in two of eight with frozen allografts, whereas all 11 DABM-supplemented frozen allografts had incorporated. Taking into account only the 23 healed reconstructions, the mean torsional strength in relation to the contralateral nonoperated on humeri was 0.81 for all three groups. Histologically, new bone enveloping, partly replacing, the implants was more abundant in DABM-supplemented reconstructions. Our study shows that osteogenic enhancement is more important than the type of nonviable bone chosen for diaphyseal repair. However, if healing is obtained, osteogenic enhancement per se does not increase the strength.

Animals↗
PubMed1990

Electrophoretic characterization of Giardia isolated from humans, cattle, sheep, and a dog in Switzerland.

Nine isolates of Giardia lamblia from humans, cattle, sheep, and 1 dog were compared by employing agarose gel isoenzyme electrophoresis and isoelectric focusing of total soluble cell protein on polyacrylamide gels. The banding patterns of the 14 enzymes examined showed remarkable similarities among the Swiss Giardia isolates. This was true also of the total soluble trophozoite proteins. The electrophoretic mobilities of most enzymes and other proteins obtained for the Swiss isolates were the same as those of 2 isolates from humans in other geographical areas, the WB and the Portland-1 strains. Only the human isolate CH-H2 could clearly be distinguished from all other isolates analyzed. The great biochemical similarities observed among the Swiss isolates contrast with the extensive heterogeneity previously demonstrated for G. lamblia by other investigators who used similar analytical techniques. These data are consistent with recent transmission studies of Giardia and suggest that in Switzerland domestic animals may serve as a reservoir of human Giardia infections and that cross-transmission between humans and animals is likely to occur.

Animals↗
PubMed1990

[The validity of sodium excretion in urine in normotensives and hypertensives in a selected population].

Salt intake of 503 people from the south western area of the GDR was investigated. Salt intake is high (151 mmol/d), but lower then expected. There are no important differences between people without (140 mmol/d) and with (161 mmol/d) a essential hypertension. Salt intake of male is higher than female persons. There is no correlation between the height of salt intake and the elevation of systolic or diastolic blood pressure.

Adult↗
PubMed1989

Litomosoides carinii: mode of action in vitro of benzothiazole and amoscanate derivatives with antifilarial activity.

It is suggested that the recently developed benzothiazole and amoscanate derivatives with antifilarial activity exert their action in vitro by an inhibition of mitochondrial-derived respiration. It was confirmed that the drugs CGP 20376, 21835, 20308, 21306, and 6140 cause a rapid immobilization in vitro of the adult filarial worm, Litomosoides carinii, the time required being similar to rotenone at the same concentration. The other drugs investigated, CGPs 20309, 21833, 24589, 23518, and 13231, were also effective; however, they required much longer incubation times. Submitochondrial particles (SMP) were prepared from Ascaris muscle and rat liver. The concentration of drug causing 50% inhibition of respiration (IC50) was calculated. It was found that the drugs most rapidly inhibiting respiration have IC50s for NADH oxidase of less than 25 microM in both Ascaris and rat liver SMP. This effect on SMP respiration could be overcome by using succinate as a substrate, indicating the site of inhibition to be within complex I of the mitochondrial respiratory chain. Further experiments showed that whereas the respiratory chain's NADH:ferricyanide reductase was unaffected by these drugs, there were pronounced effects on both Ascaris and rat liver NADH:quinone reductase activity. This suggests that the inhibition within complex I occurs after the flavoprotein dehydrogenase, but before the site of the quinone reduction. The other compounds examined, which had a slower effect on motility, also showed inhibition of the NADH oxidase, but not to as great an extent as the aforementioned compounds. The compounds most active against motility were also most effective at inhibiting respiration in intact adult L. carinii. Analysis of the aerobic end products produced by L. carinii showed that acetate production was greatly reduced even in the presence of low concentrations of the drugs. There was also a slight decrease in lactate production. However, a direct effect on the glycolytic pathway was ruled out by two observations. One, that the production of lactate from cell-free extracts of L. carinii is unaffected by the presence of the drugs, and secondly, that a protozoan, Giardia lamblia, reliant on glycolysis for energy production, can survive for long periods of time in the presence of high concentrations of the drugs. A correlation can be observed between the time for immobilization of the filarial worm and the strength of inhibition of mitochondrial respiration. Therefore, it is suggested that, at least in vitro, the mechanism of toxicity of these antifilarials in L. carinii is due to the blocking of the respiratory chain at a site similar to that of rotenone.

Anaerobiosis↗
PubMed1989

Comparison of CAD-CAM and hand made sockets for PTB prostheses.

The aim of the present study was to compare sockets for below-knee (BK) prostheses made by Computer Aided Design-Computer Aided Manufacture (CAD-CAM) to those made by hand. The patients in the study were provided with two prostheses each, which apart from the sockets, were identical. One socket was made by the CAD-CAM technique developed at the Bioengineering Centre, Roehampton, University College London and one was made by hand at the OT-Centre, Stockholm, Sweden. The results were based on investigation of eight unilateral below-knee amputees evaluating their own sockets by Visual Analogous Scale with respect to comfort, pressure, and pain. The sockets were evaluated on seven occasions, at two tests, on delivery, after use every second day for six days and every second week for two weeks. All CAD-CAM sockets except one had to be changed once as compared to the hand made of which only two had to be changed. As to comfort it could not be demonstrated that there was any significant difference between the two types of sockets and both types were well accepted by all patients. Differences in pressure and pain were rarely reported. There were obvious differences between the two types of socket with respect to height, width, and inner surface configuration. The authors feel that CAD-CAM will in the near future be an excellent tool for design and manufacture of prosthetic sockets.

Artificial Limbs↗
PubMed1989

Bacteria on stumps of amputees and the effect of antiseptics.

Amputees get stump infections usually from the natural inhabitants of the healthy skin and probably due to the unnatural environment of tight fitting sockets. The aim of the present study was to investigate the natural stump bacteria and the effect of antiseptics as well as the amputees' evaluation of such treatment. Fifteen amputees using their prostheses all day were investigated. Bacterial samplings were taken by swab technique with respect to bacteria and fungi from the stumps in the morning before prosthetic application and in the evening after a whole day's prosthetic use without antiseptic cleaning; after antiseptic cleaning with a combination of Isopropanol 45%. N-propanol 30% and N-cetyl-pyridiniumchloride 0.2% for one day: after fourteen days continuous use. The patients were asked if they liked the antiseptic and if they would like to continue to use it. Two patients did not submit bacteriological samples after the cleaning period. Before cleaning S. epidermidis, S. aureus and alpha-hemolytic streptococci were commonly found. In two instances gram negative rods were found. After the cleaning period there was a reduction of bacteria in 11 out of 13 patients. All patients liked the antiseptic and the simplicity by which the stumps and the sockets could be kept clean. The authors feel that the use of antiseptics to increase stump and socket hygiene is justified.

Adolescent↗
PubMed1989

[Triglyceride determination with the Sumal system in routine operations].

A micromethod for determination of serum triglyceride concentrations using the Sumal-system and the sampler Sumal PVS 100 will be described. The results show that the qualitative, technical and economic parameters of the method (coefficient of variation 5%, 500 specimens per day and examiner, cost of reagents 0.50 M per test) correspond to the requirements of standard techniques and methods used in prevention trials. The method is suitable for use in routine clinical laboratory.

Costs and Cost Analysis↗