Increased endothelin-1 reactivity and endothelial dysfunction in carotid arteries from rats with hyperhomocysteinemia

Background and purpose:

There are interactions between endothelin-1 (ET-1) and endothelial vascular injury in hyperhomocysteinemia (HHcy), but the underlying mechanisms are poorly understood. Here we evaluated the effects of HHcy on the endothelin system in rat carotid arteries.

Experimental approach:

Vascular reactivity to ET-1 and ET_A and ET_B receptor antagonists was assessed in rings of carotid arteries from normal rats and those with HHcy. ET_A and ET_B receptor expression was assessed by mRNA (RT-PCR), immunohistochemistry and binding of [¹²⁵I]-ET-1.

Key results:

HHcy enhanced ET-1-induced contractions of carotid rings with intact endothelium. Selective antagonism of ET_A or ET_B receptors produced concentration-dependent rightward displacements of ET-1 concentration response curves. Antagonism of ET_A but not of ET_B receptors abolished enhancement in HHcy tissues. ET_A and ET_B receptor gene expressions were not up-regulated. ET_A receptor expression in the arterial media was higher in HHcy arteries. Contractions to big ET-1 served as indicators of endothelin-converting enzyme activity, which was decreased by HHcy, without reduction of ET-1 levels. ET-1-induced Rho-kinase activity, calcium release and influx were increased by HHcy. Pre-treatment with indomethacin reversed enhanced responses to ET-1 in HHcy tissues, which were reduced also by a thromboxane A₂ receptor antagonist. Induced relaxation was reduced by BQ788, absent in endothelium-denuded arteries and was decreased in HHcy due to reduced bioavailability of NO.

Conclusions and implications:

Increased ET_A receptor density plays a fundamental role in endothelial injury induced by HHcy. ET-1 activation of ET_A receptors in HHcy changed the balance between endothelium-derived relaxing and contracting factors, favouring enhanced contractility.British Journal of Pharmacology (2009) 157, 568–580; doi:10.1111/j.1476-5381.2009.00165.x; published online 9 April 2009This article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Novel PLA/Chitosan Composite Materials Prepared by SCF-CO2 Technique

Because of the incomparable merits （nontoxicity, non-remainder, fast transfer mass） of supercritical carbon dioxide fluid technique（SC-CO2）, it was used to developed a series of novel biodegradable tissue engineering scaffold materials in this research. The novel PLA/chitosan composite materials could be molded to different shapes, and the porosity of the materials were over 200 lam and connected. Chondrocyte cultivation, subcutaneous and intramuscular implantation were mainly discussed this paper. The results showed that the cells could well adhere, grow and multiplicate on the surface of the materials, which indicated good biocompatibility of the composite materials. The plantation test revealed that the PLA materials had already dismissed 2 month late in the body, while the composite materials could still keep certain strength and shape, and the most important things is the response of the tissue toward the implanted PLA/chitosan composite materials was mild and had far less inflammation than PLA materials. 8 to 16 weeks later, fiber membrane was stable; degradation of the materials was seen clear and tissue had already spread into it.     

A familial case of X chromosome deletion ascertained by cytogenetic screening of women with premature ovarian failure

The association between X chromosome deletions and premature ovarian failure is well established. Previous anecdotal reports however, have not documented the prevalence of X deletions in women with premature ovarian failure. We therefore performed cytogenetic analyses on 79 women with primary or secondary amenorrhoea to assess the utility of screening for a genetic marker for familial premature ovarian failure. A normal karyotype was found in 77 women. One woman with primary amenorrhoea had an XY karyotype and a woman with secondary amenorrhoea had a deletion at Xq 26.1. This second case had a family history of premature ovarian failure, and her mother who underwent premature ovarian failure at 28 years shared this deletion. The early diagnosis of familial X deletions causing premature ovarian failure allowed for the prediction of impending menopause and the implementation of manoeuvres to advance conception. Although cytogenetic aberrations are rare in secondary amenorrhoea, the ability to predict premature ovarian failure can be vital.      

The mini-micro-epididymal sperm aspiration for sperm retrieval: a study of urological outcomes

Epididymal sperm aspiration and in-vitro fertilization (IVF) with intracytoplasmic sperm injection is an established treatment for obstructive azoospermia. Sperm aspiration is performed with either an incision or percutaneously. To control costs, minimize morbidity and retain the advantages of both approaches, we developed a mini-incision technique for epididymal aspiration and here report sperm retrieval and procedure-related outcomes. Twenty-six consecutive patients with obstructive azoospermia underwent epididymal sperm retrieval through a 1 cm incision with local anaesthesia to provide spermatozoa for concurrent IVF cycles. The quality of retrieved spermatozoa, the quantity of spermatozoa cryopreserved as well as anaesthetic requirement, recovery time and patient satisfaction were evaluated. Fresh epididymal spermatozoa were retrieved in 25 of 26 (96%) patients. In one patient, testicular sperm extraction was necessary. Excess motile spermatozoa were cryopreserved in 24 of 26 (92%) patients; a mean total motile count of 4.8x10(6) motile spermatozoa were banked. The procedure was performed with 62% of patients receiving minimal i.v. sedation. Post-procedure recovery was rapid, with a median time to return to work of 2.0 days with a median of 2.0 pain pills taken. Procedure-related satisfaction was high. The mini-micro-epididymal sperm aspiration achieves the goals of reliable retrieval of abundant epididymal spermatozoa with a single, minimally morbid procedure. It appears to combine the advantages of the incision and percutaneous approaches.