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Biomedical subjects

M Mayer

Publications and source records attributed to M Mayer.

At least 55 records · Page 3Linked to original sources

Synthesis and cytotoxicity of gossypol related compounds.

Gossypol, gossypolone, reduced gossypol and new Schiff's bases of racemic gossypol and gossypolone were extracted or synthesized. Their cytotoxic activities on KB human cancer cells were determined. Gossypolone and the ethylamine derivative of gossypolone were the most active compounds (IC(50) in the micromolar range in both cases). The cytotoxicity of gossypol and gossypolone was increased when the tests were performed in the absence of serum and decreased when catalase as well as mannitol were added to the culture medium.

Antineoplastic Agents↗

Structure and function of the ion channel ICln.

Normal function of organs and cells is tightly linked to the cytoarchitecture. Control of the cell volume is therefore vital for the organism. A widely established strategy of cells to counteract swelling is the activation of chloride and potassium channels, which leads to a net efflux of salt followed by water - a process termed regulatory volume decrease. Since there is evidence for swelling-dependent chloride channels (IClswell) being activated also during pathological processes, the identification of the molecular entity underlying IClswell is of utmost importance. Several proteins are discussed as the channel forming IClswell, i.e. phospholemman, p-glycoprotein, CLC-3 and ICln. In this review we would like to focus on the properties of ICln, a protein cloned from a Madin Darby canine kidney (MDCK) cell library whose expression in Xenopus laevis oocytes resulted in a nucleotide sensitive outwardly rectifying chloride current closely resembling the biophysical properties of IClswell.

Amino Acid Sequence↗

Stereoselective metabolism of the monoterpene carvone by rat and human liver microsomes.

The large amounts of carvone enantiomers consumed as food additives and in dental formulations justifies the evaluation of their biotransformation pathway. The in-vitro metabolism of R-(-)- and S-(+)-carvone was studied in rat and human liver microsomes using chiral gas chromatography. Stereoselective biotransformation was observed when each enantiomer was incubated separately with liver microsomes. 4R, 6S-(-)-Carveol was NADPH-dependently formed from R-(-)-carvone, whereas 4S, 6S-(+)-carveol was produced from S-(+)-carvone. Metabolite formation followed Michaelis-Menten kinetics exhibiting a significant lower apparent Km (Michaelis-Menten Constant) for 4R, 6S-(-)-carveol compared with 4S, 6S-(+)-carveol in rat and human liver microsomes (28.4+/-10.6 microM and 69.4+/-10.3 microM vs 33.6+/-8-55 microM and 98.3+/-22.4 microM). The maximal formation rate (Vmax) determined in the same microsomal preparations yielded 30.2+/-5.0 and 32.3+/-3.9 pmol (mg protein)(-1) min(-1) in rat liver and 55.3+/-5.7 and 65.2+/-4.3 pmol (mg protein)(-1) min(-1) in human liver microsomes. Phase II conjugation of the carveol isomers by rat and human liver microsomes in the presence of UDPGA (uridine S'-diphosphogluaronic acid) only revealed glucuronidation of 4R, 6S-(-)-carveol. Vmax for glucuronide formation was more than 4-fold higher in the rat liver compared with human liver preparations (185.9+/-34.5 and 42.6+/-7.1 pmol (mg protein)(-1) min(-1), respectively). Km values, however, showed no species-related difference (13.9+/-4.1 microM and 10.2+/-2.2 microM). This study demonstrated stereoselectivity in phase-I and phase-II metabolism for R-(-)- and S-(+)-carvone and might be predictive for carvone biotransformation in man.

Animals↗

Association of serum bilirubin concentration with risk of coronary artery disease.

BACKGROUND: Lipid oxidation and formation of oxygen radicals are important elements of arterial plaque formation and atherosclerosis, and are involved in the pathophysiology of coronary artery disease (CAD). Because bilirubin has antioxidant properties, it has been suggested that it may have a protective role in the atherosclerotic process. APPROACH: This review examines in vitro and in vivo studies indicating that bilirubin inhibits lipid oxidation and oxygen radical formation. Experimental and epidemiological evidence is presented that suggests that bilirubin may serve as a physiological antioxidant providing protection against atherosclerosis and CAD. Special attention is focused on studies that noted an inverse relationship between plasma bilirubin concentration and cardiovascular morbidity. CONTENT: Serum bilirubin concentrations in the upper portion of the reference interval reportedly reduce atherogenic risk and provide protection against CAD. In contrast, serum bilirubin concentrations in the lower portion of the reference interval may be associated with increased risk of ischemic heart disease. SUMMARY: Taken together, the evidence presented in this review supports the concept that bilirubin, via its antioxidant potential, has antiatherogenic properties and that an inverse relationship exists between circulating bilirubin concentrations and risk of CAD.

Arteriosclerosis↗

Fritless capillary electrochromatography.

The preparation of packed capillaries with stable frits of good quality can be a hurdle to obtain efficient separations in capillary electrochromatography (CEC). Especially with particles smaller than 3 microm, frit preparation is cumbersome. Highly efficient separations using packed capillaries without frits are presented. Under appropriate CEC conditions the particles were retained by electrophoretic attraction towards the anode by a tapered capillary inlet, without the need of a frit at the outlet end. Such fritless capillaries, packed with 1.5 microm nonporous reversed-phase particles, allowed separations with efficiencies of more than 500,000 plates/m. Once the capillaries were conditioned properly, more than 100 separations could be performed with good repeatability. With respect to separation efficiency, fritless capillaries packed with 3 microm particles were comparable with standard CEC capillaries with frits. Examples of separations of steroids, a pesticide and its by-products, and cardiac glycosides under various CEC conditions are shown.

Chromatography, Liquid↗

Muscle and skin biopsies are a sensitive diagnostic tool in the diagnosis of CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a microangiopathic syndrome. Although the defective gene has been identified, genetic analysis may be effort some due to its large size and various mutations. Providing a reliable diagnostic marker would therefore be helpful. Electron microscopy has revealed characteristic electron-dense granular deposits in the basal lamina of vessels of patients with CADASIL. We investigated the sensitivity of skin and muscle biopsies for diagnosing CADASIL. We examined 30 family members of three unrelated German families affected by CADASIL. In 14 of the 21 affected individuals we performed skin and muscle biopsies; two patients were clinically asymptomatic. Under electron microscopy all muscle and skin biopsy specimens showed patches of granular and electron-dense material in the basal layer of both arterioles and capillaries. These findings confirm that general microangiopathy is a typical feature of this syndrome and is present in the early phase of the disease with or without clinical manifestation. Thus, as electron microscopy of skin biopsy specimens can establish the diagnosis of CADASIL with high certainty, it may be considered the method of first choice.

Adult↗

Dipole source analysis in persistent mirror movements.

To elucidate the pathomechanism underlying persistent mirror movements (MM), we modelled the origin of electric brain activity associated with these movements. Movement-related cortical potentials (MRCP) in a group of subjects affected by persistent mirror movements were compared with those of a control group. The data of the normal subjects were best explained with two bilaterally active electric sources in the sensorimotor cortices with a clear preponderance of the hemisphere contralateral to the movement. In contrast, the MM subjects presented a fairly symmetric source activity in both hemispheres during unilateral intended movements. In the control group, the source representing the activity of the motor cortex ipsilateral to the moving finger reduced activity before the beginning of the movement; this was interpreted as an inhibition of the ipsilateral motor cortex during unilateral movement. In the MM group, however, this inhibition was not seen. Furthermore, while normal subjects demonstrated no relevant activity of an additional source placed near midline motor structures (supplementary motor area; SMA), subjects with MM showed considerable activity of this dipole source. These findings suggest that subjects with persistent MM have abnormal bilateral activation of the primary motor areas, probably together with an additional activation of mesial motor structures. This assumption fits well with the observation of an incomplete decussation of the pyramidal tract. The bilateral activation is then explained as a compensatory strategy in order to achieve sufficient force in the innervated target muscles.

Adolescent↗

[Splenic rupture as a complication of ventilation in the prone position and pneumococcal sepsis as a late complication].

We are reporting the case of a female patient who had to undergo splenectomy after she suffered splenic rupture as a result from "kinetic therapy" during the treatment for pulmonary failure secondary to sepsis. Four years later the patient was again admitted with a clinical picture consistent with sepsis. Two blood cultures were positive for pneumococci confirming the diagnosis of pneumococcal sepsis. This paper discusses the potential risks of kinetic therapy in patients with ARDS. After splenectomy there is increased risk of infection with certain bacteria, funghi, viruses and protozoa. The most common bacterial pathogen is pneumococcus. A polyvalent vaccine is available for prophylaxis. Although penicillin G is still commonly used as an antibiotic therapy for pneumococcal infection, increased resistance of pathogens to penicillin must be anticipated. Alternative antibiotic regimens are demonstrated.

Female↗

Qigong and hypertension: a critique of research.

Research studies have pointed to various health-related positive effects of qigong; however, problems in much of the current qigong research methodology have limited interpretation of the potential benefits of qigong. Examples of research on qigong and hypertension are used to bring to light some of these methodological issues. In a review of 30 representative studies, various areas of concern are addressed, including: the sources of studies, lack of random assignment, selection biases, treatment effects, placebo response issues, expectancy biases, blinded outcome assessment, adherence to treatment, reliability of blood pressure measurements, regression to the mean, publication biases, and lack of consistency of measurement. One of the longest term studies, conducted by Kuang et al. (1991) and updated by Wang et al. (1993) is examined in greater detail to illustrate these issues. This study took place over 20 years and reported significant differences between a group practicing qigong and a control group in a variety of measures including a reduction of total mortality rate. The weight of evidence suggests that practicing qigong may have a positive effect on hypertension. Whether qigong alone can affect hypertension is not necessarily the most important question. Further research will be required to better assess and understand the effect of adding qigong into an integrated, multifaceted program that selectively incorporates diet, moderate aerobic exercise, relaxation training, and social and psychological dimensions.

Breathing Exercises↗

[The bronchorelaxant effect of helicidine, a Helix pomatia extract, interferes with prostaglandin E2].

Helicidine is a biological extract prepared from the snail Helix pomatia L. and used in man as an anti-tussive agent. However, its mechanisms of action are not fully defined. In this study, we have investigated a possible relaxant effect of helicidine on guinea-pig airway smooth muscle and evaluated the role of prostanoids and airway epithelium in this relaxation. H. pomatia extract (0.001-1 mg/ml) induced a dose-dependent relaxation of guinea-pig trachea pre-contracted with histamine both in the presence and absence of tracheal epithelium. No significant difference in dose-dependency or magnitude of the relaxation was observed between tracheal segments with or without epithelium (maximal relaxant response of 35 +/- 7 and 25 +/- 7.5%, respectively). Relaxation of the trachea induced by H. pomatia extract (0.001-1 mg/ml) was inhibited by pre-treatment with the cyclooxygenase inhibitor, indomethacin, both in the presence or absence of tracheal epithelium. H. pomatia extract (1 mg/ml) induced a marked and significant increase in prostaglandin E2 release in tracheal segments with and without epithelium. These results indicate that helicidine possesses a broncho-relaxant activity which is independent of epithelium integrity and which is partly mediated by the release of the relaxant prostanoid, prostaglandin E2. The origin of prostaglandin E2 production in the airways remains to be defined.

Animals↗

Effect of nitric oxide metabolism upon peripheral blood chemiluminiscence and leukocyte and erythrocyte adherence in multiple sclerosis.

BACKGROUND: It has become increasingly apparent that nitric oxide (NO) and related metabolic and effector systems play an important role in immune regulations, in inflammatory response and in cellular and tissue damage in multiple sclerosis (MS) and in its experimental models. OBJECTIVES: Various adherence interactions and metabolism of reactive oxygen species belong to the cellular functions associated with NO metabolism. The aim of the present study was to evaluate the effect of chemical compounds affecting NO metabolism on adhesive properties of leukocytes and erythrocytes and on the blood chemiluminiscence in MS patients in comparison with controls. The effects of NG-Methyl-L-Arginine (NGMLA), a specific competitive NO antagonist, L-arginin, NO precursor, and sodium nitroprusside, an NO-releasing agent were tested. METHODS: Luminol dependent chemiluminiscence was measured with and without respective drug administration, the results were expressed as chemiluminiscence index. Adherence of peripheral blood cells to nylon wool was used for the adherence studies, the results were expressed in a form of adhesivity index. Studies were performed in a group of patients with active multiple sclerosis, in a group of neurological controls and in a group of healthy controls. The differences between MS patients and control groups were statistically evaluated using Mann and Whitney U-test. MAIN RESULTS: Sodium nitroprusside stimulated the luminol-dependent chemiluminiscence in MS patients and inhibited it in both control groups. The difference between MS patients and the control patient subgroup was proved to be statistically significant. Statistically significant inhibition of leukocyte adherence by arginine was found in MS patients in comparison to healthy controls, in whom stimulation of adherence was observed. When differentiating the effect of the agents upon particular leukocyte subpopulations the only statistically significant difference was found with arginine and granulocytes, the trend being similar as in the total leukocyte adherence. Sodium nitroprusside further stimulated the adherence of erythrocytes in MS patients and inhibited it in controls. CONCLUSIONS: Results indicate nitric oxide-dependent alterations of oxidative metabolic burst and of cellular adherence properties in patients with active multiple sclerosis. Our findings also question possible participation of granulocytes and erythrocytes in multiple sclerosis pathogenetic cascade.

Adult↗

Bed utilization performances of Slovenian and Croatian acute hospitals systems.

With Barber-Johnson-Yates scattergrams (BJYS), the performances of Slovenian and Croatian acute hospital system were explored by taking turnover interval as a predictor variable, length of stay as a dependent variable, and by looking at the variables of bed throughput and percentage of bed emptiness on installed network. The growing influences on the Slovenian hospital system of a cost-containment policy and of the past war on the Croatian hospital system are the best illustrations of the informatics potential inherent in BJYS presentations for the exploratory data analysis (EDA) used to identify systematic relations between variables in a setting of not complete a priori expectations of these relations.

Bed Occupancy↗

Essential fatty acids and related molecular and cellular mechanisms in multiple sclerosis: new looks at old concepts.

Essential polyunsaturated fatty acids, their metabolism and their effects represent a ubiquitous system important for cellular membrane stability, for immunological and inflammatory regulations, for inter- and intracellular signalling. There are complex links to other regulatory and effector mechanisms - to the reactive oxygen species, nitric oxide and peroxynitrite anion, to eicosanoids and related compounds. The relation of polyunsaturated acids to multiple sclerosis was extensively discussed some time ago. Recently, a number of data placing these concepts in a new light have emerged, which are reviewed in the present article. The recent knowledge indicates that this topic deserves further attention in both the basic and the clinical research of multiple sclerosis.

Animals↗

Some manoeuvres for releasing the hypertonus of spastic and shortened muscles.

We describe some physiotherapeutic techniques and manoeuvres releasing the increased tone of spastic and shortened muscles. The techniques can be generally characterised and summed up into three groups as follows: I. First types of manoeuvres consists in setting up the extremity or segment into the position usually opposed or antagonistic to the limited direction. This position is held for several tens of seconds. After this, partial of the originally limited range of motion could be observed. A modification of this approach is effective for persistent extensor spasticity of the lower extremities. Extremity is taken up into the internal rotation and flexion of the hip joint, into the maximal flexion of knee joint and into dorsiflexion of ankle joint, and this position is held at least for 30 seconds. After this, the extensor spasticity is usually diminished and also the voluntary movements and gait pattern improved. II. Short active jerk (not exceeding 1/2 sec) in the free direction, alternatively against mild resistance, followed by 3-4 second release and slow stretch into the restricted range. It is essentially important that the initial jerk is as brisk as possible but performed with no special effort. In case the resistance is applied, it should be only slight. Then the therapist must grasp a "melting" of the hypertonus and cautiously guide the segment into the slow and gentle stretch. III. Pressure stimulation of the particular active zones. The application of these manoeuvres and its combinations are demonstrated in case reports.

Adult↗

Characteristic MR lesion pattern and correlation of T1 and T2 lesion volume with neurologic and neuropsychological findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an arteriopathy related to a genetic defect of the notch 3 gene on chromosome 19. The purpose of this study was to evaluate lesion distribution and volume using MR imaging and to correlate the lesion volume with the neurologic and neuropsychological findings. METHODS: Twenty members of two families (14 with CADASIL as determined by linkage analysis, six healthy) were studied with MR imaging. Two observers evaluated the MR findings semiquantitatively and quantitatively. MR results were then correlated with neurologic and neuropsychological findings. RESULTS: A typical pattern of lesion distribution in patients with CADASIL was found: the frontal lobe was the site with the highest lesion load, followed by the temporal lobe and the insula. The total lesion volume on T1-weighted MR images correlated significantly with the degree of disability and the degree of impairment in neuropsychological functions (including attention, memory, and conceptual and visuospatial functions). CONCLUSION: In CADASIL patients, a common pattern of cerebral lesion distribution is found. The total T1 lesion volume is an important parameter to correlate with disability, as it may prove to be helpful in predicting the natural history of the disease.

Adult↗