Can adiponectin have an additional effect on the regulation of food intake by inducing gastric motor changes?

The regulation of food intake is a complex mechanism, and the hypothalamus is the main central structure implicated. In particular, the arcuate nucleus appears to be the most critical area in the integration of multiple peripheral signals.Among these signals, those originating from the white adipose tissue and the gastrointestinal tract are known to be involved in the regulation of food intake.The present paper focuses on adiponectin, an adipokine secreted by white adipose tissue, which is reported to have a role in the control of feeding by acting centrally. The recent observation that adiponectin is also able to influence gastric motility raises the question of whether this action represents an additional peripheral mechanism that concurs with the central effects of the hormone on food intake. This possibility, which represents an emerging aspect correlating the central and peripheral effects of adiponectin in the hunger-satiety cycle, is discussed in the present paper.     

m6A去甲基化酶ALKBH5与弱精症的相关性研究

目的探究N⁶-甲基腺嘌呤(m⁶A)去甲基化酶ALKBH5与弱精症的相关性。方法收集精液标本30份,包括弱精症患者与健康者精液标本各15份,密度梯度离心纯化精子,使用液相色谱与质谱联用(LC-MS/MS)检测精子RNA的m⁶A水平,使用实时荧光定量PCR法检测ALKBH5相对表达水平。结果弱精症患者m⁶A水平明显高于健康者,ALKBH5相对表达水平低于健康者,差异均有统计学意义(P<0.05)。精子活动度参数相关性分析结果显示,ALKBH5相对表达水平与前向运动精子数和非前向运动精子数呈正相关(r=0.512、0.377,P<0.05),与不动精子数呈负相关(r=-0.497,P<0.05);m⁶A与前向运动精子数和非前向运动精子数呈负相关(r=-0.442、-0.425,P<0.05),与不动精子数呈正相关(r=0.528,P<0.05)。结论在弱精症患者中,m⁶A及其去甲基化酶ALKBH5与精子活动度具有相关性。     

Novel phenotype of mouse spermatozoa following deletion of nine β-defensin genes

β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.     

The influence of processed total non-forward and non-motile sperm count on the outcome of artificial insemination with the husband’s semen

BackgroundArtificial insemination with the husband’s semen (AIH) is an economical and noninvasive method of infertility treatment. However, AIH’s pregnancy rate is much lower than in vitro fertilization (IVF) as its multiple and complex uncertainty factors. Semen quality has been one of the main factors which affect the pregnancy outcome of AIH.MethodsThe relevant parameters of 1,142 AIH cycles were retrospectively studied, including the general parameters and the semen quality parameters among clinical pregnancy, biochemical pregnancy, non-pregnancy group, age, infertility duration, infertility type, body mass index (BMI), cycle count, morphology in previously semen examination, and semen quality parameters on the day of AIH.ResultsThe statistically significant difference was only found on processed total non-forward and non-motile sperm count (N-TFMSC). The mean processed N-TFMSC in the biochemical pregnancy group was 6.37±4.27 million, significantly higher than the other two groups (vs. 4.40±3.15 million or vs. 4.48±3.60 million, P<0.05). The study was then divided into two groups according to processed N-TFMSC, Group 1 ≤5.0 million, and Group 2 >5.0 million. A statistical increase in biochemical pregnancy rate was observed when the processed N-TFMSC was >5.0 million (2.72% vs. 0.90%).ConclusionsProcessed N-TFMSC may be one of the independent factors on AIH’s outcome; it should be given equal attention the same as processed total forward motile sperm count (TFMSC).     

精子冷冻环无保护剂玻璃化冷冻方法的初步研究

目的探讨精子冷冻环无保护剂玻璃化冷冻方法的可行性。方法正常精液标本上游处理后,进行常规冷冻和冷冻环无保护剂的玻璃化冷冻,复苏后分别从活力参数及电镜下超微结构等指标比较两种冷冻方法的效果。结果两种方法冷冻后精子存活率、活动率之间差异无显著性(48%∶48%;44.5%∶43.5%,P>0.05),但均较未冷冻的89%和88.5%明显下降(P<0.001)。超微结构亦较未冷冻时发生了一定的改变,但核结构基本保持完整。结论精子冷冻环无保护剂的玻璃化冷冻是一种简单、方便而行之有效的冷冻方法。     

Functional mechanism underlying cyclooxygenase-2 expression in rat small intestine following administration of indomethacin: Relation to intestinal hypermotility

Background and Aim:  We recently reported that cyclooxygenase (COX)-2 is upregulated in the rat small intestine after administration of indomethacin, and this may be the key to non-steroidal anti-inflammatory drug (NSAID)-induced intestinal damage. The present study investigated the mechanism for COX-2 expression induced in the rat small intestine by indomethacin, in relation with ulcerogenic processes.
Methods:  Animals were given indomethacin or SC-560 p.o., and the intestinal mucosa was examined 24 h later.
Results:  Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility, bacterial invasion and inducible nitric oxide synthase (iNOS) activity, as well as the expression of COX-2 mRNA in the mucosa. Although SC-560 did not cause any damage, this agent caused intestinal hypermotility, the bacterial invasion and the upregulation of COX-2 expression. The mucosal PGE₂ content was decreased by SC-560 at 3 h but recovered 12 h later, and this recovery of PGE₂ was attenuated by both atropine and ampicillin, in addition to rofecoxib. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE₂ and atropine, but not ampicillin. Yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 and iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in the prevention of intestinal lesions.
Conclusion:  These results suggest that COX-2 expression in the intestinal mucosa following the administration of indomethacin is associated with intestinal hypermotility and bacterial invasion. The intestinal hypermotility caused by COX-1 inhibition may be a key to COX-2 expression after administration of NSAIDs and their intestinal ulcerogenic properties.     

Effects of erythromycin on the propulsive motility of upper gastrointestinal tract in rats

The differences between the postprandial mixing or propulsion and the interdigestive motility of the gastrointestinal (GI) tract are already known. Earlier studies showed dose-dependent differences in the effects of erythromycin on interdigestive motility. The various GI side-effects (vomiting, diarrhoea) also suggest that there are different effects of erythromycin on the GI motility. The aim of our study was to examine postprandially the propulsive effects of different doses of erythromycin on the movement of intraluminal contents in the upper GI tract of the rat. The animals were fasted for 24 h before the experiments but water was given freely. The rats received 1.5 ml 1.5% methylcellulose painted with 0.05% phenol-red intragastrically (test solution). Erythromycin(E. lactobionate) was given intravenously at doses of 0.05, 0.1, 0.25, 0.5, 1.0 and 5.0 mg/kg 15 min before the administration of a test solution. The animals were sacrificed 20,60 and 120 min after administration of methylcellulose, when the distance between the front of the painted intraluminal contents and the pylorus was measured and expressed as a percentage of the total length of small intestine. The phenol-red content in the stomach and small intestine was measured spectrophotometrically and the gastric emptying was calculated from the ratio of the measured total and intestinal phenol-red content. Our results showed that the small doses of erythromycin (0.1 and 0.25 mg/kg) accelerated gastric emptying after 20 min but did not change significantly the propulsive motility of upper small intestine; however, large doses of erythromycin (1.0 and 5.0 mg/kg) decreased gastric emptying and upper GI motility after 20 and 60 min. In summary, the prokinetic action of small doses of erythromycin was demonstrated, but its effecttime on GI motility is short and the ratio of the stimulating and inhibitory doses is 1:10. This paper was presented at the Section of IUPHAR GI Pharmacology Symposium on ’Biochemical pharmacology as an approach to gastrointestinal disorders (basic science to clinical perspectives)‘, October 12-14, 1995, Pécs, Hungary.     

Evolution of the sperm aster after microinjection of isolated human sperm centrosomes into meiotically mature human oocytes

This study examined the feasibility of isolating and transferringthe centrosome-containing region of spermatozoa to mature humanoocytes. The findings demonstrate that individual sperm centrosomescan be transferred and are capable of nucleating maternal tubulinto form a well-developed sperm aster in the recipient oocyte.The results are discussed with respect to centrosome functionin early human development and applications in clinical in-vitrofertilization in the treatment of certain forms of male factorinfertility.