Comparison of oncological outcomes after open and laparoscopic re-resection of incidental gallbladder cancer.

BACKGROUND: The safety and oncological efficacy of laparoscopic re-resection of incidental gallbladder cancer have not been studied. This study aimed to compare laparoscopic with open re-resection of incidentally discovered gallbladder cancer while minimizing selection bias. METHODS: This was a multicentre retrospective observational cohort study of patients with incidental gallbladder cancer who underwent re-resection with curative intent at four centres between 2000 and 2017. Overall survival (OS) and recurrence-free survival (RFS) were analysed by intention to treat. Inverse probability of surgery treatment weighting using propensity scoring was undertaken. RESULTS: A total of 255 patients underwent re-resection (190 open, 65 laparoscopic). Nineteen laparoscopic procedures were converted to open operation. Surgery before 2011 was the only factor associated with conversion. Duration of hospital stay was shorter after laparoscopic re-resection (median 4 versus 6 days; P < 0·001). Three-year OS rates for laparoscopic and open re-resection were 87 and 62 per cent respectively (P = 0·502). Independent predictors of worse OS were residual cancer found at re-resection (hazard ratio (HR) 1·91, 95 per cent c.i. 1·17 to 3·11), blood loss of at least 500 ml (HR 1·83, 1·23 to 2·74) and at least four positive nodes (HR 3·11, 1·46 to 6·65). In competing-risks analysis, the RFS incidence was higher for laparoscopic re-resection (P = 0·038), but OS did not differ between groups. Independent predictors of worse RFS were one to three positive nodes (HR 2·16, 1·29 to 3·60), at least four positive nodes (HR 4·39, 1·96 to 9·82) and residual cancer (HR 2·42, 1·46 to 4·00). CONCLUSION: Laparoscopic re-resection for selected patients with incidental gallbladder cancer is oncologically non-inferior to an open approach. Dissemination of advanced laparoscopic skills and timely referral of patients with incidental gallbladder cancer to specialized centres may allow more patients to benefit from this operation.

ANTECEDENTES: No se conoce la seguridad y la eficacia oncológica de la re-resección laparoscópica del cáncer incidental de vesícula biliar. Este estudio tiene como objetivo comparar las re-resecciones del cáncer incidental de vesícula biliar por vía laparoscópica y vía abierta, minimizando el sesgo de selección. MÉTODOS: Estudio de cohortes observacional, retrospectivo y multicéntrico de pacientes con cáncer incidental de vesícula biliar que se sometieron a una re-resección con intención curativa en 4 centros entre 2000 y 2017. Se analizó la supervivencia global (overall survival, OS) y la supervivencia libre de recidiva (recurrence free survival, RFS) según intención de tratamiento. Se calculó la probabilidad inversa de la ponderación del tratamiento quirúrgico utilizando puntuación de propensión. RESULTADOS: Se incluyeron 255 pacientes con re-resección (190 por vía abierta y 65 por vía laparoscópica). Se convirtieron 19 pacientes del grupo laparoscópico. El único factor relacionado con la conversión fue la realización de la cirugía antes de año 2011. La mediana de la estancia hospitalaria fue más corta tras la re-resección laparoscópica (4 versus 6 días; P < 0,001). La OS a tres años fue del 87% y del 62% (P = 0,502) para las re-resecciones laparoscópicas y abiertas, respectivamente). Los factores predictivos independientes relacionados con una peor OS fueron el hallazgo de cáncer residual en el momento de la re-resección (cociente de riesgos instantáneos, hazard ratio, HR 1,91; i.c. del 95% 1,17-3,11), una pérdida hemática > 500 ml (HR 1,83; i.c. del 95% 1,23-2,74) y la presencia de ≥ 4 ganglios positivos (HR 3,11; i.c. del 95% 1,46-6,65). En el análisis de riesgo competitivo, la RFS fue mayor para la resección laparoscópica (P = 0,038), pero no hubo diferencias en la OS entre ambos grupos. Los factores predictivos independientes de peor RFS fueron la detección de 1-3 ganglios positivos (HR 2,16; i.c. del 95% 1,29-3,60), ≥ 4 ganglio positivos (HR 4,39; i.c. del 95% 1,96-9,82) y el cáncer residual (HR 2,42; i.c. de 95% 1,46-4,0). CONCLUSIÓN: En pacientes seleccionados, los resultados oncológicos de la re-resección laparoscópica de un cáncer incidental de vesícula biliar no son inferiores a los que se obtienen por vía abierta. Una mayor difusión de las técnicas laparoscópicas avanzadas y una oportuna derivación de los pacientes con cáncer de vesícula biliar incidental a centros especializados podrían permitir que un mayor número de pacientes se beneficiaran de este abordaje.

Programa de transición: una intervención para adolescentes con diabetes tipo 1: estudio de casos y controles / Transition program: an intervention for adolescents with type 1 diabetes: cases and controls study

Introduction: The transition programs (TP) are planned interventions with specific aims which support type 1 diabetes adolescents in their process to emigrate from a pediatric care system to an adult care system. Objective: To evaluate the effectiveness of a TP in type 1 diabetes adolescents. Subjects and Method: This study was performed in 20 adolescents: 10 in TP and 10 controls (no TP) attended in an adult care system in a traditional way. The applied program included: coordination of attention dates, administrative supervision of the cases, and integral health team attention: physician every three months, psychologist with psychosocial follow-up every three months, nutricionist and university nurse according to the case necessities. After a year of the TP implementation the indicators of adherence were evaluated: continuity of care, regular medical appointments, physician/adolescent relationship, psychosocial follow-up, and to maintain or improve the HbA1c. The statistical analysis of variables comparison was performed with Kwallis Test o Mann-Whitney Test, in STATA 12.0 program. Results: At comparing groups, it was found that the intervened adolescents presented a major frequency of: continuity of diabetes care, regular medical appointments, physician/adolescent relationship and psychosocial follow-up (p < 0,01); the indicator of maintaining or improving the HbA1c was better in the patients with TP (60 percent vs 30 percent) yet not significant. Conclusion: In type 1 diabetes adolescents, with the applied TP we get better indicators of adherence to the diabetes treatment

Experiencia con insulina degludec en pacientes diabéticos Tipo 1 del Hospital San Juan de Dios Santiago / Experience with degludec insulin in Type 1 diabetic patients at the San Juan de Dios Hospital

OBJECTIVE: To study the efficacy and safety of degludec insulin in Type 1 diabetic patients. PATIENTS AND METHOD: In a prospective study, 230 type 1 diabetics patients, average aged 34 years age and 14 years of diagnosis of diabetes and treated with two doses of insulin glargine U-100, were changed to degludec. Patients had glycosylated hemoglobins (HbA1c) greater than 10 percent. Results were recorded at 3 and 6 months with parameters clinical, biochemical, insulin requirements per kilogram of weight (U/kg/wt) and hypoglycemia. Capillary glycemia was evaluated three times a day and the dose of insulin degludec every two weeks. The statistical analysis used was average and rank, standard deviation, normal Swilk test, categorical Chi2 and continuous ANOVA or Kwallis, and p < 0.05. A psychological survey was conducted to evaluate satisfaction with the new treatment. RESULTS: Fasting blood glucose decreased from 253 (range 243-270) at 180 mg/dl (172-240) at 3 months and at 156 (137-180) at 6 months after the change insulin (p < 0.05). HbA1c, initially 10.6 percent (10.4-12.2) decreased to 8.7 percent (9.3-10.1) and 8.3 percent (8.7-9.7) at 3 and 6 months, respectively (p < 0.05). There was a decrease in basal insulin requirements from 0.7 to 0.4 U/kg/60 percent reduction in hypoglycaemia; both mild and moderate and severe. Isolated nocturnal hypoglycaemias were recorded in only 4 patients in this group. CONCLUSION: Six months of treatment with degludec insulin reduces fasting blood glucose, glycosylated hemoglobin and hypoglycemia, both mild and moderate severe and nocturnal, which makes this new ultra-long acting basal insulin a safe and effective tool for the management of type 1 diabetics patients

Cetoacidosis diabética normoglicémica en el embarazo: caso clínico / Normoglycemic diabetic ketoacidosis in pregnancy: report of one case

Normoglycemic diabetic ketoacidosis should be suspected in pregnant women presenting nausea, vomiting, abdominal pain and anorexia. We report a 39 years old woman with a 32 weeks pregnancy who sought emergency care due to hyperemesis. She was hospitalized with the following diagnoses: pregnancy hypertension syndrome, gestational diabetes, morbid obesity and poor prenatal control. The evaluation of the feto-placental unit showed perception of fetal movements, non-reactive non-stress baseline record and a biophysical profile of 6/8. Fetal maturation was initiated. Laboratory tests showed a metabolic acidosis, a low pH, an increased Gap anion, elevated ketonemia and a blood glucose of 172 mg/dl. A diagnosis of normoglycemic diabetic ketoacidosis was formulated and treatment with hydration and regular insulin according to capillary blood glucose levels was started. An emergency caesarean section was performed. The newborn weighed 2.650 kg, had a length of 46 cm, was large for gestational age, had an Apgar score of 2.7, had perinatal asphyxia, convulsive syndrome and a possible congenital cardiopathy. Once the ketoacidosis was resolved during the immediate puerperium, slow acting insulin was initiated.

[Normoglycemic diabetic ketoacidosis in pregnancy: Report of one case]. / Cetoacidosis diabética normoglicémica en el embarazo: Caso clínico.

Normoglycemic diabetic ketoacidosis should be suspected in pregnant women presenting nausea, vomiting, abdominal pain and anorexia. We report a 39 years old woman with a 32 weeks pregnancy who sought emergency care due to hyperemesis. She was hospitalized with the following diagnoses: pregnancy hypertension syndrome, gestational diabetes, morbid obesity and poor prenatal control. The evaluation of the feto-placental unit showed perception of fetal movements, non-reactive non-stress baseline record and a biophysical profile of 6/8. Fetal maturation was initiated. Laboratory tests showed a metabolic acidosis, a low pH, an increased Gap anion, elevated ketonemia and a blood glucose of 172 mg/dl. A diagnosis of normoglycemic diabetic ketoacidosis was formulated and treatment with hydration and regular insulin according to capillary blood glucose levels was started. An emergency caesarean section was performed. The newborn weighed 2.650 kg, had a length of 46 cm, was large for gestational age, had an Apgar score of 2.7, had perinatal asphyxia, convulsive syndrome and a possible congenital cardiopathy. Once the ketoacidosis was resolved during the immediate puerperium, slow acting insulin was initiated.

Disfunción sexual en la mujer diabética pre y postmenopáusica / Sexual dysfunction in women with diabetes in pre and postmenopausic state

Objective: female sexual dysfunction (FSD) in diabetic women, is a topic poorly studied. The aim of this study is to determine the prevalence of FSD in typ1 1 and typ2 diabetic patients (T1D and T2D) compared with non diabetic controls. Patients and Method: interview under written consent 24 diabetic patients attended at Diabetes Unit of the San Juan de Dios Hospital and 24 healthy controls. Inclusion criteria: diagnosis of diabetes mellitus over one year, age 18-75 years old and stable partner for over a year. Exclusion criteria: antidepressants treatment. The validated survey by Rosen et al. was applied. Female Sexual Function Index (FSFI), of 19 questions that assess 6 areas of sexual function: desire, lubrication, excitement, orgasm, satisfaction and pain. A total score of 26.55 or less diagnosed DSF. In diabetic patients the metabolic control, lipid profile, creatinine and glycated hemoglobin A1c (HbA1c) was recorded. Statistical analysis was performed using median, range and Mann Whitney test. Percentages of sexual dysfunction was analysed by chi². It was considered significant at p < 0.05. Results: the results of the FSFI survey were divided and related to menopause. In premenopausal diabetic group (n = 11), the average score was 31.1 versus 32.5 in controls (NS) and in postmenopausal diabetic group (n = 13) the average score was 23,1 versus 28,5 (p = 0.05). The overall frequency of DSF in premenopausal diabetic women was 27.3 percent and 6.3 percent in controls (NS), in postmenopausal reached 69.2 percent and25.0 percent in controls (p = 0.01 ). Conclusion: in diabetic patients sexual dysfunction was more frequent than in controls; in premenopausal women the most affected area is the excitement and in postmenopausal women was lubrication.

Uso de pacientes estandarizados para la adquisición de conocimientos teórico-clínicos en estudiantes de pregrado / Use of standardized patients to the acquisition of clinical-theoretical knowledge by nursing undergraduate students / Uso de pacientes estandardizados para a aquisição de conhecimentos teórico-clínicos em estudantes de pregado

La práctica docente obliga a innovar con metodologías que faciliten el aprendizaje y resguarden los principios éticos que fundamentan el quehacer profesional, como es el caso del uso de los pacientes estandarizados (PE). Objetivo: Evaluar el efecto en los conocimientos sobre esquizofrenia y trastornos del ánimo de una intervención que combina clases teóricas estandarizadas y uso de PE en estudiantes universitarios de pregrado de la asignatura de enfermería psiquiátrica. Método: Diseño cuantitativo descriptivo sobre un universo de 157 estudiantes de enfermería de quinto y sexto semestre de formación. La recolección de los datos se realizó a través de un instrumento de medición de conocimientos sometido a pruebas de validación de contenido. Para el análisis de los datos se utilizó el programa SPSS(r). Resultados: Al medir el efecto de la intervención en la adquisición de conocimientos, se observa que la metodología de clase estandarizada incrementa en promedio un 34% los conocimientos de los estudiantes y el uso de PE contribuye con sobre un 10% adicional. Al combinar ambas estrategias, los conocimientos de los estudiantes se incrementan en 49.3% y 41.9% para esquizofrenia y trastornos del ánimo respectivamente, sin que el estudiante participe de otra instancia de estudio o profundización de los contenidos. Conclusión. El uso de estrategias metodológicas combinadas contribuye a la adquisición de los conocimientos necesarios para la formación de estudiantes de pregrado de enfermería psiquiátrica.

Teaching needs to innovate with methodologies which foster learning while, at the same time, maintain the ethical principles which give base to the professional activities. Such is the case of the use of standardized patients (SP). Objective: To assess the effects of an intervention which combines standardized theoretical classes with the use of SP, on the knowledge which undergraduate students, undergoing their psychiatric nursing subject, have on schizophrenia and mood disorders. Method This was a qualitative and descriptive study on a universe of 157 nursing students from the fifth and sixth semesters of their program. Data collection was conducted through a knowledge assessment instrument which was submitted to content validity tests. The SPSS(r) program was used to analyze these data. Results: From the intervention, it was observed that the methodology of standardized class increments in an average of 34% the students' knowledge, while the use of SP contributes with an additional 10%. When combining both methodologies, and without any other content-deepening technique, the students' knowledge on schizophrenia increased 49.4% while their knowledge on mood disorders increased 41.9%. Conclusion: The use of combined methodological strategies contributes to the acquisition of formation-needed knowledge by undergraduate psychiatric nursing students.

A prática docente obriga a inovar com metodologias que facilitem a aprendizagem e a salvaguardar os princípios éticos que fundamentam o fazer profissional, como é o caso do uso 2 pacientes estandardizados (PE). Objetivo: Avaliar o efeito nos conhecimentos sobre esquizofrenia e transtornos de ânimo de uma intervenção que combina aulas teóricas estandardizadas e uso de PE nos estudantes universitários de pregado da matéria de enfermagem psiquiátrica. Método: Desenho quantitativo descritivo sobre o universo de 157 estudantes de enfermagem de quinto e sexto semestre de formação. A recoleta 2 dados realizou-se a través de um instrumento de medição de conhecimentos submetido a testes de validação de conteúdo. Para a análise de dados utilizou-se o programa SPSS(r). Resultados Ao medir o efeito da intervenção na aquisição de conhecimentos, observa-se que a metodologia de classe estandardizada incrementa em média um 34% os conhecimentos 2 estudantes e o uso de PE contribui sobre um 10% adicional. Ao combinar ambas as estratégias, os conhecimentos 2 estudantes incrementam-se em 49.4% e 41.9% para esquizofrenia e transtornos de ânimo respectivamente, sem que o estudante participe de outra instância de estúdio e/ou aprofundamento 2 conteúdos. Conclusão: O uso de estratégias metodológicas combinadas contribui à aquisição de conhecimentos necessários para a formação de estudantes de pregado de enfermagem psiquiátrica.

Metformina asociada a insulinoterapia en pacientes diabéticos tipo 1 / Metformin associated with insulin therapy in type 1 diabetic patients

In patients with diabetes type 1 (T1D) glycemic control remains suboptimal, despite the availability of new insulin analogues and continuous infusion systems. Metformin may be a complementary therapy regarding to intensified insulin therapy since a significant percentage of T1D have insulin resistance (IR). Objective: To analyze the clinical, anthropometric and metabolic effects of the combination of metformin to insulin therapy in T1D patients. Subjects and Method: 34 T1D patients, 15 men and 19 women, mean age 41 years (range 20-64) metformin 850 mg / day was associated for 6 months (group 1) and retrospectively evaluated 18 T1D, 9 men and 9 women, age average 34 years (range 17-58), who received metformin for 36 months (group 2). It was recorded before and after treatment with metformin: nutritional status, waist circumference, index waist / hip, glucose fasting, glycosylated hemoglobin (HbA1c), HDL cholesterol, triglycerides, systolic and diastolic blood pressure (BP), glucose uptake (UG) and insulin dose (U/kg). Statistical analyses. Clinical and biochemical parameters were expressed as median, range or percentage (percent). For the statistical significance were used chi2and Fisher exact and Mann Whitney test; and was established as significant at p <0.05. Results: In group 1 significantly decreased waist circumference in men and women and improved fasting glucose, HbA1c, systolic blood pressure and triglycerides. In group 2, waist circumference and systolic blood pressure was also reduced. Conclusion: In T1D patients with clinical signs of IR the association of metformin to insulin therapy may be useful.

Alteraciones hematológicas en la diabetes mellitus / Blood disorders in diabetes mellitus

Although it has been treated in a limited way the relationship between diabetes and hematopoietic system, there is evidence demonstrating thedeleterious effect of hyperglycemia on the three cell lines: red blood cells, white cells and platelets. Different forms of anemia associated with hyperglycemia are analyzed and erythrocyte alterations observed in diabetes. In chronic decompensated patients have been demonstrated alterationsof monocytes, lymphocytes and polymorphonuclear particularly, with decreased chemotaxis, adherence, phagocytosis and opsonization. Hyperglycemia determines a prothrombotic state by platelet hyperreactivity, which is a marker of inflammation...

Diabéticos tipo 1 portadores de síndrome metabólico: cuantificación de la resistencia a la insulina / Type 1 diabetics patients carriers of metabolic syndrome: quantification of insulin resistance

The presence of insulin resistance (IR) has been indirectly assessed in Type 1 Diabetics (T1DM) through the detection of Metabolic Syndrome (MS), by applying criteria for Type 2 Diabetics(T2DM). In the EDC study (the Pittsburg Epidemiology of Diabetes Complications) a formula applicable to T1DM was validated, quantifying IR through the glucose uptake (GU) employing the usual clinical and laboratory parameters, in patients with HbA1c < 11.4 percent. Objectives: To determine in T1DM whether there exists a relationship between the presence of MS according to the Modified NCEP/ATPIII criteria and IR quantification through assessment of the glucose uptake or GU. Patients and Method: The modified NCEP/ATPIII criteria were applied to 150 T1DM patients, and those with more than 3 altered parameters were classified as MS carriers. IR was quantified through the glucose uptake (GU), applying the formula for Estimated Glucose Disposal Rate (GDR-EDC). Results: 26.6 percent of the T1DM (40 patients) complied with the modified NCEP/ATPIII criteria. When the formula for GU was applied (31 patient), 90.3 percent of the T1DM showed insulin resistance (GU value < 8.77). And when applied to 124 patients (T1DM with and without MS and HbA1c < 11,4 percent) 75 percent showed IR...

[Body composition assessment in patients with chronic renal failure]. / Evaluación de la composición corporal en pacientes con insuficiencia renal crónica.

INTRODUCTION: Assessment of body composition is paramount in early assessment of nutritional status impairments due to excess or deficit. There are, however, few field reliable methods for this objective for patients with chronic renal failure (CRF.). OBJECTIVE: To assess the reliability of the estimations of body composition by different methods as compared to dual energy X-ray absorptiometry (DEXA) as the gold standard method in patients with CRF and on regular chronic haemodialysis. PATIENTS AND METHODS: We assessed body composition in 30 haemodialysis patients (46.9 +/- 15.1 years (18-76); BMI 25.9 +/- 5.7 kg/m(2) (18.1-41.5)), observing agreement in the percentage of fat mass (%FM) between the sum of the 4 folds (SP; calibrator Lange) and bioimpedantiometry by using different equations (BIA; Biodynamics 450) versus DEXA (Lunar DPX-L). RESULTS: (X +/- SD) By BMI, 3 subjects had low weight (10%), 14 normal weight (46.7%), 7 overweight (23.3%), and 6 obesity (20%). The %FM with SP (30.7 +/- 7.1%) significantly differed from DEXA (27.3 +/- 10.3%; p < 0.001). With BIA there was a significant difference in %FM with the Deurenberg and Formica equations. The %FM obtained with the manufacturer's equations (Segal, Lukaski and Kyle) did not show a significant difference from DEXA. With Kyle's equation we observed a better agreement (difference with DEXA: -0.58 +/- 4.2%). CONCLUSIONS: We found a low percentage of patients with low weight as compared to previous studies. The skin folds show low reliability to estimate the fat mass. The bioimpedantiometry, using Kile's equation may be a good filed method to assess haemodialysis patients.

Resection of hepatocellular carcinoma: the effect of surgical margin and blood transfusion on long-term survival. Analysis of 209 consecutive patients.

BACKGROUND/AIMS: Certain prognostic factors affect the postoperative mortality and long-term survival of patients following hepatic resection for hepatocellular carcinoma (HCC) and may change the surgical strategy. METHODOLOGY: 209 consecutive patients underwent hepatic resection for HCC in our hospital. Seventy-three patients underwent major resection and 136 underwent minor resections. We looked for correlations between clinical, biological, surgical and pathological factors and postoperative mortality, disease-free survival and overall survival. RESULTS: The postoperative mortality rate was 7.7% (it fell to 0% in the last two years). The cumulative overall five-year survival rate was 27% and the overall disease-free survival rate was 7.3%. Multivariate analysis identified: (1) two independent prognostic factors for postoperative mortality: age and tumor size; (2) one risk factor for tumor recurrence: intraoperative blood transfusion, and (3) three independent prognostic factors for overall survival: infiltrative tumor type, surgical margin <10 mm and intraoperative blood transfusion. CONCLUSIONS: In addition to routine staging of the tumor, the preoperative evaluation of HCC patients should include tests to determine whether the tumor is infiltrative or expansive and whether it will be possible to obtain a surgical margin (>10 mm). This procedure should make it possible to propose an appropriate neoadjuvant treatment only to these patients. The prevention of intraoperative bleeding or blood transfusion should improve the disease-free and overall survival rates in HCC patients.

[Hemorrhage caused by the rupture of a pancreatic pseudoaneurysm. Case report]. / Hemorragia por ruptura de pseudoaneurisma pancreático. Caso clínico.

We report a 52 year old man with a pancreatic pseudocyst, that was admitted with severe abdominal pain, severe vomiting, fever and malaise. The clinical picture was considered secondary to a pseudocyst infection and the patient was operated, draining the infected cyst performing a necrosis surgery and pancreatojejunostomy. Forty eight hours after the operation, an ostomy bleeding was detected. A upper mesenteric artery angiography showed two pseudoaneurysms in the gastroduodenal artery, that were embolized. Bleeding stopped initially, but seven days later, it reappeared. The patient was subjected to an emergency pancreatoduodenectomy. Postoperative evolution was uneventful and the patient was discharged two weeks later. Spontaneous bleeding of pseudoaneurysms secondary to chronic pancreatitis is a complication with a 15 to 40% mortality that must be bore in mind.

Excitation, inhibition, and suppression by odors in isolated toad and rat olfactory receptor neurons.

Vertebrate olfactory receptor neurons (ORNs) exhibit odor-induced increases in action potential firing rate due to an excitatory cAMP-dependent current. Fish and amphibian ORNs also give inhibitory odor responses, manifested as decreases in firing rate, but the underlying mechanism is poorly understood. In the toad, an odor-induced Ca(2+)-activated K(+) current is responsible for the hyperpolarizing receptor potential that causes inhibition. In isolated ORNs, a third manner by which odors affect firing is suppression, a direct and nonspecific reduction of voltage-gated and transduction conductances. Here we show that in whole cell voltage-clamped toad ORNs, excitatory or inhibitory currents were not strictly associated to a particular odorant mixture. Occasionally, both odor effects, in addition to suppression, were concurrently observed in a cell. We report that rat ORNs also exhibit odor-induced inhibitory currents, due to the activation of a K(+) conductance closely resembling that in the toad, suggesting that this conductance is widely distributed among vertebrates. We propose that ORNs operate as complex integrator units in the olfactory epithelium, where the first events in the process of odor discrimination take place.

Odor suppression of voltage-gated currents contributes to the odor-induced response in olfactory neurons.

Olfactory chemotransduction involves a signaling cascade. In addition to triggering transduction, odors suppress ion conductances. By stimulating with brief odorant pulses, we observed a current associated with odor-induced suppression of voltage-gated conductances and studied its time dependence. We characterized this suppression current in isolated Caudiverbera caudiverbera olfactory neurons. All four voltage-gated currents are suppressed by odor pulses in almost every neuron, and suppression is caused by odors inducing excitation and by those inducing inhibition, indicating a nonselective phenomenon, in contrast to transduction. Suppression has a 10-fold shorter latency than transduction. Suppression was more pronounced when odors were applied to the soma than to the cilia, opposite to transduction. Suppression was also present in rat olfactory neurons. Furthermore, we could induce it in Drosophila photoreceptor cells, demonstrating its independence from the chemotransduction cascade. We show that odor concentrations causing suppression are similar to those triggering chemotransduction and that both suppression and transduction contribute to the odor response in isolated olfactory neurons. Furthermore, suppression affects spiking, implying a possible physiological role in olfaction.

Effects of mild protein prenatal malnutrition and subsequent postnatal nutritional rehabilitation on noradrenaline release and neuronal density in the rat occipital cortex.

There is evidence that severe malnutrition started during gestation and continued through lactation affects adversely the morphologic development of the neocortex leading to increased neuronal cell packing density and decreased dendritic branching. Nevertheless, the effect of purely mild protein prenatal malnutrition on neocortical development remains rather unexplored. This study evaluates the effects of mild protein prenatal malnutrition (8% casein diet, calorically compensated by carbohydrates) and subsequent postnatal nutritional rehabilitation (25% casein diet) on: (i) the potassium-induced release of [(3)H]-noradrenaline (NA) in occipital cortex slices obtained from 1- and 22-day-old pups; and (ii) the packing density of neurons in lateral, dorso-lateral and dorsal regions of the occipital cortex of 22-day-old pups by using the optical dissector method. The experiments were performed in rats normally fed during gestation and lactation (G(+)L(+)), malnourished during gestation but rehabilitated during lactation (G(-)L(+)) and malnourished during gestation and lactation (G(-)L(-)). At day 1 of age, no significant differences in body and brain weights were observed between prenatally well-nourished and malnourished pups. Nevertheless, at this early age, pups born from mothers submitted to the 8% casein diet had significantly higher cortical net percent NA release than pups born from mothers receiving the 25% casein diet. At weaning (22 days of age) G(-)L(+) rats had, compared to the G(+)L(+) group, similar body weight, brain weight and [(3)H]-NA release values, but significantly higher neuron density scores in the lateral region of the occipital cortex. In contrast, at 22 days of age, G(-)L(-) rats exhibited, compared to G(+)L(+) animals, significant deficits in body and brain weights as well as significant increases in cortical net percent NA release together with enhanced packing density of neurons in the lateral, dorso-lateral and dorsal regions of the occipital cortex. Moreover, in G(-)L(-) animals was not found the laterodorsal histogenetic gradient of neuronal cell packing density observed in G(+)L(+)rats. Results suggest that mild prenatal malnutrition per se is able to induce deleterious effects on cortical neuronal density, in spite of nutritional rehabilitation during lactation, through a mechanism involving central NA hyperactivity during gestation. Prosecution of malnutrition after birth magnifies both neurochemical and morphometric disorders.

NADPH-d positive neurons in the developing somatosensory cortex of the rat: effects of early and late environmental enrichment.

The effects of environmental enrichment upon the topographic arrangement of NADPH diaphorase-positive neurons (NADPH-d+ neurons) was studied in the somatosensory cortex of 56 Sprague-Dawley albino rats during early stages of development (18th, 24th, 30th and 60th postnatal days). This diaphorase is easily demonstrable, providing a convenient marker for quantitative studies. Environmental enrichment diminished the number of NADPH-d+ neurons and exerted its maximal influence during lactation, a time of exceptional cortical susceptibility. This implies that the magnitude of such effects on the density of NADPH-d+ neurons is age-dependent. Furthermore, it was found that the experience-dependent cortical changes persisted after a subsequent period without environmental stimulation. The effects of early environmental enrichment did not occur uniformly throughout the cerebral hemispheres but, instead, such effects were maximal in the latero-ventral sector of the cerebral cortex where a dramatic reduction in the number of NADPH-d+ neurons was observed. Particularly striking was the existence of a latero-medial sequence of NADPH-d+ neurons in the infragranular layer and a reversed distribution of labeled cells, in the supragranular layer. Both ontogenetic sequences of NADPH-d+ neurons remained unchanged during postnatal development in controls and enriched subjects (18th-60th postnatal days).