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Biomedical subjects

A Dupre

Publications and source records attributed to A Dupre.

At least 19 recordsLinked to original sources

Agonist high and low affinity state ratios predict drug intrinsic activity and a revised ternary complex mechanism at serotonin 5-HT(2A) and 5-HT(2C) receptors.

The ternary complex model as applied to G-protein coupled receptors (GPCR) predicts that an agonist binds with low affinity (K(L)) to the free receptor (R), leading to an agonist/receptor/G-protein complex. This ternary complex displays high agonist affinity (K(H)), resulting in signal transduction. Classical dogma states that the ratio K(L)/K(H) predicts intrinsic activity of drugs: the higher the ratio the higher the intrinsic activity. This model was based on studies in which K(L) and K(H) were indirectly determined by computer analyses of antagonist radioligand binding data. In order to investigate the relationship of K(L), K(H), and intrinsic activity for agonists at 5-HT(2A) and 5-HT(2C) receptors, we utilized (3)H-agonist and (3)H-antagonist radioligands to directly determine K(H) and K(L). Comparisons of the log K(L)/K(H) ratios and intrinsic activities of drugs for stimulating intracellular phosphatidylinositol (PI) hydrolysis revealed a strong correlation for 5-HT(2A) (r(2) = 0.92) and 5-HT(2C) (r(2) = 0.96) receptors. The data were fit to computer simulations based on the original ternary complex model and the revised ternary complex model in which an activated state of the receptor (R*) exists in equilibrium with the resting state of the receptor (R). Data produced for both 5-HT(2A) and 5-HT(2C) receptors were better-fitted to a revised ternary complex model, rather than the classical ternary complex model. These data support a revised model for the molecular events coupling GPCR to activation of G-proteins and indicate that a strong correlation between the K(L)/K(H) ratio and intrinsic activity for agonist action at GPCR is consistent with the existence of R*.

Animals↗

[Malignant degeneration on ileostomy for rectocolonic polyposis].

One case of malignant degeneration on an ileostomy following proctocolectomy for familial intestinal polyposis is reported. On the basis of a review of the literature, the nosological context of this disease, the etiopathogenesis of cancerization and the surgical consequences are determined.

Adenocarcinoma↗

The Kiricuta procedure in reconstructive surgical treatment of the breast.

A series of 50 patients with carcinoma of the breast underwent omental transposition. This palliative procedure is indicated for recurrences after conservative treatment, radiation necrosis and Stage III or IV ulcerated tumors. The operative technique is described in detail. Omentoplasties were performed upon 33 right and 17 left mammary areas. Forty-five right pedicled flaps and only four left areas were used. One patient died on the fourth postoperative day because of massive pulmonary embolus. Local repair was satisfactory in 76 per cent of the patients. Four patients presented with herniation of the abdominal wall at the site of omental tunneling. In three, the treatment consisted of sectioning the vascular pedicle and reinforcing the parietal closure with Dacron (polyester fiber) mesh.

Adult↗

Resuscitation fluid composition and myocardial performance during burn shock.

The present study examines the effects of resuscitation fluid composition on myocardial function, myocardial high-energy phosphate content, and survival following third-degree anesthetic burn to 35-40% body surface area in the guinea pig. Treatment regimens used were 1) no resuscitation, 2) isotonic saline, 3) Ringer's lactate and 4) Ringer's acetate. Fluids were administered at the rate of 0.334 ml/kg/hr/% burn for 4 hr following injury, at which time myocardial function was assessed. Nonburned animals served as controls. In isolated working hearts, significant depression of myocardial function was observed in nonresuscitated and saline-resuscitated animals as evidenced by decreased cardiac output, dP/dt, -dP/dt, and stroke work. Lactate resuscitation produced some improvement in these parameters but did not restore them to those of nonburned control animals. In contrast, Ringer's acetate resuscitation resulted in normal cardiac output and contractility. Myocardial ATP content of hearts obtained from the various resuscitation groups did not differ from that of nonburned control hearts, except for hearts from Ringer's lactate group, which were significantly lower in myocardial ATP than those of the other groups. No differences were found in creatine phosphate content. Resuscitation with the different fluid regimens for 48 hr produced significant differences in survival. Fluids were given at the rate of 4 ml/kg/% burn for 24 hr. Half of the fluid was given in the first 8 hr and the rest during the remaining 16 hr. Nonresuscitated and saline-resuscitated animals showed significant mortality by 24 hr, whereas lactate- and acetate-treated animals had survival rates of 100% and 87.5%, respectively. However, by 48 hr, only acetate-treated animals survived. These data indicate that important differences exist in the effectiveness of different resuscitation fluids and that Ringer's lactate, the fluid most often utilized clinically, may not provide optimum benefit. In light of these results, serious consideration should be given to the substitution of acetate for lactate during the resuscitation of burn shock patients.

Animals↗

Titanium pigmentation. An electron probe microanalysis study.

A patient had an unusual pigmentary disease induced by titanium dioxide. The use of a topical cream containing titanium dioxide caused a xanthomalike appearance on the patient's penis. Electron probe microanalysis was valuable in establishing the cause of this balanitis.

Adult↗

Volume regulation by human lymphocytes. Role of calcium.

Human peripheral blood lymphocytes regulate their volumes in hypotonic solutions. In hypotonic media in which Na+ is the predominant cation, an initial swelling phase is followed by a regulatory volume decrease (RVD) associated with a net loss of cellular K+. In media in which K+ is the predominant cation, the rapid initial swelling is followed by a slower second swelling phase. 86Rb+ fluxes increased during RVD and returned to normal when the original volume was approximately regained. Effects similar to those induced by hypotonic stress could also be produced by raising the intracellular Ca++ level. In isotonic, Ca++-containing media cells were found to shrink upon addition of the Ca++ ionophore A23187 in K+-free media, but to swell in K+-rich media. Exposure to Ca++ plus A23187 also increased 86Rb+ fluxes. Quinine (75 microM), an inhibitor of the Ca++-activated K+ pathway in other systems blocked RVD, the associated K+ loss, and the increase in 86Rb+ efflux. Quinine also inhibited the volume changes and the increased 86Rb fluxes induced by Ca++ plus ionophore. The calmodulin inhibitors trifluoperazine, pimozide and chlorpromazine blocked RVD as well as Ca++ plus A23187-induced volume changes. Trifluoperazine also prevented the increase in 86Rb+ fluxes and K+ loss induced by hypotonicity. Chlorpromazine sulfoxide, a relatively ineffective calmodulin antagonist, was considerably less potent as an inhibitor of RVD than chlorpromazine. It is suggested than an elevation in cytoplasmic [Ca++], triggered by cell swelling, increases the plasma membrane permeability to K+, the ensuing increased efflux of K+, associated anions, and osmotically obliged water, leading to cell shrinking (RVD).

Calcimycin↗

Volume-induced increase of anion permeability in human lymphocytes.

Peripheral blood mononuclear cells (PBM) readjust their volumes after swelling in hypotonic media. This regulatory volume decrease (RVD) is associated with a loss of cellular K+ and is thought to be promoted by an increased permeability to this ion. In contrast, no change in volume was observed when K+ permeability of PBM in isotonic media was increased to comparable or higher levels using valinomycin. Moreover, valinomycin-induced 86Rb+ loss in K+-free medium was considerably slower than in K+-rich medium. These results suggest that anion conductance limits net salt loss in isotonic media. Direct measurements of relative conductance confirmed that in volume-static cells, anion conductance is lower than that of K+. In volume-regulating cells depolarization occurred presumably as a result of increased anion conductance. Accordingly, the efflux of 36Cl from PBM was markedly increased by hypotonic stress. Since both membrane potential and intracellular 36Cl concentration are reduced in hypotonically swollen cells, the increased efflux is probably due to a change in Cl- permeability. Anions and cations seem to move independently through the volume-induced pathways: the initial rate of 86Rb uptake in swollen cells was not affected by replacement of external Cl- by SO=4; conversely, 36Cl fluxes were unaffected by substitution of K+ by Na+. The data indicate that anion conductance is rate-determining in salt and water loss from PBM. An increase in anion conductance is suggested to be the critical step of RVD of human PBM.

Anions↗

[The injection of the lymphatic system of the stomach during surgery by vital staining dye: an anatomical or surgical interest? (author's transl)].

The authors present the report of their experience of 20 injections of the lymphatic system of the stomach during surgery by vital staining dye: 19 times by Pontamine sky blue 6 BX, 1 time by patent blue violet. The results of this study are analysed; the anatomical interest is specified. Nevertheless, this technique presents no surgical interest concerning the stomach, in spite of many authors' opinion.

Aged↗