Method development for the clearance study of the Pluronic F-68 nonionic surfactant used in the upstream process of monoclonal antibody production.

Pluronic F-68 is a nonionic surfactant, which is often used in the upstream process of biopharmaceutical production. However, the number of analytical methods developed for determination of Pluronic F-68 in the in-process and drug substance samples of biological drug production process is quite low. The lack of chromophore groups on the molecule and the interference caused by the high protein content of the samples hamper analysis. In this paper the development and qualification of a mixed-mode (MM) HPLC method with charged aerosol detection is reported. The method enables the analysis of samples with up to 85 g/L protein concentration. The range of the method was set to 250-500 µg/mL, where it was found to be accurate (89-111 % recovery) and precise (0.8-3.2 % relative standard deviation). The high sensitivity of the method indicates that even lower concentration range can be feasible. The novel method successfully demonstrates Pluronic F-68 clearance during the downstream process of the monoclonal antibody production.

Synthesis of C-xylopyranosyl- and xylopyranosylidene-spiro-heterocycles as potential inhibitors of glycogen phosphorylase.

New derivatives of d-xylose with aglycons of the most efficient glucose derived inhibitors of glycogen phosphorylase were synthesized to explore the specificity of the enzyme towards the structure of the sugar part of the molecules. Thus, 2-(ß-d-xylopyranosyl)benzimidazole and 3-substituted-5-(ß-d-xylopyranosyl)-1,2,4-triazoles were obtained in multistep procedures from O-perbenzoylated ß-d-xylopyranosyl cyanide. Cycloadditions of nitrile-oxides and O-peracetylated exo-xylal obtained from the corresponding ß-d-xylopyranosyl cyanide furnished xylopyranosylidene-spiro-isoxazoline derivatives. Oxidative ring closure of O-peracetylated ß-d-xylopyranosyl-thiohydroximates prepared from 1-thio-ß-d-xylopyranose and nitrile-oxides gave xylopyranosylidene-spiro-oxathiazoles. The fully deprotected test compounds were assayed against rabbit muscle glycogen phosphorylase b to show moderate inhibition for 3-(2-naphthyl)-5-(ß-d-xylopyranosyl)-1,2,4-triazole (IC50=0.9mM) only.

Prevalence and psychosocial background of anxiety and depression emerging during the first trimester of pregnancy: data from a Hungarian population-based sample.

BACKGROUND: There are few surveys of antenatal depression and anxiety in Eastern-European countries. The aim of the present study was to gather prevalence data from a Hungarian sample and to search for associations between antenatal depression/anxiety and some psycho-social variables. SUBJECTS AND METHODS: A population-based monitoring system was created, covering every pregnant woman in the town of Szombathely, Western-Hungary for symptoms of depression and anxiety during the first trimester of pregnancy. Data were gathered in the period February 1, 2008 - February 1, 2010. Five-hundred and three pregnant women were included in the sample under survey. RESULTS: Mean age of our participants was 29.8 yr. (SD=4.94/). One fifth (19.9%; 95%CI = 16.6-23.6) of pregnant women were suffering from mild to severe depression as measured by the Beck Depression Inventory. Frequency of severe depression was low (1.4%). 14.2% of the sample (95%CI =11.5-17.6) showed signs of trait anxiety as measured by the Spielberger Inventory. Mean scores for depression and anxiety proved to be significantly higher among women who were unemployed, less than 20 years of age, having low educational or/and socio-economic status, and displaying higher level of social mistrust. Those living in common-law marriage had more depressive symptoms while reciprocity was associated only to anxiety. CONCLUSIONS: Except for prevalence of severe depression, our data did not differ from prevalence found in market economic countries. Teen age, unfavourable socio-economic conditions and high social mistrust were associated with the emergence of clinically meaningful depression and anxiety during the first trimester of pregnancy.

Synthesis of substituted 2-(ß-D-glucopyranosyl)-benzimidazoles and their evaluation as inhibitors of glycogen phosphorylase.

Microwave assisted condensation of O-perbenzoylated C-(ß-d-glucopyranosyl)formic acid with 1,2-diaminobenzenes in the presence of triphenylphosphite gave the corresponding O-protected 2-(ß-d-glucopyranosyl)-benzimidazoles in moderate yields. O-Perbenzoylated C-(ß-d-glucopyranosyl)formamide and -thioformamide were transformed into the corresponding ethyl C-(ß-d-glucopyranosyl)formimidate and -thioformimidate, respectively, by Et3O·BF4. Treatment of the formimidate with 1,2-diaminobenzenes afforded O-protected 2-(ß-d-glucopyranosyl)-benzimidazoles in good to excellent yields. Similar reaction of the thioformimidate gave these compounds in lower yields. The O-benzoyl protecting groups were removed by the Zemplén protocol. These test compounds were assayed against rabbit muscle glycogen phosphorylase (GP) b, the prototype of liver GP, the rate limiting enzyme of glycogen degradation. The best inhibitors were 2-(ß-d-glucopyranosyl)-4-methyl-benzimidazole (Ki=2.8µM) and 2-(ß-d-glucopyranosyl)-naphtho[2,3-d]imidazole (Ki=2.1µM) exhibiting a ∼3-4 times stronger binding than the unsubstituted parent compound.

Effects of depression, anxiety, self-esteem, and health behaviour on neonatal outcomes in a population-based Hungarian sample.

OBJECTIVE: To investigate possible associations of maternal antenatal depression, anxiety and self-esteem with negative neonatal outcomes controlling for the effects of demographic covariates and health behaviour in a Hungarian sample. STUDY DESIGN: A population-based monitoring system was established in 10 districts of health visitors in Szombathely, Hungary, covering every woman registered as pregnant between February 1, 2008 and February 1 2009. Three hundred and seven expectant women in the early stage of their pregnancy were surveyed using the Short Form of Beck Depression Inventory for the measurement of depression and the Spielberger Trait-Anxiety Inventory for the measurement of anxiety. Self-esteem was evaluated by the Rosenberg's Self-Esteem Scale. At the end of the follow-up period, data on 261 mothers and their singleton neonates were available. The relationship between the explanatory and outcome variables (birth weight, length, chest circumference, gestational age, and 1- and 5-min Apgar score) was tested in girls and boys separately by multiple linear regression analysis (Forward method). Categorical variables were used as "dummy variables". RESULTS: Maternal depression, anxiety and health behaviour did not show any association with neonatal outcomes. Higher level of maternal self-esteem was associated with higher birth weight and birth length in boys and higher birth length in girls. Maternal education positively correlated with birth length, gestational age and chest circumference in boys, and with birth length in girls. In girls, maternal socioeconomic status showed a positive association with birth weight and gestational age, while common law marriage had a negative effect on birth weight and chest circumference. CONCLUSIONS: Lower level of maternal self-esteem possibly leads to a higher level of maternal stress which may reduce fetal growth via physiologic changes. Gender differences in associations between demographic factors and neonatal outcome measures indicate differences in fetal development between boys and girls.

Association between health beliefs and health behavior in early pregnancy.

Folate-supplementation significantly reduces the risk of neural tube defects. The aim of this research was to reveal associations between health beliefs and folate -supplementation as well as other elements of health behavior among Hungarian women early in their pregnancy. Three-hundred and seven women in early pregnancy completed the second part of Health and Illness Scale. Factor structure of health beliefs was established and associations of factors with pregnancy planning, folate-intake, vitamin-intake, smoking-habits and alcohol-consumption were tested. A six factor health model was formulated; the factor named 'mental capacities and abilities' was associated with greater chance on folate-intake, vitamin-intake and prepared pregnancy, as well as a reduced chance of smoking. The factors 'destiny', 'measures aiming at prevention', and 'relatives and acquaintances' related to lower chance on folate-intake. The health belief factor representing Internal Health Locus of Control was associated with more than one component of healthy behavior, while factors of external dimensions (Powerful Others Health Locus of Control and Chance Health Locus of Control) were predictive on unhealthy behavioral tendencies. New approaches aiming to shift one's health beliefs and health locus of control from external causes to internal dimensions are needed in order to reach greater openness towards health-improving interventions.

[Effect of demographic factors on folate-supplementation and health-behavior of pregnant women]. / Demográfiai tényezôk hatása a várandósok folsavbevitelére és egészség-magatartására.

UNLABELLED: The aim was to scrutinize associations between folate-supplementation and other elements of health-behavior and demographic factors in pregnant women. METHODS: A population-based monitoring system was established in 10 districts of health visitors in Szombathely, Hungary. The system covered every woman registered as pregnant between 1st February 2008 and 1st February 2009. RESULTS: Young age and lower educational level is associated with less preparation for pregnancy. Those who were prepared for pregnancy, folate-intake was more than twofold, vitamin-intake was threefold higher, while prevalence of smoking was the 50% less, compared to non-prepared women . Older age, higher educational and socio-economic level was positively, while number of siblings was negatively associated with folate-supplementation. Pregnant women with low level of education (OR = 4.72; 95% CI = 2.34-9.51), and living in common-law relationships had higher chance to smoke (OR = 2.74; 95% CI = 1.54-4.89). CONCLUSIONS: Pregnant women who do not receive folate-supplementation are younger, have lower educational and socio-economical status and show other unhealthy behavioral tendencies.