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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc
    Experimental dermatology 13 (2004), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: There is good epidemiological evidence that melanin in the skin protects against sunburn and skin cancer resulting from excessive ultraviolet radiation (UVR) exposure. Melanin is synthesized in a multistep biochemical pathway within specialized cell types in human skin called melanocytes situated in the epidermis. UV light causes an increase in melanocyte-stimulating hormone (α-MSH) receptor activity on cutaneous melanocytes (MC1-R) that results in an increase of eumelanin within the epidermal melanocytes. Melanotan is a synthetic analogue of α-MSH with potent melanogenic activity in animals and humans. We have recently completed a double-blind, randomized controlled study in 80 healthy Caucasian adult subjects. A fixed dose of Melanotan (0.16 mg/kg/day) or placebo in a 3 : 1 ratio was given as three cycles of daily subcutaneous injections over 10 days each month for three consecutive months. Changes in skin pigmentation were quantified by serial skin reflectance measurements and UVR injury, as determined by ×3 MED exposure to broadband UVR, was assessed by measurement of apoptosis (sunburn cells). Results demonstrated that a highly significant increase in skin melanin was attained in all subjects on active treatment compared with placebo, and this was especially pronounced in subjects with lighter skin types (Fitzpatrick I and II; P 〈 0.0001). In these latter subjects, significant sunburn protection was also determined. The ability of Melanotan to stimulate melanin production without the associated UV-induced skin damage may prove a useful adjunct to current photoprotective strategies to stem the marked rise in skin cancer incidence. Currently, we are studying the therapeutic efficacy of a slow-release implant of Melanotan in skin disorders such as polymorphic light eruption and psoriasis.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 82 (1987), S. 576-584 
    ISSN: 1435-1803
    Keywords: 5′-nucleotidase ; adenosine deaminase ; atrialenzymes ; ventricularenzymes ; myocardial ischaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activities of the adenosine-generating enzyme 5′-nucleotidase and the adenosine-degrading enzyme adenosine deaminase were determined for four regions of rat hearts prior to and following 10–60 min of ischaemia. Whereas adenosine deaminase was uniformly active throughout the heart, 5′-nucleotidase was twice as active in atrial than in ventricular myocardium, and more active in the right than in the left ventricles in normoxic tissues. In isolated heart preparations normoxic perfusion decreased adenosine deaminase and increased 5′-nucleotidase activity compared to levelsin vivo. Global ischaemia for 10 min elevated adenosine deaminase activity but had no effect on 5′-nucleotidase activity. However, 30 min of ischaemia decreased 5′-nucleotidase activity by 50% in all regions of the heart. These changed levels were not altered by 10 min of reperfusion. The fall in 5′-nucleotidase activity with ischaemia occurred only in the 90% of this enzyme which is membrane-bound. The reasons for the marked differences in distribution and responses to ischaemia of these two enzymes have yet to be elucidated but metabolic inhibitors seem unlikely to be involved.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1803
    Keywords: Allopurinol ; xanthinedehydrogenase/oxidase activity ; adeninenucleotides ; myocardialprotection ; normothermicglobalischemia ; cardioplegia ; freeradicals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated working rat hearts were subjected to aerobic perfusion (25 min), cardioplegic infusion (3 min), global ischemia (30 min at 37°C) and reperfusion (35 min). Measurements of myocardial xanthine oxidase and dehydrogenase activity, together with various adenine nucleotides and metabolites, were made at defined stages of the protocol (n=6/group). Allopurinol pretreatment (20 mg/kg body wt/day for 3 days) improved the postischemic recovery of cardiac function; thus, aortic flow (a representative index) recovered to 68.8±4.2% compared with 53.2±2.3% in untreated controls (p〈0.05). In fresh tissue, allopurinol pretreatment inhibited xanthine dehydrogenase activity by 73.1% (from 11.9±0.5 to 3.2±0.8 mIU/g wet wt: p〈0.05) and xanthine oxidase activity by 95.2% (from 8.3±1.2 to 0.4±0.2 mIU/g wet wt: p〈0.05); however, this inhibition was not maintained during perfusion. During reperfusion, myocardial xanthine dehydrogenase and oxidase activity was reduced by 40–60% (p〈0.05) in both allopurinol pretreated and control hearts. Tissue content of creatine phosphate, adenosine triphosphate and catabolites, NAD and inorganic phosphate were not different in allopurinol pretreated or control hearts during either ischemia or reperfusion. This study does not support the concept that allopurinol protects the rat heart during ischemia and reperfusion by inhibition of xanthine oxidase activity or by conservation of purines. It appears that allopurinol achieves its protective effects by some, as yet undefined, mechanism.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-1803
    Keywords: reperfusion ; adenine ; nucleotides ; oxypurines ; electrolytes ; mechanicalwork
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated rat hearts were used to measure tissue levels of the adenine nucleotides plus their degradation products and the ‘intracellular’ electrolytes after 15 or 25 min of global ischaemia alone and also after 5 or 60 min of reperfusion. Following 15 min of ischaemia, hearts showed near complete recovery of cardiac function (aortic flow rate =92±7% of control), but recovery was severely depressed following 25 min of ischaemia (aortic flow rate =18±15% of control). Similarly, after 5 min of reperfusion, hearts made ischaemic for 25 min had a reduced tissue content of ATP (10.5 vs 18.9 μmol·g·dry wt), and NAD (4.30 vs 4.75 μmol·g·dry wt) and a 3–4-fold increase in AMP, adenosine and oxypurines, as compared with hearts ischaemic for 15 min. However, the extent of loss of oxypurines during 5 min of reperfusion was essentially similar in both groups (21% vs 18% of total purine pool). After this initial period of reperfusion a significant (p〈0.01) difference in potassium content was seen between the two groups; hearts which recovered function gained, whilst failing hearts lost, potassium. Changes in the other electrolytes were essentially similar in the two groups of hearts. Extending reperfusion from 5 to 60 min did not change ATP levels in either group but in the functionally depressed group it was associated with a 5-fold increase in calcium and a 30% reduction in potassium, together with a further loss of oxypurines. Thus, loss of nucleotide precursors does not appear to be a critical event in the relatively sudden transition from reversible to irreversible functional injury in ischaemia. There may, however, be a reduction in the activity of the ATP synthesizing processes.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 79 (1984), S. 350-362 
    ISSN: 1435-1803
    Keywords: perfusion pressure ; contracture ; no-reflow ; anoxia ; rat heart ; lactate accumulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relationships among coronary perfusion pressure (0–150 cm H2O), ventricular contracture, vascular resistance, and loss of perfusion of subendocardial myocardium were studied in anoxic isolated rat hearts. Coronary flow and myocardial pH and lactate concentrations were measured during 60 minutes, and the perfusable proportion of the ventricular wall determined after 15 and 60 minutes of global, substrate-free anoxic perfusion. Myocardial contracture in similarly treated hearts was indicated by the pressure exerted on left intraventricular balloons. Decreased perfusion pressure proportionately decreased both coronary flow and the extent of perfusion, and delayed the onset of contracture. The slower development of contracture was associated with a measured increase in lactate content and fall in pH within the ventricular wall. During anoxia the subendocardial myocardium progressively lost its capacity to be perfused, commencing at the onset of ventricular contracture, and continuing to extend even after maximum contracture pressures had been developed. Increased coronary perfusion pressures accelerated the rate of development of contracture but significantly reduced the extent of the perfusion defect, probably by opposing vascular compression.
    Type of Medium: Electronic Resource
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