Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury?

INTRODUCTION: Temporary occlusion of the hepatoduodenal ligament leads to an ischemic-reperfusion (IR) injury in the liver. Levosimendan is a new positive inotropic drug, which induces preconditioning-like adaptive mechanisms due to opening of mitochondrial KATP channels. The aim of this study was to examine possible protective effects of levosimendan in a rat model of hepatic IR injury. MATERIAL AND METHODS: Levosimendan was administered to male Wistar rats 1 hour (early pretreatment) or 24 hours (late pretreatment) before induction of 60-minute segmental liver ischemia. Microcirculation of the liver was monitored by laser Doppler flowmeter. After 24 hours of reperfusion, liver and blood samples were taken for histology, immuno- and enzyme-histochemistry (TUNEL; PARP; NADH-TR) as well as for laboratory tests. Furthermore, liver antioxidant status was assessed and HSP72 expression was measured. RESULTS: In both groups pretreated with levosimendan, significantly better hepatic microcirculation was observed compared to respective IR control groups. Similarly, histological damage was also reduced after levosimendan administration. This observation was supported by significantly lower activities of serum ALT (pearly = 0.02; plate = 0.005), AST (pearly = 0.02; plate = 0.004) and less DNA damage by TUNEL test (pearly = 0.05; plate = 0.034) and PAR positivity (pearly = 0.02; plate = 0.04). Levosimendan pretreatment resulted in significant improvement of liver redox homeostasis. Further, significantly better mitochondrial function was detected in animals receiving late pretreatment. Finally, HSP72 expression was increased by IR injury, but it was not affected by levosimendan pretreatment. CONCLUSION: Levosimendan pretreatment can be hepatoprotective and it could be useful before extensive liver resection

Determinants of woody encroachment and cover in African savannas

Savanna ecosystems are an integral part of the African landscape and sustain the livelihoods of millions of people. Woody encroachment in savannas is a widespread phenomenon but its causes are widely debated. We review the extensive literature on woody encroachment to help improve understanding of the possible causes and to highlight where and how future scientific efforts to fully understand these causes should be focused. Rainfall is the most important determinant of maximum woody cover across Africa, but fire and herbivory interact to reduce woody cover below the maximum at many locations. We postulate that woody encroachment is most likely driven by CO2 enrichment and propose a two-system conceptual framework, whereby mechanisms of woody encroachment differ depending on whether the savanna is a wet or dry system. In dry savannas, the increased water-use efficiency in plants relaxes precipitation-driven constraints and increases woody growth. In wet savannas, the increase of carbon allocation to tree roots results in faster recovery rates after disturbance and a greater likelihood of reaching sexual maturity. Our proposed framework can be tested using a mixture of experimental and earth observational techniques. At a local level, changes in precipitation, burning regimes or herbivory could be driving woody encroachment, but are unlikely to be the explanation of this continent-wide phenomenon

Protection by the NO-Donor SNAP and BNP against Hypoxia/Reoxygenation in Rat Engineered Heart Tissue

In vitro assays could replace animal experiments in drug screening and disease modeling, but have shortcomings in terms of functional readout. Force-generating engineered heart tissues (EHT) provide simple automated measurements of contractile function. Here we evaluated the response of EHTs to hypoxia/reoxygenation (H/R) and the effect of known cardiocytoprotective molecules. EHTs from neonatal rat heart cells were incubated for 24 h in EHT medium. Then they were subjected to 180 min hypoxia (93% N2, 7% CO2) and 120 min reoxygenation (40% O2, 53% N2, 7% CO2), change of medium and additional follow-up of 48 h. Time-matched controls (40% O2, 53% N2, 7% CO2) were run for comparison. The following conditions were applied during H/R: fresh EHT medium (positive control), the NO-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 10-7, 10-6, 10-5 M) or the guanylate cyclase activator brain type natriuretic peptide (BNP, 10-9, 10-8, 10-7 M). Frequency and force of contraction were repeatedly monitored over the entire experiment, pH, troponin I (cTnI), lactate dehydrogenase (LDH) and glucose concentrations measured in EHT medium. Beating activity of EHTs in 24 h-medium ceased during hypoxia, partially recovered during reoxygenation and reached time-control values during follow-up. H/R was accompanied by a small increase in LDH and non-significant increase in cTnI. In fresh medium, some EHTs continued beating during hypoxia and all EHTs recovered faster during reoxygenation. SNAP and BNP showed small but significant protective effects during reoxygenation. EHTs are applicable to test potential cardioprotective compounds in vitro, monitoring functional and biochemical endpoints, which otherwise could be only measured by using in vivo or ex vivo heart preparations. The sensitivity of the model needs improvement

Vascular adaptive responses to physical exercise and to stress are affected differently by nandrolone administration

Androgenic anabolic steroid, physical exercise and stress induce cardiovascular adaptations including increased endothelial function. The present study investigated the effects of these conditions alone and in combination on the vascular responses of male Wistar rats. Exercise was started at 8 weeks of life (60-min swimming sessions 5 days per week for 8 weeks, while carrying a 5% body-weight load). One group received nandrolone (5 mg/kg, twice per week for 8 weeks, im). Acute immobilization stress (2 h) was induced immediately before the experimental protocol. Curves for noradrenaline were obtained for thoracic aorta, with and without endothelium from sedentary and trained rats, submitted or not to stress, treated or not with nandrolone. None of the procedures altered the vascular reactivity to noradrenaline in denuded aorta. In intact aorta, stress and exercise produced vascular adaptive responses characterized by endothelium-dependent hyporeactivity to noradrenaline. These conditions in combination did not potentiate the vascular adaptive response. Exercise-induced vascular adaptive response was abolished by nandrolone. In contrast, the aortal reactivity to noradrenaline of sedentary rats and the vascular adaptive response to stress of sedentary and trained rats were not affected by nandrolone. Maximum response for 7-10 rats/group (g): sedentary 3.8 ± 0.2 vs trained 3.0 ± 0.2*; sedentary/stress 2.7 ± 0.2 vs trained/stress 3.1 ± 0.1*; sedentary/nandrolone 3.6 ± 0.1 vs trained/nandrolone 3.8 ± 0.1; sedentary/stress/nandrolone 3.2 ± 0.1 vs trained/stress/nandrolone 2.5 ± 0.1*; *P < 0.05 compared to its respective control. Stress and physical exercise determine similar vascular adaptive response involving distinct mechanisms as indicated by the observation that only the physical exercise-induced adaptive response was abolished by nandrolone.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Estadual PaulistaUniversidade Estadual PaulistaFAPESP: 06/57200-

Levosimendan Administration in Limb Ischemia: Multicomponent Signaling Serving Kidney Protection

AIMS AND OBJECTIVES: Acute renal failure is a severe complication of lower extremity major arterial reconstructions, which could even be fatal. Levosimendan is a dual-acting positive inotropic and vasodilatory agent, which is suspected to have protective effects against cardiac ischemia. However, there is no data available on lower limb or remote organ ischemic injuries therefore the aim of the study was to investigate the effect of levosimendan on lower limb ischemia-reperfusion injury and the corollary renal dysfunction. METHODS: Male Wistar rats underwent 180 min bilateral lower limb ischemia followed by 4 or 24 hours of reperfusion. Intravenous Levosimendan was administered continuously (0.2mug/bwkg/min) throughout the whole course of ischemia and the first 3h of reperfusion. Results were compared with sham-operated and ischemia-reperfusion groups. Hemodynamic monitoring was performed by invasive arterial blood pressure measurement. Kidney and lower limb muscle microcirculation was registered by a laser Doppler flowmeter. After 4h and 24h of reperfusion, serum, urine and histological samples were collected. RESULTS: Systemic hemodynamic parameters and microcirculation of kidney and the lower limb significantly improved in the Levosimendan treated group. Muscle viability was significantly preserved 4 and 24 hours after reperfusion. At the same time, renal functional laboratory tests and kidney histology demonstrated significantly less expressive kidney injury in Levosimendan groups. TNF-alpha levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion. CONCLUSION: The results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications

Functional traits driving species role in the structure of terrestrial vertebrate scavenger networks

Species assemblages often have a non-random nested organization, which in vertebrate scavenger (carrion-consuming) assemblages is thought to be driven by facilitation in competitive environments. However, not all scavenger species play the same role in maintaining assemblage structure, as some species are obligate scavengers (i.e., vultures) and others are facultative, scavenging opportunistically. We used a database with 177 vertebrate scavenger species from 53 assemblages in 22 countries across five continents to identify which functional traits of scavenger species are key to maintaining the scavenging network structure. We used network analyses to relate ten traits hypothesized to affect assemblage structure with the role of each species in the scavenging assemblage in which it appeared. We characterized the role of a species in terms of both the proportion of monitored carcasses on which that species scavenged, or scavenging breadth (i.e., the species normalized degree), and the role of that species in the nested structure of the assemblage (i.e., the species paired nested degree), therefore identifying possible facilitative interactions among species. We found that species with high olfactory acuity, social foragers, and obligate scavengers had the widest scavenging breadth. We also found that social foragers had a large paired nested degree in scavenger assemblages, probably because their presence is easier to detect by other species to signal carcass occurrence. Our study highlights differences in the functional roles of scavenger species and can be used to identify key species for targeted conservation to maintain the ecological function of scavenger assemblages

Epidemiologic and clinical updates on impulse control disorders: a critical review

The article reviews the current knowledge about the impulse control disorders (ICDs) with specific emphasis on epidemiological and pharmacological advances. In addition to the traditional ICDs present in the DSM-IV—pathological gambling, trichotillomania, kleptomania, pyromania and intermittent explosive disorder—a brief description of the new proposed ICDs—compulsive–impulsive (C–I) Internet usage disorder, C–I sexual behaviors, C–I skin picking and C–I shopping—is provided. Specifically, the article summarizes the phenomenology, epidemiology and comorbidity of the ICDs. Particular attention is paid to the relationship between ICDs and obsessive–compulsive disorder (OCD). Finally, current pharmacological options for treating ICDs are presented and discussed

Revival of the Magnetar PSR J1622–4950: Observations with MeerKAT, Parkes, XMM-Newton, Swift, Chandra, and NuSTAR

© 2018. The American Astronomical Society.. New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a quiescent state since at least early 2015, reactivated between 2017 March 19 and April 5. The radio flux density, while variable, is approximately 100 larger than during its dormant state. The X-ray flux one month after reactivation was at least 800 larger than during quiescence, and has been decaying exponentially on a 111 19 day timescale. This high-flux state, together with a radio-derived rotational ephemeris, enabled for the first time the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV pulsed fraction is comparable to the smallest observed for magnetars. The overall pulsar geometry inferred from polarized radio emission appears to be broadly consistent with that determined 6-8 years earlier. However, rotating vector model fits suggest that we are now seeing radio emission from a different location in the magnetosphere than previously. This indicates a novel way in which radio emission from magnetars can differ from that of ordinary pulsars. The torque on the neutron star is varying rapidly and unsteadily, as is common for magnetars following outburst, having changed by a factor of 7 within six months of reactivation

Pooled analysis of who surgical safety checklist use and mortality after emergency laparotomy

Background: The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods: In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results: Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89⋅6 per cent) compared with that in countries with a middle (753 of 1242, 60⋅6 per cent; odds ratio (OR) 0⋅17, 95 per cent c.i. 0⋅14 to 0⋅21, P &lt; 0⋅001) or low (363 of 860, 42⋅2 percent; OR 0⋅08, 0⋅07 to 0⋅10, P &lt; 0⋅001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference −9⋅4 (95 per cent c.i. −11⋅9 to −6⋅9) per cent; P &lt; 0⋅001), but the relationship was reversed in low-HDI countries (+12⋅1 (+7⋅0 to +17⋅3) per cent; P &lt; 0⋅001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0⋅60, 0⋅50 to 0⋅73; P &lt; 0⋅001). The greatest absolute benefit was seen for emergency surgery in low-and middle-HDI countries. Conclusion: Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries