Zinc Supplement Modifies Auditory Brainstem Responses in Patients with Tinnitus

Introduction: Zinc is an essential element for human homeostasis being clearly related to almost all metabolic pathways. It is found in some neural circuitries, probably acting as a modulator of glutamatergic excitatory synapsis. In the auditory system its presence has been demonstrated within the cochlea and cochlear nuclei. Tinnitus symptoms are correlated to zinc physiology, and it has been postulated that the oligoelement could be used as an alternative treatment for this clinical situation. Aim: This study has evaluated the brainstem responses (ABR) in patients who suffer from chronic idiophatic tinnitus, before and after being treated with zinc. Neural transmissions in the brainstem auditory structures were also compared in both conditions. Materials and Methods: Forty-one patients (22 with tinnitus and 19 controls, groups I and II, respectively) were included in the study and submitted to anamnesis, otorhinolaryngologic examinations, biochemical evaluation and audiological tests. Group I patients received an specific zinc formulation for 90 days. ABR tests were performed at the beginning of the study and at the end of the zinc treatment. Results: First ABR tests showed no differences between the groups, but on the second evaluation there was a significant prolongation of the wave V latency and an enlargement of wave V amplitude shown in group I. Conclusion: Treatment with systemic zinc could change some aspects of auditory neurotransmission in the brainstem.

Cutting Edge: Nucleotide-Binding Oligomerization Domain 1-Dependent Responses Account for Murine Resistance against Trypanosoma cruzi Infection

An effective innate immune recognition of the intracellular protozoan parasite Trypanosoma cruzi is critical for host resistance against Chagas disease, a severe and chronic illness that affects millions of people in Latin America. In this study, we evaluated the participation of nucleotide-binding oligomerization domain (Nod)like receptor proteins in host response to T cruzi infection and found that Nod1-dependent, but not Nod2-dependent, responses are required for host resistance against infection. Bone marrow-derived macrophages from Nod1(-/-) mice showed an impaired induction of NF-kappa B-dependent products in response to infection and failed to restrict T cruzi infection in presence of IFN-gamma. Despite normal cytokine production in the sera, Nod1(-/-) mice were highly susceptible to T cruzi infection, in a similar manner to MyD88(-/-) and NO synthase 2(-/-) mice. These studies indicate that Nod1-dependent responses account for host resistance against T cruzi infection by mechanisms independent of cytokine production. The Journal of Immunology, 2010, 184: 1148-1152.

Pain and distress reactivity and recovery as early predictors of temperament in toddlers born preterm

Background: Pain reactivity may reflect underlying mechanisms of constitutional aspects of temperament. Aim: To examine whether the neonatal biobehavioral reactivity and recovery responses from pain and distress, as well as the gestational age, the illness severity and the amount of painful procedures undergone the Neonatal Intensive Care Unit (NICU) stay, predict temperament later in toddlerhood, in vulnerable children born preterm. Study design: Prospective-longitudinal study. Subjects: Twenty-six preterm and very low birth weight infants followed from birth to toddlerhood. Outcome measures: Illness severity was assessed with the Clinical Risk Index for Babies (CRIB) score. The medical charts were reviewed prospectively for obtaining the amount of pain exposure in NICU. For assessing the behavioral and cardiac reactivity and recovery from pain and distress, the neonates were evaluated during routine blood collection in the NICU in the first 10 days of life. Pain and distress reactivity and recovery was measured using the Neonatal Facial Coding System score, the duration of crying. and the magnitude of average heart rate. At toddlerhood, mothers answered the Early Childhood Behavior Questionnaire. Results: Higher biobehavioral reactivity to pain and distress predicted higher temperamental Negative Affect, above and beyond gestational age, illness severity and amount of pain exposure in NICU. However, we did not find a predictive relation between gestational age, CRIB score and number of painful procedures undergone NICU and toddler`s temperament. Conclusions: The findings highlight the relevance of the neonatal individual characteristics of reactivity for identifying more vulnerable infants for future problems in biobehavioral regulation. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Inflammatory mediators involved in the nociceptive and oedematogenic responses induced by Tityus serrulatus scorpion venom injected into rat paws.

The present study investigated the role of kinins, prostaglandins (PGs) and nitric oxide (NO) in mechanical hypernociception, Spontaneous nociception and paw oedema after intraplantar (ipl) injection of Tityus serrulatus venom (Tsv) in male Wistar rats. Tsv was ipl-injected in doses of 0.01-10 mu g/paw. Pre-treatment (30 min prior) with DALBK (100 nmol/paw) and icatibant (10 nmol/paw), B1 and B2 selective kinin receptor antagonists, L-NAME (50 mg/kg, i.p., a non-selective nitric oxide synthase inhibitor) or celecoxib, selective COX-2 inhibitor, was given 1 h prior per os (5 mg/kg, p.o.), significantly reduced the hypernociceptive response (Von Frey method), the spontaneous nociception (determined by counting the number of flinches) and paw oedema (plethysmometer method) induced by Tsv at doses of 1.0 and 10 mu g/paw for both nociceptive and oedematogenic responses, respectively. Nevertheless, indomethacin (5 mg/kg, i.p.. 30 min prior) was ineffective in altering all of these events. The results of the present study show that Tsv, injected ipl into the rat paw, causes a dose-dependent paw oedema, mechanical hypernociception and flinches (a characteristic biphasic response) in which kinins and NO are substantially involved. Although celecoxib was effective against the oedema and pain caused by Tsv, COX-2 does not seem to be involved in the inflammatory response caused by Tsv. (C) 2008 Elsevier Ltd. All rights reserved.

Mild cognitive deficits associated to neocortical microgyria in mice with genetic deletion of cellular prion protein

The cellular prion protein (PrP(c)) has been implicated with the modulation of neuronal apoptosis, adhesion, neurite outgrowth and maintenance which are processes involved in the neocortical development. Malformations of cortical development (MCD) are frequently associated with neurological conditions including mental retardation, autism, and epilepsy. Here we investigated the behavioral performance of female adult PrP(c)-null mice (Prnp(%)) and their wild-type controls (Prnp(+/+)) presenting unilateral polymicrogyria, a MCD experimentally induced by neonatal freeze-lesion in the right hemisphere. injured mice from both genotypes presented similar locomotor activity but Prnp(%) mice showed a tendency to increase anxiety-related responses when compared to Prnp(+/+) animals. Additionally, injured Prnp(%) mice have a poorer performance in the social recognition task than sham-operated and Prnp(%) injured ones. Moreover the step-down inhibitory avoidance task was not affected by the procedure or the genotype of the animals. These data suggest that the genetic deletion of PrP(c) confers increased susceptibility to short-term social memory deficits induced by neonatal freezing model of polymicrogyria in mice. (C) 2008 Published by Elsevier B.V.

Pain and tactile stimuli during arterial puncture in preterm neonates

The purpose of this study was to assess the behavioral and physiological reactivity of preterm neonates during different phases of a blood collection procedure involving arterial puncture. The sample consisted of 43 preterm and very low birth weight neonates with a postnatal age of 1 to 21 days who were hospitalized in the Neonatal Intensive Care Unit. The neonates were evaluated during the whole blood collection procedure. The assessment was divided into five consecutive phases: Baseline (BL); Antispsis (A), covering the period of handling of the neonate for antisepsis prior to puncture; Puncture (P): Recovery-Dressing (RD), covering the period of handling of the neonate for dressing until positioning for rest in the isolette; and Recovery-Resting (RR). Facial activity was videotaped and analyzed using the National Facial Coding System (NFCS). The sleep-wake state and heart rate were registered at the bedside. There was a significant increases in NFCS score and heart rate, and more active behavior during phases A, P, and RD relative to BL. Regarding the tactile stimulation of the infant in pre-puncture (A) and post-puncture (RD), it was observed increased NFCS score, heart rate, and active behavior in comparison to the BL an BR phases. There was evidence of distress responses immediately before and after a painful event, quite apart form the pain reaction to the puncture procedure. Published by Elsevier B.V. on behalf of International Association for the Study of Pain.

Is pain relief equally efficacious and free of side effects with repeated doses of oral sucrose in preterm neonates?

The aim of the present study was to examine the efficacy and potential side effects of repeated doses of oral sucrose for pain relief during procedures in NICU. Thirty-three preterm neonates were randomly allocated in blind fashion into two groups, the sucrose group (SG = 17) and the control group (CG = 16). The responses of neonates to pain and distress were assessed during blood collection on four consecutive assessment (ass.) days. For the first assessment, the neonates did not receive any solution before the blood collection procedure. During the next three days, the SG received oral sucrose (25%; 0.5 ml/kg) and the CG received sterile water, 2 min before each minor acute painful procedure. The neonates were evaluated during blood collection each morning. The assessment was divided into five phases: Baseline (BL), Antisepsis (A), Puncture (P), Dressing (D), and Recovery (R). The neonates` facial activity (NFCS), behavioral state, and heart rate were evaluated. The data analysis used cut-off scores for painful and distressful responses. No side effects of using sucrose were detected. There were significantly fewer SG neonates with facial actions signaling pain than CG neonates in P (ass.2) and in A (ass.3). We found significantly fewer SG neonates in the awake state than CG neonates in P (ass.2 and ass.4). There were significantly fewer SG neonates crying during A (ass.2), P (ass.2 and ass.4), and D (ass.3). There was no statistical difference between-groups for physiological response. The efficacy of sucrose was maintained for pain relief in preterm neonates with no side effects. (C) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Serial conditional discrimination and temporal bisection in rats selectively lesioned in the dentate gyrus

In positive serial conditional discrimination, animals respond during a target stimulus when it is preceded by a feature stimulus, but they do not respond when the same target stimulus is presented alone. Moreover, the feature and target stimuli are separated from each other by an empty interval. The present work aimed to investigate if two durations (4 or 16s) of the same feature stimulus (light) could modulate the operant responses of rats to different levers (A and B) during a 5-s target stimulus (tone). In the present study, lever A was associated with the 4-s light, and lever B was associated with the 16-s light. A 5-s empty interval was included between the light and the tone. In the same training procedure, the rats were also presented with the 5-s tone without the preceding light stimuli. In these trials, the responses were not reinforced. We evaluated the hippocampal involvement of these behavioral processes by selectively lesioning the dentate gyrus with colchicine. Once trained, the rats were submitted to a test using probe trials without reinforcement. They were presented with intermediate durations of the feature stimulus (light) to obtain a temporal bisection curve recorded during the exposure to the target stimuli. The rats from both groups learned to respond with high rates during tones preceded by light and with low rates during tones presented alone, which indicated acquisition of the serial conditional discrimination. The rats were able to discriminate between the 4- and 16-s lights by correctly choosing lever A or B. In the test, the temporal bisection curves from both experimental groups showed a bisection point at the arithmetic mean between 4 and 16s. Such processes were not impaired by the dentate gyrus lesion. Thus, our results showed that different durations of a feature stimulus could result in conditional properties. However, this processing did not appear to depend on the dentate gyrus alone. (C) 2011 Published by Elsevier B.V.

Role of neurokinin-1 expressing neurons in the locus coeruleus on ventilatory and cardiovascular responses to hypercapnia

We assessed the role of NK-1 receptors (NK1R) expressing neurons in the locus coeruleus (LC) on cardiorespiratory responses to hypercapnia. To this end, we injected substance P-saporin conjugate (SP-SAP) to kill NK-1 immunoreactive (NK1R-ir) neurons or SAP alone as a control. Immunohistochemistry for NK1R, tyrosine hydroxylase (TH-ir) and Glutamic Acid Decarboxylase (GAD-ir) were performed to verify if NK1R-expressing neurons, catecholaminergic and/or GABAergic neurons were eliminated. A reduced NK1R-ir in the LC (72%) showed the effectiveness of the lesion. SP-SAP lesion also caused a reduction of TH-ir (66%) and GABAergic neurons (70%). LC SP-SAP lesion decreased by 30% the ventilatory response to 7% CO(2) and increased the heart rate (fH) during hypercapnia but did not affect MAP. The present data suggest that different populations of neurons (noradrenergic, GABAergic, and possibly others) in the LC express NK1R modulating differentially the hypercapnic ventilatory response, since catecholaminergic neurons are excitatory and GABAergic ones are inhibitory. Additionally, NK1R-ir neurons in the LC, probably GABAergic ones, seem to modulate fH during CO(2) exposure, once our previous data demonstrated that catecholaminergic lesion does not affect this variable. (C) 2010 Elsevier B.V. All rights reserved.

Effects of six carbohydrate sources on diet digestibility and postprandial glucose and insulin responses in cats

The effects of diets with different starch sources on the total tract apparent digestibility and glucose and insulin responses in cats were investigated. Six experimental diets consisting of 35% starch were extruded, each containing one of the following ingredients: cassava flour, brewers rice, corn, sorghum, peas, or lentils. The experiment was carried out on 36 cats with 6 replications per diet in a completely randomized block design. The brewers rice diet offered greater DM, OM, and GE digestibility than the sorghum, corn, lentil, and pea diets (P < 0.05). For starch digestibility, the brewers rice diet had greater values (98.6%) than the sorghum (93.9%), lentil (95.2%), and pea (96.3%) diets (P < 0.05); however, starch digestibility was > 93% for all the diets, proving that despite the low carbohydrate content of carnivorous diets, cats can efficiently digest this nutrient when it is properly processed into kibble. Mean and maximum glucose concentration and area under the glucose curve were greater for the corn-based diet than the cassava flour, sorghum, lentil, and pea diets (P < 0.05). The corn-based diets led to greater values for the mean glucose incremental concentration (10.2 mg/dL), maximum glucose incremental concentration (24.8 mg/dL), and area under the incremental glucose curve (185.5 mg.dL(-1).h(-1)) than the lentil diet (2.9 mg/dL, 3.1 mg/dL, and -40.4 mg.dL(-1).h(-1), respectively; P < 0.05). When compared with baseline values, only the corn diet stimulated an increase in the glucose response, occurring at 4 and 10 h postmeal (P < 0.05). The corn-based diet resulted in greater values for maximum incremental insulin concentration and area under the incremental insulin curve than the lentil-based diet (P < 0.05). However, plasma insulin concentrations rose in relation to the basal values for cats fed corn, sorghum, pea, and brewers rice diets (P < 0.05). Variations in diet digestibility and postprandial response can be explained by differences in the chemical composition of the starch source, including fiber content and granule structure, and also differences in the chemical compositions of the diets. The data suggest that starch has less of an effect on the cat postprandial glucose and insulin responses than on those of dogs and humans. This can be explained by the metabolic peculiarities of felines, which may slow and prolong starch digestion and absorption, leading to the delayed, less pronounced effects on their blood responses.

Influence of Photoperiod and Temperature on the Larval Behavioral Diapause of Amblyomma cajennense (Acari: Ixodidae)

Larval behavioral diapause was shown to be the major factor controlling the 1-yr generation pattern of Amblyomma cajennense (F.) (Acari: Ixodidae) in Brazil. During fieldwork, this behavior was shown to coincide with long daylength (>12 h) and high mean ground temperature (approximate to 25 degrees C), which prevail during spring-summer in Brazil. The current study evaluated biological parameters of engorged females, their eggs, and the resultant larvae inside plastic pots planted with the grass Brachiaria decumbens Stapf. held in incubators set with different combinations of temperature and photoperiod. Both the long daylength (photoperiod 14:10 [L:D]h) and high temperature (25 degrees C) during larval hatching induced larval behavioral diapause, characterized by the confinement of hatched larvae on the ground below the vegetation for many weeks. When long daylength was present during hatching, but temperature was low (15 degrees C), larvae did not enter diapause. Similarly, when short daylength (10:14 or 12:12) was present during larval hatching, larvae did not enter diapause regardless whether temperature was high (25 degrees C). Termination of diapause was induced by shifting photoperiod from 14:10 to 12:12 or the temperature from 25 to 15 degrees C. When applied to field conditions, the present results indicate that both high ground mean temperature (approximate to 25 degrees C) and long daylength (>12 h) during spring-summer (October-March) are responsible for the induction and maintenance of A. cajennense larval behavioral diapause in the field. Furthermore, both the low ground mean temperature (-20 degrees C) and the short daylength (<12h) during autumn (April-May) are responsible for termination of larval behavioral diapause in the field.

Plasticity of Opioid Receptors in the Female Periaqueductal Gray: Multiparity-Induced Increase in the Activity of Genes Encoding for Mu and Kappa Receptors and a Post-Translational Decrease in Delta Receptor Expression

The periaqueductal gray (PAG) has been reported as a potential site for opioid regulation of behavioral selection. Opioid-mediated behavioral and physiological responses differ between nulliparous and multiparous females. This study addresses the effects of multiple reproductive experiences on mu-, kappa- and delta-opioid receptor (Oprm1, Oprk1, and Oprd1 respectively) gene activity and mu, kappa and delta protein expression (MOR, KOR and DOR respectively) in the PAG of the female rats. This was done by evaluating the opioid gene expression using real-time (RT-PCR) and quantification of each protein receptor by Western blot analysis. The RT-PCR results show that multiple reproductive experiences increase Oprm1 and Oprk1 gene expression. Western blot analysis revealed increased MOR and KOR while DOR protein was decreased in multiparous animals. Taken together, these data suggest that multiple reproductive experiences influence both gene activity and opioid receptor expression in the PAG. Post-translational mechanisms seem particularly relevant for DOR expression. Thus, opioid transmission in the PAG might be modulated by different mechanisms of multiparity-induced plasticity according to the opioid receptor type.

Odor cues from tumor-bearing mice induces neuroimmune changes

Cohabitation for 14 days with an Ehrlich tumor-bearing mice was shown, among others, to increase locomotor activity, and hypothalamic noradrenaline levels and turnover, to decrease the innate immune responses and animal resistance to tumor growth. The present experiment was designed to access the relevance of tactile, olfactory, and visual communication to the neuroimmune changes induced by cohabitation with a tumor-bearing partner. Mice that were not allowed to perceive odor cues from their sick partners presented no alterations in neutrophil activity, a fact not observed after visual deprivation and physical isolation. Mice use scents for intraspecies communication in many social contexts. Tumors produce volatile organic compounds released into the atmosphere through breath, sweat, and urine. The present results strongly suggest that volatile compounds released by Ehrlich tumor-injected mice are perceived by their conspecifics, inducing the neuroimmune changes reported for cohabitation with a sick companion. (C) 2010 Published by Elsevier B.V.

Behavioral effects of LPS in adult, middle-aged and aged mice

Acute infections lead to alterations in behavior, collectively known as sickness behavior. which includes reduction in locomotion, food ingestion, sexual and social behavior, environmental exploration, and sleep profile. Although generally seen as undesired, sickness behavior represents a conserved strategy for animals to overcome disease. Aging process is associated with a variety of changes in immunity, which are referred to as immunosenescence, and include higher mortality by infectious diseases. Few works studied sickness behavior display in old animals. Thus, we sought to investigate the display of sickness related behaviors on aged mice. Adult(3-6 months old), middle-aged (12-15 m) and aged mice (18-22 m)were treated with i.p. LPS (200 mu g/kg) and their behaviors were assessed in the open field and in the elevated plus-maze. Exploratory activity was similar in aged mice treated or not with LPS in both apparati. In the open field, locomotion remained at baseline levels; in the elevated plus-maze, there was a time-dependent decrease in motor activity. (C) 2008 Elsevier Inc. All rights reserved