Aloe vera bathing improved physical and humoral protection in breeding stock after induced spawning in matrinxa (Brycon amazonicus)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Coupling between respiratory and sympathetic activities as a novel mechanism underpinning neurogenic hypertension

Enhanced sympathetic outflow to the heart and resistance vessels greatly contributes to the onset and maintenance of neurogenic hypertension. There is a consensus that the development of hypertension (clinical and experimental) is associated with an impairment of sympathetic reflex control by arterial baroreceptors. More recently, chronic peripheral chemoreflex activation, as observed in obstructive sleep apnea, has been proposed as another important risk factor for hypertension. In this review, we present and discuss recent experimental evidence showing that changes in the respiratory pattern, elicited by chronic intermittent hypoxia, play a key role in increasing sympathetic activity and arterial pressure in rats. This concept parallels results observed in other models of neurogenic hypertension, such as spontaneously hypertensive rats and rats with angiotensin II–salt-induced hypertension, pointing out alterations in the central coupling of respiratory and sympathetic activities as a novel mechanism underlying the development of neurogenic hypertension.

Effect of byrosima crassa and phenolic constituents on helicobacter pylori: induced neutrophils oxdative burst

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Resolution of tremor fluoxetine-induced in an elderly patient

Aim: To report a possible case of tremor fluoxetine-induced treated as Parkinson’s disease in an elderly female patient noncompliant with the pharmacotherapy, with uncontrolled hypertension and using fluoxetine to treat depression. Presentation of Case: Patient complained of sleepiness in the morning, agitation, anxiety, insomnia and mental confusion. Her greatest concern was about bilateral hand tremors which, in her view became, worse after biperiden was prescribed. Therefore, she stopped taking it. The initial medication was: omeprazole, losartan, biperiden, fluoxetine, atenolol + chlorthalidone, acetylsalicylic acid, atorvastatin and diazepam. Pharmacotherapeutic follow up was performed in order to check the necessity, safety and effectiveness of treatment. Discussion: During the analysis of pharmacotherapy, the patient showed uncontrolled blood pressure and had difficulty complying with the treatment. Thus, in view of the complaints expressed by the patient, our first hypothesis was a possible serotonin syndrome related to fluoxetine use. We proposed a change in the fluoxetine regime and discontinuation of biperiden. As tremors persisted, we suggested the replacement of fluoxetine by sertraline, since a possible tremor fluoxetine-induced could explain the complaint. This approach solved the drug-related problem identified. Conclusion: Tremors reported by the patient was identified as an iatrogenic event related to fluoxetine, which was solved by management of serotonin-reuptake inhibitors.

Vitamin A affects haematology, growth and immune response of Nile tilapia (Oreochromis niloticus, L.), but has no protective effect against bacterial challenge or cold-induced stress

Vitamin A (vitA) is an essential nutrient that acts as an endocrine regulator of several metabolic pathways, modulating normal growth and health status of animals. Although the importance of vitA for normal haematology and immune response is well documented for higher vertebrates, there is limited information on the physiological effects of vitA on fish. Therefore, we designed a 130-day feeding trial to evaluate the effect of vitA supplementation on growth, haematology, immune function and resistance to experimental infection with Aeromonas hydrophila and cold-induced stress. A group of 320 Nile tilapia fingerlings 7.49 ± 0.19 g weight (mean ± SD) were randomly stocked into 40 250 L-aquaria and fed practical diets containing graded levels of vitA (0, 0.06, 0.12, 0.24, 0.48, 0.96, 1.92, 3.84 mg retinol (ROH) kg−1 diet. Growth, haematology, plasma protein profile and immune response were significantly affected by vitA supplementation; however, no clear protective effect of vitA supplementation on disease and cold stress resistance were observed in this study. Clinical signs of vitA deficiency were: resting and abnormal swimming behaviour, exophthalmia, haemorrhages at the base of fins and on skin, serous fluids in abdominal cavity, neutropenia, reduction in red blood cell count, haematocrit and haemoglobin evolving to high mortality rates in a short period of time. A dietary level of vitA around 1.2 mg ROH kg−1 may be required to prevent gross deficiency signs and promote proper growth and health status of Nile tilapia. VitA does not seem to have a pronounced effect on leucocyte differentiation, but clearly plays an important role on maintaining normal erythropoiesis.

Heat stress induced alteration in bovine oocytes: functional and cellular aspects

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

INFLUENCE OF TYPE 2 BOVINE VIRAL DIARRHEA VIRUS NPRO ON ENHANCEMENT OF BOVINE RESPIRATORY SYNCYTIAL VIRUS REPLICATION MEDIATED BY ANTAGONISM OF HOST CELL INTERFERON TYPE I RESPONSES

Bovine viral diarrhea virus (BVDV) is a member of the genus Pestivirus, Family Flaviviridae. The virus can infect many species of animals of the order Artiodactyla. The BVDV genome encodes an auto protease, Npro, that degrades interferon regulatory factor-3 (IRF-3) reducing type I interferon (IFN-I) production from host cells. Bovine respiratory syncytial virus (BRSV) is a member of the genus Pneumovirus, Family Paramyxoviridae. Concurrent infection with BVDV and BRSV causes more severe respiratory and enteric disease than infection with either virus alone. Our hypothesis was that Npro modulates the innate immune responses to BVDV infection and enhances replication of BVDV or BRSV co-infection. The noncytopathic BVDV2 viruses NY93/c N- Npro 18 EGFP (a mutant with modified Npro fused with enhanced green fluorescent protein), NY93 infectious clone (NY93/c), wild-type NY93-BVDV2 (NY93-wt), and BRSV were evaluated in this study. The objectives of this study were: (1) to characterize the replication kinetics and IFN-I induction in Madin-Darby bovine kidney (MDBK) cells following infection with each of the BVDV isolates, and (2) to characterize the influence of BVDV-mediated IFN-I antagonism on enhancement of BRSV replication in bovine turbinate (BT) cells. NY93/c N- Npro 18 EGFP replicated 0.4 – 1.6 TCID50 logs lower than NY93-wt in MDBK cells. NY93/c N- Npro 18 EGFP-infected MDBK cells synthesized IFN-I significantly higher than NY93/c- and NY93-wt-infected MDBK cells. BT cells co-infected with NY93/c N- Npro 18 EGFP/BRSV or NY93-wt/BRSV were evaluated to determine the effects of co-infection on BRSV replication and IFN-I induction in BT cells. BRSV RNA levels in NY93-wt/BRSV co-infected BT cells were 2.49, 2.79, and 2.89 copy number logs significantly greater than in NY93/c N- Npro 18 EGFP/BRSV co-infected BT cells on days 5, 7, and 9 post-infection, respectively. BVDV RNA levels in NY93/c N- Npro 18 EGFP-infected BT cells were 1.64 – 4.38 copy number logs lower than in NY93-wt-infected BT cells. NY93/c N- Npro 18 EGFP single and co-infected BT cells synthesized IFN-I significantly higher than NY93-wt single and co-infected BT cells. In summary, these findings suggest: (1) NY93/c N- Npro 18 EGFP BVDV2 induced higher levels of IFN-I than BVDV2-wt and may be useful as a safer, replicating BVDV vaccine, and (2) Enhancement of BRSV infection by BVDV co-infection is mediated by antagonism of IFN-I.

Long-term sertraline treatment increases expression and decreases phosphorylation of glycogen synthase kinase-3B in platelets of patients with late-life major depression

Background: Abnormal regulation of glycogen synthase kinase 3-beta (GSK3B) activity has been implicated in the pathophysiology of mood disorders. Many pharmacological agents, including antidepressants, can modulate GSK3B. The aim of the present study was to investigate the effect of short-and long-term sertraline treatment on the expression and phosphorylation of GSK3B in platelets of patients with late-life major depression. Methods: Thirty-nine unmedicated elderly adults with major depressive disorder (MOD) were initially included in this study. The comparison group comprised 18 age-matched, healthy individuals. The expression of total and Ser-9 phosphorylated GSK3B (pGSK3B) was determined by Enzyme Immunometric Assay (EIA) in platelets of patients and controls at baseline, and after 3 and 12 months of sertraline treatments for patients only. During this period, patients were continuously treated with therapeutic doses of sertraline. GSK3B activity was indirectly estimated by calculating the proportion of inactive (phosphorylated) forms (pGSK3B) in relation to the total expression of the enzyme (i.e.. GSK3B ratio). Results: Depressed patients had significantly higher levels of pGSK3B as compared to controls (p < 0.001). Within the MDD group, after 3 months of sertraline treatment no significant changes were observed in GSK3B expression and phosphorylation state, as compared to baseline levels. However, after 12 months of treatment we found a significant increase in the expression of total GSK3B (p = 0.05), in the absence of any significant changes in pGSK3B (p = 0.12), leading to a significant reduction in GSK3B ratio (p = 0.001). Conclusions: Our findings indicate that GSK3B expression was upregulated by the continuous treatment with sertraline, along with an increment in the proportion of active forms of the enzyme. This is compatible with an increase in overall GSK3B activity, which may have been induced by the long-term treatment of late-life depression with sertraline. (C) 2012 Elsevier Ltd. All rights reserved.

Respiratory rehabilitation: a physiotherapy approach to the control of asthma symptoms and anxiety

OBJECTIVES: The objectives of this study were to verify the degree of anxiety, respiratory distress, and health-related quality of life in a group of asthmatic patients who have experienced previous panic attacks. Additionally, we evaluated if a respiratory physiotherapy program (breathing retraining) improved both asthma and panic disorder symptoms, resulting in an improvement in the health-related quality of life of asthmatics. METHODS: Asthmatic individuals were assigned to a chest physiotherapy group that included a breathing retraining program held once a week for three months or a paired control group that included a Subtle Touch program. All patients were assessed using the Diagnostic and Statistical Manual of Mental Disorders IV, the Sheehan Anxiety Scale, the Quality of Life Questionnaire, and spirometry parameter measurements. RESULTS: Both groups had high marks for panic disorder and agoraphobia, which limited their quality of life. The Breathing Retraining Group program improved the clinical control of asthma, reduced panic symptoms and agoraphobia, decreased patient scores on the Sheehan Anxiety Scale, and improved their quality of life. Spirometry parameters were unchanged. CONCLUSION: Breathing retraining improves the clinical control of asthma and anxiety symptoms and the health-related quality of life in asthmatic patients.

Chronic Intermittent Hypoxia Depresses Afferent Neurotransmission in NTS Neurons by a Reduction in the Number of Active Synapses

Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autonomic regulation. Here we identified the synaptic mechanisms of CIH-induced depression of the afferent neurotransmission in NTS neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes were observed in release probability, evidenced by absence of any CIH-elicited effects on short-term depression and failures in EPSCs evoked in low calcium. CIH also produced no changes in TS-eEPSC quantal size, since the amplitudes of both low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of Sr2+) were unchanged. Using single TS afferent fiber stimulation in slices from control and CIH rats we clearly show that CIH reduced the quantal content of the TS-eEPSCs without affecting the quantal size or release probability, suggesting a reduction in the number of active synapses as the mechanism of CIH induced TS-eEPSC depression. In accordance with this concept, the input-output relationship of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH animals. These findings open new perspectives for a better understanding of the mechanisms underlying the synaptic plasticity in the brainstem sensory neurons under challenges such as those produced by CIH in experimental and pathological conditions.

Calorie restriction increases cerebral mitochondrial respiratory capacity in a NO center dot-mediated mechanism: Impact on neuronal survival

Calorie restriction (CR) enhances animal life span and prevents age-related diseases, including neurological decline. Recent evidence suggests that a mechanism involved in CR-induced life-span extension is NO-stimulated mitochondrial biogenesis. We examine here the effects of CR on brain mitochondrial content. CR increased eNOS and nNOS and the content of mitochondria] proteins (cytochrome c oxidase, citrate synthase, and mitofusin) in the brain. Furthermore, we established an in vitro system to study the neurological effects of CR using serum extracted from animals on this diet. In cultured neurons, CR serum enhanced nNOS expression and increased levels of nitrite (a NO product). CR serum also enhanced the levels of cytochrome c oxidase and increased citrate synthase activity and respiratory rates in neurons. CR serum effects were inhibited by L-NAME and mimicked by the NO donor SNAP. Furthermore, both CR sera and SNAP were capable of improving neuronal survival. Overall, our results indicate that CR increases mitochondrial biogenesis in a NO-mediated manner, resulting in enhanced reserve respiratory capacity and improved survival in neurons. (C) 2012 Elsevier Inc. All rights reserved.

Sepsis-Induced Acute Lung Injury (ALI) Is Milder in Diabetic Rats and Correlates with Impaired NFkB Activation

Acute lung injury (ALI) develops in response to a direct insult to the lung or secondarily to a systemic inflammatory response, such as sepsis. There is clinical evidence that the incidence and severity of ALI induced by direct insult are lower in diabetics. In the present study we investigated whether the same occurs in ALI secondarily to sepsis and the molecular mechanisms involved. Diabetes was induced in male Wistar rats by alloxan and sepsis by caecal ligation and puncture surgery (CLP). Six hours later, the lungs were examined for oedema and cell infiltration in bronchoalveolar lavage. Alveolar macrophages (AMs) were cultured in vitro for analysis of I kappa B and p65 subunit of NF kappa B phosphorylation and MyD88 and SOCS-1 mRNA. Diabetic rats were more susceptible to sepsis than non-diabetics. In non-diabetic rats, the lung presented oedema, leukocyte infiltration and increased COX2 expression. In diabetic rats these inflammatory events were significantly less intense. To understand why diabetic rats despite being more susceptible to sepsis develop milder ALI, we examined the NF kappa B activation in AMs of animals with sepsis. Whereas in non-diabetic rats the phosphorylation of I kappa B and p65 subunit occurred after 6 h of sepsis induction, this did not occur in diabetics. Moreover, in AMs from diabetic rats the expression of MyD88 mRNA was lower and that of SOCS-1 mRNA was increased compared with AMs from non-diabetic rats. These results show that ALI secondary to sepsis is milder in diabetic rats and this correlates with impaired activation of NF kappa B, increased SOCS-1 and decreased MyD88 mRNA.

(+)alpha-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo

The vitamin E derivative (+)alpha-tocopheryl succinate (alpha-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RAR alpha transgenic mice, we demonstrated that alpha-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that alpha-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory chain complex I. Moreover, alpha-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for alpha-TOS, as well as mitochondrial respiratory complex I was highlighted as potential target for anticancer therapy. Leukemia (2012) 26, 451-460; doi:10.1038/leu.2011.216; published online 26 August 2011

Effects of Positive End-expiratory Pressure Titration and Recruitment Maneuver on Lung Inflammation and Hyperinflation in Experimental Acid Aspiration-induced Lung Injury

Background: In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Methods: Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Results: Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. Conclusion: In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.

Clinical characteristics and possible phenotypes of an adult severe asthma population

Background: Currently, there are no studies of well-characterized severe asthmatics in Brazil. We aimed to study a population of severe treated asthmatics still uncontrolled to characterize them and define possible phenotypes. Methods: Descriptive cross-sectional outpatient study of severe asthmatics, evaluating functional and inflammatory markers, health-related quality of life, anxiety and depression symptoms, clinical control status, and characteristics related to atopy, age of asthma onset, induced sputum eosinophil levels, and airflow limitation. We also grouped the subgroups characteristics to identify phenotypes. The study is registered on ClinicalTrial.gov NCT 01089322. Results: From 128 eligible patients with severe/uncontrolled asthma, 74 fulfilled the inclusion criteria. The cohort was comprised of 85% women, frequently with a body mass index higher than 31 kg m(-2), atopy (60%), early-onset disease (50%), sputum eosinophilia (80%), comorbidities, and reduced quality of life. Nonatopics had significant higher asthma onset (19 y.a.) and twice level of induced sputum eosinophil. Late-onset patients had significantly less atopy (57%) and higher levels of induced sputum eosinophils. Non-eosinophilics had lower levels of inflammatory markers. Patients with airflow limitation had more intensive care unit admissions (56%) and 1.5 times more airway resistance. Subgroups characteristics identified a priori four well-characterized phenotypes, with 55% presenting sputum eosinophilia. Conclusion: Our data emphasize the high burden of disease, the persistence of inflammation and the existence of clinical possible phenotypes population sharing common features with published cohorts. Despite the necessity of further investigation into pathogenic mechanisms, this study with clinically difficult patient group may help to improve future asthma care. (C) 2011 Elsevier Ltd. All rights reserved.