Maternal fructose intake aggravates the harmful effects of a Western diet in rat male descendants impacting their cholesterol metabolism.

Scope: fructose consumption from added sugars correlates with the epidemic rise in MetS and CVD. Maternal fructose intake has been described to program metabolic diseases in progeny. However, consumption of fructose-containing beverages is allowed during gestation. Cholesterol is also a well-known risk factor for CVD. Therefore, it is essential to study Western diets which combine fructose and cholesterol and how maternal fructose can influence the response of progeny to these diets. Methods and results: a high-cholesterol (2%) diet combined with liquid fructose (10%), as a model of an unhealthy Western diet, was administered to descendants from control and fructose-fed mothers. Gene (mRNA and protein) expression and plasma, fecal and tissue parameters of cholesterol metabolism were measured. Interestingly, progeny from fructose-fed dams consumed less liquid fructose and cholesterol-rich chow than males from control mothers. Moreover, descendants of fructose-fed mothers fed a Western diet showed an increased cholesterol elimination through bile and feces than males from control mothers. Despite these mitigating circumstances to develop a proatherogenic profile, the same degree of hypercholesterolemia and severity of steatosis were observed in all descendants fed a Western diet, independently of maternal intake. An increased intestinal absorption of cholesterol, synthesis, esterification, and assembly into lipoprotein found in males from fructose-fed dams consuming a Western diet could be the cause. Moreover, an augmented GLP2 signalling seen in these animals would explain this enhanced lipid absorption. Conclusions: maternal fructose intake, through a fetal programming, makes a Western diet considerably more harmful in their descendants than in the offspring from control mothers.

3D-Printed Franz cells - update on optimization of manufacture and evaluation.

OBJECTIVES: Laboratory in vitro permeation processes require the use of modified Franz type diffusion cells which are conventionally fabricated from glass. Fragility and high cost are frequently associated with this type of laboratory apparatus. The purpose of our present research was to develop a simple, economical and versatile approach to manufacture Franz type cells using additive manufacturing (AM). METHODS: Graphical Franz diffusion cell designs were reproduced with a stereolithography (SLA) 3D printer and assessed over a minimum period of 24 h. The surface morphology of AM printouts was analysed before and after compatibility studies using scanning electron microscopy (SEM). Comparative permeation studies in both glass and AM Franz type diffusion cells were conducted using a caffeine solution (1.5 mg mL-1 ), applied to a model silicone membrane. RESULTS: Testing of the 3D printed scaffolds confirmed similar recovery of the permeant when compared to glass cells: 1.49 ± 0.01 and 1.50 ± 0.01 mg mL-1 , respectively, after 72 h. No significant differences were visible from the SEM micrographs demonstrating consistent, smooth and non-porous surfaces of the AM Franz cells' core structure. Permeation studies using transparent 3D printed constructs resulted in 12.85 ± 0.53 µg cm-2 caffeine recovery in the receptor solution after 180 min with comparable permeant recovery, 11.49 ± 1.04 µg cm-2 , for the glass homologues. CONCLUSION: AM constructs can be considered as viable alternatives to the use of conventional glass apparatus offering a simple, reproducible and cost-effective method of replicating specialised laboratory glassware. A wider range of permeants will be investigated in future studies with these novel 3D printed Franz diffusion cells.

OBJECTIF: les processus de perméation in vitro en laboratoire nécessitent l'utilisation de cellules de diffusion de type Franz modifiées, fabriquées traditionnellement en verre. La fragilité et un coût élevé sont fréquemment associés à ce type d'appareil de laboratoire. L'objectif de nos travaux de recherche actuels était de développer une approche simple, économique et polyvalente pour fabriquer des cellules de type Franz à l'aide de la fabrication additive (FA). MÉTHODES: les conceptions des cellules de diffusion Franz graphiques ont été reproduites avec une imprimante 3D stéréolithographie (SLA) et évaluées sur une période minimum de 24 h. La morphologie de surface des impressions FA a été analysée avant et après des études de compatibilité à l'aide de la microscopie électronique à balayage (MEB). Des études comparatives de perméation des cellules de diffusion de type Franz en verre et FA ont été réalisées à l'aide d'une solution de caféine (1,5 mg ml-1 ) appliquée à un modèle de membrane en silicone. RÉSULTATS: les tests des supports imprimés 3D ont confirmé une récupération similaire du perméant par rapport aux cellules de verre : 1,49 ± 0,01 et 1,50 ± 0,01 mg ml-1 , respectivement, après 72 h. Aucune différence significative n'a été observée sur les micrographiques MEB, montrant des surfaces cohérentes, lisses et non poreuses de la structure centrale des cellules Franz FA. Les études de perméation utilisant des constructions transparentes imprimées en 3D ont conduit à une récupération de la caféine de 12,85 ± 0,53 µg cm-2 dans la solution de récepteur après 180 min avec une récupération de perméant comparable, 11,49 ± 1,04 µg cm-2 , pour les homologues de verre. CONCLUSION: les constructions FA peuvent être considérées comme des alternatives viables à l'utilisation d'appareils de verre conventionnels offrant une méthode simple, reproductible et rentable de réplication de la verrerie de laboratoire spécialisée. Une gamme plus large de perméants sera étudiée dans de futures études avec ces nouvelles cellules de diffusion Franz imprimées en 3D.

3D-printed Franz type diffusion cells.

OBJECTIVE: Franz cells are routinely used to measure in vitro skin permeation of actives and must be inert to the permeant under study. The aim of the present work was to develop and manufacture transparent Franz-type diffusion cells using 3D printing. Printouts were then tested using a range of model active compounds. The study also aims to identify the critical 3D-printing parameters necessary for the process, including object design, choice of printing resin, printout curing and post-curing settings and introduction of model coatings. METHODS: Transparent Franz cells were constructed using an online computer aided design program and reproduced with different stereolithography 3D printers. The two acrylate-based resins used for the fabrication process were a commercially available product and a polymer synthesised in-house. Comparative studies between glass and 3D-printed Franz cells were conducted with selected model actives: terbinafine hydrochloride (TBF), niacinamide (NIA), diclofenac free acid (DFA) and n-methyl paraben (MPB). In preliminary studies, MPB showed the lowest recovery when exposed to the receptor compartment of 3D printed cells. Consequently, in vitro permeation studies were carried out using only MPB with polydimethylsiloxane (PDMS) membrane. RESULTS: A decrease in the amounts of selected compounds was observed for transparent 3D-printed Franz cells compared to glass cells. MPB showed the lowest recovery (53.8 ± 13.1%) when compared with NIA (74.9 ± 4.0%), TBF (81.5 ± 12.0%) and DFA (90.2 ± 12.9%) after 72 h. Permeation studies conducted using 3D-printed transparent cells with PDMS membrane also showed a decrease in MPB recovery of 51.4 ± 3.7% for the commercial resin and 94.4 ± 3.5% for the polymer synthesised in-house, when compared to glass cells. Although hydrophobic coatings were subsequently applied to the 3D-printed cells, the same reduction in MPB concentration was observed in the receptor solution. CONCLUSION: Transparent Franz cells were successfully prepared using 3D printing and were observed to be robust and leak-proof. There are few resins currently available for preparation of transparent materials and incompatibilities between the actives investigated and the 3D-printed cells were evident. Hydrophobic coatings applied as barriers to the printed materials did not prevent these interactions.

Intravascular papillary endothelial hyperplasia (IPEH). Evidence supporting a piecemeal mode of angiogenesis from vein endothelium, with vein wall neovascularization and papillary formation.

Intravascular papillary endothelial hyperplasia (IPEH) is a reactive process of questioned pathogenesis (primary proliferation of endothelial cells/ECs versus organizing thrombi). The aim of this study is to assess the organization of morphologic patterns, with precise location of neovascularization and papillary distribution in IPEH to clarify the role of the vein wall (mainly vein intimal ECs) in lesion development and papillary formation. We studied 12 cases of IPEH in skin and subcutaneous veins by serial histological sections and immunohistochemical procedures. In four well-structured cases (the remaining cases showed overlapping events), we found four principal histological patterns organized by zone: 1) invaginated vein wall zone with microvascular networks. The intraparietal microvessels presented CD34+ and CD31+ ECs arising from ECs of the vein intima, and αSMA+ pericyte-like cells originating from modified SMCs of the media layer. 2) Papillary zone, generally with myriad papillae, formed by ECs of intraparietal microvessel networks encircling vein wall components (parietal papillae). 3) Organizing thrombotic zone from microvascular networks of invaginated vein wall zone. 4) Unorganized thrombotic zone partially covered by ECs, also originating from vein intimal endothelium and arranged in a monolayer or encircling thrombotic fibrin (thrombotic papillae). In conclusion, the capacity of vein intimal ECs and those originating from them (in newly-formed microvessels in the vein itself and covering the unorganized thrombi) to encircle vein wall components or fibrin, and to form papillae (ECs form the cover and encircled components the core) supports a piecemeal mode of angiogenesis as a pathogenic basis of IPEH. This mechanism encompasses the two histogenetic hypotheses outlined above.

Bisfosfonatos en cirugía oral: Revisión de literatura / Bisphosphonates in Oral Surgery: Literature Review

Los bisfosfonatos son fármacos de gran utilidad en el diagnóstico y tratamiento de ciertas enfermedades metabólicas óseas. Son utilizados en el tratamiento de mielomas múltiples, metástasis óseas y la hipercalcemia maligna, así como en la prevención y tratamiento de enfermedades del sistema óseo esquelético como la enfermedad de Paget y especialmente la osteoporosis. El objetivo de la presente revisión de literatura es presentar las consideraciones para el tratamiento de los pacientes medicados con bifosfonatos que van a ser sometidos a alguna intervención de cirugía oral a fin de ofrecerles las mejores alternativas terapéuticas que garanticen el correcto manejo de los tejidos bucales y mejoren su calidad de vida.

Bisphosphonates are drugs useful in the diagnosis and treatment of metabolic bone diseases. They are used in the treatment of multiple myeloma, bone metastases, malignant hypercalcemia and in the prevention and treatment of diseases of the skeletal system as Paget’s disease and especially osteoporosis. The aim of this review is to present the considerations for the treatment of patients taking bisphosphonates that will be undergoing any type of oral surgery in order to provide the best treatment options to ensure the correct handling of the oral tissues and improve their quality of life.

Evolución del porcentaje de episiotomía en un hospital comarcal entre los años 2003–2009. Factores de riesgo de los desgarros graves de periné / Evolution of the episiotomy rate in a community hospital, between 2003–2009. Severe perineal tears risk factors

Objetivo El objetivo primario de este trabajo es presentar la evolución del porcentaje de episiotomías entre los años 2003-2009, siguiendo una política de uso restrictivo y su posible influencia en el porcentaje de desgarros graves y en la morbilidad perinatal a corto plazo. Material y método El diseño del estudio es de cohorte retrospectiva, constituida por las mujeres que acuden a parir a nuestro centro (9.023 gestantes). Los parámetros que valoramos son: evolución del porcentaje de episiotomías y de desgarros graves de periné, según se realice episiotomía o no, en los partos eutócicos frente a los instrumentales y según el tipo de parto instrumental. Para valorar la relación entre los factores de riesgo y la incidencia de desgarros graves se realiza una regresión logística multivariante. Resultados La tasa de episiotomía osciló entre el 40,37% en el año 2003 y el 8% en el año 2009, siendo la tendencia a la disminución estadísticamente significativo. El porcentaje de desgarros graves se mantuvo entre el 0,49 y el 1,04% sin que la variación fuera estadísticamente significativa ((X2 = 3,47, p = 0,32). No hubo variación significativa en el porcentaje de Test de Apgar menor de 7, a los 5 min. La Odds ratio (OR) de presentar un desgarro grave de periné es 2,99 (IC 95% 1,47-6,05) en las mujeres que se realizó episiotomía frente a las que no se les realizó, de 2,40 (IC 95% 1,16-4,99) en los partos instrumentales frente a partos eutócicos es y de 6,43 (IC 95% 1,50-27,49) en los partos con fórceps, frente a los partos por ventosa. Conclusiones En un periodo de 7 años se ha reducido el porcentaje de episiotomías en un 80% sin modificarse la proporción de desgarros graves de periné, así mismo no ha habido aumento en la morbilidad perinatal a corto plazo (AU)

Objective The primary objective of this paper is to present the evolution of the episiotomy rate between the years 2003-2009, following a policy of restrictive use and its possible influence on the rate of severe lacerations and perinatal morbidity in the short term. Methods This is a retrospective study based on a cohort made up of women who gave birth in our hospital (9023 women). The valued parameters are: changes in the episiotomy rate, percentage of severe perineal tears according to the use of episiotomy or not. Normal vaginal deliveries versus instrumental ones and the type of instrumental delivery. Apgar score below 7 at five minutes. A multivariable logistic regression was performed in order to assess the relationship between risk factors and the incidence of severe tears. Results The episiotomy rate ranged between 40.37% in 2003 and 8% in 2009, the downward trend was statistically significant. The rate of severe tears remained between 0.49% and 1.04% that change was not statistically significant. There was no significant variation in the rate of Apgar score less than 7 at 5 minutes. The odds ratio (OR) of having a serious perineal tear is 2.99 (95% CI 1.47 to 6.05) in women who had an episiotomy compared with those that did not have it, the 2.40 (95% CI 1.16 to 4.99) in the instrumental delivery versus eutocic delivery and the 6.43 (95% CI 1.50 to 27.49) in forceps deliveries compared with vacuum deliveries. Conclusions Over a period of 7 years the episiotomy rate was reduced by 80% without modifying the rate of serious perineal tears, and the short-term perinatal morbidity remained constant (AU)

Nivel de cumplimiento de la Norma Oficial Mexicana 168-SSA1-1998. Una perspectiva del profesional de Enfermería / Level of fulfillment of the Mexican Health Standard NOM 168-SSA1-1998. A perspective from the Nursing Professional

Introducción: Los registros que realiza el profesional de enfermería son el soporte de los cuidados que brinda a cada una de las personas que le son asignadas en su jornada laboral, además son un elemento primordial para la toma de decisiones en la gestión del cuidado; por lo tanto es importante que los registros se realicen dando cumplimiento a la NOM 168-SSA1-1998 del expediente clínico para favorecer la continuidad y seguridad del cuidado; por lo cual el objetivo del estudio fue comparar el nivel de cumplimiento de la NOM 168-SSA1.1998 del expediente clínico en dos Institutos Nacionales de Salud, desde la perspectiva del profesional de enfermería. Material y métodos: Se realizó un estudio transversal, observacional, descriptivo y comparativo, la muestra estuvo integrada por 186 enfermeras. El nivel de cumplimiento de la NOM 168-SSA1-1998 se midió con una escala tipo likert modificado con 5 opciones de respuesta; para el análisis de datos se utilizó estadística descriptiva e inferencial. Resultados: Los datos obtenidos mostraron que la mayoría de las enfermeras refieren utilizar en sus registros lenguaje técnico, abreviaturas universales y letra legible, evitan realizar tachaduras y enmendaduras. Se observaron diferencias entre los dos institutos con relación al nivel de cumplimiento de la NOM 168-SSA1-1998 con un valor de p< 0.05. Conclusiones: Desde el punto de vista de las enfermeras el nivel de cumplimiento en la norma es adecuado lo cual puede limitar su disposición para participar en programas de mejora.

Introduction: Mexican nursing professionals back up their care interventions through registers, and this information becomes fundamental in the process of decision-making. Therefore, in order to promote care continuity and security, it is important that these registers fulfill the Mexican health standard NOM 168- SSA1-1998. The objective of this study was to compare the levels of fulfillment of this standard in two National Institutes of Health. Methods and material: A basic, observational, and comparative study was conducted with a sample of 186 nurses. The level of standard fulfillment was estimated using a 5 point Likert Scale. Descriptive and inferential statistics were performed. Results: our findings suggest that the majority of nurses use technical language with legible and neat writing. A difference was found between the two institutes (p < .05). Conclusions: from the perspective of these nurses, the level of fulfillment of this standard was adequate.

Resultados obstétricos tras conización. Hospital de León. Período 1999-2007 / Obstetrics results after conization. Leon Hospital. 1999-2007 period

Objetivo determinar el resultado obstétrico en mujeres a las que se les realizó conización en el Hospital de León de 1999 a 2007. Material y método estudio de cohorte retrospectivo. Se analizaron 338 conizaciones. Durante este período, 36 mujeres quedaron embarazadas y se obtuvieron 46 embarazos en total. Se incluyeron las siguientes variables: edad materna, paridad, hábito tabáquico, diagnóstico que motivó la conización y diagnóstico de la pieza, así como altura del cono extirpado, intervalo entre la conización y el parto, tipo de parto, edad gestacional y peso del recién nacido. Resultados de los 30 embarazos que superaron las 24 semanas, el 20% nació pretérmino. La comparación en función del hábito tabáquico no mostró diferencias. Ningún recién nacido tuvo bajo peso (BP) respecto a la edad gestacional. Conclusiones se observó asociación estadísticamente significativa entre prematuridad y conización, con independencia de la longitud del cono extirpado y del intervalo entre conización y parto. No se observó asociación entre el BP al nacimiento y la conización (AU)

Objective: To determine the obstetric results after conisation at the Leon Hospital (Spain)between 1999 and 2007.Material and method: We performed a retrospective cohort study of 338 conisations. Thirty-six women conceived and a total of 46 pregnancies were obtained during the study period. The following variables were analysed: maternal age, obstetric antecedents, smoking, the diagnoses motivating the conisation, final histopathological diagnosis, height of the extirpated cone, conisation-childbirth interval, type of labor, and gestational age and weight of the newborn. Results: Of the 30 pregnancies that exceeded 24 weeks, 20% ended preterm. No differences were found when the groups were compared according to smoking. None of the newborns was underweight for gestational age. Conclusions: A significant statistical association was observed between conisation and preterm delivery, independently of cone length or the conisation-labor interval. No statistical association was found between low birth weight and conisation (AU)

Circadian rhythms of prolactin secretion in neonatal female rabbits after acute separation from their mothers.

Newborn rabbits (Oryctolagus cuniculus) are only nursed for 3-5 min every 24 h and show a circadian increase in activity in anticipation of nursing. The objective of this study was to determine, in neonatal female rabbits after acute separation from the doe for 48 h, the changes in 24-h rhythms of plasma prolactin and median eminence and anterior pituitary concentration of dopamine (DA) and serotonin (5HT). In addition, median eminence concentration of the excitatory amino acid transmitters glutamate (GLU) and aspartate (ASP) and of the inhibitory amino acid transmitters gamma-aminobutyric acid (GABA) and taurine (TAU) was measured. A significant 21% increase of circulating prolactin occurred in isolated pups. In controls pups, plasma prolactin levels showed two peaks, during the first half of the light phase and at the beginning of the scotophase, respectively. In the isolated pups, a phase advance of about 4 h occurred for the two prolactin peaks. Hemicircadian changes of median eminence DA were found in controls, whereas a single daily peak (at 17:00 h) was found in the separated pups. Plasma prolactin and median eminence DA correlated significantly and inversely in the control group only. Pituitary DA content exhibited a single peak in controls and a hemicircadian pattern in isolated pups. Plasma prolactin and pituitary DA correlated significantly in isolated pups only 00000. Pup isolation decreased median eminence 5HT levels, augmented pituitary 5HT levels and disrupted their 24 h rhythmicity. Circulating prolactin correlated inversely with median eminence 5HT and directly with adenohypophysial 5HT only in controls. Isolation of pups generally modified the 24 h pattern of median eminence excitatory and inhibitory amino acid content by causing a prominent decrease at the beginning of the light phase. The results indicate that circadian rhythmicity of prolactin secretory mechanisms in female rabbit pups is significantly affected by pup's isolation from the doe.

Twenty-four hour rhythm of plasma prolactin in female rabbit pups. Correlation with hypothalamic and adenohypophysial dopamine, serotonin, gamma-aminobutyric acid and taurine content.

Lactation in the rabbit is a nocturnal activity, extremely short and regular, that can be a strong synchronizer for the development of circadian rhythmicity in the pups. In the present study, 24-h rhythmicity of plasma prolactin and median eminence and anterior pituitary content of dopamine (DA), serotonin (5HT), gamma-aminobutyric acid (GABA) and taurine were examined in 11 days old female pups kept under 16 h light:8 h dark photoperiods (lights on at 08:00 h). Groups of six to seven female rabbit pups were killed by decapitation at six different time points throughout a 24-h cycle, starting at 09:00 h. Plasma prolactin levels changed significantly throughout the day, showing two peaks, one at first half of rest span (at 13:00 h) and another one at the beginning of the scotophase (at 01:00 h), just preceding doe visit. Median eminence DA content changed in a bimodal way as a function of time of day, displaying two maxima, at the beginning of the rest span and of the activity phase. Median eminence DA and plasma prolactin correlated significantly in an inverse way. Two maxima in median eminence 5HT levels were found, about 4 h in advance to the prolactin peaks. Circulating prolactin correlated inversely with median eminence 5HT content and directly with adenohypophysial 5HT content. Median eminence GABA content reached its maximum at the beginning of the scotophase and correlated significantly with plasma prolactin concentration. A positive correlation between plasma prolactin and adenohypophysial taurine content was observed. These results show that the circadian rhythmicity in prolactin secretory mechanisms in female rabbit pups develops during the early neonatal life.

Superior cervical ganglionectomy differentially modifies median eminence and anterior and mediobasal hypothalamic GABA content in male rats: effects of hyperprolactinemia.

This work was undertaken to analyze the changes in GABA concentrations in the anterior and mediobasal hypothalamus and in the median eminence after acute or chronic superior cervical ganglionectomy (SCGx), and whether high prolactin levels interfere with the effects of SCGx on GABA content. Acute but not chronic SCGx increased GABA content in all the areas studied, as compared to controls. The presence of a pituitary graft abolished the effects of acute SCGx in the median eminence and anterior hypothalamus, as compared to controls, but potentiated its effects in the mediobasal hypothalamus. Chronic SCGx increased GABA content in the mediobasal and anterior hypothalami, as compared to pituitary grafted controls. Acute SCGx decreased plasma prolactin and GH levels, but chronic surgery did not modify these hormone plasma levels. Acute SCGx increased plasma ACTH levels, whereas chronic SCGx did not modify them. Pituitary grafting increased circulating values of prolactin, ACTH and GH, as compared to controls. Acute SCGx did not modify plasma prolactin levels in grafted animals, although it increased plasma GH levels and decreased those of ACTH in this experimental group. Chronic SCGx further increased both plasma prolactin and GH levels, without modifying plasma ACTH levels. These results suggest that SCGx differentially modifies GABA content within the hypothalamus and median eminence. Induction of hyperprolactinemia in the neonatal age interferes with SCGx effects on both GABA content within the hypothalamus and median eminence and the secretory patterns of the pituitary hormones studied.

Differential effects of light/dark recombinant human prolactin administration on the submaxillary lymph nodes and spleen activity of adult male mice.

OBJECTIVES: Day/night variations in cellularity, percentage of CD4+, CD8+ and double-positive (CD4+-CD8+) lymphocytes, lipopolysaccharide (LPS)- and concanavalin A (Con A)-induced lymphocyte proliferation and natural killer (NK) activity, and the effect of timed administration of recombinant human prolactin (h-PRL) on the above-mentioned parameters were investigated in the submaxillary lymph nodes and spleen of adult male mice. RESULTS: In controls, the percentage of CD4+, double-positive lymphocytes, LPS- or Con A-induced blastogenic proliferation and NK activity in the spleen differ during the dark phase as compared to the light phase. When administered during the dark period, h-PRL induced immunosuppresion in the percentage of CD4+, double-positive (CD4+-CD8+) lymphocytes. Con A- and LPS-induced lymphocyte proliferation and NK activity as compared to untreated controls. When h-PRL was administered during the light period, the cellularity increased, and h-PRL was immunosuppressive in Con A- and LPS-induced lymphcoyte proliferation and NK activity as compared to controls. Moreover, in control submaxillary lymph nodes the cellularity, percentage of CD8+, double-positive lymphocytes, blastogenic proliferation in the presence of Con A and LPS and NK activity differ when comparing the dark with the light phase. When administered during the dark period h-PRL induced immunosuppression in the percentage of double-positive (CD4+-CD8+) lymphocytes, Con A- and LPS-induced lymphocyte proliferation as compared to controls. When h-PRL is administered during the light period, no effects were observed. CONCLUSIONS: These results indicate the existence of differential day/night variations in the cellular immune response depending upon the lymphoid organ considered. Because of the administration of h-PRL a differential modulation of this circadian variation was also observed.

Superior cervical ganglionectomy effects on median eminence and anterior and mediobasal hypothalamic taurine content in male rats: effects of hyperprolactinemia.

The neuroendocrine sequelae of acute or chronic superior cervical ganglionectomy in control or pituitary-grafted rats were studied by analyzing both plasma prolactin, growth hormone (GH) and ACTH levels, and taurine (TAU) content in the hypophysiotropic area of the hypothalamus or the median eminence. As expected, after either acute or chronic ganglionectomy, norepinephrine (NE) content decreased in the brain areas studied, although the values remained higher in hyperprolactinemic rats. TAU content was differentially modified by acute vs. chronic surgeries, thus indicating the possible existence of hypothalamic interactions between TAU and NE to regulate pituitary hormone secretion. Indeed, associated differential changes in plasma prolactin, GH and ACTH levels may be due to the observed TAU changes. As expected, pituitary grafting increased plasma prolactin, GH and ACTH levels, so that the presence of a pituitary graft differentially interferes with the effects of either surgery not only on TAU content but also on the plasma levels of the hormone studied. Globally, ongoing studies confirm the differential effects of acute and chronic superior cervical ganglionectomy on plasma prolactin, GH and ACTH levels, and provide new evidence about its effects on TAU content in the hypophysiotropic area of the hypothalamus and the median eminence that may partially explain the changes observed in the pituitary hormones studied.

Effects of overexpression of growth hormone on T cell activity in transgenic mice.

Growth hormone plays a key role in the maturation and maintenance of the immune response, however, the effects of chronic high circulating concentrations of the hormone on the immune system is poorly understood. Transgenic mice overexpressing bovine growth hormone (b-GH) gene, fused to the rat phosphoenolpyruvate carboxykinase promoter (PEPCK), with very high plasma concentration of heterologous b-GH and their littermate normal siblings were used. Spleen cellularity, percentages of total T lymphocytes, CD4+ and CD8+ cells, ratio of T cell subpopulations, mitogen-induced lymphocyte proliferation and natural killer (NK) cell activity were examined in male transgenic mice and normal littermate mice at 2 and 6 months of age. The number of splenic lymphocytes was greater in transgenic mice than in matched normal littermates at both ages. The NK cell activity was lower in transgenic mice than in the matched normal littermates at both ages, with the lowest values found in older mice. The b-GH transgenic mice had lower percentages of T cells at both ages, however, in young transgenic mice, the percentage of CD4+ cells was reduced while percentage of CD8+ cells was increased in comparison to normal controls. Both basal and mitogen-induced proliferation capacity of splenocytes were reduced in PEPCK-b-GH-25 mice as compared to normal littermates of both ages. Proliferative indexes in response to concanavalin A and phytohemagglutinin were markedly decreased in 6 month old PEPCK-b-GH-25 mice as compared to littermate controls or younger mice. These results indicate that overexpression of b-GH in mice is associated with decreased T cell function and that these abnormalities are age-dependent.

[Pharmacovigilance study of azithromycin tablets (500 mg) in the treatment of adult patients with respiratory tract infections]. / Estudio de farmacovigilancia de azitromicinacomprimidos (500 mg) en el tratamiento de pacientesadultos con infecciones de vías respiratorias. Grupo colaborador.

Our aim was to study a new form of azithromycin (500 mg tablets) in order to evaluate the tolerability and the influence of the ingestion of food on tolerability, the efficacy and treatment compliance in a large number of patients with respiratory tract infections. We carried out an open, non-comparative, multicenter, observational and prospective pharmacovigilance study of 3223 outpatients with respiratory tract infections randomly assigned to receive a daily dose of azithromycin for three months taken either during or outside meals. Patients were evaluated during an initial visit and two later ones in order to record the adverse events and establish the clinical efficacy. The diagnostics were as follows: pharyngotonsillitis (1200), acute otitis media (394), acute bronchitis (1134), exacerbation of chronic bronchitis (436), and community-acquired pneumonia (53). The overall therapeutic efficacy was satisfactory (cure or improvement) in 96% to 97% at the second visit and in 93% to 94% in the third (pharyngotonsillitis, 93%; acute otitis media, 91%; acute bronchitis, 94%; exacerbation of chronic bronchitis, 94%; and community-acquired pneumonia, 96%). A total of 170 adverse events were reported in 141 patients (4.4%); 12 were severe yet not related to the study medication. Eighty-eight patients showed adverse events presumed to be related to azithromycin; most were in the digestive tract. No differences in tolerability were observed in relation to food intake. Treatment compliance was high (97%). The elevated clinical efficacy, adequate compliance and the excellent tolerability profile of azithromycin tablets make them a safe and effective alternative in the treatment of respiratory tract infections.

Phase II trial of gemcitabine and UFT modulated by leucovorin in patients with advanced pancreatic carcinoma. The ONCOPAZ Cooperative Group.

BACKGROUND: Use of chemotherapy for advanced pancreatic carcinoma (APC) pursues a palliative objective. Gemcitabine is active against this tumor and shows in vitro synergism with 5-fluorouracil. UFT is a combination of tegafur (a prodrug of 5-flouorouracil) and uracil that can be given orally. The administration of UFT for several weeks may simulate the effects of a continuous infusion of 5-fluorouracil. The objective of the current study was to assess the efficacy and toxicity of the combination gemcitabine-UFT-leucovorin in the treatment of APC. METHODS: Forty-two patients with bidimensionally measurable APC were included. The study regimen consisted of gemcitabine 1000 mg/m(2) once weekly for 3 consecutive weeks, followed by a 1-week rest, intravenous 6S-steroisomer of leucovorin (6SLV) 250 mg/m(2) in 2 hours on Day 1, oral 6SLV 7.5 mg/12 hours on Days 2-14, and oral UFT 390 mg/m(2)/day (in 2 doses) on Days 1-14. Cycles were repeated every 4 weeks for a minimum of 3 per patient unless progressive disease was detected. RESULTS: One hundred eighty-three courses were given, with a median of 4 per patient. World Health Organization Grade 3-4 toxicity was: diarrhea in 7 patients (17%), leucopenia in 2 (5%), nausea/vomiting in 2 (5%), and anemia in 1 (4%). Among 38 patients evaluable for response, 6 achieved a partial response (16%; 95% confidence interval (CI), 6-31. 4), 15 had stable disease (39%), and 17 had progression (45%). Improvement in performance status and symptoms (pain, analgesic consumption, and weight) was present in 11 (29%) and 17 (45%) patients, respectively. Eighteen patients (47%; 95% CI, 31.5-54.5) experienced a clinical benefit response. CONCLUSIONS: The combination of gemcitabine-UFT-6SLV is convenient and moderately active and shows a low toxicity for the palliative treatment of patients with APC.

[Agranulocytosis caused by metamizol. Anesthetic attitude]. / Agranulocitosis por metamizol. Actitud anestésica.

Agranulocytosis induced by metamizole is uncommon, with a frequency of less than one case per million treatments. We describe such a case in a patient requiring emergency surgery. An 85-year-old man with a history of infantile paralysis with mental retardation and Paget's disease and X-ray signs of the right femur came to the emergency room with a diaphysial fracture. He received 1 g metamizole i.v. every 8 hours for analgesia. Ten hours after admission a routine blood cell count showed a rapid fall in the number of leukocytes; at 24 hours the count was 600 x 10(9)/l. The diagnosis was agranulocytosis induced by metamizole. Postponement of surgery was advisable and treatment with granulocyte colony stimulating factor (GCSF) at a dose of 5 micrograms/kg/day. Agranulocytosis resolved after 3 days of treatment, after which time the bone was set with a straight femoral plate under subarachnoid anesthesia. Two packs of red blood cells were required during the immediate postoperative period. Twelve days after surgery the patient was released. We review the anesthetic approach to agranulocytosis and its treatment.

[An analysis of the care for a tubercular patient. Problem detection]. / Análisis de la atención al paciente tuberculoso. Detección de problemas.

OBJECTIVE: Make a epidemiological and descriptive analysis of the tuberculosis patients care, researching problems which may be the etiology of the increase of illness. DESIGN: Descriptive observing retrospective study. SETTING: Soria County. PATIENTS: 186 cases with positive Mycobacterium tuberculosis culture, since January 1, 1983 until December 31, 1993. RESULTS: The 65.4% of patients were hospitalized to make the diagnostic and/or to begin treatment. We found delayed diagnostics much as 5.5 years. The mean was 120.9 +/- 244.7 days until the diagnostic was performed, 1991 y 1992 were the highest delayed time to diagnostic years of the study. The diagnostic and control of the 99.5% of patients was done at hospital. Only a 64% of patients could be considered as healthy at the onset of his control. CONCLUSIONS: Most of physicians consider the tuberculosis as a hospital illness, so there are delayed diagnostic and therapeutics and worse control of evolution, therapy compliance and contacts study.