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Iron is often accumulated in the liver during pathological conditions such as cirrhosis and cancer. Elevated expression of glucose transporters GLUT1 and GLUT3 is associated with reduced overall survival in patients with hepatocellular carcinoma. However, it is not known whether iron can regulate glucose transporters and contribute to tumor proliferation. In the present study, we found that treatment of human liver cell line HepG2 with ferric ammonium citrate (FAC) resulted in a significant upregulation of GLUT3 mRNA and protein in a dose-dependent manner. Similarly, iron accumulation in mice fed with high dietary iron as well as in mice injected intraperitoneally with iron dextran enhanced the GLUT3 expression drastically in the liver. We demonstrated that iron-induced hepatic GLUT3 upregulation is mediated by the LKB1/AMPK/CREB1 pathway, and this activation was reversed when treated with iron chelator deferiprone. In addition, inhibition of GLUT3 using siRNA prevented iron-mediated increase in the expression of cell cycle markers and cellular hyperproliferation. Furthermore, exogenous sodium beta-hydroxybutyrate treatment prevented iron-mediated hepatic GLUT3 activation both in vitro and in vivo. Together, these results underscore the importance of iron, AMPK, CREB1 and GLUT3 pathways in cell proliferation and highlight the therapeutic potential of sodium beta-hydroxybutyrate in hepatocellular carcinoma with high GLUT3 expression.

Competing Interests: Conflict of interest: The authors report no conflict of interest.

Trypanosoma cruzi , the aetiologic agent of Chagas disease, releases vesicles containing a wide range of surface molecules known to affect the host immunological responses and the cellular infectivity. Here, we compared the secretome of two distinct strains (Y and YuYu) of T. cruzi , which were previously shown to differentially modulate host innate and acquired immune responses. Tissue culture-derived trypomastigotes of both strains secreted extracellular vesicles (EVs), as demonstrated by electron scanning microscopy. EVs were purified by exclusion chromatography or ultracentrifugation and quantitated using nanoparticle tracking analysis. Trypomastigotes from YuYu strain released higher number of EVs than those from Y strain, enriched with virulence factors trans -sialidase (TS) and cruzipain. Proteomic analysis confirmed the increased abundance of proteins coded by the TS gene family, mucin-like glycoproteins, and some typical exosomal proteins in the YuYu strain, which also showed considerable differences between purified EVs and vesicle-free fraction as compared to the Y strain. To evaluate whether such differences were related to parasite infectivity, J774 macrophages and LLC-MK2 kidney cells were preincubated with purified EVs from both strains and then infected with Y strain trypomastigotes. EVs released by YuYu strain caused a lower infection but higher intracellular proliferation in J774 macrophages than EVs from Y strain. In contrast, YuYu strain-derived EVs caused higher infection of LLC-MK2 cells than Y strain-derived EVs. In conclusion, quantitative and qualitative differences in EVs and secreted proteins from different T. cruzi strains may correlate with infectivity/virulence during the host-parasite interaction.

Introduction: Sensory blockade of the brachial plexus with local anaesthetics for perioperative analgesia leads to stable haemodynamics intraoperatively, smoother emergence from general anaesthesia and decreased need for supplemental analgesics or suppositories in the Post-operative period. However, increasing the duration of local anaesthetic action is often desirable because it prolongs surgical anaesthesia and analgesia. Various studies in adults prove that steroids increase the duration of action of local anaesthetics when used as adjuncts., Aim: The study aimed at determining the efficacy of dexame-thasone as an adjuvant to bupivacaine for Post-operative analgesia following sensory blockade of the brachial plexus in paediatrics., Materials and Methods: The study was divided into two groups of 15 each, group BD receiving dexamethasone (0.1mg/kg) as an adjunct to bupivacaine 0.125% and group B receiving bupivacaine alone. The duration of analgesia was taken as time from completion of the block to the patient receiving rescue analgesia, the haemodynamics were measured until 180 minutes after surgery, the incidence of Post-operative Nausea and Vomiting (PONV) was measured., Results: The duration of analgesia in the group BD was 27.1±13.4 hours and was significantly higher as compared to the group B, in which it was 13.9±11.3 hours (p<0.05). The pulse rate measured Post-operatively between both groups at 20 minutes (p-value 0.634), 60 minutes (p-value 0.888), 120 minutes (p-value 0.904) and 180 minutes (p-value 0.528) showed no statistical significance. Likewise the mean blood pressure measured between the two groups at 20 minutes, 60 minutes, 120 minutes and 180 minutes Post-operatively showed no significance. There was no significant difference in incidence of PONV in both groups with p-value of 0.624., Conclusion: Dexamethasone as an adjuvant to local anaesthetic in brachial plexus blocks significantly, prolongs duration of analgesia in children undergoing upper limb surgeries.

Introduction: Anaesthesia and upper abdominal surgeries alter lung compliance and functional residual capacity resulting from atelectasis. Upper abdominal surgeries also cause a decrease in peak expiratory flow rates, cough reflex due to pain limited inspiration., Aim: This study aimed to study the effect of thoracic epidural analgesia (TEA) on the peak expiratory flow rates in patients undergoing upper abdominal surgeries., Materials and Methods: A total of 44 patients posted for elective surgery were enrolled. Group 1 patients received GA + 0.125% bupivacaine infusion TEA and Group 2 received GA + Inj. Diclofenac sodium 50 mg slow i.v. TID for Postoperative analgesia. Haemodynamics, VAS pain score, PEFR measurements were done at 60 minutes, 24 hours, 48 hours and 4 days after surgery in both groups. ABG analysis was taken pre operatively and 24 hours after surgery., Results: The SBP and DBP values obtained at 60 minutes (p<0.016) 24 and 48 hours (p<0.001) and day 4 (p<0.02) postoperative showed highly significant difference between the two groups which indicate better haemodynamic parameters in patients receiving epidural analgesia. Postoperatively the difference in PEFR values at 60 minutes, 24 hour, 48 hour and day 4 were very highly significant. (p<0.001). Group1 had a 10.739% deficit on day 4 from its pre operative baseline value while group 2 showed a 34.825 % deficit which was very highly significant (p<0.001). The difference in VAS scores recorded at 60 minutes, 24 hours, 48 hours and day 4 post op were very highly statistically significant (p < 0.001). The ABG taken at 24 hours shows statistically significant difference with patients in group 2 showing decreased values in pCO2 and pO2 reflecting poorer ventilation and oxygenation., Conclusion: Thoracic epidural analgesia provides superior analgesia, better cough reflex as seen by better PEFR values, were haemodynamically more stable and their ABG values were better than the NSAID group.

Background: Optimizing cardiovascular function to ensure adequate tissue oxygen delivery is a key objective in the care of critically ill patients with burns. Hemodynamic monitoring may be necessary to optimize resuscitation in serious burn patients with reasonable safety. Invasive central venous pressure (CVP) monitoring has become the corner stone of hemodynamic monitoring in patients with burns but is associated with inherent risks and technical difficulties. Previous studies on perioperative patients have shown that measurement of peripheral venous pressure (PVP) is a less invasive and cost-effective procedure and can reliably predict CVP., Objective: The aim of the present prospective clinical study was to determine whether a reliable association exists between changes in CVP and PVP over a long period in patients admitted to the Burns Intensive Care Unit (BICU)., Subjects and Methods: The CVP and PVP were measured simultaneously hourly in 30 burns patients in the BICU up to 10 consecutive hours. The predictability of CVP by monitoring PVP was tested by applying the linear regression formula and also using the Bland-Altman plots of repeated measures to evaluate the agreement between CVP and PVP., Results: The regression formula revealed a reliable and significant association between CVP and PVP. The overall mean difference between CVP and PVP was 1.628 ± 0.84 mmHg (P < 0.001). The Bland-Altman diagram also showed a perfect agreement between the two pressures throughout the 10 h period., Conclusion: Peripheral venous pressure measured from a peripheral intravenous catheter in burns patients is a reliable estimation of CVP, and its changes have good concordance with CVP over a long period of time.

This study evaluated the in vivo potential antihypertensive effect of hydroalcoholic extract of Syzygium cumini leaves (HESC) in normotensive Wistar rats and in spontaneously hypertensive rats (SHR), as well as its in vitro effect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01-4.0 mg/kg) in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day), orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (E max⁡) of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL). This study demonstrated that Syzygium cumini reduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.