累及右侧心腔的静脉内平滑肌瘤病(附2例报告)

目的探讨累及右侧心腔的静脉内平滑肌瘤病的诊断和治疗方法。方法对2例累及右侧心腔的静脉内平滑肌瘤病患者采用腹部B超和心脏超声、增强CT等检查。手术治疗官分期进行,一期行心脏及下腔静脉肿瘤切除术,二期于术后1个月行子宫切除并盆腔清扫术。结果2例患者手术均获成功,1例随访3年,另1例随访4．5年,均存活。结论累及右侧心腔的静脉内平滑肌瘤病罕见,详尽的术前检查、分期手术切除以及相关学科的协作是根治本病的关键。     

大鼠脑缺血后脑内MPO、NSE活性变化

目的 通过测定大鼠局灶性脑缺血-再灌流后不同时点脑组织中髓过氧化物酶(MPO)和神经元特异性烯醇化酶(NSE)活性的变化,探讨炎症反应与脑缺血损伤的关系.方法 用线栓法制备大鼠左侧大脑中动脉缺血-再灌流模型,检测缺血3h再灌流后6h、12h、24h、48h、72h和7d脑组织中MPO和NSE活性、脑梗死体积的变化.结果 缺血组脑组织中NSE和MPO活性升高,再灌流后48h的NSE为(5.44±0.95)ng/ml,MPO为4.49±0.22;72h分别为(5.36±0.65)ng/l和5.96±0.19,升高最为明显.脑梗死体积随再灌流时间延长而增加,第7d梗死体积百分比为(39.18±0.63)%.局灶性缺血脑组织中MPO活性与组织损伤(NSE活性)间具有高度正相关性.结论 炎症反应是加重脑缺血损伤的重要因素.     

Saroclazines A–C,thio-diketopiperazines from mangrove-derived fungi <Emphasis Type="Italic">Sarocladium kiliense</Emphasis> HDN11-84

Three new diketopiperazine derivatives (DKPs), saroclazines A–C (1–3) along with three known DKPs (4–6) were isolated from mangrove-derived fungi Sarocladium kiliense HDN11-84. Saroclazines A–B (1 and 2) possessed a free amide structure, which was first found in sulfur-containing aromatic DKPs. Their structures were elucidated by NMR, HRESIMS and X-ray. The cytotoxic activity of new compounds (1–3) was tested against HeLa cell lines, among which compound 2 showed an IC₅₀ value of 4.2 µM.     

Association between sperm mitochondrial ND2 gene variants and total fertilization failure

The objective of this study was to explore the association of sperm mitochondrial ND2 (MT-ND2) gene variants with total fertilization failure (TFF). A retrospective comparative study of 246 cases of fresh in vitro fertilization (IVF) cycles or half-intracytoplasmic sperm injection cycles in the Han Chinese population was performed from July 2011 to May 2017. A total of 59 cases undergoing TFF, and 187 control cases with normal fertilization (fertilization rates >50%) were included. The sperm mitochondrial genovariation was determined using nested sequencing. A total of 32 homoplasmic variants and 47 heteroplasmic variants of MT-ND2 gene were observed in this study. There were no significant differences in the frequencies of the 32 homoplasmic variants of MT-ND2 gene between the TFF and control groups. A total of 53 pair-wise comparisons were performed, and the general characteristics of the IVF failure and control subjects were adjusted in logistic models. Data suggested that there were no significant differences in the frequencies of point 4914, 5320, and 5426 heteroplasmic variants of MT-ND2 gene between the TFF and control groups. In addition, no significant difference was observed in the frequency of mtDNA haplogroup D or haplogroup G between the IVF failure group and the normal fertilization group. This study suggests that the MT-ND2 gene variants might not be associated with TFF.

Abbreviations: ATP: adenosine triphosphate; dNTP: deoxy-ribonucleoside triphosphate; FADH2: flavin adenine dinucleotide; FDR: false discovery rate; FSH: follicle-stimulating hormone; IVF: in vitro fertilization; LH: luteinizing hormone; MTATP6: mitochondrially encoded ATP synthase 6; MTCYB: mitochondrially encoded cytochrome b; mtDNA: mitochondrial DNA; MT-ND2: mitochondrial ND2; NADH: nicotinamide adenine dinucleotide; ND2: NADH dehydrogenase subunit 2; OXPHOS: oxidative phosphorylation; PCR: single nucleotide polymorphisms; SNPs: single nucleotide polymorphisms; TFF: total fertilization failure     

Evaluation of Transdermal Drug Permeation as Modulated by Lipoderm and Pluronic Lecithin Organogel

The transdermal delivery of 2 fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from 2 commercially available transdermal bases, pluronic lecithin organogel, and Lipoderm^® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free acid) through porcine skin was evaluated. Retention and depth distribution profiles in skin were obtained by tape stripping and then followed by optical sectioning using multiphoton microscopy. The results showed that Lipoderm^® led to an enhanced penetration of the hydrophilic compound, fluorescein sodium. For the lipophilic compound fluorescein (free acid), Lipoderm^® performed similar to pluronic lecithin organogel base, where minimal drug was detected in either receptor phase. The skin retention and depth distribution results also showed that the hydrophilic fluorescein sodium had high skin retention with Lipoderm^®, whereas fluorescein (free acid) had very low penetration and retention with increasing skin depth. Moreover, optical sectioning by multiphoton microscopy revealed an uneven distribution of probes across the skin in the x-y plane for both transdermal bases. This work showed that a hydrophilic compound has significantly increased skin penetration and retention when formulated with Lipoderm^®, and the skin retention of the probe was the main determinant of its skin flux.     

Prediction of Human Brain Penetration of P-glycoprotein and Breast Cancer Resistance Protein Substrates Using In Vitro Transporter Studies and Animal Models

Four P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrates with human cerebrospinal fluid (CSF) concentrations and preclinical neuropharmacokinetics were used to assess in vitro–in vivo extrapolation of brain penetration in preclinical species and the ability to predict human brain penetration. Unbound brain (C_b,u), unbound plasma (C_p,u), and CSF compound concentrations (C_CSF) were measured in rats and nonhuman primates (NHPs), and the unbound partition coefficients (C_b,u/C_p,u and C_CSF/C_p,u) were used to assess brain penetration. The results indicated that for P-gp and BCRP dual substrates, brain penetration was severally impaired in all species. In comparison, for P-gp substrates that are weak or non-BCRP substrates, improved brain penetration was observed in NHPs and humans than in rats. Overall, NHP appears to be more predictive of human brain penetration for P-gp substrates with weak or no interaction with BCRP than rat. Although C_CSF does not quantitatively correspond to C_b,u for efflux transporter substrates, it is mostly within 3-fold higher of C_b,u in rat and NHP, suggesting that C_CSF can be used as a surrogate for C_b,u. Taken together, a holistic approach including both in vitro transporter and in vivo neuropharmacokinetics data enables a better estimation of human brain penetration of P-gp/BCRP substrates.     

Sustained Release of Minocycline From Minocycline-Calcium-Dextran Sulfate Complex Microparticles for Periodontitis Treatment

It is important to address the periodontitis-associated bacteria in the residual subgingival plaque after scaling and root planing to successfully treat periodontitis. In this study, we explored the possibility of exploiting the ion pairing/complexation of minocycline, Ca²⁺, and sulfate/sulfonate-bearing biopolymers to develop an intrapocket delivery system of minocycline as an adjunct to scaling and root planing. Minocycline-calcium-dextran sulfate complex microparticles were synthesized from minocycline, CaCl₂, and dextran sulfate. They were characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. An in vitro release study was conducted to evaluate the release kinetics of minocycline from these microparticles. Agar disk diffusion assays and biofilm-grown bacteria assays were used to assess antibacterial capability. High loading efficiency (96.98% ± 0.12%) and high loading content (44.69% ± 0.03%) for minocycline were observed for these complex microparticles. Mino-Ca-DS microparticles achieved sustained release of minocycline for at least 9 days at pH 7.4 and 18 days at pH 6.4 in phosphate-buffered saline, respectively. They also demonstrated potent antimicrobial effects against Streptococcus mutans and Aggregatibacter actinomycetemcomitans in agar disk diffusion and biofilm assays. These results suggested that the ion pairing/complexation of minocycline, Ca²⁺, and sulfonate/sulfate-bearing biopolymers can be exploited to develop complex microparticles as local delivery systems for periodontitis treatment.     

Pharmacokinetics and tissue distribution of crotonoside

1.?Crotonoside is a bioactive ingredient from Croton Herba with a strong antitumour activity. This study aimed to develop a highly sensitive and selective high-performance liquid chromatography (HPLC) method to quantify crotonoside in biological samples for pharmacokinetics and distribution studies.

2.?Protein precipitation by perchloric acid was used to separate crotonoside from the biological samples, and the recovery rates for crotonoside and the internal standard (luteoloside) were >80%. All calibration curves examining the crotonoside levels in plasma and tissues were linear (all correlation coefficients >?0.99).

3.?The response to crotonoside appeared to be dose disproportional to the maximum plasma concentration and the area under the time–concentration curve in plasma over the range of 12.5–50.0?mg/kg, and crotonoside was highly distributed in tissues after intravenous administration. The highest crotonoside level was detected in the liver (28.79?±?14.96?μg/g), whereas crotonoside was undetected in the brain.