Lactated Ringer Solution Research Articles

Gastrointestinal Bleeds.

Gastrointestinal Bleeds.

Efficacy of Rectal Misoprostol in Active Management of Third Stage of Labour in Comparison with Oxytocin

Background Third stage of labour is defined as the time from delivery the baby to complete delivery of the placenta and its attached membranes Most common complications of the third stage of labour are postpartum hemorrhage (PPH). Active management of third stage of labour (AMTL) prevents PPH. Misoprostol is a prostaglandin E1 analogue has been suggested as an alternative of the routine prophylactic oxytocic agents in AMTL. Rectal route had been chosen because it avoids gastrointestinal side effects Objectives: To asses effectiveness of (400 mcg) rectally administered misoprostol tablet in the AMTL in comparison with standard oxytocin regimen Patients and Methods In prospective case-control study, 100 women were randomized, 50 patients received either 400mcg misoprostol tablets rectally (study medication) the other 50 received 10 IU oxytocin in 500 ml Ringer lactate solution IV. As a method of AMTL. Patient with risk factor for PPH had been excluded. A comparison between the two groups in their amount of blood loss, drop in hemoglobin level from admission to 24 hr. after delivery, duration of third stage of labour and any side effects appear done Results Maximum amount of blood loss in both groups of the study was 440 ml, so we had no case of PPH. There was no stastically significant difference in mean blood loss, mean difference in Hb level (gm/dl) on admission and 24 hours after delivery, and duration of third stage of labour found between study groups [p values= 0.138, 0.227, 0.08 respectively]. More shivering occurs in cases but the difference was not significant. Conclusions: Misoprostol in a dose of 400 mcg rectally shows promising results, it seems safe and effective drug that can be used in the management of third stage of labour.

Na+-K+-ATPase plays a major role in mediating cutaneous thermal hyperemia achieved by local skin heating to 39°C.

Na+-K+-ATPase is integrally involved in mediating cutaneous vasodilation during an exercise-heat stress, which includes an interactive role with nitric oxide synthase (NOS). Here, we assessed if Na+-K+-ATPase also contributes to cutaneous thermal hyperemia induced by local skin heating, which is commonly used to assess cutaneous endothelium-dependent vasodilation. Furthermore, we assessed the extent to which NOS contributes to this response. Cutaneous vascular conductance (CVC) was measured continuously at four forearm skin sites in 11 young adults (4 women). After baseline measurement, local skin temperature was increased from 33°C to 39°C to induce cutaneous thermal hyperemia. Once a plateau in CVC was achieved, each skin site was continuously perfused via intradermal microdialysis with either: 1) lactated Ringer solution (control), 2) 6 mM ouabain, a Na+-K+-ATPase inhibitor, 3) 20 mM l-NAME, a NOS inhibitor, or 4) a combination of both. Relative to the control site, CVC during the plateau phase of cutaneous thermal hyperemia (∼50% max) was reduced by the lone inhibition of Na+-K+-ATPase (-19 ± 8% max, P = 0.038) and NOS (-32 ± 4% max, P < 0.001), as well as the combined inhibition of both (-37 ± 9% max, P < 0.001). The magnitude of reduction was similar between NOS inhibition alone and combined inhibition (P = 1.000). The administration of both Na+-K+-ATPase and NOS inhibitors fully abolished the plateau of CVC with values returning to preheating baseline values (P = 0.439). We show that Na+-K+-ATPase contributes to cutaneous thermal hyperemia during local skin heating to 39°C, and this response is partially mediated by NOS.NEW & NOTEWORTHY Cutaneous thermal hyperemia during local skin heating to 39°C, which is highly dependent on nitric oxide synthase (NOS), is frequently used to assess endothelium-dependent cutaneous vasodilation. We showed that Na+-K+-ATPase mediates the regulation of cutaneous thermal hyperemia partly via NOS-dependent mechanisms although a component of the Na+-K+-ATPase modulation of cutaneous thermal hyperemia is NOS independent. Thus, as with NOS, Na+-K+-ATPase may be important in the regulation of cutaneous endothelial vascular function.

Investigation of biomarkers for impending fluid overload in a feline acute haemorrhage-resuscitation model

ObjectiveTo determine biomarkers for impending fluid overload during intravenous fluid administration in a feline haemorrhage-resuscitation model. Study designRandomized crossover study. AnimalsA group of six domestic cats (mean age and weight: 21 months; 4.9 kg, respectively). MethodsThe cats underwent three treatments, 2 months apart. They were anaesthetized and instrumented to measure a range of physiological, blood gas, haematological and biochemical variables over time. Samples were taken during a health check, before haemorrhage, after haemorrhage and then at 30 minute intervals during fluid resuscitation and 24 hours later. The three treatments were: 1) control, sham haemorrhage and resuscitation; 2) lactated Ringer’s solution (LRS); and 3) 6% tetrastarch 130/0.4 (Vol) where the cats underwent a controlled haemorrhage then resuscitation by administering LRS and Vol at 60 and 20 mL kg–1 hour–1, respectively, for 120 minutes. Fluid overload was identified by nasal discharge and radiographic evidence. Biomarkers were variables that exceeded the reference interval for cats during treatment. Potential biomarkers were analysed using receiver operating characteristic curves (p < 0.05). ResultsMean ± standard deviation total blood loss was 10.2 ± 2.3, 29.3 ± 9.0 and 29.1 ± 6.3 mL kg–1 for control, LRS and Vol, respectively. The total volume of LRS and Vol administered was 120 and 40 mL kg–1, respectively. Haematocrit, albumin, magnesium, chloride-to-sodium ratio and sodium-chloride difference were identified as potential biomarkers. These variables exceeded the reference intervals from 30 minutes of resuscitation onwards. A chloride-to-sodium ratio > 0.84 was the most sensitive (90%) and specific (75%) of all potential biomarkers. Conclusions and clinical relevanceChanges in physiological variables, haematocrit and albumin were poor biomarkers of impending fluid overload compared with electrolytes. Finding the ideal biomarker to identify impending fluid overload of commonly used intravenous fluids should improve the safety of their administration in cats.

Comparative Trial of Continuous Flow Enteral and Intravenous Fluid Therapy in Horses.

Continuous flow enteral fluid therapy with isotonic and hypotonic enteral electrolyte solutions are as safe and effective as intravenous fluid therapy. The aim of this study was to carry out a comparative assessment between continuous flow enteral and intravenous (IV) fluid therapy in adult experimentally dehydrated horses. Six experimentally dehydrated adult mares were used in a study carried out in a 6 × 3 crossover design, which each animal received three different treatments (isotonic enteral fluid therapy—EsISO, hypotonic enteral fluid therapy—EsHYPO and intravenous fluid therapy with Lactate Ringer Solution—LR IV, all in continuous flow). Solutions were administered at a rate of 15 mL−1.kg−1.h−1 for 8 h, after 36 h of water and food deprivation. Serum and urinary biochemical assessment; urinary volume, pH and specific gravity; and blood gas analysis were measured at −36, 0, 2, 4, 6, and 8 h. The dehydration period (DP) caused discrete hydroelectrolytic and acid base imbalances. The EsISO, EsHYPO and LR IV increased blood volume. Enteral solutions restored the imbalances yielded by the DP and all treatments increased urine volume. Also, the EsHYPO and LR IV showed no effects in acid base balance, while EsISO showed slightly acidifying effect. The present study certifies the efficacy and safety of isotonic and hypotonic continuous flow enteral fluid therapy in comparison to IV fluid therapy in dehydrated horses.

Glucose detection of ringer-lactate solution using electrical bioimpedance: preliminary results

Continuous glucose monitoring is essential to reduce the damages caused by diabetes and for choosing the right treatment approach. In most cases, non-invasive glucose measurement devices generate their results through statistical tools (e.g., artificial neural networks) with an error that increases the further away from the training sample the measurement is. An analytical model would contain only propagated errors. Impedance measurements of lactate ringer’s solutions with egg albumin containing different concentrations of sugar were performed to validate the model proposed for measuring glycemia in human blood using the electrical bioimpedance meter AD5933. The curve fitting showed errors lower than 1.5%. Chemical phenomena, such as reduced sugar, fructosamine and solvation, might explain the behaviors observed in the experiments. The results suggest that the relaxation coefficient has significant changes with the increase of sugar in the solutions. The findings encourage future research with bovine blood for a more realistic analytical model.

Randomized control trial to study the efficacy and safety of platelet-rich plasma as intraoperative holding solution in hair restoration surgery: A pilot study

BackgroundHair restoration surgery is a definitive surgical procedure undertaken for androgenetic alopecia (AGA). Platelet-rich plasma (PRP) therapy has gained importance in recent times as a valuable adjunct to therapy in hair restoration. However, the various beneficial effects of PRP as intraoperative holding solution hair restoration surgery remain to be objectively defined. MethodsTwenty cases of AGA were allocated into two groups (PRP and non-PRP). The follicular grafts harvested were stored in platelet-rich plasma/chilled ringers lactate solution depending on subject/control and were implanted in receding hairline using hair implanters. Patients were reviewed at the end of 2 weeks, 4 weeks, 8 weeks, 3 months, and 6 months using clinical and folliculoscopic images. The analysis was performed using SPSS version 20.0. ResultsFollicular growth as assessed using the percentage of grafts in actively growing phase posttransplant showed faster recovery from ‘shock effluvium’ in the PRP group when compared with the non-PRP group from Week 4, through Week 8 and 3 months with the ‘lead’ increases of percentage growth difference being statistically significant(P = 0.02) between the two groups. At the end of 6 months, 100% of patients recorded a hair shaft length of >10 mm in the PRP group, whereas only 20% achieved >10 mm length. The difference in hair densities between PRP and the non-PRP group from 4 weeks up to 6 months in the non PRP group remained significant (P < 0.05). ConclusionIntraoperative PRP as a holding solution improves outcome in hair restoration surgery by a significant improvement in the mean density of the implanted follicular unit grafts at 6 months.

Plasma‐activated Ringer's lactate solution inhibits the cellular respiratory system in HeLa cells

AbstractNonequilibrium atmospheric pressure plasma has enabled a variety of new applications in medicine, agriculture, and other industries. It is particularly noteworthy that plasma itself and/or plasma‐activated culture medium have been shown to preferentially kill various cancer cells. We have previously developed a plasma‐activated Ringer's lactate solution (PAL) for use as a new cancer treatment. In this study, behaviors of extracellular and intracellular reactive oxygen and nitrogen species in the cellular respiratory system of PAL‐treated HeLa cells were investigated using an extracellular flux analyzer and a probe to measure mitochondrial membrane potential. In PAL‐treated HeLa cells, extracellular hydrogen peroxide in PAL was found to be responsible for the induction of intracellular hydrogen peroxide and apoptosis, while other components in PAL are responsible for the induction of non‐H2O2 intracellular ROS and non‐apoptotic cell death, which should be clarified by further experiments. We believe that these are long‐lived species derived from plasma‐activated lactates. Furthermore, we found that the plasma‐activated lactates inhibited glycolysis and the tricarboxylic acid (TCA) cycle, but not the electron transport chain in HeLa cells. These results suggest that PAL induces multiple modes of cell death, including apoptosis through hydrogen peroxide, and non‐apoptotic cell death associated with the impairment of mitochondrial functions (glycolysis and TCA cycle). These findings shed light on the novel mechanism underlying plasma‐activated lactate‐induced cell death.

Involvement of Toll-Like Receptor 4 in Decreased Vasopressor Response Following Trauma/Hemorrhagic Shock.

OBJECTIVES:Refractory vascular failure due to the inability of vascular smooth muscle to respond to vasoconstrictors such as phenylephrine is a final common pathway for severe circulatory shock of any cause, including trauma/hemorrhagic shock. Increased inflammation, Toll-like receptor 4 activation, and decreased response of the alpha-1 adrenergic receptors which control vascular tone have been reported in trauma/hemorrhagic shock.HYPOTHESIS:In trauma/hemorrhagic shock, Toll-like receptor 4 activation contributes to vascular failure via decreased bioavailability of adrenergic receptors.DESIGN AND MEASUREMENTS:Trauma/hemorrhagic shock was induced in Wistar rats (laparotomy combined with mean arterial pressure at 40 mm Hg for 90 min followed by 2 hr resuscitation with Lactated Ringers solution). To inhibit Toll-like receptor 4, resatorvid (TAK-242) and resveratrol were used, and plasma was collected. Smooth muscle cells were incubated with lipopolysaccharide (10 ng/mL) or plasma. Inflammatory cytokines were screened using dot-blot. Toll-like receptor 4 and nuclear factor κB activation and cellular localization of the alpha-1 adrenergic receptor were measured by immunofluorescence imaging and Western blot analysis. Clustered regularly interspaced short palindromic repeats/Cas9 was used to knock out Toll-like receptor 4, and calcium influx following stimulation with phenylephrine was recorded.MAIN RESULTS:Trauma/hemorrhagic shock caused a decreased response to phenylephrine, whereas Toll-like receptor 4 inhibition improved blood pressure. Trauma/hemorrhagic shock plasma activated the Toll-like receptor 4/nuclear factor κB pathway in smooth muscle cells. Double labeling of Toll-like receptor 4 and the alpha-1 adrenergic receptor showed that these receptors are colocalized on the cell membrane. Activation of Toll-like receptor 4 caused cointernalization of both receptors. Calcium influx was impaired in cells incubated with trauma/hemorrhagic shock plasma but restored when Toll-like receptor 4 was knocked out or inhibited.CONCLUSIONS:Activation of the Toll-like receptor 4 desensitizes vascular smooth muscle cells to vasopressors in experimental trauma/hemorrhagic shock by reducing the levels of membrane alpha-1 adrenergic receptor.

Effect of Reformation of the Anterior Chamber by Air or by Ringer’s lactate solution on Corneal Endothelial count and morphology after Phacoemulsification

Background:The corneal endothelium has no ability of regeneration, so any decrease in its density is irreversible and can lead to permanent blurring of vision and pain. Direct contact between air and the corneal endothelium may cause endothelial damage. Aim:To compare the effect of reformation of the anterior chamber after phacoemulsification, using air and ringer’s lactate solution injection, on corneal endothelial count and morphology. Subject and method:A prospective interventional randomized comparative study includes 76 eyes of 76 patients, prepared for phacoemulsification surgery in the period from October 2018 to March 2019. Corneal endothelial morphology and count examined by specular microscopy, and the results recorded for all cases before the surgery. Patients examined by slit lamp biomicroscope and divided randomly into two groups, and both groups were diagnosed with grade 1-2 age related nuclear cataract (according to Lens opacity classification system III). Both groups underwent phacoemulsification surgery with IOL implantation by single well-trained surgeon, group 1 will be subjected to anterior chamber reformation with 0.1 ml air injection while group 2 will be subjected to reformation of the anterior chamber with ringer’s lactate solution. Corneal endothelial morphology and count to be evaluated at 1 week, 1 month and 3 months postoperatively. Results:no significant statistical difference regarding the percentage of CCT changes, cell loss, coefficient of variation and hexagonality between the two groups at baseline and all subsequent visits. Conclusion:no significant difference between air and ringer's lactate solution on the corneal endothelial count and morphology.

Balanced Salt Solution Versus Normal Saline in Resuscitation of Pediatric Sepsis: A Randomized, Controlled Trial.

Current evidences in resuscitation of adult sepsis have pointed to the importance of types of crystalloid fluid-related complications on resuscitation outcomes, but evidences are lacking in pediatric populations. In this study, the authors aimed to compare outcomes of pediatric sepsis resuscitation with different types of crystalloid. They randomly assigned pediatric sepsis patients requiring fluid bolus into three groups to receive either normal saline solution (NSS), Ringer lactate solution (RLS), or Sterofundin as fluid bolus therapy. Forty-two patients were included in the study. Median age was 29 mo and, weight 13 kg. After fluid bolus, the complications were not different among groups. However, in the RLS group, the patients who received large dose of the fluid showed significant reduction in urinary neutrophil gelatinase-associated lipocalin (uNGAL) level. It is concluded that fluid bolus therapy with different types of crystalloid solution did not result in different outcomes but large dose of RLS was associated with greater reduction of uNGAL level, compared to other fluids.Trial Registration: Thai Clinical Trial Registry (TCTR) identification number TCTR20170605001 (retrospectively registered on 1st June 2017). https://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task20=search&task2=view1&id=2576

Effect of hydroxyapatite/alumina composite coatings using HVOF on immersion behavior of NiTi alloys.

Hydroxyapatite (HA) coatings have been widely used to improve biocompatibility of metal alloys. This paper discusses the effect of hydroxyapatite (HA) and HA/alumina coated NiTi on their corrosion and dissolution behavior in Phosphate Buffer Saline (PBS) and Ringer's lactate solutions. The HA was synthesized from biogenic method and used as initial powder in High-Velocity Oxygen Fuel (HVOF) spray technique for the deposition of two coating types, fully HA and HA + 15 wt.% alumina composite coating. The as-synthesized HA had irregular porous structure with relatively low Ca/P ratio of 1.52. Tafel polarization curves obtained from electrochemical test had showed that both coatings increased the corrosion resistance of the NiTi substrates significantly. The ICP-MS analysis results that indicated a low nickel dissolved in both solutions after immersion in 21 days had supported these findings. The nickel levels in the solutions from all samples, either bared substrate or coated samples, in fact below the maximum limit for allergies of the human body. Immersion testing showed the stability of HA and HA/alumina layers as a barrier which maintains its morphology in PBS solution but slightly changed in Ringers.

Effects of different fluid resuscitation on renal function and glycocalyx in septic shock rats

To investigate the effects of different fluid resuscitation on renal function and glycocalyx in septic shock rats. The septic shock SD rats (induced by lipopolysaccharide) were randomly divided into control group, normal saline resuscitation group, Lactate Ringer's solution resuscitation group and succinyl gelatin resuscitation group (n=6 each). The mean arterial pressure, heart rate, serum creatinine (Scr), urea nitrogen (BUN), renal blood flow, renal tissue pathology, serum interleukin-6, tumor necrosis factor α and glycocalyx were measured at baseline, the development of septic shock, 0 hour and 8 hours after resuscitation. When shock was established, the renal blood flow significantly decreased (P<0.05) and recovered to normal at 0 hour and 8 hours after resuscitation. Compared with normal saline group and succinyl gelatin group, the levels of Scr, BUN and glycocalyx components (heparan sulfate, syndecan-1) were significant lower in Lactate Ringer's solution group (P<0.05). The pathology of kidney tissue suggested that the microscopic ischemic damage with Lactate Ringer's solution were minor than the other two groups. Compared with normal saline and succinyl gelatin, Lactate Ringer's solution can reduce the damage of renal function and glycocalyx in septic shock rats.

Effects of Normoxia, Hyperoxia, and Mild Hypoxia on Macro-Hemodynamics and the Skeletal Muscle Microcirculation in Anesthetised Rats.

Objectives: Excessive oxygen (O2) administration may have a negative impact on tissue perfusion by inducing vasoconstriction and oxidative stress. We aimed to evaluate the effects of different inhaled oxygen fractions (FiO2) on macro-hemodynamics and microvascular perfusion in a rat model.Methods: Isoflurane-anesthetised spontaneously breathing male Wistar rats were equipped with arterial (carotid artery) and venous (jugular vein) catheters and tracheotomy, and randomized into three groups: normoxia (FiO2 21%, n = 6), hyperoxia (FiO2 100%, n = 6) and mild hypoxia (FiO2 15%, n = 6). Euvolemia was maintained by infusing Lactate Ringer solution at 10 ml/kg/h. At hourly intervals for 4 h we collected measurements of: mean arterial pressure (MAP); stroke volume index (SVI), heart rate (HR), respiratory rate (by means of echocardiography); arterial and venous blood gases; microvascular density, and flow quality (by means of sidestream dark field videomicroscopy on the hindlimb skeletal muscle).Results: MAP and systemic vascular resistance index increased with hyperoxia and decreased with mild hypoxia (p < 0.001 in both cases, two-way analysis of variance). Hyperoxia induced a reduction in SVI, while this was increased in mild hypoxia (p = 0.002). The HR increased under hyperoxia (p < 0.05 vs. normoxia at 3 h). Cardiax index, as well as systemic O2 delivery, did not significantly vary in the three groups (p = 0.546 and p = 0.691, respectively). At 4 h, microvascular vessel surface (i.e., the percentage of tissue surface occupied by vessels) decreased by 29 ± 4% in the hyperoxia group and increased by 19 ± 7 % in mild hypoxia group (p < 0.001). Total vessel density and perfused vessel density showed similar tendencies (p = 0.003 and p = 0.005, respectively). Parameters of flow quality (microvascular flow index, percentage of perfused vessels, and flow heterogeneity index) remained stable and similar in the three groups.Conclusions: Hyperoxia induces vasoconstriction and reduction in skeletal muscle microvascular density, while mild hypoxia has an opposite effect.

SURFACE MODIFICATION OF COMMERCIALLY PURE TITANIUM BY GOLD-ION IRRADIATION FOR BIOMEDICAL APPLICATIONS

This research work’s aim was to enhance the biocompatibility of the commercially pure titanium (cpTi-2) surface via Au-ion irradiation. Various ion dosages, i.e. [Formula: see text] (Au-11), [Formula: see text] (Au-12) and [Formula: see text] (Au-13) ions[Formula: see text][Formula: see text][Formula: see text]cm[Formula: see text], were produced by exposing the polished cpTi-2 samples to Au-ion beam at room temperature. The surface topographic features of cpTi-2 and the effects of Au-ion-implanted surfaces were examined by atomic force microscopy and XRD analysis. Open-Circuit Potential (OCP), Potentiodynamic Polarization Scans (PPS) and Electrochemical Impedance Spectroscopy (EIS) were used to compare the electrochemical behavior of the cpTi-2 and Au-ion-implanted samples in Ringer’s lactate (RL) solution at 37∘C. The effects of Au-ion irradiation on the proliferation of mesenchymal stem cells (MSCs) were estimated during 24[Formula: see text]h and 48[Formula: see text]h of exposure. Based on the experimental results, Au-12 samples presented more positive OCP and lower corrosion rate in RL solution than the Au-11 and Au-13 samples. No significant change in the morphology of the MSCs was observed after exposure to the Au-ion-implanted samples. Similar to the controlled medium, the percentage of viability of the cells of the cells on Au-12 increased from 75% to 165% on the surface of Au-13 samples during 48[Formula: see text]h of incubation indicating the positive effects of Au-ion irradiation for biocompatibility.

006 The effect of sodium oxybate on cataplexy in orexin knockout mice

Abstract Introduction Narcolepsy is a neurological disorder that is characterized by the loss of orexin neurons in the lateral hypothalamus. Cataplexy is a symptom of narcolepsy and is identified by a sudden loss of muscle tone during wakefulness. Cataplexy abruptly interrupts day-to-day activities, and makes activities like driving dangerous and potentially fatal. It is hypothesized that cataplexy occurs due to the intrusion of REM sleep muscle atonia during wakefulness. It has been demonstrated that a GABAergic mechanism is responsible for silencing the REM sleep atonia circuit and preventing REM sleep muscle atonia from occurring during wakefulness. Sodium oxybate (SXB), a low affinity agonist of GABAB receptors, is currently an approved treatment for narcolepsy; however, its mechanism of action in the brain remains unknown. Here, we investigate the hypothesis that SXB prevents cataplexy through a GABAB mediated mechanism by potentially suppressing the REM sleep atonia circuit. Methods We intraperitoneally (IP) injected orexin-/- mice with one of five treatments; either Lactated Ringers Solution, SXB at 50, 100, or 200 mg/kg, or Phaclophen at 10 mg/kg followed by SXB at 100 mg/kg. Cataplexy was assessed by video recordings. We gathered and analyzed data at three distinct chronological time points (i.e, at baseline, after three consecutive weeks of daily dosing with a treatment, and after one week of no treatment). These experiments were designed and conducted to determine whether; 1) SXB reduces cataplexy, 2) the cessation of SXB administration has an effect on cataplexy, 3) SXB is mediated through a GABAB mechanism. Results We first confirmed that mice used were indeed orexin-/- using immunohistochemical analysis to show that no orexin-a expressing neurons were located in the lateral hypothalamus. Then, we determined that: 1) SXB reduces cataplexy compared to time matched controls (unpaired t-test, p=0.0027, n=18); 2) When we stopped administering SXB IP injections, cataplexy levels increased towards control levels (paired t-test, p=0.0024, n=18); 3) it remains unclear if SXB’s effect is solely mediated through a GABAB mechanism. Conclusion Our findings demonstrate that SXB effectively reduces cataplexy in orexin-/- mice. Support (if any) This research was funded by Jazz Pharmaceuticals

Assessment of the physical compatibility of injectable enrofloxacin with commonly used intravenous fluids and drugs during simulated Y-port administration

To evaluate physical compatibility of small animal (SAE) and large animal (LAE) injectable formulations of enrofloxacin with select IV fluids and drugs. 162 admixtures containing SAE or LAE with saline (0.9% NaCl) solution, lactated Ringer solution (LRS), Plasma-Lyte A (PLA), 6% hydroxyethylstarch 130/0.4 (HES), metoclopramide, or ampicillin-sulbactam. In the first of 2 simultaneously conducted experiments, admixtures containing enrofloxacin (10 mg/kg) and a volume of IV fluid that would be administered over a 20-minute period when dosed at the maintenance infusion rate (40 mL/kg/d for saline solution, LRS, and PLA and 20 mL/kg/d for HES) were created. In the second experiment, enrofloxacin (10 mg/kg) was admixed with saline solution (40 mL/kg/d) and metoclopramide (2 mg/kg/d) or ampicillin-sulbactam (30 mg/kg). In both experiments, admixture components were infused into a flask over 20 minutes assuming patient weights of 5, 10, and 20 kg. Admixtures were created by use of undiluted SAE and SAE diluted 1:1 with saline solution and undiluted LAE and LAE diluted 1:1 and 1:10 with saline solution. Admixtures were assessed for physical incompatibility at 0, 15, 30, and 60 minutes after completion of mixing. Physical incompatibility was defined as gross precipitation, cloudiness, Tyndall effect, or change in turbidity. Admixtures containing undiluted SAE or LAE were physically incompatible with saline solution, PLA, LRS, and HES. Because saline solution was used to dilute SAE and LAE, all admixtures containing diluted SAE or LAE were also physically incompatible. Physical compatibility of enrofloxacin with metoclopramide or ampicillin-sulbactam could not be assessed because those admixtures also contained saline solution. Enrofloxacin was physically incompatible with all tested solutions.

TRPA1 channel activation with cinnamaldehyde induces cutaneous vasodilation through NOS, but not COX and KCa channel, mechanisms in human

Transient receptor potential (TRP) channels exist in various cells and tissues including nerves and vascular endothelium. TRP channels are implicated in the regulation of several sensory organs associated with pain, pressure, and temperature. While there exists a number of TRP channels, transient receptor potential vanilloid 1 (TRPV1) and 4 (TRPV4) channels in human skin have been shown to modulate cutaneous vasodilation (Fujii et al., 2019; Wong et. al., 2012). Transient receptor potential ankyrin 1 (TRPA1) subtype, which belongs to the TRP channel, is thought to be activated by cold and possibly warm/hot temperatures (Wang and Siemens, 2015). Recently, we showed that TRPA1 channel activation with cinnamaldehyde induced cutaneous vasodilation in humans (Fujii et al., 2020). However, the mechanisms underlying this response remains to be determined. A previous study using mouse ear showed that nitric oxide (NO) synthase (NOS), which is a meditator of endothelium-dependent vasodilation, can modulate the TRPA1 channel induced cutaneous vasodilation (Aubdool et al., 2016). However, it is unclear if this relationship exists in humans. Moreover, whether cyclooxygenase (COX) and Ca2+ activated K+ (KCa) channels, which are also established modulators of endothelium-dependent vasodilation, contribute to TRPA1 channel induced cutaneous vasodilation remains to be directly assessed in humans. Based on the above, we evaluated the hypothesis that NOS, COX, and KCa channels mediate the TRPA1 channel induced cutaneous vasodilation in humans. To assess our hypothesis, cutaneous vascular conductance (CVC) was assessed in 9 healthy young adults (29 ± 6 years, 4 women) at four dorsal forearm skin sites treated by intradermal microdialysis with either: 1) vehicle control (98 % propylene glycol + 0.015% lactated Ringer solution + 1.985 % dimethyl sulfoxide), 2)10 mM N(G)-Nitro-L-arginine methylester, a non-selective NOS inhibitor, 3)10 mM ketorolac, a non-selective COX inhibitor, or 4) 50 mM tetraethylammonium, a non-selective KCa channel blocker. Cinnamaldehyde, a TRPA1 channel activator, was administered to each skin site in a dose-dependent manner (2.9, 8.8, 26 and 80% of cinnamaldehyde concentrations, each lasting at least 30min). Administration of ≥8.8 % cinnamaldehyde increased CVC from baseline at the vehicle control site (e.g., 27.4± 2.7 % increase in CVC, P<0.05). NOS inhibition attenuated the cinnamaldehyde induced-cutaneous vasodilation at 2.9, 8.8, 26 and 80% concentrations relative to the vehicle control site (all P<0.05). COX inhibition and KCa channel blockade did not attenuate the cinnamaldehyde induced-cutaneous vasodilation relative to the vehicle control site at all concentrations (all P>0.05). We conclude that in human skin in vivo, NOS plays a role in modulating the regulation of cutaneous vasodilation in response to TRPA1 channel activation with negligible contributions of COX and KCa channels.

Aggressive hydration with lactated ringer solution in prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: A systematic review and meta-analysis.

Background:Acute pancreatitis is the most common complication of Endoscopic Retrograde Cholangiopancreatography (ERCP). There was no conclusion on the prevention of Post-ERCP Pancreatitis (PEP) by Lactated Ringer Solution.Aim:The purpose of this meta analyses is to determine whether aggressive hydration with Lactated Ringer Solution reduced the incidence of PEP.Methods:We retrieved randomized clinical trials comparing the preventive effects of aggressive hydration with Lactated Ringer Solution and standard hydration on PEP from PubMed, the Cochrane Library, Embase, the Web of Science, Clinical Trial.gov, Scopus database, CNKI, CQVIP and WanFang Data. Primary outcome was incidence of PEP. Secondary outcomes included incidence of hyperamylasemia, abdominal pain and adverse events.Results:Ten randomized controlled trials with 2200 patients were included in this meta-analysis. Meta-analysis showed that compared with standard hydration, aggressive hydration reduced the incidence of PEP (odds ratio [OR], 0.40; 95% confidence intervals [CI], 0.26–0.63; P < .0001). Compared with standard hydration, aggressive hydration also reduced the incidence of hyperamylasemia after ERCP (OR, 0.48; 95% CI, 0.38–0.60; P < .0001). There was significant difference between aggressive hydration and standard hydration in the incidence of abdominal pain (OR, 0.29; 95% CI, 0.11–0.73; P = .008). There was no difference in adverse events between aggressive hydration and standard hydration (OR, 0.93; 95% CI, 0.21–4.13; P = .93). Sensitivity analyses showed that neither alternative effect measures nor statistical models regarding heterogeneity affected the conclusions of this meta-analysis.Conclusion:Aggressive hydration with Lactated Ringer Solution during perioperative period of ERCP can prevent PEP.

Intrauterine Blood Plasma Platelet-Therapy Mitigates Persistent Breeding-Induced Endometritis, Reduces Uterine Infections, and Improves Embryo Recovery in Mares.

Microorganisms, including pathogenic or opportunistic bacteria and fungi, may gain access to the uterus during breeding, and infectious endometritis plays a major role in equine subfertility. This study aimed to assess the post-breeding inflammatory response, endometrial culture, and embryo recovery of mares susceptible to persistent breeding-induced endometritis (PBIE) treated with plasma-rich (PRP) or -poor (PPP) plasma. Mares (n = 12) susceptible to PBIE had three cycles randomly assigned to receive intrauterine infusions of lactate ringer solution (LRS, control), or autologous PRP or PPP pre- (−48 and −24 h) and post-breeding (6 and 24 h). Mares were bred with fresh semen from one stallion. Intrauterine fluid accumulation (IUF) and endometrial neutrophils were assessed every 24 h up to 96 h post-breeding. Uterine cytokines (Ilβ, IL6, CXCL8, and IL10) were evaluated before (0 h), 6, and 24 h post-breeding, and endometrial culture three and nine days after breed. Embryo flushing was performed 8 days post-ovulation. Data were analyzed with mixed model, Tukey’s post-hoc test, and multivariate regression. PRP treatment reduced endometrial neutrophils, post-breeding IUF, and pro-inflammatory cytokines when compared to control-assigned cycles, but not significantly different than PPP. Controls had a significantly higher percentage of positive bacterial cultures (33%) in comparison to PRP-assigned cycles (0%), whereas cycles treated with PPP were not significantly different from the other groups (25%). The PRP-assigned cycles had significantly greater embryo recovery rates (83%) than the control (33%), though not significantly different than PPP (60%). Plasma infusion reduced the duration and intensity of the post-breeding inflammatory response and improved embryo recovery in mares susceptible to PBIE. Platelets incrementally downregulate PBIE and appear to have a dose-dependent antimicrobial property.