The effects of air pollution on acute respiratory conditions

OBJECTIVE: Air pollution and its potential health effects are very important worldwide. It is particularly problematic in densely populated cities of developing countries that suffer from a lack of both short- and long-term programmes for air pollution control. We decided to study the short-term effects of air pollution on lung health by assessing the relationship between the levels of six air pollutants and emergency visits for asthma and COPD exacerbations in Tehran, Iran. METHODOLOGY: We monitored the daily attendances for acute respiratory conditions (asthma attacks and COPD exacerbations) to the emergency departments of five major hospitals together with the daily concentrations of six major pollutants during a 5-month period in Tehran. The association between these acute respiratory conditions and the levels of air pollutants was determined by multiple stepwise regression. RESULTS: A correlation was observed between the number of hospital admissions for asthma and the weekly mean concentration of nitrogen dioxide (P < 0.05). The 3-day and 10-day mean concentrations of sulphur dioxide were also found to be directly associated with the number of asthma admissions during this period (P < 0.05). No direct correlation was observed for other variables. CONCLUSION: This study further emphasizes the deleterious effects of air pollution on respiratory health in major populated cities such as Tehran and suggests that increased attention needs to be given to urgent control of air pollution problems.     

Social support, self-efficacy and psychological stress responses among outpatients with diabetes in Yogyakarta, Indonesia

We attempted to study whether social support promotes self-efficacy and reduces stress responses of patients with diabetes in Yogyakarta, Indonesia. Diabetic outpatients at Dr. Sardjito Hospital voluntarily participated in a questionnaire survey. Data from 125 patients were subjected to analysis. The questionnaires included the scales and subscales of social support, self-efficacy, psychological stress response, and demographic measure. Data were analyzed by Spearman's rank correlation test to examine the relationships between parameters, Mann-Whitney U-test and Kruskal-Wallis test to compare the scales by characteristics, and structural equation modeling to explore the best-fit model. This study was performed in September 2003. It was found that augmentation of emotional support to patients significantly increased the 'active coping for the disease' and 'controllability of health', and that 'helplessness' was reduced significantly. Behavioral support affected only 'controllably of health'. Self-efficacy reduced stress response of the patients. It was also found that subjects who received support from their children significantly scored higher in perceived availability of social support than those without support from their children. To know their behavioral support better as well as emotional support may be one area to focus on in improving the health status of people with diabetes in Yogyakarta.     

GM-CSF priming of human monocytes is dependent on ERK1/2 activation

The ability to augment monocyte functions such as TNF-alpha-producing capacities confers a high immunostimulating potential to GM-CSF. In the present investigation, the mechanism of the GMCSF-mediated enhancement of monocyte cytokine production was analysed with regard to the involvement of intracellular signalling pathways. GM-CSF primes human monocytes dose- and time-dependently for enhanced LPS-stimulated TNF-alpha synthesis. Pre-incubation with 10 ng/ml GM-CSF for 6 h before LPS stimulation (10 ng/ml) caused a 3.4 +/- 1.9-fold increase in TNF-alpha release compared to unprimed controls. This was associated with increased phosphorylation of IkappaBalpha and elevated nuclear levels of the NF-kappaB components p50 and p65 and NF-kappaB binding to DNA. LPS-induced AP-1 binding to DNA was also enhanced in GM-CSF-pre-incubated cells. GMCSF treatment also caused a slight increase in TLR4 expression on monocytes while CD14 expression remained unchanged. GM-CSF-priming was unaffected by inhibitors of p38 MAPK (SB203580) and lipoxygenase (NDGA). In contrast, the broad-spectrum tyrosine kinase inhibitor genistein and the MEK-1 inhibitor (PD98059) abrogated GM-CSF priming of TNF-alpha release and activation of both NF-kappaB and AP-1. It is concluded that a tyrosine kinase of the GM-CSF-triggered ERK1/2 pathway augments the LPS-induced NF-kappaB and AP-1 activation.     

Spinal epidural lipomatosis in children with hematologic malignancies

Abnormal fat deposition in the epidural space or spinal epidural lipomatosis (SEL) due to corticosteroid treatment or obesity may cause obstruction to cerebrospinal fluid flow. Little is known about SEL in patients with hematologic malignancies who require frequent lumbar punctures and corticosteroid treatment that places them at risk. Records and radiologic images of patients with SEL and leukemia or non-Hodgkin lymphoma (NHL) treated at a single institution from 1999?C2009 were reviewed. Risk factors were compared with 405 control patients with leukemia. Fourteen patients with leukemia or NHL were diagnosed with SEL. The majority of patients underwent diagnostic imaging after unsuccessful lumbar punctures within 1?month of their primary diagnosis. Prior to SEL diagnosis, all patients received systemic and/or intrathecal corticosteroids. SEL diagnosis led to modification of intrathecal administration in eight patients, including Ommaya reservoir placement in four patients. All patients completed protocol-specified chemotherapy without neurologic symptoms or surgical intervention. Risk factors for developing SEL include older age and high body mass index. Investigation for SEL in leukemia or lymphoma patients with difficult lumbar punctures is warranted. Placement of an Ommaya reservoir may facilitate safe CNS-directed therapy in severely affected patients.     

BH<Subscript>4</Subscript> therapy impacts the nutrition status and intake in children with phenylketonuria: 2-year follow-up

The impact of tetrahydrobiopterin (BH₄) treatment on phenylalanine tolerance, medical-food consumption, and nutrition status in patients with phenylketonuria (PKU) was investigated. Six children (5–12 years) with well-controlled PKU, responding to a BH₄ dose of 20 mg/kg per day, were assessed for 24 months. Mean dietary phenylalanine tolerance increased from 421 ± 128 to 1470 ± 455 mg/day. Height Z scores significantly improved from 0.25 ± 0.99 at baseline to 0.53 ± 1.16 at 24 months (p for trend < 0.001). Patients tolerated more phenylalanine and more intact protein and required less medical food (protein supplement). Improved linear growth and nutrition status was seen over the course of the 24-month follow-up. Due to the variation in phenylalanine tolerance, dietary recommendations should be tailored to the patient’s individual requirements.     

Docosahexaenoic acid status in females of reproductive age with maple syrup urine disease

Individuals with maple syrup urine disease (MSUD) have impaired metabolism of branched-chain amino acids (BCAA) valine, isoleucine, and leucine. Life-long dietary therapy is recommended to restrict BCAA intake and thus prevent poor neurological outcomes and death. To maintain adequate nutritional status, the majority of protein and nutrients are derived from synthetic BCAA-free medical foods with variable fatty acid content. Given the restrictive diet and the importance of omega-3 fatty acids, particularly docosahexaenoic acid (DHA), in neurological development, this study evaluated the dietary and fatty acid status of females of reproductive age with MSUD attending a metabolic camp. Healthy controls of similar age and sex were selected from existing normal laboratory data. Total lipid fatty acid concentration in plasma and erythrocytes was analyzed using gas chromatography–mass spectroscopy. Participants with MSUD had normal to increased concentrations of plasma and erythrocyte alpha linolenic acid (ALA) but significantly lower concentrations of plasma and erythrocyte docosahexaenoic acid (DHA) as percent of total lipid fatty acids compared with controls (plasma DHA: MSUD 1.03 ± 0.35, controls 2.87 ± 1.08; P = 0.001; erythrocyte DHA: MSUD 2.58 ± 0.58, controls 3.66 ± 0.80; P = 0.011). Dietary records reflected negligible or no DHA intake over the 3-day period prior to the blood draw (range 0–2 mg). These results suggest females of reproductive age with MSUD have lower blood DHA concentrations than age-matched controls. In addition, the presence of ALA in medical foods and the background diet may not counter the lack of preformed DHA in the diet. The implications of these results warrant further investigation.     

Brain Volume and Survival from Age 78 to 85: The Contribution of Alzheimer‐Type Magnetic Resonance Imaging Findings

OBJECTIVES: To test the prediction of survival using magnetic resonance imaging (MRI)–derived global and regional brain volumes in subjects aged 78 to 79 without dementia. DESIGN: Observational follow‐up study. SETTING: University teaching hospital. PARTICIPANTS: Participants born in 1921, recruited in 1997/98 to a longitudinal study, who underwent brain MRI in 1999/2000. MEASUREMENTS: Vital status on May 12, 2006, global and regional brain volumes. RESULTS: Thirty‐seven of 98 (34.9%) participants died during follow‐up. After adjustment for cognitive ability at time of MRI examination, childhood intelligence, sex, hypertension, smoking history, obesity, hyperlipidemia, and age at MRI, proportion of intracranial volume occupied by the brain (brain fraction) predicted death before age 85 (P=.04). Participants with brain fraction less than 0.726 had more than twice the relative risk (2.8, 95% confidence interval=1.1–7.3) of death than participants with brain fraction greater 0.726. Lower survival was significantly associated with lower gray matter volumes in bilateral parietal and left frontoparietal areas and with lower white matter volumes in left parietal and right posterior temporal regions. Cox regression analysis showed that parietal white matter volume (P=.003), a subsequent diagnosis of dementia (P<.001), and sex (P=.004) were independent predictors of survival. CONCLUSION: In participants aged 78 to 79, a lower global brain fraction predicted survival to approximately age 85. Smaller regional volumetric brain reductions, seen in Alzheimer's disease (AD), also predicted survival independent of dementia. The presence of prodromal AD probably explain the main findings.     

C-peptide improves neuropathy in type 1 diabetic BB/Wor-rats

BACKGROUND: The spontaneously diabetic BB/Wor-rat is a close model of human type 1 diabetes and develops diabetic polyneuropathy (DPN) similar to that seen in type 1 patients. Here we examine the therapeutic effects of C-peptide, delivered as continuous infusion or once daily subcutaneous injections on established DPN. METHODS: Diabetic rats were treated from four to seven months duration of diabetes with full continuous replacement dose of rat C-peptide via (a) osmopumps (OS), (b) full replacement dose (HSC) or (c) one-third of full replacement dose (LSC) by once daily injections. RESULTS: Diabetic rats treated with OS showed improvements in motor nerve conduction velocity (p < 0.001), sural nerve myelinated fibre number (p < 0.005), size (p < 0.05), axonal area (p < 0.001), regeneration (p < 0.001) and overall neuropathy score (p < 0.001). The progressive decline in sensory nerve conduction velocity was fully prevented. The frequencies of Wallerian degeneration were decreased (p < 0.005). HSC-treated rats showed prevention of further progression of DPN (p < 0.001), whereas LSC-treated rats showed a milder progression of DPN (p < 0.001) compared to untreated rats as assessed by neuropathy score. CONCLUSION: We conclude that (1) C-peptide is effective in the treatment of established DPN, (2) its effect is dose-dependent and (3) replacement by continuous infusion is the most effective administration of C-peptide.     

Type 1 diabetic neuropathy and C-peptide

The most common microvascular diabetic complication, diabetic peripheral polyneuropathy (DPN), affects type 1 diabetic patients more often and more severely. In recent decades, it has become increasingly clear that perpetuating pathogenetic mechanisms, molecular, functional, and structural changes and ultimately the clinical expression of DPN differ between the two major types of diabetes. Impaired insulin/C-peptide action has emerged as a crucial factor to account for the disproportionate burden affecting type 1 patients. C-peptide was long believed to be biologically inactive. However, it has now been shown to have a number of insulin-like glucose-independent effects. Preclinical studies have demonstrated dose-dependent effects on Na+,K(+)-ATPase activity, endothelial nitric oxide synthase (eNOS), and endoneurial blood flow. Furthermore, it has regulatory effects on neurotrophic factors and molecules pivotal to the integrity of the nodal and paranodal apparatus and modulatory effects on apoptotic phenomena affecting the diabetic nervous system. In animal studies, C-peptide improves nerve conduction abnormalities, prevents nodal degenerative changes, characteristic of type 1 DPN, promotes nerve fiber regeneration, and prevents apoptosis of central and peripheral nerve cell constituents. Limited clinical trials have confirmed the beneficial effects of C-peptide on autonomic and somatic nerve function in patients with type 1 DPN. Therefore, evidence accumulates that replacement of C-peptide in type 1 diabetes prevents and even improves DPN. Large-scale food and drug administration (FDA)-approved clinical trials are necessary to make this natural substance available to the globally increasing type 1 diabetic population.