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Biomedical subjects

M J Varkarakis

Publications and source records attributed to M J Varkarakis.

At least 19 recordsLinked to original sources

The response of the juxtaglomerular apparatus to stimuli effecting renin or erythropoietin release in canine renal allografts.

The functioning canine renal allograft produces plasma renin activity (PRA) and erythropoietin (ESF) activity and can maintain normal blood pressure and normal erythropoiesis. Moreover, in response to various provocative stimuli it can: (i) increase plasma renin activity in response to low sodium intake; (ii) suppress PRA in response to high sodium intake; (iii) produce increased serum erythropoietin in response to hypoxia. The granulation activity of the juxtaglomerular apparatus correlates best with the degree of graft rejection and with the PRA in groups manipulated by changing sodium balance. This is not the case with hypoxia. Thus, the juxtaglomerular apparatus, even in the presence of vascular changes seen with the severe degree of rejection in renal allografts, can respond to stimuli that can regulate renin release. Renin production by the transplanted kidney can be dissociated from ESF secretion. Blood pressure changes in the present model were not directly associated with increased PRA or juxtaglomerular apparatus activity. In such conditions hypertension can exist in the presence of suppressed PRA and without hypergranulation of the apparatus. The majority of correlations of this study thus establish a close association of the degree of juxtaglomerular index activity with PRA levels, rather than ESF.

Animals↗

Prognosis of bladder carcinoma in patients treated with cystectomy.

Prognostic criteria for bladder tumors are the stage and grade of the tumor in the present series of 82 patients, in which all patients received the same treatment. These criteria are related and the combined evaluation increases the prognostic accuracy for the disease. In addition, the diameter and not the number of bladder tumors on primary diagnosis is an important prognostic sign. A significant number of tumors at the first clinical evaluation were apparently understaged and undergraded and to a lesser degree overstaged and overgraded as compared with cystectomy specimen evaluations. Despite the total cystectomy, even the patients with superficial bladder lesions, a significant number died from the bladder tumor and 1/4 of the patients had metastases at post mortem examination. The 5 year overall survival with total cystectomy was 40% and for 10 years 15%. Other adjuvant forms of therapy pre- and post-operatively must be assessed.

Adult↗

Comparison and significance of respiration and glycolysis of prostatic tissue from various species.

The respiration and glycolysis of prostatic tissue from baboons, rhesus monkeys, dogs and rats were compared to the respiration and glycolysis in human prostatic tissue. All the primate prostates had a high glycolytic ability and a low respiration in contrast to the rat and dog prostate. Treatment of baboons with drugs clinically effective against prostatic cancer did not change the prostatic metabolism despite a marked prostatic atrophy. In vitro the drugs reduced respiration markedly. The metabolic similarity between the human and the baboon and rhesus monkey prostate indicates that nonhuman primates should be investigated in the evaluation of chemotherapeutic agents for treatment of prostatic cancer.

Animals↗

Antiprostatic effects of a nitrogen mustard of estriol.

The chemical ester of a nitrogen mustard with estriol was tested for its antiprostatic effects in dogs and rats. The E33-mustard was shown to interfere with the uptake of labeled estriol in the dog prostate and by the ventral prostate of the rat; and to increase the uptake of the radioactivity associated with testosterone in the dog prostate. The weights of the ventral and dorsolateral prostates of the rat were significantly reduced following the administration of E3-mustard for 2 days. The results are interpreted to be very similar to those obtained with the mustard of E (Estracyt) and the effects are probably a combination of the actions of the released estrogen (D) and/or mustard, either adding individually or in concert.

Animals↗

Direct effect of prostaglandins in renal function and renin release in the presence of renal ischemia in the dog.

Prostaglandins PGE-1 or PGA-1 (0.5 to 1 mug per min) were infused into the stenosed renal artery of anesthetized hypertensive dogs. Increased urine volume, sodium and potassium excretion, and p-aminohippurate clearance were found during the prostaglandin infusion period in the infused kidney as compared to the control periods before infusion. Creatinine clearance was increased during infusion of PGE-1. The noninfused, nonischemic kidney showed no effect at the time of infusion with PGE-1 but in the case of PGA-1, the p-aminohippurate and creatinine clearances and urine diuresis were decreased. As a result, the mean aortic blood pressure decreased. Both prostaglandins increased the renal vein renin in the infused kidney. PGA-1 did affect renin release of the noninfused kidney, but PGE-1, which is rapidly inactivated by the lung, did not have this effect. Renin release seems to be influenced by electrolyte diuresis operating through the macula densa mechanism. However, the lowering of blood pressure seen in this study cannot exclude the involvement of the stretch receptors (the juxtaglomerular cells) for renin release. The increased renin release after prostaglandin administration seems to be a protective renal mechanism against the drug-induced hypotension. It seems to be induced by the direct sodium and water diuretic effects of prostaglandins.

Animals↗

Prostatic effects of a nonsteroidal antiandrogen.

The possible mechanisms for the antiprostatic effects of a nonsteroidal antiandrogen, SCH 13521 (4'-nitro-3'-trifluoromethylisobutyranilide), were investigated in rats and dogs. The influence of administered SCH 13521 on the deposition of the radioactivity associated with labeled testosterone, dihydrotestosterone, and estriol (E-3) in the prostate and other tissues of the dog, and rat was determined in short term experiments. SCH 13521 definitely interfered with the localization of the radioactivity of these steroids in the prostate and indicated a competitive situation between SCH 13521 and the steroids. Even though in vitro binding data were generally in accord with in vivo results, he descrepancies regarding E-3 and the more intense effects of SCH 13521 observed in vivo, as compared to those in vitro, lead us to suggest that a metabolite of the compound may also play an important competitive role in vivo. Of particular interest was the competition between SCH 13521 and estrogens in vitro (estradiol-17-beta) and in vivo (E-3). Sch 13521 greatly decreased the volume of prostatic secretion whereas id minor effects on prostatic 5-alpha-reductase and arginase activities. The latter is surprising, since both enzymes are very highly androgen-dependent. Thus, even though the mechanisms of action of SCH 13521 on the prostate may involve competition with androgens at the cellular level, we think that its competition with some estrogens points to a more complicated action than observed with other antiandrogens.

Androgen Antagonists↗

Changes of renal ATPase enzymes in different types of kidney preservation.

After 24-hr storage of canine kidneys with extracellular or intracellular (Ursol) solutions, the cortical and medullary renal ATPase enzymes (total Na+ + K+ and Mg-ATPase, Na+ + K+ -ATPase, and Mg-ATPase) were examined. It was found that storage with extracellular solution decreased all cortical enzymes. This was not the case with intracellular solution or in kidneys cooled and stored without any solution. A decrease in the potassium concentration of the Ursol solution decreased cortical (Na+ + K+)-ATPase enzymatic activity. The medullary enzymatic changes were similar in the different groups, and lower than in unstored controls. It appears that the changes on the level of the ATPase enzyme system which is related to the cation transport system might play a significant role in explaining the different results seen in clinical or experimental renal preservation systems. These changes can be related to the injury of preservation due to environmental effects of the cation concentrations and to a lesser degree to the damage of the enzyme system which provides the energy for cation transport.

Adenosine Triphosphatases↗

Morphological responses of benign human prostatic hypertrophic tissue to chemotherapeutic agents in an in vitro culture system.

The in vitro maintenance of hypertrophic tissue with fluid containing cytotoxic drugs showed more degenerative changes in prostatic epithelium and stroma of the tissue compared with concurrently cultured aliquots of control tissue. It is suggested that theses morphological changes can be related with functional activity of the tissue. The mechanism of such an action is at present unsettled, but an interference on known enzymatic systems regulating prostatic growth seems likely. This system provides an added technique for the evaluation of drugs considered for possible therapeutic testing in human prostatic cancer states.

Aged↗