Physiological pH Research Articles

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.

Enteral plasma feeding improves gut function and immunity in piglets after birth asphyxia.

Birth asphyxia may negatively affect gut function and immunity in newborns. Conversely, immunomodulatory milk diets may protect the gut and immune system against damage caused by asphyxia. Using caesarean-derived pigs as models, we hypothesised that enteral feeding with plasma improves gut and immune functions in asphyxiated newborns. Near-term pig fetuses (98% gestation,) were delivered by caesarean section after 8 min umbilical cord occlusion, leading to transient birth asphyxia (ASP, n = 75) and compared with non-occluded controls (CON, n = 69). Piglets were further randomised to supplementation with/without porcine plasma (plasma, PLA/vehicle, VEH), into bovine colostrum (first 24 h) or formula (until 72 h). Compared with CON, ASP piglets took longer to achieve stable respiration and showed reduced blood pH, weight gain and survival. Independent of asphyxia, plasma supplementation reduced gut haemorrhagic lesions, permeability and inflammatory cytokines together with improved villous morphology and brush-border enzyme activities. Asphyxia reduced blood cytokine responses to ex vivo bacterial stimulation, whereas plasma supplementation ameliorated this effect. Dietary plasma supplementation improves survival, gut functions and immunity in both normal and asphyxiated newborns. The components in plasma that mediate gut-protective effects in piglets remain to be identified, but may benefit also birth-compromised newborn infants. Complicated deliveries leading to birth asphyxia, may negatively affect gut, liver and immune adaptation in the first days after birth. Using a model of birth asphyxia in caesarean-derived piglets, we show that enteral feeding with maternal plasma exerts gut maturational and immunomodulatory effects in both control and asphyxiated animals in the first days of life. The mechanisms behind the gut-protective effects of plasma are unknown, but plasma components hold potential for new oral therapies for compromised newborn infants as well as piglets.

Molecularly Imprinted Polymeric Nanoparticles as Drug Delivery System for Tenofovir, an Acyclic Nucleoside Phosphonate Antiviral.

A molecularly imprinted polymer of Tenofovir (1), an FDA-approved acyclic nucleoside phosphonate with antiviral activity, was synthesized using a non-covalent approach. A pre-polymerization complex was formed between (1) and DMAEMA and in-house synthetic N1-[(2-methacryloyloxy)ethyl] thymine, with EGDMA as a cross-linker in an MeCN/H2O (9:1, 1:1) mixture as a porogen, giving an imprinting factor (IF) of 5.5 at 2.10-5 mol/L. Binding parameters were determined by the Freundlich-Langmuir model, Qmax and Ka, and well as the particle morphology for MIP and NIP. Finally, the release profiles, for MIP and NIP, were obtained at 25 °C and 37 °C, which is body temperature, in a phosphate buffer saline, pH 7.4, mimicking the blood pH value, to determine the potential sustained release of our polymeric materials.

Translational insights into the hormetic potential of carbon dioxide: from physiological mechanisms to innovative adjunct therapeutic potential for cancer.

Carbon dioxide (CO2), traditionally viewed as a mere byproduct of cellular respiration, plays a multifaceted role in human physiology beyond simple elimination through respiration. CO2 may regulate the tumor microenvironment by significantly affecting the release of oxygen (O2) to tissues through the Bohr effect and by modulating blood pH and vasodilation. Previous studies suggest hypercapnia (elevated CO2 levels) might trigger optimized cellular mechanisms with potential therapeutic benefits. The role of CO2 in cellular stress conditions within tumor environments and its impact on O2 utilization offers a new investigative area in oncology. This study aims to explore CO2's role in the tumor environment, particularly how its physiological properties and adaptive responses can influence therapeutic strategies. By applying a structured translational approach using the Work Breakdown Structure method, the study divided the analysis into six interconnected work packages to comprehensively analyze the interactions between carbon dioxide and the tumor microenvironment. Methods included systematic literature reviews, data analyses, data integration for identifying critical success factors and exploring extracellular environment modulation. The research used SMART criteria for assessing innovation and the applicability of results. The research revealed that the human body's adaptability to hypercapnic conditions could potentially inform innovative strategies for manipulating the tumor microenvironment. This could enhance O2 utilization efficiency and manage adaptive responses to cellular stress. The study proposed that carbon dioxide's hormetic potential could induce beneficial responses in the tumor microenvironment, prompting clinical protocols for experimental validation. The research underscored the importance of pH regulation, emphasizing CO2 and carbonic acid's role in modulating metabolic and signaling pathways related to cancer. The study underscores CO2 as vital to our physiology and suggests potential therapeutic uses within the tumor microenvironment. pH modulation and cellular oxygenation optimization via CO2 manipulation could offer innovative strategies to enhance existing cancer therapies. These findings encourage further exploration of CO2's therapeutic potential. Future research should focus on experimental validation and exploration of clinical applications, emphasizing the need for interdisciplinary and collaborative approaches to tackle current challenges in cancer treatment.

A review of the key ingredients in industrial formulations of baby wet wipes.

The skin of newborns is classified as sensitive, with a higher risk of skin barrier disruption and irritation of a diapered area. Despite dermatologist recommendations to use only water and a cloth for cleaning, most of the population still relies on the comforts of modern parenting, which includes intensive daily usage of baby wet wipes. Novel baby formulations are designed following the concept of infant skin health, containing a gentle cleanser, suitable emollient, and buffer system enabling a slightly acidic pH value and they are free of ethyl alcohol. Thus, it is important to understand the chemical background of such a complex liquid formulation, with emphasis on its safety. In line with this, the present paper discusses the scientific background of various chemical compounds found in baby wipe formulations to improve the understanding of wet wipe designs and direct them toward more skin-friendly solutions.

Outstanding Superoxide Dismutase Catalytic Activity Of Simple Peptide‐Based Nickel(II) Complexes

We present here the most active synthetic Ni superoxide dismutase (NiSOD) mimic reported to date. Reactive oxygen species are aggressive compounds, which concentrations are tightly regulated in vivo. Among them, the superoxide anion, O2⸱‐, is controlled by superoxide dismutases. Capitalizing on the versatility of the Amino‐Terminal CuII‐ and NiII‐binding (ATCUN) peptide motif, we introduced positive charges around the NiII center to favor the interaction with the superoxide radical anion. At physiological pH, the pentapeptide H‐Cys‐His‐Cys‐Arg‐Arg‐NH2 coordinates NiII after the deprotonation of one thiol, two amides, and either the second thiol or the N‐terminal ammonium, leading to an equilibrium between the two N3S1 and N2S2 coordination modes. Under catalytic conditions, a kcat value of 8.6(4) x 106 L.mol‐1.s‐1 was measured. Within the first second, the catalyst remained undegraded with quantitative consumption of O2⸱‐ (completed up to 37 catalytic cycles). An extra arginine (Arg) was introduced at the peptide C‐terminus to increase the global charge of the NiII complex from +1 to + 2. This had no effect on the catalytic performance, highlighting the critical role of charge distribution in space as a determining factor influencing the reactivity.

Outstanding Superoxide Dismutase Catalytic Activity Of Simple Peptide-Based Nickel(II) Complexes.

We present here the most active synthetic Ni superoxide dismutase (NiSOD) mimic reported to date. Reactive oxygen species are aggressive compounds, which concentrations are tightly regulated in vivo. Among them, the superoxide anion, O2⸱-, is controlled by superoxide dismutases. Capitalizing on the versatility of the Amino-Terminal CuII- and NiII-binding (ATCUN) peptide motif, we introduced positive charges around the NiII center to favor the interaction with the superoxide radical anion. At physiological pH, the pentapeptide H-Cys-His-Cys-Arg-Arg-NH2 coordinates NiII after the deprotonation of one thiol, two amides, and either the second thiol or the N-terminal ammonium, leading to an equilibrium between the two N3S1 and N2S2 coordination modes. Under catalytic conditions, a kcat value of 8.6(4) x 106 L.mol-1.s-1 was measured. Within the first second, the catalyst remained undegraded with quantitative consumption of O2⸱- (completed up to 37 catalytic cycles). An extra arginine (Arg) was introduced at the peptide C-terminus to increase the global charge of the NiII complex from +1 to + 2. This had no effect on the catalytic performance, highlighting the critical role of charge distribution in space as a determining factor influencing the reactivity.

Bioelectronic Sutures with Electrochemical pH‐Sensing for Long‐Term Monitoring of the Wound Healing Progress

AbstractThe physiological pH level at wound sites is one of the fundamental factors for monitoring wound conditions in clinical practice. To continuously assess the wound conditions, a variety of bioelectronic pH sensors are extensively developed. However, despite significant advances in bioelectronics for wound monitoring, the application of existing bioelectronic devices, primarily designed as bandages or patches, remains challenging for monitoring pH levels in deep wounds. Here, a flexible pH‐sensing suture is introduced that can be simultaneously used as both a precise pH sensor for wound monitoring and a conventional medical suture. The electrochemical pH‐sensing suture comprises Au nanoparticle‐based flexible electrodes functionalized with polyaniline for the working electrode and Ag/AgCl for the reference electrode, seamlessly integrated onto a standard medical suturing thread. This dual‐function sensing suture offers a reliable and high sensitivity of 58.9 mV pH−1, negligible hysteresis, high stability, and excellent selectivity in pH sensing. The biocompatibility of the sensing suture is systematically verified for its in vivo use. To demonstrate the capabilities of the pH‐sensing suture, it is successfully applied to an incision and chronic wound model of mouse to perform continuous and accurate monitoring of the inflammation and healing progress of the wound throughout the healing period.

Observer-based adaptive memory event-triggered consensus tracking control for high-speed train under DoS attacks

This paper focuses on the event-triggered consensus tracking of high-speed trains under denial-of-service (DoS) attacks. A novel anti-disturbance control strategy is proposed, based on an adaptive memory state observer and a disturbance observer. A memory is introduced to buffer system output information which enhancing the precision of the state observer, and the gust disturbance during the high-speed train operation is estimated by the disturbance observer. The Linear Matrix inequality technique is used to obtain the observer feedback coefficient and the controller gain, and the Lyapunov theory is employed to demonstrate the controller’s consistency tracking performance. Applying the memory to the event-triggered mechanism, a new adaptive memory event-triggered scheme is designed to better ensure system performance and effectively prevent the occurrence of Zeno behavior. To achieve precise identification of DoS attacks in the event-triggered environment, a new detection algorithm is proposed. Finally, simulation examples are used to validate the effectiveness and practicality of the proposed scheme.

Can we Predict Drug Excretion into Saliva? A Systematic Review and Analysis of Physicochemical Properties.

Saliva is a patient-friendly matrix for therapeutic drug monitoring (TDM) but is infrequently used in routine care. This is due to the uncertainty of saliva-based TDM results to inform dosing. This study aimed to retrieve data on saliva-plasma concentration and subsequently determine the physicochemical properties that influence the excretion of drugs into saliva to increase the foundational knowledge underpinning saliva-based TDM. Medline, Web of Science and Embase (1974-2023) were searched for human clinical studies, which determined drug pharmacokinetics in both saliva and plasma. Studies with at least ten subjects and five paired saliva-plasma concentrations per subject were included. For each study, the ratio of the area under the concentration-time curve between saliva and plasma was determined to assess excretion into saliva. Physicochemical properties of each drug (e.g. pKa, lipophilicity, molecular weight, polar surface area, rotatable bonds and fraction of drug unbound to plasma proteins) were obtained from PubChem and Drugbank. Drugs were categorised by their ionisability, after which saliva-to-plasma ratios were predicted with adjustment for protein binding and physiological pH via the Henderson-Hasselbalch equation. Spearman correlation analyses were performed for each drug category to identify factors predicting saliva excretion (α = 5%). Study quality was assessed by the risk of bias in non-randomised studies of interventions tool. Overall, 42 studies including 40 drugs (anti-psychotics, anti-microbials, immunosuppressants, anti-thrombotic, anti-cancer and cardiac drugs) were included. The median saliva-to-plasma ratios were similar for drugs in the amphoteric (0.59), basic (0.43) and acidic (0.41) groups and lowest for drugs in the neutral group (0.21). Higher excretion of acidic drugs (n = 5) into saliva was associated with lower ionisation and protein binding (correlation between predicted versus observed saliva-to-plasma ratios: R2 = 0.85, p = 0.02). For basic drugs (n = 21), pKa predicted saliva excretion (Spearman correlation coefficient: R = 0.53, p = 0.02). For amphoteric drugs (n = 10), hydrogen bond donor (R = - 0.76, p = 0.01) and polar surface area (R = - 0.69, p = 0.02) were predictors. For neutral drugs (n = 10), protein binding (R = 0.84, p = 0.004), lipophilicity (R = - 0.65, p = 0.04) and hydrogen bond donor count (R = - 0.68, p = 0.03) were predictors. Drugs considered potentially suitable for saliva-based TDM are phenytoin, tacrolimus, voriconazole and lamotrigine. The studies had a low-to-moderate risk of bias. Many commonly used drugs are excreted into saliva, which can be partly predicted by a drug's ionisation state, protein binding, lipophilicity, hydrogen bond donor count and polar surface area. The contribution of drug transporters and physiological factors to the excretion needs to be evaluated. Continued research on drugs potentially suitable for saliva-based TDM will aid in adopting this person-centred TDM approach to improve patient outcomes.

Pyruvate dehydrogenase deficiency in a young boy: a clinical case

BACKGROUND: Pyruvate dehydrogenase deficit is a severe hereditary mitochondrial metabolic disease characterized by impaired energy metabolism and manifested by a wide range of neurological symptoms. The difficulty in selecting therapy is due to insufficient data on the management of children with this pathology owing to death at an early age and insufficient diagnosis during life. The accurate prevalence of the disease is unknown, presumably 1 in 1,000,000, which makes it attributable to orphan diseases. CLINICAL CASE DESCRIPTION: This article presents a case of a child with a rare neurometabolic disease pyruvate dehydrogenase complex E1 deficiency. The diagnosis was suspected after his birth based on neurological symptoms, neonatal hyperammonemia, and hyperlactatemia and confirmed after exome sequencing, where a homozygous variant of the nucleotide sequence in the PDNA1 gene (X-19359612-C-E) was determined. At the age of 2 months, he began to receive a ketogenic diet — a high-fat, low-carbohydrate dry mixture for enteral nutrition, metabolic therapy, and Vit B1 (300 mg/day). The article presents indicators of biochemical blood testing, acid-base state of blood, and dynamics of the neurological picture during the period of observation of the patient. CONCLUSION: Early diagnosis and initiation of therapy is crucial for the physical and neuropsychiatric development of children with this pathology. Despite the lack of highly effective etiotropic treatment, in some cases, an improvement in the clinical course is observed with the use of thiamine preparations and adherence to a ketogenic diet.

Ischemic stroke: focus on hyperuricemia

Uric acid is a weak organic acid with a molecular weight of 168.112 g/mol. Most uric acid at normal blood pH circulates as urates, negatively charged weak salts derived from uric acid. Being the end product of the process of purine catabolism, uric acid is excreted from the human body in urine until kidney function is impaired. Hyperuricemia may occur due to decreased excretion, increased production, or a combination of both mechanisms. Over the past decades, several studies in the adult population have attempted to establish the correlation between the risk of stroke and serum uric acid concentrations, and how these levels influence the patient's neurological outcome after stroke. Our review is devoted to the study of the mechanisms of normal purine metabolism, disorders of purine metabolism and pathogenetic mechanisms of the development of ischemic stroke in hyperuricemia.

Comparison of the effects of norepinephrine and phenylephrine on shivering and hypothermia in patients undergoing caesarean section under spinal anaesthesia at a tertiary hospital in China：a randomised, double-blind, controlled trial protocol

IntroductionPeripheral vasodilation causes a redistribution of body temperature from the core to the periphery, resulting in shivering and hypothermia. These are normal pathological and physiological processes during spinal anaesthesia. Two...

In silico-guided discovery and in vitro validation of novel sugar-tethered lysinated carbon nanotubes for targeted drug delivery of doxorubicin

ContextMultiwalled carbon nanotubes (MWCNTs) functionalized with lysine via 1,3-dipolar cycloaddition and conjugated to galactose or mannose are potential nanocarriers that can effectively bind to the lectin receptor in MDA-MB-231 or MCF-7 breast cancer cells. In this work, a method based on molecular dynamics (MD) simulation was used to predict the interaction of these functionalized MWCNTs with doxorubicin and obtain structural evidence that allows a better understanding of the drug loading and release process. The MD simulations showed that while doxorubicin only interacted with pristine MWCNTs through π-π stacking interactions, functionalized MWCNTs were also able to establish hydrogen bonds, suggesting that the functionalized groups improve doxorubicin loading. Moreover, the elevated adsorption levels observed for functionalized nanotubes further support this enhancement in loading efficiency. MD simulations also shed light on the intratumoral pH-specific release of doxorubicin from functionalized MWCNTs, which is induced by protonation of the daunosamine moiety. The simulations show that this change in protonation leads to a lower absorption of doxorubicin to the MWCNTs. The MD studies were then experimentally validated, where functionalized MWCNTs showed improved dispersion in aqueous medium compared to pristine MWCNTs and, in agreement with the computational predictions, increased drug loading capacity. Doxorubicin-loaded functionalized MWCNTs demonstrated specific release of doxorubicin in tumor microenvironment (pH = 5.0) with negligible release in the physiological pH (pH = 7.4). Furthermore, doxorubicin-free MWNCT nanoformulations exhibited insignificant cytotoxicity. The experimental studies yielded nearly identical results to the MD studies, underlining the usefulness of the method. Our functionalized MWCNTs represent promising non-toxic nanoplatforms with enhanced aqueous dispersibility and the potential for conjugation with ligands for targeted delivery of anti-cancer drugs to breast cancer cells.MethodsThe computational model of a pristine carbon nanotube was created with the buildCstruct 1.2 Python script. The lysinated functionalized groups were added with PyMOL and VMD. The carbon nanotubes and doxorubicin molecules were parameterized using the general AMBER force field, and RESP charges were determined using Gaussian 09. Molecular dynamics simulations were carried out with the AMBER 20 software package. Adsorption levels were calculated using the water-shell function of cpptraj. Cytotoxicity was evaluated via a MTT assay using MDA-MB-231 and MCF-7 breast cancer cells. Drug uptake of doxorubicin and doxorubicin-loaded MWCNTs was measured by fluorescence microscopy.

Microwave-Assisted Synthesis of β-N-Aryl Glycoamphiphiles with Diverse Supramolecular Assemblies and Lectin Accessibility.

Glycoamphiphiles have attracted considerable interest in a broad range of application fields owing to their solution and bulk-state self-assembly abilities. Despite their importance, the straightforward synthesis of glycoamphiphiles consisting of a hydrophilic carbohydrate linked to a hydrophobic aglycone remains one of the major challenges in glycosciences. Here, a rapid, simple, and efficient synthetic access to chemically stable glycoamphiphiles at physiological pH, namely, N-(β-d-glycosyl)-2-alkylbenzamide, is reported. It leverages the nonreductive amination of unprotected carbohydrates with ortho-substituted aniline derivatives which could be readily obtained by reacting commercially available primary alkylamines with isatoic anhydride. This strategy avoids protection and deprotection of sugar hydroxyl groups and the use of reductive agents, which makes it advantageous in terms of atom and step economy. Moreover, in order to circumvent the cons of classical N-aryl glycosylation, we investigate the use of microwave as a heat source that provides fast, clean, and high-yield β-N-arylation of unprotected carbohydrates. Their self-assembly into water led to multiple morphologies of dynamic supramolecular glycoamphiphiles that were characterized to assess their ability to bind to lectins from pathogenic bacteria. Biophysical interactions probed by isothermal titration microcalorimetry revealed micromolar affinities for most of the synthesized glycoamphiphiles.

Injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel for local treatment of osteomyelitis: Fabrication, characterization, and in vitro performance evaluation.

The conventional treatment of osteomyelitis with antibiotic-loaded nondegradable polymethylmethacrylate (ATB-PMMA) beads has certain limitations, including impeded bone reconstruction and the need for secondary surgery. To overcome this challenge, this study aimed to develop and characterize an injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel (VC-SF/MC-CAPs). The VC-SF/MC-CAPs solution can be easily administered at room temperature with a low injectability force of ≤30 N and a high vancomycin (VC) content of ~96%. Additionally, at physiological temperature (37 °C), the solution could transform into a rigid hydrogel within 7 minutes. In vitro drug release performed under both physiological (pH 7.4) and infection conditions (pH 4.5) revealed a prolonged release pattern of VC-SF/MC-CAPs following the Peppas-Sahlin kinetic model. In addition, the released VC from VC-SF/MC-CAPs hydrogels exhibited antibacterial activity against Staphylococcus aureus for a period exceeding 35 days, as characterized by the disk diffusion assay. Furthermore, at pH 7.4, the VC-SF/MC-CAPs demonstrated >60% degradation within 35 days. Importantly, when exposed to physiological pH conditions, CAPs are transformed into bioactive hydroxyapatite, which benefits bone formation. Therefore, VC-SF/MC-CAPs showed significant potential as a local drug delivery system for treating osteomyelitis.

Independent variables of pH: Ten Knights of the Hydrogen Ion Kingdom-Part I. A prospective observational study.

CO2, HCO3, SID, and total weak acids have been defined as pH's independent variables. However, according to Gamble, HCO3 should be equal to the difference between the sum of cations and the sum of anions besides HCO3. Therefore, if this mathematical expression is substituted for HCO3 in the Henderson-Hasselbalch equation, all independent variables of pH can be demonstrated. Our aim is to test this theory in this study. This prospective observational study was conducted between 2019 and 2020. All admitted patients to the intensive care unit who were >18 years old were included. Demographic data, blood gas parameters, albumin, magnesium, and inorganic phosphorus levels, and outcomes were recorded twice (at admission and at the 24th hour). The multivariate linear regression model was used to determine pH's independent variables. In the multivariate linear regression model, pH was significantly increased by each unit increase in Na, K, Ca, and Mg (mmol L-1). In contrast, pH was significantly decreased by each unit increase in CO2, Cl, lactate, albumin (g dL-1), inorganic phosphorus (mg dL-1), and the strong ion gap. Ten independent variables can accurately predict the changes in pH. For this reason, all ten independent variables should be separately evaluated when interpreting the acid-base status. With this understanding, all algorithms regarding acid-base evaluation may become unnecessary.

The Ninhydrin Reaction Revisited: Optimisation and Application for Quantification of Free Amino Acids.

The ninhydrin reaction is commonly used for the detection of amino acids. However, in the literature, different conditions with respect to the buffer system, its pH and concentration, type of organic solvent, incubation time, and temperature, as well as the concentrations of the reagents, are described. To identify the most suitable conditions, colour development with reagents of varying compositions and different reaction temperatures and times were investigated using asparagine as a model amino acid. Asparagine was selected since it is one of the most abundant free amino acids in many types of samples. The optimal reaction mixture consisted of 0.8 mol L-1 potassium acetate, 1.6 mol L-1 acetic acid, 20 mg mL-1 ninhydrin and 0.8 mg mL-1 hydrindantin in DMSO/acetate buffer 40/60 (v/v) (final concentrations). The best reaction condition was heating the samples in 1.5 mL reaction tubes to 90 °C for 45 min. Afterwards, the samples were diluted with 2-propanol/water 50/50 (v/v) and the absorbance was measured at 570 nm. The proteinogenic amino acids showed a similar response except for cysteine and proline. The method was highly sensitive and showed excellent linearity as well as intra-day and inter-day reproducibility.