An in vitro model of ischemic-like stress in retinal pigmented epithelium cells: protective effects of antioxidants.

We have developed a model of in vitro cell oxidative stress in bovine retinal pigment epithelium cells exposed to a ischemia-like condition obtained by interference with glucose utilization through both oxidative phosphorylation and glycolysis. This resulted in a statistically significant decrease of the intracellular ATP levels, which reflects a bioenergetic decline similar to that associated with mitochondrial damage or loss in normal post-mitotic cells aging in vivo. This new model of cellular oxygen stress seems adequate for investigation of the protective action of antioxidants, in agreement with our finding of a statistically significant increase in the ATP levels over the values of the non-treated samples in retinal pigment epithelium cells exposed to the above oxygen stress in medium supplemented with 300 microM vitamin C or 10 mM N-acetylcysteine.

Inhibition of adrenomedullary catecholamine release by propranolol isomers and clonidine involving mechanisms unrelated to adrenoceptors.

1 Transmural electrical stimulation (10 Hz, 40 V, 1 ms for 60s) increased total catecholamine secretion from perfused cat adrenal glands; this response was enhanced by neostigmine and inhibited by mecamylamine, suggesting that release of acetylcholine from splanchnic nerve terminals was stimulating nicotinic receptors and enhancing catecholamine secretion. 2 Isoprenaline, (-)-propranolol and (+)-propranolol (10(-7)-10(-5)M) inhibited the electrically-evoked secretory response by 40-70%; similar reductions were obtained with clonidine and yohimbine. Neither, (+)-propranolol nor (-)-propranolol inhibited K-evoked secretion from cat adrenals; in contrast, nimodipine potently inhibited it (IC50 = 24 nM). 3 Either, racemic propranolol or the (+)- or (-)-isomers (1-10 microM) equally inhibited [3H]-noradrenaline release evoked by nicotine or acetylcholine from cultured bovine adrenal chromaffin cells; clonidine (10 microM) inhibited secretion by 50% and yohimbine or isoprenaline did not affect it. 4 The results indicate that adrenomedullary catecholamine release evoked by splanchnic nerve stimulation is not modulated by alpha- or beta-adrenoceptors and suggest that propranolol may inhibit secretion by blocking ion fluxes through the acetylcholine receptor ionophore. Clonidine may inhibit secretion by this same mechanism, and/or by interfering with some intracellular event in the secretory mechanism.

Stimulus frequency affects c-fos expression in the rat visual system.

We have characterised the c-fos expression patterns in various centers of the visual pathway of adult rats monocularly stimulated either by continuous or flickering light at different frequencies. Results show different immunocytochemical patterns in all centers studied, the geniculate lateral complex (LGC), superior colliculus (SC) and primary visual cortex (Oc1), depending on the physical characteristics of the stimulus (blinking frequency and light wavelength). After stimulation of the left eye, the ipsilateral pathway presents a substantial density of immunoresponsive cells, which is greater than expected with respect to the number of fibers that project ipsilaterally from the retina to the LGC and the superficial layers of the SC. A surprisingly high positive immunoresponsiveness is obtained in all cases with coherent light stimulation in the red spectrum (634 nm).

Trisomy of the long arm of chromosome 1 in patients with hematologic malignancies and solid tumors: report of six cases.

Complete or partial trisomy of the long arm of chromosome #1 was observed in six patients with malignant disorders. Four patients suffered from hematologic diseases (two cases of refractory anemia with excess of blasts and one case each of acute myeloblastic leukemia and Burkitt lymphoma), and two had solid tumors (retinoblastoma and Ewing's sarcoma). In all cases the excess material included the distal part of chromosome #1. Such material was translocated to chromosomes #16 (three patients), #3, #9, and Y (one patient each), and this was accompanied by additional cytogenetic changes in five of the six patients. The present and other previously published observations support the hypothesis of the localization of genes responsible for malignant growth in the distal segments of chromosome #1.

11q23 abnormalities in children with acute nonlymphocytic leukemia (M4-M5). Association with previous chemotherapy.

Cytogenetic studies of 12 patients aged less than 14 years with acute nonlymphoblastic leukemia (ANLL) (M4-M5) showed structural abnormalities on chromosome 11 at band q23-q24 in five cases (41.8%). Four of these 12 patients had ANLL (M4-M5) after treatment with cytostatics for non-Hodgkin lymphoma in one case and for an acute lymphoblastic leukemia (ALL) in the other three. Three of these four cases had 11q23 abnormalities [one [one 46,XY,t(11;17)(q23;25); another 47,XY,+8,-15,del(11)(q23),+der(15)t(15;?)(p11;?); the third 47,XX,+8,t(3;17) (p11;q25),t(4;11)(q21;q23)] and one had a normal karyotype on being diagnosed ANLL (M4-M5). The notable increase of ANLL (M4-M5) in our patients who had received cytostatics as treatment for a previous neoplasia makes evaluation of our results timely in comparison with those of other groups who use these therapeutic protocols.

Interaction of opioid drugs with human platelet alpha 2-adrenoceptors.

Morphine, naltrexone and naloxone inhibited the binding of [3H]clonidine to the alpha 2-adrenoceptors in human platelet membranes, provided that Mg2+ was present in the medium. In the presence of 5'-guanylyl imidophosphate (Gpp(NH)p) or in the absence of Mg2+ morphine did not modify the binding of [3H]clonidine. Neither [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAGO), nor [D-Pen2,D-Pen5]enkephalin (DPDPE), nor dynorphin-(1-17) affected the [3H]clonidine binding. The presence of 1 mM naloxone did not alter the affinity of either [3H]clonidine or [3H]yohimbine, but reduced the number of binding sites of [3H]clonidine, having no effect on [3H]yohimbine. Naloxone inhibited the binding of adrenaline to high- but not low-affinity sites. It is concluded that morphine and semisynthetic antagonist derivatives interact with alpha 2-adrenoceptors only in the high-affinity state.

Inhibition of COX in ocular tissues: an in vitro model to identify selective COX-2 inhibitors.

The aim of this work was to study the regulation of LPS-stimulated PGE 2 synthesis by traditional NSAIDs (piroxicam and diclofenac) and a selective COX-2 inhibitor (NS-398), in cultured bovine corneal endothelial cells and retinal pigmentary epithelial cells. The IC50 values of piroxicam and diclofenac were compared with IC50 values of NS-398, diclofenac, in both types of cells, showed higher potency than piroxicam. Diclofenac seemed to be a COX-2 inhibitor because its IC50 values were similar to the IC50 values of NS-398. We suggest that this in vitro cell assay system could be useful for identifying compounds that selectively inhibit COX-2 in ocular tissues.

Tapentadol vs. pregabalina asociada a otros opioides en dolor crónico. Análisis de coste-efectividad / Tapentadol vs. pregabalin associated with other opioids in chronic pain management. Cost-effectiveness analysis

Fundamento: el tapentadol es un nuevo analgésico con mecanismo de acción dual como agonista opioide m e inhibidor de la recaptación de noradrenalina. El coste del tratamiento puede suponer un problema a la hora de prescribirlo. Objetivo: analizar si el tratamiento con tapentadol puede resultar coste-efectivo frente a otros opioides asociados a pregabalina. Pacientes y método: se incluyeron 21 pacientes en tratamiento por dolor crónico con opioides asociados a pregabalina y mal control analgésico (EVA > 4). Se les propuso rotar a tratamiento con tapentadol en dos fases: primero sustituyendo el opioide por tapentadol y posteriormente retirando progresivamente la pregabalina. Se registraron el dolor (EVA), el coste diario del tratamiento y la incidencia de efectos adversos antes y tras la introducción del nuevo tratamiento. Resultados: cuatro pacientes abandonaron el tratamiento y volvieron al previo por mayor incidencia de efectos secundarios. En el grupo restante el dolor mejoró de 5,7 (EVA) a 3,4 (EVA) (p < 0,001), mientras que el coste de tratamiento pasó de 4,57 Euros/día a 3,78 Euros/día (p < 0,05). Conclusión: el tratamiento con tapentadol puede resultar coste-efectivo frente a la combinación de otros opioides con pregabalina en pacientes con dolor crónico moderado-grave. Se requieren estudios más amplios que confirmen estos hallazgos (AU)

Background: Tapentadol is a new oral analgesic with a dual mode of action as a mu-opioid receptor agonist and as norepinephrine reuptake inhibitor. The cost of treatment can be argued as a problem for prescribing it. Objective: The aim of this study was to compare the cost-effectiveness of tapentadol to that of associations of other opioids with pregabalin. Patients and methods: 21 patients suffering chronic pain under treatment with opioids and pregabalin for more than 3 months and pain poorly controlled (VAS > 4) were proposed to change to tapentadol in a progressive manner: First changing the opioid to tapentadol and then removing pregabalin. Pain(VAS), daily cost of treatments and adverse effects incidence were registered. Results: Four patients returned to prior treatment becauseof higher incidence of adverse effects. In the group of 17 patients who completed the change of treatment pain improved from 5.7 (VAS) to 3.4 (VAS) (p < 0.001), and the cost of treatment from 4.57 Euros/day to 3.78 Euros/day (p < 0.05). Conclusion: Tapentadol treatment may be cost-effective when compared with associations of other opioids and pregabalin in patients suffering moderate to severe chronic pain. More extensive studies must be done in this sense (AU)

[Experimental analysis of cardiac regulation in the chick embryo]. / Analyse expérimentale de la régulation cardiaque sur l'embryon de poulet

Homochronous homografts of prospective cardiac area labeled with 3H thymidine have been carried out in chicken embryos at stages 5 and 6 of Hamburger and Hamilton. It has been observed how a heart tube or a vesicle, sometimes contractile, is developed by the graft. This vesicle, which is partly joined or not joined, to the receptor's heart, is always in close dependence on the pharynx normogenesis.

[Neuromuscular inhibition of new aminoglycoside antibiotics]. / Inhibition neuromusculaire de nouveaux antibiotiques aminoglucosidiques.

The curarizing effect of three new aminoglucosidic antibiotics (amikacine, dibékacine and sisomicine) is compared to that the streptomycin. The experiment was carried out on mice. In the first group of experiments, the curare-like action of increasing doses of the antibiotics is studied on a diaphragm-phrenic nerve preparation. In the second group, the dosage of each antibiotic necessary to induce apnea is sought. The results show that all the antibiotics have a curarizing activity, variable according to the product, and which increases with the doses used. The relationship between the therapeutic doses and the curarizing doses had a greater margin of security with the three antibiotics than with streptomycin.

Effect of fosfomycin on the thrombocytal aggregation induced by ADP.

The effect of fosfomycin on the thrombocytal aggregation induced by ADP was studied. Plasma rich in thrombocytes was used. It was obtained from blood donors. Fosfomycin was used in concentrations of 1.3 X 10(-3); 1.3 X 10(-2), and 1.3 X 10(-1)M and the ADP in concentrations of 1.17, 2.34 and 3.51 X 10(-6)M. Two experimental groups were used: the first group was made up of five experiments, with an incubation time for the fosfomycin with the thrombocytes of 2 min; the second experimental group was made up of five experiments whose incubation times were 5 and 10 min. Fosfomycin inhibits the thrombocytal aggregation which is induced by ADP. This inhibition (1) is larger, the smaller the concentration of ADP, (2) for a single concentration of ADP it is proportional to the concentration of fosfomycin that is used, and (3) there are no significant differences according to the time of incubation. This thrombocytal anti-aggregating activity is related to the presence of a phosphonic group in the molecule of fosfomycin.