The deficit in low molecular weight thiols as a target for antiageing therapy

The popular use of antioxidative vitamins illustrates the growing awareness of oxidative stress as an important hazard to our health and as an important factor in the ageing process. Superoxide radicals and superoxide-derived reactive oxygen species (ROS) are constantly formed in most cells and tissues. To ensure that ROS can function as biological signaling molecules without excessive tissue damage, ROS are typically scavenged by antioxidants such as glutathione and the vitamins A, C, and E. "Oxidative stress" occurs if the production of ROS is abnormally increased or antioxidant concentrations are decreased. Genetic studies in mice, Drosophila, and C.elegans suggested that ageing may be mechanistically linked to oxidative stress. Several manifestations of oxidative stress were shown to increase with age, whereas tissue levels of vitamin E, plasma concentrations of vitamin C, and intracellular glutathione concentrations decrease with age. In at least two independent studies, cysteine supplementation on top of the normal protein diet has shown significant beneficial effects on each of several different parameters relevant to ageing, including skeletal muscle functions. As the quality of life in old age is severely compromised by the loss of skeletal muscle function, and as muscle function can be measured with satisfactory precision, loss of muscle function is one of the most attractive surrogate parameters of ageing. The mechanisms by which a deficit in glutathione and its precursor cysteine contributes to various ageing-related degenerative processes appears to be related largely but not exclusively to the dysregulation of redox-regulated biological signaling cascades.     

Stereoselectivity of central alpha-adrenoceptors involved in sleep induced by clonidine in chickens

The stereoselectivity of central alpha 2-adrenoceptors involved in sleep induced in chicks by clonidine, suggested by the results observed with the stereoisomers of idazoxan, was further investigated with the stereoisomers of (imidazolinyl-2)-2-dihydro-2,3-benzofurane (S9871) and those of (imidazolinyl-2)-2-benzocyclobutane (S10089). As for the stereoisomers of idazoxan, there was not a good separation between the effects of the stereoisomers of S10089. In contrast, there was a clearcut separation between the effects of (+)S9871 (antagonist) and (-)S9871 (no effect against the action of clonidine). Therefore, these results strongly support the view that central alpha 2-adrenoceptors which mediate sedation are stereoselective for alpha 2-antagonists.     

Efficacy of crystalloid cardioplegic solutions in patients undergoing myocardial revascularization. Effect of infusion route and regional wall motion on preservation of adenine nucleotide stores

The effect of varying the mode of cardioplegic delivery and the presence of regional wall motion abnormalities on myocardial protection by crystalloid cardioplegic solutions was assessed in 68 patients undergoing coronary artery bypass grafting. Serial transmural biopsy specimens from the left ventricular apex were assayed for adenosine triphosphate. All patients had more than 75% stenosis of the left anterior descending coronary artery. They were prospectively randomized into Groups I and II to receive (I) all cardioplegic solution infused via the aortic root or (II) reinfusions of cardioplegic solution given both centrally and through the completed distal left anterior descending anastomosis. Patients were also stratified as to the presence of normal (N) or impaired (Ab) apicoanterior regional wall motion. Inadequate delivery of cardioplegia during ischemia in Group I was manifested by a 41% (p less than 0.01) depletion of adenosine triphosphate stores in abnormally contracting myocardium distal to the left anterior descending stenosis that was not repleted after restoration of coronary flow and a 27% (p less than 0.05) decline in ATP stores during reperfusion in myocardium with normal preoperative wall motion. In contrast, nucleotide stores were preserved at preischemic levels throughout ischemia and reperfusion in Group II regardless of preoperative wall motion. Preservation of ATP did not correlate with duration of ischemia, highest recorded septal temperature, or volume of cardioplegic solution infused. Two patients in each group had a new perioperative infarction. However, 38% of patients in Group IAb required transient inotropic support versus 5% in Group IIAb (p less than 0.05). These data emphasize that reinfusion of cardioplegic solutions distal to coronary obstructions is mandatory for optimal myocardial protection during coronary revascularization.     

Origin of the hypotensive and sympathoinhibitory effect of morphinomimetic agents

In vagotomized dogs, lesions of the lateral reticular nucleus (LRN) region did not change arterial blood pressure and sympathetic nerve activity. The hypertensive and tachycardic responses elicited by section of both carotid sinus nerves and both vagus nerves were not altered. However the sympathoinhibitory component of the baroreflex arc was attenuated. These lesions also abolished the hypotensive and sympathoinhibitory effects of fentanyl (10 micrograms/kg i.v.). In debuffered dogs, bilateral lesions of the LRN regions attenuated the effects of fentanyl (20 micrograms/kg i.v.) on arterial blood pressure and splanchnic discharges. Microinfusion of naloxone into the LRN reduced the effects of fentanyl (10 micrograms/kg) administered intravenously. Microinfusion of [D-Ala2,Met5]enkephalinamide (0.1-1 microgram) into the LRN region produced a dose dependent decrease in arterial blood pressure and sympathetic nerve activity. Lesions of the nucleus ambiguus (NA) region also reduced the effects of fentanyl. In contrast, lesions placed in the ventral median reticular formation or above the NA were ineffective in changing the sympathoinhibitory effect of fentanyl. These results indicate that the lateral reticular formation ventral to the nucleus ambiguus including the lateral reticular nucleus region is involved in the sympathoinhibitory effect of morphinomimetic agents.     

Antibody to soluble nuclear antigens in dogs (German shepherd) with a lupus like syndrome.

Dogs (German shepherd) show febrile polyarthritis characterized by wasting and cutaneous lesions associated with the presence of high titres of antinuclear antibodies (ANAB) which when stained give a reticulated pattern to leucocyte nuclei. These antibodies react with extractable nuclear antigen (ENA) in immunodiffusion giving 2 lines: one is ribonucleoprotein (RNP) and the other is Sm. Immunofluorescence and electron microscope studies demonstrated immunoglobulins deposits at the dermo-epidermal junction and alteration of the basal membrane in skin biopsies of these dogs, observations similar to those in cases of human lupus. These deposits appear to be associated with the presence of ANAB-ENA complexes.     

Significance of radiotherapy in the treatment of soft tissue sarcomas

Postoperative photon- or electron irradiation has been well established in the treatment of soft tissue sarcomas. For further improvement of these results, neutron- or neutron-boost irradiation was introduced at several centres of radiation therapy. In this report, the 3.5 year results of 112 patients are analysed. The majority (62%) had T3-tumours (UICC classification, Geneva 1978). 58 patients presented with gross tumour at the beginning of radiotherapy, and 54 patients without clinical evidence of tumour. 39 patients (35%) had recurrent tumours. A highly statistical difference in local tumour control was found between the group of patients with gross tumour (47%) and the group of patients without clinical evidence of tumour (81%). A statistical difference in local control and survival was also found between the group of patients with T1-tumours (100%), T2 tumours (76.8%) and T3 tumours (44.5%), whereas no differences were found in terms of grading. The high complication rate of 25%, which was found after neutron therapy, was reduced to 7% after introduction of a neutron boost. The statistical significance of this treatment modality is presently being evaluated in a randomised EORTC trial. Adjuvant chemotherapy is recommended für all G3 tumours.     

Gibt es eine medikamentöse Beeinflussung der Frakturheilung?

Zusammenfassung Die Art und Wirkungsweise von Medikamenten, die die Knochenbruchheilung beschleunigen sollen, werden besprochen. Dann wurden einige dieser Präparate im klinischen Versuch kontrolliert. Weder Vitamine, Hormone, Organpräparate, Trockenzellen, Bogomoletzserum und hyperämisierende Medikamente konnten nach unseren Ergebnissen eine wesentliche Verkürzung der Knochenbruchheilung bewirken, so daß nach wie vor für die Behandlung der Fraktur in erster Linie die klassischen Gesichtspunkte der Reposition und Fixierung gelten.