Modeling of drug delivery into tissues with a microneedle array using mixture theory

In this paper, we apply mixture theory to quantitatively predict the transient behavior of drug delivery by using a microneedle array inserted into tissue. In the framework of mixture theory, biological tissue is treated as a multi-phase fluid saturated porous medium, where the mathematical behavior of the tissue is characterized by the conservation equations of multi-phase models. Drug delivery by microneedle array imposes additional requirements on the simulation procedures, including drug absorption by the blood capillaries and tissue cells, as well as a moving interface along its flowing pathway. The contribution of this paper is to combine mixture theory with the moving mesh methods in modeling the transient behavior of drug delivery into tissue. Numerical simulations are provided to obtain drug concentration distributions into tissues and capillaries.     

DNA methylation changes in photoperiod-thermo-sensitive male sterile rice PA64S under two different conditions

Epigenetic modification can occur at a high frequency in crop plants and might generate phenotypic variation without changes in DNA sequences. DNA methylation is an important epigenetic modification that may contribute to environmentally-induced phenotypic variations by regulating gene expression. Rice Photoperiod-Thermo-Sensitive Genic Male Sterile (PTGMS) lines can transform from sterility to fertility under lower temperatures and short-day (SD) conditions during anther development. So far, little is known about the DNA methylation variation of PTGMS throughout the genome in rice. In this study, we investigated DNA cytosine methylation alterations in the young panicles of PTGMS line PA64S under two different conditions using methylation sensitive amplified polymorphism (MSAP) method. Compared with the DNA methylation level of PA64S under lower temperatures and SD conditions (fertility), higher methylation was observed in PA64S (sterility). The sequences of 25 differentially amplified fragments were successfully obtained and annotated. Three methylated fragments, which are homologous to D2, NAD7 and psaA, were confirmed by bisulfite sequencing and their expression levels were also evaluated by qPCR. Real time quantitative PCR analysis revealed that five of the six selected methylated genes were downregulated in PA64S (sterility). These results suggested that DNA methylation may be involved in the sterility–fertility transition of PA64S under two different environmental conditions.     

六六六在水环境中转移、积累和归趋研究——3.六六六在鱼体的积累释放

鳃是六六六进入鱼体的主要通道,鱼体的残留水平决定于水与体脂间的分配平衡。要使背肌六六六残留低于0.5毫克/公斤,则水中六六六含量要低于0.024毫克/升。鱼体六六六残留向水体释放的速度与温度有关,温度低,释放慢;当温度低于10℃时,释放的速度极慢以至难以检出。建议采用清水寄养的方法,让鱼体释放六六六,降低残毒,提高商品质量。这种方法估计也适用于其它脂溶性的与水分配系数不是太大的污染物。       

一氧化氮增加常氧和缺氧豚鼠心室肌细胞持续性钠电流

运用全细胞膜片钳记录缺氧条件下豚鼠心室肌持续性钠电流(INa.P)的变化及施加药物对其的影响,以探讨 INa.P 的本质及缺氧增大 INa.P 的机制。结果显示:(1)在常氧条件下,一氧化氮(NO)前体 L- 精氨酸(L-Arg)和供体硝普钠(SNP)浓度依赖性地增大INa.P; (2)INa.P 随缺氧时间延长而增大, 缺氧15 min 后施加 NO 合酶(NOS)抑制剂L- 硝基精氨酸甲酯(L-NAME), 不能使增大的INa.P 明显回复[(1.344 ±0.320) vs (1.301 ±0.317) pA/pF, P>0.05, n=5]; (3)缺氧时含L-NAME 的灌流液可使INa.P 明显减小,与单纯缺氧相比有显著差异[(0.914 ± 0.263), n=5 vs (1.344 ± 0.320) pA/pF, n=6, P<0.05], 但仍比常氧条件下增大[(0.914 ±0.263) vs (0.497 ±0.149) pA/pF, P<0.05, n=5]; (4)还原剂1,4-二硫代苏糖醇(DTT)不但可使L-Arg 及缺氧后施加SNP 增大的 INa.P 回复[(1.449 ± 0.522) vs (0.414 ± 0.067) pA/pF, P<0.01, n = 6 和(0.436 ± 0.141) vs (1.786 ± 0.636) pA/pF,P<0.01, n=5],而且使正常的 INa.P 减小[(0.396 ± 0.057) pA/pF vs (0.442 ± 0.056) pA/pF, P<0.01, n=6]。本实验结果表明缺氧可增大心室肌细胞的INa.P, 其作用机制可能是缺氧时心肌产生的NO 通过氧化细胞膜上钠通道蛋白所致,正常INa.P 的产生     

Metabolic alteration of the N-glycan structure of a protein from patients with a heterozygous protein deficiency

Glycosylation, an important post-translation modification, could alter biological activity or influence the clearance rates of glycoproteins. We report here the first example of a heterozygous protein deficiency leading to metabolic alteration of N-glycan structures in residual secreted protein. Analysis of C1 esterase inhibitor (C1INH) glycans from normal individuals and patients with hereditary deficiency of C1INH demonstrated identical O-glycan structures but the N-glycans of patients with a heterozygous genetic deficiency were small, highly charged and lacked sialidase releasable N-acetylneuraminic acid. Structural studies indicate that the charge character of these aberrant N-glycan structures may result from the presence of mannose-6-phosphate residues. These residues might facilitate secretion of C1INH through an alternate lysosomal pathway, possibly serving as a compensatory mechanism to enhance plasma levels of C1INH in these deficient patients.     

利用假型反转录病毒对大部分胰腺切除后再生细胞的世系追踪

胰腺是一个重要的内外分泌混合腺, 胰腺发生损伤后能够再生。为了探讨胰腺活体细胞世系追踪的方法和胰腺损伤后再生细胞的来源,分别通过胰腺伤口涂抹并胰内注射、尾静脉注射及腹腔注射三种方法, 利用假型反转录病毒对成体小鼠大部分切除后胰腺的细胞进行世系追踪。结果发现在活体条件下, 与尾静脉注射及腹腔注射法相比, 胰腺伤口涂抹并胰腺内注射反转录病毒的方法能够更有效的标记胰腺细胞; 而且, 通过对标记细胞的世系追踪研究证明, 在胰腺损伤后, 胰腺腺泡细胞能够接受损伤信号刺激发生再生。为今后进一步利用反转录假病毒对活体胰腺进行细胞命运追踪研究奠定基础, 为利用反转录病毒载体进行胰腺疾病的基因治疗提供线索。     

Rapid effects of the intravenous injection of a medium-chain triglyceride: fish oil emulsion on the triglyceride fatty acid pattern of soleus muscle from omega3 fatty acid-depleted rats.

Second generation rats depleted in long-chain polyunsaturated omega3 fatty acids display several features of the metabolic syndrome, including visceral obesity, liver steatosis, insulin resistance, hypertension, and cardiac hypertrophy. In the framework of an extensive study on such metabolic, hormonal and functional perturbations, the phospholipid fatty acid pattern and ex vivo metabolism of D-glucose were recently investigated in the soleus muscle of these omega3-depleted rats. The present study deals with the triglyceride fatty acid content and pattern of the soleus muscle in control animals and omega3-depleted rats. Some of the latter rats were injected intravenously 60-120 minutes before sacrifice with either an omega3 fatty acid-rich medium-chain triglyceride/fish oil emulsion (omega3-FO rats) or a control medium-chain triglyceride/olive oil emulsion (omega3-OO rats). The total fatty acid content of triglycerides was comparable in control and omega3-depleted rats and, in both cases, inversely related to their C20:4omega6 relative content. At variance with the situation found in control rats, no long-chain polyunsaturated omega3 fatty acid (C18:3omega3, C20:5omega3, C22:5omega3, C22:6omega3) was detected in the omega3-depleted rats. Unexpectedly, the triglyceride content in most long-chain polyunsaturated omega6 fatty acids (C18:2omega6, C20:3omega6, C20:4omega6 and C22:4omega6) had also decreased in the latter rats. Moreover, the activity of Delta9-desaturase was apparently increased in the omega3-depleted rats, as judged from the C16:1omega7/C16:0 and C18:1omega9/C18:0 ratios. The omega3-FO rats differed from omega3-OO rats by a lower contribution of C18:2omega6 metabolites (C18:3omega6, C20:3omega6, C20:4omega6 and C22:4omega6). These findings indicate that the prior injection of the medium-chain triglyceride/fish oil emulsion, known to increase the muscle phospholipid content in long-chain polyunsaturated omega3 fatty acids, may nevertheless accentuate the depletion in long-chain polyunsaturated omega6 fatty acids otherwise found in the triglycerides of omega3-depleted rats. Such a dual effect is reminiscent of that observed, under the same experimental conditions, for selected variables in D-glucose metabolism in the soleus muscle.     

Identification of salt-stress responsive genes in rice (Oryza sativa L.) by cDNA array

To identify salt stress-responsive genes, we constructed a cDNA library with the salttolerant rice cultivar, Lansheng. About 15000 plasmids were extracted and dotted on filters with Biomeck 2000 HDRT system or by hand. Thirty genes were identified to display altered expression levels responding to 150 mmol/L NaCl. Among them eighteen genes were up-regulated and the remainders downregulated. Twenty-seven genes have their homologous genes in GenBank Databases. The expression of twelve genes was studied by Northern analysis. Based on the functions, these genes can be classified into five categories, including photosynthesis-related gene, transportrelated gene, metabolismrelated gene, stress-or resistancerelated gene and the others with various functions. The results showed that salt stress influenced many aspects of rice growth. Some of these genes may play important roles in plant salt tolerance.