Rab Proteins: Insights into Intracellular Trafficking in Endometrium.

Rab proteins belong to the Ras superfamily of small monomeric GTPases. These G proteins are the main controllers of vesicular transport in every tissue, among them, the endometrium. They are in charge of to the functional subcellular compartmentalization and cargo transport between organelles and the plasma membrane. In turn, intracellular trafficking contributes to endometrial changes during the menstrual cycle, secretion to the uterine fluid, and trophoblast implantation; however, few reports analyze the role of Rab proteins in the uterus. In general, Rab proteins control the release of cytokines, growth factors, enzymes, hormones, cell adhesion molecules, and mucus. Further, the secretion of multiple compounds into the uterine cavity is required for successful implantation. Therefore, alterations in Rab-controlled intracellular transport likely impair secretory processes to the uterine fluid that may correlate with abnormal endometrial development and failed reproductive outcomes. Overall, they could explain recurrent miscarriages, female infertility, and/or assisted reproductive failure. Interestingly, estrogen (E2) and progesterone (P) regulate gene expression of Rab proteins involved in secretory pathways. This review aims to gather information regarding the role of Rab proteins and intracellular trafficking in the endometrium during the different menstrual phases, and in the generation of a receptive stage for embryo implantation, modulated by E2 and P. This knowledge might be useful for the development of novel reproductive therapies that overcome low implantation rates of assisted reproductive procedures.

[HBD-1 and hBD-2 are expressed in cervico-vaginal lavage in female genital tract due to microbial infections]. / Ekspresja hBD-1 i hBD-2 w popluczynach pochwowo-szyjkowych z dróg rodnych kobiet w stanach zapalnych wywolanych drobnoustrojami.

OBJECTIVES: The aim of this study was to evaluate and compare concentration of selected human beta-defensins (hBD-1, hBD-2) in cervico-vaginal lavage (CVL), obtained from women with candidiasis, chlamydiasis and other bacterial infections. MATERIAL AND METHODS: beta-defensins were detected quantitatively by RT-PCR (7000 Taqman, Applied Biosystems) in cervico-vaginal lavage collected from 120 (79 women in the study group and 41 controls) non-pregnant women, aged 18-40 (mean age 28.5 +/- 6.29). The study group patients were divided into three subgroups on the basis of clinical and microbiological diagnosis: women with candidiasis (n=13); with chlamydiasis (n=13), and with other bacterial infections (n=12). RESULTS: The highest count of hBD-1 RNA copies was found in women with bacterial infections and candidiasis (335.84 and 320.10 respectively), and hBD-2--with chlamydiasis. The difference between RNA copies of hBD-1/microg in candidiasis, chlamydiasis and bacterial pathogens was statistically significant; for hBD-2 only in case of chlamydiasis. CONCLUSIONS: Chlamydia trachomatis infection activates the production of hBD-2. Candida albicans, Chlamydia trachomatis, and bacterial pathogens induced variable increases of hBD-1 concentration.

Vaccination with MIP or Pgp3 induces cross-serovar protection against chlamydial genital tract infection in mice.

Previously we reported that recombinant Chlamydia muridarum macrophage infectivity potentiator (MIP) provided partial protection against C. muridarum genital tract infection in mice. On the other hand, Chlamydia trachomatis plasmid encoded Pgp3could induce the protection against C. muridarum air way infection. This study aimed to evaluate the immunogenicity of MIP and Pgp3 from C. trachomatis serovar D and further investigate whether MIP and Pgp3 provide cross-serovar protection against C. muridarum genital tract infection in mice. Our results showed that vaccination by any regimen, including MIP alone, Pgp3 alone or MIP plus Pgp3, induced specific serum antibody production and Th1-dominant cellular responses in mice. Live chlamydial shedding from the vaginal and inflammatory pathologies in the oviduct markedly reduced. However, MIP + Pgp3 vaccination did not provide better protection than the single immunization. In conclusion, this study demonstrated that both MIP and Pgp3 can induce cross-serovar protective against chlamydial genital tract infection, and provided the guide for the development of optimal multisubunit vaccines against C. trachomatis infection.

Effect of cytokine level variations in individuals on the progression and outcome of bacterial urogenital infections--a meta-analysis.

Bacterial urogenital infections such as chlamydia, gonorrhoea and syphilis are widespread inflammatory diseases, which may be accompanied by severe complications. These complications can range from basic inflammation to tubal pathology, infertility and neurological dysfunction, though infections go unnoticed in the majority of cases. Cytokines in the host play a vital role in both the initial and long-term immune response and inflammation. However, levels of cytokine expression vary between individuals. A meta-analysis was performed to evaluate the effect of cytokine expression differences on severity of infections with these pathogens. Studies comparing expression of cytokines in humans with inflammation or inflammation-based complications were identified using NCBI, Google Scholar and Cochrane databases. Only studies into human cytokine expressions were included, and three articles per subject were required to be suitably analysed during meta-analysis. A total of 52 articles were included for meta-analysis. It was shown that differences in IL-1, IL-6, IL-8, IL-10, TNFα and IFNγ affect the clinical outcome of Chlamydia trachomatis infection significantly. Similarly, IL-1 and IL-8 expression during Neisseria gonorrhoeae infection significantly affects the outcome of the disease. For Treponema pallidum infection, it was shown that IFNγ variation in hosts could be linked to severity of disease. However, a lack of studies to use in the meta-analysis and fluctuation in the resulting data depending on the adjustments makes adequate evaluation difficult.

Clinical pharmacokinetics of ceftriaxone.

Ceftriaxone is a third-generation cephalosporin that exhibits saturable plasma protein binding, which influences its pharmacokinetic parameters depending on the dose. Systemic clearance and volume of distribution of total drug show dependence on both concentration and time, whereas for unbound drug these parameters remain constant. The decrease in renal or non-renal clearance with age or in the presence of disease states is often compensated by the concurrent increase in free fraction, resulting in no apparent changes in half-life and no need for dose adjustment. Because of its unusually long plasma half-life, the availability of intramuscular administration and its high intrinsic activity against many organisms, ceftriaxone has become a popular agent in once-daily therapy of infections in paediatric patients, gonococcal infections and outpatient management of pneumonia and osteomyelitis.