抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Reactive oxygen species

Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

In Vivo Endoscopic Optical Biopsy with Optical Coherence Tomography

The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141(+) DC subset. CD141(+) DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-beta, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c(+) DC subset. Polyinosine-polycytidylic acid (poly I:C)-activated CD141(+) DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8(+) cytotoxic T lymphocytes than poly I:C-activated CD1c(+) DCs. Importantly, CD141(+) DCs, but not CD1c(+) DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141(+) DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8 alpha(+) DC subset. The data demonstrate a role for CD141(+) DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.

Human CD141(+) (BDCA-3)(+) dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens

Fitzpatrickʼs Dermatology in General Medicine

This study was carried out to determine whether polymorphisms of organic anion-transporting polypeptide 1B1 (OATP1B1) have an effect on rosuvastatin pharmacokinetics in Koreans. Among 200 subjects genotyped for OATP1B1 c.388A>G, and c.521T>C, 30 subjects were selected for the rosuvastatin pharmacokinetic study. The area under the concentration-time curve for 0 to infinity (AUC(0-infinity)) of rosuvastatin for group 1 (*1a/*1a, *1a/*1b, *1b/*1b), group 2 (*1a/*15, *1b/*15), and group 3 (*15/*15) were 111+/-49.3, 126+/-45.2, and 191+/-31.0 ng h/ml, respectively, with significant differences among the three groups (P=0.0429) and between *15/*15 and the other groups (P=0.0181). The maximum plasma concentration (Cmax) also showed a significant difference between *15/*15 and the other groups (P=0.0181). There were no significant differences in rosuvastatin-lactone pharmacokinetics among the three groups. The pharmacokinetic exposure of rosuvastatin was higher in the OATP1B1*15/*15 subjects than the others, suggesting a potential association between the OATP1B1 genetic polymorphisms and altered rosuvastatin pharmacokinetics in Korean populations.

Influence of OATP1B1 genotype on the pharmacokinetics of rosuvastatin in Koreans

Oxidative stress results from a prooxidant-antioxidant imbalance, leading to cellular damage It is mediated by free radicals, such as reactive oxygen species or reactive nitrogen species, that are generated during physiological aerobic metabolism and pathological inflammatory processes Skin serves as a protective organ that plays an important role in defending both external and internal toxic stimuli and maintaining homeostasis It is becoming increasingly evident that oxidative stress is involved in numerous skin diseases and that antioxidative strategies can serve as effective and easy methods for improving these conditions Herein, we review dysregulated antioxidant systems and antioxidative therapeutic strategies in dermatology

https://www.tandfonline.com/doi/pdf/10.1179/1351000215Y.0000000015

Oxidative stress and antioxidant strategies in dermatology

The objective of this retrospective study is to assess neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as inflammatory markers in patients with psoriasis and psoriatic arthritis (PsA). A hundred and eleven psoriasis patients and 25 PsA patients were compared with 94 healthy controls. Demographic, clinical and laboratory information were collected and analyzed. NLR and PLR were calculated. White blood cell (WBC), neutrophils, eosinophils and NLR were increased in psoriasis patients compared with controls. WBC, neutrophils, NLR, monocytes, platelets and PLR were increased in PsA patients compared with both controls and psoriasis patients. Erythrocyte sedimentation rate (ESR) and C-reactive protein were significantly higher in PsA patients compared with psoriasis patients. Among psoriasis patients, Psoriasis Area and Severity Index (PASI) score correlated positively with platelets, NLR and PLR. These parameters were all significantly higher in moderate to severe psoriasis patients (PASI ≥ 10) compared with mild patients (PASI < 10). Elevated platelets, NLR and PLR were significantly associated with the increased PASI scores in multivariate analysis. NLR, PLR and ESR were statistically significant predictors for the presence of PsA in psoriasis patients. NLR was the strongest predictor (odds ratio = 3.351, P = 0.005). In conclusion, elevated NLR and PLR were significantly associated with psoriasis and PsA. Both NLR and PLR were strong predictors for the presence of PsA among psoriasis patients.

Assessments of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in Korean patients with psoriasis vulgaris and psoriatic arthritis

We evaluated the effect of the pregnane X receptor (PXR) agonist rifampin on metformin pharmacokinetics, organic cation transporter 1 (OCT1) and OCT2 mRNA levels, and glucose levels, using the oral glucose tolerance test (OGTT) in 16 healthy subjects. The glucose-lowering effects of metformin were evaluated by OGTT before and after metformin treatment on days 1 and 2 and again on days 13 and 14 after a 10-day course of rifampin. Rifampin increased the difference in maximum glucose levels (ΔGmax) by 41.9% (P = 0.024) and the area under the concentration–time curve (AUC) during the first 60 min after glucose ingestion (ΔAUCgluc60) by 54.5% (P = 0.020). Renal clearance (CLR) of metformin was increased by 16% (P = 0.008), but the systemic exposure was only slightly increased (13%, P = 0.049), possibly because of increased absorption. Rifampin increased OCT1 mRNA levels 4.1-fold in peripheral blood cells (P = 0.001); however, OCT2 mRNA was not detected. Our results suggest that rifampin increases OCT1 expression and hepatic uptake of metformin, leading to enhanced glucose-lowering action.



Clinical Pharmacology & Therapeutics (2011) 89 3, 416–421. doi:10.1038/clpt.2010.266

Rifampin enhances the glucose-lowering effect of metformin and increases OCT1 mRNA levels in healthy participants.

Skin cancer is the most common malignancy in humans. Therapeutic modalities for skin cancer are local destruction, radiotherapy and surgery. External radiation therapy leads to good results, however, generally 5–6 wk of treatment is needed to deliver optimal radiation dose to tumors. In this study, a beta-emitting radionuclide, 166HO, impregnated in a specially designed patch, was used on superficial skin cancers and Bowen9s disease for local irradiation. Methods: Ten mice with chemically induced skin tumors were studied. Five millimeter size patches containing 22.2–72.15 MBq (0.6–1.95 mCi) 166HO were applied to the tumor surface for 1–2 hr. In a human trial, patients with squamous-cell carcinoma(n = 3), basal cell carcinoma (n = 1) and Bowen9s disease (n = 1) were treated with patches containing 273.8–999 MBq (74–27 mCi) of 166HO for 30 min to 1 hr. Pathologic examination was performed 4–7 wk after treatment in an animal model. Skin biopsy was performed 8 wk post-treatment in four patients. Results: Tumor destruction was seen 1 wk posttreatment, however, radiation dermatitis or ulceration developed at the site of radionuclide application. Those reactions healed gradually with fibrosis or epithelialization, which was confirmed pathologically. No significant adverse reaction to radiation except subcutaneous fibrosis was found. Conclusion: Superficial skin tumors could be successfully treated by topical application of beta-emitting radionuclides.

https://jnm.snmjournals.org/content/38/5/697.full.pdf

Min Geol Lee

Papers

Influence of OATP1B1 genotype on the pharmacokinetics of rosuvastatin in Koreans

Oxidative stress and antioxidant strategies in dermatology

Assessments of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in Korean patients with psoriasis vulgaris and psoriatic arthritis

Rifampin enhances the glucose-lowering effect of metformin and increases OCT1 mRNA levels in healthy participants.

Radionuclide therapy of skin cancers and Bowen's disease using a specially designed skin patch.