Preliminary spectroscopic characterization of PEGylated mucin, a novel polymeric drug delivery system

The objective of this study was to evaluate, spectrophotometrically, the compatibility of non-mucinated polyethylene glycol (PEG) 4000 and non-PEGylated mucin in a PEGylated mucin matrices for drug delivery application. Mucin was extracted from the giant African land snails (Archachatina maginata) using chilled acetone and characterized in terms of qualitative properties and solubility profile. Polymeric matrices composed of PEG 4000 and mucin in ratios of 2:0 (A), 1:1 (B), 2:1(C) and 3:1 (D) were prepared by co-precipitation using chilled acetone. The matrices were characterized with respect to compatibility using the Fourier transform infrared (FT-IR) spectroscopy. Results of the qualitative tests performed on the snail mucin showed that carbohydrates, proteins and trace amounts of fats were present; the extracted mucin was light-brownish in colour, with a pleasant meaty odour. Snail mucin, when dispersed in water yielded a slightly viscous dispersion, but is not soluble in ethanol, acetone, 0.1 M sodium hydroxide, ammonium hydroxide and sulphuric acid. The presence of different peaks in the FT-IR spectra of the PEGylated mucin matrices compared with the non-PEGylated mucin (2:0) matrix and non-mucinated PEG 4000 (0:2) matrix indicated the formation of new polymers, which could be employed in drug delivery. This study has shown that PEGylation of mucin gives rise to new polymeric system with principal FT-IR peaks quite different from those of non-PEGylated mucin and nonmucinated PEG, and this may be employed in the delivery of drugs.Key words: PEGylation, drug delivery, mucin, Fourier transform infrared (FT-IR) spectroscopy, Archachatina maginata

Genetic Associations with Gestational Duration and Spontaneous Preterm Birth

BACKGROUND Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODS We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P<5.0x10(-8)) or an association with suggestive significance (P<1.0x10(-6)) in the discovery set. RESULTS In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. CONCLUSIONS In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement.Peer reviewe

Ancient transposable elements transformed the uterine regulatory landscape and transcriptome during the evolution of mammalian pregnancy

A major challenge in biology is determining how evolutionarily novel characters originate; however, mechanistic explanations for the origin of new characters are almost completely unknown. The evolution of pregnancy is an excellent system in which to study the origin of novelties because mammals preserve stages in the transition from egg laying to live birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including genes that mediate maternal-fetal communication and immunotolerance. Furthermore, thousands of cis-regulatory elements that mediate decidualization and cell-type identity in decidualized stromal cells are derived from ancient mammalian transposable elements (TEs). Our results indicate that one of the defining mammalian novelties evolved from DNA sequences derived from ancient mammalian TEs co-opted into hormone-responsive regulatory elements distributed throughout the genome.Vincent J. Lynch, Mauris C. Nnamani, Aurélie Kapusta, Kathryn Brayer, Silvia L. Plaza, Erik C. Mazur, Deena Emera, Shehzad Z. Sheikh, Frank Grützner, Stefan Bauersachs, Alexander Graf, Steven L. Young, Jason D. Lieb, Francesco J. DeMayo, Cédric Feschotte, Günter P. Wagne

Ectopic pregnancy at a tertiary hospital in North Eastern Nigeria: a 2 year review of the clinical presentations and management

Background: Ectopic pregnancy is a life threatening gynaecological condition associated with adverse reproductive health consequences. It commonly implants in the fallopian tube and most patients in the developing world present &nbsp;late when it has ruptured leading to maternal morbidity and mortality if intervention is delayed. Method: This was a descriptive cross-sectional retrospective study of patients with ectopic pregnancy managed at Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, North east Nigeria between 1st January, 2013 and 31st December, 2014. Data on the age, parity, clinical symptoms and signs and the types of surgical treatment offered was extracted and computed using excel spreadsheet and statistical analysis was done using SPSS (version 23) and results presented as frequency tables, percentages, and mean (± SD). Results: There were 1,577 gynaecological admissions during the period of study and 98 of them (6.2%) were ectopic pregnancies. The total number of deliveries during the same period was 6,738, putting the incidence of ectopic pregnancy to be 1.45% of all deliveries. Majority of the affected patients (39.2%) were between 25- 29 years with a mean and SD of 26.5 ± 4.9 years. Majority of the patients who had ectopic pregnancy 26 (35.1%) were nulliparous women. Of these patients, 97.3% presented with symptoms of abdominal pain, amenorrhoea (83.8%) and vaginal bleeding (68.9%). 97.3% of them had salpingectomy of the affected side. Conclusion: Ectopic pregnancy is a common life-threatening emergency in early pregnancy. Efforts made to improve early diagnosis prior to tubal rupture, would help reduce the associated maternal morbidity and eliminate mortality from this condition

Effects of Vitamin E Supplementation in Male Rats with Crude Oil-Induced Reproductive Toxicity

Crude oil intoxication is a major threat among people and animals living around the crude oil producing regions of the world, hence the search for ameliorating agents. Forty-four male Wistar rats assigned into three groups were used to investigate the effects of vitamin E supplementation on crude oil-induced reprotoxicity (reproductive toxicity) in male rats. Group A represented the unexposed control, whereas groups B and C were exposed orally to 0.15 and 0.3 ml of crude oil respectively every other day for 56 days. Both the low dose and high dose oral administration of crude oil caused a significant reduction in the serum testosterone level (STL) and cauda epididymal sperm reserve (CESR) of the exposed rats when compared to the control. Crude oil withdrawal and vitamin E supplementation significantly improved the cauda epididymal sperm reserve (CESR) in all the subgroups. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities of the control and low dose group were significantly lower than those of the high dose group. The high dose crude oil administration significantly decreased the mean serum total protein (STP) and sodium ions (Na+) concentration. The mean serum total cholesterol (STC) value of the low dose group was significantly higher than those of the control and high dose group. However, crude oil withdrawal and vitamin E supplementation did not significantly alter the mean serum total protein (STP) and mean serum total cholesterol (STC) values in all the subgroups. Vitamin E supplementation following low dose crude oil withdrawal enhanced the mean serum Chloride ions (Cl-)concentration. The present findings revealed that Nigerian Qua Iboe Brent crude oil induced serious reprotoxic effects in male rats which vitamin E administration within 28 days did not completely reverse

An Integral Experiment on Polyethylene Using Radiative Capture in Indium Foils in a High Flux D-D Neutron Generator

We report here the results of a measurement of the scattered versus unscattered neutron fluence on polyethylene determined via neutron activation of multiple natural indium foils from a deuterium-deuterium (D-D) neutron generator. The neutrons were produced by the High Flux Neutron Generator (HFNG) at the University of California, Berkeley, a specially designed source to maximize neutron flux on a sample while minimizing the total neutron yield. During the experiment, approximately 108 n/s were produced with the energies at the indium foils ranging from 2.2 to 2.8&nbsp;MeV. Both the angle-integrated and the partial angle differential results are consistent with the predictions of the Monte Carlo N-Particle Transport (MCNP) code, using ENDF/B-VII.1. This supports shielding calculations in the fast energy region with high-density polyethylene

An Integral Experiment on Polyethylene Using Radiative Capture in Indium Foils in a High Flux D-D Neutron Generator

We report here the results of a measurement of the scattered versus unscattered neutron fluence on polyethylene determined via neutron activation of multiple natural indium foils from a deuterium-deuterium (D-D) neutron generator. The neutrons were produced by the High Flux Neutron Generator (HFNG) at the University of California, Berkeley, a specially designed source to maximize neutron flux on a sample while minimizing the total neutron yield. During the experiment, approximately 108 n/s were produced with the energies at the indium foils ranging from 2.2 to 2.8&nbsp;MeV. Both the angle-integrated and the partial angle differential results are consistent with the predictions of the Monte Carlo N-Particle Transport (MCNP) code, using ENDF/B-VII.1. This supports shielding calculations in the fast energy region with high-density polyethylene

The mammalian decidual cell evolved from a cellular stress response.

Among animal species, cell types vary greatly in terms of number and kind. The number of cell types found within an organism differs considerably between species, and cell type diversity is a significant contributor to differences in organismal structure and function. These observations suggest that cell type origination is a significant source of evolutionary novelty. The molecular mechanisms that result in the evolution of novel cell types, however, are poorly understood. Here, we show that a novel cell type of eutherians mammals, the decidual stromal cell (DSC), evolved by rewiring an ancestral cellular stress response. We isolated the precursor cell type of DSCs, endometrial stromal fibroblasts (ESFs), from the opossum Monodelphis domestica. We show that, in opossum ESFs, the majority of decidual core regulatory genes respond to decidualizing signals but do not regulate decidual effector genes. Rather, in opossum ESFs, decidual transcription factors function in apoptotic and oxidative stress response. We propose that rewiring of cellular stress responses was an important mechanism for the evolution of the eutherian decidual cell type

Sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance

Petra Obioma Nnamani,1,2 Agatha Adaora Ugwu,1 Emmanuel Chinedu Ibezim,1 Franklin Chimaobi Kenechukwu,1 Paul Achile Akpa,1 John-Dike Nwabueze Ogbonna,1 Nicholas Chinedu Obitte,3 Amelia Ngozi Odo,4 Maike Windbergs,2 Claus-Michael Lehr,2,5,6 Anthony Amaechi Attama1 1Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria; 2Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Saarland University, Saarbr&uuml;cken, Germany; 3Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, 4Department of Human Kinetics and Health Education, University of Nigeria, Nsukka, Nigeria; 5PharmBioTec GmbH, 6Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbr&uuml;cken, Germany Abstract: The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether&ndash;lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol&reg; ATO 5/Transcutol&reg; HP and tallow fat/Transcutol&reg; HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65). Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage yield and encapsulation efficiency were ~92% and 93% for Precirol&reg; ATO 5/Transcutol&reg; HP batch, then 81% and 95% for tallow fat/Transcutol&reg; HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol&reg; ATO 5/Transcutol&reg; HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32%) than tallow fat/Transcutol&reg; HP-BL3 (77.9%). Non-Fickian (anomalous) diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%), superior to the reduction obtained with commercial antimalarial formulations: Coartem&reg; tablets (86%) and chloroquine phosphate tablets (66%). No significant difference (P&lt;0.05) in parasite reduction between double (4/24 mg/kg) and single (2/12 mg/kg) strength doses of AL compacts was observed. Our result highlights that AL could be formulated in much lower doses (4/24 mg/kg), for once-in-two days oral administration to improve patient compliance, which is currently not obtainable with conventional AL dosage forms. Keywords: malaria, artemisinin-based combination therapy, antiplasmodial activity, liquisolid compacts, nanostructured lipid carrier