Kerosene lighting contributes to household air pollution in rural Uganda.

The literature on the contribution of kerosene lighting to indoor air particulate concentrations is sparse. In rural Uganda, kitchens are almost universally located outside the main home, and kerosene is often used for lighting. In this study, we obtained longitudinal measures of particulate matter 2.5 microns or smaller in size (PM2.5 ) from living rooms and kitchens of 88 households in rural Uganda. Linear mixed-effects models with a random intercept for household were used to test the hypotheses that primary reported lighting source and kitchen location (indoor vs outdoor) are associated with PM2.5 levels. During initial testing, households reported using the following sources of lighting: open-wick kerosene (19.3%), hurricane kerosene (45.5%), battery-powered (33.0%), and solar (1.1%) lamps. During follow-up testing, these proportions changed to 29.5%, 35.2%, 18.2%, and 9.1%, respectively. Average ambient, living room, and kitchen PM2.5 levels were 20.2, 35.2, and 270.0 µg/m3 . Living rooms using open-wick kerosene lamps had the highest PM2.5 levels (55.3 µg/m3 ) compared to those using solar lighting (19.4 µg/m3 ; open wick vs solar, P=.01); 27.6% of homes using open-wick kerosene lamps met World Health Organization indoor air quality standards compared to 75.0% in homes using solar lighting.

Orally active microtubule-targeting agent, MPT0B271, for the treatment of human non-small cell lung cancer, alone and in combination with erlotinib.

Microtubule-binding agents, such as taxanes and vinca alkaloids, are used in the treatment of cancer. The limitations of these treatments, such as resistance to therapy and the need for intravenous administration, have encouraged the development of new agents. MPT0B271 (N-[1-(4-Methoxy-benzenesulfonyl)-2,3-dihydro-1H-indol-7-yl]-1-oxy-isonicotinamide), an orally active microtubule-targeting agent, is a completely synthetic compound that possesses potent anticancer effects in vitro and in vivo. Tubulin polymerization assay and immunofluorescence experiment showed that MPT0B271 caused depolymerization of tubulin at both molecular and cellular levels. MPT0B271 reduced cell growth and viability at nanomolar concentrations in numerous cancer cell lines, including a multidrug-resistant cancer cell line NCI/ADR-RES. Further studies indicated that MPT0B271 is not a substrate of P-glycoprotein (P-gp), as determined by flow cytometric analysis of rhodamine-123 (Rh-123) dye efflux and the calcein acetoxymethyl ester (calcein AM) assay. MPT0B271 also caused G2/M cell-cycle arrest, accompanied by the up-regulation of cyclin B1, p-Thr161 Cdc2/p34, serine/threonine kinases polo-like kinase 1, aurora kinase A and B and the downregulation of Cdc25C and p-Tyr15 Cdc2/p34 protein levels. The appearance of MPM2 and the nuclear translocation of cyclin B1 denoted M phase arrest in MPT0B271-treated cells. Moreover, MPT0B271 induced cell apoptosis in a concentration-dependent manner; it also reduced the expression of Bcl-2, Bcl-xL, and Mcl-1 and increased the cleavage of caspase-3 and -7 and poly (ADP-ribose) polymerase (PARP). Finally, this study demonstrated that MPT0B271 in combination with erlotinib significantly inhibits the growth of the human non-small cell lung cancer A549 cells as compared with erlotinib treatment alone, both in vitro and in vivo. These findings identify MPT0B271 as a promising new tubulin-binding compound for the treatment of various cancers.

The HDAC inhibitor, MPT0E028, enhances erlotinib-induced cell death in EGFR-TKI-resistant NSCLC cells.

Epidermal growth factor receptor (EGFR), which promotes cell survival and division, is found at abnormally high levels on the surface of many cancer cell types, including many cases of non-small cell lung cancer. Erlotinib (Tarceva), an oral small-molecule tyrosine kinase inhibitor, is a so-called targeted drug that inhibits the tyrosine kinase domain of EGFR, and thus targets cancer cells with some specificity while doing less damage to normal cells. However, erlotinib resistance can occur, reducing the efficacy of this treatment. To develop more effective therapeutic interventions by overcoming this resistance problem, we combined the histone deacetylase inhibitor, MPT0E028, with erlotinib in an effort to increase their antitumor effects in erlotinib-resistant lung adenocarcinoma cells. This combined treatment yielded significant growth inhibition, induced the expression of apoptotic proteins (PARP, γH2AX, and caspase-3), increased the levels of acetylated histone H3, and showed synergistic effects in vitro and in vivo. These effects were independent of the mutation status of the genes encoding EGFR or K-Ras. MPT0E028 synergistically blocked key regulators of the EGFR/HER2 signaling pathways, attenuating multiple compensatory pathways (e.g., AKT, extracellular signal-regulated kinase, and c-MET). Our results indicate that this combination therapy might be a promising strategy for facilitating the effects of erlotinib monotherapy by activating various networks. Taken together, our data provide compelling evidence that MPT0E028 has the potential to improve the treatment of heterogeneous and drug-resistant tumors that cannot be controlled with single-target agents.

The effectiveness of IDF and ATP-III in identifying metabolic syndrome and the usefulness of these tools for health-promotion in older Taiwanese.

OBJECTIVES: The aim of this study was to compare the effectiveness of IDF (International Diabetes Federation) and ATP-III (National Cholesterol Education Program-Adult Treatment Panel III) for predicting metabolic syndrome, and to evaluate the usefulness of these definitions for health promotion. DESIGN: A cross-sectional study. SETTING: A national random sample. PARTICIPANTS: A population representative sample of 1021 54-91 year-old Taiwanese. MEASUREMENTS: Subjects were measured for anthropometric and biochemical indicators and rated for the presence of metabolic syndrome using the two definitions. We evaluated the effectiveness of the two definitions in predicting MetS among those who had specific metabolic disorders. Results were analyzed with Student t-test and McNemar's test. RESULTS: Among the 918 subjects who had one or more MetS-item disorders, ATP-III rated greater proportions of subjects as having MetS than IDF, but both definitions predicted less than 50% (37.7% and 45.4%, respectively) as having MetS. CONCLUSION: Compared to IDF, ATP-III rated a greater proportion of subjects as having MetS, but both definitions missed more than 50% of subjects who had metabolic disorder(s). Since those who are missed have as much need for lifestyle intervention, the definitions appear not appropriate for health promotion.

The association of age, gender, body fatness and lifestyle factors with plasma C-reactive protein concentrations in older Taiwanese.

OBJECTIVE: This study determined the population distribution of plasma C-reactive protein (CRP) and evaluated its association with age, body fatness status and lifestyle factors in elderly Taiwanese. DESIGN: A crosssectional-study. SETTING: A population-representative sample. The "1999-2000 Elderly Nutrition and Health Survey in Taiwan". PARTICIPANTS: 2432 non-institutionalized population-representative Taiwanese, 65 y or older. MEASUREMENTS: Plasma CRP-concentrations and factors that impact plasma CRP concentrations. RESULTS: Results showed that weighting-adjusted plasma CRP concentration (mean +/- SE) was 2.50 +/- 0.10 mg/L for men and 2.70 +/- 0.10 mg/L for women. Cigarette smoking was positively associated with plasma CRP concentrations in both men and women. Age was positively (P < 0.05) but physical activity was negatively (P <0.05) associated with plasma CRP concentrations in men. These associations were not significant in women. Waist circumference but not BMI was significantly (P < 0.05) associated with plasma CRP in women. Both associations were not significant in men. Alcohol drinking and betel nut-chewing were not significantly associated with CRP concentrations. CONCLUSION: Results suggest that there are gender-related differences in the degree of association of CRP concentrations with age, waist circumference, BMI and physical activity in older Taiwanese. Results also suggest population-related differences in the strength of many associations when compared to observations made in Western countries. These findings may help delineate the differences in cardiovascular risk among various populations.

Validation of the Mini Nutritional Assessment short-form (MNA-SF): a practical tool for identification of nutritional status.

OBJECTIVE: To validate a revision of the Mini Nutritional Assessment short-form (MNA(R)-SF) against the full MNA, a standard tool for nutritional evaluation. METHODS: A literature search identified studies that used the MNA for nutritional screening in geriatric patients. The contacted authors submitted original datasets that were merged into a single database. Various combinations of the questions on the current MNA-SF were tested using this database through combination analysis and ROC based derivation of classification thresholds. RESULTS: Twenty-seven datasets (n=6257 participants) were initially processed from which twelve were used in the current analysis on a sample of 2032 study participants (mean age 82.3y) with complete information on all MNA items. The original MNA-SF was a combination of six questions from the full MNA. A revised MNA-SF included calf circumference (CC) substituted for BMI performed equally well. A revised three-category scoring classification for this revised MNA-SF, using BMI and/or CC, had good sensitivity compared to the full MNA. CONCLUSION: The newly revised MNA-SF is a valid nutritional screening tool applicable to geriatric health care professionals with the option of using CC when BMI cannot be calculated. This revised MNA-SF increases the applicability of this rapid screening tool in clinical practice through the inclusion of a "malnourished" category.

Outcomes of penetrating keratoplasty with imported donor corneas.

PURPOSE: To analyze factors influencing the surgical success of penetrating keratoplasty and long-term graft survival when using imported donor corneas. METHODS: Sixty-three donor corneas imported to Taipei from the Cincinnati Eye Bank from July 1992-June 1993 were used for penetrating keratoplasty. The corneal endothelium was examined using specular microscopy on arrival in Taiwan. The endothelial morphology and endothelial cell density (ECD) were compared with the photograph of the same cornea taken in the United States. The relationships of the surgical success rate with donor age, death to enucleation time, death to surgery time, and ECD were analyzed. The long-term graft survival and ECD of clear grafts were analyzed 4 years after surgery. RESULTS: On specular microscopic examination. the imported corneas showed diminished endothelial reflection, blurred cellular borders, and increased dark areas, which were markedly different from the pictures of the corneal endothelium taken in the United States. The average ECD before transportation was 2,525+/-267/mm2 and decreased to 1,934+/-250/mm2 after transportation (p < 0.001), with an average endothelial cell loss of 590+/-247/mm2. The overall surgical success rate was 89% and did not correlate with any of the donor factors tested except death to surgery time. The surgical success rate decreased when the time from death to surgery was >7 days (p = 0.05), mainly because of poor reepithelialization. Four years after surgery, 24 grafts remained clear. The ECD had decreased by 72+/-5% in the clear grafts. CONCLUSIONS: Our findings show that endothelial changes in imported donor corneas do occur after transportation, but the surgical success rate may not be influenced significantly if the penetrating keratoplasty is performed within 7 days after donor death. However, the ECD in the clear grafts 4 years after surgery is low.

Clinical evaluation of ciprofloxacin ophthalmic solution in the treatment of refractory bacterial keratitis.

Ciprofloxacin is a fluoroquinolone antimicrobial agent inhibiting bacterial DNA gyrase, with good in vitro and in vivo activity against many Gram-positive and Gram-negative ocular pathogens. It has low toxicity, low resistance rate and low minimum inhibitory concentration. The purpose of this study was to evaluate the efficacy of ciprofloxacin in treating bacterial keratitis refractory to conventional therapy. Thirty patients with smear-proven bacterial ulcers were treated by conventional therapy. Of these, cultures were positive in 28 (93.3%) patients. Pseudomonas aeruginosa was isolated in 13 (46.4%) patients, nontuberculous mycobacteria in nine (32.1%) and other bacteria in six (21.4%). Fifteen patients (50%) were cured with conventional therapy. Four patients (13.3%) underwent surgery due to impending corneal perforation. Eleven patients were shifted to ciprofloxacin therapy because of poor results with conventional treatment. Of these, eight (72.7%) patients were treated successfully. No adverse events were encountered except a white crystalline precipitate in two cases which resolved spontaneously after discontinuation of therapy. In view of its effectiveness and low toxicity, ciprofloxacin should be considered in treating bacterial keratitis which is refractory to conventional therapy.

Effects of soy polysaccharide on postprandial plasma glucose, insulin, glucagon, pancreatic polypeptide, somatostatin, and triglyceride in obese diabetic patients.

The effect of soy polysaccharide on postprandial plasma glucose levels was examined in a crossover experiment involving seven obese noninsulin dependent maturity-onset diabetic patients fed a standard meal without or with 10 g of this fiber source. Postprandial concentrations of plasma insulin, glucagon, pancreatic polypeptide, and somatostatin were measured to explore the mechanism of action. The effect on plasma triglyceride levels was also studied. Supplementation of soy polysaccharide significantly enhanced return of serum glucose levels towards fasting level during the latter half of the meal test. Addition of soy polysaccharide had no effect on plasma insulin levels but appeared (p greater than 0.05) to lessen postprandial increases in glucagon and pancreatic polypeptide levels while it raised somatostatin levels. Soy polysaccharide significantly reduced the rise of postprandial plasma triglyceride levels. The changes in plasma glucagon, pancreatic polypeptide, and somatostatin levels may have been instrumental in the observed postprandial glucose and triglyceride effects.

Contribution of growth, fatness, and activity to weight disturbance after septohypothalamic cuts in adult hamsters.

The mechanism responsible for weight stability in adult hamsters was investigated by (a) transecting the dorsoventrally oriented nerve pathways between the septal area and hypothalamus (SH cuts) and (b) partitioning the observed increases in the rate of weight gain into three contributory components: changes in somatic growth, in body fatness, and in energy expended as voluntary activity on horizontal disks. Between 60% and 70% of the weight increase after SH cuts was due to acquisition of lean body mass, and 30%-40% of weight increase consisted of excess body fat. After SH cuts, serum growth hormone and insulin concentrations were increased on Day 14, food intake was increased between Day 2 and Day 42, skeletal lengths were greater on Day 77, and voluntary activity levels were 84% lower on Days 10-45, relative to control hamsters. It is concluded that dorsoventrally oriented nerve pathways in the septal area are involved in the control of growth, maintenance of body fat reserves, and voluntary activity and that they contribute to the maintenance of stable body weight in adult hamsters.

Studies of the effect of dietary cholesterol on hepatic protein synthesis, reduced glutathione levels and serine dehydratase activity in the rat.

A basal diet or a basal diet plus 1% of cholesterol and 0.33% cholic acid was fed to rats for varying lengths of time and (1) the activities of liver phosphoenolpyruvate-carboxykinase (PEP-CK), tyrosine transaminase (TT), and serine dehydratase (SD); (2) the rate of total hepatic protein synthesis and (3) the concentration of hepatic reduced glutathione (GSH) were quantitated. The specific activity of PEP-CK was significantly depressed by cholesterol plus cholic acid feeding, while the specific activity of TT was unchanged. No significant effect of dietary cholesterol plus cholic acid was found on the total liver activities. In contrast, SD specific activity was increased 3-fold. The rate of (U-14C)-L-leucine incorporation into total TCA precipitable protein following ingestion of cholesterol plus acid was significantly reduced when the data were expressed as dpm (U-14C)-L-leucine/mg protein. After correcting this expression for specific radioactivity of the liver tissue free leucine pool, no significant effect of dietary cholesterol plus cholic acid on hepatic protein synthesis existed. In fact, the amount of 14C-leucine incorporated into protein on a total liver basis was 50% greater for the cholesterol group. On a per gram of liver basis, the concentration of GSH in the liver of rats fed a cholesterol plus cholic acid diet was significantly decreased. Considering the liver enlargement in rats fed cholesterol plus cholic acid, total organ GSH was found to be significantly greater than for rats fed a basal diet.

Influence of dietary safflower oil and tallow on growth, plasma lipids and lipogenesis in rats, pigs and chicks.

Rats, chicks and pigs were fed diets containing safflower oil or tallow. Plasma triglyceride levels were elevated when tallow, rather than safflower oil was added to the diet of rats, unchanged in chicks and lowered when tallow, rather than safflower oil was fed to pigs. The rate of fatty acid synthesis in rat and chick liver was higher, whereas the rate of lipogenesis in adipose tissue preparations from rats and pigs was lower when tallow, rather than safflower oil was fed. These results indicate that there are species-specific, as well as organ-specific, metabolic responses to various dietary fats.