Enhanced Expression of Sodium Hydrogen Exchanger (NHE)-1, 2 and 4 in the Cervix of Ovariectomised Rats by Phytoestrogen Genistein

Restoring the pH of cervicovaginal fluid is important for the cervicovaginal health after menopause. Genistein, which is a widely consumed dietary health supplement to overcome the post-menopausal complications could help to restore the cervicovaginal fluid pH. We hypothesized that genistien effect involves changes in expression of NHE-1, 2 and 4 proteins and mRNAs in the cervix. This study investigated effect of genistein on NHE-1, 2 and 4 protein and mRNA expression in the cervix in order to elucidate the mechanisms underlying possible effect of this compound on cervicovaginal fluid pH after menopause. Methods: Ovariectomised adult female rats received 25, 50 and 100 mg/kg/day genistein for seven consecutive days. At the end of the treatment, animals were sacrificed and cervix was harvested. Expression of Nhe-1, 2 and 4 mRNA were analyzed by Real-time PCR while distribution of NHE-1, 2 and 4 protein were observed by immunohistochemistry. Results: Treatment with 50 and 100 mg/kg/day genistein caused marked increase in the levels of expression and distribution of NHE-1, 2 and 4 proteins in the endocervical epithelia. Levels of Nhe-1, 2 and 4 mRNA in the cervix were also increased. Coadministration of ICI 182 780 and genistein reduced the expression levels of NHE-1, 2 and 4 proteins and mRNAs in the cervix. Conclusions: Enhanced expression of NHE-1, 2 and 4 proteins and mRNAs expression in cervix under genistein influence could help to restore the cervicovaginal fluid pH that might help to prevent cervicovaginal complications related to menopause.     

Large interlayer spacing Nb4C3Tx (MXene) promotes the ultrasensitive electrochemical detection of Pb2+ on glassy carbon electrodes

A Nb₄C₃T_x (MXene)-modified glassy carbon electrode was used for the electrochemical detection of Pb²⁺ ions in aqueous media. The sensing platform was evaluated by anodic stripping analysis after optimizing the influencing factors such as pH, deposition potential, and time. The large interlayer spacing, high c lattice parameter and higher conductivity of Nb₄C₃T_x compared to other MXenes enhance the electrochemical detection of Pb²⁺. The developed sensor can reach a detection limit of 12 nM at a potential ∼−0.6 V. Additionally, the developed sensor showed promising selectivity in the presence of Cu²⁺ and Cd²⁺, and stability for at least 5 cycles of continuous measurements with good repeatability. This work demonstrates the potential applications of Nb₄C₃T_x towards the development of effective electrochemical sensors.

Large interlayer spacing Nb₄C₃T_x (MXene) promotes the ultrasensitive electrochemical detection of Pb²⁺ on glassy carbon electrodes     

A systematic review of the applications of free tissue transfer in burns

Introduction

Free tissue transfer is a rarely indicated procedure in burns. However, in well selected cases it may play a pivotal role in optimizing outcomes in both primary and secondary burn reconstruction. We undertook a systematic review, based on the PRISMA statement for systematic reviews, of all published literature relating to the use of free flaps in acute burns and in secondary reconstructive procedures.

Methods

Inclusion and exclusion criteria were defined and Medline, Embase, PubMed and Google Scholar databases were searched from 1980 onwards to May 2013 with the search terms: “free flaps”, “free tissue transfer”, “microvascular”, “burns”, “acute burns”, “primary reconstruction” and “secondary reconstruction”.

Results

A total of 346 studies were retrieved following the search of which 30 studies met the inclusion criteria and were included in the review.

Discussion

We present the indications, timing, complications and failure rates for free flaps in primary and secondary reconstruction based on the available literature. We also provide a list of the various free flap options for the commonest sites undergoing reconstruction following burns. Finally an algorithm to ensure optimal success of free flaps when used in primary and in secondary burn reconstruction is presented.     

Epidemiology,clinical picture and long-term outcomes of FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia: Data from 151 patients

FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM.     

Quercetin induces morphological and proliferative changes of rat’s uteri under estrogen and progesterone influences

This study investigated the effect of 10 or 100 mg/kg/day quercetin on the uterus of ovariectomized adult female rats receiving sex-steroid replacement regime mimicking changes in hormonal profiles during the reproductive cycle. Following seven days of treatment with estrogen and progesterone with or without quercetin, uteri were harvested for histological and proliferative cell nuclear antigen (PCNA) protein and mRNA expression and PCNA protein distribution analyses. Our findings indicated that co-administration of 10 mg/kg/day quercetin with estrogen and progesterone caused a significant decrease in the size of uterine lumen and epithelial heights with lower PCNA protein and mRNA expression as compared to estrogen plus progesterone-only treatment (P < 0.05). Concomitant treatment with estrogen and progesterone with 100 mg/kg/day quercetin resulted in a marked increase in the number of glands with increased PCNA protein and mRNA expression. Significantly higher PCNA distribution was observed in the stroma and glands as compared to estrogen plus progesterone-only treatment (P < 0.05). In conclusion, at 10 mg/kg/day, quercetin affects uterine morphology but not proliferation, however at 100 mg/kg/day, quercetin induced significant stromal and glandular proliferation which could predispose the uterus towards neoplastic development.     

5-phenylthioacyclouridine: a potent and specific inhibitor of uridine phosphorylase

5-Phenylthioacyclouridine (PTAU or 1-[(2-hydroxyethoxy)methyl]-5-phenylthiouracil) was synthesized as a highly specific and potent inhibitor of uridine phosphorylase (UrdPase, EC 2.4.2.3). PTAU has inhibition constant (K(is)) values of 248 and 353 nM towards UrdPase from mouse and human livers, respectively. PTAU was neither an inhibitor nor a substrate for thymidine phosphorylase (EC 2.4.2.4), uridine-cytidine kinase (EC 2. 7.1.48), thymidine kinase (EC 2.7.1.21), dihydrouracil dehydrogenase (EC 1.3.1.2), orotate phosphoribosyltransferase (EC 2.4.2.10), or orotidine 5'-monophosphate decarboxylase (EC 4.1.2.23), the enzymes that could utilize the substrate (uridine or thymidine) or products (uracil or thymine) of UrdPase. Different isomers of 5-tolylthiouracil also were synthesized and tested as inhibitors of UrdPase. The meta-substituted isomer was 3- to 4-fold more potent as an inhibitor of UrdPase than the para- or ortho-substituted isomers. These data indicate that the hydrophobic pocket in the active site of UrdPase adjacent to the 5-position of the pyrimidine ring can accommodate the meta-substituted 5-phenyluracils better than the other isomers, leading to improved inhibition. Therefore, it is anticipated that the potency of PTAU can be increased further by the addition of certain hydrophobic groups at the meta position of the phenyl ring. PTAU has potential usefulness in the therapy of cancer and AIDS as well as other pathological and physiological disorders that can be remedied by the administration of uridine.     

Nosocomial transmission of syphilis during haemodialysis in a developing country

Patients with end-stage renal disease (n = 187) secondary to diverse aetiologies who underwent haemodialysis (HD) between November 1996 and November 2000 were routinely screened for syphilis using the rapid plasma reagin (RPR) test and confirmed by means of a microhemagglutination assay for Treponema pallidum. All the confirmed syphilis patients were asymptomatic and were diagnosed serologically. A true seroprevalence of 6.9% (13/187) and a biological false seropositivity of 4.2% (8/187) for syphilis were recorded. Most (11/13) of the true seropositive patients were aged between 51 and 80 y. Whilst 10/13 patients were true syphilis seropositive at the time of first HD, 3/13 patients became true seropositive an average of 12 months (range 10-14 months) after HD. Penicillin treatment was given to all 13 patients simultaneously only after the appearance of 3 new true syphilis seropositive cases. Complete seroreversion was observed in 4/10 patients in the pre-HD true syphilis seropositive group of presumptive transmitters who became RPR-negative, whereas the 3 new true seropositive cases showed a serial 4-fold decline in RPR titres 12 months after penicillin therapy, suggestive of an active disease with adequate therapeutic response. These results clearly indicate that latent syphilis is prevalent in long-term elderly HD patients. The true seroconversion of 3 new patients who had undergone HD for an average of 12 months is indicative of nosocomial transmission and the silently active nature of the disease, which necessitates regular monitoring of syphilis serology among HD patients.