Behavioral and physiological methods for early quantitative assessment of spinal cord injury and prognosis in rats

Methods for reliable evaluation of spinal cord (SC) injury in rats at short periods (2 and 24 h) after lesion were tested to characterize the mechanisms implicated in primary SC damage. We measured the physiological changes occurring after several procedures for producing SC injury, with particular emphasis on sensorimotor functions. Segmental and suprasegmental reflexes were tested in 39 male Wistar rats weighing 250-300 g divided into three control groups that were subjected to a) anesthesia, b) dissection of soft prevertebral tissue, and c) laminectomy of the vertebral segments between T10 and L1. In the lesion group the SC was completely transected, hemisected or subjected to vertebral compression. All animals were evaluated 2 and 24 h after the experimental procedure by the hind limb motility index, Bohlman motor score, open-field, hot-plate, tail flick, and paw compression tests. The locomotion scale proved to be less sensitive than the sensorimotor tests. A reduction in exploratory movements was detected in the animals 24 h after the procedures. The hot-plate was the most sensitive test for detecting sensorimotor deficiencies following light, moderate or severe SC injury. The most sensitive and simplest test of reflex function was the hot-plate. The hemisection model promoted reproducible moderate SC injury which allowed us to quantify the resulting behavior and analyze the evolution of the lesion and its consequences during the first 24 h after injury. We conclude that hemisection permitted the quantitation of behavioral responses for evaluation of the development of deficits after lesions. Hind limb evaluation scores and spontaneous exploration events provided a sensitive index of immediate injury effects after SC lesion at 2 and 24 h. Taken together, locomotion scales, open-field, and hot-plate tests represent reproducible, quantitatively sensitive methods for detecting functional deficiencies within short periods of time, indicating their potential for the study of cellular mechanisms of primary injury and repair after traumatic SC injury.

Hypoxic-ischemic injury decreases anxiety-like behavior in rats when associated with loss of tyrosine-hydroxylase immunoreactive neurons of the substantia nigra

Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time) on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra (SN). The mild and severe HI groups were exposed to hypoxia (8% O2/92% N2) for 90 and 150 min, respectively. The elevated plus-maze (EPM) test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT) and OAT%, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT% in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05). The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2%) and severe HI groups (16.3, 32.2, and 43.8%, respectively; P < 0.05). The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.

Inovação aberta na gestão pública: análise do plano de ação brasileiro para a Open Government Partnership

Este estudo objetivou analisar o Plano de Ação brasileiro para o Governo Aberto, baseado na teoria da inovação aberta na gestão pública. Utilizou-se de uma pesquisa documental, com vistas a aprofundar o conhecimento do fenômeno em questão. O documento foi escolhido intencionalmente, por ser exemplo basilar das políticas públicas relacionadas à inovação aberta brasileira. Os resultados mostram que os compromissos firmados pelo governo brasileiro estão consoantes com o processo de inovação aberta pública. As ações previstas no Plano estão especificamente relacionadas a transparência, abertura de dados e preparação do corpo estatal para o processo aberto de inovação.

Mid-point for open-ended income category and the effect of equivalence scales on the income-health relationship

To estimate the mid-point of an open-ended income category and to assess the impact of two equivalence scales on income-health associations. Data were obtained from the 2010 Brazilian Oral Health Survey ( Pesquisa Nacional de Saúde Bucal – SBBrasil 2010). Income was converted from categorical to two continuous variables ( per capita and equivalized) for each mid-point. The median mid-point was R$ 14,523.50 and the mean, R$ 24,507.10. When per capita income was applied, 53% of the population were below the poverty line, compared with 15% with equivalized income. The magnitude of income-health associations was similar for continuous income, but categorized equivalized income tended to decrease the strength of association.

Description of an injury in a human caused by a false tocandira (Dinoponera gigantea, Perty, 1833) with a revision on folkloric, pharmacological and clinical aspects of the giant ants of the genera Paraponera and Dinoponera (sub-family Ponerinae)

The authors observed an injury caused by the sting of a false tocandira ant in the hand of an amateur fisherman and they describe the clinical findings and the evolution of the envenoming, which presented an acute and violent pain, cold sweating, nausea, a vomiting episode, malaise, tachycardia and left axillary's lymphadenopathy. About three hours after the accident, still feeling intense pain in the place of the sting, he presented an episode of great amount of blood in the feces with no history of digestive, hematological or vascular problems. The intense pain decreased after eight hours, but the place stayed moderately painful for about 24 hours. In that moment, he presented small grade of local edema and erythema. The authors still present the folkloric, pharmacological and clinical aspects related to the tocandiras stings, a very interesting family of ants, which presents the largest and more venomous ants of the world.

ACUTE KIDNEY INJURY CAUSED BY Crotalus AND Bothrops SNAKE VENOM: A REVIEW OF EPIDEMIOLOGY, CLINICAL MANIFESTATIONS AND TREATMENT

SUMMARY Ophidic accidents are an important public health problem due to their incidence, morbidity and mortality. An increasing number of cases have been registered in Brazil in the last few years. Several studies point to the importance of knowing the clinical complications and adequate approach in these accidents. However, knowledge about the risk factors is not enough and there are an increasing number of deaths due to these accidents in Brazil. In this context, acute kidney injury (AKI) appears as one of the main causes of death and consequences for these victims, which are mainly young males working in rural areas. Snakes of the Bothrops and Crotalus genera are the main responsible for renal involvement in ophidic accidents in South America. The present study is a literature review of AKI caused by Bothrops and Crotalus snake venom regarding diverse characteristics, emphasizing the most appropriate therapeutic approach for these cases. Recent studies have been carried out searching for complementary therapies for the treatment of ophidic accidents, including the use of lipoic acid, simvastatin and allopurinol. Some plants, such as Apocynaceae, Lamiaceae and Rubiaceae seem to have a beneficial role in the treatment of this type of envenomation. Future studies will certainly find new therapeutic measures for ophidic accidents.

Acute kidney injury in a tropical country: a cohort study of 253 patients in an infectious diseases intensive care unit

Introduction: Acute kidney injury (AKI) is a frequent and potentially fatal complication in infectious diseases. The aim of this study was to investigate the clinical aspects of AKI associated with infectious diseases and the factors associated with mortality. Methods: This retrospective study was conducted in patients with AKI who were admitted to the intensive care unit (ICU) of a tertiary infectious diseases hospital from January 2003 to January 2012. The major underlying diseases and clinical and laboratory findings were evaluated. Results: A total of 253 cases were included. The mean age was 46±16 years, and 72% of the patients were male. The main diseases were human immunodeficiency virus (HIV) infection, HIV/acquired immunodeficiency syndrome (AIDS) (30%), tuberculosis (12%), leptospirosis (11%) and dengue (4%). Dialysis was performed in 70 cases (27.6%). The patients were classified as risk (4.4%), injury (63.6%) or failure (32%). The time between AKI diagnosis and dialysis was 3.6±4.7 days. Oliguria was observed in 112 cases (45.7%). The Acute Physiology and Chronic Health Evaluation (APACHE) II scores were higher in patients with HIV/AIDS (57±20, p-value=0.01) and dengue (68±11, p-value=0.01). Death occurred in 159 cases (62.8%). Mortality was higher in patients with HIV/AIDS (76.6%, p-value=0.02). A multivariate analysis identified the following independent risk factors for death: oliguria, metabolic acidosis, sepsis, hypovolemia, the need for vasoactive drugs, the need for mechanical ventilation and the APACHE II score. Conclusions: AKI is a common complication in infectious diseases, with high mortality. Mortality was higher in patients with HIV/AIDS, most likely due to the severity of immunosuppression and opportunistic diseases.

Laparoscopic versus open splenectomy in the management of hematologic diseases

Splenectomy is the best available treatment for severe forms of hereditary spherocytosis, idiopathic thrombocytopenic purpura, and other hematologic conditions when these prove refractory to conservative management. It has been employed for many decades with low mortality and favorable remission rates. The use of laparoscopic splenectomy in recent years has been rapidly and even enthusiastically adopted in this field. However, the exact role of laparoscopic versus open surgery for hematologic diseases is still debated. In this study of 58 adult patients, laparoscopic procedures were compared with conventional splenectomies for similar indications. METHODS: All patients were operated on within an 8-year period. Subjects underwent similar procedures under the supervision of the same surgical school and were compared regarding age, gender, body mass index, and diagnosis. Laparoscopically managed cases (Group I, n = 30) were prospectively followed according to a written protocol, whereas the same investigation was retrospectively done with regard to traditional laparotomy (Group II, n = 28). Methods included general and demographic findings, duration and technical steps of operation, blood loss, weight of spleen, need for conversion (in minimally invasive subjects), intraoperative and postoperative complications, time until realimentation, postoperative hospitalization, mortality, and late follow-up including recurrence rate. RESULTS: Idiopathic thrombocytopenic purpura was the surgical indication in over 50% of the patients in both groups, but familial spherocytosis, thalassemia, myelodysplasia, and lymphomas were also represented in this series. Laparoscopic procedures took more time to perform (P = 0.004), and postoperative hospitalization was 2 days shorter, but this difference was not statistically significant. Postoperative hematocrit and volume of blood transfusions was equivalent, although the laparoscopic cases had a somewhat lower preoperative hematocrit (NS) and displayed better recovery for this measurement (P = 0.03). More patients in Group I were able to accept oral food on the first day than subjects undergoing conventional operations (P < 0.05). Relatively few conversions were necessary during the minimally invasive surgeries (13.3%), and postoperative early and late complications as well as recurrences occurred in similar proportions. Also, the mean weight of the spleen was not statistically different between the groups, although there was a marked numerical tendency toward larger masses in conventional procedures. No spleen in Group I exceeded 2.0 kg, whereas in Group II values up to 4.0 kg occurred, and the mean weight was 50% higher in the latter group. CONCLUSIONS: 1) Minimally invasive splenectomy was essentially comparable to open surgery with regard to safety, efficacy, and late results; 2) Advantages concerning shorter postoperative hospitalization could not be shown, despite earlier food intake and a non-significant tendency toward earlier discharge; 3) This new modality should be considered an option in cases of hematologic conditions whenever the spleen is not hugely enlarged.

A multicenter, open-label study of the efficacy and safety of telmisartan in mild to moderate hypertensive patients

OBJECTIVE: To evaluate the efficacy and tolerability of telmisartan, given once a day to patients with mild to moderate hypertension, as well as to assess the 24-hour blood pressure profile with ABPM. METHODS: Initially, 163 patients over 18 were selected, regardless of sex, with blood pressure levels >140/90mmHg at visit 1, which was confirmed at visit 2. One hundred thirty-four patients completed the study. After a 4-week placebo run-in phase, telmisartan 40mg/daily was given for 6 weeks. In those patients whose blood pressure (BP) levels were lower than 140/90mmHg, the same dosage was kept for an additional period of 6 weeks. For those who had BP higher than 140/90mmHg, the dosage was increased to 80mg/daily. Sixty-two patients were included in a subgroup that underwent ABPM 3 different times during the study. RESULTS: In the overall group, blood pressure reduction ranged from 162.3±14.5/101.3±5.75 mmHg (baseline) to 147.3±20.1/90.8±10.9 mmHg (week 12) (p<0.05). Mean blood pressure decreases were 14.4mmHg for systolic BP and 10.3mmHg for diastolic BP, after 12 weeks of active treatment. A subanalysis showed that 47 (35%) patients took telmisartan 40mg throughout the study and 81 (65%) had the dosage increased to 80mg daily. Using ABPM, an 8-mmHg reduction in systolic BP as well as a 5-mmHg reduction in diastolic BP were observed, when compared with baseline values in the final 6 hours (18-24 hours after the last dose of study medication). CONCLUSION: Our results confirm that telmisartan given once a day is effective in reducing blood pressure levels in mild to moderate hypertensive patients. This reduction occurs in a sustained and gradual manner during a 24-hour period confirmed by ABPM.

Behavior of inflammatory markers of myocardial injury in cardiac surgery: laboratory correlation with the clinical picture of postpericardiotomy syndrome

OBJECTIVE: To verify the association of serum markers of myocardial injury, such as troponin I, creatinine kinase, and creatinine kinase isoenzyme MB, and inflammatory markers, such as tumor necrosis factor alpha (TNF-alpha), C-reactive protein, and the erythrocyte sedimentation rate in the perioperative period of cardiac surgery, with the occurrence of possible postpericardiotomy syndrome. METHODS: This was a cohort study with 96 patients undergoing cardiac surgery assessed at the following 4 different time periods: the day before surgery (D0); the 3rd postoperative day (D3); between the 7th and 10th postoperative days (D7-10); and the 30th postoperative day (D30). During each period, we evaluated demographic variables (sex and age), surgical variables (type and duration , extracorporeal circulation), and serum dosages of the markers of myocardial injury and inflammatory response. RESULTS: Of all patients, 12 (12.5%) met the clinical criteria for a diagnosis of postpericardiotomy syndrome, and their mean age was 10.3 years lower than the age of the others (P=0.02). The results of the serum markers for tissue injury and inflammatory response were not significantly different between the 2 assessed groups. No significant difference existed regarding either surgery duration or extracorporeal circulation. CONCLUSION: The patients who met the clinical criteria for postpericardiotomy syndrome were significantly younger than the others were. Serum markers for tissue injury and inflammatory response were not different in the clinically affected group, and did not correlate with the different types and duration of surgery or with extracorporeal circulation.

Tramadol Alleviates Myocardial Injury Induced by Acute Hindlimb Ischemia Reperfusion in Rats

AbstractBackground:Organ injury occurs not only during periods of ischemia but also during reperfusion. It is known that ischemia reperfusion (IR) causes both remote organ and local injuries.Objective:This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR.Methods:Thirty healthy mature male Wistar rats were allocated randomly into three groups: Group I (sham), Group II (IR), and Group III (IR + tramadol). Ischemia was induced in anesthetized rats by left femoral artery clamping for 3 h, followed by 3 h of reperfusion. Tramadol (20 mg/kg, intravenous) was administered immediately prior to reperfusion. At the end of the reperfusion, animals were euthanized, and hearts were harvested for histological and biochemical examination.Results:The levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were higher in Groups I and III than those in Group II (p < 0.05). In comparison with other groups, tissue malondialdehyde (MDA) levels in Group II were significantly increased (p < 0.05), and this increase was prevented by tramadol. Histopathological changes, including microscopic bleeding, edema, neutrophil infiltration, and necrosis, were scored. The total injuryscore in Group III was significantly decreased (p < 0.05) compared with Group II.Conclusion:From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model.

The Effect of Sleep Deprivation on Cardiac Function and Tolerance to Ischemia-Reperfusion Injury in Male Rats

Abstract Background: Sleep deprivation (SD) is strongly associated with elevated risk for cardiovascular disease. Objective: To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR) injury in male rats. Method: SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP); heart rate (HR); and the maximum rate of increase and decrease of left ventricular pressure (±dp/dt). Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP) was measured at start and end of study. Results: In the SD group, the baseline levels of LVDP (19%), +dp/dt (18%), and -dp/dt (21%) were significantly (p < 0.05) lower, and HR (32%) was significantly higher compared to the controls. After ischemia, hearts from SD group displayed a significant increase in HR together with a low hemodynamic function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days. Conclusion: Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR.