Profile of organ donors in Ceará, northeastern Brazil, from 1998 to 2012.

The use of cadaver donors for transplantation is often the only alternative in the treatment of patients with organ failure. The purpose of this study was to draw a comprehensive profile of solid organ donors in Ceará, northeastern Brazil, from 1998 to 2012. The study was retrospective and based on secondary data regarding sex, age, blood typing, and cause of brain death obtained from the solid organ donor database of the Ceará Transplantation Center covering the period November 1998 to December 2012. During the study period, 976 donors (69% male) were used. Donors were distributed in 4 age groups as follows: 12.9% <18 years, 50.9% 18-40 years, 28.5% 41-60 years, and 7.7% >60 years. The average age was 35 ± 16 years. On the average, female donors were older than male donors (38.4 ± 17 y vs 33.5 ± 16 y; P < .0001). Men were predominant in the age groups 18-40 y (75.3%; P < .0001) and 41-60 y (59.4%; P < .0001). The main causes of brain death were traumatic brain injury (TBI) (56.7%) and stroke (33.1%). The former was more common in men (P < .0001), the latter in women (P < .0001). TBI was caused by traffic accidents (51.4%), of which 50.7% were motorcycle accidents, and urban violence (22.6%), of which 71.2% were associated with firearms. The number of donations increased in the study period (11.2 donors per million population in 1998-2002 to 68.1 in 2008-2012). In Ceará, solid organ donation is on the rise. The predominant donor profile was young men aged 18-40 years with brain death due to TBI caused by traffic accidents and urban violence.

Ocorrência de Hepatozoon spp. (Apicomplexa, Hepatozoidae) em serpentes do gênero Bothrops de cativeiro / Occurrence of Hepatozoon spp. (Apicomplexa, Hepatozoidae) in snakes of genus Bothrops in captivity

The occurrence of Hepatozoon gamont in the blood cells of Bothrops jararaca and B. jararacussu in captivity was analyzed. The prevalence of infection by Hepatozoon spp. was 50 percent and few erythrocytes contained the gamonts. Results suggest that the infection by Hepatozoon spp. occurred in the natural environment or after the captivity.

Histological and biochemical effects induced by sublethal doses of Bothrops jararacussu venom in mice

Snake venom is characterized by hemorrhagic, coagulant, proteolytic and myotoxic activities which in Bothrops jaracussu venom are related to intraspecific variations. In the present study, female Swiss mice were divided into two groups: treated with 25æg or 50æg venom. These were subdivided into three groups of six animals each, according to blood collection: 2, 4 or 24h after venom injection. Animals were anesthetized using diethyl-ether inhalation and 1ml of blood was collected by heart puncture. Then, the following organs were removed: spleen, skeletal muscle, kidneys, liver and lungs; histological sections were obtained and stained with hematoxylin-eosin (HE). The following biochemical parameters were analyzed: aspartate aminotransferase (AST/GOT), alanine aminotransferase (ALT/GPT), total lactate dehydrogenase (LDH), glucose, creatinine and urea levels, and total protein content. Results showed significant alterations in AST, LDH, glucose and urea levels, and total protein content, as well as important tissue alterations in the liver, kidneys and lungs. It could be concluded that, even using sublethal doses of venom, there were significant changes in almost all the tested biochemical parameters as well as tissue alterations in the kidneys and lungs.(AU)

Effects of fetal growth restriction on lung development before and after birth: a morphometric analysis.

Our aim was to determine the effects of fetal growth restriction (FGR) during late gestation on the structure of the lungs in the fetus near term and at 8 weeks after birth. The studies were performed using two groups of pregnant sheep and their offspring. In both groups, FGR was induced by umbilico-placental embolisation (UPE); for fetal studies, UPE was performed from 120 days of gestation until 140 days (term, approximately 146 days), when fetuses were killed for tissue analysis. For postnatal studies, UPE continued from 120 days until delivery at term; postnatal lambs were killed at 8 weeks after birth for tissue analysis. UPE led to a thicker pulmonary blood-air barrier at 140 days of gestation and this difference, which was due to a thickened basement membrane, was still present at 8 weeks after birth. At 8 weeks, we also observed a smaller number of alveoli per respiratory unit, thicker interalveolar septa, and a greater volume density of lung tissue in FGR lambs compared to controls. These changes would be expected to impair gas exchange and alter the mechanical properties of the lungs. Our data show that structural alterations in the lungs induced by placental insufficiency were more evident at 8 weeks of postnatal age than near term, indicating that the effects of FGR on the lung may become more serious with age and may affect respiratory health later in life.

Effects of intrauterine growth restriction on lung liquid dynamics and lung development in fetal sheep.

OBJECTIVE: The aim of this study was to determine the effects of intrauterine growth restriction on fetal lung liquid and lung development. STUDY DESIGN: Intrauterine growth restriction was induced in 7 fetal sheep from 120 to 140 days' gestation (term, approximately 147 days' gestation) by umbilicoplacental embolization. We used 6 control fetuses. Volumes and production rates of fetal lung liquid were measured, and lungs were removed post mortem (140 days' gestation) for analysis of concentrations of deoxyribonucleic acid, protein, and messenger ribonucleic acid for surfactant proteins A, B, and C. RESULTS: Umbilicoplacental embolization induced fetal hypoxemia, hypoglycemia, and intrauterine growth restriction. At 140 days' gestation lung weight was reduced by 34%, and the fetal lung liquid production rate (15.9 +/- 1.8 mL/h for intrauterine growth restriction vs 24.8 +/- 3.9 mL/h for control) and volume (110.9 +/- 16.3 mL for intrauterine growth restriction vs 178.1 +/- 11.9 mL for control) were reduced in the intrauterine growth restriction group. After adjustment for body weight, however, values were not different from those in the control group. Pulmonary deoxyribonucleic acid and plasma cortisol concentrations were elevated by intrauterine growth restriction, but levels of messenger ribonucleic acid for surfactant proteins were unchanged. CONCLUSION: In intrauterine growth restriction, lung liquid and lung growth were proportionate to body weight, and surfactant protein expression was unaffected. Alterations in lung deoxyribonucleic acid concentrations suggest that the lungs may be structurally immature.

The compromised intra-uterine environment: implications for future lung health.

1. Epidemiological studies of infants, children and adults indicate that prenatal compromises that restrict fetal growth and cause low birthweight increase the risk of respiratory deficiencies after birth. 2. It is apparent that the lung has a limited ability to recover from early developmental compromises and that altered development can permanently impair lung architecture. 3. Lung development in utero can be adversely affected by factors associated with fetal growth restriction, namely fetal hypoxaemia, reduced substrate supply and hypercortisolaemia. 4. We have conducted a series of studies of respiratory development in chronically catheterized ovine fetuses and postnatal lambs in which growth restriction was induced during late gestation by embolizing the umbilico-placental vascular bed, a technique that replicates key aspects of human placental insufficiency. 5. During late gestation, restricting the growth of the ovine fetus did not alter lung weight or lung liquid secretion or volume when each factor was related to bodyweight, but it did lead to increased lung DNA concentrations and an increased thickness of the air-blood barrier. Expression of pulmonary surfactant proteins A, B and C were not altered and, hence, it was unlikely that surfactant protein synthesis had been impaired by growth restriction. 6. When growth restriction continued to term, lambs were born with a low birthweight and remained small compared with controls for 8 weeks after birth. Low-birthweight lambs were mildy hypoxaemic and compliances of their lungs and chest wall were, respectively, decreased and increased relative to controls. Pulmonary surfactant proteins A, B and C were not deficient, indicating that decreased lung compliance most likely had a structural basis.

Human and ovine amniotic fluid composition differences: implications for fluid dynamics.

OBJECTIVE: The ovine model is frequently utilized to extrapolate data regarding fetal and amniotic fluid dynamics to human pregnancy. The ovine amnion is highly vascularized, facilitating intramembranous exchange of water and solutes between the amniotic fluid and fetal plasma. In comparison, the relatively avascular human amniotic membrane may have a reduced potential for intramembranous absorption. In view of these anatomical differences, we hypothesized that comparison of human and ovine amniotic fluid composition would provide insight into differences in the mechanisms of amniotic fluid exchange. METHODS: Amniotic fluid was sampled from 43 patients upon hospital admission, and from 27 ovine ewes at five days following amniotic fluid catheter placement. Both human (32 to 39 weeks' gestation) and ovine pregnancies (125 to 136 days' gestation) were sampled during the last 20% of gestation. Samples were analyzed for osmolality and sodium, potassium and chloride concentrations. The contribution of electrolytes to amniotic fluid osmolality and changes in osmolality and electrolyte composition versus gestational age were assessed by regression and covariance analysis. RESULTS: Mean (+/-SEM) amniotic fluid sodium concentration (134.6+/-1.9 vs. 127.1+/-2.0 mEq/1) was greater and potassium (4.6+/-0.1 vs. 6.1+/-0.6 mEq/l) and osmolality (263.9+/-3.7 vs. 285.1+/-1.6 mOsm/kg) less in human than sheep. The range of amniotic fluid osmolality was greater in human (223 to 336 mOsm/kg) than in sheep (274 to 298 mOsm/kg). Human amniotic fluid osmolality was highly correlated with amniotic fluid sodium (r = 0.97) and chloride (r = 0.96) while ovine amniotic fluid osmolality was only weakly correlated with amniotic fluid sodium (r = 0.75) and chloride (r = 0.51). The slope of the regression line of amniotic fluid sodium and osmolality was greater for human than for sheep amniotic fluid (P < 0.0001). The percent of amniotic fluid osmolality accounted for by sodium, chloride and potassium concentrations was greater for human (97%) than for sheep (86%; P < 0.0001). CONCLUSIONS: The results suggest that human amniotic fluid osmolality is comprised almost entirely of the major electrolytes while alternative solutes (e.g., fructose) contribute to ovine amniotic fluid osmolality. Extrapolation of fetal and amniotic fluid dynamics from ovine models to humans should incorporate differences in amniotic fluid osmolality and electrolyte composition.

Mechanism of arginine vasopressin suppression of ovine fetal lung fluid secretion: lack of V2-receptor effect.

Fetal lung liquid production is essential for in utero pulmonary development, and the resorption of lung liquid at birth facilitates neonatal transition. Lung liquid also contributes importantly to amniotic fluid volume. Factors that influence lung liquid production/resorption may, therefore, impact fetal pulmonary growth and development as well as amniotic fluid homeostasis. Arginine vasopressin (AVP) inhibits fetal lung liquid production and facilitates lung liquid resorption. In view of studies administering fetal AVP or the V2 receptor agonist, 1 desamino 8-D AVP (dDAVP) for the regulation of amniotic fluid volume, we sought to determine the impact of AVP V2 receptor stimulation on fetal lung liquid production. Eight near-term ovine fetuses (130 +/- 2 d; term = 145 d) were prepared with hind limb vascular catheters, a bladder catheter, and a tracheal catheter. Each ewe received vascular and amniotic catheters. After 5 days of recovery, the animals were studied for a 2-hr control period and for 2 hr following intravenous dDAVP injection (1 ng/kg). Lung liquid and urine flow rates and plasma electrolyte and osmolality composition were determined at 30-min intervals. To confirm fetal lung liquid suppression in response to AVP, two animals received an intravenous injection of AVP (2 ng/kg) 24 hr after the first experiment. dDAVP administration had no effect on lung liquid production (3.4 +/- 0.4 ml/kg/h), electrolyte concentrations, or osmolality. Fetal urine electrolyte concentrations and osmolality (154 +/- 24-295 +/- 22 mOsm/kg H2O) increased in response to dDAVP, whereas urine flow decreased (9.4 +/- 2.5-4.2 +/- 1.5 ml/kg/h). In the fetuses exposed to AVP, lung liquid production decreased (3.3-1.6 ml/kg/h). As AVP, although not dDAVP, inhibited fetal lung liquid production, these results indicate that AVP effects on lung liquid are likely mediated via the AVP V1 receptor, not the V2 receptor. The use of fetal administration of dDAVP for the regulation of urine production and amniotic fluid volume will not adversely impact lung liquid production.

The effects of amidantel (BAY d 8815) and its deacylated derivative (BAY d 9216) on Caenorhabditis elegans.

The paralyzing effects of the anthelmintic drugs amidantel (BAY d 8815) and its deacylated derivative (BAY d 9216) on whole and cut C. elegans were investigated. The minimum effective concentrations with whole worms were 350 and 180 microM, respectively, compared to only 4 microM for another anthelmintic drug, levamisole. After rendering the worms permeable by cutting them at their approximate midsections, the minimum effective concentrations were: amidantel 0.30 microM, deacylated amidantel 0.07 microM and levamisole 0.15 microM. Comparison of the effects produced by amidantel and deacylated amidantel with those produced by levamisole, a known cholinergic agonist, suggested a common mode of action for all three drugs. The drugs were moderately potent inhibitors of both E. electricus and C. elegans acetylcholinesterase but at concentrations too high to account for their abilities to contract cut worms. Their primary mode of action appears to be as agonists at the level of the acetylcholine receptor, a view supported by the observation that their effects may be blocked by the nicotinic antagonists d-tubocurarine and gallamine.