Cinnamaldehyde increases the susceptibility of quorum-sensing-mediated biofilms to conventional antibiotics

The role of bacterial communication, also known as quorum sensing is an important mechanism in biofilm formation which is fundamental to the development of anti-biofilm strategies. In this current study, the synergy between a quorum sensing inhibitor (cinnamaldehyde) and two antibiotics (ceftazidime and levofloxacin) was evaluated in an attempt to develop a strategy for biofilm disruption using the high-throughput minimum biofilm eliminating concentration (MBEC) assay. Klebsiella pneumoniae and Proteus mirabilis biofilms of initial broth suspensions of 108 colony forming units (CFU) per mL, cultivated on the pegs of the MBEC device were challenged with 5120 µg/ml of ceftazidime and levofloxacin in a double dilution assay in the presence of 500 µM cinnamaldehyde. The minimum inhibitory concentrations (MIC) in the presence of cinnamaldehyde for ceftazidime and levofloxacin were 0.125% (640 µg/mL) and 0.0625% (320 µg/mL) respectively with no significant bacterial growth on LB agar. The MBECs for ceftazidime and levofloxacin were above 5120 and 2560 µg/mL respectively which yielded over 70% reduction in both Klebsiella pneumoniae and Proteus mirabilis biofilms. The above results indicate the possibility that the synergy between antimicrobial agents may lead to biofilm eradication.

Habitual coffee and tea drinkers experienced increases in blood pressure after consuming low to moderate doses of caffeine; these increases were larger upright than in the supine posture

Caffeine users have been encouraged to consume caffeine regularly to maintain their caffeine tolerance and so avoid caffeine’s acute pressor effects. In controlled conditions complete caffeine tolerance to intervention doses of 250 mg develops rapidly following several days of caffeine ingestion, nevertheless, complete tolerance is not evident for lower intervention doses. Similarly complete caffeine tolerance to 250 mg intervention doses has been demonstrated in habitual coffee and tea drinkers’ but for lower intervention doses complete tolerance is not evident. This study investigated a group of habitual caffeine users following their self-determined consumption pattern involving two to six servings daily. Cardiovascular responses following the ingestion of low to moderate amounts caffeine (67, 133 and 200 mg) were compared with placebo in a double-blind, randomised design without caffeine abstinence. Pre-intervention and post-intervention (30 and 60 min) 90 s continuous cardiovascular recordings were obtained with the Finometer in both the supine and upright postures. Participants were 12 healthy habitual coffee and tea drinkers (10 female, mean age 36). Doses of 67 and 133 mg increased systolic pressure in both postures while in the upright posture diastolic pressure and aortic impedance increased while arterial compliance decreased. These vascular changes were larger upright than supine for 133 mg caffeine. Additionally 67 mg caffeine increased dp/dt and indexed peripheral resistance in the upright posture. For 200 mg caffeine there was complete caffeine tolerance. Cardiovascular responses to caffeine appear to be associated with the size of the intervention dose. Habitual tea and coffee drinking does not generate complete tolerance to caffeine as has been previously suggested. Both the type and the extent of caffeine induced cardiovascular changes were influenced by posture.

Conhecimentos, atitudes e práticas de médicos e enfermeiros, dos cuidados de saúde primários, no tratamento da obesidade : existe uma associação com as práticas pessoais de actividade física?

Resumo - As doenças crónicas não transmissíveis são uma ameaça crescente à Saúde Pública em Portugal. As principais causas de mortalidade e morbilidade são doenças relacionadas com os estilos de vida, hábitos alimentares e de actividade física. Os Cuidados de Saúde Primários estão na linha da frente para dar resposta a estas patologias. Os profissionais de saúde, nomeadamente médicos e enfermeiros, sentem dificuldades para as tratar, como a falta de tempo, de conhecimentos e de confiança para o fazer, bem como uma descrença na efectividade das suas intervenções no âmbito da mudança comportamental destes pacientes. A dificuldade em referenciar estes pacientes a outros profissionais, especializados, como os nutricionistas e os fisiologistas do exercício, implica dotar médicos e enfermeiros com as competências básicas de aconselhamento alimentar e de actividade física, bem como serem capazes de assumirem uma atitude centrada no paciente e motivadora da mudança comportamental. O objectivo deste estudo é avaliar os conhecimentos, atitudes e práticas no tratamento da obesidade e sua associação com o nível de actividade física reportado por médicos e enfermeiros. Este é um estudo observacional, transversal, que recorre à aplicação de um questionário de resposta directa. --------Abstract - Non communicable chronic diseases are increasingly relevant public health threats. The main causes of mortality and morbidity in Portugal are lifestyle, food and exercise habits, related diseases. Primary health care services are in the front line to adress this pathologies. Health care professionals, namely physicians and nurses, face numerous barriers like reduced consultation time, knowledge and confidence to deal with this problems, as well as a disbelief in the efectiviness of their intervention in patients health behaviour change. The inhability to reference this patients to nutrition and exercise specialists, increases the need to give physicians and nurses the adequate nutrition and exercise basic counselling skills, as well as promoting a patient centred attitude that enables them to increase patients motivation to health behaviour change. The study sought to assess the nutrition knowledge, atittudes and practice and its associations with self - reported personal physical activity habits of primary health care professionals. This is a descriptive, cross- sectional stu

Activity-Dependent Neurorehabilitation Beyond Physical Trainings: "Mental Exercise" Through Mirror Neuron Activation

The activity dependent brain repair mechanism has been widely adopted in many types of neurorehabilitation. The activity leads to target specific and non-specific beneficial effects in different brain regions, such as the releasing of neurotrophic factors, modulation of the cytokines and generation of new neurons in adult hood. However physical exercise program clinically are limited to some of the patients with preserved motor functions; while many patients suffered from paralysis cannot make such efforts. Here the authors proposed the employment of mirror neurons system in promoting brain rehabilitation by "observation based stimulation". Mirror neuron system has been considered as an important basis for action understanding and learning by mimicking others. During the action observation, mirror neuron system mediated the direct activation of the same group of motor neurons that are responsible for the observed action. The effect is clear, direct, specific and evolutionarily conserved. Moreover, recent evidences hinted for the beneficial effects on stroke patients after mirror neuron system activation therapy. Finally some music-relevant therapies were proposed to be related with mirror neuron system.

Potential Therapeutic Effects of Physical Exercise for Bipolar Disorder

Cognitive deficits are observed in a variety of domains in patients with bipolar disorder (BD). These deficits are attributed to neurobiological, functional and structural brain factors, particularly in prefrontal cortex. Furthermore, cortical alterations in each phase (mania/hypomania, euthymia and depression) are also present. A growing basis of evidence supports aerobic exercise as an alternative treatment method for BD symptoms. Its benefits for physical health in healthy subjects and some psychiatric disorders are fairly established; however evidence directly addressed to BD is scant. Lack of methodological consistency, mainly related to exercise, makes it difficult accuracy and extrapolation of the results. Nevertheless, mechanisms related to BD physiopathology, such as hormonal and neurotransmitters alterations and mainly related to brain-derived neurotrophic factors (BDNF) can be explored. BDNF, specially, have a large influence on brain ability and its gene expression is highly responsive to aerobic exercise. Moreover, aerobic exercise trough BDNF may induce chronic stress suppression, commonly observed in patients with BD, and reduce deleterious effects caused by allostatic loads. Therefore, it is prudent to propose that aerobic exercise plays an important role in BD physiopathological mechanisms and it is a new way for the treatment for this and others psychiatric disorders.

Effects of the Mediterranean diet and exercise in subjects with coronary artery disease

Introduction The association of the Mediterranean diet and exercise appears to have a protective role, reducing cardiovascular risk. This study investigated the effects of education sessions on the Mediterranean diet and an exercise program in modifying eating behaviors, body composition and abdominal fat. Methods An experimental study was performed on 20 subjects with known coronary heart disease randomly assigned to experimental (n=10) and control (n=10) groups. Both groups received education sessions on the Mediterranean diet, but the experimental group also followed an eight-week program of specific exercises. A semiquantitative food frequency questionnaire was administered to analyze food intake, bioimpedance was used to measure weight, fat mass and lean mass, and waist circumference was measured to calculate waist-to-height ratio. Results After eight weeks, protein (p<0.05) and cholesterol (p<0.05) intake in the experimental group had decreased significantly compared with the control group. Between the beginning and end of the study, there were significant decreases in the control group in carbohydrate (p<0.05) and saturated fat intake (p<0.05). In both groups the percentage of total fat (p<0.05) and fat mass (p<0.05) was significantly decreased. In the experimental group the waist-to-height ratio was significantly reduced (p<0.05). Conclusion The Mediterranean diet reduced carbohydrate and saturated fat intake, reflected in reduced fat mass. The association of the exercise program showed additional benefits in reduction of protein and cholesterol intake and abdominal fat.

A mathematical model to describe fat oxidation kinetics during graded exercise.

PURPOSE: The purpose of this study was to develop a mathematical model (sine model, SIN) to describe fat oxidation kinetics as a function of the relative exercise intensity [% of maximal oxygen uptake (%VO2max)] during graded exercise and to determine the exercise intensity (Fatmax) that elicits maximal fat oxidation (MFO) and the intensity at which the fat oxidation becomes negligible (Fatmin). This model included three independent variables (dilatation, symmetry, and translation) that incorporated primary expected modulations of the curve because of training level or body composition. METHODS: Thirty-two healthy volunteers (17 women and 15 men) performed a graded exercise test on a cycle ergometer, with 3-min stages and 20-W increments. Substrate oxidation rates were determined using indirect calorimetry. SIN was compared with measured values (MV) and with other methods currently used [i.e., the RER method (MRER) and third polynomial curves (P3)]. RESULTS: There was no significant difference in the fitting accuracy between SIN and P3 (P = 0.157), whereas MRER was less precise than SIN (P < 0.001). Fatmax (44 +/- 10% VO2max) and MFO (0.37 +/- 0.16 g x min(-1)) determined using SIN were significantly correlated with MV, P3, and MRER (P < 0.001). The variable of dilatation was correlated with Fatmax, Fatmin, and MFO (r = 0.79, r = 0.67, and r = 0.60, respectively, P < 0.001). CONCLUSIONS: The SIN model presents the same precision as other methods currently used in the determination of Fatmax and MFO but in addition allows calculation of Fatmin. Moreover, the three independent variables are directly related to the main expected modulations of the fat oxidation curve. SIN, therefore, seems to be an appropriate tool in analyzing fat oxidation kinetics obtained during graded exercise.

Sub-cortical and brainstem sites associated with chemo-stimulated increases in ventilation in humans.

We investigated the neural basis for spontaneous chemo-stimulated increases in ventilation in awake, healthy humans. Blood oxygen level dependent (BOLD) functional MRI was performed in nine healthy subjects using T2 weighted echo planar imaging. Brain volumes (52 transverse slices, cortex to high spinal cord) were acquired every 3.9 s. The 30 min paradigm consisted of six, 5-min cycles, each cycle comprising 45 s of hypoxic-isocapnia, 45 s of isooxic-hypercapnia and 45 s of hypoxic-hypercapnia, with 55 s of non-stimulatory hyperoxic-isocapnia (control) separating each stimulus period. Ventilation was significantly (p<0.001) increased during hypoxic-isocapnia, isooxic-hypercapnia and hypoxic-hypercapnia (17.0, 13.8, 24.9 L/min respectively) vs. control (8.4 L/min) and was associated with significant (p<0.05, corrected for multiple comparisons) signal increases within a bilateral network that included the basal ganglia, thalamus, red nucleus, cerebellum, parietal cortex, cingulate and superior mid pons. The neuroanatomical structures identified provide evidence for the spontaneous control of breathing to be mediated by higher brain centres, as well as respiratory nuclei in the brainstem.

Trazodone increases arousal threshold in obstructive sleep apnoea.

A low arousal threshold is believed to predispose to breathing instability during sleep. The present authors hypothesised that trazodone, a nonmyorelaxant sleep-promoting agent, would increase the effort-related arousal threshold in obstructive sleep apnoea (OSA) patients. In total, nine OSA patients, mean+/-sd age 49+/-9 yrs, apnoea/hypopnoea index 52+/-32 events.h(-1), were studied on 2 nights, one with trazodone at 100 mg and one with a placebo, in a double blind randomised fashion. While receiving continuous positive airway pressure (CPAP), repeated arousals were induced: 1) by increasing inspired CO(2) and 2) by stepwise decreases in CPAP level. Respiratory effort was measured with an oesophageal balloon. End-tidal CO(2 )tension (P(ET,CO(2))) was monitored with a nasal catheter. During trazodone nights, compared with placebo nights, the arousals occurred at a higher P(ET,CO(2)) level (mean+/-sd 7.30+/-0.57 versus 6.62+/-0.64 kPa (54.9+/-4.3 versus 49.8+/-4.8 mmHg), respectively). When arousals were triggered by increasing inspired CO(2) level, the maximal oesophageal pressure swing was greater (19.4+/-4.0 versus 13.1+/-4.9 cm H(2)O) and the oesophageal pressure nadir before the arousals was lower (-5.1+/-4.7 versus -0.38+/-4.2 cm H(2)O) with trazodone. When arousals were induced by stepwise CPAP drops, the maximal oesophageal pressure swings before the arousals did not differ. Trazodone at 100 mg increased the effort-related arousal threshold in response to hypercapnia in obstructive sleep apnoea patients and allowed them to tolerate higher CO(2) levels.

Y1 receptor knockout increases nociception and prevents the anti-allodynic actions of NPY.

OBJECTIVE: Recent pharmacologic studies in our laboratory have suggested that the spinal neuropeptide Y (NPY) Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY. To rule out off-target effects, the present study used Y1-receptor-deficient (-/-) mice to further explore the contribution of Y1 receptors to pain modulation. METHODS AND RESULTS: Y1(-/-) mice exhibited reduced latency in the hotplate test of acute pain and a longer-lasting heat allodynia in the complete Freund's adjuvant (CFA) model of inflammatory pain. Y1 deletion did not change CFA-induced inflammation. Upon targeting the spinal NPY systems with intrathecal drug delivery, NPY reduced tactile and heat allodynia in the CFA model and the partial sciatic nerve ligation model of neuropathic pain. Importantly, we show for the first time that NPY does not exert these anti-allodynic effects in Y1(-/-) mice. Furthermore, in nerve-injured CD1 mice, concomitant injection of the potent Y1 antagonist BIBO3304 prevented the anti-allodynic actions of NPY. Neither NPY nor BIBO3304 altered performance on the Rotorod test, arguing against an indirect effect of motor function. CONCLUSION: The Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY.

Taurine increases hippocampal neurogenesis in aging mice.

Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging.