Plasma pH Research Articles

Effects of Physiological-Scale Variation in Cations, pH, and Temperature on the Calibration of Electrochemical Aptamer-Based Sensors.

Electrochemical aptamer-based (EAB) sensors are the first technology supporting high-frequency, real-time, in vivo molecular measurements that is independent of the chemical reactivity of its targets, rendering it easily generalizable. As is true for all biosensors, however, EAB sensor performance is affected by the measurement environment, potentially reducing accuracy when this environment deviates from the conditions under which the sensor was calibrated. Here, we address this question by measuring the extent to which physiological-scale environmental fluctuations reduce the accuracy of a representative set of EAB sensors and explore the means of correcting these effects. To do so, we first calibrated sensors against vancomycin, phenylalanine, and tryptophan under conditions that match the average ionic strength, cation composition, pH, and temperature of healthy human plasma. We then assessed their accuracy in samples for which the ionic composition, pH, and temperature were at the lower and upper ends of their physiological ranges. Doing so, we find that physiologically relevant fluctuations in ionic strength, cation composition, and pH do not significantly harm EAB sensor accuracy. Specifically, all 3 of our test-bed sensors achieve clinically significant mean relative accuracy (i.e., better than 20%) over the clinically or physiologically relevant concentration ranges of their target molecules. In contrast, physiologically plausible variations away from the temperature used for calibration induce more substantial errors. With knowledge of the temperature in hand, however, these errors are easily ameliorated. It thus appears that physiologically induced changes in the sensing environment are likely not a major impediment to clinical application of this in vivo molecular monitoring technology.

The Effect of the Acid-Base Imbalance on the Shape and Structure of Red Blood Cells.

Red blood cells respond to fluctuations in blood plasma pH by changing the rate of biochemical and physical processes that affect the specific functions of individual cells. This study aimed to analyze the effect of pH changes on red blood cell morphology and structure. The findings revealed that an increase or decrease in pH above or below the physiological level of pH 7.4 results in the transformation of discocytes into echinocytes and causes significant alterations in the membrane, including its roughness, cytoskeleton structure, and the cell's elastic modulus. Furthermore, the study shown a strong connection between critical acidosis and alkalosis with increased intracellular reactive oxygen species production.

Calcium propionate is an alkalizing agent in exercising Standardbreds

The objective of this study was to determine if calcium propionate is an alkalizing agent in exercising Standardbreds and if it alters plasma glucose and serum insulin concentrations. This study used a randomized crossover design to test the hypotheses that calcium propionate alters total CO2 (tCO2), Ca++, pH, strong ion difference (SID), glucose, and insulin in Standardbreds completing a simulated race test (SRT) on a high-speed equine treadmill. Blood was collected from eight horses (mean age ± SD = 16 ± 2.7 years; range = 13 - 21 years) at 10 and 5 min prior to treatment or control administration, just prior to the subsequent SRT, directly after the SRT, and at 60- and 90-min post SRT. Plasma pH and plasma concentrations of tCO2, glucose, Ca++, and Na+, K+, Cl-, Lac- (for SID calculation) were measured in duplicate by blood gas analyzer and serum insulin by radioimmunoassay. Data were analyzed by two-way repeated-measures ANOVA. For plasma pH, Na+, K+, Cl-, Lac-, SID, insulin and glucose, no effects of treatment or treatment by sampling-timepoint interaction were found (p>0.05). Plasma tCO2, Ca++, pH, Na+, SID, and glucose concentrations were significantly lower, and Lac- was significantly higher, directly after the SRT compared to all other timepoints (p<0.05). Plasma tCO2, HCO3- and Ca++ were significantly higher in treated than in control horses at multiple sampling timepoints after treatment/control administration (p<0.05). Serum insulin concentration, measured only pre and 30 min post treatment/control administration, was unaffected by treatment. Calcium propionate is an alkalizing agent in horses.

Intestinal-Target and Glucose-Responsive Smart Hydrogel toward Oral Delivery System of Drug with Improved Insulin Utilization.

An intelligent insulin delivery system targeting intestinal absorption and glucose responsiveness can enhance the bioavailability through oral insulin therapy, offering promising diabetes treatment. In this paper, a glucose and pH dual-response polymer hydrogel using carboxymethyl agarose modified with 3-amino-phenylboronic acid and l-valine (CPL) was developed as an insulin delivery carrier, exhibiting excellent biocompatibility and effective insulin encapsulation. The insulin encapsulated in the hydrogel (Ins-CPL) was released in a controlled manner in response to the in vivo stimulation of blood glucose and pH levels with higher levels of intracellular uptake and utilization of insulin in the intestinal environment simultaneously. Notably, the Ins-CPL hydrogel effectively regulated blood sugar in diabetic rats over a long period by simulating endogenous insulin, responding to changes in plasma pH and glucose levels, and overcoming the intestinal epithelium barrier. This indicates a significant boost in oral insulin bioavailability and broadens its application prospects.

Docetaxel-tethered di-Carboxylic Acid Derivatised Fullerenes: A Promising Drug Delivery Approach for Breast Cancer.

Docetaxel (DTX) has become widely accepted as a first-line treatment for metastatic breast cancer; however, the frequent development of resistance provides challenges in treating the disease.C60 fullerene introduces a unique molecular form of carbon, exhibiting attractive chemical and physical properties. Our study aimed to develop dicarboxylic acid-derivatized C60 fullerenes as a novel DTX delivery carrier. This study investigated the potential of water-soluble fullerenes to deliver the anti-cancer drug DTX through a hydrophilic linker. The synthesis was carried out using the Prato reaction. The spectroscopic analysis confirmed the successful conjugation of DTX molecules over fullerenes. The particle size of nanoconjugate was reported to be 122.13 ± 1.63nm with a conjugation efficiency of 76.7 ± 0.14%. The designed conjugate offers pH-dependent release with significantly less plasma pH, ensuring maximum release at the target site. In-vitro cell viability studies demonstrated the enhanced cytotoxic nature of the developed nanoconjugate compared to DTX. These synthesized nanoscaffolds were highly compatible with erythrocytes, indicating the safer intravenous route administration. Pharmacokinetic studies confirmed the higher bioavailability (~ 6 times) and decreased drug clearance from the system vis-à-vis plain drug. The histological studies reveal that nanoconjugate-treated tumour cells exhibit similar morphology to normal cells. Therefore, it was concluded that this developed formulation would be a valuable option for clinical use.

Quantitatively Predicting Effects of Exercise on Pharmacokinetics of Drugs Using a Physiologically Based Pharmacokinetic Model.

Exercise significantly alters human physiological functions, such as increasing cardiac output and muscle blood flow and decreasing glomerular filtration rate (GFR) and liver blood flow, thereby altering the absorption, distribution, metabolism, and excretion of drugs. In this study, we aimed to establish a database of human physiological parameters during exercise and to construct equations for the relationship between changes in each physiological parameter and exercise intensity, including cardiac output, organ blood flow (e.g., muscle blood flow and kidney blood flow), oxygen uptake, plasma pH and GFR, etc. The polynomial equation P = ΣaiHRi was used for illustrating the relationship between the physiological parameters (P) and heart rate (HR), which served as an index of exercise intensity. The pharmacokinetics of midazolam, quinidine, digoxin, and lidocaine during exercise were predicted by a whole-body physiologically based pharmacokinetic (WB-PBPK) model and the developed database of physiological parameters following administration to 100 virtual subjects. The WB-PBPK model simulation results showed that most of the observed plasma drug concentrations fell within the 5th-95th percentiles of the simulations, and the estimated peak concentrations (Cmax) and area under the curve (AUC) of drugs were also within 0.5-2.0 folds of observations. Sensitivity analysis showed that exercise intensity, exercise duration, medication time, and alterations in physiological parameters significantly affected drug pharmacokinetics and the net effect depending on drug characteristics and exercise conditions. In conclusion, the pharmacokinetics of drugs during exercise could be quantitatively predicted using the developed WB-PBPK model and database of physiological parameters. SIGNIFICANCE STATEMENT: This study simulated real-time changes of human physiological parameters during exercise in the WB-PBPK model and comprehensively investigated pharmacokinetic changes during exercise following oral and intravenous administration. Furthermore, the factors affecting pharmacokinetics during exercise were also revealed.

Nanotherapeutic kidney cell-specific targeting to ameliorate acute kidney injury

Acute kidney injury (AKI) increases the risk of in-hospital death, adds to expense of care, and risk of early chronic kidney disease. AKI often follows an acute event such that timely treatment could ameliorate AKI and potentially reduce the risk of additional disease. Despite therapeutic success of dexamethasone in animal models, clinical trials have not demonstrated broad success. To improve the safety and efficacy of dexamethasone for AKI, we developed and characterized a novel, kidney-specific nanoparticle enabling specific within-kidney targeting to proximal tubular epithelial cells provided by the megalin ligand cilastatin. Cilastatin and dexamethasone were complexed to H-Dot nanoparticles, which were constructed from generally recognized as safe components. Cilastatin/Dexamethasone/H-Dot nanotherapeutics were found to be stable at plasma pH and demonstrated salutary release kinetics at urine pH. In vivo, they were specifically biodistributed to the kidney and bladder, with 75% recovery in the urine and with reduced systemic toxicity compared to native dexamethasone. Cilastatin complexation conferred proximal tubular epithelial cell specificity within the kidney in vivo, and enabled dexamethasone delivery to the proximal tubular epithelial cell nucleus in vitro. The Cilastatin/Dexamethasone/H-Dot nanotherapeutic improved kidney function and reduced kidney cellular injury when administered to male C57BL/6 mice in two translational models of AKI (rhabdomyolysis and bilateral ischemia reperfusion). Thus, our design-based targeting and therapeutic loading of a kidney-specific nanoparticle resulted in preservation of the efficacy of dexamethasone, combined with reduced off-target disposition and toxic effects. Hence, our study illustrates a potential strategy to target AKI and other diseases of the kidney.

Selected Chromatographic Methods for Determining the Biological Activity of Substances

This paper presents various aspects of the use of chromatography to determine the biological activity of substances. On the one hand, the use of chromatography to determine the lipophilicity of a substance, a property that affects all LADME steps in various biomimetic systems, is presented, using various descriptors such as the retention factor in pure water (or buffer with physiological plasma pH), the CHI value, and Chrom logD. The use of chromatography in biomimetic systems to determine the interaction of substances with phospholipids (IAM stationary phases) and transport proteins (stationary phases with immobilised proteins) is also discussed. On the basis of the retention data obtained in these systems, the volume of distribution of the substance and the degree of binding of the substance with the proteins in question can be determined. Chromatography is also a method used to determine the interaction of substances with specific membrane receptors at their site of action using membrane chromatography (MCM). Thanks to biological detection, chromatography can also be used to determine the antimicrobial activity (bioautography) of substances and the effect of substances on biochemical reactions taking place in organisms, such as antioxidant properties and the inhibitory activity of various enzymes (biological assay).

Assessment of Blood Gas Pattern amongst Artisanal Refinery Operators in Rivers State, Nigeria

Some identified setbacks of the legitimate and illegitimate explorations/exploitations of crude oil and its derivatives in the Niger Delta are degraded environment, weak economy, and deteriorating health of the populace. Therefore, the current study evaluated the effect of artisanal refinery operation on respiratory blood gases and renal functions of its workers in Rivers State. As a cross-sectional investigation with sparse population, the multistage sampling technique (including purposive and snowball tools) was adopted to recruit 203 (including 120 operators of artisanal refinery―OAR-actively exposed and 83 non-OAR- actively exposed) willing and apparently healthy male and female adult subjects. Following receipt of ethical approval and consent, five milliliter of blood was taken from each subject from their antecubital vein after sterilizing the portion of the cubital fossa. The sample was then put into plain sample bottle and centrifuged to recover serum. Thereafter, the automated blood gas analyzer was used to measure the arterial blood gases of the subjects. The result showed marked (P&lt;0.05) reductions in the partial pressure of oxygen (PO2) and oxygen saturation (SO2) levels in artisanal refinery operators (actively exposed) when compared to that of the passively-exposed subjects. Again, there were marked (P&lt;0.05) elevations in the plasma pH and bicarbonate ions (HCO-3) levels in the actively exposed subjects compared to their passively-exposed counterparts. In conclusion, there could be adverse impact on respiratory blood gases and incidences of metabolic alkalosis over chronic exposures to the OAR activities.

Effect of seawater temperature and pH on the sperm motility of the European eel

The current climate change situation could bring critical effects for marine species, especially those already considered endangered. Although some species can adapt fast to the environmental changes, it is necessary to get into the worst scenario and develop tools to anticipatedly assess the physiological effects of such environmental change. With this purpose, our study aims to determine the effect of a range of seawater temperatures and pHs on sperm motility in the European eel (Anguilla anguilla). Low seawater pH (6.5–7.4) decreased the eel sperm motility in comparison to the control (pH = 8.2). We also studied the combined effect of the pH of the artificial seminal plasma (the plasma where the sperm cells are suspended) with the pH of Artificial Sea Water (ASW, pH 7.8 or and 8.2). We did not find statistical differences in sperm motility and kinetic parameters caused by the artificial seminal plasma pH. However, seawater pH induced significantly higher values of total sperm motility, and the percentage of fast spermatozoa with a pH of 8.2 in comparison with a pH of 7.8. In contrast, the seawater temperature did not affect sperm motility parameters or sperm longevity. To study the effect of the interaction between seawater temperature and pH on sperm motility, two temperatures: 4 and 24 °C, and two pHs 7.8 and 8.2, were tested. There were significant differences between temperature and pH in several kinetic parameters and, in general, the lowest values were observed in the samples activated at low temperature and low pH (4 °C, pH 7.8). This work suggest that eel sperm motility and kinetics will not be affected by the expected changes in pH or temperature due to the climate change.

Physiological evaluation of seasonal sperm quality in a biannual spawner, Pacific abalone: Effects on in-vitro fertilization and cryotolerance

Pacific abalone, Haliotis discus hannai, is a highly valuable gastropod mollusk commonly found in Southeast Asia. The present study aims to analyze the seminal plasma quality, sperm quality, and cryotolerance of the Pacific abalone sperm during its reproductive season. The seminal plasma quality was evaluated by analyzing biochemical and metabolite composition, enzymatic activity (superoxide dismutase, catalase, and glutathione), and lipid peroxidation (LPO) activity. The sperm quality was evaluated by analyzing motility, concentration, volume, ATP content, acrosome integrity (AI), plasma membrane integrity (PMI), mitochondrial membrane potential (MMP), DNA integrity, and fertilization potential. The cryotolerance capacity was evaluated by analyzing post-thaw motility, AI, PMI, MMP, and DNA integrity. Seminal plasma osmolarity was significantly higher (1123.3 ± 1.5 mOsmL-1) in May compared to other reproductive periods, with Cl- (516.8 ± 0.5 mM) and Na+ (460.2 ± 0.4 mM) as the dominant ions. The seminal plasma pH remained constant at 6.8 throughout the reproductive season. Improved enzymatic activity and lower LPO were detected in May or June. Sperm quality indicators were similar in May and June, except for sperm production. The fertilization potential (May: 93.0 ± 4.4%, June: 86.0 ± 7.2%) and hatching rate (May: 86.6 ± 5.78%, June: 82.3 ± 3.2%) of Pacific abalone were significantly higher in May or June than they were in other reproductive seasons. The motility (May: 50.19 ± 2.35%, June: 49.96 ± 1.60%), AI (May: 44.02 ± 3.46%, June: 42.16 ± 3.61%), PMI (May: 54.12 ± 3.29%, June: 52.82 ± 2.58%), and MMP (May: 44.02 ± 3.46%, June: 42.16 ± 3.61%) of the cryopreserved sperm were similar in May and June compared with those preserved in other reproductive seasons. The DNA integrity of the cryopreserved sperm was similar in May (80.3 ± 6.7%) or June (78.9 ± 7.4%) and had a higher cryotolerance than in other reproductive seasons. Hence, it can be suggested that May and/or June are suitable periods for sperm physiology experiments, artificial reproduction, and sperm cryopreservation of Pacific abalone.

A Comparative Kidney Transcriptome Analysis of Bicarbonate-Loaded insrr-Null Mice.

The maintenance of plasma pH is critical for life in all organisms. The kidney plays a critical role in acid-base regulation in vertebrates by controlling the plasma concentration of bicarbonate. The receptor tyrosine kinase IRR (insulin receptor-related receptor) is expressed in renal β-intercalated cells and is involved in alkali sensing due to its ability to autophosphorylate under alkalization of extracellular medium (pH > 7.9). In mice with a knockout of the insrr gene, which encodes for IRR, urinary bicarbonate secretion in response to alkali loading is impaired. The specific regulatory mechanisms in the kidney that are under the control of IRR remain unknown. To address this issue, we analyzed and compared the kidney transcriptomes of wild-type and insrr knockout mice under basal or bicarbonate-loaded conditions. Transcriptomic analyses revealed a differential regulation of a number of genes in the kidney. Using TaqMan real-time PCR, we confirmed different expressions of the slc26a4, rps7, slc5a2, aqp6, plcd1, gapdh, rny3, kcnk5, slc6a6 and atp6v1g3 genes in IRR knockout mice. Also, we found that the expression of the kcnk5 gene is increased in wild-type mice after bicarbonate loading but not in knockout mice. Gene set enrichment analysis between the IRR knockout and wild-type samples identified that insrr knockout causes alterations in expression of genes related mostly to the ATP metabolic and electron transport chain processes.

In vitro evaluation of tropolone absorption, metabolism, and clearance

Tropolone compounds can inhibit hepatitis B virus (HBV) replication at sub-micromolar levels and are synergistic upon co-treatment with nucleos(t)ide analog drugs. However, only a few compounds within this chemotype have been screened for their pharmacological properties. Here, we chose 36 structurally diverse tropolones from six subclasses to characterize their in vitro pharmacological parameters. All compounds were more soluble in pHs that reflect the gastrointestinal tract (pH 5 and 6.5) than plasma (pH 7.4). Those compounds that had solubility limits >100 μM were tested in a passive permeability assay, and there was no general trend in the compounds' passive permeability at any pH. Twenty-nine compounds with the best absorption parameters were tested in HEK293 cells to assess potential cytotoxicity; measured toxicities were similar to those in the hepatic HepDES19 cells used for screening (R2 = 0.55). Sixteen representative compounds were tested against five major CYP450 isoforms and there was no substantial inhibition by any compound against any of the enzymes tested (<50%). The t1/2 values of 15 compounds were determined in the microsome stability assay and 12 compounds were evaluated in plasma protein binding assays to assess factors affecting their rate of clearance. All compounds with detectable analyte peaks had t1/2 > 30 min, and while 4 of 12 had statistically significant decreased potency in conditions with increased albumin concentrations, only one compound's potency was biologically significant. These data indicate that the tropolones have pharmacological characteristics that reflect approved drugs and inform future structure activity relationships during drug design.

Study of the Stability of Zeolites in Model Biological Environments

The stability of synthetic and natural zeolites in model biological media simulating the environment of the stomach (pH 1.8), blood plasma (pH 6.9), and intestines (pH 8) is studied. The effect of long-term exposure (up to 7 days) to biological media on the crystal structure of Beta, Rho, Y, and clinoptilolite zeolites is studied. The degree of degradation of the crystal structure of zeolites is controlled by X-ray phase analysis. Based on the results obtained, conclusions are drawn on the prospects for the use of synthetic and natural zeolites as drug carriers.

Exploring the potential of silica mixed zinc phosphate bioactive glasses for bone regeneration: In vitro bioactivity and antibacterial activity analysis

Biomaterials development is currently the main active research area in the field of bone tissue engineering. In the present study, the bioactive glasses with different chemical compositions (mol %) of zinc oxide, silica, calcium oxide, sodium oxide, and phosphates were synthesized by the melt-quench technique. We studied the thermal, physical, and other structural characteristics of the glasses to know the structural stability and potentiality to use as implant material. The in-vitro studies were performed to test the apatite forming ability and biocompatible nature of the prepared bioglass samples by immersing in simulated body fluid (SBF) solution with ion concentrations nearly equal to those in human blood plasma (pH =7.4 at 37 °C). All glass samples showed the formation of a clear layer of hydroxyapatite (HAP) on their surfaces after 14, and 21 days of immersion in SBF and the crystallization phases, morphology and functional groups of the hydroxyapatite layer (HAP) were confirmed by the characterizations of X-ray diffraction (XRD), scanning electron microscope (SEM), and Fourier transform infrared (FTIR) analyses respectively. The antimicrobial studies of the silica containing phosphate bioglasses against Escherichia coli (E. coli), carried out for 24 h confirmed their potential antibacterial activity. The overall obtained results of the as developed silica containing phosphate bioglasses with enhanced properties suggested to use as potential bone regenerative implant material in the field of biomedicine.

DEEPENING THEORETICAL KNOWLEDGE AND EXPLORING THE PROPERTIES OF LOCAL ANESTHETICS

Local anesthetics are indispensable agents in medical practice, offering targeted pain relief while maintaining patient consciousness. Their applications span a wide range of medical fields, including anesthesiology, surgery, and dentistry. Despite their widespread use, the complex pharmacology and potential for adverse effects necessitate a comprehensive understanding of these agents. This narrative review aims to provide an in-depth analysis of the physiology, pharmacology, and clinical applications of local anesthetics. A systematic search was conducted on PubMed, focusing on articles published in English between 2018 and 2023. Local anesthetics have evolved significantly since the first use of cocaine in the late 19th century, with newer derivatives like Lidocaine and Bupivacaine offering improved safety and efficacy. These agents are categorized into aminoesters and aminoamides based on their molecular structure, which also influences their pharmacokinetics and pharmacodynamics. The primary mechanism of action involves the modulation of voltage-gated sodium channels, although the complete mechanism remains an area of active research. Various factors, including lipid solubility, plasma pH, and pKa, influence the drug's onset, duration, and potential for toxicity. Adjuvants like adrenaline can enhance the drug's properties. Local anesthetics are a cornerstone in modern medicine, offering targeted anesthesia with a relatively favorable safety profile. Understanding their complex pharmacology is crucial for optimizing their clinical use. Future research should focus on elucidating the complete mechanisms of action and exploring the potential for new adjuvants to improve efficacy and safety.

Hexavalent chromium reduction by atmospheric plasma bubbles

The effective removal of carcinogenic and mutagenic hexavalent chromium [Cr(VI)] from contaminated water is of key environmental and societal importance. However, it is challenging due to its recalcitrance and lack of treatment technologies. Non-thermal plasma (NTP) is gaining increasing attention as an alternative to conventional chemical methods for wastewater remediation. However, there is a lack of understanding regarding the mechanisms of action of plasma-liquid interactions, particularly for heavy metal remediation. In this study, an atmospheric plasma bubble (APB) reactor that combines two types of plasma discharge, namely a dielectric barrier discharge (DBD) and pulsed spark discharge, was developed. This design enables the efficient transfer of plasma species for Cr(VI) reduction. The performance of Cr(VI) reduction was found to be influenced by several factors, including feeding gas, applied voltage, initial Cr(VI) concentration, plasma exposure time, pH and radical scavenger additions. A reduction of over 98% was achieved when the initial pH was adjusted to below 3 or when ethanol (1%) was used as an oxidative species scavenger. This resulted in an energy efficiency of greater than 0.7 g/kWh. Cytotoxicity studies revealed that the APB treatment could effectively reduce the toxicity of Cr(VI)-containing wastewater, as evidenced by the increased viability in human cell lines. This study provides insights into the fundamental aspects of plasma oxidation/reduction chemistry and would support further applications of plasma-based water remediation.

Penaeid shrimp counteract high ammonia stress by generating and using functional peptides from hemocyanin, such as HMCs27

Agricultural and anthropogenic activities release high ammonia levels into aquatic ecosystems, severely affecting aquatic organisms. Penaeid shrimp can survive high ammonia stress conditions, but the underlying molecular mechanisms are unknown. Here, total hemocyanin and oxyhemocyanin levels decreased in Penaeus vannamei plasma under high ammonia stress. When shrimp were subjected to high ammonia stress for 12 h, 24 hemocyanin (HMC) derived peptides were identified in shrimp plasma, among which one peptide, designated as HMCs27, was chosen for further analysis. Shrimp survival was significantly enhanced after treatment with the recombinant protein of HMCs27 (rHMCs27), followed by high ammonia stress. Transcriptome analysis of shrimp hepatopancreas after treatment with or without rHMCs27 followed by high ammonia stress revealed 973 significantly dysregulated genes, notable among which were genes involved in oxidation and metabolism, such as cytochrome C, catalase (CAT), isocitrate dehydrogenase, superoxide dismutase (SOD), trypsin, chymotrypsin, glutathione peroxidase, glutathione s-transferase (GST), and alanine aminotransferase (ALT). In addition, levels of key biochemical indicators, such as SOD, CAT, and total antioxidant capacity (T-AOC), were significantly enhanced, whereas hepatopancreas malondialdehyde levels and plasma pH, NH3, GST, and ALT levels were significantly decreased after rHMCs27 treatment followed by high ammonia stress. Moreover, high ammonia stress induced hepatopancreas tissue injury and apoptosis, but rHMCs27 treatment ameliorated these effects. Collectively, the current study revealed that in response to high ammonia stress, shrimp generate functional peptides, such as peptide HMCs27 from hemocyanin, which helps to attenuate the ammonia toxicity by enhancing the antioxidant system and the tricarboxylic acid cycle to decrease plasma NH3 levels and pH.

Review of the Case Reports on Metformin, Sulfonylurea, and Thiazolidinedione Therapies in Type 2 Diabetes Mellitus Patients.

Type 2 diabetes mellitus (T2DM) is the world's most common metabolic disease. The development of T2DM is mainly caused by a combination of two factors: the failure of insulin secretion by the pancreatic β-cells and the inability of insulin-sensitive tissues to respond to insulin (insulin resistance); therefore, the disease is indicated by a chronic increase in blood glucose. T2DM patients can be treated with mono- or combined therapy using oral antidiabetic drugs and insulin-replaced agents; however, the medication often leads to various discomforts, such as abdominal pain, diarrhea or constipation, nausea and vomiting, and hypersensitivity reactions. A biguanide drug, metformin, has been used as a first-line drug to reduce blood sugar levels. Sulfonylureas work by blocking the ATP-sensitive potassium channel, directly inducing the release of insulin from pancreatic β-cells and thus decreasing blood glucose concentrations. However, the risk of the failure of sulfonylurea as a monotherapy agent is greater than that of metformin or rosiglitazone (a thiazolidinedione drug). Sulfonylureas are used as the first-line drug of choice for DM patients who cannot tolerate metformin therapy. Other antidiabetic drugs, thiazolidinediones, work by activating the peroxisome proliferator-activated receptor gamma (PPARγ), decreasing the IR level, and increasing the response of β-cells towards the glucose level. However, thiazolidines may increase the risk of cardiovascular disease, weight gain, water retention, and edema. This review article aims to discuss case reports on the use of metformin, sulfonylureas, and thiazolidinediones in DM patients. The literature search was conducted on the PubMed database using the keywords 'metformin OR sulfonylureas OR thiazolidinediones AND case reports', filtered to 'free full text', 'case reports', and '10 years publication date'. In some patients, metformin may affect sleep quality and, in rare cases, leads to the occurrence of lactate acidosis; thus, patients taking this drug should be monitored for their kidney status, plasma pH, and plasma metformin level. Sulfonylureas and TZDs may cause a higher risk of hypoglycemia and weight gain or edema due to fluid retention. TZDs may be associated with risks of cardiovascular events in patients with concomitant T2DM and chronic obstructive pulmonary disease. Therefore, patients taking these drugs should be closely monitored for adverse effects.

Sodium bicarbonate for the treatment of severe metabolic acidosis with moderate or severe acute kidney injury in the critically ill: protocol for a randomised clinical trial (BICARICU-2)

IntroductionWhen both severe metabolic acidemia (pH equal or less than 7.20; PaCO2 equal or less than 45 mm Hg and bicarbonate concentration equal or less than of 20 mmol/L) and...