R.G. del Moral

Role of P-glycoprotein in chronic cyclosporine nephrotoxicity and its relationship to intrarenal angiotensin II deposits.

CYCLOSPORINE (CsA), among other actions in the kidney, induces P-glycoprotein (P-gp) overexpression in tubular cells. P-gp expels hydrophobic xenobiotics from the cytoplasm, including chemotherapeutic and immunosuppressive agents such as CsA, tacrolimus, and rapamycin. One of the main secondary effects of CsA treatment is nephrotoxicity. Morphologic findings of CsA nephrotoxicity include vacuolar isometric degeneration of kidney tubules, hyaline arteriopathy, and stripped and diffuse interstitial fibrosis. Experimental models in rats have shown that low sodium (LS) diets decrease renal blood flow and intensify histopathologic lesions of CsA nephrotoxicity, especially hyaline arteriopathy and stripped tubulointerstitial fibrosis, parallel with the upregulation of the renin-angiotensin system (RAS). In this context, some studies have found that blockers of angiotensin II receptors, as well as angiotensin II–converting enzyme inhibitors: (a) prevent the development of interstitial fibrosis in experimental models of chronic CsA nephrotoxicity; and (b) reduce the accumulation of TGF-b1 and proteins of the extracellular matrix in CsA-induced chronic nephropathy. Our aim was to analyze the alterations induced by CsA in P-gp expression in kidney tubular cells of Sprague–Dawley rats and to characterize the relationship of these changes with the angiotensin II deposits and chronic CsA nephrotoxicity lesions.

Effects of testosterone on brain mRNA levels of steroid 5α-reductase isozymes in early postnatal life of rat

The enzyme 5alpha-reductase (5alpha-R) (EC 1.3.99.5) exists as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2), and both are present in the brain. 5alpha-R1 has been proposed as a constitutive enzyme that essentially plays a catabolic and neuron protective role whereas 5alpha-R2 has been associated with sexually dimorphic functions of the male. In this work, we studied the effects of testosterone (T), the masculinizing hormone of the central nervous system (CNS), on mRNA levels of both 5alpha-R isoforms in the prefrontal cortex of male and female rats during the postnatal sexual differentiation of the CNS in the rat, using one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis (LIF-CE). We found an increase in 5alpha-R2 mRNA levels in both male and female rats after T treatment, while 5alpha-R1 mRNA levels were decreased in the same experimental conditions. Our results clearly indicated that T regulates the expression of both 5alpha-R1 and 5alpha-R2 genes in an opposite manner and independently of the sex. This could point to a crucial role of T in the sexual dimorphism for both 5alpha-R isozymes in the neonatal brain. These results open up a new research line that could improve understanding of the role of 5alpha-R isozymes in the physiology of the CNS.

Synthesis of some retinoids bearing different heterocyclic rings with anticancer activity

The synthesis of a series of pyrrole and imidazole retinoids is reported. The compounds were obtained by means of reactions of phosphoranes or phosphonates with aldehydes. Several of these retinoids were evaluated against different tumor systems and some were found to have an activity comparable to that of all-trans retinoic acid.

Taste and olfactory status in a gourmand with a right amygdala lesion

In a patient with a lesion of the right amygdala and temporal pole who had the characteristics of the gourmand syndrome, sensory and hedonic testing was performed to examine the processing of taste, olfactory, and some emotional stimuli. The gourmand syndrome describes a preoccupation with food and a preference for fine eating and is associated with right anterior lesions. It was found that the taste thresholds for sweet, salt, bitter, and sour were normal; that the patient did not dislike the taste of salt (NaCl) at low and moderate concentrations as much as age-matched controls; that this also occurred for monosodium glutamate (MSG); that there were some olfactory differences from normal controls; and that there was a marked reduction in the ability to detect face expressions of disgust.

El Metronidazol en los agrandamientos gingivales secundarios a Ciclosporina A

Introduccion: El agrandamiento gingival (AG) secundario a farmacos continua siendo un problema importante para los periodoncistas. Han sido comunicadas remisiones parciales o totales del AG tras tratamientos cortos con diversos antibioticos. Metodos: Hemos realizado un estudio aleatorio controlado a doble ciego para determinar el efecto del tratamiento con metronidazol durante siete dias (250 mg/3 veces al dia) sobre el AG incipiente secundario a ciclosporina A en pacientes adultos trasplantados renales. La valoracion cuantitativa del AG se realizo semiautomaticamente con tecnicas de Analisis Digital de Imagen. Resultados: En ninguno de los 26 pacientes incluidos en el estudio se obtuvo la remision completa del AG al finalizar el estudio. El indice de AG obtenido a tiempo cero fue en los pacientes tratados con metronidazol (grupo MNZ) 0.90+/-0.16 y en los controles (grupo placebo) 1.11+/-0.33. Transcurridos 30 dias de evolucion el indice de AG en el grupo MNZ no se modifico (0.92+/-0.28) y en los pacientes que tomaron placebo se incremento ligeramente (1.18+/-0.3), aunque sin llegar a ser estadisticamente significativo. El indice AG disminuyo en el 54.4% de los pacientes del grupo MNZ, mientras que solo lo hizo en el 23.1% en el grupo placebo. A pesar de que no existieron diferencias en el indice de AG entre los dos grupos al principio del ensayo al finalizar el mismo el mayor incremento del IAG en el grupo placebo dio como resultado una diferencia estadisticamente significativa (MNZ 0.92+/-0.28 vs placebo 1.18+/-0.3, p<0.05 t de Student), diferencia que se acentuo cuando se compararon solo los pacientes de ambos grupos con AG clinico grado 1 o 2 (MNZ 0.96+/-0.31 vs placebo 1.24+/-0.31, t de Student p<0.05). Conclusion: Los resultados del presente estudio indican que el tratamiento con metronidazol durante siete dias no induce la regresion completa de los agrandamientos gingivales producidos por CsA, pero puede frenar parcialmente el curso clinico del AG, posiblemente al reducir la sobreinfeccion bacteriana y la inflamacion gingival. Palabras Clave: Metronidazol, ciclosporina A, sobrecrecimiento gingival.