Assessing exposure to diesel exhaust particles: a case study

The assessment of the vehicular contributions to urban pollution levels is of particular importance given the current interest in the possible adverse health effects. This study focused on human exposure to diesel-engine-derived particulate matter. Diesel vehicles are known to emit fine particulate matter (PM2.5) containing carcinogens such as polycyclic aromatic hydrocarbons (PAHs), and have therefore received considerable attention. In this study, the physical (mass and number concentration, and size distribution) and chemical (PAHs) properties were investigated at a major bus interchange in Singapore, influenced only by diesel exhausts. Number concentration and size distribution of particles were determined in real time, while the mass concentrations of PM2.5, and PAHs were measured during operating and nonoperating hours. The average mass concentrations of PM2.5 and PAHs increased by a factor of 2.34 and 5.18, respectively, during operating hours. The average number concentration was also elevated by a factor of 5.07 during operating hours. This increase in the concentration of PM2.5 particles and their chemical constituents during operating hours was attributable to diesel emissions from in-use buses based on the particle size analysis, correlation among PAHs, and the commonly used PAHs diagnostic ratios. To evaluate the potential health threat due inhalation of air pollutants released from diesel engines, the incremental lifetime cancer risk was also calculated for a maximally exposed individual. The findings indicate that the air quality at the bus interchange poses adverse health effects.     

The prevalence and associations of sleep disturbances in patients with systemic lupus erythematosus

The aim of this study was to analyze sleep complaints in patients with systemic lupus erythematosus (SLE) and to determine its prevalence and associations. Fifty outpatients with SLE and an equal number of age- and sex-matched controls were included in the study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) in both cases and controls. Depressed mood, functional disability and pain severity were assessed in patients using standardized questionnaires. Disease severity, cumulative damage and presence of fibromyalgia were determined by clinical examination. Bivariate associations between sleep quality and disease-related variables as well as demographic variables were calculated. A series of hierarchical regression analyses were computed to determine the independent determinant of sleep quality. PSQI scores were significantly higher in patients with SLE. Prevalence of sleep disturbance was 62%. Functional disability, disease activity and depressed mood correlated positively with sleep disturbances. 36% of the patients satisfied ACR criteria for fibromyalgia. In multiple regression analyses disease activity was found to be an independent determinant of sleep quality. The prevalence of poor sleep quality in patients with SLE was higher than it is generally perceived to be. Functional disability, disease activity and depressed mood contributed significantly to sleep disturbances in SLE.     

Change in lipid profile in celiac disease: beneficial effect of gluten-free diet

Purpose

Celiac disease is associated with hypocholesterolemia, which is thought to contribute to a favorable cardiovascular risk profile. This led to suggestions that the diagnosis of celiac disease and its treatment with a gluten-free diet may result in elevation of the serum cholesterol level and worsen this risk profile. However, no study proves this in adults. We therefore examined the effect of a gluten-free diet on the lipid profile in patients with celiac disease.

Subjects and methods

We identified 132 patients with celiac disease who adhered to a gluten-free diet and had lipid profiles performed before and after a median of 20.5 months on the diet. The patients lacked diseases that may affect serum lipids.

Results

There were significant increases in total cholesterol and high-density lipoprotein (HDL) cholesterol (P < .0001) but not low-density lipoprotein (LDL) cholesterol (P = .06). The LDL/HDL ratio decreased by 0.36 ± 0.7 (P < .0001). Both men and women had a significant increase in total cholesterol and HDL and a significant decrease in the LDL/HDL ratio. Only men had increases in LDL (P = .02). The greatest increase in lipid values was seen in those with the lowest initial values. The largest increase in HDL was seen in subjects with more severe disease as indicated by low albumin level and presence of total villous atrophy.

Conclusions

Diagnosis of celiac disease and its treatment with a gluten-free diet resulted in improvement in the lipoprotein profile, which included an increase in HDL and a decrease in the LDL/HDL ratio.     

Cadmium-induced Oxidative Stress and Evaluation of Embilica Officinalis and Stressroak in Broilers

Cadmium (Cd) toxicity was studied in broilers, and efficacy of Emblica officinalis (500 ppm in feed), vitamin E (300 ppm in feed), and stressroak (1 g/kg feed) were evaluated for prophylactic and therapeutic management of Cd toxicity. One-day-old male broiler chicks were randomly divided into eight groups consisting of 10 chicks in each. Groups 1 and 2 were maintained as plain control and Cd (100 ppm in feed) toxic control (for six weeks). Groups 3, 4, and 5 were maintained on a combination of Cd (100 ppm in feed) and Emblica officinalis, vitamin E, and stressroak for six weeks. Groups 6, 7, and 8 were maintained with Cd for the first four weeks and on Emblica officinalis, vitamin E, and stressroak during the subsequent two weeks without Cd. Body weights, feed consumed, Feed conversion ratio (FCR), and glulathione (GSH) were significantly (P<0.05) decreased, whereas the activities of antioxidant enzymes (catalase and Superoxide dismutase (SOD)) and concentration of Thiobarbituric acid reacting substances (TBARS) were significantly (P<0.05) increased in toxic control group. After treatment with Emblica officinalis, vitamin E, and stressroak in groups 6, 7, and 8 during last two weeks and discontinuation of Cd, the parameters revealed improvement. From this study, it is concluded that Cd induces toxicity by oxidative stress, and supplementing Emblica officinalis, vitamin E, and stressroak in feed is useful in preventing and treating the toxicity.     

Spontaneous left atrial echo contrast,mitral annular systolic velocity,and left atrial appendage late emptying velocity in predicting improvement of left atrial function after percutaneous balloon mitral valvuloplasty

Background

Thromboembolic events are the major cause of morbidity and mortality in patients with mitral stenosis (MS). This study aims to investigate left atrial spontaneous echo contrast (LA SEC), mitral annular systolic velocity (Sa‐wave), left atrial appendage (LAA) late emptying velocity (LAAEV), LAA filling velocity (LAAFV) pre‐ and postpercutaneous balloon mitral valvuloplasty (PBMV) for MS. This also aims to study the association of LA SEC with inflammatory marker, high‐sensitivity C‐reactive protein (hs‐CRP) in MS.

Methods

The study population consisted of 100 patients with symptomatic MS with sinus rhythm who underwent PBMV. Transthoracic echo (TTE), tissue Doppler imaging (TDI), and transesophageal echo (TEE) examinations were carried out before and 14 days following PBMV. High‐sensitivity C‐reactive protein (hs‐CRP) was measured at the time of admission.

Results

The mean age was 33.2 ± 10.3 years with female preponderance (71%). There was a decrease in SEC grading, (pre‐PBMV 2.8 ± 0.9 and post‐PBMV 0.4 ± 0.1; P < .01), increase in LAAEV (pre‐PBMV 23.0 ± 7.9 cm/s and post‐PBMV 40.9 ± 8.4 cm/s; P < .01), and LAAFV (pre‐PBMV 31.8 ± 9.3 cm/s and post‐PBMV 51.2 ± 8.7 cm/s; P < .01).A significant positive correlation was present between LAAEV and Sa‐wave (r = .52, P < .01). Correlation between hs‐CRP and SEC was positive and significant (r = .33, P < .01). Optimal cutoff value of hs‐CRP for prediction of moderate to dense SEC was >2.3 mg/dL, the cutoff value of Sa‐wave was≤ 5.5 cm/s for prediction of the presence of inactive LAA (LAAEV < 25 cm/s).

Conclusion

Mitral annular systolic velocity (Sa‐wave) is an independent predictor of inactive LAA and a useful parameter in estimating inactive LAA in MS. Sa‐wave and hs‐CRP are independent predictors for SEC. PBMV improves LAA function in patients with MS.     

Development and pharmacological evaluation of a PEG based nanoparticulate camptothecin analog for oral administration

The aim of this study was to formulate polyethylene glycol (PEG) based nanoparticulate camptothecin analog for oral administration and to evaluate its pharmacological activity. Camptothecin analog (CA) belongs to topoisomerase-I inhibitor class of compounds with proven antitumor activity but exhibits poor solubility. To enhance solubility and oral bioavailability, a PEG based nanoparticulate formulation was developed using a high pressure homogenization technique. The saturation solubility and dissolution characteristics of the nanoparticulate formulation were investigated and compared with as-is drug formulation to ascertain the impact of particle size on drug dissolution in physiologically relevant dissolution media. Systemic exposure of nanoparticulate formulation were evaluated in Wistar rats for increase in the rate and extent of drug absorption. The antitumor activity of nanoparticulate formulation was evaluated on human tumor xenografts (NCI-H460 cell lines) grown in athymic nude mice and compared with a positive control, Irinotecan Hydrochloride administered intravenously. The saturation solubility and dissolution rate of the nanoparticulate formulation were significantly higher as compared to as-is drug formulation. Pharmacokinetic (PK) studies in Wistar rats indicated significant increase in the rate and extent of absorption for the nanoparticulate formulation. Pharmacological activity of nanoparticles in athymic nude mice with implanted tumors revealed that the tumor inhibition activity was equivalent to Irinotecan Hydrochloride intravenous formulation with comparable safety profile at lower doses. These studies demonstrated the feasibility of developing a safe and efficacious oral formulation for a sparingly soluble camptothecin analog that may provide a viable, patient compliant and, cost effective option for the treatment of solid tumors.     

Targeting cap-dependent translation blocks converging survival signals by AKT and PIM kinases in lymphoma

New anticancer drugs that target oncogenic signaling molecules have greatly improved the treatment of certain cancers. However, resistance to targeted therapeutics is a major clinical problem and the redundancy of oncogenic signaling pathways provides back-up mechanisms that allow cancer cells to escape. For example, the AKT and PIM kinases produce parallel oncogenic signals and share many molecular targets, including activators of cap-dependent translation. Here, we show that PIM kinase expression can affect the clinical outcome of lymphoma chemotherapy. We observe the same in animal lymphoma models. Whereas chemoresistance caused by AKT is readily reversed with rapamycin, PIM-mediated resistance is refractory to mTORC1 inhibition. However, both PIM- and AKT-expressing lymphomas depend on cap-dependent translation, and genetic or pharmacological blockade of the translation initiation complex is highly effective against these tumors. The therapeutic effect of blocking cap-dependent translation is mediated, at least in part, by decreased production of short-lived oncoproteins including c-MYC, Cyclin D1, MCL1, and the PIM1/2 kinases themselves. Hence, targeting the convergence of oncogenic survival signals on translation initiation is an effective alternative to combinations of kinase inhibitors.