Physiological pH Research Articles

Therapeutic efficacy of Strobilanthes urticifolia-infused pectin/polyacrylic acid hydrogel for targeted hepatorenal fibrosis mitigation: A multifaceted biomaterial approach.

Pectin/polyacrylic acid (PPAA) hydrogel is a unique and versatile biomaterial with applications in drug delivery, wound healing, tissue engineering, and agriculture, owing to its tailored properties and multifunctional attributes. This study aims to harness the therapeutic potential of Strobilanthes urticifolia extract within a PPAA hydrogel matrix to attenuate liver and kidney fibrosis through targeted and sustained delivery of biologically active substances. PPAA hydrogel was prepared by free radical polymerization, followed by its porosity and swelling determination. The results depicted the porous nature of PPAA hydrogel and improved swelling properties at pH 7.4, confirming its drug delivery promise. The polyphenolic-enriched S. urticifolia extracts of leaf and flower were loaded onto PPAA hydrogel, and the loading efficiency was 87% (leaf) and 62.5% (flower). Moreover, slow-release studies showed controlled and prolonged release of polyphenols for 7 days. The polyphenolic-enriched hydrogel's microstructure was characterized using SEM, FTIR, and thermogravimetric analysis (TGA). SEM results revealed a highly porous structure of polyphenol enriched PPAA hydrogel, while FTIR analysis confirmed the presence of functional groups such as OH group of carboxylic acid, aliphatic CH2 stretching due to acrylic acid grafting with pectin, CO stretching due to acid linkage with pectin, CH of aromatic ring, and CH of carboxylate salt in PPAA hydrogel. TGA of PPAA hydrogel showed its stability up to 488°C. Additionally, the S. urticifolia extract loaded PPAA hydrogel displayed significant antibacterial properties and minimum inhibitory concentrations against both Gram-positive and Gram-negative bacteria. In vivo studies carried out on rats demonstrated that polyphenolic enriched PPAA hydrogel significantly attenuates liver and kidney fibrosis. Therefore, it is concluded from the present study that loading of polyphenolic enriched extract from leaves and flower of S. urticifolia enhanced the biomedical applications of PPAA hydrogel. RESEARCH HIGHLIGHTS: The PPAA hydrogel developed in this study exhibits a highly porous structure and improved swelling properties at physiological pH (7.4), making it an excellent candidate for drug delivery systems. S. urticifolia extracts, rich in polyphenols, were successfully incorporated into the PPAA hydrogel with high loading efficiencies of 87% for leaf and 62.5% for flower extracts. Loading of polyphenolic enriched extracts of S. urticifolia onto PPAA enhanced its biological activities such as antibacterial, hepatoprotective, and reno-protective activities as depicted by in vitro and in vivo studies.

One-Pot Detection of Proteins Using a Two-Way Extension-Based Assay with Cas12a.

Protein biomarkers are an important class of biomarkers in disease diagnosis and are traditionally detected by enzyme-linked immunosorbent assay and mass spectrometry, which involve multiple steps and a complex workflow. In recent years, many CRISPR-Cas12a-based methods for protein detection have been developed; however, most of them have not overcome the workflow complications observed in traditional assays, limiting their applicability in point-of-care testing. In this work, we designed a single-step, one-pot, and proximity-based isothermal immunoassay integrating CRISPR Cas12a for homogeneous protein target detection with a simplified workflow and high sensitivity. Probes consisting of different binders (small molecule, aptamer, and antibody) conjugated with oligonucleotides undergo two-way extension upon binding to the protein targets, leading to downstream DNA amplification by a pair of nicking enzymes and polymerases to generate target sequences for Cas12a signal generation. We used the streptavidin-biotin model to demonstrate the design of our assay and proved that all three elements of protein detection (target protein binding, DNA amplification, and Cas12a signal generation) could coexist in one pot and proceed isothermally in a single buffer system at a low reaction volume of 10 μL. The plug-and-play applicability of our assay has been successfully demonstrated using four different protein targets, streptavidin, PDGF-BB, antidigoxigenin antibody, and IFNγ, with the limit of detection ranging from fM to pM.

Storage Media for Dental Avulsion: A Literature Review

Tooth avulsion is a critical dental emergency where immediate and appropriate management is essential for the successful reimplantation of the tooth. The choice of storage medium during the extra-alveolar period significantly impacts the viability of periodontal ligament (PDL) cells, crucial for the long-term retention of the replanted tooth. This review examines various storage media proposed for avulsed teeth, assessing their pH, osmolality, and overall efficacy in maintaining PDL cell viability. A comprehensive literature search was conducted across databases including PubMed, Scopus, and Google Scholar, identifying media such as Hank’s Balanced Salt Solution (HBSS), milk, saline, propolis, coconut water, and more. Ideal storage media should exhibit antimicrobial properties, maintain physiological osmolality and pH, support PDL cell viability, and be readily available. HBSS is highlighted as the gold standard, with its ability to preserve PDL cells for up to 48 hours. Other effective media like milk, soy milk, and oral rehydration solutions are discussed for their accessibility and performance. Emerging media such as propolis and epigallocatechin-3-gallate show promise but require further research. This review emphasizes the importance of public awareness and accessibility to effective storage media to improve the prognosis of avulsed teeth. Keywords: Storage Media, Dental Avulsion, PDL viability.

A Water-Soluble Multifunctional Probe for Colorimetric Copper Sensing, Lysosome Labelling and Live-Cell Imaging.

We report a water-soluble fluorescence and colorimetric copper probe (LysoBC1); this system can also serve for lysosome labeling and for the dynamic tracking of Cu2+ in living cells. The sensing mechanism takes advantage of the synergic action by the following three components: i) a lysosome targeting unit, ii) the spirolactam ring-opening for the selective copper chelation and iii) the metal-mediated hydrolysis of the rhodamine moiety for fluorescence enhancement. In aqueous environment the molecule acts as a fluorescent reversible pH sensor and as colorimetric probe for Cu2+ at physiological pH; the hydrolysis of the copper targeting unit resulted in a 50-fold increase of the fluorescence intensity. Most importantly, in vitro cell analyses in undifferentiated (SH SY5Y) and differentiated (d-SH SY5Y) neuroblastoma cells, LysoBC1 is able to selectively accumulate into lysosome while the copper binding ability allowed us to monitor intracellular copper accumulation into lysosome.

Cord Blood pH and Lactate- A Step Ahead in Diagnosis of Fetal Acidaemia in Patients with Abnormal Cardiotocography

OBJECTIVES: Electronic fetal monitoring (EFM) is used to identify early signs of fetal deterioration. However, caution is advised when interpreting cardiotocographic parameters. A promising alternative is umbilical cord blood sampling. The analysis of blood gases and lactate levels in the cord within the ini-tial minutes of life is a recommended approach. STUDY DESIGN: This prospective cohort study, conducted over eighteen months from June 2021 to December 2022, enrolled 70 patients with non-reactive and 70 with reactive cardiotocograph (CTG) pat-terns. APGAR scores were recorded at 1 and 5-minute intervals. 1 ml of umbilical artery blood was as-sessed in an arterial blood gas machine and fetal acidosis was defined as pH <7.0 and a lactate con-centration exceeding 4 mmol/L. RESULTS: In the non-reactive CTG group, 35.7% had early decelerations, 37.1% had variable decel-erations, and 17.1% had late decelerations (p<0.001). The mean cord blood lactate was 5.220±1.970 mmol/L in the non-reactive CTG group and 3.400±0.228 mmol/L in the reactive CTG group. Similarly, the mean cord blood pH was 7.030±0.007 in the non-reactive CTG group and 7.170±0.076 in the reac-tive CTG group (p<0.001). 14.3% of cases in the non-reactive CTG group had a 5-minute APGAR <7, with a higher APGAR score in the reactive group. CONCLUSION: The study suggests that abnormal or indeterminate CTG readings are linked to a higher risk of intrapartum fetal acidosis. Non-reactive CTG results were associated with higher mean cord blood lactate and pH levels and more number of Neonatal Intensive Care Unit (NICU) admissions. There is a definite correlation between abnormal CTG patterns and poorer neonatal outcomes.

Clinical implications of a Couvelaire uterus with placental abruption: A retrospective study.

This study aimed to clarify the maternal and neonatal outcomes based on the presence or absence of a Couvelaire uterus with placental abruption. This single-center retrospective study was conducted at a tertiary perinatal center in Japan, including patients diagnosed with acute placental abruption who delivered live births via cesarean section between 2016 and 2023. Patients were divided into two groups based on the presence or absence of a Couvelaire uterus during surgery: the Couvelaire and normal uterus groups. Maternal and neonatal outcomes were assessed. This study included 76 patients: 24 in the Couvelaire group and 52 in the normal uterus group. No patients underwent hysterectomies. The Couvelaire group had significantly higher intraoperative blood loss (median 1152 vs 948 g, P = 0.010), blood transfusion rates (58% vs 31%, P = 0.022), fibrinogen administration rates (38% vs 13%, P = 0.038), intensive care unit/high care unit admission rates (29% vs 7.7%, P = 0.013), and disseminated intravascular coagulation complication rates (25% vs 7.7%, P = 0.038). There were no differences in birth weight, gestational age (median 2387 vs 2065 g, P = 0.082), Apgar score <4 at 5 min (4.2% vs 3.9%, P = 0.95), umbilical artery blood pH <7.1 (25% vs 22%, P = 0.82), and neonatal death (4.2% vs 1.9%, P = 0.57). A Couvelaire uterus indicated adverse maternal outcomes but not neonatal ones. Its presence necessitates preparation for blood transfusions and/or intensive patient follow-up.

Dual Mode Ratiometric Analysis of Cu2+ and Ni2+ Ions at Physiological pH: Effect of Signalling Units on Analytical Efficacy

AbstractHerein, we report the metal ion sensing property of two 2,2’‐bis (pyridylmethyl) amine‐based chromogenic probes at physiological pH in buffered media. The binding of metal ions to the bispicolyl site alters its electronic property, which subsequently influences the optical property of the covalently‐linked signaling unit. The compound experienced a change in the solution color from red to deep and light yellow respectively upon the addition of Cu2+ and Ni2+ ions. Further, it is observed that by modifying the signaling unit, one can tune the mode of metal ion binding and sensitivity. The compound with an electron‐deficient quinolinium unit as the signaling moiety, showed 2 : 1 stoichiometry of binding with metal ions, while the compound functionalized with a pyrene unit formed complexes with 1 : 1 stoichiometry. It was conferred that changes in the signaling moiety not only alter the basicity/nucleophilicity of the pyridine nitrogen ends but also influence their aggregation properties. Such kind of studies will be beneficial for engineering new optical probes with tuneable sensitivity.

Pathophysiological role of ion channels and transporters in hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) has continued to increase annually worldwide, and HCC has become a common cause of cancer-related death. Despite great progress in understanding the molecular mechanisms underlying HCC development, the treatment of HCC remains a considerable challenge. Thus, the survival and prognosis of HCC patients remain extremely poor. In recent years, the role of ion channels in the pathogenesis of diseases has become a hot topic. In normal liver tissue, ion channels and transporters maintain water and electrolyte balance and acid‒base homeostasis. However, dysfunction of these ion channels and transporters can lead to the development and progression of HCC, and thus these ion channels and transporters are expected to become new therapeutic targets. In this review, ion channels and transporters associated with HCC are reviewed, and potential targets for new and effective therapies are proposed.

Rapid, efficient and highly selective separation and enrichment of glycoprotein by surface-imprinted MOF nanoparticles loaded with high-density boric acid

Usually, glycoproteins are related to diseases or physiological processes; however, a serious challenge remains in realizing their highly specific recognition and enrichment via an imprinting strategy owing to their large molecular size, water solubility and high flexibility. Herein, we reported novel molecularly imprinted polymers based on a metal–organic framework (MOF) material, which achieved the specific enrichment of the target glycoprotein ovalbumin (OVA) by combining a boronate affinity strategy with directional surface imprinting technique. The MOF skeleton has a large specific surface area, thus resulting in a high loading density for the boric acid group (4.66 %) and a satisfactory adsorption capacity (482.56 mg/g). Boronate affinity strategy and the surface imprinting technique resulted in a high specificity of the target glycoprotein. Surface imprinting led to imprinting sites located on the shallow surface of nanoparticles, thus resulting in a rapid kinetic adsorption equilibrium (20 min). And the presence of an acyl group on phenylboronic acid led to the best enrichment effect under physiological pH (7.4). Furthermore, OVA in the real egg white was successfully analyzed, which confirmed the universality of this strategy.

Microfluidic aerosol-assisted synthesis of gefitinib anticancer drug nanocarrier based on chitosan natural polymer

An aerosol-assisted approach was devised to synthesize gefitinib anticancer drug-loaded chitosan nanocarriers (GefNCs). The nanocarrier synthesis involves mixing and interacting gefitinib molecules with chitosan natural polymer within a microfluidic chip. The combination was nebulized with an on-chip integrated micropneumatic nebulizer with N2 as the nebulizer gas. The aerosol was collected in a beaker containing a glutaraldehyde cross-linking agent while magnetically stirring. The chip was created by CO2 laser engraving on polymethyl methacrylate sheets. The synthesized GefNCs were characterized using FTIR, DLS, FESEM, and TEM. The FESEM images revealed a nanoparticle size distribution of 18.5 ± 4.6 nm. After adjusting numerous experimental parameters such as chip design, polymer concentration, solution flow rate, and nebulizer gas flow rate, the synthesized nanocarrier's release mechanism was investigated using various kinetic models. The results demonstrated that the release behavior of GefNCs is pH-sensitive and greater at acidic pH values than physiological pH, making the synthesized nanocarrier a potential for targeted gefitinib delivery to cancer cells. Furthermore, the kinetic studies revealed that the drug's release mechanism best matches Fick's diffusion rule. Under optimal conditions, the encapsulation efficiency was 77.8 %. The cytotoxicity of the produced nanocarrier was investigated on the A549 non-small cell lung carcinoma. The MTT test revealed that the produced nanocarrier had a lower IC50 than the free medication. Furthermore, cytotoxicity experiments on empty nanocarriers revealed that the materials utilized to synthesize nanocarriers have no appreciable cytotoxicity. The developed microfluidic-assisted approach provides a quicker synthesis procedure with a high encapsulation efficiency.

Nanodroplets Engineered with Folate Carbon Dots for Enhanced Cancer Cell Uptake toward Theranostic Application.

The research in nanotherapeutics is rapidly advancing, particularly in the realm of nanoconstructs for drug delivery. This study introduces folate-based carbon dot-decorated nanodroplets (f-Dnm), synthesized from a binary mixture of negatively charged folic acid carbon dots (f-CDs) and cationic-branched polyethylenimine (PEI). The uniformly spherical nanodroplets with an average diameter of 115 ± 15 nm exhibit notable photoluminescence. Surface potential analysis reveals a significant change upon coacervation, attributed to strong electrostatic interactions between f-CD and PEI. The engineered nanodroplets show excellent colloidal and photostability even after 6 months of storage at room temperature. The pH-dependent self-assembly and disassembly properties of f-Dnm are explored for drug loading and release studies using doxorubicin (DOX) as a model anticancer drug. Moreover, the f-Dnm nanocarrier demonstrates significantly higher drug loading capabilities (∼90%). In vitro release studies of doxorubicin-loaded f-Dnm [f-Dnm(DOX)] reveal 5 times higher drug release at lysosomal pH 5.4 compared to that at physiological blood pH 7.4. Cytocompatibility assessments using the MTT assay on HeLa, A549, and NIH-3T3 cells confirm the nontoxic nature of f-Dnm, even at high concentrations. Additionally, f-Dnm(DOX) exhibits higher cytotoxicity in HeLa cells compared to f-CD(DOX) at similar DOX concentrations. Cellular uptake studies show an increased uptake of f-Dnm in folate receptor-positive HeLa and MDA-MB 231 cells. Hemolysis assay validated the biocompatibility of the developed formulation. Overall, these engineered nanodroplets represent a class of nontoxic nanocarriers that offer promising potential as nanotherapeutics for folate receptor-positive cells.

Negative dietary cation and anion difference supplementation of twin-bearing Merino ewes grazing pasture in late gestation did not affect lamb growth or survival.

Each year in Australia, 53% of lamb mortalities are attributed to dystocia, with subclinical maternal calcium deficiencies likely contributing to dystocia rates. A negative dietary cation and anion difference (DCAD) diet has increased circulating calcium in sheep. Therefore, this study aimed to investigate the effects of supplementing twin-bearing, grazing ewes with a negative DCAD partial mixed ration (PMR) during late gestation on ewe calcium and magnesium concentrations and subsequent lamb growth and survival. On day 120 of gestation (dG), blood samples were collected from 115 twin-bearing Merino ewes and analyzed for glucose, ketone bodies, pH, ionized calcium, and serum calcium and magnesium. On dG 130, ewes were moved into lambing paddocks and placed in the following 2 treatment groups; ewes receiving a positive DCAD PMR (DCAD = 287 mEq/kg DM; n = 58) and ewes receiving a negative DCAD PMR (DCAD = -125 mEq/kg DM; n = 57) fed as a PMR. On dG 140, a blood and urine sample were collected. The urine was tested for pH. Pasture samples were taken on dG 133 and 149 and tested for DCAD and mineral content. When a lamb was 6 to 18h old, survival, vigor score, liveweight (LW), rectal temperature, blood glucose, and body morphology were recorded. At 10 d of age, lamb LW and survival were recorded and a milk sample was collected from ewes. At 44 d of age, lamb LW and survival were recorded. The DCAD of the pastures across the 6 paddocks ranged from 598 to 893 mEq/kg DM. There were no differences in lamb survival, weight, or viability at any timepoint (P > 0.05). There were no differences in mineral status, metabolic state, or acid-base balance between the positive and negative DCAD-supplemented ewes (P > 0.05) during supplementation (dG 140). Supplementing a negative DCAD diet to ewes grazing pasture during late gestation did not improve lamb survival. The blood and urine pH of the negative DCAD-supplemented ewes indicated a mild metabolic acidosis was not reached due to the high DCAD of the pastures. Further research needs to take careful consideration of the DCAD of pasture when designing a negative DCAD supplement in order for it to be effective.

Enhancing Therapeutic Efficacy of Cerium Oxide Nanoparticles (CNP) Conjugated with S-Nitroso-N-acetyl Penicillamine for Multifunctional Biomedical Applications

Nanoparticles are extensively used because their small size, unique orientation, and distinct physical properties can significantly modify the behavior of the materials they interact with. Cerium oxide nanoparticles (CNP) also known as nanoceria are gaining popularity in a multitude of sectors, including Biomedical science as drug delivery, therapeutics, and enzyme mimetics. Nanoceria are preferred over typical antioxidants or enzymes because they can scavenge numerous types of free radicals. Studies such as In vitro and in vivo methods have shown that nanoceria may be employed as a carrier for targeted medication and gene delivery. Nanoceria works as an antioxidant therapeutics in healthy cells by scavenging ROS (at physiological pH) free radicals. Furthermore, S-Nitroso-N-acetyl penicillamine (SNAP), a nitroso thiol derivative, releases nitric oxide (NO) under physiological conditions. This makes SNAP a valuable tool for researching the pharmacological and physiological effects of NO. The conjugation of CNP and SNAP along with bacterial cellulose enhances its antimicrobial, SOD, and antidiabetic activities. CNP was synthesized using the Wet chemistry method and optimized using a UV/Vis Spectrophotometer. Further, the conjugate solution was characterized by UV-Vis (i.e., within the range of 230-280 nm) and SEM shows a perfect conjugate solution by its morphology and elements. The anti-microbial activity was administered, and a moderate zone was observed. The zone of inhibition activity was shown 4 mm against gram-negative bacteria and 7 mm against gram-positive bacteria. The conjugate solution examined cellular viability of approximately 50.6 % in HACAT cells which shows less toxicity. These observations concluded that the procedure for nanoparticle synthesis is advantageous and synthesized nanomaterial was found to be highly Antioxidative.

Electrochemical Determination of Cyclobenzaprine Hydrochloride Muscle Relaxant Using Novel S-GCN/TiO2-Based Carbon Electrode.

We have successfully prepared the titanium dioxide (TiO2) nanoparticles (NPs) and sulfur-incorporated graphitic carbon nitride (S-GCN)-modified carbon paste electrode (CPE). The CPEs modified with TiO2 NPs and S-GCN were employed for detecting and quantifying the skeletal muscle relaxant cyclobenzaprine hydrochloride (CBP) using cyclic voltammetry and square wave voltammetry (SWV) techniques. Optimal electrochemical conditions were indicated by the pH study results, with the highest peak current observed at a physiological pH of 7.4. The electrochemical process was determined to involve an equivalent number of protons (H+) and electrons (e-). The concentration variation of CBP (ranging from 0.06 to 10 × 10-7 mol L-1) was explored using SWV. The limits of detection and quantification were determined as 6.4 × 10-9 and 2.1 × 10-8 M, respectively. The proposed electrode configuration was applied to analyze real samples, including water, biomedical, and pharmaceutical specimens.

Synthesis of a highly thermostable insulin by phenylalanine conjugation at B29 Lysine

Globally, millions of diabetic patients require daily life-saving insulin injections. Insulin heat-lability and fibrillation pose significant challenges, especially in parts of the world without ready access to uninterrupted refrigeration. Here, we have synthesized four human insulin analogs by conjugating ε-amine of B29 lysine of insulin with acetic acid, phenylacetic acid, alanine, and phenylalanine residues. Of these, phenylalanine-conjugated insulin, termed FHI, was the most stable under high temperature (65 °C), elevated salt stress (25 mM NaCl), and varying pH levels (ranging from highly acidic pH 1.6 to physiological pH 7.4). It resists fibrillation for a significantly longer duration with sustained biological activity in in vitro, ex vivo, and in vivo and displays prolonged stability over its native counterpart. We further unravel the critical interactions, such as additional aromatic π-π interactions and hydrogen bonding in FHI, that are notably absent in native insulin. These interactions confer enhanced structural stability of FHI and offer a promising solution to the challenges associated with insulin heat sensitivity.

Free serum concentrations of antibiotics determined by ultrafiltration: extensive evaluation of experimental variables.

Aim: To assess the impact of experimental conditions on free serum concentrations as determined by ultrafiltration and HPLC-DAD analysis in a wide range of antibiotics. Materials & methods: Relative centrifugation force (RCF), temperature, pH and buffer were varied and the results compared with the standard protocol (phosphate buffer pH 7.4, 37°C, 1000×g). Results: Generally, at 10,000×g the unbound fraction (fu) decreased with increasing molecular weight, and was lower at 22°C. In unbuffered serum, the fu of flucloxacillin or valproic acid was increased, that of basic or amphoteric drugs considerably decreased. Comparable results were obtained using phosphate or HEPES buffer except for drugs which form metal chelate complexes. Conclusion: Maintaining a physiological pH is more important than strictly maintaining body temperature.

Histidine in Proteins: pH-Dependent Interplay between π-π, Cation-π, and CH-π Interactions.

Histidine (His) stands out as the most versatile natural amino acid due to its side chain's facile propensity to protonate at physiological pH, leading to a transition from aromatic to cationic characteristics and thereby enabling diverse biomolecular interactions. In this study, our objective was to quantify the energetics and geometries of pairwise interactions involving His at varying pH levels. Through quantum chemical calculations, we discovered that His exhibits robust participation in both π-π and cation-π interactions, underscoring its ability to adopt a π or cationic nature, akin to other common residues. Of particular note, we found that the affinity of protonated His for aromatic residues (via cation-π interactions) is greater than the affinity of neutral His for either cationic residues (also via cation-π interactions) or aromatic residues (via π-π interactions). Furthermore, His frequently engages in CH-π interactions, and notably, depending on its protonation state, we found that some instances of hydrogen bonding by His exhibit greater stability than is typical for interamino acid hydrogen bonds. The strength of the pH-dependent pairwise energies of His with aromatic residues is supported by the abundance of pairwise interactions with His of low and high predicted pKa values. Overall, our findings illustrate the contribution of His interactions to protein stability and its potential involvement in conformational changes despite its relatively low abundance in proteins.

Does placental VEGF-A protein expression predict early neurological outcome of neonates from FGR complicated pregnancies?

Fetal hypoxia due to placental dysfunction is thehallmark of fetal growth restriction (FGR). Preferential perfusion of the brain (brain-sparing effect), as a part of physiological placental cardiovascular compensatory mechanisms to hypoxia, in FGR was reported. Therefore, the correlation between vascular endothelial growth factor A (VEGF-A) protein expression in the FGR placentas and newborns' early neurological outcome was examined. This study included 50 women with FGR complicated pregnancies and 30 uneventful pregnancies. Fetal hemodynamic parameters, neonatal acid-base status after delivery, placental pathohistology and VEGF-A expression were followed. Early neonatal morphological brain evaluation by ultrasound and functional evaluation of neurological status by Amiel- Tison Neurological Assessment at Term (ATNAT) were performed. VEGF-A protein expression level was significantly higher in the FGR placentas than normal term placentas (Fisher-Freeman-Halton's test, p≤0.001). No statistically significant correlation between placental VEGF-A expression and different prenatal and postnatal parameters was noticed. Whereas the alteration of an early neurological status assessed by ATNAT was found in 58 % of FGR newborns, morphological brain changes evaluated by UZV was noticed in 48 % of cases. No association between the level of placental VEGF-A expression and the early neurological deficits was found. As far as we know this is the first study of a possible connection between VEGF-A protein expression in the FGR placentas and neonates' early neurological outcomes. The lack of correlation between the FGR placental VEGF-A expression and neonates' neurological outcome could indicate that optimal early neurodevelopment may take place due to compensatory mechanism not related to placental VEGF-A expression.

Real-world safety and effectiveness of intravenous fomepizole in patients with ethylene glycol and methanol poisoning in Japan: results of a 7-year post-marketing surveillance study

ABSTRACT Background Fomepizole is a competitive alcohol dehydrogenase inhibitor used for the treatment of ethylene glycol and methanol poisoning. We evaluated the safety and effectiveness of fomepizole in patients with ethylene glycol or methanol poisoning in Japan. Research design and methods This retrospective post-marketing surveillance study conducted in Japan registered patients who received fomepizole intravenous infusion per the package insert (January 2015−June 2022). Endpoints included adverse drug reactions/infections (ADRs), arterial blood pH, and treatment outcomes. Results Of 147 patients registered (91 institutions), 131 and 126 were included in the safety and effectiveness analysis sets, respectively. Mean age was 43.6 years, and 66.4% were male. Mean time from poison ingestion to treatment was 15.1 hours; 66.4% received concomitant hemodialysis. No serious ADRs were reported. ADRs were reported in seven patients; the most-reported ADR was vomiting (2.3%). Seven patients died, 105 survived without sequelae, and 19 survived with sequelae. Most common sequelae were renal failure or renal dysfunction. Mean arterial blood pH increased to 7.4 by 4 hours of treatment, remaining stable for 24 hours post-treatment. Conclusions Fomepizole is well tolerated and helps improve clinical outcomes in patients with ethylene glycol or methanol poisoning in Japan. Trial registration Japanese Pharmaceutical Information Center (JapicCTI-152817).

Enteric neuroprotection-A matter of balancing redox potentials, limiting inflammation, and boosting resilience.

The enteric nervous system (ENS) orchestrates intricate and autonomous functions throughout the gastrointestinal (GI) tract. Disruptions in ENS function are associated GI disorders. This mini review focuses on the past decade's research, utilizing rodent models, with an emphasis on protecting enteric neurons from loss. The review specifically looks at efforts to reduce oxidative stress, limit inflammation, and enhance neuronal resilience. Protective interventions including administration of antioxidants and compounds targeting cellular redox buffer systems, are evaluated for their effectiveness in preventing loss of enteric neurons in the ischemia-reperfusion model and streptozotocin-induced diabetes model. Interventions such as engrafting mesenchymal stem cells and targeting inflammatory signaling pathways in enteric neurons and glial cells are evaluated in inflammatory bowel disease models including the Winnie mouse, DSS-, and DNBS/TNBS-induced colitis models. The review also touches upon neuronal resilience, particularly in the context of Parkinson's disease models. Including estrogen's neuroprotective role, and the influence of metal ions on enteric neuronal protection. Understanding the dynamic interplay within the ENS and its role in disease pathogenesis holds promise for developing targeted therapies to effectively manage and treat various GI ailments.