The legacy effect in early-stage diabetes: Don't stay by me, cardiovascular disease!

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Results of Hepatitis B Vaccination 3 Years After a Primary Vaccine Series in Medical Students

Objective：To investigate the significance of additional hepatitis B （HB） vaccination in medical students who were unresponsive to a primary vaccine series or those who had lost antibody to hepatitis B surface antigen （anti-HBs）.Methods：Subjects were followed up for 3 years after completion of a primary HB vaccine series. One additional dose was given to those who lost the anti-HBs within 3 years after the initial series, while 3 doses were given to those who had not responded to the initial vaccination. Subjects：100 medical students （59 men and 41 women；mean age on admission to university, 19.4±1.6 years） enrolled at the School of Medicine, Dokkyo Medical University in April 2012.Results：The rate of positivity for anti-HBs was 98％ soon after completion of the primary HB vaccine series and decreased without the need for additional vaccination to 79％, 61％, and 55％ at 1, 2, and 3 years after the primary series, respectively. Eighteen vaccinated subjects （18％） lost the anti-HBs 2 years after the primary series, and all of them responded to 1 additional dose. Another 18 successfully vaccinated subjects （18％） were anti-HBs negative both 1 and 2 years after the primary series；17 of them responded to 1 additional dose. As for 2 subjects （2％） who were unresponsive to the primary series, 1 became anti-HBs-positive for the first time after 3 additional doses given 2 years after the primary series.Conclusion：A number of students became or remained anti-HBs negative after the primary HB vaccination, indicating that its timing and dose of additional vaccination need to be studied further to evaluate its utility

Drug-eluting stents

Stent implantation was developed to overcome the acute recoil and high restenosis rate of balloon angioplasty, but resulted in the development of chronic in-stent restenosis related to specific factors regarding patient, stent, lesion and procedural characteristics. Some factors are not modifiable, such as patient and lesion characteristics, whereas procedural characteristics may be improved by better implantation technique and stent design. Drug-eluting stents are a novel approach in stent technology and design with local drug delivery to inhibit intimal thickening by interfering with different pathways involved in the development of inflammation, migration, proliferation and/or secretion of the extracellular matrix. Both the drug and the delivery vehicle must fulfill pharmacological, pharmacokinetic and mechanical requirements. Current successful drug eluting stents require a polymer coating for drug delivery. Clinical trials examining several pharmaceutical agents, particularly sirolimus and paclitaxel, have demonstrated marked reduction in restenosis following stenting. Sirolimus is a natural macrocyclic lactone and paclitaxel is a cytotoxic agent against many tumors. Both compounds block cell cycle progression and thus inhibit smooth muscle cell proliferation. The development of drug-eluting stents is one of the major revolutions in the field of Interventional Cardiology. Restenosis rate has been significantly reduced, in comparison to bare metal stents. The ideal drug to prevent restenosis must have an anti-proliferative and anti-migratory effect on smooth muscle cells but on the other hand must also enhance re-endothelialization, in order to prevent late thrombosis. Additionally, it should effectively inhibit the anti-inflammatory response after balloon induced arterial injury. Currently sirolimus, paclitaxel and more recently, ABT-578-eluting stents are commercially available, but ongoing research and clinical trials will result in new stents coming to market with novel designs loaded with a variety of compounds. As drug-eluting stent implantation becomes more liberal leading to an extensive use of this technology, the problem of restenosis in drug-eluting stents will become more common. However, for the time being, little is known regarding optimal treatment of in-stent restenosis following drug-eluting stent implantation. Future research is mandatory to further clarify, whether these patients should be treated with the same drug-eluting stent, with a different drug-eluting stent or with increased doses. Further improvements, including expansion of drug-loading capacity, coatings with programmable pharmacokinetic capacity and the discovery of new drugs may in the future further enhance the efficacy and safety of these stents. Although, drug-eluting stents have significantly reduced angiographic restenosis rate and have improved the clinical outcome, late thrombosis and restenosis remain an important subject of ongoing research. As drug-eluting stents are extensively used to treat all lesions, more efficacious agents and improved stent platforms are required. Synthetic or biological polymers can be used as matrixes for drug incorporation, but concerns have been raised regarding bio-compatibility, sterility or potential induction of inflammation. Currently, alterations on stent-backbone design (biodegradable, bioabsorbable, nanoporous etc.) are being explored. Clearly, the anti-proliferative compounds sirolimus and paclitaxel have dominated up to date clinical practice, whereas their analogues are readily emerging. In the future, however, it is likely that drugs, currently under investigation, will address additional mechanisms associated with neointimal formation leading to restenosis, either as single agents or in combination with anti-proliferative compounds

Myofibroblasts acquire retinoic acid–producing ability during fibroblast-to-myofibroblast transition following kidney injury

腎障害における線維化の正の側面の発見 --線維化が腎臓を修復する--. 京都大学プレスリリース. 2019-01-18.Tubular injury and interstitial fibrosis are the hallmarks of chronic kidney disease. While recent studies have verified that proximal tubular injury triggers interstitial fibrosis, the impact of fibrosis on tubular injury and regeneration remains poorly understood. We generated a novel mouse model expressing diphtheria toxin receptor on renal fibroblasts to allow for the selective disruption of renal fibroblast function. Administration of diphtheria toxin induced upregulation of the tubular injury marker Ngal and caused tubular proliferation in healthy kidneys, whereas administration of diphtheria toxin attenuated tubular regeneration in fibrotic kidneys. Microarray analysis revealed down-regulation of the retinol biosynthesis pathway in diphtheria toxin-treated kidneys. Healthy proximal tubules expressed retinaldehyde dehydrogenase 2 (RALDH2), a rate-limiting enzyme in retinoic acid biosynthesis. After injury, proximal tubules lost RALDH2 expression, whereas renal fibroblasts acquired strong expression of RALDH2 during the transition to myofibroblasts in several models of kidney injury. The retinoic acid receptor (RAR) RARγ was expressed in proximal tubules both with and without injury, and αB-crystallin, the product of an RAR target gene, was strongly expressed in proximal tubules after injury. Furthermore, BMS493, an inverse agonist of RARs, significantly attenuated tubular proliferation in vitro. In human biopsy tissue from patients with IgA nephropathy, detection of RALDH2 in the interstitium correlated with older age and lower kidney function. These results suggest a role of retinoic acid signaling and cross-talk between fibroblasts and tubular epithelial cells during tubular injury and regeneration, and may suggest a beneficial effect of fibrosis in the early response to injury