Megakaryocyte/platelet-derived TGF-ß1 inhibits megakaryopoiesis in bone marrow by regulating thrombopoietin production in liver.

Transforming growth factor ß1 (TGF-ß1) regulates a wide variety of events in adult bone marrow (BM), including quiescence of hematopoietic stem cells, via undefined mechanisms. Because megakaryocytes (MKs)/platelets are a rich source of TGF-ß1, we assessed whether TGF-ß1 might inhibit its own production by comparing mice with conditional inactivation of Tgfb1 in MKs (PF4Cre;Tgfb1flox/flox) and control mice. PF4Cre;Tgfb1flox/flox mice had ∼30% more MKs in BM and ∼15% more circulating platelets than control mice (P < .001). Thrombopoietin (TPO) levels in plasma and TPO expression in liver were approximately twofold higher in PF4Cre;Tgfb1flox/flox than in control mice (P < .01), whereas TPO expression in BM cells was similar between these mice. In BM cell culture, TPO treatment increased the number of MKs from wild-type mice by approximately threefold, which increased approximately twofold further in the presence of a TGF-ß1-neutralizing antibody and increased the number of MKs from PF4Cre;Tgfb1flox/flox mice approximately fourfold. Our data reveal a new role for TGF-ß1 produced by MKs/platelets in regulating its own production in BM via increased TPO production in the liver. Additional studies are required to determine the mechanism.

Intravenous dexamethasone as an adjunct to improve labor analgesia: A randomized, double-blinded, placebo controlled clinical trial.

OBJECTIVE: To study the role of intravenous (i.v.) dexamethasone as an analgesic adjunct in labor analgesia. DESIGN: Double-blinded randomized controlled trial. SETTING: Labor analgesia in a tertiary-care teaching hospital. PATIENTS: Eighty consenting ASA I-II parturients, age>18year, nulliparous, single gestation, cephalic presentation at ≥36 wk. of gestation, in early spontaneous labor (cervical dilatation≤5cm) requesting epidural analgesia. INTERVENTIONS: The patients were randomized to two groups. The Dexa group received 8mg of dexamethasone i.v. in 50ml normal saline approximately 45min before the procedure. Placebo group patients received 50ml normal saline only. All patients underwent epidural labor analgesia per hospital protocol. After an initial bolus, they received continuous background infusion of 5ml/h of 0.1% of levobupivacaine with 2µg/ml of fentanyl, with the provision of patient controlled boluses of 5ml of the same drug combination with a lockout interval of 12min if needed. MEASUREMENTS: Primary outcome measure: hourly average consumption of neuraxially administered levobupivacaine-fentanyl combination. Secondary outcomes and observations: pain score, maternal satisfaction, sensory and motor block characteristics, hemodynamic parameters of mother, fetal heart rate, duration of second stage of labor, mode of delivery, Apgar scores at 1 and 5min, and adverse effects. MAIN RESULTS: Average hourly drug consumption was significantly lower in Dexa group as compared to Placebo group (10.34±1.79ml/h vs. 11.34±1.83ml/h; mean difference 1.007, 95% CI 0.199-1.815; P=0.015). The median number of bolus doses was 4 (interquartile-range [IQR] 3-5.75) and 5 (IQR 3-6) in the Dexa and Placebo groups, respectively (P=0.162). There was no significant difference between groups with regard to pain scores, maternal satisfaction and hemodynamics, mode of delivery, and adverse effects. CONCLUSIONS: I.v. dexamethasone significantly decreased hourly average drug consumption of levobupivacaine-fentanyl combination through the epidural route, demonstrating the epidural drug dose sparing effect during labor analgesia.

Coinfections in Intensive Care Unit with pulmonary tuberculosis and mucormycosis: A clinical dilemma.

Herein, we present the case report of an adult male diabetic patient who had coinfection with Mycobacterium tuberculosis and mucormycosis, which otherwise is a rare clinical entity. Diabetes mellitus may predispose a patient to tuberculosis (TB) infection which further weakens immune system thus making him susceptible to other fungal or bacterial infections which may pose various treatment difficulties. Therefore, there is a need for mycological and bacteriological investigations in patients with pulmonary TB to rule out secondary coinfections thus contributing to better management.