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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 541 records · Page 30Linked to original sources
PubMed1988

Peptide conformation. 48. Conformation and biological activity of proline containing cyclic retro-analogues of somatostatin.

Six cyclic retro-analogues of the peptide hormone somatostatin have been synthesized using the solid phase technique. The peptides cyclo(-Xaa1-Phe2-Thr3-Lys4-Ybb5-Phe6-) and cyclo(-Phe1-Xaa2-Thr3-Lys4-Ybb5-Phe6-) with Xaa = D- or L-Pro and Ybb = D- or L-Trp were cyclized via the azide method. The conformations of the cyclic hexapeptides in DMSO-d6 solution were determined by a number of homo- and heteronuclear two-dimensional n.m.r.-techniques including 2D rotating frame NOE-spectroscopy. Two-step coherence transfers, ROE and chemical exchange, are observed for the first time in ROESY spectra. The backbone conformation of the all-trans cyclopeptides consists of a beta-turn containing the Pro residue in the position i + 1. These retro-analogues of somatostatin exhibit a high activity in the inhibition of cholate and phalloidin uptake by liver cells (cytoprotective effect); however, the hormonal activities of the natural hormone are completely suppressed. The constitutional and conformational requirements for the cytoprotective activity are discussed.

Amino Acid Sequence↗
PubMed1988

[Reye-like syndrome following valproate therapy in an adult].

Three months after anticonvulsive regulation by means of the spasmolytic agent Convulsofin, a 46-year-old man suffered severe hepatosis, and when the preparation was discontinued he suffered a severe cerebral dysfunction. The clinical picture is interpreted as being "similar to the Reye syndrome", and distinctions between this and previously reported cases are noted. There has been very little observation of such complications among adult patients.

Chemical and Drug Induced Liver Injury↗
PubMed1988

High affinity dextromethorphan binding sites in guinea pig brain: further characterization and allosteric interactions.

Dextromethorphan (DM), a non-narcotic antitussive with anticonvulsant activity, binds to high (Kd, 57 nM)- and low-affinity sites (Kd, 24 microM) in the guinea pig brain. This work, done at physiological pH, expands previous results obtained at pH 8.3. Phenytoin (PHT) produces an allosteric increase in the binding of [3H]DM, which is more marked than that reported previously: PHT (100 microM,) at pH 7.4, increased the binding affinity of [3H]DM to brain homogenates 4-fold, without changing the concentration of DM sites. Moreover, ropizine (SC-13504) an anticonvulsant benzhydryl piperazine, also produced a marked concentration-dependent increase in the binding of [3H]DM, which is mediated by a decrease in the dissociation rate of [3H]DM. Importantly, the effects of ropizine are fully apparent at 10 microM, 10-fold lower than those of PHT. The effects of PHT and ropizine show that the affinity of the DM sites can be increased by other ligands, suggesting that these sites are located on macromolecules that can exist in at least two conformational states. [3H]DM also binds to peripheral tissues, but the brain displays the highest affinity. Besides, the central and peripheral sites are different as determined by competition studies with caramiphen and carbetapentane, which are DM site ligands with antitussive and anticonvulsant activity. The results reported in this communication are consistent with the hypothesis that the high-affinity DM binding sites mediate antitussive and anticonvulsant activity when occupied by the appropriate ligand.

Animals↗
PubMed1988

[Reduced suppression of gastric acid by ranitidine in severe reflux esophagitis. A pilot study].

Repeated intragastric long-term pH recordings for 24 h were conducted in 13 patients with reflux oesophagitis grade III and IV (Savary and Miller) during treatment with ranitidine 150 mg b.i.d. and 300 mg b.i.d. and omeprazole 40 mg mane (n = 5). Ranitidine led to a significantly less pronounced increase in median gastric pH in oesophagitis than in healthy controls. The magnitude of intragastric pH increase showed parallelism to symptomatic response and healing. Omeprazole increased intragastric pH above 4 for 24 h and caused rapid healing in non-responders. It is concluded that in patients with severe reflux oesophagitis ranitidine is less effective in increasing intragastric pH than in controls, whereas omeprazole reveals potent antisecretory activity accompanied by rapid healing.

Adult↗
PubMed1987

The hospital as a vector of measles in the community.

Over a 16-month period 77 consecutive cases of life-threatening measles admitted to the intensive care unit of the Red Cross War Memorial Children's Hospital were surveyed. Twenty-eight children died and 9 were left with chronic respiratory disease. Twenty of these 77 children probably caught the disease in hospital. Of these, 10 (50%) died compared with 18 (32%) of the 57 who acquired measles in the community, confirming that hospital-acquired measles is particularly severe. It is concluded that hospitals contribute substantially to the spread of measles in the community. Optimal strategies for dealing with this problem are urgently needed.

Child↗
PubMed1987

Soft tissue pseudotumor following intramuscular injection of "DPT": a pitfall in magnetic resonance imaging.

We report the time-dependent magnetic resonance imaging (MRI) changes that resulted from an intramuscular injection of a commonly-used pediatric sedation regiment ("DPT"). These changes at the site of injection consist of a focal abnormality characterized by a slight increase in signal intensity on T1 weighted images and markedly increased signal intensity on T2 weighted images. Alterations in signal are detectable almost immediately after the injection and progress over the first 31 hours. This abnormality, which could be mistaken for real disease, persists up to 36 days following injection.

Child↗
PubMed1987

Allosteric modulation of dextromethorphan binding sites.

The nonopioid antitussives dextromethorphan (DM), carbetapentane and caramiphen are efficacious anticonvulsant agents in the rat MES test. The findings presented strongly suggest the existence of a novel allosteric mechanism by which drugs acting at two different but interacting sites, exert their effects. This mechanism has marked similarities with the gamma-aminobutyric acid (GABA)-benzodiazepine interactions, even though their binding sites are different. The allosteric interactions of dextromethorphan and phenytoin in the binding assay and the potentiation of the anticonvulsant effects of phenytoin by dextromethorphan suggest that drugs that bind to the dextromethorphan sites could be used to reduce the effective dose of phenytoin and reduce its side effects, at least those which are not an extension of its specific pharmacological actions. It is evident that the investigation of the molecular mechanisms described may help to open new approaches to understand and treat convulsive disorders, to find novel anticonvulsant drugs and to further explain some of the molecular mechanisms of neuronal excitability.

Animals↗
PubMed1987

[Nutrient dependence of energy conservation requirements in rats. 4. The influence of protein levels of food on energy conservation requirements of rats during growth and after conclusion of the intensive growth phase].

Albino rats bred in the institute (Wistar line) divided into 3 groups of 9 animals each received, beginning at the age of 4 weeks, feed mixtures with 10, 40 and 70% protein in the rations over a period of 24 weeks divided into 14 subperiods of study. The feed mixture changed cyclically for the groups of animals after each sub-period. Every period was divided into a growth period (8 days) with the rats kept in metabolism cages and a period of feeding on maintenance level (4 days) with the rats kept in respiration chambers. In both periods the temperature was kept constant at 30 degrees C. On 3 days of feeding on the maintenance level the metabolism parameters of energy, C and N metabolism were measured and energy maintenance requirement was ascertained. Both the energy maintenance requirement of the growing rats (up to 200 g live weight) and that of the nearly fully grown and fully grown rats resp. (greater than 200 g live weight) significantly depended on the nutrient composition of the feed mixtures supplied. It increased with the increasing protein and simultaneously decreasing carbohydrate quotas in the feed. On an average of the studies the rats had, in the sequence of 10, 40 and 70% protein content, an energy maintenance requirement of 383 +/- 31 (n = 105), 415 +/- 31 (n = 106) and 459 +/- 36 kJ metabolizable energy/kg LW0.75.d (n = 102). Energy maintenance requirement behaved relatively like 100:108:120. Based on the fact that energy maintenance requirement may be considered the requirement of ATP, relative expectancy values for energy maintenance requirement can be calculated with the energetic efficiency of the ATP synthesis (kJ metabolizable energy/Mol ATP gain) in nutrient catabolism from the relation of the experimentally ascertained nutrient metabolism at a variant supply of protein of 100:110:118. The hypothesis that the efficiency of ATP synthesis in the catabolism of the main nutrients supplying energy can be considered a relative measure of the dependence of the energy maintenance requirement on nutrient composition has been confirmed in this experiment. Different findings in earlier experiments raise the question if those findings were influenced by adaptation effects. An experimental solution of this question is considered important.

Adenosine Triphosphate↗
PubMed1987

[Consequences of nutritional and husbandry factors on the heat production of rats and broilers. 2. Effect of environmental temperature on the heat production of fully grown broilers and rats].

In an experiment with broilers (origin Tetra B) and with rats (albino, Wistar line) with 2 animals each, heat production was ascertained by measuring CO2 production and O2 consumption over 20 minutes after their feeding 18 h and 1 h before the beginning of measuring at ambient temperatures of 30, 25, 20, 15 and 10 degrees C. Every variant was followed through over 6 h/d in 12 measuring sections. The feed amount/ánimal and day was adapted to energy maintenance requirement. At the beginning of the experiments the broilers and rats were 14 and 21 weeks old resp. and weighed 2.2 kg and 220 g resp. The variation of the ambient temperature did not influence the heat production of the broilers. In contrast to this, the time of feeding in relation to the beginning of measuring had a distinct effect on heat production. Whereas a heat production of 342 +/- 34 kJ/kg LW0.75.d was ascertained in the postabsorptive state 18 h after the last feed intake, it increased by 11% to 393 +/- 32 kJ/kg LW0.75.d when measuring began 1 h after feeding. The very act of feed intake increased heat production by 75%. Rats showed a distinct increase of heat production caused by a decreasing ambient temperature. In the temperature range of 30-25 degrees C the increase was shallower than in the range of 25-10 degrees C. Per 1 degrees C below 25 degrees C heat production increased by 30 kJ/kg LW0.75.d. The increase was independent of the metabolism level, which was influenced by the feeding variants. The results are discussed in connection with Rubner's theory of heat compensation.

Animal Feed↗
PubMed1987

Antihypertensive and hypotensive actions of atiprosin (AY-28,228) in rats, dogs, and monkeys.

Atiprosin, a chemically novel octahydro-pyrazino-pyrido-indole, exerts antihypertensive effects in spontaneously hypertensive, deoxycorticosterone acetate hypertensive, and renal-hypertensive rats over a dose range of 0.1-10 mg/kg per os (p.o.). In terms of relative potency, atiprosin was calculated to be seven to fifteen times less potent than prazosin, five to sixteen times more potent than ketanserin, and 14-25 times more potent than indoramin, depending on the hypertensive model examined. Atiprosin had good oral bioavailability (p.o./i.v. ratio = 1.25), and there was no evidence from rat studies for tolerance on repeated administration. The compound also exerted hypotensive effects in normotensive rats and monkeys at 1-10 mg/kg p.o.; in neither species was there evidence of drug-induced tachycardia. Experiments in anesthetized dogs suggest that atiprosin may be similar to prazosin with respect to its liability to produce orthostatic hypotension as a side effect.

Administration, Oral↗
PubMed1987

Reconstruction of mandibular and floor of mouth defects using the trapezius osteomyocutaneous flap.

The trapezius osteomyocutaneous island flap has evolved in postablative head and neck reconstruction as a versatile and hardy local flap which can provide intraoral lining, well-vascularized bone, and muscle bulk for the reconstruction of a complex defect. This investigative study examines the anatomy of 20 osteomyocutaneous flaps in 10 fresh cadavers and in 8 clinical patients. In our series, 80 percent (type I) of the major vascular pedicle arose from the thyrocervical trunk. In 20 percent (type II), the major pedicle arose separately from the subclavian artery. The regions perfused by the vascular trunk were further examined with microopaque and Prussian blue injections through the transverse cervical artery. Consistent areas of cutaneous staining as well as bony staining were noted over the shoulder, arm, and back and into the scapula itself. Experience with eight clinical applications of this osteomyocutaneous flap resulted in successful healing with an excellent aesthetic and functional result. Long-term follow-up was maintained on the patients for up to 36 months. Panorex radiographs and biopsies of the grafted bone were obtained on several patients. These disclosed evidence of bony remodeling and viable bone tissue. Tetracycline labeling also revealed evidence of active bony turnover.

Cadaver↗