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Biomedical subjects

G Holl

Publications and source records attributed to G Holl.

12 recordsLinked to original sources

Effect of aged garlic extract on caspase-3 activity, in vitro.

In neurodegeneration, such as Alzheimer's disease (AD), apoptosis results in the loss of valuable neurons. A key mechanism in apoptosis is the activation of caspase-3. Caspase-3 activity first becomes detectable early in apoptosis, continues to increase as cells undergo apoptosis, and rapidly declines in late stages of apoptosis. Its activity is an early marker of cells undergoing apoptosis. Caspase-3 catalyzes the formation of beta-amyloid peptide, a hallmark of AD. The purpose of the study was to determine whether dietary aged garlic extract (AGE), with known antioxidant properties and neuroprotection against Alzheimer's beta-amyloid cytotoxicity, inhibits the caspase-3 activity in vitro. Caspase-3 activity was assayed according to the prescribed protocol and incubated overnight at ambient temperature. We report that AGE inhibits caspase-3 in dose dependent manner. Caspase-8 was not inhibited by AGE. As a caspase-3 inhibitor, AGE may be effective in reducing apoptotic death of neurons since caspase inhibitors have been shown to inhibit neuronal cell death. We propose a scheme for the ameliorative effect of AGE on deleterious effects of beta-amyloid and possibly uncontrolled caspase-3 activity.

Amyloid beta-Peptides↗

[N(2)H(5)](+)(2)[N(4)C-N=N-CN(4)](2-): a new high-nitrogen high-energetic material.

The reaction of [N(2)H(5)](+)(2)[SO(4)](2-) with barium 5,5'-azotetrazolate gave new high-energy-density materials (HEDM) based on the 5,5'-azotetrazolate dianion. The dihydrazinium salt of [N(4)C-N=N-CN(4)](2-) 1, its dihydrate 2, and its dihydrazinate 3 were prepared in high yield. Synthesis in water afforded yellow needles of [N(2)H(5)](2)(+)[N(4)C-N=N-CN(4)](2-).2H(2)O (2): monoclinic, P2/c, a = 8.958(2) A, b = 3.6596(7) A, c = 16.200(3) A, beta = 96.834(3) degrees, V = 527.3(2) A(3), Z = 2; synthesis in anhydrous hydrazine gave yellow [N(2)H(5)](2)(+)[N(4)C-N=N-CN(4)](2-).2N(2)H(4) (3): triclinic, P1, a = 4.6208(6) A, b = 8.585(1) A, c = 9.271(1) A, alpha = 108.486(2) degrees, beta = 95.290(2) degrees, gamma = 102.991(2) degrees, V = 334.51(8) A(3), Z = 1. The compounds were characterized by elemental analysis and vibrational (IR, Raman) and multinuclear NMR spectroscopy ((1)H, (13)C, (14)N, (15)N). The new compounds represent new high-nitrogen HEDMs with one of the highest nitrogen contents reported to date ([N(2)H(5)](+)(2)[N(4)C-N=N-CN(4)](2-) 85.2%; [N(2)H(5)](+)(2)[N(4)C-N=N-CN(4)](2-).2H(2)O 73.3%; [N(2)H(5)](+)(2)[N(4)C-N=N-CN(4)](2-).2N(2)H(4) 85.7%). The standard heat of formation of the solvate-free compound 1 was computed at the MP2(FULL)/6-311+G(d,p) level of theory to be DeltaH degrees (f) = 264 kcal mol(-1), which translates to 1147 kcal kg(-1) and is one of the highest ever reported. The compounds are stable at room temperature, almost insensitive to friction and impact, but detonate violently when the explosion is initiated, e.g., by rapid heating over the decomposition temperature or by using an initiator.

Journal Article↗

Effect of the cholinesterase inhibiting substance galanthamine on human EEG and visual evoked potentials.

The action of galanthamine (GAL), a cholinesterase inhibiting substance, on resting EEG and on flash visual evoked potentials (VEPs) was tested in 9 healthy subjects. Alpha power was increased significantly in 4 of 8 subjects after the infusion of 10 mg, which provided a median inhibition of 47% of acetylcholinesterase in erythrocytes. Mean alpha frequency and peak alpha frequency decreased significantly in 5 of the 8 subjects by 0.22-0.98 Hz. Alpha power increase and alpha frequency decrease were not accompanied by changes in theta power. The amplitudes of the late components of the flash VEP were increased in 8 of 9 subjects receiving doses of 10-35 mg of GAL, while the early components remained unaffected. Increase of late VEP components was significantly correlated with the strength of cholinesterase inhibition. The synchronizing effect of GAL in these healthy volunteers obviously contrasts with the known desynchronizing effect of physostigmine in animal experiments.

Adult↗

A technique for eliciting muscular reflex responses using position controlled dc motors.

A method for generating fast ramp movements is described. A direct current (dc) motor serves as a drive in position feedback mode. In addition to a regulator and a power amplifier, basically only two relatively simple analog circuits are required. One is a ramp function generator with continuously adjustable parameters. The ramp function can be adjusted to the electromechanic transfer function of the motor. A second circuit comprises an analog position storage and allows the ramp to be started from any resting position.

Electric Stimulation↗

A method for separation of superimposed electromyographic responses in man.

Superposition of electromyographic potentials occurs when motor nerves are excited at intervals that are shorter than the duration of one single muscular signal. The method introduced here allows the separation of compound responses into their constituents in experiments with two closely spaced stimuli (conditioning stimulus and test stimulus), each of them eliciting a defined electromyographic response. Stimulus generation is controlled by a small laboratory computer which produces paired stimuli or the conditioning stimulus alone in random order. All responses are classified according to the size of the initial part of the response to the conditioning stimulus and averaged. The response to the test stimulus is obtained by a subtraction procedure. The method takes into account the considerable variability of reflex responses in man. It was tested in the analysis of recovery curves of spinal reflexes elicited by short vibratory pulses onto the tendons of relaxed human arm muscles.

Animals↗

Prospective multicentre study on the prediction of relapse after antithyroid drug treatment in patients with Graves' disease.

Graves' disease is an autoimmune disease characterized by a course of remission and relapse. Since the introduction of antithyroid drug treatment, various parameters have been tested for their ability to predict the clinical course of a patient with Graves' disease after drug withdrawal. Nearly all these studies were retrospective [corrected] and often yielded conflicting results. In a prospective multicentre study with a total of 451 patients, we investigated the significance of a variety of routine laboratory and clinical parameters for predicting a patient's clinical course. Patients who had positive TSH receptor antibodies activity at the end of therapy showed a significantly higher relapse rate than those without (P less than 0.001). However, the individual clinical course cannot be predicted exactly (sensitivity 0.49, specificity 0.73, N = 391). The measurement of microsomal (P = 0.99, sensitivity 0.37, specificity 0.63, N = 275) or thyroglobulin antibodies (P = 0.76, sensitivity 0.18, specificity 0.84, N = 304) at the end of antithyroid drug therapy did not show a statistically significant difference in the antibody titre between the patients of the relapse and those of the remission group. Additionally, HLA-DR typing (HLA-DR3: P = 0.37, sensitivity 0.36, specificity 0.58, N = 253) was proven to be unsuitable for predicting a patient's clinical course. Patients with abnormal suppression or an abnormal TRH test at the end of antithyroid drug therapy relapse significantly more often (P less than 0.001) than patients with normal suppression or normal TRH test. Patients with a large goitre also have a significantly (P less than 0.001) higher relapse rate than those with only a small enlargement. The sensitivity and specificity values of all these parameters, however, were too low to be useful for daily clinical decisions in the treatment of an individual patient. This is also true for the combinations of different parameters. Though the highest sensitivity value (0.94) was found for a combination of the suppression and the TRH test at the end of therapy, the very low specificity value (0.13) for this combination reduced its clinical usefulness.

Follow-Up Studies↗

[Use of digital technics in the display of electromyography signals].

The use of digital techniques for the display of electromyographic signals often introduces grave errors in the visualization of the high frequency signal components. The causes for this can be quantitatively deduced from the technical principles of the systems. In the digital storage oscilloscope, the accuracy of reproduction is determined by the sampling rate and the memory capacity. In addition, there may be a considerable loss of quality in the visual display of systems using computer graphics despite accurate signal acquisition. Based on the quantitative analysis recommendations as to the technical equipment and use of digital neurophysiological systems are given.

Analog-Digital Conversion↗

False-positive granulocyte scintigraphy in a patient with acute leukemia.

This study describes a 12-year-old patient who was hospitalized because of arthritislike symptoms. A scintigraphy performed with in vivo labelled granulocytes revealed, in addition to a few foci, an abnormal intravasal persistence of the labelled cells. An acute leukemia was found that was restricted to the bone marrow.

Acute Disease↗

Primidone and essential tremor.

To clarify whether primidone itself, and not only its metabolite phenobarbitone, suppresses essential tremor, the effect of a high single dose of primidone was tested. Of 11 patients, 8 showed a reduction of their tremor by 54%-69% for up to 28 h. The serum concentration of primidone was as expected, whereas those of the metabolites phenyl-ethyl-malonamide and phenobarbitone were very low. The tremor suppression can thus be considered to be an effect of primidone. Three of the 11 patients did not show a reduction of tremor.

Adult↗

Do HLA-DR-typing and measurement of TSH-receptor antibodies help in the prediction of the clinical course of Graves' thyrotoxicosis after antithyroid drug treatment?

In patients with Graves' hyperthyroidism, the relapse rate after antithyroid drug treatment is in the range of about 30-70%. Different attempts have been made to obtain criteria for the prediction of the clinical outcome after drug therapy, especially HLA-DR typing and measurement of TSH receptor antibodies. So far, very conflicting results have been reported. This is not surprising in view of the many genetically controlled and environmental factors that play a role in the pathogenesis of this disease. Moreover, most reports are based on retrospective studies with a relatively small number of patients. Our own data, obtained in a prospective multicenter study, yield strong evidence against the relevance of HLA-DR3 typing (n = 187, sensitivity = 0.38, specificity = 0.67) or measurement of TSH receptor antibodies at the end of therapy (n = 269, sensitivity = 0.49, specificity = 0.72) for the prediction of the clinical course after drug treatment.

Antithyroid Agents↗

[Effect of cefaclor and tobramycin on the phagocytic activity of peritoneal macrophages in mice].

The influence of Cefaclor and of Tobramycin on phagocytosis of sheep erythrocytes by murine peritoneal macrophages was investigated. The antibiotics in various concentrations were either added to the cells directly during the phagocytosis period or injected i.v. into cell donor mice at different times before cell harvest and the cells subsequently assayed for phagocytic activity in vitro. When antibiotic was added during the phagocytosis a dose-dependent inhibition of phagocytosis was observed which, however, became significant only at extremely high concentrations of the antibiotic. In all other experimental set-ups, phagocytosis was not influenced by antibiotics. Restrictive usage of either antibiotic in clinical situation does not appear mandatory on the basis of the reported observations.

Animals↗

Hydrodynamic aspects of bladder-outlet obstruction: consequences of functional micturition disorders.

Functional disturbances of micturition lead to secondary structural changes. Both factors may change the physical properties--shape, elasticity and consistency--of the posterior urethra and of the bladder neck. In order to demonstrate their influence on urodynamics experimental studies were undertaken, elastic models, straight tubes of equal diameter throughout their length, were used. One model was a straight elastic tube of PVC material, three other models had nonelastic segments of different shape but with the same square area as the undeformed elastic parts. Perfusion was performed under equal conditions. The experiments showed firstly that nonelastic segments in an elastic system reduce the flow rate and secondly, that flow depends on cross section versus circumference, which is expressed by the so-called hydraulic diameter. Elasticity, consistency and shape of the bladder-outlet, frequently altered in patients with neurogenic bladder disease, are therefore important factors regarding loss of friction. Our results support the clinical experience, that a functional obstruction has to be eliminated before secondary structural changes occur which alter the physical properties of the bladder outlet and therefore make flow conditions even worse.

Elasticity↗