Nutritional intervention in patients with juvenile systemic lupus erythematosus: protective effect against the increase in fat mass.

Patients with juvenile systemic lupus erythematosus (JSLE) usually have an increase in fat mass and decrease in lean body mass. The purpose of this study was to assess the effect of a nutritional intervention on changes in body composition and food consumption of adolescents with JSLE compared with a control group and its variation over time and to assess the association of total fat mass with clinical parameters. This randomized controlled study evaluated 31 girls. Body composition and food intake were evaluated at baseline. The patients were randomly allocated into a nutritional intervention group and a control group. The intervention group received monthly nutritional guidelines for 9 months. After this period, evaluations were repeated. The carbohydrates intake decreased in the intervention group compared with the control group (p = 0.031) at the end of the study period. Additionally, a significant decrease was observed in the intake of energy (p = 0.023), carbohydrates (p = 0.031), protein (p = 0.024), total fat (p = 0.027), saturated fat (p = 0.012), and trans fat (p = 0.029) in the intervention group between baseline and the end of the study. There was an average increase of 3.7 kg (95% CI 0.8-6.5) in the total fat mass (p = 0.013) and 0.36 kg/m2 (95% CI 0.10-0.62) in the appendicular fat mass (p = 0.007) in the control group during the study period; this finding was not observed in the intervention group. A 9-month nutritional intervention in JSLE patients improved their eating habits and protected against the excessive gain of weight and body fat.

Lipid profile among girls with systemic lupus erythematosus.

The aim of the study was to describe biomarkers of lipid metabolism associated with increased cardiovascular risk and their correlation with disease variables and markers of inflammation in adolescent females with systemic lupus erythematosus (SLE). This cross-sectional controlled study evaluated 33 adolescent females with juvenile SLE and 33 healthy controls. Anthropometric data, SLE disease activity index (SLEDAI), medications, proteinuria, ultra-sensitive C-reactive protein (us-CRP), lipid profile (total cholesterol, LDL-c, HDL-c and triglycerides), apolipoproteins A and B (Apo A-I and B), paraoxonase, and myeloperoxidase were evaluated. Median age of the patients and the median disease duration were 16.7 years and 54 months, respectively. SLEDAI scores above 4 were observed in 11 (33.3 %) patients. Moreover, 12 (36.4 %) patients were overweight, and 5 (15.2 %) had low height for age ratios. Dyslipidemia was observed in 13 (39.4 %) patients and in 7 (21.2 %) controls with a decrease in HDL-c concentrations in SLE patients even after adjustment for their nutritional status. In the group with SLE, us-CRP concentrations were inversely correlated with LDL-c/ApoB ratio (p = 0.031). After multivariate regression analysis, the SLE group showed lower concentration of Apo A-I and a decreased LDL-c/ApoB ratio. SLE adolescent females with low disease activity, with preserved kidney function and on low dose of corticosteroids, regardless of nutritional status and food intake, have proatherogenic lipid biomarkers, which may contribute to an increased atherosclerotic risk.

Adsorption characteristics of cellulase and ß-glucosidase on Avicel, pretreated sugarcane bagasse, and lignin.

Although adsorption is an essential step in the enzymatic hydrolysis of lignocellulosic materials, literature reports controversial results in relation to the adsorption of the cellulolitic enzymes on different biomasses/pretreatments, which makes difficult the description of this phenomenon in hydrolysis mathematical models. In this work, the adsorption of these enzymes on Avicel and sugarcane bagasse pretreated by the hydrothermal bagasse (HB) and organosolv bagasse (OB) methods was evaluated. The results have shown no significant adsorption of ß-glucosidase on Avicel or HB. Increasing solids concentration from 5% (w/v) to 10% (w/v) had no impact on the adsorption of cellulase on the different biomasses if stirring rates were high enough (>100 rpm for Avicel and >150 rpm for HB and OB). Adsorption equilibrium time was low for Avicel (10 Min) when compared with the lignocellulosic materials (120 Min). Adsorption isotherms determined at 4 and 50 °C have shown that for Avicel there was a decrease in the maximum adsorption capacity (Emax) with the temperature increase, whereas for HB increasing temperature increased Emax . Also, Emax increased with the content of lignin in the material. Adsorption studies of cellulase on lignin left after enzymatic digestion of HB show lower but significant adsorption capacity (Emax = 11.92 ± 0.76 mg/g).

Increased susceptibility of brain acetylcholinesterase activity to methylmalonate in young rats with renal failure.

Tissue methylmalonic acid (MMA) accumulation is the biochemical hallmark of methylmalonic acidemia. Clinically, the disease is characterized by progressive neurological deterioration and renal failure, whose pathophysiology is still undefined. In the present study we investigated the effect of acute MMA administration on some important parameters of brain neurotransmission in cerebral cortex of rats, namely Na(+), K(+)-ATPase, ouabain-insensitive ATPases and acetylcholinesterase activities, in the presence or absence of kidney injury induced by gentamicin administration. Initially, thirty-day old Wistar rats received one intraperitoneal injection of saline or gentamicin (70 mg/kg). One hour after, the animals received three consecutive subcutaneous injections of MMA (1.67 µmol/g) or saline, with an 11 h interval between each injection. One hour after the last injection the animals were killed and the cerebral cortex isolated. MMA administration by itself was not able to modify Na(+), K(+)-ATPase, ATPases ouabain-insensitive or acetylcholinesterase activities in cerebral cortex of young rats. In rats receiving gentamicin simultaneously with MMA, it was observed an increase in the activity of acetylcholinesterase activity in cerebral cortex, without any alteration in the activity of the other studied enzymes. Therefore, it may be speculated that cholinergic imbalance may play a role in the pathogenesis of the brain damage. Furthermore, the pathophysiology of tissue damage cannot be exclusively attributed to MMA toxicity, and control of kidney function should be considered as a priority in the management of these patients, specifically during episodes of metabolic decompensation when MMA levels are higher.

Antidepressant-like effect of extract from Polygala paniculata: involvement of the monoaminergic systems.

CONTEXT: Polygala paniculata Linnaeus (Polygalaceae) has shown neuroprotective effects, but there is no report about its antidepressant potential. OBJECTIVE: The antidepressant-like effect of the hydroalcoholic extract from P. paniculata and some of the possible mechanisms involved in this effect were investigated in forced swimming test (FST). MATERIALS AND METHODS: Mice received extract by oral route and were submitted to FST and open-field test. Animals were forced to swim and the total immobility time was registered (6-min period). A reduction in the immobility time is considered an antidepressant-like effect. In order to investigate the involvement of the monoaminergic systems, mice were treated with pharmacological antagonists before administration of the extract. RESULTS: The acute administration of the hydroalcoholic extract from P. paniculata produced an antidepressant-like effect, since it significantly reduced the immobility time in FST (0.01-30 mg/kg) as compared to control group, without changing locomotor activity. Pretreatment of mice with yohimbine (1 mg/kg, i.p., α2-adrenoceptor antagonist), propranolol (1 mg/kg, i.p., ß-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., dopamine D1 receptor antagonist) or sulpiride (50 mg/kg, i.p., dopamine D2 receptor antagonist) prevented the antidepressant-like effect of the extract in FST (30 mg/kg). Moreover, ketanserin (5 mg/kg, i.p., preferential 5-HT(2A) receptor antagonist) enhanced the effect of the extract in FST. DISCUSSION AND CONCLUSION: The results of the present study indicate that the extract from P. paniculata has an antidepressant-like action that is likely mediated by an interaction with the serotonergic (5-HT2A receptors), noradrenergic (α2 and ß-receptor) and dopaminergic (D1 and D2 receptors) systems.

Analysis of the vaccination status of older adults.

OBJECTIVE: To describe the sociodemographic characteristics, functional capacity and vaccination status of older adults, and to verify the factors associated with the incomplete vaccination status and the absence of the vaccination card. METHOD: Cross-sectional and analytical study conducted with older adults living in the city of Uberaba (MG). The following analyzes were carried out: descriptive, bivariate and multinomial logistic regression (p<0.05). RESULTS: A total of 576 older adults participated. Most of them were women, in the 70-80 age group, with partner, low education and income, living with someone, independent in basic activities of daily living and with partial dependence on instrumental activities. The highest percentage was for older adults who had incomplete vaccination status, especially regarding the absence of immunization for Hepatitis B. Individual monthly income < 1 minimum wage (p=0.002) and single-person housing arrangement (p=0.010) were associated with the incomplete vaccination status, and the absence of the vaccination card, with the lowest level of education (p=0.039). CONCLUSION: Low income and education, as well as living alone, are factors associated with inadequate vaccination status among older adults in the community. The need for primary care nurses to develop strategies to increase vaccination coverage among older adults with these characteristics is emphasized.

Antidepressant-Like Effects of Chronic Guanosine in the Olfactory Bulbectomy Mouse Model.

Major depressive disorder (MDD) leads to pervasive changes in the health of afflicted patients. Despite advances in the understanding of MDD and its treatment, profound innovation is needed to develop fast-onset antidepressants with higher effectiveness. When acutely administered, the endogenous nucleoside guanosine (GUO) shows fast-onset antidepressant-like effects in several mouse models, including the olfactory bulbectomy (OBX) rodent model. OBX is advocated to possess translational value and be suitable to assess the time course of depressive-like behavior in rodents. This study aimed at investigating the long-term behavioral and neurochemical effects of GUO in a mouse model of depression induced by bilateral bulbectomy (OBX). Mice were submitted to OBX and, after 14 days of recovery, received daily (ip) administration of 7.5 mg/kg GUO or 40 mg/kg imipramine (IMI) for 45 days. GUO and IMI reversed the OBX-induced hyperlocomotion and recognition memory impairment, hippocampal BDNF increase, and redox imbalance (ROS, NO, and GSH levels). GUO also mitigated the OBX-induced hippocampal neuroinflammation (IL-1, IL-6, TNF-α, INF-γ, and IL-10). Brain microPET imaging ([18F]FDG) shows that GUO also prevented the OBX-induced increase in hippocampal FDG metabolism. These results provide additional evidence for GUO antidepressant-like effects, associated with beneficial neurochemical outcomes relevant to counteract depression.

Caffeine prevents neurodegeneration and behavioral alterations in a mice model of agitated depression.

Longitudinal and some experimental studies have showed the potential of caffeine to counteract some depressive behaviors and synaptic dysfunctions. In this study, we investigated the potential of caffeine in preventing behavioral outcomes, neurodegeneration and synaptic proteins alterations in a mice model of agitated depression by bilateral olfactory bulbectomy (OB). For this purpose, bulbectomized mice received caffeine (0.3 g/L and 1.0 g/L, drinking water), during the active cycle, for seven weeks (two before the surgery and throughout five weeks after OB). Caffeine prevented OB-induced hyperactivity and recognition memory impairment and rescue self care and motivational behavior. In the frontal cortex, bulbectomized mice presented increase in the adenosine A1 receptors (A1R) and GFAP, while adenosine A2A receptors (A2AR) increased in the hippocampus and striatum and SNAP-25 was decreased in frontal cortex and striatum. Caffeine increased A1R in the striatum of bulbectomized mice and in SHAM-water group caffeine increased A2AR in the striatum and decreased SNAP-25 in the frontal cortex. Astrogliosis observed in the polymorphic layer of the dentate gyrus of OB mice was prevented by caffeine as well as the neurodegeneration in the striatum and piriform cortex. Based on these behavioral and neurochemical evidences, caffeine confirms its efficacy in preventing neurodegeneration associated with memory impairment and may be considered as a promising therapeutic tool in the prophylaxis and/or treatment of depression.

The effect of voluntary wheel running on the antioxidant status is dependent on sociability conditions.

Voluntary wheel running is widely used as a physical activity (PA) model in rodents, but most studies investigate the beneficial effects of this intervention in socially isolated mice. Social isolation stress (SIS) is associated with vulnerability to oxidative stress and reduced mitochondrial activity. Thus, the aim of this study was to investigate the effects of free access to a running wheel for 21 days on the various markers of the cellular redox/antioxidant status as well as mitochondrial function of mice subjected to SIS or maintained in groups of 3 in the homecage. SIS increased thiobarbituric acid reactive substance (TBARS) levels in the cerebral cortex, and PA intervention was not able to reverse such alteration. PA reduced TBARS levels in the liver of grouped mice and gastrocnemius of socially isolated mice. PA increased nonprotein thiol (NPSH) levels in the cerebral cortex of grouped mice. Furthermore, socially isolated mice presented lower glutathione peroxidase (GPx) activity in the cerebellum and gastrocnemius, and glutathione reductase (GR) activity in the cerebral cortex and liver. By contrast, SIS induced higher GPx activity in the cerebral cortex and heart. PA reduced GPx (cerebral cortex) and GR (cerebral cortex and liver) activities of socially isolated mice. SIS caused higher activity of mitochondrial complexes I and II in the cerebral cortex, and the PA paradigm was not able to alter this effect. Interestingly, the PA produced antidepressant-like effect at both SIS and control groups. In conclusion, the results showed the influence of SIS for the effects of PA on the antioxidant status, but not on the mitochondrial function and emotionality.

Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: evidence for the involvement of the serotonergic and noradrenergic systems.

We have recently shown that the hexanic extract from leaves of Schinus molle produces antidepressant-like effects in the tail suspension test in mice. This study investigated the antidepressant-like effect of the ethanolic extract from aerial part of S. molle in the forced swimming test and tail suspension test in mice, two predictive models of depression. Moreover, we investigated the antidepressant potential of rutin, a flavonoid isolated from the ethanolic extract of this plant and the influence of the pretreatment with the inhibitors of serotonin or noradrenaline synthesis, p-chlorophenylalanine methyl ester (PCPA) and alpha-methyl-p-tyrosine (AMPT), respectively in the antidepressant-like effect of this flavonoid. The administration of the ethanolic extract produced a reduction in the immobility time in the tail suspension test (dose range 600-1000 mg/kg, p.o.), but not in the forced swimming test. It also produced a reduction in the ambulation in the open-field test in mice not previously habituated to the arena, but no effect in the locomotor activity in mice previously habituated to the open-field. The administration of rutin reduced the immobility time in the tail suspension test (0.3-3 mg/kg, p.o.), but not in the forced swimming test, without producing alteration in the locomotor activity. In addition, pretreatment of mice with PCPA (100 mg/kg, i.p., for 4 consecutive days) or AMPT (100 mg/kg, i.p.) prevented the anti-immobility effect of rutin (0.3 mg/kg, p.o.) in the tail suspension test. The results firstly indicated the antidepressant-like effect of the ethanolic extract of S. molle in the tail suspension test may be dependent on the presence of rutin that likely exerts its antidepressant-like effect by increasing the availability of serotonin and noradrenaline in the synaptic cleft.

Interaction of zinc with antidepressants in the tail suspension test.

The antidepressant-like effect of zinc has been shown in several animal models of depression. In this study, zinc chloride (ZnCl2) was given alone or in combination with different classes of antidepressants by oral route (p.o.) to mice and the behavioral response in the tail suspension test (TST), a predictive test of antidepressant action, was investigated. ZnCl2 at a dose of 10 and 30 mg/kg, p.o., reduced the immobility time in the TST, without affecting the locomotor activity in open-field test. The antidepressants fluoxetine, paroxetine, imipramine, desipramine and bupropion produced a significant reduction in the immobility time in TST at the doses of 10, 1, 1, 1 and 10 mg/kg, p.o., respectively. The combined treatment of sub-effective doses of ZnCl2 (1 mg/kg) with sub-effective doses of fluoxetine (5 mg/kg), paroxetine (0.1 mg/kg), desipramine (0.1 mg/kg), imipramine (0.1 mg/kg) or bupropion (1 mg/kg) induced a significant reduction in the immobility time in the TST when compared with the groups treated with ZnCl2 or with antidepressants alone. The treatment with sub-effective doses of ZnCl2 and antidepressants alone or in combination did not affect the locomotion in open-field test, except that desipramine alone reduced the ambulation. The results first indicate that ZnCl2 administered by p.o. route produces an antidepressant-like effect in the TST. Moreover, synergistic effects of zinc with antidepressants were shown in the TST, suggesting that an improvement in the response to the antidepressant therapy occurs when zinc is combined with different classes of antidepressants.

Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: evidence for the involvement of the monoaminergic system.

Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the treatment of depression. In this study, the antidepressant-like effect of the hexanic extract from leaves of S. molle was investigated in the mouse tail suspension test (TST), a predictive model of depression. The immobility time in the TST was significantly reduced by the extract (dose range 30-600 mg/kg, p.o.), without accompanying changes in ambulation when assessed in an open-field test. The efficacy of extract was found to be comparable to that of fluoxetine (10 mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a D(2) receptor antagonist). It may be concluded that the hexanic extract of S. molle produces an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. These results provide evidence that the extract from S. molle shares with established antidepressants some pharmacological effects, at least at a preclinical level.

Olfactory bulbectomy in mice triggers transient and long-lasting behavioral impairments and biochemical hippocampal disturbances.

Major depressive disorder (MDD) is a neuropsychiatric disease that is associated with profound disturbances in affected individuals. Elucidating the pathophysiology of MDD has been frustratingly slow, especially concerning the neurochemical events and brain regions associated with disease progression. Thus, we evaluated the time-course (up to 8weeks) behavioral and biochemical effects in mice that underwent to a bilateral olfactory bulbectomy (OBX), which is used to modeling depressive-like behavior in rodents. Similar to the symptoms in patients with MDD, OBX induced long-lasting (e.g., impairment of habituation to novelty, hyperactivity and an anxiety-like phenotype) and transient (e.g., loss of self-care and motivational behavior) behavioral effects. Moreover, OBX temporarily impaired hippocampal synaptosomal mitochondria, in a manner that would be associated with hippocampal-related synaptotoxicity. Finally, long-lasting pro-oxidative (i.e., increased levels of reactive oxygen species and nitric oxide and decreased glutathione levels) and pro-inflammatory (i.e., increased levels of pro-inflammatory cytokines IL-1, IL-6, TNF-α and decreased anti-inflammatory cytokine IL-10 levels) effects were induced in the hippocampus by OBX. Additionally, these parameters were transiently affected in the posterior and frontal cortices. This study is the first to suggest that the transient and long-lasting behavioral effects from OBX strongly correlate with mitochondrial, oxidative and inflammatory parameters in the hippocampus; furthermore, these effects show a weak correlation with these parameters in the cortex. Our findings highlight the underlying mechanisms involved in the biochemical time course of events related to depressive behavior.

Analysis of the vaccination status of older adults / Análisis de la situación vacunal de los adultos mayores / Análise da situação vacinal de idosos

ABSTRACT Objective: To describe the sociodemographic characteristics, functional capacity and vaccination status of older adults, and to verify the factors associated with the incomplete vaccination status and the absence of the vaccination card. Method: Cross-sectional and analytical study conducted with older adults living in the city of Uberaba (MG). The following analyzes were carried out: descriptive, bivariate and multinomial logistic regression (p<0.05). Results: A total of 576 older adults participated. Most of them were women, in the 70-80 age group, with partner, low education and income, living with someone, independent in basic activities of daily living and with partial dependence on instrumental activities. The highest percentage was for older adults who had incomplete vaccination status, especially regarding the absence of immunization for Hepatitis B. Individual monthly income < 1 minimum wage (p=0.002) and single-person housing arrangement (p=0.010) were associated with the incomplete vaccination status, and the absence of the vaccination card, with the lowest level of education (p=0.039). Conclusion: Low income and education, as well as living alone, are factors associated with inadequate vaccination status among older adults in the community. The need for primary care nurses to develop strategies to increase vaccination coverage among older adults with these characteristics is emphasized.

RESUMEN Objetivo: Describir las caracteristicas sociodemograficas, la capacidad funcional y la situacion vacunal de los adultos mayores y comprobar los factores asociados con la situacion vacunal incompleta y la ausencia del carnet de vacunacion. Método: Se trata de un estudio transversal y analitico llevado a cabo con adultos mayores residentes en el area urbana de Uberaba, Minas Gerais, mediante un analisis descriptivo, bivariado y de regresion logistica multinomial (p<0,05). Resultados: Participaron 576 adultos mayores. Predominaban las mujeres de edad avanzada, 70├80 anos, con pareja, bajo nivel de escolaridad e ingresos, que vivian solas, independientes en las actividades basicas de la vida diaria y parcialmente dependientes de las actividades instrumentales. El porcentaje mas alto correspondia a los adultos mayores que tenian un estado de vacunacion incompleto, especialmente en lo que respecta a la ausencia de inmunizacion contra la hepatitis B. Los ingresos mensuales individuales ≤ 1 salario minimo (p=0,002) y la disposicion de una vivienda unifamiliar (p=0,010) estaban asociados con el estado de vacunacion incompleta, y la ausencia del carnet de vacunacion, con un nivel de escolaridad bajo (p=0,039). Conclusión: Los ingresos bajos y la educacion, asi como el hecho de vivir solo, son factores que estan asociados a un estado de vacunacion inadecuado en adultos mayores de la comunidad. Es importante que el enfermero de atencion primaria desarrolle estrategias para aumentar la cobertura de vacunacion entre los adultos mayores con dichas caracteristicas.

RESUMO Objetivo: Descrever as caracteristicas sociodemograficas, a capacidade funcional e a situacao vacinal de idosos, e verificar os fatores associados a situacao vacinal incompleta e a ausencia do cartao de vacinas. Método: Estudo transversal e analitico conduzido com idosos residentes na zona urbana de Uberaba (MG). Procedeu-se as analises descritiva, bivariada e regressao logistica multinomial (p<0,05). Resultados: Participaram 576 idosos. Predominaram os idosos do sexo feminino, na faixa etaria de 70├80 anos, com companheiro, baixa escolaridade e renda, que moravam acompanhados, independentes nas atividades basicas da vida diaria e com dependencia parcial nas atividades instrumentais. O maior percentual foi para os idosos que possuiam situacao vacinal incompleta, sobretudo em relacao a ausencia da imunizacao para Hepatite B. Foram associados a situacao vacinal incompleta a renda individual mensal ≤ 1 salario minimo (p=0,002) e o arranjo de moradia unipessoal (p=0,010); e a ausencia do cartao de vacinas, a menor escolaridade (p=0,039). Conclusão: As baixas renda e escolaridade, bem como residir sozinho, sao fatores associados as situacoes vacinais inadequadas dos idosos da comunidade. Ressalta-se a necessidade de que o enfermeiro da atencao primaria desenvolva estrategias para aumentar a cobertura vacinal entre os idosos com essas caracteristicas.

Locus of pain control associated with medication adherence behaviors among patients after an orthopedic procedure.

BACKGROUND: Locus of pain control (LPC) is characterized by the behavior of people coping with their health problems, as a result of their own actions (internal control) or external factors or other people (external control). This parameter can be associated with medication adherence, in addition to other psychosocial factors that may also influence this behavior. This study was performed to investigate the influence of the LPC on medication adherence in patients undergoing an orthopedic procedure. SUBJECTS AND METHODS: We conducted a prospective cohort study on patients who attended an orthopedic clinic for arthroscopy treatment. The patients' LPC and pain intensity data were obtained on the day of admission through the use of the LPC scale and the visual analog scale (VAS), respectively, both being validated tools. After arthroscopic surgery, the patients received drug prescriptions and were reassessed after 15 days regarding treatment adherence, using the Morisky test. A P-value <0.05 was considered statistically significant. RESULTS: We assessed 79 individuals from both the internal LPC group (n=35) and external LPC group (n=44) and found that there were no group differences in sex, affected limb, cause of injury, repetitive strain injury, duration of pain, or pain intensity. However, there was a higher proportion of patients in the external LPC group that adhered to the prescribed medication compared with the internal LPC group (P<0.01). CONCLUSION: The results showed that among patients who underwent an orthopedic procedure, there was a higher adherence rate to prescribed medication in the external LPC group compared with the internal LPC group.

Evidence for the involvement of 5-HT1A receptor in the acute antidepressant-like effect of creatine in mice.

Creatine was previously shown to produce an antidepressant-like effect in the tail suspension test through a modulation of the dopaminergic system. In this study, the mechanisms underlying its antidepressant-like effect were further evaluated by investigating the involvement of the serotonergic system in its effect. The anti-immobility effect of creatine (1mg/kg) was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA; 100mg/kg, i.p., for 4 consecutive days, an inhibitor of serotonin (5-HT) synthesis). Creatine (0.01 mg/kg, sub-effective dose) in combination with sub-effective doses of WAY100635 (0.1mg/kg, s.c., a 5-HT1A receptor antagonist), 8-OH-DPAT (0.1mg/kg, i.p., a 5-HT1A receptor agonist) or selective serotonin reuptake inhibitors fluoxetine (5mg/kg, p.o.), paroxetine (0.1mg/kg, p.o.), citalopram (0.1mg/kg, p.o.) and sertraline (3mg/kg, p.o.) reduced the immobility time in the tail suspension test as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an interaction with 5-HT1A receptors. Of note, the present results also indicate that creatine improves the effectiveness of the selective serotonin reuptake inhibitors, a finding that may have therapeutic implications for the treatment of depressive disorders.

The activation of α1-adrenoceptors is implicated in the antidepressant-like effect of creatine in the tail suspension test.

The antidepressant-like activity of creatine in the tail suspension test (TST) was demonstrated previously by our group. In this study we investigated the involvement of the noradrenergic system in the antidepressant-like effect of creatine in the mouse TST. In the first set of experiments, creatine administered by i.c.v. route (1 µg/site) decreased the immobility time in the TST, suggesting the central effect of this compound. The anti-immobility effect of peripheral administration of creatine (1 mg/kg, p.o.) was prevented by the pretreatment of mice with α-methyl-p-tyrosine (100 mg/kg, i.p., inhibitor of tyrosine hydroxylase), prazosin (1 mg/kg, i.p., α1-adrenoceptor antagonist), but not by yohimbine (1 mg/kg, i.p., α2-adrenoceptor antagonist). Creatine (0.01 mg/kg, subeffective dose) in combination with subeffective doses of amitriptyline (1 mg/kg, p.o., tricyclic antidepressant), imipramine (0.1 mg/kg, p.o., tricyclic antidepressant), reboxetine (2 mg/kg, p.o., selective noradrenaline reuptake inhibitor) or phenylephrine (0.4 µg/site, i.c.v., α1-adrenoceptor agonist) reduced the immobility time in the TST as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an activation of α1-adrenoceptor and that creatine produces synergistic effects in the TST with antidepressants that modulate noradrenaline transporter, suggesting that an improvement in the response to the antidepressant therapy may occur when creatine is combined with these antidepressants. Furthermore, the synergistic effect of creatine (0.01 mg/kg, p.o.) and reboxetine (2 mg/kg, p.o.) combination was abolished by the α1-adrenoceptor antagonist prazosin, indicating that the antidepressant-like effect of combined therapy is likely mediated by an activation of α1-adrenoceptor.

The antidepressant-like effect of physical activity on a voluntary running wheel.

PURPOSE: Physical activity is currently being considered an effective alternative in the treatment of depression. At the preclinical level, the voluntary running wheel is a useful method of increasing physical activity in rodents and induces an antidepressant-like effect in some behavioral paradigms. METHODS: This study investigated the effect of physical activity on a voluntary running wheel in mice submitted to the forced swimming test (FST) and tail suspension test, two predictive tests of antidepressant properties. Moreover, the influence of the inhibition of serotonin and noradrenaline synthesis as well as the inhibition of protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CAMK-II) activity by pharmacological agents in the antidepressant-like action of physical activity was investigated. RESULTS: Physical activity on a voluntary running wheel by 21 d produced a reduction in the immobility time in the FST and tail suspension test, without producing alteration on locomotor activity in the open-field test. The antidepressant-like effect in the FST elicited by physical activity lasted for 7 d after removal of the running wheel. The anti-immobility effect of physical activity was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (100 mg·kg, i.p., once a day, for four consecutive days, inhibitor of serotonin synthesis), α-methyl-p-tyrosine (100 mg·kg, i.p., an inhibitor of noradrenaline and dopamine synthesis), H-89 (1 µg per site, i.c.v., a PKA inhibitor), and KN-62 (1 µg per site, i.c.v., a CAMK-II inhibitor). CONCLUSIONS: Taken together, these results first suggest that the effect of physical activity on the FST is dependent on either the increase in the bioavailability of monoamines in the synaptic cleft or an activation of intracellular signaling pathways mediated by PKA and CAMK-II.

Fluoxetine modulates hippocampal cell signaling pathways implicated in neuroplasticity in olfactory bulbectomized mice.

The olfactory bulbectomy (OB) animal model of depression is a well-established model that is capable of detecting antidepressant activity following chronic drug therapy, and the surgery results in behavioral and biochemical changes that are reminiscent of various symptoms of depression. In the present study, we investigated the degree to which 14 days of p.o. administration of the classic antidepressant fluoxetine (10mg/kg) were able to reverse OB-induced changes in behavior (namely, hyperactivity in the open-field test and reduced motivational and self-care behaviors in the splash test) and in the activation of hippocampal cell signaling pathways that are thought to be involved in synaptic plasticity. OB caused significant increases in ERK1 and CREB (Ser(133)) phosphorylation and in the expression of BDNF immunocontent, all of which were prevented by fluoxetine administration. Moreover, fluoxetine administration also caused a significant decrease in ERK2 phosphorylation in mice that had undergone OB. Neither Akt nor GSK-3ß phosphorylation was altered in any experimental condition. In conclusion, the present study shows that OB can induce significant behavioral changes that are accompanied by the activation of hippocampal signaling pathways, namely the ERK1/CREB/BDNF pathway, which is involved in the synaptic plasticity. Conversely, fluoxetine prevented these OB-induced behavioral changes and avoided the activation of ERK1/CREB/BDNF in the hippocampus. Taken together, our results extend the data from the existing literature regarding OB-induced behavioral and neurochemical changes, and suggest a possible underlying mechanism that can account for the antidepressant effect of fluoxetine in this model.

Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L.

The aim of this study was to investigate the antidepressant-like effect of fractions from Rosmarinus officinalis L.: ethyl acetate 1 and 2 (AcOEt1 and 2), hexane (HEX), ethanolic (ET), and essential oil-free (EOF) fractions, as well as essential oil, the isolated compounds carnosol and betulinic acid in the tail suspension test, a predictive test of antidepressant activity. Swiss mice were acutely administered by oral route (p.o.) with fractions, essential oil or isolated compounds, 60 min before the tail suspension test or open-field test. All of them produced a significant antidepressant-like effect: AcOEt1, ET, EOF fractions and essential oil (0.1-100mg/kg, p.o); HEX (0.1-10mg/kg, p.o) and AcOEt2 fraction (0.1-1mg/kg, p.o), carnosol (0.01-0.1mg/kg, p.o.) isolated from the HEX fraction and betulinic acid (10mg/kg, p.o.), isolated from the AcOEt1 and AcOEt2 fractions. No psychostimulant effect was shown in the open-field test, indicating that the effects in the tail suspension test are specific. This study suggests that carnosol and betulinic acid could be responsible for the anti-immobility effect of extracts from R. officinalis.