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The current diagnosis of attention deficit hyperactivity disorder (ADHD) is based on history, clinical observation, and behavioral tests. There is a high demand to find biomarkers for the diagnosis of ADHD. The aim of this study is to analyze the serum profiles of several biomarkers, including homocysteine (Hcy), vitamin B12, vitamin D, ferritin, and iron, in a cohort of 133 male subjects (6.5-12.5 years), including 67 individuals with an ADHD diagnosis based on DSM-V criteria and 66 age-matched healthy boys (healthy controls, HC). Assessments for ADHD included the Iowa Conners' Teacher Rating Scale (CPRS) and the ADHDT test, as well as cognitive assessments using the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the TROG-2 language comprehension test. Hcy and iron were quantified using spectrophotometry, while vitamin B12 and total 25-hydroxy vitamin D levels were determined using an electrochemiluminescence immunoassay (ECLIA) and ferritin was measured using a particle-enhanced immunoturbidimetric assay. The results showed significantly increased Hcy levels and decreased vitamin B12 levels in ADHD patients compared to HCs. Multiple logistic regression analysis indicated that Hcy is a potential prognostic indicator for ADHD. These results suggest that elevated homocysteine and decreased vitamin B12 may serve as markers for the diagnosis and prognosis of ADHD.
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BACKGROUND: Although attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, its aetiology remains unclear. We aimed to establish a relationship between ADHD diagnosis and serum levels of glucose, free thyroxine (FT4), and thyroid stimulating hormone (TSH) in primary school aged boys. METHODS: In a cross-sectional study, we enrolled 133 participants aged 6.5-12.5 years, 67 of whom met DSM-5 criteria for ADHD and 66 healthy age-matched boys. The ADHDT test (ADHDT) was used to assess ADHD symptoms and the Wechsler Intelligence Scale for Children - Revised was used to exclude participants with cognitive deficits. The ADHD participants were tested using the Iowa Conners' Teacher Rating Scale. RESULTS: The ADHD participants had lower glucose levels, higher TSH values, and significantly lower FT4 values than the control group. The multiple logistic regression analysis showed that TSH is a parameter that is 2.7% more likely to occur in the ADHD group. We found a significant correlation between the TSH level and the symptoms of hyperactivity (r = 0.318, p = 0.009) and impulsivity (r = 0.275, p = 0.024) as well as between the glucose level and the symptoms of hyperactivity (r = 0.312, p = 0.010). CONCLUSIONS: Certain ADHD symptoms may correlate with certain hormonal patterns. Our results suggest that the likelihood of suffering from ADHD was lower when FT4 levels were elevated. One biochemical parameter that was significantly and independently associated with the diagnosis of ADHD was the serum TSH level. TRIAL REGISTRATION: On June 26, 2018, at its VI session in 2018, the Ethics Committee of the Institute for Mental Health in Belgrade, Serbia, has considered and unanimously approved the conduct of the research, under the number 1704/1.
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Transtorno do Deficit de Atenção com Hiperatividade , Tiroxina , Masculino , Criança , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Estudos Transversais , Projetos Piloto , Tireotropina , GlucoseRESUMO
The recovery of patients after general anesthesia is usually estimated by using clinical scores. Since there is a lack of objective methods for assessing psychomotor recovery, the aim of this study was to evaluate three psychological tests for this purpose. Patients, scheduled for ambulatory gynecological surgery, underwent 3 standard psychological tests before (T1), 15 min after the surgery (T2) and on discharge from the recovery room (T3). The tests used were Wechsler memory scale (test 1, working memory capacity), d2-test (test 2, concentration endurance) and computer-based 4-choice-reaction time (4CRT, test 3, reaction time) as well as Postanesthesia Discharge Scoring System (PADSS). The same test battery was used in healthy female volunteers, all test results were compared at the different time points. In 109 patients, working memory capacity and concentration (tests 1 and 2) decreased, the reaction time (test 3) was prolonged at T2 in comparison with T1 and T3 (P < 0.01). PADSS increased from 8 (T2) to 10 (T3) (medians, P < 0.001). Fifty-seven healthy volunteers demonstrated a practice effect in all 3 tests through the course of the study (P <0.01). 4CRT test had shortest duration and enabled computerized data processing. All three tests objectively assess the recovery of psychomotor function in patients after general anesthesia, the computer-based 4CRT seems to be the most convenient for the clinical routine.
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Período de Recuperação da Anestesia , Anestesia Geral/instrumentação , Procedimentos Cirúrgicos em Ginecologia/instrumentação , Alta do Paciente , Adulto , Computadores , Feminino , Voluntários Saudáveis , Humanos , Memória de Curto Prazo , Pessoa de Meia-Idade , Período Perioperatório , Propofol , Psicometria , Curva ROC , Tempo de Reação , Sala de Recuperação , Sensibilidade e Especificidade , Adulto JovemRESUMO
Traumatic brain injury (TBI) causes substantial neurological disabilities and mental distress. Annual TBI incidence is in magnitude of millions, making it a global health challenge. Categorization of TBI into severe, moderate and mild by scores on the Glasgow coma scale (GCS) is based on clinical grounds and standard brain imaging (CT). Recent research focused on repeated mild TBI (sport and non-sport concussions) suggests that a considerable number of patients have long-term disabling neurocognitive and neurobehavioral sequelae. These relate to subtle neuronal injury (diffuse axonal injury) visible only by using advanced neuroimaging distinguishing microstructural tissue damage. With advanced MRI protocols better characterization of TBI is achievable. Diffusion tensor imaging (DTI) visualizes white matter pathology, susceptibility weight imaging (SWI) detects microscopic bleeding while functional magnetic resonance imaging (fMRI) provides closer understanding of cognitive disorders etc. However, advanced imaging is still not integrated in the clinical care of patients with TBI. Patients with chronic TBI may experience many somatic disorders, cognitive disturbances and mental complaints. The underlying pathophysiological mechanisms occurring in TBI are complex, brain injuries are highly heterogeneous and include neuroendocrine dysfunctions. Post-traumatic neuroendocrine dysfunctions received attention since the year 2000. Occurrence of TBI-related hypopituitarism does not correlate to severity of the GCS scores. Complete or partial hypopituitarism (isolated growth hormone (GH) deficiency as most frequent) may occur after mild TBI equally as after moderate-to-severe TBI. Many symptoms of hypopituitarism overlap with symptoms occurring in patients with chronic TBI, i.e. they have lower scores on neuropsychological examinations (cognitive disability) and have more symptoms of mental distress (depression and fatigue). The great challenges for the endocrinologist are: (1) detection of hypopituitarism in patients with TBI prospectively (in the acute phase and months to years after TBI), (2) assessment of the extent of cognitive impairment at baseline, and (3) monitoring of treatment effects (alteration of cognitive functioning and mental distress with hormone replacement therapy). Only few studies recently suggest that with growth hormone (rhGH) replacement in patients with chronic TBI and with abnormal GH secretion, cognitive performance may not change while symptoms related to depression and fatigue improve. Stagnation in post-TBI rehabilitation progress is recommended as a signal for clinical suspicion of neuroendocrine dysfunction. This remains a challenging area for more research.
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Lesões Encefálicas Traumáticas/patologia , Encéfalo/patologia , Animais , Encéfalo/diagnóstico por imagem , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/patologia , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Testes NeuropsicológicosRESUMO
Objectives: The easily performed "cough-trick" (CT) reduces pain during venipuncture (VP), although the underlying mechanism remains unclear. The aim was to investigate the pain-reducing effect of CT during VP in comparison with two distraction methods, as well as under the influence of naloxone. Methods: 54 healthy male volunteers participated in 3 investigations. Pain during standardized VP with CT was compared to a "weak" distraction (squeezing a rubber ball; investigation 1; n=20) and to a "strong" distraction (inflating a tourniquet to a given pressure; investigation 2; n=21). In investigation 3 (n=13), pain at a VP without intervention was compared to pain at VP with CT under naloxone; pressure pain thresholds before and after naloxone administration were also measured. Pain was assessed using a 100 mm visual analogue scale. Data were compared within each sample using Student's t-test for paired samples. Results: Pain intensity at VP with CT was lower than under "weak" distraction (mean difference 5 mm; 95% CI: 0.5 to 9.6; P=0.03). Pain levels under CT and "strong" distraction were comparable. There was no difference between pain under CT after naloxone infusion and pain without intervention. Pressure pain threshold decreased (mean difference 1 mm; 95% CI: 0.1 to 1.0 mm; P=0.02) after naloxone administration. Conclusion: Pain-reducing effect of CT during VP is superior to that of simple motor distraction and equivalent to a complex distraction method. This might be due to the activation of segmental pain inhibitory pathways during coughing indicated through the lack of pain reduction due to CT under opioid antagonist blockage.
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Tosse , Manejo da Dor/métodos , Dor/prevenção & controle , Dor/fisiopatologia , Flebotomia/efeitos adversos , Adulto , Atenção/fisiologia , Estudos Cross-Over , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Masculino , Naloxona/farmacologia , Dor/etiologia , Adulto JovemRESUMO
OBJECTIVE: Intrinsic imperfections of thyroid hormone replacement therapy may affect long-term general well-being. In patients with Hashimoto thyroiditis (HT), cognitive functioning may be affected via altered thyroid hormones action as well as by the autoimmune process. The aim of this study was to evaluate cognitive function and quality of life (QoL) in patients on long-term levothyroxine replacement for HT in relation to thyroid function tests and TPO (thyroid-peroxidase) antibody (TPOAb) status. DESIGN: Retrospective cross-sectional study. PATIENTS AND MEASUREMENTS: One-hundred-and thirty patients with HT on long-term levothyroxine replacement and 111 euthyroid control subjects. Both groups were divided into two age subgroups, 20-49 years (N = 59 vs N = 79) and > 50 years (N = 71 vs N = 32). Evaluation included biochemical and neuropsychological tests, evaluating attention, global cognitive status, verbal and working memory, executive function, depression and anxiety, and quality of life. We used ANOVA and partial correlations to test for significant associations. RESULTS: FT4 (free-thyroxine), FT3 (free-triiodothyronine) levels and FT3/FT4 ratio were not different between patients and controls. Mean TSH (thyroid-stimulating hormone) was normal in all subjects but significantly higher in the patients (20-49 yrs:3.64 ± 2.74 vs 1.93 ± 1.10, >50 yrs:3.93 ± 2.84 vs 1.91 ± 0.90). Antibodies (TgAb,TPOAb) were higher in patients. Global cognitive function (MMSE-Mini mental state examination), conceptual tracking (TMT-Trail Making Test:A/B), verbal divergent thinking (like Phonemic fluency test), and anxiety and depression scores were significantly worse in patients vs controls. QoL was impaired in patients. there was a significant negative correlation between antibodies (TPOAb, TgAb) and quality in life (total SF36 score). CONCLUSION: Patients on long-term levothyroxine replacement show persistent impairments in both cognitive functioning and general well-being.
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Cognição/fisiologia , Doença de Hashimoto/psicologia , Terapia de Reposição Hormonal/psicologia , Qualidade de Vida/psicologia , Tiroxina/uso terapêutico , Adulto , Atenção/fisiologia , Estudos Transversais , Função Executiva/fisiologia , Feminino , Doença de Hashimoto/tratamento farmacológico , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Retrospectivos , Adulto JovemRESUMO
It has been observed, that patients who were treated medically for dyslipoproteinemia had a potentially lower risk of complications during infection and sepsis, regarding both morbidity and mortality. Aim of this study in experimental sepsis was to elucidate the impact of lipid metabolism modulation by simvastatin, HDL, or bezafibrate, respectively, on the intestinal microcirculation which plays a crucial role in the development of multiple organ failure in sepsis. Experimental sepsis was induced in Lewis rats by intravenous lipopolysaccharide (LPS) administration. Animals were treated with simvastatin, HDL or bezafibrate. By means of intestinal intravital microscopy (IVM), the inflammatory response in the microcirculation was studied by leukocyte adherence assessment (LA) and functional capillary density (FCD) measurements. In addition, plasma levels of pro-inflammatory cytokines were determined. Bezafibrate treatment led to a reduction in leukocyte adherence, improved functional capillary density (FCD), and a reduction in interleukin-1α (IL-1α), tumour necrosis factor α (TNF-α) and granulocyte macrophage colony stimulating factors (GM-CSF) plasma levels in experimental sepsis. Contrary to this, the administration of HDL increased leukocyte adherence as well as the number of rolling leukocytes. Only IL-1α plasma levels were decreased by HDL. No significant changes were observed following simvastatin treatment. In summary, only bezafibrate showed anti-inflammatory effects in endotoxemia. This effect cannot be explained by the HDL-enhancing effect of the bezafibrate, since the direct administration of HDL showed opposite effects. Bezafibrate induced reduction of inflammation in sepsis should be investigated in further studies.
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Anti-Inflamatórios/farmacologia , Bezafibrato/farmacologia , Capilares/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Intestinos/irrigação sanguínea , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas HDL/farmacologia , Microcirculação/efeitos dos fármacos , Sepse/tratamento farmacológico , Sinvastatina/farmacologia , Animais , Velocidade do Fluxo Sanguíneo , Capilares/metabolismo , Capilares/fisiopatologia , Citocinas/sangue , Modelos Animais de Doenças , Mediadores da Inflamação/sangue , Microscopia Intravital , Migração e Rolagem de Leucócitos/efeitos dos fármacos , Lipopolissacarídeos , Masculino , Microscopia de Fluorescência , Microscopia de Vídeo , Ratos Endogâmicos Lew , Fluxo Sanguíneo Regional , Sepse/induzido quimicamente , Sepse/metabolismo , Sepse/fisiopatologiaRESUMO
BACKGROUND: Sepsis involves dysfunctional glucose metabolism. Among patients with sepsis, hyperglycemia is frequent and insulin administration has been evaluated for glycemic control to improve patient outcomes. Only few studies have examined the hyperglycemic microcirculation and the impact of insulin on the microvasculature in sepsis. OBJECTIVE: To study the functional capillary density (FCD) and leukocyte activation within the intestinal microcirculation in endotoxin-induced experimental sepsis. METHODS: In 50 male Lewis rats, endotoxemia was induced with lipopolysaccharide (LPS; 5â¯mg/kg). Low dose (LD) glucose was administered to avoid insulin-induced hypoglycemia. High dose (HD) glucose was administered to model sepsis-related hyperglycemia. Animals in LD and HD glucose groups received an insulin bolus (1.4â¯IU/kg). Two hours after LPS administration, intravital microscopy (IVM) of the terminal ileum was performed, and FCD and leukocyte adherence were measured in a blinded fashion. Blood glucose levels were measured every 30â¯min following the onset of endotoxemia. Plasma samples were collected 3â¯h after the onset of endotoxemia to measure IFN-γ, TNF-α, IL-1α, IL-4, GM-CSF and MCP-1 levels using multiplex bead immunoassay. RESULTS: Endotoxemia significantly reduced FCD and increased leukocyte adherence within the intestinal microvasculature. LD and HD glucose administration combined with insulin improved the FCD and decreased the adherence of leukocytes in endotoxemic animals as did HD glucose administration alone. Consistent with these results, IL-4, IL-1α, GM-CSF and IFN-γ levels were decreased following combined HD glucose and insulin administration in endotoxemic animals. CONCLUSIONS: Insulin administration, as well as an endogenous insulin response triggered by HD glucose administration, improved the FCD and decreased leukocyte activation in endotoxemic rats. The results of this study give insight into the immune and vaso-modulatory role of insulin administration during experimental endotoxemia, and may be extrapolated for clinical sepsis and other critical illnesses with marked microcirculatory dysfunction.
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Glicemia/efeitos dos fármacos , Capilares/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Intestinos/irrigação sanguínea , Microcirculação/efeitos dos fármacos , Sepse/tratamento farmacológico , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Capilares/metabolismo , Capilares/fisiopatologia , Adesão Celular/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Hiperglicemia/fisiopatologia , Mediadores da Inflamação/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Leucócitos/patologia , Lipopolissacarídeos , Masculino , Ratos Endogâmicos Lew , Sepse/sangue , Sepse/induzido quimicamente , Sepse/fisiopatologiaRESUMO
We explored the relationship between acute ischaemic stroke (IS) early functional outcome and serum levels of homocysteine, vitamin B12, and D in a noninterventional prospective clinical study. We enrolled 50 patients with first-ever IS and performed laboratory tests and functional assessment at three time points: on admission and three and six months after stroke. Modified Rankin Scale (mRS), NIHSS scale, and Barthel index (BI) scores were assessed in all participants by trained examiner blinded to laboratory data. Patients did not receive treatment that might alter laboratory data. Admission NIHSS correlated with homocysteine levels (r = 0.304, p < 0.05), B12 level (r = -0.410, p < 0.01), and vitamin D levels (r = -0.465, p < 0.01). Functional outcome measures (BI and mRS) did not significantly correlate with homocysteine and vitamin D3 levels at 3 and 6 months. However, a positive correlation with vitamin B12 levels was detected for BI both at 3 and 6 months and mRS at 6 months. Higher serum vitamin B12 levels were associated with better functional outcome at follow-up.
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Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Homocisteína/sangue , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Vitamina B 12/sangue , Vitamina D/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Técnicas de Apoio para a Decisão , Aparelhos Ortodônticos Fixos , Adolescente , Humanos , PaisRESUMO
INTRODUCTION: It has been assumed that there is causality of the achieved level of functional independence with the degree of preservation of cognitive function in stroke patients. Demographic characteristics may be important for monitoring the achieved level of functional independence. OBJECTIVE: The aim of this study was to examine the relationship of demographic characteristics and functional independence in regard to the level of cognitive impairment in stroke patients. METHODS: The study included 50 stroke patients after rehabilitation, as well as age- and gender-matched 50 subjects selected randomly, according to the demographic characteristics of the studied sample, who in their medical history had no neurological disorders. For the assessment of functional independence, the Functional Independence Measure (FIM) test was used.The general cognition was estimated by the Mini-Mental State Examination (MMSE) test. The statistical analyses included the Mann-Whitney test, for two independent samples, measures of canonical correlation, and χ2 test. RESULTS: There was a statistically significant difference between the groups in relation to risk factors, hypertension and diabetes mellitus type II (p < 0.001); There was a statistically significant difference within the groups in relation to the cognitive impairment in all the examined demographic characteristics (p<0.001); the differences within the groups in relation to the cognitive impairment are present on all subscales of the FIM test (p < 0.05); the differences within the groups in relation to handedness, hemiparesis, show that mild cognitive impairment is more common among left hemiparesis, while a more severe one is more common among right-sided hemiparesis (p < 0.05); More severe cognitive impairment is common among women, the elderly and in persons with lower education (p < 0.05). CONCLUSION: By prevention of risk factors, and prevention of possible cognitive impairment, consequences of stroke can be reduced, the recovery can be made more successful, and quality of life can be improved.
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Cognição/fisiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Reabilitação do Acidente Vascular CerebralRESUMO
OBJECTIVES: Studying the quality of life of people with a spinal cord injury is of great importance as it allows the monitoring of both functioning and adaptation to disability. The aim of this study was to determine the difference between persons with a spinal cord injury involved in sports activities and those not involved in sports activities in relation to their quality of life and the presence of secondary health conditions (pressure ulcers, urinary infections, muscle spasms, osteoporosis, pain, kidney problems-infections, calculosis and poor circulation). METHODS: The study included a total of 44 participants with spinal cord injury-paraplegia of both genders; 26 of them were athletes and 18 were not athletes. The athletes were training actively for the last two years, minimally 2-3 times per week. A specially designed questionnaire, medical documentation and the Spinal Cord Injury Quality of Life Questionnaire (SCI QL-23) were used for research purposes. Chi-square test was used to analyze the differences between the groups, while multiple analysis of variance (MANOVA) was used to determine the differences between the sets of variables. RESULTS: Among the participants, the athletes perceived higher quality of life than the non-athletes (male gender p<0.001 and female gender p<0.05). Regarding secondary health conditions, the athletes reported the presence of less pain (p=0.034) and a subjective feeling of better circulation (p=0.023). CONCLUSION: The implementation of sports activities significantly improves quality of life in the population of people with spinal cord injury-paraplegia. However, sports activities only partially affect secondary health conditions.
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INTRODUCTION: Toll like receptor 4 (TLR4) represents a critical cellular link for endotoxin-induced pathology. The aim of this study was to evaluate the potential role of TLR4 inhibition on the intestinal microcirculation during experimental endotoxemia. MATERIALS AND METHODS: The intestinal microcirculation was studied by intravital microscopy in four groups of Lewis rats (n=10 per group): healthy controls (CON group), endotoxemic animals (15mg/kg lipopolysaccharide, LPS group), endotoxemic animals treated with a TLR4 antagonist (1mg/kg CRX-526, LPS+CRX526 group), and controls treated with CRX-526 (C-CRX526 group). Plasma samples were obtained for cytokine measurements at the end of the experiments. RESULTS: Endotoxemia significantly increased leukocyte adhesion in intestinal submucosal venules (e.g., V1 venules: CON 20.4±6.5n/mm(2), LPS 237.5±36.2n/mm(2), p<0.05) and reduced capillary perfusion of the intestinal wall (e.g., longitudinal muscular layer: CON 112.5±5.9cm/cm(2), LPS 71.3±11.0cm/cm(2), p<0.05) at 2h. TLR4 inhibition significantly reduced endotoxemia-associated leukocyte adhesion (V1 venules: 104.3±7.8n/mm(2)) and improved capillary perfusion (longitudinal muscular layer: 111.0±12.3cm/cm(2)). Cytokine release was not significantly affected. CONCLUSIONS: The TLR4 pathway may be a target in clinical Gram-negative sepsis since administration of the TLR4 antagonist CRX-526 improved intestinal microcirculation parameters in experimental endotoxemia.
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Endotoxemia/tratamento farmacológico , Endotoxemia/patologia , Intestinos/irrigação sanguínea , Microcirculação/efeitos dos fármacos , Receptor 4 Toll-Like/fisiologia , Animais , Capilares/patologia , Adesão Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Glucosamina/análogos & derivados , Glucosamina/química , Bactérias Gram-Negativas , Inflamação , Microscopia Intravital , Leucócitos/citologia , Lipopolissacarídeos/química , Masculino , Perfusão , Ratos , Ratos Endogâmicos Lew , Sepse/microbiologia , Receptor 4 Toll-Like/antagonistas & inibidoresRESUMO
Gut ischemia and reperfusion (IR), e.g. in small bowel transplantation or during resuscitation, may result in severe impairment of the intestinal microcirculation. Potential sequelae are mucosal damage, loss of intestinal barrier function, bacterial translocation, systemic inflammation, multiple organ failure and death. We hypothesized a protective role for extracellular adenosine signalling in intestinal IR injury. Using intravital microscopy we investigated the effects of the adenosine receptor (AR) agonist NECA (5'-N-ethyl carboxamide adenosine) on leukocyte-endothelial interactions and capillary perfusion in the intestinal microcirculation following intestinal IR. Six groups of Lewis rats (n = 44) were studied: control, NECA (5'-N-ethyl carboxamide adenosine), IR (30 minutes of intestinal ischemia, 2 hours of reperfusion), IR + NECA, IR + NECA + MRS1754 (A(2B)AR antagonist), IR + NECA + DPCPX (A(1)AR antagonist). All substances were administered i.v. immediately after declamping of the superior mesenteric artery. Intravital microscopy was performed after 2 hours of reperfusion. Following IR we observed a significant increase of leukocyte adhesion in the intestinal submucosal venules and a reduced capillary perfusion within the muscular layers. NECA reduced leukocyte activation and improved capillary perfusion significantly. Administration of A(2B)AR antagonist completely reversed the NECA effect, whereas A(1)AR inhibition only partially abolished the action of NECA. The data support the hypothesis that adenosine signalling is involved in intestinal IR injury. A(2B)AR may be more important than A(1)AR because A(2B)AR inhibition by MRS1754 completely reversed the effect of the adenosine receptor agonist NECA.
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Intestinos/irrigação sanguínea , Microcirculação/efeitos dos fármacos , Receptores Purinérgicos P1/genética , Receptores Purinérgicos P1/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Endogâmicos Lew , Traumatismo por ReperfusãoRESUMO
The effects of Mg2+ on Ni(2+)-induced epileptiform bursting activity and input membrane resistance during this activity of leech Retzius neurons were examined using intracellular recordings. To induce epileptiform activity, 3 mmol/l NiCl2 was added into superfusing Ringer (Ri) saline. To test for dose-dependence of the effects of Mg2+ on the induced epileptiform activity, MgCl2 was added in concentrations from 1 mmol/l to 20 mmol/l Mg2+ to the Ni(2+)-containing Ri saline. Input membrane resistance (IMR) was measured in standard Ri, Ni2+ Ri and 20 mmol/l Mg2+Ni2+ Ri saline. Superfusion with Ni2+ Ri induced epileptiform bursting activity characterized by generation of paroxysmal depolarization shifts (PDSs). Parameters of epileptiform activity including PDS frequency, PDS duration, PDS amplitude and the number of spikes/PDS were measured. Magnesium suppressed Ni(2+)-induced epileptiform activity, significantly reducing values of all parameters observed in a concentration-dependent manner. The highest concentration applied of 20 mmol/l Mg2+ completely eliminated epileptiform activity. To test for the effect of Mg2+ on membrane conductance during bursting, IMR was measured. Magnesium significantly increased IMR during bursting suppression.
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Sanguessugas/citologia , Magnésio/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Animais , Células Cultivadas , Neurônios/citologia , Níquel/farmacologiaRESUMO
BACKGROUND: Dehydroepiandrosterone (DHEA) was shown to improve the immune function and survival in experimental sepsis. This study examined the effect of DHEA on intestinal leukocyte recruitment during experimental sepsis, considering factors of gender (male, female and ovariectomized female animals) and combined treatment using orthovanadate (OV) in two models of sepsis. METHODOLOGY/FINDINGS: Male rats underwent colon ascendens stent peritonitis (CASP) or endotoxemia. DHEA was administered after induction of experimental sepsis. Changes in leukocyte adherence and capillary perfusion (measured as intestinal functional capillary density - FCD) were assessed using intravital microscopy. While DHEA increased baseline leukocyte adherence in control animals, DHEA reduced leukocyte adherence and increased FCD in male animals with CASP. These effects were also observed in DHEA-treated ovariectomized female rats with CASP. Similarly, the administration of DHEA reduced the number of adherent leukocytes to intestinal venules by 30% in the endotoxemia model. The combined treatment of DHEA and OV significantly reduced adherence of leukocytes to intestinal venules and improved FCD. CONCLUSIONS: Our results indicate that DHEA is able to reduce intestinal leukocyte recruitment induced by experimental sepsis. Combination of DHEA with OV inhibits leukocyte adherence to intestinal endothelium, similar to what is achieved by the single administration of DHEA but with significantly improved FCD. These findings suggest a potential role for DHEA and OV in clinical sepsis.
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Quimiotaxia de Leucócito/efeitos dos fármacos , Desidroepiandrosterona/administração & dosagem , Intestinos/irrigação sanguínea , Intestinos/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Sepse/tratamento farmacológico , Vanadatos/administração & dosagem , Animais , Capilares/efeitos dos fármacos , Capilares/imunologia , Capilares/fisiopatologia , Adesão Celular/efeitos dos fármacos , Citocinas/sangue , Modelos Animais de Doenças , Quimioterapia Combinada , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Feminino , Mediadores da Inflamação/sangue , Intestinos/imunologia , Intestinos/fisiopatologia , Leucócitos/imunologia , Leucócitos/metabolismo , Masculino , Microcirculação/efeitos dos fármacos , Ovariectomia , Ratos , Ratos Endogâmicos Lew , Sepse/sangue , Sepse/imunologia , Sepse/fisiopatologia , Fatores Sexuais , Circulação Esplâncnica/efeitos dos fármacosRESUMO
Some open access journals are believed to have devaluated the highly respected image of the scientific journal. This has been, it is claimed, verified. Yet the project we believe failed and we show why we think that it failed. The study itself was badly conducted and the report, which Science published, was itself a perfect example of "bad science". If the article that was published in Science were to be taken as one of the "test" articles and Science as a victim journal (a perfect control though), the study would show the opposite of what author concluded in his paper: 100% of the controls (normal non-open access journals, in the present study this was Science) accepted the "bait" paper for publication, while in the experimental group only about 60% (open access journals) accepted the bait paper for publication. The conclusion is that, with respect to non-open access and open access, the probability of accepting pseudoscience is well in favor of this being done by a non-open access journal. Since this interpretation is based on some facts that were not included in the project itself, the only warranted result of this study would be that nothing could be concluded from it. It is concluded that the method that Bohannon used was heavily flawed and in addition immoral; that the report that was published by Science was inconclusive and that the act of publishing such report cannot be morally justified either. Various methods to improve the quality of published papers exist but scientific fraud with "good intentions" as a method to promote scientific publishing should be avoided.