Changes of early post-traumatic osteoarthritis in an ovine model of simulated ACL reconstruction are associated with transient acute post-injury synovial inflammation and tissue catabolism

SummaryThe study described here tested the hypothesis that early intra-articular inflammation is associated with the development of post-traumatic osteoarthritis (PTOA) in a sheep model. We extended previously published work in which we investigated joint gross morphology and synovial mRNA expression of inflammatory and catabolic molecules 2 weeks after anatomic Anterior cruciate ligament (ACL) autograft reconstructive surgery (ACL-R). The same variables have been analyzed at 20 weeks post surgery together with new experimental variables at both time points. Animals were sacrificed at 20 weeks post ACL-R surgery and their joints graded for signs of PTOA. Synovial samples were harvested for histological grading plus mRNA and protein analysis for a panel of inflammatory and catabolic molecules. The mRNA expression levels for this panel plus connective tissue matrix turnover molecules were also investigated in cartilage samples. Results of gross morphological assessments at 20 weeks post surgery showed some changes consistent with early OA, but indicated little progression of damage from the 2 week time point. While significant alterations in mRNA levels for synovial inflammatory and catabolic molecules were detected at 2 weeks, values had normalized by 20 weeks. Similarly, all mRNA expression levels for inflammatory and catabolic molecules in articular cartilage had returned to normal levels by 20 weeks post ACL-R surgery. We conclude that synovial inflammatory processes are initiated very early after ACL-R surgery and may instigate events that lead to the gross cartilage and joint abnormalities observed as early as 2 weeks. However, the absence of sustained inflammation and joint instability may prevent OA progression

Smart Polymers in Drug Delivery Applications

Acknowledgements: The authors sincerely acknowledge the financial supports of the UGC, New Delhi under UPE-FARI Program [F.No. 14-3/2012 (NS/PE)] and the DST, New Delhi under DST-PURSE-Phase-II Program [F.No. SR/PURSE Phase 2/13(G)]. Furthermore, this research was supported by the European Regional Development Fund (FEDER), through COMPETE2020 under the PT2020 program (POCI-01-0145-FEDER-023423), and by the Portuguese Foundation for Science and Technology (UID/Multi/04044/2013) and PAMI (ROTEIRO/0328/2013; Nº 022158).The most important components of living cells such as carbohydrates, proteins and nucleic acids are the polymeric molecules. Nature utilizes polymers both as constructive elements and as a part of the complicated cell machinery of living things. The rapid advancement in biomedical research has led to many creative applications for biocompatible polymers. With the development of newer and more potent drugs, a parallel expansion in more sophisticated drug delivery systems becomes mandatory. Smart polymeric drug delivery systems can respond to environmental changes and consequently, alter their properties reversibly enabling an efficient and safe drug delivery. This review comprehensively discusses various aspects of these polymers classified in different categories as per the type of stimulus.info:eu-repo/semantics/publishedVersio

Fluorescent Pigment and Phenol Glucosides from the Heartwood of Pterocarpus marsupium

The fluorescence shown by extracts of the heartwood of Pterocarpus marsupium is attributed to salts of the new compound 1, whose structure was elaborated using detailed spectroscopic/ spectrometric studies. The plant material also contains the nonfluorescent compounds 2 and 3. The absolute configuration of 1 was determined by experimental and theoretically calculated electronic CD spectra, while that of 3 was deduced from ECD comparison with reported results in the α-hydroxydihydrochalcone series

Effect of the 3'APOB-VNTR polymorphism on the lipid profiles in the Guangxi Hei Yi Zhuang and Han populations

<p>Abstract</p> <p>Background</p> <p>Apolipoprotein (Apo) B is the major component of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and chylomicrons. Many genetic polymorphisms of the Apo B have been described, associated with variation of lipid levels. However, very few studies have evaluated the effect of the variable number of tandem repeats region 3' of the Apo B gene (3'APOB-VNTR) polymorphism on the lipid profiles in the special minority subgroups in China. Thus, the present study was undertaken to study the effect of the 3'APOB-VNTR polymorphism on the serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations.</p> <p>Methods</p> <p>A total of 548 people of Hei Yi Zhuang were surveyed by a stratified randomized cluster sampling. The epidemiological survey was performed using internationally standardized methods. Serum lipid and apolipoprotein levels were measured. The 3'APOB-VNTR alleles were determined by polymerase chain reaction (PCR) followed by electrophoresis in polyacrylamide gels, and classified according to the number of repeats of a 15-bp hypervariable elements (HVE). The sequence of the most common allele was determined using the PCR and direct sequencing. The possible association between alleles of the 3'APOB-VNTR and lipid variables was examined. The results were compared with those in 496 people of Han who also live in that district.</p> <p>Results</p> <p>Nineteen alleles ranging from 24 to 64 repeats were detected in both Hei Yi Zhuang and Han. HVE56 and HVE58 were not be detected in Hei Yi Zhuang whereas HVE48 and HVE62 were totally absent in Han. The frequencies of HVE26, HVE30, HVE46, heterozygote, and short alleles (< 38 repeats) were higher in Hei Yi Zhuang than in Han. But the frequencies of HVE34, HVE38, HVE40, homozygote, and long alleles (≥ 38 repeats) were lower in Hei Yi Zhuang than in Han (<it>P </it>< 0.05–0.01). The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and Apo B in Hei Yi Zhuang but not in Han were higher in VNTR-LS (carrier of one long and one short alleles) than in VNTR-LL (the individual carrying two long alleles) genotypes. The levels of TC, triglycerides (TG), LDL cholesterol, and Apo B in Hei Yi Zhuang were higher in both HVE34 and HVE36 alleles than in HVE32 allele. The levels of TC, TG, HDL-C and Apo B in Hei Yi Zhuang were also higher in homozygotes than in heterozygotes. There were no significant differences in the detected lipid parameters between the VNTR-SS (carrier of two short alleles) and VNTR-LS or VNTR-LL genotypes in both ethnic groups.</p> <p>Conclusion</p> <p>There were significant differences of the 3'APOB-VNTR polymorphism between the Hei Yi Zhuang and Han populations. An association between the 3'APOB-VNTR polymorphism and serum lipid levels was observed in the Hei Yi Zhuang but not in the Han populations.</p

Brevianes Revisited

Breviones are a new family of secondary metabolites that were originally isolated from the New Zealand endemic fungus Penicillium brevicompactum var. Dierckx. These compounds are generally characterized by a new carbon skeleton, known as breviane, which that has three possible structural variations, such as breviane, abeo-breviane, and abeo-norbreviane. Brevianes present a basic diterpenic tricyclic core that is mevalonic in origin and is similar to that of perhydrophenanthrene. The core bears four methyl groups at positions C4, C8, C10, and C13 and has defined stereochemistry at positions C5, C8, C9, C10, and C14. The C1'-C7' side chain has been proposed to have a polyketide biosynthetic origin and is joined to the diterpenic moiety through carbons C2'-C15'. The cyclization and lactonization of this part of the molecule leads to the characteristic breviane spiranic ring fused to the α-pyrone

Metagenomic next-generation sequencing of the 2014 Ebola Virus disease outbreak in the Democratic Republic of the Congo

We applied metagenomic next-generation sequencing (mNGS) to detect Zaire Ebola virus (EBOV) and other potential pathogens from whole-blood samples from 70 patients with suspected Ebola hemorrhagic fever during a 2014 outbreak in Boende, Democratic Republic of the Congo (DRC) and correlated these findings with clinical symptoms. Twenty of 31 patients (64.5%) tested in Kinshasa, DRC, were EBOV positive by quantitative reverse transcriptase PCR (qRT-PCR). Despite partial degradation of sample RNA during shipping and handling, mNGS followed by EBOV-specific capture probe enrichment in a U.S. genomics laboratory identified EBOV reads in 22 of 70 samples (31.4%) versus in 21 of 70 (30.0%) EBOV-positive samples by repeat qRT-PCR (overall concordance = 87.1%). Reads from Plasmodium falciparum (malaria) were detected in 21 patients, of which at least 9 (42.9%) were coinfected with EBOV. Other positive viral detections included hepatitis B virus (n = 2), human pegivirus 1 (n = 2), Epstein-Barr virus (n = 9), and Orungo virus (n = 1), a virus in the Reoviridae family. The patient with Orungo virus infection presented with an acute febrile illness and died rapidly from massive hemorrhage and dehydration. Although the patient's blood sample was negative by EBOV qRT-PCR testing, identification of viral reads by mNGS confirmed the presence of EBOV coinfection. In total, 9 new EBOV genomes (3 complete genomes, and an additional 6 ≥50% complete) were assembled. Relaxed molecular clock phylogenetic analysis demonstrated a molecular evolutionary rate for the Boende strain 4 to 10× slower than that of other Ebola lineages. These results demonstrate the utility of mNGS in broad-based pathogen detection and outbreak surveillance