羟甲基戊二酰辅酶A还原酶抑制剂的研究进展

目的：介绍ＨＭＧＣｏＡ 还原酶抑制剂类药的研究进展,为临床合理用药提供参考。方法：以国内外发表的论文为基础,经分析,归纳,从药理作用、体内过程、临床应用、副作用及产品发展概况等方面介绍洛伐他汀、普伐他汀、辛伐他汀、氟伐他汀及西伐他汀等药品。结果与结论：大量资料表明,ＨＭＧＣｏＡ 还原酶抑制剂是一类疗效显著、毒副作用少,耐受性好的理想降血脂药物,该类药的问世为治疗高胆固醇血症开辟了新途径。     

LESS THAN HALF OF ACL‐RECONSTRUCTED ATHLETES ARE CLEARED FOR RETURN TO PLAY BASED ON PRACTICE GUIDELINE CRITERIA: RESULTS FROM A PROSPECTIVE COHORT STUDY

Background:A recently published Dutch practice guideline emphasizes criterion-based rehabilitation after anterior cruciate ligament reconstruction (ACLR) instead of time-based. As a consequence of this criterion-based rehabilitation, return to play is only suggested when athletes meet specific return to play (RTP) criteria.Purpose:The goal of this prospective observational study was to analyze if physical therapists adhere to ACLR practice guideline RTP criteria for testing and return to sport decisions, and to explore whether there is a difference in adherence between physical therapists specialized in sports versus those who are not.Methods:When the treating physical therapist cleared an athlete for RTP after ACLR, the primary researcher performed RTP measurements according to the ACLR practice guideline to investigate if all nine quantitative and qualitative RTP criteria were met.Results:Of the 158 athletes (54 females and 104 males, mean age 24 ± 6 years, 12 ± 3 months after surgery), 69 (44%) had performed the RTP measurements with their primary physical therapist. Of the athletes tested by their primary physical therapist 23% met all RTP criteria compared to 10% of the athletes who were not tested at all by their primary physical therapist (p = 0.026). Of the athletes rehabilitating with a sports physical therapist, 52% had been tested by their primary physical therapist compared to 34% of the athletes rehabilitating with a non-sports physical therapist (p = 0.024).Conclusion:Only 44% of the athletes were tested according to the guideline RTP criteria and only 23% of them were given an RTP advice consistent with the ACLR guideline. Although sports physical therapists adhered to the guideline more often than non-sports physical therapists, the adherence is still alarmingly low. More attention for the implementation of ACLR guidelines and RTP criteria is needed.Level of evidence:Therapy, level 2b.     

Dual-contrast agent photon-counting computed tomography of the heart: initial experience

To determine the feasibility of dual—contrast agent imaging of the heart using photon-counting detector (PCD) computed tomography (CT) to simultaneously assess both first-pass and late enhancement of the myocardium. An occlusion-reperfusion canine model of myocardial infarction was used. Gadolinium-based contrast was injected 10 min prior to PCD CT. Iodinated contrast was infused immediately prior to PCD CT, thus capturing late gadolinium enhancement as well as first-pass iodine enhancement. Gadolinium and iodine maps were calculated using a linear material decomposition technique and compared to single-energy (conventional) images. PCD images were compared to in vivo and ex vivo magnetic resonance imaging (MRI) and histology. For infarct versus remote myocardium, contrast-to-noise ratio (CNR) was maximal on late enhancement gadolinium maps (CNR 9.0?±?0.8, 6.6?±?0.7, and 0.4?±?0.4, p?<?0.001 for gadolinium maps, single-energy images, and iodine maps, respectively). For infarct versus blood pool, CNR was maximum for iodine maps (CNR 11.8?±?1.3, 3.8?±?1.0, and 1.3?±?0.4, p?<?0.001 for iodine maps, gadolinium maps, and single-energy images, respectively). Combined first-pass iodine and late gadolinium maps allowed quantitative separation of blood pool, scar, and remote myocardium. MRI and histology analysis confirmed accurate PCD CT delineation of scar. Simultaneous multi-contrast agent cardiac imaging is feasible with photon-counting detector CT. These initial proof-of-concept results may provide incentives to develop new k-edge contrast agents, to investigate possible interactions between multiple simultaneously administered contrast agents, and to ultimately bring them to clinical practice.     

1141644472Surface Enhanced Laser Desorption and Ionization (SELDI) mass spectrometry for investigation of human embryo conditioned IVF culture medium

Background:  Fetal programming is the notion that adverse environmental conditions in utero can cause short term survival adaptations that may have long-term consequences, such as chronic disease in subsequent lifetime. Recently, some authors reported that the increase of allergy prevalence in childhood may be linked with fetal immune development. In this regard, literature survey inspired to study the influence of two conjugated linoleic acid (CLA)-isomers (c9,t11 and t10,c12) on parameters of the immune system in pregnancy.
Methods:  Lymphocytes from allergic and non-allergic mothers, cord blood of their newborns, and the decidual layer of term placentae were isolated and cultured for 2 days and supplemented or not with relevant allergens, c9,t11 CLA, t10,c12 CLA or linoleic acid, respectively. Expression of CD69 (activation marker) and CD71 (transferrin receptor; proliferation marker) on B and T lymphocytes and T helper cell type 1 (Th1) and Th2 cytokines in culture supernatant were analyzed.
Results:  Both CLA isomers led to an increase of the IFN-γ/IL-10 ratio in supernatants of peripheral maternal and cord blood cells from allergic patients and non-allergic-control. CLA supplementation decreased IL-10 secretion of peripheral maternal and decidual lymphocytes and the portion of CD71⁺ maternal B cells. Linoleic acid induced a similar effect.
Conclusion:  An immunological effect of CLA on maternal and fetal lymphocyte responses could be demonstrated. It would be expected that further investigations could reveal differences in effects of CLA and linoleic acid.     

Correlates of Sexual Risk among Recent Gay and Bisexual Immigrants from Western and Eastern Africa to the USA

We examined correlates of sexual risk among gay and bisexual men, who recently migrated from western and eastern African countries to the USA and lived in New York City and who are HIV negative or of unknown status. These men migrate from countries where same-sex sexuality is socially rejected and mostly illegal contributing to the motivation to migrate. Their background might predispose these men to engagement in sexual risk practices, while they are not specifically addressed in HIV prevention programming. Participants (N?=?62) reported in face-to-face interviews on pre- and postmigration experiences, psychosocial determinants of sexual risk, and current sexual practices. Operationalization of sexual risk was based on the number of men with whom they had condomless receptive and/or insertive anal sex. Over a third of the men reported always having used condoms in the past year; among the other men, sexual risk varied. Multivariate analyses showed that sexual risk was lower among men with a stronger motivation to avoid HIV infection and higher among men who currently engaged in transactional sex. Further analyses indicated that housing instability was independently associated with reduced motivation to avoid HIV infection and with engagement in transactional sex in the USA. In recent western and eastern African gay and bisexual immigrants to the USA, structural factors, including housing instability, are strongly associated with sexual risk.     

Maturation of human spermatozoa (from selected epididymides of prostatic carcinoma patients) with respect to their morphology and ability to undergo the acrosome reaction

Spermatozoa were recovered form three regions of the epididymisof six prostatic carcinoma patients. After washing and incubatingfor 3 h in Ham's F-10 medium, with or without 5 µM A23187for the last 30 min, spermatozoa were tested for vitality byhypotonic swelling and permeated with methanol to detect theacrosome with peanut agglutinin. Whereas the extent of spontaneousacrosome reactions was similar for spermatozoa from all regionsof the duct, 17 and 28% of spermatozoa from all regions of theduct, 17 and 28% of spermatozoa from the corpus and cauda epididymidisrespectively, responded to stimulation by A23187 with acrosomereactions but there was no stimulation by A23187 of spermatozoafrom the efferent ducts. The percentage of morphologically normalspermatozoa increased stepwise towards the distal regions, withabnormalities being mostly enlarged heads in more proximal regions:they were largely absent form the cauda epididymidis. Spermhead swelling was similarly observed in cynomolgus monkey spermatozoafrom the caput epididymidis but not the more distal regions.These forms were not observed when spermatozoa were fixed beforesmearing, indicating that they were artefacts of sperm preparation.The changes in the susceptibility of non-fixed epididymal spermatozoato produce morphological artefacts and the gain in their acrosomalresponse to ionophore demonstrate maturational changes of spermatozoain the human epididymis.     

Marked aneuploidy and loss of multiple chromosomes are common in autosomal mutants isolated from normal mouse kidney epithelium

Marked aneuploidy and loss of multiple chromosomes are hallmarks of cancer, but whether these events are only present in malignant cells is not known. In prior work, we showed that approximately half of spontaneous autosomal mutants isolated directly from normal kidney epithelium arose from loss of a marker chromosome 8 containing the wild type Aprt gene. Chromosome loss was detected by loss of heterozygosity (LOH) for all chromosome 8 polymorphic loci examined. To determine whether loss of chromosome 8 reflected a larger mitotic event, LOH was examined for polymorphic loci on 11 nonselected chromosomes in Aprt mutants that lost the selected chromosome 8 homologue. LOH events were detected for one or more nonselected chromosomes in 38% of these mutants. The additional LOH events also reflected apparent chromosome loss based on the molecular analysis. Metaphase spreads from mutants that lost chromosome 8 were markedly aneuploid, and chromosome painting revealed reduced levels for any chromosome shown to be lost with the LOH analysis. In contrast, LOH on nonselected chromosomes was infrequent in Aprt mutants exhibiting intragenic events or mitotic recombination for chromosome 8, and marked aneuploidy was absent. These observations suggest that the mechanism leading to chromosome loss in somatic mammalian cells is often not a simple nondisjunction event and instead could result from a single catastrophic event. They also suggest that cells with characteristics of malignancy are present in normal appearing tissue.