Energy and protein intake and its relationship with pulmonary function in chronic obstructive pulmonary disease (COPD) patients

Chronic Obstructive Pulmonary Disease (COPD) is a public health problem worldwide. Increased energy and protein needs, decreased energy and protein intake are common in COPD patients. Adequate intake is essential to improve pulmonary function and immune system, prevention of weight loss and maintaining muscle mass and strength. Assessment of energy and protein intake and its relationship with pulmonary function in COPD patients was performed in this study. The study group included 63 COPD patients. For all subjects, evaluation of energy and protein intake by Food Frequency Questionnaire (FFQ) and 24-hour recall, spirometry for measuring pulmonary function and determining disease severity were performed. The subjects were divided into three groups based on disease severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages. Relationship between energy and protein intake with pulmonary function was assessed. Energy and protein intake were lower than the calculated energy and protein demand for all groups. Significant relationship was found between the amount of protein intake extrapolated from food frequency questionnaire with Forced Vital Capacity (FVC) (r=0.2, P=0.02) and Vital Capacity (VC) (r=0.3, P=0.008). The results of the study suggest that accurate evaluation of protein and energy intake and requirements should be included in the goals of medical treatment of COPD patients.     

Corticospinal function in severe brain injury assessed using magnetic stimulation of the motor cortex in man.

We have assessed corticospinal function in 19 post-coma patients severely brain-injured by anoxia or physical trauma. Eleven patients were unresponsive (Category 1) and eight demonstrated minimal, non-verbal responses to simple commands (Category 2). Motor evoked potentials (MEPs) could be elicited in hand and leg muscles in nine Category 1 and all eight Category 2 patients in response to transcranial magnetic stimulation (TMS). In comparison with normal subjects, threshold to TMS was significantly elevated in Category 1 but not in Category 2. Central conduction times were within the normal range except for two patients (one in each category) in whom they were prolonged. The variability in MEP amplitude to constant TMS was not significantly different from normal in either category. The size of MEPs recorded simultaneously in different hand muscles were correlated in all three groups. The presence of H-reflexes in hand muscles was associated with an absence of MEPs or a high threshold to TMS. Variability of MEPs was substantially greater than that of H-reflexes. We conclude that brain injury of a severity that may preclude consciousness and voluntary movement does not invariably predicate a non-functional motor cortex and corticospinal system.     

Central chemosensitivity and breathing asleep in unilateral medullary lesion patients: comparisons to animal data.

The rostro-ventrolateral medulla (RVLM) is a site of chemosensitivity in animals; such site(s) have not been defined in humans. We studied the effect of unilateral focal lesions in the rostrolateral medulla (RLM) of man, on the ventilatory CO(2) sensitivity and during awake and sleep breathing. Nine patients with RLM lesions (RLM group), and six with lesions elsewhere (non-RLM group) were studied. The ventilatory CO(2) sensitivity was lower in the RLM compared with the non-RLM group (mean (S.D.), RLM, 1.4 (0.9), non-RLM 3.0 (0.6) L min(-1) mmHg(-1)). In both groups resting breathing was normal. During sleep all RLM patients had frequent arousals, four had significant sleep disordered breathing (SDB), only one non-RLM patient had SDB. Our findings in humans resemble those in animals with focal RVLM lesions. This review provides evidence that in humans there is an area of chemosensitivity in the RLM. We propose that in humans, dorsal displacement of the RVLM area of chemosensitivity in animals, arises from development of the olive plus the consequences of the evolution of the cerebellum/inferior peduncle.     

The Feyrter cell in hypoxia

Moosavi, H., Smith, P., and Heath, D. (1973).Thorax,28, 729-741. The Feyrter cell in hypoxia. It is clear that the bronchial tree has functions beyond the mere conduction of air into the alveolar spaces. In addition to the familiar ciliated respiratory epithelial cells the bronchus is lined by non-ciliated Clara and Feyrter cells. In the present study we investigated the histological and ultrastructural features of the bronchial argyrophilic (Feyrter) cell of the neonatal rat. On electron microscopy this cell has all the features of an APUD cell which is associated with the secretion of polypeptide hormones. It bears a close ultrastructural resemblance to the chief cell of the carotid body and shows the same changes in its membrane-bound bodies on exposure to chronic hypoxia. These are strong grounds for believing that the bronchi and bronchioles have either a chemoreceptor or an endocrine function in the neonatal period.     

l-carnitine protects rat hepatocytes from oxidative stress induced by T-2 toxin

Context: Oxidative stress and mitochondrial dysfunction are thought to be the main mechanism of T-2 toxin toxicity. T-2 toxin is the most potent trichothecene mycotoxin which is present in agricultural products. L-carnitine, besides its anti-oxidative properties, facilitates the transportation of long-chain fatty acids in to mitochondrial matrix. Objective: In this study we tested whether L-carnitine, an antioxidant and a facilitator for long-chain fatty acid transportation across mitochondrial membranes, could protect rat hepatocytes against toxicity induced by T-2 toxin. Materials and methods: L-carnitine in low and high doses (50 and 500?mg/kg) was administered for five consecutive days to male Wistar rats. Hepatocytes were isolated and freshly exposed to appropriate concentration of T-2 toxin for 2?h followed by oxidative stress and cell death evaluations. Results: Glutathione depletion, ROS overproduction and mitochondrial membrane potential collapse were determined under T-2 toxin exposure. Pretreatment with L-carnitine particularly at high-dose reduced toxicity and prevented the hepatocytes from abnormal caspase-3 activity and apoptosis. Conclusion: Low toxicity of L-carnitine and its mitochondrial protective effects promises an effective way to reduce or prevent the toxicity induced by certain environmental pollutants, including T-2 toxin.     

The role of PI3/Akt pathway in the protective effect of insulin against corticosterone cell death induction in hippocampal cell culture

Corticosterone induces neuroanatomical and neurochemical changes in the hippocampus that are associated with cognitive impairments. In the present study corticosterone induced cell death in primary hippocampal neurons cultured in Neurobasal + B27 medium. Insulin prevents neuronal cell death induced in a concentration dependent manner. The neuroprotective effect of insulin was reversed by LY294002, a phosphatidylinositol 3'-kinase (PI3 kinase) inhibitor, whereas the mitogen-activated protein kinase (MAPK) inhibitor PD98059, an upstream blocker of MAPK had no effect. Western blot analyses showed that insulin induced the activation of protein kinase B (Akt). These results suggest that insulin can prevent neuronal cell death induced by corticosterone in hippocampal neurons by modulating the activity of the PI3 kinase/Akt pathway.     

3-Hydrogenkwadaphnin from Dendrostellera lessertii induces differentiation and apoptosis in HL-60 cells

3-Hydrogenkwadaphnin (3-HK) is a new diterpene ester, recently isolated from the leaves of Dendrostellera lessertii with potent anti-tumoral and anti-metastatic activities. Herein, we report that 3-HK induces differentiation and apoptosis in HL-60 cells. The drug at 2.5 - 40 nM inhibited proliferation of HL-60 cells after 24 - 96 h of treatment. Cell viability was also decreased by 57 % after 96 h treatment with the drug. NBT reducing assay and phagocytic activity revealed that the inhibition of proliferation is associated with differentiation especially toward macrophages-like morphology. Indeed, the drug at 2.5 - 10 nM induced differentiation by 5 - 49 % in HL-60 cells. Acridine orange/ethidium bromide (AO/EtBr) double staining and DNA fragmentation assays revealed that apoptosis occurred after differentiation of HL-60 cells. Guanosine at 50 microM decreased the apoptotic cell death and the differentiation caused by the drug. Therefore, GTP depletion, as a result of inhibition of inosine monophosphate dehydrogenase (IMPDH), is considered as one of the main reasons for differentiation and apoptotic cell death by this new drug.     

Additive effect of dextromethorphan on the inhibitory effect of anti-NT4 on morphine tolerance

It has been proposed that opioid tolerance is a model of neuronal plasticity similar to learning and memory. Recent evidence suggests that neurotrophins may be involved in synaptic development and plasticity. Observations indicate that neurotrophin 4 (NT4) is required for the synaptic plasticity mediating both tolerance and memory. Also there are lines of evidence to indicate that NMDA receptors are involved in the neural plasticity underlying the development of opiate tolerance. Neurotrophins affect central transmission postsynaptically by enhancing NMDA receptor responsiveness. So we used the clinically available NMDA receptor antagonist, dextromethorphan, and the neurotrophin 4 antibody, anti-NT4, concomitantly and alone to investigate their effects on morphine tolerance. Tolerance was induced by injecting morphine (7 and 10 mg/kg i.p.) once per day for 4 days. Anti-NT4 (1 microg/rat i.c.v.) was administered 15 min before morphine. Results showed that chronic concomitant treatment of anti-NT4 with morphine in both doses inhibited the development of morphine tolerance. Also acute treatment of anti-NT4 significantly reversed the tolerance that was induced by morphine 7 mg/kg but failed to reverse the tolerance of morphine 10 mg/kg. Dextromethorphan in both doses (10 or 30 mg/kg) has an additive effect on the inhibitory effect of anti-NT4 on the reversal of morphine tolerance (7 mg/kg). These findings provide additional support for the hypothesis that NMDA receptor and NT4 may be involved in neural plasticity underlying opiate tolerance.