A multicenter comparative trial of triphasic and monophasic, low-dose combined oral contraceptives

A comparative multicenter clinical trial of two combined oral contraceptives (OCs) was conducted at clinics located in the Sudan, Sri Lanka, Chile, the Dominican Republic and Ecuador. The trial was designed to determine if there were differences in efficacy, safety and acceptability between a triphasic and a low-dose monophasic OC. This report includes analysis of 1088 women. At each center, subjects were randomly allocated to one of the two OCs. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. There were two accidental pregnancies attributed to user failure reported during the study period; one in the triphasic group and one in the monophasic group. Adverse experiences were mainly minor with headaches and dizziness being the most common complaints; frequency of reports was similar in both groups. Cycle control was good in both groups with women in the triphasic group reporting fewer complaints of intermenstrual bleeding. Both OCs were safe and effective.     

A quasi-static discomfort measure in whole-body vibration

A new methodology for objective evaluation of discomfort in whole-body vibration (WBV) is introduced in this work. The proposed objective discomfort characterizes discomfort based on the relative motion between adjacent segments of the human body from neutral positions. It peaks when the joints reach their limits. The objective discomfort has been tested on five subjects in the fore-aft direction using discrete sinusoidal frequencies of 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12, 14, and 16 Hz. Each frequency file runs for 15 s with a 3 s resting period as a reference for discomfort comparison. All files run at a constant acceleration of 0.7 m/s(2). The subjects were tested with back support and without back support, and their subjective discomfort was reported based on the Borg CR-10 scale. The proposed objective discomfort has shown significant correlation with the subjective discomfort. The objective discomfort has also been tested on five subjects under multiple-axis random WBV with three common industrial seating configurations (seat-mounted control, floor-mounted control, and steering wheel), and has shown promising results.     

Selective synthesis of alpha monoglycerides by a clean method: Techno-economic and environmental assessment

This work proposes an alternative green and selective biocatalytic route for Glycerin Monostearate (α-monostearin) production. The conventional method of production uses an elevated temperature. Apart from the high energy consumption, such high temperatures darken the final product's color, lead to random reactions, and produce high orders of diglycerides and triglycerides instead of monoglycerides. The proposed production process was performed by esterifying stearic acid with glycerin in an organic medium using Candida antarctica lipase (Novozym 435) at a mild temperature. The reaction conditions were optimized using the response surface methodology (RSM): optimum conditions were a temperature of 60 °C, glycerin to stearic acid molar ratio of 8:1, and Novozym 435 amount of 6% w/w. The solvent addition remarkably improved the α-monostearin yield to nearly 80% without the need for the energy-intensive distillation step. The conventional autocatalytic esterification (AUT) process was also performed to investigate the comparative monoglyceride yield, and it was found to be 22.5%. Proton nuclear magnetic resonance and gas-chromatography confirmed that α-monostearin could be produced with the highest purity using the proposed enzymatic method (ENZ). Economic and environmental analyses were also conducted for the proposed ENZ process, and the results were compared with those of the AUT process. The total capital investment of α-monostearin production, considering a projected capacity of 4950 t year^?1 and 11% interest for the proposed ENZ process, was favorably 2.5 times lower than that of the AUT process, suggesting a promising investment opportunity. However, the total production costs showed unfavorable negative net present value (NPV) and return on investment (ROI) for the ENZ process and favorable positive NPV and ROI for the AUT process, indicating that the proposed venture is not profitable for α-monostearin production. However, the process can be profitable at improved operational stability of Novozym 435 up to 1 kg per 3-ton product. The carbon footprint was calculated on the basis of the given capacity and conditions of 50 and 656 t CO₂ eq./year for the ENZ and AUT processes, respectively. The synthesis of α-monostearin using the proposed route can be considered a building block toward a cleaner large-scale production of α-monoglycerides.     

Particulate black carbon and gaseous emission from brick kilns in Greater Dhaka region,Bangladesh

Eighteen brick kilns of three brick-making technologies (Fixed Chimney Kiln (FCK), Zigzag, and Hoffmann) were selected to measure the concentrations of particulate matter (PM_2.5) with Aerocet 531S (USA) sampler, black carbon (BC) with Magee Scientific, OT-21 Soot scan Transmissometer (USA), and gaseous pollutants (CO₂, CO, SO₂, NO_x, and volatile organic carbon (VOC)) with Aeroqual 500 gas sampler (New Zealand) to understand the emission scenario from brick sector in Greater Dhaka region, Bangladesh. Emission factor (EF) of each pollutant was computed from their respective concentration for three brick kiln technologies. Ambient PM_2.5 and PM₁₀ were measured in brick kiln premises and 1 km far from the respective kilns to see the effect on the surrounding areas. The PM_2.5 concentration was found on an average of 141?±?86, 128?±?72, and 110?±?53 mg/m³ in FCK, Zigzag, and Hoffmann kilns, respectively. The average BC concentration was found 16.6?±?7.1 (FCK), 11.8?±?4.2 (Zigzag), and 8.9?±?4.4 (Hoffmann) mg/m³. FCK has a greater emission of CO, whereas Zigzag has a higher CO₂ emission. A comparatively higher value of CO₂ and lower value of CO indicates effective combustion of coal, and this is found to be more efficient for Zigzag and Hoffmann compared to traditional FCK. SO₂ and VOC emissions were depending not only on the kiln types but also on the fuel qualities. From EF calculation, approximately 4526 t of PM_2.5, 340 t of BC, 209,776 t of CO₂, 8700 t of CO, 19,441 t of SO₂, and 835,450 t of VOC per year found to emit from 1000 brick kilns. The conversion of traditional FCK to improved one, i.e., Zigzag and/or Hoffman is not a straight forward solution, as CO₂ emission was higher in Zigzag whereas BC and PM_2.5 emissions were higher in FCK. Therefore, considering EF of various pollutants from these three types of kilns, conversion of FCK to Zigzag or Hoffmann could be a better choice.     

Association Between Copper Excess,Zinc Deficiency,and TP53 Mutations in Esophageal Squamous Cell Carcinoma From Kashmir Valley,India—A High Risk Area

Trace element deficiency or excess is implicated in the development or progression in some cancers. Here we report the elevated level of copper and low level of zinc in the plasma of esophageal cancer patients in Kashmir India—a high incidence area. The average level of copper was significantly higher (P < 0.0001) for patients than for controls, with a mean concentration of 169 μg/dl and 149 μg/dl for patients and controls, respectively. The control group consisted of 55 healthy individuals matched for age, sex, and place of residence of the patients. In contrast, the average level of zinc in patients was significantly lower than in controls (P < 0.0001), with a mean concentration of 86.8 μg/dl and 96.1 μg/dl for patients and controls, respectively. The levels of both copper and zinc showed significant differences based on gender and age in patients as compared to controls. Similarly, smokers depicted a significant increase in serum copper (N = 39, P = 0.002) and a decrease in serum zinc approaching level of significance in the patient group as compared to controls. The copper and zinc levels were significantly altered in patients (N = 40) when compared to controls as a function of snuff consumption. The differences in the levels of copper and zinc showed significant association with the consumption of local salted tea up to 1,500 ml per day, but the changes were insignificant beyond that. Patients with poorly differentiated tumors (N = 7) had a higher copper concentration than those with moderately or well-differentiated tumors (P < 0.0001). To validate the general notion that imbalance in copper and zinc levels may lead to higher prevalence of TP53 mutations, we compared the 3 variables, and no association was found between copper concentration and TP53 mutation status; but patients with TP53 mutant tumor had lower zinc levels than those with no mutation. In conclusion, our results point toward a role of the trace element imbalance in the esophageal tumorigenesis in high-risk Kashmiri population exposed to a range of nitroso compounds or their precursors. Further prospective cohort studies are warranted to determine whether change in the plasma zinc and copper homeostasis may represent an independent risk factor for this malignancy as well as a possible target for preventive intervention.     

Modulation of inflammatory paw oedema by cysteamine in the rat.

Cysteamine, a potent somatostatin depletor, was used in the present study to investigate the role of endogenous somatostatin in acute peripheral inflammation. The acute inflammation was induced by intraplantar injection of carrageenan (1%), histamine (5 micromol), or formalin (2.5%) in the rat hind paw. The induced inflammation and the formation of oedema were determined by measurement of the paw thickness. Given subcutaneously (s.c.) 1 h before carrageenan, cysteamine caused significant, dose-dependent and long-lasting inhibition of rat paw oedema induced by carrageenan. At doses of 12.5, 25, 50 or 100 mg kg (-1), cysteamine significantly inhibited the carrageenan-induced paw oedema at 4 h by 52.3, 40, 40.7 or 26.3%. Cysteamine given at 300 mg kg (-1), a dose well known to deplete tissue somatostatin, reduced oedema by only 16.2% vs control values. Significant inhibition of the carrageenan-induced rat paw oedema was still evident 24 h post-injection at cysteamine doses of 12.5, 25, 50 or 100 mg kg (-1). Given s.c. at 300 mg kg (-1), 4 h prior to carrageenan, cysteamine decreased rat paw oedema at 4 h by 14.9%. Cysteamine (300 mg kg (-1)), 4 h beforehand, had little modulatory effect on the oedema induced by formalin (2.5%) but reduced that caused by intraplantar histamine (5 micromol). The anti-oedematogenic effect of indomethacin, but not that of the selective COX-2 inhibitor celecoxib, was less marked in rats pre-treated with cysteamine at 300 mg kg (-1). Cysteamine (0.3 microg- 0.3 mg paw (-1)) co-administered with carrageenan was devoid of anti-inflammatory effect and even promoted inflammation at low concentrations. Cysteamine given locally alone induced slight paw oedema. These data indicate that systemic cysteamine possesses potent and long-lasting anti-inflammatory effects and modulates the anti-inflammatory effect of cyclooxygenase inhibitors in a model of peripheral inflammation in the rat. The effect of cysteamine is likely to be mediated via central action.     

Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro: Cellular Senescence,Enhanced Telomere Erosion,and Degradation of Werner’s Syndrome Protein

Background: Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence.Objectives: We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF).Methods: We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length.Results: We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner’s syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening.Conclusions: These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation.Citation: Jang JH, Bruse S, Huneidi S, Schrader RM, Monick MM, Lin Y, Carter AB, Klingelhutz AJ, Nyunoya T. 2014. Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner’s syndrome protein. Environ Health Perspect 122:955–962; http://dx.doi.org/10.1289/ehp.1306911     

Coronary artery disease prevalence and outcome in patients hospitalized with acute heart failure: an observational report from seven Middle Eastern countries

Objectives: The purpose of this study was to report prevalence, clinical characteristics, precipitating factors, management and outcome of patients with coronary artery disease (CAD) among patients hospitalized with heart failure (HF) in seven Middle Eastern countries and compare them to non-CAD patients.

Methods: Data were derived from Gulf CARE (Gulf aCute heArt failuRe rEgistry), a prospective multicenter study of 5005 consecutive patients hospitalized with acute HF during February-November 2012 in 7 Middle Eastern countries.

Results: The prevalence of CAD among Acute Heart Failure (AHF) patients was 60.2% and varied significantly among the 7 countries (Qatar 65.7%, UAE 66.6%, Kuwait 68.0%, Oman 65.9%, Saudi Arabia 62.5%, Bahrain 52.7% and Yemen 49.1%) with lower values in the lower income countries. CAD patients were older and more likely to have diabetes, hypertension, dyslipidemia and chronic kidney disease. Moreover, CAD patients were more likely to have history of cerebrovascular and peripheral vascular disease when compared to non-CAD patients. In-hospital mortality rates were comparable although CAD patients had more frequent re-hospitalization and worse long-term outcome. However, CAD was not an independent predictor of poor outcome.

Conclusion: The prevalence of CAD amongst patients with HF in the Middle East is variable and may be related to healthcare sources. Regional and national studies are needed for assessing further the impact of various etiologies of HF and for developing appropriate strategies to combat this global concern.     

Extended-release niacin with laropiprant : a review on efficacy, clinical effectiveness and safety

INTRODUCTION: Although treatment with statins reduces cardiovascular (CV) events in patients with dyslipidemia, a residual 60 - 70% CV risk remains. This CV risk may be inversely related to high-density lipoprotein-cholesterol (HDL-C). Interest in niacin has re-emerged because of its HDL-C raising effects. The flushing associated with niacin which has previously affected patient compliance can now be significantly blocked with laropiprant (LRPT). AREAS COVERED: This review aims to assess the efficacy, clinical effectiveness and safety of extended-release niacin (ERN) with LRPT. The authors searched PubMed and MEDLINE for literature published between January 2006 and November 2011, for efficacy, clinical effectiveness and safety reports of ERN with LRPT. EXPERT OPINION: Niacin has been shown to prevent CV events, reduce mortality and has beneficial effects on vascular endothelial function. Evidence suggests that this is due to its broad-spectrum lipid altering properties, including lowering lipoprotein (a) (Lp(a)), and its pleiotropic actions. While side effects associated with niacin have limited its use in the past, the extended-release formulations and co-administration of LRPT have increased its tolerability, particularly by reducing flushing. The authors advise that ERN should be used in patients with a high risk of cardiovascular disease, who have failed to reach conventional targets.