Inheritance of resistance to pyrethroids in Triatoma infestans, the main Chagas disease vector in South America.

An outbreak of pyrethroid resistance was recently detected in Triatoma infestans from northern Argentina. To analyze the inheritance of the resistant phenotype, we carried out experimental crosses between resistant (R) and susceptible (S) strains captured in Argentina during 2005. The R strain was collected from sprayed houses in the north of the province of Salta while the S strain was collected in the province of Chaco. Both strains were bred in the laboratory for reciprocal crosses (F1), intercrosses (F2) and backcrosses (BC). The descendents were tested by a standard insecticide resistance bioassay. Resistance ratios were 1 for S strain, 103.36 for R strain and 18.34 for F1. The regression lines of F1 generations (R×S and S×R) showed no significant differences and were closer to that of the R parents, indicating that inheritance of deltamethrin resistance in T. infestans is autosomal and incompletely dominant (D=0.20). Chi-square analysis from responses of intercross and backcross progenies rejected the hypothesis of a single gene being responsible for resistance. The minimum number of independent segregation genes was three, as calculated with Lande's method. The genetic basis here described for the resistant phenotype indicate that, under pyrethroid selective pressure, the resistant genotypes could be easily spread to susceptible insects from resistant individuals, posing a major threat to vectorial control of Chagas disease.

Simultaneous measurement of right and left ventricular volume by the conductance catheter technique in the newborn lamb.

BACKGROUND: Measurement of absolute ventricular volume with the conductance catheter technique has been documented extensively for the left ventricle (LV). More recently, the same technique has been applied in studies of right ventricular (RV) performance. In the present study we performed simultaneous measurements of LV and RV volumes. Conversion of measured conductances to absolute volumes requires the assessment of slope factor alpha (α) and parallel conductance correction volume (Vc) for both the RV and LV. We investigated the magnitude and variability of these calibration factors during a typical study period of four hours. METHODS: In five anaesthetised, ventilated newborn lambs, conductance catheters were introduced into the LV and RV and a thermodilution catheter was positioned in the pulmonary artery. Alphas and Vc's were determined by thermodilution and hypertonic saline dilution, respectively, at one hourly intervals. At the same time points, biventricular haemodynamic parameters were obtained. Results were analysed by multiple linear regression analysis. RESULTS: During the course of the experiments all haemodynamic parameters were stable. There were no significant changes in Vc or α for either ventricle. RV-Vc was systematically higher than LV-Vc: both as absolute values and as percentage of the uncalibrated conductance signal (79% for RV, and 49% for LV, respectively). This probably reflects the geometrical differences of the two ventricles. Right ventricular ejection fraction (RV-EF) was higher than left ventricular ejection fraction (LV-EF), and neither changed significantly during four hours. CONCLUSION: These results show that calibration factors α and Vc for the RV, as well as EF, show values that are consistent with the observed haemodynamic stability and in line with the LV factors. These results indicate that the conductance catheter method can be used satisfactorily for biventricular function assessment.

Resultados preliminares da utilizaçäo de cultivos de anéis de traquéia para o estudo de estirpes brasileiras do vírus da bronquite infecciosa das galinhas / A preliminary use of tracheal organ cultures for evaluating Brazilian infectious bronchitis virus strains

Tracheal organ cultures (TOC) were prepared and used for evaluating four Brazilian isolates of infectious bronchitis virus (IBV). IBV field isolates and vaccine strains were titrated in TOC and results compared to those from chicken embrionated eggs. Serum neutralization (SN) employing IBV strain-specific serum was performed for evaluating relationships between isolates. Titration results of tests performed in TOC or eggs were in mutual agreement and were considered for validating the adapted TOC methodology as alternative for virological studies in our laboratory. Sera specific to M41 (Massachusetts) or A5968 (Connecticut) did neutralize their respective IBV strains only. Field strains 208 and 29-78 specific sera did neutralize Massachusetts serotype strains M41 and H120, but PM2 serum did only M41. Strain PM4 specific serum did not neutralize any of the reference IBV analyzed, including M41, A5968 and H120 and may indicate that the isolate is serologically different from the Massachusetts serotype, currently adopted for vaccine strains in Brazil

Produçäo e caracterizaçäo de anticorpos monoclonais contra o vírus da bronquite infecciosa das galinhas / Production and characterization of monoclonal antibodies specific to infectious bronchitis virus

Um painel de anticorpos monoclonais (AcM) específicos contra o vírus da bronquite infecciosa das galinhas (VBIG) amostra Massachusetts M41 foi desenvolvido com a finalidade de possibilitar ferramentas para futuros estudos de amostras locais de VBIG. Os clones produtores de AcM foram detectados e caracterizados por ELISA, e para a determinaçäo quanto à especificidade ao componente de VBIG foi utilizado western blotting (WB). Os híbridos produtivos foram clonados por diluiçäo limitante, expandidos in vitro e mantidos em nitrogênio líquido. As bandas protéicas reconhecidas em WB pelos AcM apresentaram pesos moleculares que variaram de 180 a 30 kDa. Oito AcM reconheceram apenas um polipeptídeo e quatro ligaram-se ao polipeptídeo S (3, 18, 52 e 57) inteiro, com a banda de peso molecular aproximado de 180 kDa. Cinco AcM (5, 12, 41, 70 e 72), ligaram-se em mais de uma banda de VBIG. Outros sete AcM näo se ligaram a nenhum polipeptídeo de VBIG. Entre os AcM que apresentam perspectivas de utilizaçäo em pesquisa e diagnóstico de VBIG incluem-se os produzidos pelo clone 42, dirigido contra S1, os produzidos pelos clones 34, 43 e 71, dirigidos contra S2, pelos clones 7 e 22, dirigidos contra M e pelos clones 15 e 50, cujos AcM reagiram contra a nucleoproteína N

Endothelin-1 plasma concentration increases in the early phase of pulmonary hypertension development during respiratory distress syndrome: a study in newborn lambs.

OBJECTIVE: Elevated plasma concentrations of endothelin-1 (ET-1) have been reported with pulmonary hypertension during respiratory distress syndrome (RDS). However, the exact role of ET-1 in the development of pulmonary hypertension during RDS is unclear. The relative time-course of changes in ET-1 concentrations and pulmonary artery pressure (P(ap)) during RDS may give insight in the role of ET-1. METHODS: ET-1 and P(ap) changes were studied in an experimental model of RDS, induced by lung lavages in seven newborn lambs. Five other lambs served as controls. RESULTS: Lung lavages induced a twofold increase of mean P(ap) (from 15 to 34 mm Hg) that remained present throughout the 4-h study period. Along with the increased P(ap), ET-1 plasma concentration showed a significant increase 15 min after induction of RDS at all three sample locations (pulmonary artery 198%, aorta 181% and right atrium 195% compared to baseline). This increased concentration remained high at 1 and 4 h of RDS. In control animals, no significant changes in ET-1 concentrations were observed. Plotting ET-1 concentration values against mean P(ap), in RDS and control animals at all time points, a correlation was found between the severity of the pulmonary hypertension and ET-1 concentration. CONCLUSION: This experimental model of RDS shows that ET-1 concentration increases concomitant with the development of pulmonary hypertension, from an early time point onward. More severe pulmonary hypertension is associated with higher ET-1 concentrations, but whether ET-1 is a marker or a mediator of pulmonary hypertension remains as yet unsettled.

Enhanced systolic function of the right ventricle during respiratory distress syndrome in newborn lambs.

Respiratory distress syndrome (RDS) causes pulmonary hypertension. It is often suggested that this increased afterload for the right ventricle (RV) might lead to cardiac dysfunction. To examine this, we studied biventricular function in an experimental model. RDS was induced by lung lavages in seven newborn lambs. Five additional lambs served as controls. Cardiac function was quantified by indexes derived from end-systolic pressure-volume relations obtained by pressure-conductance catheters. After lung lavages, a twofold increase of mean pulmonary arterial pressure (from 15 to 34 mmHg) was obtained and lasted for the full 4-h study period. Stroke volume was maintained (5.2 +/- 0.6 ml at baseline and 6.1 +/- 1.4 ml at 4 h of RDS), while RV end-diastolic volume showed only a slight increase (from 6.5 +/- 2.3 ml at baseline to 7.7 +/- 1.3 ml at 4 h RDS). RV systolic function improved significantly, as indicated by a leftward shift and increased slope of the end-systolic pressure-volume relation. Left ventricular systolic function showed no changes. In control animals, pulmonary arterial pressure did not increase and right and left ventricular systolic function remained unaffected. In the face of increased RV afterload, the newborn heart is able to maintain cardiac output, primarily by improving systolic RV function through homeometric autoregulation.

Right ventricular function in respiratory distress syndrome and subsequent partial liquid ventilation. Homeometric autoregulation in the right ventricle of the newborn animal.

Infant respiratory distress syndrome (IRDS) and subsequent partial liquid ventilation (PLV) cause increased pulmonary vascular resistance, thus raising afterload. In nine newborn lambs the effects of IRDS and subsequent PLV on right (RV) and left ventricular (LV) contractility and systolic pump function were assessed using indices derived from RV and LV pressure-volume relations, obtained by micromanometric and conductance catheters during transient inferior vena cava occlusion. Pulmonary function deteriorated during IRDS with a significant decrease in the ratio of arterial oxygen pressure to fraction of inspired oxygen (Pa(O(2))/FI(O(2))) whereas pulmonary artery pressure (Ppa) showed a significant increase and pulmonary vascular resistance showed a substantial though not significant increase. Cardiac output (Q), stroke volume (SV), and end-diastolic volume (EDV) did not change. RV contractility showed a significant increase during IRDS: the slope of the end-systolic pressure-volume relation (RV-E (ES)) increased whereas its volume intercept at 5 kPa (RV-V(5)) decreased. The preload-corrected time derivative of ventricular pressure (RV-dP/dt(max)), however, did not change significantly. LV pump function and contractility were unchanged. During PLV pulmonary function showed a recovery but Ppa and pulmonary vascular resistance remained high; indices for RV contractility showed a sustained significant increase compared with baseline conditions whereas indices for LV pump function and contractility remained unchanged. These results show that the right ventricle of the newborn heart, in the face of increased pulmonary vascular resistance, is able to maintain cardiac output through homeometric autoregulation.

Improved contractile performance of right ventricle in response to increased RV afterload in newborn lamb.

Pulmonary hypertension results in an increased afterload for the right ventricle (RV). To determine the effects of this increased afterload on RV contractile performance, we examined RV performance before and during 4 h of partial balloon occlusion of the pulmonary artery and again after releasing the occlusion in nine newborn lambs. RV contractile performance was quantified by indexes derived from systolic RV pressure-volume relations obtained by a combined pressure-conductance catheter during inflow reduction. An almost twofold increase of end-systolic RV pressure (from 22 to 38 mmHg) was maintained during 4 h. Cardiac output (CO) (0.74 +/- 0.08 l/min) and stroke volume (4.3 +/- 0.4 ml) were maintained, whereas end-diastolic volume (7.9 +/- 1.3 ml) did not change significantly during this period. RV systolic function improved substantially; the end-systolic pressure-volume relation shifted leftward indicated by a significantly decreased volume intercept (up to 70%), together with a slightly increased slope. In this newborn lamb model, maintenance of CO during increased RV afterload is not obtained by an increased end-diastolic volume (Frank-Starling mechanism). Instead, the RV maintains its output by improving contractile performance through homeometric autoregulation.

Electrocortical brain activity during hypoxia and hypotension in anesthetized newborn lambs.

Blood gas and blood pressure disturbances do influence cerebral blood flow in newborns. To what extent cerebral blood flow changes affect electrocortical brain activity remains uncertain. We studied the effect of severe hypoxia and hemorrhagic hypotension on carotid artery blood flow and electrocortical brain activity in newborn anesthetized lambs. During hypoxia carotid artery blood flow increased significantly, whereas electrocortical brain activity remained unchanged. The hemorrhagic hypotension study showed that the lower limit of the autoregulatory ability of the cerebral vascular bed was 60 mmHg. Electrocortical brain activity however remained stable until mean aortic pressure had dropped below 30 mmHg, carotid artery blood flow below 10.6 ml/kg/min, and cerebral oxygen delivery below 1.4 ml/kg/min.

Nitric oxide inhibition after hypoxia-ischemia elevates pulmonary arterial pressure and increases oxygen need.

Inhibition of nitric oxide (NO) production may reduce post-hypoxic-ischemic (HI) neonatal brain damage, but may also induce pulmonary hypertension by inhibiting endogenous NO production in the pulmonary vascular bed. The aim of this study was to evaluate the effect of nitric oxide inhibition on pulmonary artery pressure and oxygen need after hypoxic ischemia. Severe HI was produced in 18 newborn lambs. After completion of HI the lambs were divided into three groups of 6 animals receiving either placebo (Cont), low dose N omega-nitro-L-arginine (10 mg/kg i.v., NLA-10) or high dose (40 mg/kg i.v., NLA-40) to block NO production. Pulmonary artery pressure (Pap), aortic pressure, blood gases, inspiratory oxygen concentration and ventilator settings were recorded before and 15, 60, 120 and 180 min after HI. Mean Pap rose initially significantly as compared to baseline in all groups at 15 min post-HI, decreased to normal in Cont but not in treated animals; 180 min post-HI mean Pap was significantly higher in both treated groups as compared to control (NLA-10: 32 mm Hg, NLA-40: 34 mm Hg, Cont: 25 mm Hg, p < 0.05 for NLA-10 and NLA-40 vs. Cont). Moreover, in both NLA-treated groups the oxygenation index was significantly elevated 120 and 180 min post-HI as compared to those of the Cont group. NO synthase inhibition after HI causes a prolonged increase in pulmonary artery pressure leading to a higher oxygen need.

Inhalation of nitric oxide: effect on cerebral hemodynamics and activity, and antioxidant status in the newborn lamb.

Ventilation with nitric oxide (NO) is increasingly being used to treat pulmonary hypertension in the newborn. In the brain, NO has vasoactive properties and is involved in neurotransmission. However, the effect of inhaled NO on the cerebral blood flow (CBF) and on the cerebral activity is not known. Furthermore, there is little information on the influence of this free radical gas on the redox status in pulmonary vessels. We therefore investigated the effect of inhaled NO (2-60 ppm) on CBF, cerebral activity and redox status in blood effluent from the pulmonary circulation in 6 ventilated newborn lambs before and during group B streptococci (GBS)-induced pulmonary hypertension. Blood pressure in the pulmonary artery (P(ap)) and aorta (Pao), carotid artery blood flow (Qcar) to assess changes in CBF, and electrocortical activity were measured. Blood gases, indices of free radical status and methemoglobin were determined in blood samples obtained from the left ventricle. Inhalation of NO, before and during GBS-induced pulmonary hypertension, decreased P(ap) and PCO2 and increased PO2. Multiple linear regression revealed that Qcar was positively related to PCO2, but not to inhaled NO or PO2 before or during GBS conditions. Electrocortical activity and indices of antioxidative capacity and lipid peroxidation did not change significantly. Methemoglobin was not detected. In conclusion, inhalation of NO (up to 60 ppm) lowered P(ap) without directly affecting CBF, electrocortical activity, and redox status in the pulmonary vessels. CBF, however, can indirectly be influenced by NO-mediated changes in PCO2.

Primary mandibular reconstruction with bridging plates.

25 cases in which the mandible was resected and reconstructed using a reconstruction plate (AO titanium reconstruction system and Leibinger titanium reconstruction system) are presented. 16 patients suffered from oral carcinoma, 7 presented with odontogenic tumours and 2 had chronic osteomyelitis of the mandible. The mean age was 54.2 years, the male to female ratio was 2.6:1. 3 patients had a reconstruction plate for mandibular resection without continuity defect (marginal resection), in all the other patients the reconstruction plate bridged a mandibular resection with a continuity defect: 13 were located in the body, body-angle or ascending ramus with preservation of the mandibular condyle; 4 hemimandibulectomies with disarticulation of the TMJ; and 5 involved the anterior arch, crossing the midline. 12 patients received radiotherapy (3 pre-operatively). Only 3 patients with significant local side effects needed the treatment to be stopped for a period of time. There was no perioperative mortality. Only one plate was removed. Although minor complications were noted in 11 patients, the general improvement in the functional and cosmetic balance of the patients when compared with patients in whom no plate was used, justifies the use of this reconstruction system, in our opinion.

Biotherapeutic role of fermented milk.

Fermented milk was used as therapy in infantile diarrhoea due to post-gastroenteritis syndrome. This treatment eliminated the disease in 4.0 days (mean value, SD = 2.8; n = 13) and allowed patients to return to free feeding according to their age. The weight percentile variation during treatment with fermented milk (15 days) was higher in the patients showing 3rd degree malnutrition than in other children. Bacteriotherapy can restore faecal flora which has been lowered by diarrhoea. Our results showed that levels higher than 10(6) UFC lactobacilli/g of faeces correlated with a healthy status of the children. Clinical applications of fermented milk with a mixture of Lactobacillus casei and Lactobacillus acidophilus in the prevention of gastrointestinal disorders are possible.

Bioterapia de la diarrea del niño desnutrido / Biotheraphy of diarrhea in undernourished children

El ecosistema microbiano enteral, capaz de resistir o autocorrregir alteraciones de su composición, resulta totalmente pervertido en casos de desnutrición, lo que explica el complejo cuadro de la Enteropatía Ambiental. Esta situación es modificable por la ingesta de lactobacilos seleccionados por su actividad antimicrobiana, enzimática e inmunopotenciadora. 137 niños hospitalizados por este cuadro recibieron como único tratamiento leche fermentada por lactobacilos, contrastando el resultado con el obtenido en 33 niños tratados con leche libre de lactosa y antibióticos no absorbibles. Los grupo estaban conformados por un 26% de desnutridos de 1º; 41% de 2º y 33% de 3º. Todos marasmáticos. El resultado se midió en días desde el inicio del tratamiento hasta la eliminación de heces pastosas y fue de 3,5 días promedio para el grupo tratado con leche fermentada y 7 días para el grupo control. La efectividad del tratamiento alcanzó el 0.97. Estos resultados impulsan la idea de estar en presencia de un alimento-medicamento de gran potencialidad, bajo costo y fácil preparación domiciliaria por lo que resultaría de gran utilidad en la primera barrera sanitaria. Pero se destaca que un orden social más ético que permita el equilibrio biológico adecuado de la especie humana sería la mejor solución para este tipo de problemas de salud (AU)

Bioterapia de la diarrea del niño desnutrido / Biotheraphy of diarrhea in undernourished children

El ecosistema microbiano enteral, capaz de resistir o autocorrregir alteraciones de su composición, resulta totalmente pervertido en casos de desnutrición, lo que explica el complejo cuadro de la Enteropatía Ambiental. Esta situación es modificable por la ingesta de lactobacilos seleccionados por su actividad antimicrobiana, enzimática e inmunopotenciadora. 137 niños hospitalizados por este cuadro recibieron como único tratamiento leche fermentada por lactobacilos, contrastando el resultado con el obtenido en 33 niños tratados con leche libre de lactosa y antibióticos no absorbibles. Los grupo estaban conformados por un 26% de desnutridos de 1§; 41% de 2§ y 33% de 3§. Todos marasmáticos. El resultado se midió en días desde el inicio del tratamiento hasta la eliminación de heces pastosas y fue de 3,5 días promedio para el grupo tratado con leche fermentada y 7 días para el grupo control. La efectividad del tratamiento alcanzó el 0.97. Estos resultados impulsan la idea de estar en presencia de un alimento-medicamento de gran potencialidad, bajo costo y fácil preparación domiciliaria por lo que resultaría de gran utilidad en la primera barrera sanitaria. Pero se destaca que un orden social más ético que permita el equilibrio biológico adecuado de la especie humana sería la mejor solución para este tipo de problemas de salud

A high-frequency albinism variant on the gulf coast of Papua.

An apparently recessively inherited albinism variant characterized by skin tanning, light but not white hair, uniformly pigmented irides varying in colour from hazel to dark brown, slight nystagmus, divergent strabismus, mild hyperkeratosis and only slight or absent photophobia, occurs among the Elema-speaking peoples of the Gulf Province of Papua New Guinea at frequencies indicating that the gene which produces it is polymorphic. It is readily distinguishable from both classical types of albinism, from the "redskin" variant also found in Papua New Guinea, and from the "yellow mutant" albinism of North America. The differences from the African types of "albinoidism" or "partial albinism" are less marked, and it may represent a similar mutation with simply a different distribution of the melanosomes in the two peoples, Allelism, or lack of it, with classical tyrosinase-positive albinism has not been determined.