Methamidophos,dichlorvos, O‐methoate and diazinon pesticides used in Turkey make a covalent bond with butyrylcholinesterase detected by mass spectrometry

Organophosphorus pesticides used most commonly in Turkey include methamidophos, dichlorvos, O‐methoate and diazinon. These toxic chemicals or their metabolites make a covalent bond with the active site serine of butyrylcholinesterase. Our goal was to identify the adducts that result from the reaction of human butyrylcholinesterase with these pesticides. Highly purified human butyrylcholinesterase was treated with a 20‐fold molar excess of pesticide. The protein was denatured by boiling and digested with trypsin. MS and MSMS spectra of HPLC‐purified peptides were acquired on a MALDI‐TOF‐TOF 4800 mass spectrometer. It was found that methamidophos added a mass of +93, consistent with addition of methoxy aminophosphate. A minor amount of adduct with an added mass of +109 was also found. Dichlorvos and O‐methoate both made dimethoxyphosphate (+108) and monomethoxyphosphate adducts (+94). Diazinon gave a novel adduct with an added mass of +152 consistent with diethoxythiophosphate. Inhibition of enzyme activity in the presence of diazinon developed slowly (15 h), concomitant with isomerization of diazinon via a thiono‐thiolo rearrangement. The isomer of diazinon yielded diethoxyphosphate and monoethoxyphosphate adducts with added masses of +136 and +108. MSMS spectra confirmed that each of the pesticides studied made a covalent bond with serine 198 of butyrylcholinesterase. These results can be used to identify the class of pesticides to which a patient was exposed.     

Insulin detemir improves glycemic control and reduces hypoglycemia in children with type 1 diabetes: findings from the Turkish cohort of the PREDICTIVE™ observational study

Background: Insulin detemir is a basal insulin analog designed to produce a superior pharmacokinetic profile to basal formulations of human insulin. It has shown consistently improved tolerability in comparison to neutral protamine Hagedorn (NPH) insulin in adult cohorts, but there are relatively few publications involving pediatric cohorts. Methods: The efficacy and safety of insulin detemir in children with type 1 diabetes was assessed using data from the Turkish cohort of PREDICTIVE? (a large, multinational, observational) study. The children investigated were using basal–bolus therapy involving NPH insulin or insulin glargine at baseline but were switched to insulin detemir as part of routine clinical care by their physicians. Results: Twelve weeks of treatment with insulin detemir significantly reduced mean hemoglobin A1c (9.7–8.9%, p < 0.001) and mean fasting glucose [185–162 mg/dL (10.3–9 mmol/L), p < 0.01]. Fasting glucose variability was also lower after treatment with insulin detemir than previously (on either NPH or glargine, p < 0.05). The frequencies of total, major and nocturnal hypoglycemic events were significantly reduced with insulin detemir relative to baseline, with an estimated mean of 6.89 fewer events/patient/yr overall (p < 0.001) and 2.6 fewer nocturnal events/patient/yr (p < 0.01). Weight and insulin dose remained relatively unchanged. Conclusions: Twelve weeks of treatment with insulin detemir improved glycemic control and reduced hypoglycemia in children with type 1 diabetes. This improved tolerability might allow further dose titration and therefore additional improvements in glucose control.     

Effect of cervical mucus aspiration before intrauterine insemination

Objective

To determine whether cervical mucus aspiration before intrauterine insemination (IUI) has any effect on clinical pregnancy rates.

Method

The outcomes of 186 IUI cycles in 95 consecutive patients in whom mucus was aspired prior to IUI were compared retrospectively with those of 1057 IUI cycles in 505 women.

Results

The pregnancy rate was 15.1% (28 pregnancies for 186 cycles) in the cervical mucus aspiration group and 9.9% (105 pregnancies for 1057 cycles) in the control group (P = 0.05). Mucus aspiration led to significantly increased pregnancy rates for women with unexplained infertility (24% in the aspiration group vs 9.5% in the control group; P = 0.04).

Conclusion

Cervical mucus aspiration before IUI might improve clinical pregnancy rates by yet-to-be-defined mechanisms.     

Susceptibility of red blood cell lipids to in vitro oxidation and antioxidant status in preeclampsia

Objective

To investigate susceptibility of red blood cell (RBC) lipids to oxidation and antioxidant status in preeclampsia.

Study design

Twenty-one women with mild preeclampsia, 21 women with severe preeclampsia, and 20 healthy pregnant women were included in this cross-sectional study. Susceptibility of RBC to oxidative stress was determined by measuring RBC-malondialdehyde levels after incubation with hydrogen peroxide. Vitamins E and C, total carotenoids and erythrocyte superoxide dismutase and glutathione peroxidase (GPx) activities and serum total antioxidant capacity (TAC) were determined spectrophotometrically. One-way analysis of variance and correlation analysis were used for statistical analyses.

Results

Compared with the normal pregnant women, susceptibility of RBC to oxidation was enhanced in the mild (p < 0.05) and severe (p < 0.01) preeclampsia groups, TAC was lower in the mild (p < 0.01) and severe (p < 0.001) preeclampsia groups. Vitamin C level was decreased in severe preeclampsia and total carotene level was decreased in mild and severe preeclampsia groups (p < 0.05). GPx activity was also decreased in the mild (p < 0.01) and severe (p < 0.05) preeclampsia groups.

Conclusion

The results of the present study supported the oxidative stress hypothesis of preeclampsia and it is possible that RBC play a role in the pathophysiology of the disease.     

Contact-Free Support Structures for the Direct Metal Laser Melting Process

Although Direct Metal Laser Melting (DMLM), a powder bed fusion (PBF) Additive Manufacturing (AM) for metallic materials, provides many advantages over conventional manufacturing such as almost unlimited design freedom, one of its main limitations is the need for support structures beneath overhang surfaces. Support structures are generally in contact with overhang surfaces to physically prop them up; therefore, they need to be removed after manufacturing due to not constituting a part of the main component design. The removal of supports is a process sequence adding extra time and cost to the overall manufacturing process and could result in damaging the main component. In this study, to examine the feasibility of contact-free supports for overhang surfaces in the DMLM process, coupons with these novel types of supports were prepared from CoCrMo alloy powder. This study aims to understand the effect of two parameters: the gap distance between supports and overhang surfaces and the inclination angle of overhang surfaces, on the surface topography and microstructural properties of these surfaces. Visual inspection, roughness measurements, and optical microscopy were utilized as characterization methods The roughness parameters (Ra, Rq, and Rz) were obtained using the focus variation method, and optical microscope analysis was performed on the cross-sections of the overhang surfaces to investigate the sub-surface microstructure and surface topology. Results showed that contact-free supports have a positive effect on decreasing surface roughness at all build angles when the gap distance is correctly set to avoid sintering of the powder in between the overhang and supports or to avoid too large gaps eliminating the desired effect of the higher thermal conductivity.