Alternating magnetic field damages the reproductive function of murine testes / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the relationship between physical and biological effects of alternating magnetic field and study the influence of the magnetic field on the reproductive function of murine testes.</p><p><b>METHODS</b>Thirty ICR mice were randomized into 5 groups: normal control, X-ray radiation, weak magnetic field (1000 Hz), 1 h strong magnetic field and 2 h strong magnetic field (2000 Hz). The mice were sacrificed at 7 days after the exposure for the analysis of testicular sperm motility, observation of histopathological changes in the testis by HE staining and evaluation of the changes by modified Johnsen grade criteria.</p><p><b>RESULTS</b>The rates of sperm motility were (42.37 +/- 10.24)% in the normal control group, (39.00 +/- 12.35)% in the X-ray radiation group, (36.00 +/- 17.28)% in the weak magnetic field group, (10.72 +/- 5.67)% in the 1 h strong magnetic field group and (4.44 +/- 2.87)% in the 2 h strong magnetic field group, respectively. Johnsen's scores decreased and the testis damage increased in a dose- and time-dependent manner.</p><p><b>CONCLUSION</b>Magnetic field, either strong or weak, may damage the testis function by inducing injury to seminiferous tubules and Leydig cells, thickening of the basal membrane, derangement, exfoliation, massive apoptosis and necrosis of spermatogenic cells in the lumen, situation of the epididymis, and consequently the absence of sperm.</p>

Study on the differential expression of lipid metabolism-related genes in young LDLR knockout mice liver / 中华病理学杂志

<p><b>OBJECTIVE</b>To clarify the differential expression of the genes related to the lipid metabolism in the early stage of atherosclerosis in the young LDLR-/- mice of different ages.</p><p><b>METHODS</b>A RT-PCR assay was used to analyse the gene expression patterns in the livers of LDLR-/- mice and wild type (WT) mice from 14 to 90 days. The characteristics of early lipid deposition in intima were evaluated using biochemical and pathological techniques.</p><p><b>RESULTS</b>In LDLR-/- mice, when compared to WT mice, the mRNA level of the apolipoprotein A IV (apoA IV), fatty acid translocase (Fat/CD36) and carnitine palmitoyl transferase I (CPT I) changed prominently at the age of 14-days (P < 0.05). At 30 days, the mRNA level of apolipoprotein A I (apoA I) was up regulated, but apolipoprotein F (apoF), CD36 and CPT I were down regulated (P < 0.05). At 60 days, the mRNA levels of apoA I, CPT I and liver X receptor alpha (LXRalpha) were up regulated, but apoA IV was down regulated (P < 0.05). At 90 days, the level of the apoA I was higher, but the expression of the apoA IV, apoF and acyl-coenzymeA oxidase 1 (ACOX1) were down regulated (P < 0.05), whereas the expression of apolipoprotein A V (apoA V), apolipoprotein E (apoE), peroxidase proliferator-activated receptor alpha (PPARalpha) and angiopoietin-like protein 3 (angptl 3) had no significant changes (P > 0.05). The serum levels of TC (P < 0.05), TG (P < 0.05) and LDLC (P < 0.05) in LDLR-/- mice were significantly higher than those in wild type mice with the same age.</p><p><b>CONCLUSIONS</b>The mRNA levels of the apoA I, apoA IV, apoF, FAT/CD36, CPT I, ACOX1 and LXRalpha of the LDLR-/- mice were significantly changed compared to the WT mice. The genes may be of some relevance to the complicated lipid metabolism network, and have effect in the early stage of atherogenesis.</p>

Differential expressions of lipid metabolism related genes in the liver of young apoE knockout mice / 生理学报

The work was aimed to investigate the differential expressions of lipid metabolism related genes in the early stage of atherosclerosis in the young apolipoprotein E deficient (apoE(-/-)) mice at different ages with normal chow diet. The genotypes of mice were identified by using multiplex polymerase chain reaction (multi-PCR) analysis. The semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR were used to analyze the expressions of lipid metabolism related genes in the liver of apoE(-/-) and age-matched wild type (WT) mice of 14-day old, 1-month old, 2-month old, 3-month old. The serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) contents were assayed using COD-PAP and GPO-PAP methods. The serum apolipoprotein B100 (apoB100) content was quantitated by immune turbidimetry. The hearts were perfusion-fixed in 4% formaldehyde, infiltrated with 30% gum sucrose for 24 h at 4 °C, and embedded in OCT compound. The aortic sinus tissues were serially sectioned at -15 °C, stained with Sudan IV, and counterstained with light green. The results were shown as follows. Compared with that in WT mice, the mRNA levels of apoA I and apoA IV in apoE(-/-) mice aged from 14-day old to 3-month old changed prominently (P<0.05), with apoA I up-regulated and apoA IV down-regulated. At the age of 1 month, the expression of apoB100 in apoE(-/-) mice was higher than that in WT mice (P<0.05). The expression of apoA V was up-regulated (P<0.05) and there was obvious lipid deposition in the aortic intima in apoE(-/-) mice at the age of 2 months. The expressions of fatty acid translocase (Fat/CD36) and angiopoietin-like protein 3 (Angptl 3) in apoE(-/-) mice were higher than those in WT mice at the age of 3 months (P<0.05), while the expressions of peroxisome proliferator-activated receptor α (PPARα), liver X receptor α (LXRα), carnitine palmitoyl transferase I (CPT I) and acyl coenzyme A oxidase 1 (ACOX1) showed no significant changes. The serum TC, TG, LDL-C and HDL-C contents in apoE(-/-) mice aged from 14-day old to 3-month old were higher than those in age-matched WT mice. apoE(-/-) mice showed a marked increase in serum apoB100 content, consistent with the trend of serum LDL-C content and apoB100 mRNA content in the liver. The results suggest that the mRNA expressions of apoA I, apoA IV, apoA V, apoB100 and Angptl 3 in apoE(-/-) mice change significantly compared with those in WT mice, and these genes might be relevant to the complicated lipid metabolism network, and involved in the early stage of atherogenesis.

Pharmacokinetics and bioequivalence of eperisone hydrochloride tablet in healthy subjects / 药学学报

<p><b>AIM</b>To develop a HPLC-ESI-MS assay for determination of eperisone hydrochloride in human plasma and investigate the pharmacokinetics and bioequivalence of two eperisone hydrochloride tablets in human.</p><p><b>METHODS</b>Buflomedil hydrochloride was used as the internal standard. After alkalized with saturated sodium bicarbonate solution, plasma was extracted with diethylether-cyclohexane (1:1) and separated using HPLC on a reversed-phase C18 column with a mobile phase of 10 mmol x L(-1) ammonium acetate buffer solution (adjusted to pH 3.88 with acetic acid)-methanol (20:80). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 260 for eperisone and m/z 308 for the internal standard. A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 100 mg dose of each tablet was administered to each volunteer.</p><p><b>RESULTS</b>Calibration curve was linear over the range of 0.02-20 microg x L(-1). The limit of quantification for eperisone hydrochloride in plasma was 0.02 microg x L(-1). The main pharmacokinetics parameters T1/2, Tmax and Cmax were (2.7 +/- 0.4) h, (1.1 +/- 0.5) h and (2.8 +/- 2.8) microg x L(-1) for the reference tablet; (2.8 +/- 0.5) h, (1.1 +/- 0.4) h and (3 +/- 4) microg x L(-1) for the test tablet, respectively. The relative bioavalability of the test tablet was (101 +/- 13)%.</p><p><b>CONCLUSION</b>The assay was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.</p>

Bioequivalence of donepezil capsule and tablet in human / 药学学报

<p><b>AIM</b>To develop an HPLC-MS assay for determination of donepezil in human plasma and to investigate the pharmacokinetics and bioequivalence of donepezil capsule in healthy volunteers.</p><p><b>METHODS</b>A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 5 mg dose of either capsule or tablet was administered to each volunteer. After spiked with the internal standard (phenoprolamine) and treated with saturated sodium bicarbonate, plasma was extracted with ethyl acetate and separated with a C18 reversed phase column. LC-ESIMS was used in the selected ion monitoring (SIM) mode with target ions at m/z 380 for donepezil and m/z 344 for phenoprolamine. The fragmentor voltage was 120 V. The main pharmacokinetic parameters of donepezil and the bioequivalence of its two preparations were calculated.</p><p><b>RESULTS</b>The main pharmacokinetic parameters T1/2, Tmax and Cmax were (63 +/- 10) h, (3.3 +/- 0.4) h and (8.5 +/- 0.4) microgram.L-1 for the capsule; (57 +/- 9) h, (3.4 +/- 1.0) h and (8.1 +/- 1.0) microgram.L-1 for the tablet, respectively. The relative bioavailability of the donepezil capsule was 102% +/- 11%.</p><p><b>CONCLUSION</b>The assay was shown to be sensitive, accurate and convenient. The two preparations of donepezil were bioequivalent.</p>