No abstract

As a complex Ca2+-rich fluid mixture of water, casein, lactose and several ions, milk secretion requires a number of unknown transporters, which can be identified by a genome-wide microarray study in mammary tissues of lactating animals. Ca2+ was reported to be secreted across mammary epithelial cells through the transcellular pathway, presumably involving TRPC (canonical transient receptor potential) channels. In the present study, we have used quantitative real-time PCR to demonstrate that the human mammary cell line MCF-7, as well as rat mammary tissues from pregnant and lactating rats, expressed TRPC1, TRPC5 and TRPC6. Expression of TRPC1, TRPC5 and TRPC7 were markedly up-regulated, whereas that of TRPC3 and TRPC4 was down-regulated in the early lactating period. To further identify other transporter genes affected by lactation, a highly sensitive Illumina microarray featuring Bead Array technology was performed on RNA samples from mammary tissues of lactating rats. We found that, of the 384 transcripts changed during lactation, 31 transcripts were involved in the transport of water and electrolytes, such as Ca2+, Na+, K+, Cl-, I-, Fe2+, sulfate and phosphate. The present study, therefore, provides information for further investigation of the mechanism of lactation-induced transport adaptation in mammary epithelial cells.

Background: Multiple studies have shown that perineural dexamethasone improves postoperative analgesia. However, some studies have shown minimal benefit, and have raised concerns regarding adverse physio-chemical effects of perineural dexamethasone. Furthermore, there is a paucity of studies wherein control (IV) dexamethasone was considered. Objective: The purpose of this meta-analysis was to evaluate the effectiveness of different concentrations of perineural dexamethasone injection on postoperative analgesia, as well as complications from its use for brachial plexus blocks. Methods: A systematic literature search was conducted using the Cochrane Central Registry of Controlled Trials, PubMed, and Scopus. Trials comparing control and local dexamethasonetreated groups, and those which reported duration of analgesia and/or pain scores/opioid consumptions were selected. Meta-analysis was performed using the Review Manager (RevMan) software 5.1. Results: Fourteen studies consisting of a total of 1,022 patients were included. Perineural dexamethasone significantly prolonged the duration of postoperative analgesia in patients receiving both low-dose (4 – 5 mg) [SMD 2.41 (95% CI: 1.47, 3.35 P = 0<0.00001) I2 = 82%], and higher-doses (8 – 10 mg) [SMD 4.46 (95% CI 3.54, 5.38 P < 0.00001) I2 = 94%]. However, the duration of motor block was also prolonged [SMD 2.52 (95% CI: 1.06, 3.98 P = 0.0007) I2 = 97%] and dexamethasone delayed latency of onset of sensory [SMD -0.49 (95% CI: -0.89, -0.09 P = 0.02) I2 = 76%] and motor [SMD -0.56 (95% CI: -1.13, 0.00 P = 0.05) I2 = 87%] blocks. Postoperative pain scores were improved at both 24 hours [SMD -1.46 (95% CI: -2.43, -0.50 P = 0.003) I2 = 95%] and 48 hours [SMD -1.20 (95% CI: -2.26, -0.13 P = 0.03) I2 = 95%] in dexamethasone-treated groups, whereas opioid consumption was reduced only at 48 hours [SMD -2.97 (95% CI: -4.17, -1.76 P < 0.00001) I2 = 88%]. Complications were comparable between control and dexamethasone-adjuvant groups, except for the excessively prolonged nerve block that was observed predominantly in the dexamethasone-adjuvant group. Limitations: The limitations include different definitions used for the measurements of certain parameters such as the duration of analgesia and duration of motor block, number of studies assessing certain parameters having high heterogeneity, and varying types of local anesthetics used in various studies. Conclusions: Perineural dexamethasone addition to local anesthetic solutions significantly improved postoperative pain in brachial plexus block without increasing complications. However, perineural adjuvant dexamethasone delayed the onset of sensory and motor block, and prolonged the duration of motor block. Smaller doses of dexamethasone (4 – 5 mg) were as effective as higher doses (8 – 10 mg). Key words: Dexamethasone, perineural, brachial plexus block, postoperative pain, metaanalysis, systematic review

Mammary gland ion transport is essential for lactation and is regulated by prolactin and glucocorticoids. This study delineates the roles of prolactin receptors (PRLR) and long-term prolactin and dexamethasone (P-D)-mediation of [Ca2+]i and Cl− transport in HC-11 cells. P-D (24 h) suppressed ATP-induced [Ca2+]i. This may be due to decreased Ca2+ entry since P-D decreased transient receptor potential channel 3 (TRPC3) but not secretory pathway Ca2+-ATPase 2 (SPCA2) mRNA. ATP increased Cl− transport, measured by iodide (I−) efflux, in control and P-D-treated cells. P-D enhanced I− efflux response to cAMP secretagogues without altering Cl− channels or NKCC cotransporter expression. HC-11 cells contain only the long form of PRLR (PRLR-L). Since the short isoform, PRLR-S, is mammopoietic, we determined if transfecting PRLR-S (rs) altered PRLR-L-mediated Ca2+ and Cl− transport. Untreated rs cells showed an attenuated [Ca2+]i response to ATP with no further response to P-D, in contrast to vector-transfected (vtc) controls. P-D inhibited TRPC3 in rs and vtc cells but increased SPCA2 only in rs cells. As in wild-type, cAMP-stimulated Cl− transport, in P-D-treated vtc and rs cells. In summary, 24 h P-D acts via PRLR-L to attenuate ATP-induced [Ca2+]i and increase cAMP-activated Cl− transport. PRLR-S fine-tunes these responses underscoring its mammopoietic action.