Bicarbonate Buffer System Research Articles

Visible Light-Driven CO2 Capture and Release Using Photoactive Pyranine in Water in Continuous Flow.

The urgent need to address climate change and its environmental consequences demands innovative carbon capture technologies, given the relationship between rising global temperatures and increased atmospheric CO2 levels. Here, we present a reversible photochemical carbon capture and release strategy and system utilizing photoactive pyranine in an aqueous bicarbonate buffer system. Control experiments suggested that the photoacid effect occurs at the surface which contributes to CO2 release, complemented by the photothermal effect at the surface and in the bulk. A continuous flow setup employing a tube-in-tube configuration with a hollow fiber membrane demonstrates the efficiency and reliability of the visible light-driven carbon capture system, with the release of CO2 captured from a 15% CO2 feed in the dark, at a rate of 0.48 mmol CO2 per hour to a nitrogen sweep stream under light irradiation at 200 W/m2, a level comparable to solar intensity of visible light (150 W/m2 of blue light -250 W/m2 of blue and green light). The robustness and scalability of the system has been demonstrated, with long-term operation over 7 days yielding 60 mmol (1.34 L CO2 at STP) of cumulated CO2 separation. Additionally, we explored the potential for direct air capture, yielding 3 μmol of CO2 separation over 2 h of operation from a bicarbonate buffer solution saturated with ambient air (420 ppm). This work introduces the prospect of photoswing of carbon capture systems, which can avoid external energy input beyond solar irradiation, offering promising avenues for addressing the challenges associated with climate change.

Elevated blood bicarbonate levels and long-term adverse outcomes in patients with chronic heart failure.

The bicarbonate (HCO3 -) buffer system is crucial for maintaining acid-base homeostasis and blood pH. Recent studies showed that elevated serum HCO3 - levels serve as an indicator of the beneficial effects of acetazolamide in improving decongestion in acute heart failure. In this study, we sought to clarify the clinical relevance and prognostic impact of HCO3 - in chronic heart failure (CHF). This cohort study enrolled 694 hospitalized patients with CHF (mean age 68.6±14.6, 62% male) who underwent arterial blood sampling and exhibited neutral pH ranging from 7.35 to 7.45. We characterized the patients based on HCO3 - levels and followed them to register cardiac events. Among the patients, 17.3% (120 patients) had HCO3 - levels exceeding 26mmol/L. Patients presenting HCO3 ->26mmol/L were more likely to use loop diuretics and had higher serum sodium and lower potassium levels, but left ventricular ejection fraction did not differ compared with those with HCO3 - between 22 and 26 (379 patients) or those with HCO3 -<22mmol/L (195 patients). During a median follow-up period of 1950days, Kaplan-Meier analysis revealed that patients with HCO3 ->26mmol/L had the lowest event-free survival rate from either cardiac deaths or heart failure-related rehospitalization (P<0.01 and 0.03, respectively). In the multivariable Cox model, the presence of HCO3 ->26mmol/L independently predicted increased risks of each cardiac event with a hazard ratio of 2.31 and 1.69 (P<0.01 and 0.02, respectively), while HCO3 -<22mmol/L was not associated with these events (hazard ratios, 0.99 and 1.19; P=0.98 and 0.43, respectively). Elevated blood HCO3 - levels may signify enhanced proximal nephron activation and loop diuretic resistance, leading to long-term adverse outcomes in patients with CHF, even within a normal pH range.

Analysis of Self-Assembled Micelle Inhibitory RNA (SAMiRNA) Drug Using Ion-Pairing Reversed-Phase Liquid Chromatography Combined with Mass Spectrometry.

Small interfering RNA (siRNA) is known for its ability to silence the expression of specific genes, demonstrating its promising potential as a therapeutic approach. Self-assembled micelle inhibitory RNA (SAMiRNA) is an oligonucleotide duplex developed to overcome the in vivo delivery limitations of siRNA. SAMiRNA has hydrophilic and hydrophobic groups at both ends of a sense strand, forming a spherical nanostructure that enhances the in vivo delivery efficiency. Ion-pairing reversed-phase liquid chromatography (IP-RPLC) is the most commonly used method for the analysis of oligonucleotides. Since SAMiRNA is heavily chemically modified, the behavior of SAMiRNA in IP-RPLC combined with mass spectrometry (MS) is anticipated to differ from that of the conventional siRNA drug. The current investigation using IP-RPLC-MS revealed that a distinct duplex peak along with two minor separate strands of antisense and sense was observed at column temperatures below 35 °C in the IP-RPLC system with a 100 mM ammonium bicarbonate buffer system. At column temperatures higher than 35 °C, however, two fully denatured single strands were observed. The mass spectrum from the chromatographic peak of the SAMiRNA duplex contained signals from the duplex, the antisense, and the sense, probably due to duplex denaturation during the MS ionization process. The current comprehensive analysis results will make a substantial contribution to the future application of IP-RPLC-MS in the analysis of SAMiRNA.

Механизм повреждения мелких холангиоцитов при первичном билиарном холангите

Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults. Damage to cholangiocytes triggers the development of intrahepatic cholestasis, which progresses to cirrhosis in the terminal stage of the disease. Accumulating data indicate that damage to biliary epithelial cells [(BECs), cholangiocytes] is most likely associated with the intracellular accumulation of bile acids, which have potent detergent properties and damaging effects on cell membranes. The mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen, which is controlled by the bicarbonate (HCO3-) buffer system "biliary HCO3- umbrella". The impaired production and entry of HCO3- from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA 506. Based on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC, we propose a hypothesis explaining the pathogenesis of the first morphologic (ductulopenia), immunologic (antimitochondrial autoantibodies) and clinical (weakness, malaise, rapid fatigue) signs of the disease in the asymptomatic stage. This review focuses on the consideration of these mechanisms.

Abstract 12042: Elevated Levels of Bicarbonate Predict Adverse Outcomes in Patients With Chronic Heart Failure

Background: The bicarbonate (HCO3 - ) buffer system plays a crucial role in maintaining acid-base homeostasis, and HCO3 - levels are affected by multiple factors in heart failure. Recently, a sub-analysis of the ADVOR trial for acute heart failure revealed that patients with elevated serum HCO3 - levels experienced beneficial effects of decongestion by acetazolamide. However, the significance of HCO3 - levels in chronic heart failure has not been fully understood. Aim: We sought to clarify whether HCO3 - levels have clinical relevance or prognostic impact in patients with chronic heart failure. Methods and Results: We conducted a prospective study involving hospitalized patients with stage C/D heart failure and measured HCO3 - levels in arterial blood gas samples prior to discharge. We enrolled a total of 718 patients (mean 68.3 years old and 62.1% male), with neutral pH ranging from 7.35 to 7.45, and found that 132 (18.4%) had HCO3 - levels exceeding 26 mmol/L. Patients with HCO3 - &gt; 26 mmol/L were more likely to be male and to use loop diuretics, and had higher serum sodium, as well as lower potassium levels, compared to those with HCO3 - &lt; 26 mmol/L, whereas there were no differences in B-type natriuretic peptide levels or left ventricular ejection fraction between the two groups. In a Kaplan-Meier analysis, patients with HCO3 - &gt; 26 mmol/L had lower event-free survival rates from cardiac deaths and decompensated heart failure as well as the composite of the cardiac events over a median follow-up period of 1540 days ( Figure ). In a multivariable Cox proportional hazard model after adjusting confounding variables, the presence of HCO3 - &gt; 26 mmol/L was independently associated with increased risks of the composite of cardiac events (hazard ratio, 1.64; P &lt; 0.01). Conclusion: Elevated HCO3 - levels may indicate enhanced proximal nephron activation and resistance to loop diuretics, which predicted adverse outcomes in patients with chronic heart failure, even within a normal pH range.

New insights into the pathogenesis of primary biliary cholangitis asymptomatic stage.

Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults. Damage to cholangiocytes triggers the development of intrahepatic cholestasis, which progresses to cirrhosis in the terminal stage of the disease. Accumulating data indicate that damage to biliary epithelial cells [(BECs), cholangiocytes] is most likely associated with the intracellular accumulation of bile acids, which have potent detergent properties and damaging effects on cell membranes. The mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen, which is controlled by the bicarbonate (HCO3-) buffer system "biliary HCO3- umbrella". The impaired production and entry of HCO3- from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA 506. Based on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC, we propose a hypothesis explaining the pathogenesis of the first morphologic (ductulopenia), immunologic (antimitochondrial autoantibodies) and clinical (weakness, malaise, rapid fatigue) signs of the disease in the asymptomatic stage. This review focuses on the consideration of these mechanisms.

Establishment of a reference interval for total carbon dioxide using indirect methods in Chinese populations living in high-altitude areas: A retrospective real-world analysis

BackgroundHypoxia leads to different concentrations of the bicarbonate buffer system in Tibetan people. Indirect methods were used to establish the reference interval (RI) for total carbon dioxide (tCO2) based on big data from the adult population of Tibet, a high-altitude area in Western China. MethodsAnonymous tCO2 test data (n = 442,714) were collected from the People's Hospital of the Tibet Autonomous Region from January 2018, to December 2021. Multiple linear regression and variance component analyses were performed to assess the effects of sex, age, and race on tCO2 levels. Indirect methods, including Hoffmann, Bhattacharya, expectation maximization (EM), kosmic and refineR, were used to calculate the total RI and ethnicity-partitioned RI. ResultsA total of 230,821 real-world tCO2 test results were eligible. Sex, age, and race were significantly associated with the tCO2 levels. The total and ethnically-partitioned RIs estimated using the five indirect methods were comparable. The total RI of tCO2 was 14–24 mmol/L (calculated using Hoffmann and refineR) and 15–24 mmol/L (Bhattacharya, EM and kosmic). For Han nationality, the RIs were 14–25 mmol/L (calculated using Hoffmann and Bhattacharya), 16–23 mmol/L (EM), 15–24 mmol/L (kosmic), and 14.2–24.5 mmol/L (refineR). For the Tibetan population, the RIs were 14–24 mmol/L (calculated using Hoffmann and refineR), 15–24 mmol/L (Bhattacharya and kosmic), and 15–23 mmol/L (EM). The established RIs were significantly lower than those living at lower altitudes area (22–29 mmol/L) that was provided by the manufacturer. ConclusionThe tCO2 RI of the populations living on the Tibetan Plateau was significantly lower than those at the lower altitudes. The RIs established using indirect methods are suitable for clinical applications in Tibet.

Cardiorespiratory Coordination in Collegiate Rowing: A Network Approach to Cardiorespiratory Exercise Testing.

Collegiate rowing performance is often assessed by a cardiopulmonary exercise test (CPET). Rowers’ on-water performance involves non-linear dynamic interactions and synergetic reconfigurations of the cardiorespiratory system. Cardiorespiratory coordination (CRC) method measures the co-variation among cardiorespiratory variables. Novice (n = 9) vs. Intermediate (n = 9) rowers’ CRC (H0: Novice CRC = Intermediate CRC; HA: Novice CRC < Intermediate CRC) was evaluated through principal components analysis (PCA). A female NCAA Division II team (N = 18) grouped based on their off-water performance on 6000 m time trial. Rowers completed a customized CPET to exhaustion and a variety of cardiorespiratory values were recorded. The number of principal components (PCs) and respective PC eigenvalues per group were computed on SPSS vs28. Intermediate (77%) and Novice (33%) groups showed one PC1. Novice group formed an added PC2 due to the shift of expired fraction of oxygen or, alternatively, heart rate/ventilation, from the PC1 cluster of examined variables. Intermediate rowers presented a higher degree of CRC, possible due to their increased ability to utilize the bicarbonate buffering system during the CPET. CRC may be an alternative measure to assess aerobic fitness providing insights to the complex cardiorespiratory interactions involved in rowing during a CPET.

Dissolution of a Biopharmaceutics Classification System Class II Free Acid from Immediate Release Tablets Containing a Microenvironmental pH Modulator: Comparison of a Biorelevant Bicarbonate Buffering System with Phosphate Buffers

Poor water dissolution of active pharmaceutical ingredients (API) limits the rate of absorption from the gastrointestinal tract. Increasing the pH of a solid form microenvironment can enhance the dissolution of weakly acidic drugs, but data on this phenomenon in a physiologically relevant bicarbonate media are lacking. In this paper, we examined the effect of a microenvironmental pH modulator (Na2HPO4) on the dissolution of a Biopharmaceutics Classification System (BCS) class II free weak acid (ibuprofen) at biorelevant conditions, including an automatic bicarbonate buffering system, as well as in compendial (50 mM) and low-concentration (10 mM) phosphate buffers with no external pH control. The tablets of 200 mg ibuprofen with either Na2HPO4 (phosphate formulation, PF) or NaCl (reference formulation, RF) were manufactured using a compression method. In a pH 2 simulated gastric fluid, only PF produced a transient supersaturation of ibuprofen, dissolving a fourfold higher drug amount than RF. In a bicarbonate-buffered simulated intestinal fluid with a dynamically controlled pH (5.7, 7.2, and 5.8 to 7.7 gradient), PF dissolved more drug within 30 min than RF (p ≤ 0.019). Of note, the use of a 50 mM phosphate buffer pH 7.2 provided opposite results—RF dissolved the API much faster than PF. Moreover, 10 mM phosphate buffers of pH 5.6 and 7.2 could neither maintain a constant pH nor mimic the bicarbonate buffer performance. In conclusion, the use of a bicarbonate-buffered intestinal fluid, instead of phosphate buffers, may be essential in dissolution tests of BCS class II drugs combined with pH modulators.Graphical abstract

Histologic evaluation of dentin bridge formation by pachymic acid and biodentine in human tooth culture model

Histologic evaluation of dentin bridge formation by pachymic acid and biodentine in human tooth culture model

Dissolution Kinetics of Nifedipine-Ionizable Polymer Amorphous Solid Dispersion: Comparison Between Bicarbonate and Phosphate Buffers.

The intestinal fluid pH is maintained by the bicarbonate buffer system that shows unique properties regarding drug dissolution. Nevertheless, current compendial dissolution tests use phosphate buffers. The purpose of the present study was to investigate the effect of bicarbonate and phosphate buffers on the dissolution profiles of amorphous solid dispersions (ASD) composed of ionizable polymers. Hydroxypropylmethylcellulose acetate succinate (HPMCAS), amino methacrylate copolymer (AMC), and hydroxypropylmethylcellulose (HPMC) were employed as acidic, basic, and neutral polymers, respectively. Nifedipine (NIF) was used as a model drug. Dissolution profiles were measured in pH 6.5 bicarbonate and phosphate buffers by a mini-scale paddle dissolution test. The pH of bicarbonate buffers was maintained by the floating lid method. The pH change of the bicarbonate buffer was suppressed to less than + 0.25 pH for 3h by the floating lid method. In all cases, the NIF concentration was supersaturated against the solubility of crystalline NIF. The dissolution rates of HPMCAS and AMC ASDs were 1.5 to 2.0-fold slower in the bicarbonate buffer than in the phosphate buffer when compared at the same buffer capacity. The dissolution profile of HPMC ASD was not affected by the buffer species. The higher the buffer capacity and ionic strength, the faster the dissolution rate of HPMCAS ASD. The dissolution rate of ASDs with ionizable polymers would be overestimated by using unphysiological phosphate buffer solutions. It is important to use a biorelevant bicarbonate buffer solution for dissolution testing.

Spontaneous Alteration of Blood pH By a Bicarbonate Buffer System During Experimental Hypercalcaemia in Cows.

IntroductionMaintaining mineral homeostasis as well as the secretion and metabolism of mineralotropic hormones is important for healthy of periparturient dairy cows. To increase the activity of mineralotropic hormones, blood pH can be adjusted. The purpose of this study was to investigate changes in blood pH and the mechanism of action of this change in induced hypercalcaemic cows.Material and MethodsSix non-lactating Holstein cows were used in a 2 × 2 crossover design. To induce hypercalcaemia, calcium borogluconate was administered subcutaneously to experimental cows and normal saline was administered subcutaneously to control cows. Blood and urine samples were collected serially after administration. Whole blood without any anticoagulant was processed with a portable blood gas analyser. Plasma concentration and urinary excretion of calcium were measured.ResultsIn hypercalcaemic cows, both blood and urine calcium levels were significantly increased at 8 h compared to those at 0 h (P < 0.05), and a spontaneous increase in blood pH was also observed. The calcium concentration in plasma was highest at 2 h after administration (3.02 ± 0.27 mmol/L). The change in pH correlated with that in bicarbonate (r = 0.781, P < 0.001) rather than that in partial pressure of CO2 (r = 0.085, P = 0.424).ConclusionHypercalcaemia induced a spontaneous change in blood pH through the bicarbonate buffer system and this system may be a maintainer of calcium homeostasis.

Modeling the anaerobic digestion of wastewater sludge under sulfate-rich conditions.

Anaerobic digestion (AD) is a biological treatment process to stabilize organic solids and produce biogas. If present, sulfate is reduced to sulfide by anaerobic sulfate-reducing bacteria and the sulfide can be toxic to anaerobic microorganisms. Here, the effect of high initial sulfate concentration on AD of wastewater sludge was investigated using lab-scale batch experiments. Additionally, a systematic mathematical modeling approach was applied for insight into the experimental results. Cumulative biogas and methane production decreased with increasing initial sulfate doses (0-3.300mgSL-1 ). The correlation between the sulfate dose and methane production was consistent with theoretical predictions and model results, indicating no toxic effect of sulfide on methane production. The carbon dioxide content in the biogas decreased linearly with the increasing sulfate dose, which is consistent with the model-predicted behavior of the bicarbonate and hydrogen sulfide buffering system. The examined high sulfate concentrations resulted in no clear negative effects on the COD removal or VSS destruction of the wastewater sludge, indicating negligible inhibition by sulfide toxicity. Even considering the possibility of ferrous sulfide precipitation and the low model estimates of residual sulfide concentration the residual sulfide concentration was higher than reported concentrations that trigger process inhibition. PRACTITIONER POINTS: The effect of sulfate loading on anaerobic digestion of waste activated sludge was characterized. The stoichiometry of sulfate reduction allows accurate prediction of CH4 loss. High sulfate levels (up to 3300mg/L as S) did not affect COD/VSS removal. Sulfide formation increases effluent COD; often misinterpreted as sulfide toxicity. Correcting COD for sulfide's contributions is crucial for results interpretation.

The role of HIF proteins in maintaining the metabolic health of the intervertebral disc.

The physiologically hypoxic intervertebral disc and cartilage rely on the hypoxia-inducible factor (HIF) family of transcription factors to mediate cellular responses to changes in oxygen tension. During homeostatic development, oxygen-dependent prolyl hydroxylases, circadian clock proteins and metabolic intermediates control the activities of HIF1 and HIF2 in these tissues. Mechanistically, HIF1 is the master regulator of glycolytic metabolism and cytosolic lactate levels. In addition, HIF1 regulates mitochondrial metabolism by promoting flux through the tricarboxylic acid cycle, inhibiting downsteam oxidative phosphorylation and controlling mitochondrial health through modulation of the mitophagic pathway. Accumulation of metabolic intermediates from HIF-dependent processes contribute to intracellular pH regulation in the disc and cartilage. Namely, to prevent changes in intracellular pH that could lead to cell death, HIF1 orchestrates a bicarbonate buffering system in the disc, controlled by carbonic anhydrase 9 (CA9) and CA12, sodium bicarbonate cotransporters and an intracellular H+/lactate efflux mechanism. In contrast to HIF1, the role of HIF2 remains elusive; in disorders of the disc and cartilage, its function has been linked to both anabolic and catabolic pathways. The current knowledge of hypoxic cell metabolism and regulation of HIF1 activity provides a strong basis for the development of future therapies designed to repair the degenerative disc.

Using nutrient-rich solutions and adding multiple cytoprotective agents as new strategies to develop lung preservation solutions.

Commonly, donor lungs are preserved with low-potassium dextran glucose solution at low temperature. We hypothesized that adding nutrients and/or cytoprotective agents to preservation solutions improves donor lung quality. Human lung epithelial cells and human pulmonary microvascular endothelial cells cultured at 37°C with serum containing medium were switched to designated testing solutions at 4°C with 50% O2 for different cold ischemic time, followed by switching back to serum containing culture medium at 37°C to simulate reperfusion. We found that bicarbonate buffer system should be avoided in preservation solution. When pH was maintained at physiological levels, cell culture media showed better cell survival than in low-potassium dextran glucose solution. Phosphate-buffered cell culture media were further improved by adding colloid dextran 40. When rat donor lungs were preserved at 4°C for 24 h, phosphate-buffered Roswell Park Memorial Institute-1640 medium [RPMI-1640(p)] plus dextran 40 or adding cytoprotective agents (alpha 1 antitrypsin, raffinose, and glutathione) to low-potassium dextran glucose solution prevented alveolar wall swelling, apoptosis, activation of endothelial cells, and cellular edema. Using nutrient-rich solution and/or adding multiple cytoprotective agents is a new direction for designing and developing organ preservation solutions. Cell culture model, as a screening tool, reduces the use of animals and provides potential underlying mechanisms.

Simple bicarbonate buffer system for dissolution testing: Floating lid method and its application to colonic drug delivery system

In this study, we developed a simple and easy method to use bicarbonate buffer solutions for dissolution tests. A floating lid was newly introduced to prevent the evaporation of CO2 from bicarbonate buffer solutions (the floating lid method). This method was used to evaluate the dissolution profiles of 5-aminosalicylic acid (5-ASA) colonic delivery tablets with a pH-sensitive film coating (5-ASA CDT) (Asacol® 400 mg tablet and the generic products A and B). A sodium bicarbonate solution was added to the dissolution test vessel, covered with the floating lid made of foamed styrol, and adjusted to each pH with an HCl solution (total 500 mL, 2–50 mM, pH 6.0 to 7.5). Without the floating lid, the pH value increased by more than one pH unit within 3.5 h. The floating lid suppressed the increase in pH to less than 0.1 pH unit at 3.5 h and 0.7 pH unit at 22 h. According to the drug product information, all 5-ASA CDTs show similar disintegration times (approximately 0.5 h) and release profiles in the diluted McIlvaine buffer (pH 7.5, 50 mM phosphate, 25 mM citrate). However, in the bicarbonate buffer (pH 7.5, 10 mM), the disintegration time was prolonged to 4.3 h for Asacol®, 8.0 h for generic A, and 7.6 h for generic B. The floating lid method would be useful for formulation development.

Effect of Carbohydrate-Electrolyte Solution Including Bicarbonate Ion Ad Libitum Ingestion on Urine Bicarbonate Retention during Mountain Trekking: A Randomized, Controlled Pilot Study.

We investigated whether bicarbonate ion (HCO3−) in a carbohydrate-electrolyte solution (CE+HCO3) ingested during climbing to 3000 m on Mount Fuji could increase urine HCO3− retention. This study was a randomized, controlled pilot study. Sixteen healthy lowlander adults were divided into two groups (six males and two females for each): a tap water (TW) group (0 kcal with no energy) and a CE+HCO3 group. The allocation to TW or CE+HCO3 was double blind. The CE solution contains 10 kcal energy, including Na+ (115 mg), K+ (78 mg), HCO3− (51 mg) per 100 mL. After collecting baseline urine and measuring body weight, participants started climbing while energy expenditure (EE) and heart rate (HR) were recorded every min with a portable calorimeter. After reaching a hut at approximately 3000 m, we collected urine and measured body weight again. The HCO3− balance during climbing, measured by subtracting the amount of urine excreted from the amount of fluid ingested, was −0.37 ± 0.77 mmol in the CE+HCO3, which was significantly higher than in the TW (−2.23 ± 0.96 mmol, p < 0.001). These results indicate that CE containing HCO3− supplementation may increase the bicarbonate buffering system during mountain trekking up to ~3000 m, suggesting a useful solution, at least, in the population of the present study on Mount Fuji.

4081 Quantifying pH buffering capacity and kinetics of tumor and healthy tissue to understand and exploit differences in biology

OBJECTIVES/GOALS: The purpose of this work is to investigate natural buffering capacity of liver tissue and tumors, to understand and exploit differences for therapy. Using this work, we will determine the concentrations of reagents (acids or bases) used in ablation treatment to optimize treatment by increasing tumor toxicity and minimizing healthy tissue toxicity. METHODS/STUDY POPULATION: For this preliminary study, two methods will be used: benchtop pH experiments ex vivo and non-invasive imaging using acidoCEST MRI in vivo. For ex vivo, two types of tissues will be tested: non-cancerous liver and tumor tissue from HepG2 inoculated mice (n = 10). After mice are euthanized, pH will be measured in tissue homogenates at baseline and then the homogenates will be placed in either acidic (acetic acid) or basic (sodium hydroxide) solutions with varied concentrations (0.5–10M) and time recorded until pH returns to baseline. For in vivo imaging, Mia PaCA-2 flank model mice (n = 10) will be imaged with acidoCEST MRI to quantify pH at baseline. Mice will then be injected intratumorally with (up to 100 μL of) acid or base at increasing concentrations and imaged to quantify pH changes in the tumor. RESULTS/ANTICIPATED RESULTS: For this study, buffering capacity is defined as the concentration threshold for which tissue can buffer pH back to within normal range. Non-cancerous tissue is likely to buffer a wider range of concentrations compared to tumor tissue. From the benchtop experiment, comparison of time-to-buffer will be made for each concentration of acid/base for the two tissue types. AcidoCEST MRI will provide in vivo buffering capacity and potentially demonstrate tumor heterogeneity of buffering capacity. For both experiments, a pH vs. concentration curve for the two tissue types will allow for comparison of ex vivo to in vivo experiments, which will differentiate contributions of local tissue buffering capacity from the full body’s natural bicarbonate buffer system that depends on respiration and blood flow. DISCUSSION/SIGNIFICANCE OF IMPACT: The pH of the body must be maintained within a narrow range. With cancer, impairment in regulation of tumor metabolism causes acidosis, lowering extracellular pH in tumors. It remains unclear if pH plays a role in local recurrence or tumor toxicity. This work will determine if acidoCEST MRI can measure deliberate alteration of pH and how this change affects biology.

Çuha Çiçeği (Oenothera biennis) ve Tatlı Badem (Prunus dulcis Mill) Yağlarının Anti-enzim Aktivitelerinin Araştırılması

In our study, the question of what might be the effects of Primrose (Oenothera biennis) and sweet almond (Prunus dulcis Mill.) oils on two different enzyme activities was asked. The first enzyme in our study is carbonic anhydrase I-II isoenzymes that play a very important role in many physiological events, by transforming catalysis of CO2 hydration and HCO3-dehydration in living things, by creating an intracellular bicarbonate buffer system. The second enzyme, the acetylcholinesterase enzyme, which was located in the synapse between the muscle cell and nerve, catalyzes the decomposition of the acetylcholine molecule. Inhibitors of both enzymes have the potential to be drugs. Therefore, the inhibition effect of the specified oils was investigated. For this purpose, the first carbonic anhydrase I-II isoenzyme was purified by the sepharose-4B-L tyrosine-sulfonamide affinity column. Then, by looking at enzyme activity in at least five different inhibitor concentrations, effects of evening primrose (Oenothera biennis) and sweet almond (Prunus dulcis Mill.) oils on enzyme activities were investigated. Finally, IC50 values of Primrose (Oenothera biennis) and sweet almond (Prunus dulcis Mill.) oils were determined by drawing activity%-[I] graph. Carbonic anhydrase I isoenzyme was purified from human erythrocytes 119 times in 20.12% yield, while carbonic anhydrase II isoenzyme was purified 535.72 times in 83.05% yield. IC50 values of the primrose oils (Oenothera biennis) on carbonic anhydrase I-II and acetylcholinesterase enzyme activity were 0,1950, 0,1406 and 0,1097 mg / mL, respectively. IC50 values of the sweet almond oil (Prunus dulcis Mill.) on carbonic anhydrase I-II and acetylcholine esterase enzyme activity were 0.0345, 0.0266 and 0.0394 mg/mL respectively. When both oils used in the study are compared, we see that sweet almond oil (Prunus dulcis Mill.) is more effective on both enzyme activities. Therefore, instead of synthetic drugs, sweet almond (Prunus dulcis Mill.) oil is thought may be used as a supplement in the treatment of diseases caused by the enzymes in question.

What is the extent of water brownification in Lake Onego, Russia?

In the past 26 years the transport of allochthonous matter into Lake Onego has increased. Water brownification in Petrozavodsk Bay, a northwestern bay in Lake Onego, and in the Shuya River, a tributary of the bay, was shown earlier to begin in spring. The goal of this paper was to find out whether brownification spreads from Petrozavodsk Bay to the central part of the lake in summer. Spearman’s correlation coefficient and linear correlation coefficient confirm a significant (p < 0.05) increase in water color in Petrozavodsk Bay in the summers of 1992–2018. A tendency for increasing water color was found in the Central Onego’s epilimnion. Total iron and CO2 concentrations in the epilimnion have increased and pH values have decreased both in Petrozavodsk Bay and in the Central Onego. In the Central Onego’s hypolimnion, only total iron and CO2 concentrations have considerably increased. However, the present lake ecosystem is resistant to the increased effect of allochthonous matter due to long water renewal time and self-purification. In spite of a significant increase in CO2 concentration in the lake water, the bicarbonate buffer system maintains the acid-base equilibrium and the changes revealed are not considered critical for the ecosystem.