L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury

© 2018, The Author(s). There is a need for pharmaceutical agents that can reduce neuronal loss and improve functional deficits following traumatic brain injury (TBI). Previous research suggests that oxidative stress and mitochondrial dysfunction play a major role in neuronal damage after TBI. Therefore, this study aimed to investigate two drugs known to have antioxidant effects, L-carnitine and exendin-4, in rats with moderate contusive TBI. L-carnitine (1.5 mM in drinking water) or exendin-4 (15 µg/kg/day, ip) were given immediately after the injury for 2 weeks. Neurological function and brain histology were examined (24 h and 6 weeks post injury). The rats with TBI showed slight sensory, motor and memory functional deficits at 24 h, but recovered by 6 weeks. Both treatments improved sensory and motor functions at 24 h, while only exendin-4 improved memory. Both treatments reduced cortical contusion at 24 h and 6 weeks, however neither affected gliosis and inflammatory cell activation. Oxidative stress was alleviated and mitochondrial reactive oxygen species was reduced by both treatments, however only mitochondrial functional marker protein transporter translocase of outer membrane 20 was increased at 24 h post injury. In conclusion, L-carnitine and exendin-4 treatments immediately after TBI can improve neurological functional outcome and tissue integrity by reducing oxidative stress

Absence of association between behavior problems in childhood and hypertension in midlife

Background It is known that behavior in childhood is associated with certain physical and mental health problems in midlife. However, there is limited evidence on the role of childhood behavior problems in the development of hypertension in adulthood. The present study aimed to examine whether behavior problems in childhood influenced the risk of hypertension in midlife in the United Kingdom 1958 birth cohort. Methods The 1958 British birth cohort comprised 17,638 individuals born in the first week of March 1958 in the United Kingdom. Behavior problems were assessed at 7, 11, and 16 years of age by parents and teachers. At age 45, blood pressure was measured and hypertension was recorded if blood pressure was ≥140/90 mm Hg or if the participants were informed by their health professionals that they had high blood pressure. Behavioral information was reported according to the Rutter Children's Behaviour Questionnaire (RCBQ) and the Bristol Social Adjustment Guide (BSAG). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to examine behavior problems in childhood in relation to hypertension at 45 years of age according to logistic regression analysis, with adjustment for sex, social class in childhood and adulthood, childhood cognition, birth weight, gestational age at birth, body mass index (BMI), smoking, alcohol consumption, and physical activity. Results Behavior problems reported by parents at 7, 11, and 16 years were not associated with hypertension in midlife (OR, 0.93; 95% CI, 0.81, 1.07; OR, 0.95; 95% CI, 0.81, 1.11; OR, 0.98; 95% CI, 0.85, 1.12, respectively). Similarly, teacher-reported behavior problems at 7, 11, and 16 years were not associated with hypertension in midlife (OR, 0.92; 95% CI, 0.72, 1.18; OR, 0.92; 95% CI, 0.84, 1.02; OR, 1.03; 95% CI, 0.92, 1.15, respectively). Further separate analyses showed similar results for males and females. Conclusion There is no association between behavior problems in childhood and hypertension in midlife

Prevention of catheter lumen occlusion with rT-PA versus heparin (Pre-CLOT): study protocol of a randomized trial [ISRCTN35253449]

BACKGROUND: Many patients with end-stage renal disease use a central venous catheter for hemodialysis access. A large majority of these catheters malfunction within one year of insertion, with up to two-thirds due to thrombosis. The optimal solution for locking the catheter between hemodialysis sessions, to decrease the risk of thrombosis and catheter malfunction, is unknown. The Prevention of Catheter Lumen Occlusion with rt-PA versus Heparin (PreCLOT) study will determine if use of weekly rt-PA, compared to regular heparin, as a catheter locking solution, will decrease the risk of catheter malfunction. METHODS/DESIGN: The study population will consist of patients requiring chronic hemodialysis thrice weekly who are dialyzed with a newly inserted permanent dual-lumen central venous catheter. Patients randomized to the treatment arm will receive rt-PA 1 mg per lumen once per week, with heparin 5,000 units per ml as a catheter locking solution for the remaining two sessions. Patients randomized to the control arm will receive heparin 5,000 units per ml as a catheter locking solution after each dialysis session. The study treatment period will be six months, with 340 patients to be recruited from 14 sites across Canada. The primary outcome will be catheter malfunction, based on mean blood flow parameters while on hemodialysis, with a secondary outcome of catheter-related bacteremia. A cost-effectiveness analysis will be undertaken to assess the cost of maintaining a catheter using rt-PA as a locking solution, compared to the use of heparin. DISCUSSION: Results from this study will determine if use of weekly rt-PA, compared to heparin, will decrease catheter malfunction, as well as assess the cost-effectiveness of these locking solutions

Zoledronic acid treatment impairs protein geranyl-geranylation for biological effects in prostatic cells

BACKGROUND: Nitrogen-containing bisphosphonates (N-BPs) have been designed to inhibit osteoclast-mediated bone resorption. However, it is now accepted that part of their anti-tumor activities is related to interference with the mevalonate pathway. METHODS: We investigated the effects of zoledronic acid (ZOL), on cell proliferation and protein isoprenylation in two tumoral (LnCAP, PC-3,), and one normal established (PNT1-A) prostatic cell line. To assess if inhibition of geranyl-geranylation by ZOL impairs the biological activity of RhoA GTPase, we studied the LPA-induced formation of stress fibers. The inhibitory effect of ZOL on geranyl geranyl transferase I was checked biochemically. Activity of ZOL on cholesterol biosynthesis was determined by measuring the incorporation of (14)C mevalonate in cholesterol. RESULTS: ZOL induced dose-dependent inhibition of proliferation of all the three cell lines although it appeared more efficient on the untransformed PNT1A. Whatever the cell line, 20 μM ZOL-induced inhibition was reversed by geranyl-geraniol (GGOH) but neither by farnesol nor mevalonate. After 48 hours treatment of cells with 20 μM ZOL, geranyl-geranylation of Rap1A was abolished whereas farnesylation of HDJ-2 was unaffected. Inhibition of Rap1A geranyl-geranylation by ZOL was rescued by GGOH and not by FOH. Indeed, as observed with treatment by a geranyl-geranyl transferase inhibitor, treatment of PNT1-A cells with 20 μM ZOL prevented the LPA-induced formation of stress fibers. We checked that in vitro ZOL did not inhibit geranyl-geranyl-transferase I. ZOL strongly inhibited cholesterol biosynthesis up to 24 hours but at 48 hours 90% of this biosynthesis was rescued. CONCLUSION: Although zoledronic acid is currently the most efficient bisphosphonate in metastatic prostate cancer management, its mechanism of action in prostatic cells remains unclear. We suggest in this work that although in first intention ZOL inhibits FPPsynthase its main biological actitivity is directed against protein Geranylgeranylation

Hemodialysis vascular access options in pediatrics: considerations for patients and practitioners

Recent data indicate that the incidence of end-stage renal disease (ESRD) in pediatric patients (age 0–19 years) has increased over the past two decades. Similarly, the prevalence of ESRD has increased threefold over the same period. Hemodialysis (HD) continues to be the most frequently utilized modality for renal replacement therapy in incident pediatric ESRD patients. The number of children on HD exceeded the sum total of those on peritoneal dialysis and those undergoing pre-emptive renal transplantation. Choosing the best vascular access option for pediatric HD patients remains challenging. Despite a national initiative for fistula first in the adult hemodialysis population, the pediatric nephrology community in the United States of America utilizes central venous catheters as the primary dialysis access for most patients. Vascular access management requires proper advance planning to assure that the best permanent access is placed, seamless communication involving a multidisciplinary team of nephrologists, nurses, surgeons, and interventional radiologists, and ongoing monitoring to ensure a long life of use. It is imperative that practitioners have a long-term vision to decrease morbidity in this unique patient population. This article reviews the various types of pediatric vascular accesses used worldwide and the benefits and disadvantages of these various forms of access

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Multidimensional pain assessment of preterm newborns at the 1st, 3rd and 7th days of life

CONTEXT AND OBJECTIVE: It is challenge to assess and treat pain in premature infants. The objective of this study was to compare the multidimensional pain assessment of preterm neonates subjected to an acute pain stimulus at 24 hours, 72 hours and seven days of life. DESIGN AND SETTING: Prospective cohort study, at Universidade Federal de São Paulo (UNIFESP). METHODS: Eleven neonates with gestational age less than 37 weeks that needed venepuncture for blood collection were studied. The exclusion criteria were Apgar score < 7 at five minutes, presence of any central nervous system abnormality, and discharge or death before seven days of life. Venepuncture was performed in the dorsum of the hand, and the heart rate, oxygen saturation and pain scales [Neonatal Facial Coding System (NFCS), Neonatal Infant Pain Scale (NIPS), and Premature Infant Pain Profile (PIPP)] were assessed at 24 hours, 72 hours and 7 days of life. NFCS and NIPS were evaluated prior to procedure (Tpre), during venepuncture (T0), and two (T2) and five (T5) minutes after needle withdrawal. Heart rate, O2 saturation and PIPP were measured at Tpre and T0. Mean values were compared by repeated-measurement analysis of variance. RESULTS: The pain parameters did not differ at 24 hours, 72 hours and 7 days of life: heart rate (p = 0.22), oxygen saturation (p = 0.69), NFCS (p = 0.40), NIPS (p = 0.32) and PIPP (p = 0.56). CONCLUSION: Homogeneous pain scores were observed following venepuncture in premature infants during their first week of life.CONTEXTO E OBJETIVO: É um desafio avaliar e tratar a dor do bebê prematuro. O objetivo deste estudo foi comparar, diante de um mesmo estímulo doloroso agudo, as respostas multidimensionais à dor obtidas ao longo da primeira semana de vida de prematuros. TIPO DE ESTUDO E LOCAL: Coorte prospectiva, na Universidade Federal de São Paulo (UNIFESP). MÉTODOS: Estudo de 11 neonatos com idade gestacional inferior a 37 semanas e necessidade de punção venosa para coleta de sangue, sendo excluídos aqueles com Apgar < 7 aos cinco minutos, alterações do sistema nervoso central e os que faleceram ou tiveram alta até sete dias de vida. A punção venosa foi feita no dorso da mão e avaliou-se a freqüência cardíaca, a saturação de oxigênio e as seguintes escalas de dor: NFCS (Neonatal Facial Coding System), NIPS (Neonatal Infant Pain Scale) e PIPP (Premature Infant Pain Profile) com 24, 72 horas e no sétimo dia de vida. A NFCS e a NIPS foram pontuadas antes da punção venosa (Tpré), durante (T0), dois (T2) e cinco (T5) minutos após. A freqüência cardíaca, a saturação de oxigênio e a PIPP foram analisadas em Tpré e T0. Compararam-se os valores médios das variáveis nos três momentos por análise de variância com medidas repetidas. RESULTADOS: Não houve diferenças no primeiro, terceiro e sétimo dias para freqüência cardíaca (p = 0,22), saturação de oxigênio (p = 0,69), NFCS (p = 0,40), NIPS (p = 0,32) e PIPP (p = 0,56). CONCLUSÃO: Houve homogeneidade da avaliação da dor causada por punção venosa em prematuros, ao longo da primeira semana de vida.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of PediatricsUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of Preventive MedicineUNIFESP, EPM, Department of PediatricsUNIFESP, EPM, Department of Preventive MedicineCAPES: 1068-02SciEL