Acid Saline Research Articles

Catalysts Containing Transition Metals on Nitrogen and Carbon Structures for Hydrogen Production through Salt Water Electrolysis

Hydrogen as an energy carrier is promising as it does not produce green-house gas (GHG) emissions at points of use and can be obtained from sources of low, or even neutral or negative GHG intensities [1,2]. One pathway to produce low emission hydrogen is water electrolysis when using a renewable power source [3]. However, freshwater, commonly used in this process, is relatively scarce, demand is high and expected to rise, and gets scarcer every day because of pollution [4,5,6]. An alternative is using saltwater, either through desalination or directly via adequate electrolysers [4]. Regarding direct use, a major challenge concerns catalyst, typically made of precious metals like Pt in the cathode, which are expensive, limited and susceptible to poisoning, e.g., by chlorine [7]. Likewise, in the anode chlorine is corrosive and reduces faradaic efficiency [4]. In this context, metal-coordinated nitrogen-carbon (M-N-C) nanostructures have proven to be attractive vis-à-vis these challenges [8]. To study their potential for saltwater electrolysis, five materials were synthesized following Malko et al. [8] using 1,5-diaminonaphthalene and 1% wt metallic sulphate salts of Co, Ni, Fe, Ni with Fe, and a blank without metal. The resulting material were suspended in 2-propanol and cast onto a vitreous carbon rotating ring disk electrode in both acidic solution 0,5M H2SO4 and saline medium 0,5M NaCl. Following electrode conditioning with cyclic voltammetries and electrochemical impedance characterization, linear sweep voltammetries (LSVs) were carried out in order to assess activity towards hydrogen evolution reaction (HER), coupled to hydrogen oxidation (HOR) at the Pt electrode in a ring-RDE (RRDE) fashion at constant potential of 0,3 V.The image presents HER and HOR plots in RRDE experiments at 1800 rpm, using either N-C or NiFe-N-C at a load of 0,27 mg cm-2 of catalyst at the disk and a Pt ring: (top) LSV at the disk (current normalized by geometric area, v = 2 mV/s), and (bottom) polarization at the Pt ring (E=0.3V vs NHE). Shown are both acidic medium (0.5 M H2SO4, N-C in 1 blue and NiFe-N-C in 2 red) and saline medium (0,5 M NaCl, N-C in 3 cyan and NiFe-N-C in 4 magenta). It was found that NiFe-N-C catalyst is active towards HER in saline medium at near neutral pH. As anticipated, the activity in acidic media is significantly higher than on saline medium, attributing this difference to several aspects such as conductivity limitations, chlorine presence and absence of free H+ ions and the need of additional steps for water dissociation [9]. In acidic media the metal-free catalyst (N-C) shows larger currents for most of the potential widow. On the other hand, the ring electrode does not show activity at all for N-C, thus it may be concluded that there is no H2 evolution and therefore the current is mostly capacitive, this capacitive contribution will be subtracted from the final results. In contrast, in saline medium N-C shows no activity at all towards HER, even showing smaller capacitive currents, while NiFe-C shows smaller albeit significant currents given the large differences in pH between media. The metal catalysts, the blank and a Pt/C in acidic and saline medium, will be compared using onset potentials, overpotentials at 10 mA/cm2 and Tafel slopes. References Blagojević , V. Minić, D. Minić D. & Grbović Novaković J. Hydrogen Economy: Modern Concepts, Challenges and Perspectives, Hydrogen Energy, IntechOpen (2012).Zhang,Y. & Zou, X. Noble metal-free hydrogen evolution catalysts for water splitting, Chemical Society Reviews, 15, (2015).IEA webstore, The Future of Hydrogen Seizing today´s opportunities, (2019).Dresp, S. Dionigi, F. Klingenhof, M. & Strasser, P. Direct Electrolytic Splitting of Seawater: Opportunities and Challenges, ACS Energy Letters (2019).Boretti, A. y Rosa L. Reassessing the projections of the World Water Development Report, npj Clean Water, 2, 15, (2019).Vos, J. & Koper, M. Measurement of competition between oxygen evolution and chlorine evolution using rotating ring-disk electrode voltammetry, Journal of Electroanalytical Chemistry, 819, (2018).Sethuraman, V. A. & .Weidner, J. W. Analysis of Sulfur Poisoning on a PEM Fuel Cell Electrode, Electrochimical acta, 55, 20, (2010).Malko, D. Lopes, T. Symianakis§a E. & Kucernak, A. The intriguing poison tolerance of non-precious metal oxygen reduction reaction (ORR) catalysts, Mater. Chem. A, 4, (2016).Zhou, Z. Pei, Z. Wei, L. Zhao, S. Jian, X. & Chen, Y. Electrocatalytic Hydrogen Evolution under Neutral pH Conditions: Current Understandings, Recent Advances, and Future Prospects, Energy Environ. Sci., 10, (2020) Figure 1

Extracellular Protons Mediate Presynaptic Homeostatic Potentiation at the Mouse Neuromuscular Junction

At the vertebrate neuromuscular junction (NMJ), presynaptic homeostatic potentiation (PHP) refers to the upregulation of neurotransmitter release via an increase in quantal content (QC) when the postsynaptic nicotinic acetylcholine receptors (nAChRs) are partially blocked. The mechanism of PHP has not been completely worked out. In particular, the identity of the presumed retrograde signal is still a mystery. We investigated the role of acid-sensing ion channels (ASICs) and extracellular protons in mediating PHP at the mouse NMJ. We found that blocking AISCs using benzamil, psalmotoxin-1 (PcTx1), or mambalgin-3 (Mamb3) prevented PHP. Likewise, extracellular acidification from pH 7.4 to 7.2 triggered a significant, reversable increase in QC and this increase could be prevented by PcTx1. Interestingly, an acidic saline (pH 7.2) also precluded the subsequent induction of PHP. Using immunofluorescence we observed ASIC2a and ASIC1 subunits at the NMJ. Our results indicate that protons and ASIC channels are involved in activating PHP at the mouse NMJ. We speculate that the partial blockade of nAChRs leads to a modest decrease in the pH of the synaptic cleft (∼0.2 pH units) and this activates ASIC channels on the presynaptic nerve terminal.

Comparison of Vascular Morphometry in Jawbones and Long Bones: Micro-CT Study in a Rat Model Treated with Zoledronic Acid

The study was aimed at investigating the effect of zoledronic acid on vascular morphometry in jawbones and long bones on a rat model. Twenty-four skeletal mature Sprague-Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla and a bone defect creation on the femur. After the surgical procedures, ZA or saline treatment was continued until sacrifice at week 2, week 4, and week 8 postoperatively. Vascular perfusion with MICROFIL was performed on all the animals. Micro-CT analysis demonstrated a tendency of decreased vessel density and vessel number in ZA-treated groups but no statistical difference. In conclusion, the neovessel formation is suppressed but not significantly by ZA treatment, indicating that angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role.

TRPV1 Responses in the Cerebellum Lobules VI, VII, VIII Using Electroacupuncture Treatment for Chronic Pain and Depression Comorbidity in a Murine Model.

Depression is a prominent complex psychiatric disorder, usually complicated through expression of comorbid conditions, with chronic pain being among the most prevalent. This comorbidity is consistently associated with a poor prognosis and has been shown to negatively impact patient outcomes. With a global rise in this condition presenting itself, the importance of discovering long-term, effective, and affordable treatments is crucial. Electroacupuncture has demonstrated renowned success in its use for the treatment of pain and is a widely recognized therapy in clinical practice for the treatment of various psychosomatic disorders, most notably depression. Our study aimed to investigate the effects and mechanisms of Acid-Saline (AS) inducing states of chronic pain and depression comorbidity in the cerebellum, using the ST36 acupoint as the therapeutic intervention. Furthermore, the role of TRPV1 was relatedly explored through the use of TRPV1−/− mice (KO). The results indicated significant differences in the four behavioral tests used to characterize pain and depression states in mice. The AS and AS + SHAM group showed significant differences when compared to the Control and AS + EA groups in the von Frey and Hargreaves’s tests, as well as the Open-Field and Forced Swimming tests. This evidence was further substantiated in the protein levels observed in immunoblotting, with significant differences between the AS and AS + SHAM groups when compared to the AS + EA and AS + KO groups being identified. In addition, immunofluorescence visibly served to corroborate the quantitative outcomes. Conclusively these findings suggest that AS-induced chronic pain and depression comorbidity elicits changes in the cerebellum lobules VI, VII, VIII, which are ameliorated through the use of EA at ST36 via its action on TRPV1 and related molecular pathways. The action of TRPV1 is not singular in CPDC, which would suggest other potential targets such as acid-sensing ion channel subtype 3 (ASIC3) or voltage-gated sodium channels (Navs) that could be explored in future studies.

Hyaluronic acid vs. physiological saline for enlarging deficient gingival papillae: a randomized controlled clinical trial and an in vitro study.

Backgroundloss of the interdental papillae leads to the formation of a black triangle, which compromises smile esthetics and contributes to food impaction and plaque accumulation. The aim of this study was to evaluate the efficacy of the injection of hyaluronic acid (HA) and compare it to that of physiological saline solution in the restoration of deficient gingival papillae in vivo and in vitro.MethodsTwenty-four patients with 68 deficient gingival papillae were recruited for this clinical trial with a split-mouth design. The deficient gingival papillae on one side of the anterior maxilla were injected with HA, and those on the other side were injected with physiological saline solution. The heights of the gingival papillae and the areas of the black triangles were measured from clinical photographs obtained before and 6 and 12 months after treatment. Additionally, the proliferation and migration of gingival fibroblasts were evaluated after HA and physiological saline treatment by an in vitro study.Resultsthe results revealed that the injection of HA yielded 0.198 and 0.28 mm gingival papilla increasement at 6 and 12 months, respectively, relative to the baseline (P<0.05). However, deficient gingival papillae also grew by 0.278 mm at 12 months in the group that received physiological saline solution (P<0.05). The injection of HA significantly improved deficient gingival papillae 6 months earlier than the injection of physiological saline solution. HA also significantly accelerated the proliferation and migration of gingival fibroblasts in vitro.ConclusionsThe present study confirms that the injection of HA could increase the height of gingival papillae for improving gingival papilla defects. However, the effect is not superior to that of physiological saline solution. This trial was registered in the Chinese Clinical Trial Registry (ChiCTR-ONC-17011781) (28/06/2017). http://www.chictr.org.cn/showproj.aspx?proj=19931

Mirogabalin, a novel ligand for α2δ subunit of voltage-gated calcium channels, improves cognitive impairments in repeated intramuscular acidic saline injection model rats, an experimental model of fibromyalgia

Mirogabalin is a novel potent and selective ligand for the α2δ subunit of voltage-gated calcium channels, and shows potent and sustained analgesic effects in neuropathic pain and fibromyalgia models. Fibromyalgia is often associated with multiple comorbid symptoms, such as anxiety, depression and cognitive impairment. In the present study, we investigated the effects of mirogabalin on cognitive impairments in an experimental animal model for fibromyalgia, repeated intramuscular acidic saline injection model (Sluka model) rats. Male rats received two repeated intramuscular injections of pH 4 acidic saline into their gastrocnemius muscle. After developing mechanical hypersensitivity as identified in the von Frey test, the animals received the test substance orally once daily for 13 days and were subjected to four cognitive function tests, (Y-maze, novel object recognition, Morris water maze and step-through passive avoidance). Sluka model rats showed cognitive impairments in all four tests. Oral administration of mirogabalin (3 and 10 mg/kg) improved the cognitive impairments in these rats. In conclusion, mirogabalin improved the impaired cognitive function in Sluka model rats. It may thus also alleviate cognitive impairments as well as painful symptoms in fibromyalgia patients.

Comparison of the corticosteroid injection and hyaluronate in the treatment of chronic subacromial bursitis: A randomized controlled trial

Objective: To analyse the effectiveness of corticosteroid (CS) and hyaluronic acid (HA) subacromial – subdeltoid (SASD) injection compared with normal saline (NS) in patients with chronic subacromial bursitis (CSB). Design: A prospective three-arm double-blinded randomised controlled trial. Setting: Rehabilitation department of two teaching hospitals. Subjects: Patients with CSB (N = 186) divided into CS (N = 68), HA (N = 60), and NS (N = 58) groups. Interventions: Three SASD injections under ultrasound guidance: group A, 20 mg of triamcinolone; group B, 2.5 mL of HA; and group C, 2.5 mL of NS. Outcome measures: The primary outcome measures were the pain visual analogue scale (VAS) score at eight weeks. The secondary outcomes were scores on the Shoulder Pain and Disability Index (SPADI) and Shoulder Disability Questionnaire. Results: At eight weeks, the pain VAS scores during activity were 2.56 ± 2.29, 3.65 ± 2.50, and 4.71 ± 2.83 in the CS, HA, and NS groups, respectively (CS vs NS, P < 0.001; HA vs NS, P = 0.013; CS vs HA, P = 0.010). SPADI scores were 40.83 ± 21.75, 36.92 ± 22.78, and 33.35 ± 23.38 in the CS, HA, and NS groups, respectively (CS vs NS, P < 0.001; HA vs NS, P = 0.197; CS vs HA, P = 0.004). Conclusion: Ultrasound-guided corticosteroid injection into the subacromial – subdeltoid bursa was proven to be effective and superior to hyaluronic acid and normal saline injection for treating CSB. Hyaluronic acid injection was only marginally more effective than normal saline injection. Trial Registration: ClinicalTrials.gov: NCT02702206

Chronic generalized pain disrupts whole brain functional connectivity in mice

Fibromyalgia (FM) is a generalized chronic pain condition whose pathophysiology is poorly understood, and both basic and translational research are needed to advance the field. Here we used the Sluka model to test whether FM-like pain in mice would produce detectable brain modifications using resting-state (rs) functional Magnetic Resonance Imaging (fMRI). Mice received intramuscular acid saline treatment, images were acquired at 7T 5days post-treatment, and pain thresholds tested 3weeks post-scanning. Data-driven Independent Component Analysis revealed significant reduction of functional connectivity (FC) across several component pairs, with major changes for the Retrosplenial cortex (RSP) central to the default mode network, and to a lesser extent the Periaqueductal gray (PAG), a key pain processing area. Seed-to-seed analysis focused on 14 pain-related areas showed strongest FC reduction for RSP with several cortical areas (somatosensory, prefrontal and insular), and for PAG with both cortical (somatosensory) and subcortical (habenula, thalamus, parabrachial nucleus) areas. RSP-PAG FC was also reduced, and this decreased FC tended to be positively correlated with pain levels at individual subject level. Finally, seed-voxelwise analysis focused on PAG confirmed seed-to-seed findings and, also detected reduced PAG FC with the anterior cingulate cortex, increasingly studied in aversive pain effects. In conclusion, FM-like pain triggers FC alterations in the mouse, which are detected by rs-fMRI and are reminiscent of some human findings. The study reveals the causal fingerprint of FM-like pain in rodents, and indicates that both RSP and PAG connectional patterns could be suitable biomarkers, with mechanistic and translational value, for further investigations.

Impact of sex and environmental conditions on the responses to pain in zebrafish

ABSTRACT BACKGROUND AND OBJECTIVES: Adult zebrafish (Danio rerio) has been proposed as a low-cost and simple alternative to the use of rodents in laboratory research on novel compounds with antinociceptive potential. This study aimed to assess whether there is an influence of animal sex and the test environment on the orofacial nociceptive behavior of the adult zebrafish. METHODS: First, cinnamaldehyde, menthol, capsaicin, acidic saline, or glutamate was applied into the lips of the adult male or female zebrafish. Naive groups were included as control. The orofacial nociception was quantified in terms of locomotor activity. In other series of experiments, it was evaluated whether the apparatus, acclimatization, period of test, temperature of the water and color of the open field would alter the nociceptive response to cinnamaldehyde. RESULTS: The nociceptive behavior did not depend on the sex of the animal, apparatus, time the test was performed or the color of the open field. However, acclimatization promoted nociceptive behavior in naive animals and did not alter the nociceptive response to cinnamaldehyde (p<0.01 vs acclimatized naive). The nociception behavior was presented only when the test was performed at a temperature of 26oC (p<0.01 vs naive). CONCLUSION: The results suggest the need to control the environment and water temperature as an environmental source of variation during the nociceptive behavior test of the adult zebrafish.

In vitro investigation of the antisickling properties of aqueous fruits extracts of Citrus paradisi, Musa acuminata and Malus domestica

Sickle cell disease (SCD) is a genetic blood disorder that affects the shape and transportation of red blood cells (RBCs) in blood vessels, leading to various clinical complications. Many drugs that are available for treating the disease are insufficiently effective, toxic, or too expensive. Therefore, there is a pressing need for safe, effective, and inexpensive therapeutic agents from indigenous plants used in ethnomedicine. In the current study, the potentials of aqueous extracts of Citrus paradisi, Musa acuminata, Malusdomestica fruit in sickle cell disease management were investigated in vitro using P-hydroxybenzoic acid and normal saline as positive and negative control respectively. The method employed the inhibition of sodium metabisulphite induced sickling of HbSS red blood cells, collected from confirmed sickle cell patients. Results obtained showed that; 50 mg/ml aqueous extract of Musa acuminata showed the lowest sickling inhibition (80.3%) at 60 minutes while 1 mg/ml gave the highest inhibition of 97.3% at 90 minutes. For Citrus paradisi, lowest (83.3%) and highest (98%) sickling inhibitions were obtained with 25 mg/ml and 50 mg/ml fruit extracts at 30 minutes and 60 minutes respectively. Malus domestica had the highest antisickling activities of 99% and 99.33% respectively at 30 and 60 minutes. In all, the sickling inhibition was least with Musa acuminata but highest with Malus domestica. Also, highest inhibitions were observed at 60 minutes (optimum time) and 10 mg/ml (optimum concentration). This study has demonstrated that; Malus domestica, Citrus paradisi and Musa acuminata possess antisickling potentials useful in the management or therapy of sickle cell diseases.

Recombinant human hyaluronidase PH20-mediated dermal spreading activity in mice is not altered by steroids, antihistamines, or salicylic acid.

Drug-drug interaction studies for hyaluronidase safety assessments have evaluated only animal-derived enzyme preparations. We therefore set out to evaluate whether high-dose administration of two antihistamines, a potent corticosteroid, steroid hormone, adrenocorticotropic hormone (ACTH), or salicylic acid would alter the dispersive activity of recombinant human hyaluronidase PH20 (rHuPH20). NCr nu/nu mice were pretreated with diphenhydramine, cetirizine, dexamethasone, estrogen, ACTH, salicylic acid, and/or neutral-buffered saline (NBS). An hour following final pretreatment, dosed mice were anesthetized with ketamine/xylazine and placed in an imaging chamber. A 120mg/mL immunoglobulin G (IgG) solution with 0.3μg/mL IgGDL755 (labeled IgG) was injected intradermally, with/without 2,000U/mL rHuPH20. Fluorescent images of labeled IgG dispersion were acquired≤20min post injection. Dispersion of high-concentration labeled IgG combined with rHuPH20 was greater at all time points vs. antibody alone. At 20min post injection (last time point), the antibody dispersion area was significantly increased with rHuPH20 vs. without rHuPH20 (p≤0.005). The relative percent increase in antibody dispersion with rHuPH20 ranged from 22.8‒106.6% over the 20-min time course, compared with the corresponding non-rHuPH20 treated groups. The area of labeled IgG dispersion was statistically similar between rHuPH20 groups pretreated with an active compound and their paired NBS pretreated controls. The addition of 2,000U/mL rHuPH20 to a high-concentration antibody solution reproducibly incre-ased local antibody dispersion. Systemic pretreatment with diphenhydramine, cetirizine, dexamethasone, estrogen, ACTH, or salicylic acid did not affect the enzymatic spreading activity of rHuPH20, as measured by intradermal dispersion of labeled IgG in mice.

Allodynia by Splenocytes From Mice With Acid-Induced Fibromyalgia-Like Generalized Pain and Its Sexual Dimorphic Regulation by Brain Microglia.

Fibromyalgia (FM), a disease of unknown etiology characterized by chronic generalized pain, is partly recapitulated in an animal model induced by repeated acid saline injections into the gastrocnemius muscle. Here, we attempted to investigate the sex difference in pain hypersensitivity (mechanical allodynia and hypersensitivity to electrical stimulation) in the repeated acid saline-induced FM-like generalized pain (AcGP) model. The first unilateral acid injection into gastrocnemius muscle at day 0/D0 and second injection at D5 (post day 0, P0) induced transient and long-lasting mechanical allodynia, respectively, on both sides of male and female mice. The pretreatment with gonadectomy did not affect the first injection-induced allodynia in both sexes, but gradually reversed the second injection-induced allodynia in male but not female mice. Moreover, the AcGP in male mice was abolished by intracerebroventricular minocycline treatments during D4–P4 or P5–P11, but not by early treatments during D0–D5 in male but not female mice, suggesting that brain microglia are required for AcGP in late-onset and sex-dependent manners. We also found that the intravenous treatments of splenocytes derived from male but not female mice treated with AcGP caused allodynia in naive mice. In addition, the purified CD4+ T cells derived from splenocytes of acid-treated male mice retained the ability to cause allodynia in naive mice. These findings suggest that FM-like AcGP has multiple sexual dimorphic mechanisms.

Characterisation of cough evoked by inhaled treprostinil and treprostinil palmitil

Cough is induced by inhaled prostacyclin analogues including treprostinil (TRE), and, at higher doses, treprostinil palmitil (TP), a prodrug of TRE. In this report, we have investigated mechanisms involved in TRE- and TP-induced cough, using a dry powder formulation of TP (TPIP) to supplement previous data obtained with an aqueous suspension formulation of TP (TPIS).Experiments in guinea pigs and rats investigated the prostanoid receptor subtype producing cough and whether it involved activation of sensory nerves in the airways and vasculature. Experiments involved treatment with prostanoid, tachykinin and bradykinin receptor antagonists, a cyclooxygenase inhibitor and TRE administration to the isolated larynx or intravenously.In guinea pigs, cough with inhaled TRE (1.23 µg·kg−1) was not observed with an equivalent dose of TPIP and required higher inhaled doses (12.8 and 35.8 µg·kg−1) to induce cough. TRE cough was blocked with IP and tachykinin NK1 receptor antagonists but not with EP1, EP2, EP3, DP1 or bradykinin B2 antagonists or a cyclooxygenase inhibitor. TRE administered to the isolated larynx or intravenously in rats produced no apnoea or swallowing, whereas citric acid, capsaicin and hypertonic saline had significant effects.The mechanisms inducing cough with inhaled TRE likely involves the activation of prostanoid IP receptors on jugular C-fibres in the tracheobronchial airways. Cough induced by inhaled dry powder and nebulised formulations of TP occurs at higher inhaled doses than TRE, presumably due to the slow, sustained release of TRE from the prodrug resulting in lower concentrations of TRE at the airway sensory nerves.

Updates in techniques for improved visualization in sinus surgery.

Adequate visualization during endoscopic sinus surgery (ESS) is one of the most critical aspects of performing well tolerated and successful surgery. The topic of visualization encompasses a broad spectrum of preoperative and intraoperative manoeuvres the surgeon can perform that aid in the understanding of the patient's anatomy and in the delivery of efficient surgical care. Preoperative considerations to improve visualization include optimization of haemostasis through management of comorbidities (e.g. hypertension, coagulopathies), medication management (e.g. blood thinners) and systemic versus topical corticosteroids. New technologies allow preoperative visual mapping of surgical plans. Advances in knowledge of intraoperative anaesthesia have encouraged a move toward noninhaled anaesthetics to reduce bleeding. High definition cameras, angled endoscopes, 3D endoscopes and more recently augmented reality, image-guided surgery, and robotic surgery, represent the state of the art for high-quality visualization. Topical interventions, such as epinephrine, tranexamic acid and warm isotonic saline, can help to reduce bleeding and improve the operative field. Surgical manoeuvres, such as polyp debulking, septoplasty, carefully controlled tissue manipulation and a consistent repeatable approach remain fundamental to appropriate intraoperative surgical visualization. This chapter delineates medical, technical and technological means - preoperatively and intraoperatively - to achieve optimized visualization of the surgical field in ESS.

Antinociceptive effect of triterpene acetyl aleuritolic acid isolated from Croton zehntneri in adult zebrafish (Danio rerio)

Croton zehntneri is a plant known as canelinha de cunhã, prevalent in the northeast region of Brazil. Many constituents of the vegetable have already been studied, and their pharmacological properties have been proven, but this is the first study to analyze the antinociceptive effect in adult zebrafish (ZFa) of the triterpene acetyl aleuritolic acid (AAA) isolated from the stem bark. The animals (ZFa; n = 6/group) were treated intraperitoneally (ip; 20 μL) with AAA (0.1 or 0.3 or 1.0 mg/mL) or vehicle (0.9% saline; 20 μL), and submitted to the locomotor activity test, as well as 96 h acute toxicity. Other groups (n = 6/each) received the same treatments and underwent acute nociception tests (formalin, cinnamaldehyde, glutamate, acid saline, capsaicin, and hypertonic saline). Possible neuromodulation mechanisms were evaluated. AAA (0.1 or 0.3 or 1.0 mg/mL) reduced the nociceptive behavior induced by acid saline and capsaicin, as well as inhibited corneal nociception induced by hypertonic saline, both without altering the animals’ locomotor system and without toxicity. These analgesic effects of AAA were significantly (p > 0.05) similar to those of morphine, used as a positive control. The antinociceptive effect of AAA was inhibited by methylene blue, ketamine, camphor, ruthenium red, amiloride, and mefenamic acid. The antinociceptive effect of AAA on the cornea of animals was inhibited by capsazepine. Therefore, AAA showed pharmacological potential for the treatment of acute pain, and this effect is modulated by cGMP, NMDA receptors, transient receptor potential channels (TRPs), ASICs and has pharmacological potential for the treatment of corneal pain modulated by the TRPV1 channel.

Efficacy and safety of tranexamic acid in total hip arthroplasty via direct anterior approach

To evaluate the efficacy and safety of local application of tranexamic acid (TXA) in reducing perioperative blood loss in total hip arthroplasty via direct anterior approach (DAA). From July 2013 to September 2018, 46 patients with avascular necrosis of the femoral head were divided into tranexamic acid group (n=23) and saline group (n=23). In the tranexamic acid group, there were 14 males and 9 females, aged 52 to 72(63.70±5.34) years old. They were diluted with 3 g tranexamic acid in 50 ml normal saline and immersed in the joint cavity for 3 min after prosthesis replacement;in the normal saline group, there were 13 males and 10 females, aged 55 to 73 (61.26±5.78) years, who were treated with the sameamount of normal saline. The blood loss, hemoglobin value, number of blood transfusion cases, the time of first landing after operation, the incidence of thrombosis and incision adverse events were compared between the two groups. Harris score was used to evaluate hip joint function at 1 and 3 months after operation. The incision healed well and no obvious complications occurred in the two groups. All patients were followed up for 12 to 59 months(averaged 31.11 months). No hip pain was found in the follow-up patients. Hip joint function was improved effectively and no prosthesis loosening occurred. The total perioperative blood loss in tranexamic acid group and normal saline group was(740.09±77.14) ml and (1 069.07±113.53) ml respectively, 24 hours after operation, the drainage volume was (87.61±9.28) ml, (233.83±25.62) ml, the hidden blood loss was (409.65±38.01) ml and (588.33±57.16) ml. the difference of hemoglobin before and after operation was (24.78±2.19) g / L and (33.57±2.95) g / L, the difference was statistically significant (P<0.05). There was no significant difference in blood loss, incidence of deep vein thrombosis and pulmonary embolism, and Harris score of hip joint between the two groups (P>0.05). local application of tranexamic acid in total hip arthroplasty through direct anterior approach can safely and effectively reduce perioperative blood loss, and does not increase the risk of thrombosis, and does not affect the normal recovery of joint function.

Bortezomib Aqueous Solubility in the Presence and Absence of D-Mannitol: A Clarification With Formulation Implications

The solubility of bortezomib, a boronic acid, in water and normal saline is often misquoted in the literature. Here we confirm that bortezomib equilibrium solubility in water and normal saline is 0.59 ± 0.07 and 0.52 ± 0.11 mg/mL, respectively. The aqueous solubility is significantly enhanced, 1.92 ± 0.14 and 3.40 ± 0.21 mg/mL, respectively, in the presence of 55 mM and 137 mM D-mannitol in normal saline, as in the commercial formulation, Velcade®, after reconstitution. This is due to reversible ester formation between bortezomib and D-mannitol. Based on the pH-solubility profile curve for bortezomib in the absence of added D-mannitol, bortezomib's pKa value is estimated to be 8.8 ± 0.2. Boric acid, glycine and a combination of the two, used in an alternative formulation to that of Velcade® do not enhance the equilibrium aqueous solubility of bortezomib.

APXS‐Derived Compositional Characteristics of Vera Rubin Ridge and Murray Formation, Gale Crater, Mars: Geochemical Implications for the Origin of the Ridge

AbstractThe resistant ~50 m thick Vera Rubin ridge (VRR) situated near the base of Mount Sharp, Gale crater, Mars, has been deemed a high priority science target for the Mars Science Laboratory mission. This is because of (1) its position at the base of the 5 km layered strata of Mount Sharp and (2) the detection of hematite from orbit, indicating that it could be the site of enhanced oxidation. The compositional data acquired by the Alpha Particle X‐ray Spectrometer (APXS) during Curiosity's exploration of VRR help to elucidate questions pertaining to the formation of the ridge. APXS analyses indicate that VRR falls within the compositional range of underlying lacustrine mudstones, consistent with a continuation of that depositional environment and derivation from a similar provenance. Lower Fe concentrations for VRR compared to the underlying strata discounts the addition of large amounts of hematite to the strata, either as cement or as detrital input. Compositional trends are associated with VRR cross‐cut stratigraphy, indicating postdepositional processes. Higher Si and Al and lower Ti, Fe, and Mn than the underlying mudstone, particularly within distinct patches of gray/blue bedrock, are consistent with the addition of Si and Al. Lateral and vertical compositional variations suggest enhanced element mobility and fluid flow (possibly via multiple events) through VRR, increasing toward the top of the ridge, consistent with the action of warm (~50–100°C), locally acidic saline fluids as inferred from the mineralogy of drilled samples.

Waveform and Frequency Spectrum Property of Ground-Penetrating Radar for Coarse-Grained Weak Sulfuric Acid Saline Soil Subgrade

To accurately obtain the waveform and spectral characteristics of saline soil subgrade, on the basis of the provincial highway widening project of Ruoqiang-Weili county in Sinkiang, the field detection of coarse-grained weak sulfuric acid saline soil subgrade was carried out by using the type LTD-2100 ground-penetrating radar (GPR) to obtain the original measured files under different water content (ω) levels. IDSP analysis program was used to process the measured file and obtain the initial characteristics of waveform and frequency spectrum. To verify the initial characteristics, a rectangular model box was created in the laboratory with the field packing (the size was 1×0.8×0.8 m), and the water content of the model packing and temperature were manually adjusted. The model property of the waveform and frequency spectrum was obtained by detecting the model. A comparison of the initial property with the model property shows that under a positive temperature, the increase in ω will enhance the electromagnetic reflection, and when 8% 32%, the electromagnetic loss is significantly intensified as the line mapping shows typical snowflake-like characteristics, and the point mapping shows typical linear characteristics, the spectrum energy is concentrated, the main frequency distribution range is 20-65 MHz, and the low frequency characteristics are evident. The results can provide a relevant reference for GPR detection and interpretation of coarse-grained weak sulfuric acid saline soil subgrade.

Ortho-silicic Acid Inhibits RANKL-Induced Osteoclastogenesis and Reverses Ovariectomy-Induced Bone Loss In Vivo.

Numerous experiments in vitro and in vivo have shown that an appropriate increase intake of silicon can facilitate the synthesis of collagen and its stabilization and promote the differentiation and mineralization of osteoblasts. In this study, we examined whether ortho-silicic acid restrains the differentiation of osteoclast through the receptor activator of nuclear factor κB ligand (RANKL)/receptor activator of nuclear factor κB (RANK)/osteoprotegerin (OPG) signaling pathway by investigating its effect in vitro and in vivo. Bone marrow macrophage (BMM) cells were isolated and cultured with or without ortho-silicic acid, and then TRAP staining and immunofluorescence were performed to detect the differentiation of osteoclast. The RANKL-induced osteoclast marker gene and protein expression including c-Fos, nuclear factor of activated T cells cl (NFATcl), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B P50 (NF-κB P50), NF-κB P52, RANK, integrin β3, cathepsin K (CTSK), DC-STAMP, and TRAP were quantitatively detected by western blot and RT-PCR. Ovariectomized (OVX) rats were injected with ortho-silicic acid (OVX+Si group) and normal saline (OVX group), and sham-operated rats were injected with normal saline (Sham group). And micro-CT, H&E, and TRAP staining, ELISA, and western blot were performed. Ortho-silicic acid could inhibit the differentiation of osteoclast, and the marker genes and proteins were decreased. The OVX-induced bone loss could be reversed by ortho-silicic acid. Our finding demonstrated that ortho-silicic acid suppresses RANKL-induced osteoclastogenesis and has potential value as a therapeutic agent for OVX-induced bone loss.