Menstrual Cycle Phase is a Potential Confound in Psychophysiology Research

Effects of menstrual cycle phase on physiological levels and reactivity were studied in a withinsubject design with 20 women aged 18–30 years. Basal body temperature was monitored daily; follicular and luteal recording sessions occurred before and after the ovulatory temperature rise, respectively. The design consisted of task and rest periods, presented in counterbalanced order across phases. Half the subjects began during their follicular phase and half began during their luteal phase. Follicular and luteal phases were compared for differences between baseline resting levels, as well as for reactivity. The results showed menstrual phase differences in heart rate, pulse transit time, and EEG alpha, particularly during tasks, but no difference in reactivity. Habituation effects in the group that began during the follicular phase often masked luteal activation. In spite of the fact that not all statistical results achieved significance, the consistency of most trends supports the conclusion that physiological recording sessions with women might best be restricted to the follicular phase.     

Rat self administration of ethanol: Enhancement by darkness and exogenous melatonin

Using an FT 60 schedule, rats on 100% free feeding tested in the dark phase of a 12:12 light-dark cycle were trained to self-administer ethanol intravenously. The effect was dose-dependent with 20% ethanol being the preferred dose as measured by the number of infusions. Daily administration of 1.5 mg/kg melatonin significantly increased ethanol self-injection in the dark but not in the light. The time of day of testing and/or drug administration may be an important variable in studies on self-administration of drugs. Testing in the dark may eliminate the need for reducing body weight when inducing self-administration of ethanol.     

Serum fluctuations of total and free tryptophan levels during the menstrual cycle are related to gonadotrophins and reflect brain serotonin utilization

BACKGROUND: Serotoninergic (5-HT) neurons are suggested to regulate estrous cycle in animal models. In the present study we evaluated whether a relationship exists between the serotoninergic precursors in the central nervous system and the gonadotrophin-ovarian cyclic function. METHODS: We measured 5-HT precursors [free (FT) and total (TT) tryptophan] and LH, FSH and 17beta-estradiol (E2) levels in the serum of 15 fertile women with normal menstrual cycles during the follicular (cycle days 1-5, 7-11), mid-cycle (cycle days 14-16) and luteal (cycle days 17-19, 22-24) phases. RESULTS: TT and FT were significantly increased in the 7-11 and 17-19 cycle days and were decreased at mid-cycle (P < 0.01), with a cyclic and opposite behaviour when compared to that of FSH and LH. Indeed, correlation analysis through the matrix of mean values showed that LH was negatively correlated to TT (r = -0.636) and FT (r = -0.574), as well as FSH (TT, r = -0.655; FT, r = -0.663), and that TT and FT were positively correlated to each other (r = 0.801; P < 0.001). Furthermore, whilst the two FT peaks reached approximately the same levels in the follicular and luteal phase, TT levels were approximately 30% higher in the luteal than in the follicular phase of the cycle: thus in the first (follicular) phase FT peak was relatively higher than that of TT, whereas the contrary occurred in the second (luteal) phase of the cycle. CONCLUSIONS: Both TT and FT levels have cyclic variations throughout the menstrual cycle, being lowest at mid-cycle (14-16 cycle days), concomitant with the highest LH and FSH concentrations, and higher before and after mid-cycle phase, coinciding with the lowest circulating LH/FSH levels. Since TT and FT levels in the plasma have cyclic changes, our study: (i) suggests that a consumption of serum serotonin precursors takes place concomitant with gonadotrophin release during menstrual cycle; (ii) may represent an in vivo model to investigate this relationship in women in different physiopathological conditions.     

Isolation of a Toxoplasma gondii cyclin by yeast two-hybrid interactive screen

GAL4-based yeast two-hybrid cDNA libraries from Toxoplasma gondii RH strain were constructed and screened for interactors of a putative T. gondii cdc2-related kinase, TgCRK2. A screen of 3.2 million transformants yielded a single yeast clone that harbored a protein fusion capable of specifically interacting with TgCRK2. Sequencing revealed the cDNA insert (TgCYC1) had homology to the cyclin class of proteins. The TgCYC1 cDNA fragment was used to probe a conventional T. gondii cDNA library and a 2.65 kb cDNA coding for a predicted protein of 582 amino acids was obtained. Based on comparison with a 5'-RACE product from tachyzoite mRNA, the 2.65 kb cDNA for TgCYC1 appeared to be complete. TgCYC1 had the highest similarity to Plasmodium falciparum CYC1 and displayed sequence characteristics that place it in the cyclin H class of eukaryotic cyclins. In synchronous tachyzoite populations the level of TgCYC1 mRNA was unchanged indicating it is not cell cycle regulated at the mRNA level. TgCYC1 rescues the G(1)/S cyclin cell cycle defect in S. cerevisiae strain DL1 demonstrating that this apicomplexan cyclin can function in an established heterologous model system.     

Quercetin inhibits the invasion and mobility of murine melanoma B16-BL6 cells through inducing apoptosis via decreasing Bcl-2 expression

Quercetin has been known to have anti-tumor and anti-oxidation activities. In the present study, we have investigated its in vitro anti-metastatic activity. Quercetin inhibited the invasion and mobility of murine melanoma B16-BL6 cells in a dose-dependent manner but did not affect their adhesion to either laminin, fibronectin, or type VI collagen. Moreover, quercetin significantly inhibited the proliferation of B16-BL6 cells only in the case of time incubation longer than 48 h. Quercetin dose-dependently decreased the cell rates in S and G2–M phases of cell cycle. The effect of quercetin to cause a remarkable apoptosis of B16-BL6 cells was also demonstrated by flow cytometric assay as well as DNA fragmentation with a typical 180-bp ladder band in agarose electrophoresis and a quantitative analysis. Furthermore, quercetin markedly inhibited the expression of anti-apoptotic protein Bcl-2 but hardly influenced Bcl-X_L. These results suggest that the inhibition of quercetin on invasiveness and migration of B16-BL6 cells are closely associated with the arrest of cell cycle as well as the induction of apoptosis by decreasing the Bcl-2 expression. This revised version was published online in July 2006 with corrections to the Cover Date.     

人骨髓MSC对PHA活化T细胞周期以及表型和细胞因子分泌的影响

目的研究人骨髓间充质干细胞(MSC)对T细胞周期和活化的影响,探讨MSC对T细胞增殖抑制的作用机制。方法Ficoll密度梯度离心法分离纯化人骨髓MSC,体外扩增培养3代后用于实验。应用流式细胞术分析MSC对PHA作用下T细胞周期和早期表型CD25、CD69表达的影响,ELISA法检测细胞因子水平。结果人骨髓MSC体外可使PHA刺激下的T细胞滞留于细胞周期的G0/G1期,下调活化T细胞早期表型CD25、CD69的表达,抑制IL-2、IFN-r的分泌。结论人骨髓MSC体外可通过对T细胞周期的影响抑制其活化和增殖。     

Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist (Cetrorelix): a pilot study with minimal stimulation

Natural cycles were abandoned in in-vitro fertilization (IVF) embryo transfer, due to premature luteinizing hormone (LH) surges--and subsequent high cancellation rates. In this study, we investigated the administration of a new gonadotrophin-releasing hormone antagonist (Cetrorelix) in the late follicular phase of natural cycles in patients undergoing IVF and intracytoplasmic sperm injection (ICSI). A total of 44 cycles from 33 healthy women [mean age 34.1 +/- 1.4 (range 26-36) years] were monitored, starting on day 8 by daily ultrasound and measurement of serum concentrations of oestradiol, LH, follicle stimulating hormone (FSH) and progesterone. When plasma oestradiol concentrations reached 100-150 pg/ml, with a lead follicle between 12-14 mm diameter, a single injection (s.c.) of 0.5 mg (19 cycles) or 1 mg (25 cycles) Cetrorelix was administered. Human menopausal gonadotrophin (HMG; 150 IU) was administered daily at the time of the first injection of Cetrorelix, and repeated thereafter until human chorionic gonadotrophin (HCG) administration. Four out of 44 cycles were cancelled (9.0%). No decline in follicular growth or oestradiol secretion was observed after Cetrorelix administration. A total of 40 oocyte retrievals leading to 22 transfers (55%) was performed. In 10 cycles (25%), no oocyte was obtained. Fertilization failure despite ICSI occurred in six cycles (15%). In two patients the embryo was arrested at the 2 pronuclear (PN) stage. The stimulation was minimal (4.7 +/- 1.4 HMG ampoules). A total of seven clinical pregnancies was obtained (32.0% per transfer, 17.5% per retrieval), of which five are ongoing. Thus, a spontaneous cycle and the GnRH antagonist Cetrorelix in single dose administration could represent a first-choice IVF treatment with none of the complications and risks of current controlled ovarian hyperstimulation protocols, and an acceptable success rate.     

Visual perception in women during the menstrual cycle

Twelve females were tested at four times during the menstrual cycle with a visual detection task and a visual pattern discrimination task. Mood levels and confidence ratings were evaluated for each session. In addition to the behavioral testing, plasma samples were collected and radioimmunoassayed for estradiol, progesterone, luteinizing hormone, and follicle stimulating hormone levels. Visual detection fluctuated significantly during the menstrual cycle with impaired performance occurring at the premenstrual session. In contrast to previous reports, the impaired performance was not related to lowered confidence ratings or to mood levels.     

The number of proliferating cell nuclear antigen positive cells in endometriotic lesions differs from that in the endometrium

Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) was studied in the endometrium and in endometriotic lesions during the menstrual cycle and in post-menopausal patients. During the menstrual cycle, in the basal layer of the endometrium, an increase in the number of positive indices (PI) of PCNA was observed in epithelial cells from the menstrual phase. It reached a maximum in the proliferative phase and decreased in the secretory phase. However, no change was observed in the stromal cells of the basal layer. In the functional layer of the endometrium, the PI of the epithelial cells showed a high peak in the late proliferative phase, decreased sharply in the secretory phase and remained unchanged thereafter. The PI of the stromal cells in the functional layer showed two peaks, one in the late proliferative and the other in the mid and late secretory phase. In the endometriotic lesions, except for the proliferative phase, the number of PI was significantly higher than that of the corresponding endometrium and no significant changes were observed during the menstrual cycle. In post-menopausal endometriotic lesions, the number of PI was also higher than that of the corresponding endometrium. Thus the numbers of PI differed between the endometrium and endometriotic lesions in the same patients. These results imply that the endometriotic lesions are constantly more proliferative than the endometrium irrespective of the hormonal milieu during both the menstrual cycle and in a post-menopausal environment.