What are the similarities between stress, sudden cardiac death in Gallus gallus and sudden unexpected death in people with epilepsy

Individuals with epilepsy are at higher risk of sudden unexpected death in epilepsy (SUDEP), responsible for 7.5% to 17% of all deaths in epilepsy. Many factors are current associated with SUDEP and possible effect of stress and cardiac arrhythmia are still not clear. Sudden death syndrome (SDS) in chickens is a disease characterized by an acute death of well-nourished and seeming healthy Gallus gallus after abrupt and brief flapping of their wings, similar to an epileptic seizure, with an incidence estimated as 0.5 to 5% in broiler chickens. A variety of nutritional and environmental factors have been included: but the exactly etiology of SDS is unknown. Studies had suggested that the hearts of broiler chickens are considerably more susceptible to arrhythmias and stress may induce ventricular arrhythmia and thus, sudden cardiac death. In this way, SDS in Gallus gallus could be an interesting model to study SUDEP.

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF). Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine) can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg) by intraperitoneal injections of thioacetamide (200 mg/kg). Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL·kg-1·day-1) and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a) reduced the relative mRNA expression of the genes: Col-α1 (-53%), TIMP-1 (-31.7%), TGF-β1 (-57.7%), and MMP-2 (-41.6%), whereas Plau mRNA remained unchanged; b) reduced GGT (-43.1%), ALT (-17.6%), and AST (-12.2%) serum levels; c) increased liver weight (11.3%), and reduced liver collagen (-37.1%), regenerative nodules size (-22.1%), and fibrous septum thickness. Progranulin protein (immunohistochemistry) and mRNA (in situ hybridization) were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression.

Evaluation of the efficacy of hydrated sodium aluminosilicate in the prevention of aflatoxin-induced hepatic cancer in rainbow trout

The use of aluminum silicates for decontaminating animal feed containing aflatoxins has yielded encouraging results in chicken and turkey poults. In contrast, very few studies have tested these substances in aquaculture. In this work, we investigated the efficacy of a trout diet containing 0.5% hydrated sodium aluminosilicate (HSAS) in protecting against contamination with aflatoxin B1. Trout were reared on these diets for one year and the experimental groups were examined monthly for hepatic presumptive preneoplastic and neoplastic lesions. Regardless of the presence of HSAS, all of the fish that received aflatoxin in their diet have shown hepatic lesions indicative of a carcinogenic process, presenting also the development of cancer in some fish. The concentration of HSAS used in this study was ineffective in preventing the onset of hepatic lesions induced by aflatoxin B1 in rainbow trout.

Protective effects of mate tea (Ilex paraguariensis) on H2O2-induced DNA damage and DNA repair in mice

Yerba mate (Ilex paraguariensis) is rich in several bioactive compounds that can act as free radical scavengers. Since oxidative DNA damage is involved in various pathological states such as cancer, the aim of this study was to evaluate the antioxidant activity of mate tea as well as the ability to influence DNA repair in male Swiss mice. Forty animals were randomly assigned to four groups. The animals received three different doses of mate tea aqueous extract, 0.5, 1.0 or 2.0 g/kg, for 60 days. After intervention, the liver, kidney and bladder cells were isolated and the DNA damage induced by H2O2 was investigated by the comet assay. The DNA repair process was also investigated for its potential to protect the cells from damage by the same methodology. The data presented here show that mate tea is not genotoxic in liver, kidney and bladder cells. The regular ingestion of mate tea increased the resistance of DNA to H2O2-induced DNA strand breaks and improved the DNA repair after H2O2 challenge in liver cells, irrespective of the dose ingested. These results suggest that mate tea could protect against DNA damage and enhance the DNA repair activity. Protection may be afforded by the antioxidant activity of the mate tea's bioactive compounds

Evaluation of Femtosecond Laser-Induced Breakdown Spectroscopy for Analysis of Animal Tissues

The aim of this work was to evaluate the performance of femtosecond laser-induced breakdown spectroscopy (fs-LIBS) for the determination of elements in animal tissues. Sample pellets were prepared from certified reference materials, such as liver, kidney, muscle, hepatopancreas, and oyster, after cryogenic grinding assisted homogenization. Individual samples were placed in a two-axis computer-controlled translation stage that moved in the plane orthogonal to a beam originating from a Ti:Sapphire chirped-pulse amplification (CPA) laser system operating at 800 mu and producing a train of 840 mu J and 40 fs pulses at 90 Hz. The plasma emission was coupled into the optical fiber of a high-resolution intensified charge-coupled device (ICCD)-echelle spectrometer. Time-resolved characteristics of the laser-produced plasmas showed that the best results were obtained with delay times between 80 and 120 ns. Data obtained indicate both that it is a matrix-independent sampling process and that fs-LIBS can be used for the determination of Ca, Cu, Fe, K, Mg, Na, and P, but efforts must be made to obtain more appropriate detection limits for Al, Sr, and Zn.

Changes in Glucose and Glutamine Lymphocyte Metabolisms Induced by Type I Interferon alpha

In lymphocytes (LY), the well-documented antiproliferative effects of IFN-alpha are associated with inhibition of protein synthesis, decreased amino acid incorporation, and cell cycle arrest. However, the effects of this cytokine on the metabolism of glucose and glutamine in these cells have not been well investigated. Thus, mesenteric and spleen LY of male Wistar rats were cultured in the presence or absence of IFN-alpha, and the changes on glucose and glutamine metabolisms were investigated. The reduced proliferation of mesenteric LY was accompanied by a reduction in glucose total consumption (35%), aerobic glucose metabolism (55%), maximal activity of glucose-6-phosphate dehydrogenase (49%), citrate synthase activity (34%), total glutamine consumption (30%), aerobic glutamine consumption (20.3%) and glutaminase activity (56%). In LY isolated from spleen, IFN alpha also reduced the proliferation and impaired metabolism. These data demonstrate that in LY, the antiproliferative effects of IFN alpha are associated with a reduction in glucose and glutamine metabolisms.

Hyperglycemia can delay left ventricular dysfunction but not autonomic damage after myocardial infarction in rodents

Background: Although clinical diabetes mellitus is obviously a high risk factor for myocardial infarction (MI), in experimental studies disagreement exists about the sensitivity to ischemic injury of an infarcted myocardium. Recently, our group demonstrated that diabetic animals presented better cardiac function recovery and cellular resistance to ischemic injury than nondiabetics. In the present study, we evaluated the chronic effects of MI on left ventricular (LV) and autonomic functions in streptozotocin (STZ) diabetic rats. Methods: Male Wistar rats were divided into 4 groups: control (C, n = 15), diabetes (D, n = 16), MI (I, n = 21), and diabetes + MI (DI, n = 30). MI was induced 15 days after diabetes (STZ) induction. Ninety days after MI, LV and autonomic functions were evaluated (8 animals each group). Left ventricular homogenates were analyzed by Western blotting to evaluate the expression of calcium handling proteins. Results: MI area was similar in infarcted groups (similar to 43%). Ejection fraction and + dP/dt were reduced in I compared with DI. End-diastolic pressure was additionally increased in I compared with DI. Compared with DI, I had increased Na(+)-Ca(2+) exchange and phospholamban expression (164%) and decreased phosphorylated phospholamban at serine(16) (65%) and threonine(17) (70%) expression. Nevertheless, diabetic groups had greater autonomic dysfunction, observed by baroreflex sensitivity and pulse interval variability reductions. Consequently, the mortality rate was increased in DI compared with I, D, and C groups. Conclusions: LV dysfunction in diabetic animals was attenuated after 90 days of myocardial infarction and was associated with a better profile of calcium handling proteins. However, this positive adaptation was not able to reduce the mortality rate of DI animals, suggesting that autonomic dysfunction is associated with increased mortality in this group. Therefore, it is possible that the better cardiac function has been transitory, and the autonomic dysfunction, more prominent in diabetic group, may lead, in the future, to the cardiovascular damage.

Vibration-induced extra torque during electrically-evoked contractions of the human calf muscles

Background: High-frequency trains of electrical stimulation applied over the lower limb muscles can generate forces higher than would be expected from a peripheral mechanism (i.e. by direct activation of motor axons). This phenomenon is presumably originated within the central nervous system by synaptic input from Ia afferents to motoneurons and is consistent with the development of plateau potentials. The first objective of this work was to investigate if vibration (sinusoidal or random) applied to the Achilles tendon is also able to generate large magnitude extra torques in the triceps surae muscle group. The second objective was to verify if the extra torques that were found were accompanied by increases in motoneuron excitability. Methods: Subjects (n = 6) were seated on a chair and the right foot was strapped to a pedal attached to a torque meter. The isometric ankle torque was measured in response to different patterns of coupled electrical (20-Hz, rectangular 1-ms pulses) and mechanical stimuli (either 100-Hz sinusoid or gaussian white noise) applied to the triceps surae muscle group. In an additional investigation, M(max) and F-waves were elicited at different times before or after the vibratory stimulation. Results: The vibratory bursts could generate substantial self-sustained extra torques, either with or without the background 20-Hz electrical stimulation applied simultaneously with the vibration. The extra torque generation was accompanied by increased motoneuron excitability, since an increase in the peak-to-peak amplitude of soleus F waves was observed. The delivery of electrical stimulation following the vibration was essential to keep the maintained extra torques and increased F-waves. Conclusions: These results show that vibratory stimuli applied with a background electrical stimulation generate considerable force levels (up to about 50% MVC) due to the spinal recruitment of motoneurons. The association of vibration and electrical stimulation could be beneficial for many therapeutic interventions and vibration-based exercise programs. The command for the vibration-induced extra torques presumably activates spinal motoneurons following the size principle, which is a desirable feature for stimulation paradigms.

Paracoccidioides brasilinsis-Induced Migration of Dendritic Cells and Subsequent T-Cell Activation in the Lung-Draining Lymph Nodes

Paracoccidioidomycosis is a mycotic disease caused by a dimorphic fungus, Paracoccidioides brasiliensis (Pb), that starts with inhalation of the fungus; thus, lung cells such as DC are part of the first line of defense against this microorganism. Migration of DC to the lymph nodes is the first step in initiating T cell responses. The mechanisms involved in resistance to Pb infection are poorly understood, but it is likely that DC play a pivotal role in the induction of effector T cells that control Pb infection. In this study, we showed that after Pb Infection, an important modification of lung DC receptor expression occurred. We observed an increased expression of CCR7 and CD103 on lung DC after infection, as well as MHC-II. After Pb infection, bone marrow-derived DC as well lung DC, migrate to lymph nodes. Migration of lung DC could represent an important mechanism of pathogenesis during PCM infection. In resume our data showed that Pb induced DC migration. Furthermore, we demonstrated that bone marrow-derived DC stimulated by Pb migrate to the lymph nodes and activate a T helper (Th) response. To the best of our knowledge, this is the first reported data showing that Pb induces migration of DC and activate a T helper (Th) response.

Anomalous diffusion in non-Markovian walks having amnestically induced persistence

We report numerically and analytically estimated values for the Hurst exponent for a recently proposed non-Markovian walk characterized by amnestically induced persistence. These results are consistent with earlier studies showing that log-periodic oscillations arise only for large memory losses of the recent past. We also report numerical estimates of the Hurst exponent for non-Markovian walks with diluted memory. Finally, we study walks with a fractal memory of the past for a Thue-Morse and Fibonacci memory patterns. These results are interpreted and discussed in the context of the necessary and sufficient conditions for the central limit theorem to hold.

Spontaneous symmetry breaking in amnestically induced persistence

We investigate a recently proposed non-Markovian random walk model characterized by loss of memories of the recent past and amnestically induced persistence. We report numerical and analytical results showing the complete phase diagram, consisting of four phases, for this system: (i) classical nonpersistence, (ii) classical persistence, (iii) log-periodic nonpersistence, and (iv) log-periodic persistence driven by negative feedback. The first two phases possess continuous scale invariance symmetry, however, log-periodicity breaks this symmetry. Instead, log-periodic motion satisfies discrete scale invariance symmetry, with complex rather than real fractal dimensions. We find for log-periodic persistence evidence not only of statistical but also of geometric self-similarity.

Defects in vesicle core induced by Escherichia coli dihydroorotate dehydrogenase

Dihydroorotate dehydrogenase (DHODH) catalyzes the oxidation of dihydroorotate to orotate during the fourth step of the de novo pyrimidine synthesis pathway. In rapidly proliferating mammalian cells, pyrimidine salvage pathway is insufficient to overcome deficiencies in that pathway for nucleotide synthesis. Moreover, as certain parasites lack salvage enzymes, relying solely on the de novo pathway, DHODH inhibition has turned out as an efficient way to block pyrimidine biosynthesis. Escherichia coli DHODH (EcDHODH) is a class 2 DHODH, found associated to cytosolic membranes through an N-terminal extension. We used electronic spin resonance (ESR) to study the interaction of EcDHODH with vesicles of 1,2-dioleoyl-sn-glycero-phosphatidylcholine/detergent. Changes in vesicle dynamic structure induced by the enzyme were monitored via spin labels located at different positions of phospholipid derivatives. Two-component ESR spectra are obtained for labels 5- and 1 0-phosphatidylcholine in presence of EcDHODH, whereas other probes show a single-component spectrum. The appearance of an additional spectral component with features related to fast-motion regime of the probe is attributed to the formation of a defect-like structure in the membrane hydrophobic region. This is probably the mechanism used by the protein to capture quinones used as electron acceptors during catalysis. The use of specific spectral simulation routines allows us to characterize the ESR spectra in terms of changes in polarity and mobility around the spin-labeled phospholipids. We believe this is the first report of direct evidences concerning the binding of class 2 DHODH to membrane systems.

Loxosceles gaucho Venom-Induced Acute Kidney Injury - In Vivo and In Vitro Studies

Background: Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. Methodology/Principal Findings: In order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. Conclusions/Significance: Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite.

Factitious thyrotoxicosis induced by mesotherapy: A case report

Context: Mesotherapy consists of cutaneous injections of a mixture of compounds and has recently been used for cosmetic purposes to reduce local fat and cellulite. To date, several reports have described only local adverse events related to this therapy. We describe the first report of a female patient who developed thyrotoxicosis due to cosmetic mesotherapy with triiodothyroacetic acid in its formulation. Apart from mechanical rupture of the epidermal barrier, a disturbance of type III deiodinase activity or skin fibroblast paracrine function and vascular alterations related to simultaneously injected vasoactive compounds were observed. These findings could be related to thyroid hormone metabolite absorption and systemic consequences in the reported case. Conclusion: We describe factitious thyrotoxicosis induced by mesotherapy, to raise awareness of a systemic adverse effect resulting from this widespread cosmetic practice.

ECG scar quantification correlates with cardiac magnetic resonance scar size and prognostic factors in Chagas' disease

Objective To test the hypothesis that 12-lead ECG QRS scoring quantifies myocardial scar and correlates with disease severity in Chagas' heart disease. Design Patients underwent 12-lead ECG for QRS scoring and cardiac magnetic resonance with late gadolinium enhancement (CMR-LGE) to assess myocardial scar. Setting University of Sao Paulo Medical School, Sao Paulo, Brazil. Patients 44 Seropositive patients with Chagas' disease without a history of myocardial infarction and at low risk for coronary artery disease. Main outcome measures Correlation between QRS score, CMR-LGE scar size and left ventricular ejection fraction. Relation between QRS score, heart failure (HF) class and history of ventricular tachycardia (VT). Results QRS score correlated directly with CMR-LGE scar size (R=0.69, p<0.0001) and inversely with left ventricular ejection fraction (R=-0.54, p=0.0002), which remained significant in the subgroup with conduction defects. Patients with class II or III HF had significantly higher QRS scores than those with class I HF (5.1 +/- 3.4 vs 2.1 +/- 3.1 QRS points (p=0.002)) and patients with a history of VT had significantly higher QRS scores than those without a history of VT (5.3 +/- 3.2% vs 2.6 +/- 3.4 QRS points (p=0.02)). A QRS score >= 2 points had particularly good sensitivity and specificity (95% and 83%, respectively) for prediction of large CMR-LGE, and a QRS score >= 7 points had particularly high specificity (92% and 89%, respectively) for predicting significant left ventricular dysfunction and history of VT. Conclusions The wide availability of 12-lead ECG makes it an attractive screening tool and may enhance clinical risk stratification of patients at risk for more severe, symptomatic Chagas' heart disease.