Henderson-Hasselbalch Research Articles

PH Determination of Acetic Acid-Sodium Acetate Buffer: An Application of Henderson-Hasselbalch Equation at Room Temperature

In article, we have reported the applying of Henderson-Hasselbalch equation in determination of pH of acetic acid and sodium acetate buffer solutions at about 298 Kelvin as room temperature. In preparation of these buffer solutions, we have taken 1.5 ml of glacial acetic acid into 100 ml of standard flask for making up 0.2M of acetic acid solution, and 0.64 gm of sodium acetate were dissolved into 100 ml distilled water. Now, we taken 36.2 ml prepared solution of sodium acetate into 100 ml of standard flask and added 14.8 ml of prepared acetic acid to make its volume 100 ml by using of distilled water, it is a buffer. In measuring of pH of prepared buffer solutions, we have been using a calibrated digital pen pH meter for accurate and quick reading. In observation, the pH of buffer solutions a quite fluctuation was appeared. But, it has gradually raised by adding small amount of basic 5N NaOH solution into buffer sample, and, an adjusted pH was being to 4.7 as well.

8226 A Diagnostic Challenge: Factitious Hypobicarbonatemia in Severe Hypertriglyceridemia

Abstract Disclosure: U. Rafat: None. S. Azmat: None. M. Siddiqui: None. R. Alshantti: None. D. Kircheva: None. V. Trendafilova: None. Background: Serum CO2 levels measured by a chemistry analyzer usually correlate with calculated bicarbonate levels on an ABG. There are some instances however, when this is not the case. Severe hypertriglyceridemia can cause serum bicarbonate levels to appear falsely low on metabolic panel. Clinical Case: A 48-year-old man was referred to Endocrinology Clinic for evaluation of hypogonadism and severe hypertriglyceridemia. Routine labs revealed a plasma CO2 of 11 mmol/L (20-31). Na was 133 mmol/L (136-145), K was 4.4 mmol/L (3.5-4.7), Chloride was 101 mmol/L (98-109) and anion gap was 25 (8-20) measured using a Siemens Vista enzymatic chemistry analyzer. His triglycerides were > 1100 mg/dL (0-150), above upper detection limits of the analyzer. The patient reported fatigue and mild abdominal pain. He was admitted to the hospital for further evaluation. His lipase was 41 U/L (12-73), lactic acid 1.2 mmol/L (0.50-2.20). ABG showed pH of 7.41, HCO3 of 26.6 mmol/L (22-29), and anion gap of 7 (10-20). The patient was well-appearing with normal vital signs and normal physical exam. He was made NPO and started on pravastatin, fenofibrate and fish oil. Once his triglycerides were < 1000 mg/dL, he was started on a very low-fat, low-carbohydrate diet. The CO2 level on BMP normalized on day 3 of hospitalization, when triglycerides measured 1010 mg/dL. No other treatment was given for the low CO2 levels. It does not appear that other lab indices were significantly affected by the hypertriglyceridemia. Review of Literature: A BMP measures serum total carbon dioxide using a chemistry analyzer using either an enzymatic/spectro-photometric method, or an electrode-based method; an ABG sample calculates plasma bicarbonate with the Henderson-Hasselbach equation, using the pH and partial pressure of pCO2 in the sample. Enzymatic analyzers measure CO2 using spectrophotometry and decrease in light absorbance is proportional to the sample’s CO2 levels. It is postulated that severely high triglycerides can interfere with this reaction and cause spuriously low CO2 levels, a phenomenon called pseudohypobicarbonatemia. One proposed mechanism for interference with the enzymatic assay method is turbidity causing a falsely low measured CO2 level. Verghese et al found that the severity of the CO2 measurement error positively correlates with the severity of triglyceride elevation. Conclusion: Awareness of the phenomenon of hypertriglyceridemia-induced pseudohypobicarbonatemia can prevent misdiagnosis or delays in diagnosis, as well as unwarranted testing and treatment. Presentation: 6/3/2024

A-333 Comparison between measured total carbon dioxide and calculated bicarbonate in hospitalized patients

Abstract Background Bicarbonate (HCO3-) is a key indicator of anion excess or deficit and important clinically for assessing acid-base balance. For patient care, HCO3- may be reported as a calculated value from blood gas analysis or measured on automated chemistry analyzers. When measured, the final result includes HCO3-, carbonate (CO32-) and carbamino compounds and thus is reported as total CO2 (TCO2). Anecdotally, some patients have discrepancies between HCO3- and TCO2. However, there is limited data in the published literature assessing agreement between the two methods. Our study aims to compare the calculated HCO3- values with measured TCO2 obtained from simultaneously collected clinical specimens. Methods This study included all results from physician ordered HCO3- and TCO2 between 01/2019 to 12/2020 retrospectively retrieved from the laboratory information system (Cerner). Specimens were collected by nursing staff within 5 minutes of each other. TCO2 was assessed on a Roche cobas 702 (CV = 4.2%) according to the manufacturer’s instructions using an enzymatic phosphoenolpyruvate carboxylase method in lithium heparin tubes. HCO3- was calculated using a Radiometer ABL800 blood gas analyzer from arterial or venous blood gas samples according to the manufacturer’s instructions. Briefly, HCO3- is calculated using the Henderson-hasselbalch equation and the measurement of PCO2 (CV= 1.75%), and pH (CV = 0.06%). Deming regression was performed. The CLIA total allowable error of 4 mmol/L and a reference change value (RCV, Cv Individual = 4%) of -13 and + 14 for TCO2 was used to assess agreement. All data was analyzed in R. Results There were 101,895 paired HCO3- and TCO2 results during the study period. The values ranged from 4 to 56 mmol/L and the mean was 25.7. The mean difference between the calculated HCO3- and measured TCO2 was 1.33 mmol/L. Relative to HCO3-, there were 2,119 (2.1%) TCO2 results with a negative bias exceeding 4 mmol/L and 427 (0.4%)[FC1] with a positive bias exceeding 4 mmol/L. Twenty-two samples exceeded the positive RCV of 14% and 22 samples exceeded the negative RCV. Deming regression revealed a slope of 1.09 (95% CI: 1.087-1.092) an intercept of -2.19 (-2.18 to -2.06), and a Pearson correlation of 0.960 (0.959 to 0.960). We also analyzed differences between HCO3- and TCO2 in arterial and venous samples. The Pearson r for venous samples was 0.956 (0.955 to 0.957) and for arterial samples was 0.966 (0.966-0.966). Deming regression revealed a slope of 1.099 (0.195 to 1.104) and 1.071 (1.068 to 1.074) for venous and arterial samples respectively. The intercept for venous samples was -1.441 (-1.559 to -1.324) and for arterial was -2.005 (-2.072 to -1.938). Conclusions There is bias between HCO3- calculations and TCO2 measurements in simultaneously drawn samples. A small proportion of samples (2.5%) exceed the CLIA total allowable error between the results but very few exceed the RCV. This may due to differences in matrices, with different correlations and slopes observed between arterial and venous specimens. Further studies are required to distinguish the causes of the observed differences between HCO3- and TCO2.

Metabolic alkalosis: a new red flag in status epilepticus

BackgroundStatus epilepticus (SE) is a heterogeneous neurological emergency with significant variability in prognosis, influenced by underlying disease and pathophysiological context. Acid–base disturbances are common in critically ill patients, yet their distribution and impact in SE patients remain poorly understood.MethodsThis was an observational cohort study including non-hypoxic SE patients with available blood gas analysis within the first 24 h of SE, treated at the University Hospital of Geneva, Switzerland between 2015 and 2023. Acid–base disturbances were classified using the Henderson–Hasselbalch equation, with prevalent metabolic alkalosis confirmed through the Stewart approach. Primary outcomes were in-hospital mortality, Glasgow Outcome Scale (GOS) at discharge, and return to premorbid neurologic function.FindingsAmong 540 SE patients, 365 were included. Half of patients exhibited acid–base disturbances within the initial 24 h of SE, with metabolic and respiratory acidosis being the most prevalent, though not prognostically significant. After correction for possible confounders, metabolic alkalosis (6%) was associated with increased in-hospital mortality (P = 0.011; OR = 4.87, 95% CI = 1.29–7.84), worse GOS (P = 0.012; OR = 3.18, 95% CI = 1.29–7.84), and reduced likelihood of returning to premorbid function (P = 0.017; OR = 3.30, CI95% = 1.24–8.80). Following the Stewart approach, 9% of patients had predominant metabolic alkalosis, associated with worse GOS (P = 0.005; OR:3.37, 95%CI = 1.45–7.82), and reduced chance of returning to baseline (P = 0.012; OR = 3.29, CI95% = 1.30–8.32). Metabolic alkalosis was related to hypoalbuminemia and lower serum potassium.ConclusionMetabolic alkalosis strongly predicts mortality and adverse functional outcome in SE patients. Prospective studies should assess whether early detection and correction of metabolic alkalosis and related electrolyte imbalances can improve SE prognosis.

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.

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.

Determination of ionization/protonation constant values of some guanine derivative drugs by traditional/ green RPLC and UV–Vis spectrophotometric methods

In this study, the greenreverse-phase liquid chromatography (RPLC) method was used in addition to the traditional RPLC method to determine the ionization/protonation constants (pKa) of the guanine derivatives ganciclovir, valacyclovir, and valganciclovir. The determination of these values was carried out in binary acetonitrile–water mixtures (for the traditional RPLC method), ethanol–water binary mixtures (for the green RPLC method), and in aqueous solution of a micelle-forming surfactant (for pure micellar chromatography). The pKa values sspKa of the compounds were calculated using the linear solvation energy relationship (LSER) method in the studied hydro-organic and micellar solvent-free mixtures. Moreover, the UV–Vis spectrophotometric method was used to compare the sspKa values of ganciclovir, valaciclovir, and valganciclovir obtained in a acetonitrile–water medium using another method. The pKa values ​​of the examined compounds in water were calculated using the linear relationship between the sspKa values ​​determined in hydroorganic mixtures and some macroscopic values ​​of acetonitrile and ethanol. Additionally, wwpKa values ​​were determined in the micellar solvent-free mobile phase. Subsequently, the wwpKa values calculated by these direct and indirect methods were compared and the agreement between them was excellent. By using the wwpKa value calculated for each compound, the ionization percentages were calculated at different pH (1–12) values with the Henderson-Hasselbalch equation. The environmental impact of the RPLC methods used in this study was assessed using the green metrics tools GAPI and AGREE. The result of the investigation was that the environmental suitability of the green methods is satisfactory.

C.I. Acid Black 1 transfer from dilute solution to perlite framework in organic waste management

Dyes, considered as toxic and persistent pollutants, must be removed from organic wastes prior to their composting and application in sustainable agriculture. Azo dyes, capable of altering the physicochemical properties of soil, are difficult to expel by conventional wastewater treatments. C.I. Acid Black 1 (AB 1), a sulfonated azo dye, inhibits nitrification and ammonification in the soil, lessens the nitrogen use efficacy in crop production and passes substantially unaltered through an activated sludge process. The retention of C.I. Acid Black 1 by raw and expanded perlite was investigated in order to examine the potential effectiveness of this aluminosilicate material toward organic waste cleanup. Dye adsorption proved spontaneous and endothermic in nature, increasing with temperature for both perlites. Expanded perlite having a more open structure exhibited a better performance compared to the raw material. Several of the most widely recognized two-parameter theoretical models, i.e., Langmuir, Freundlich, Temkin, Brunauer–Emmett–Teller (BET), Harkins–Jura, Halsey, Henderson, and Smith, were applied to reveal physicochemical features characterizing the adsorption. The Langmuir, Freundlich, Temkin, BET, Henderson, and Smith equations best fitted experimental data indicating that the adsorption of anionic dye on perlites is controlled by their surface, i.e., non-uniformity in structure and charge. This heterogeneity of surface is considered responsible for promoting specific dye adsorption areas creating dye “islands” with local dye supersaturations.

Apical pH regulates calcium-activated chloride secretion across human airway epithelia

Anion secretion across airway epithelia contributes to host defense by increasing airway surface liquid (ASL) volume and pH. Anion channels in the apical membrane of airway epithelia include Ca2+-activated Cl− channels (CaCCs) and cystic fibrosis transmembrane conductance regulator (CFTR) channels. Mutations in the CFTR gene that encode nonfunctional CFTR channels cause cystic fibrosis (CF); thus, activating CaCCs may restore anion secretion in people with CF. ATP secreted into the ASL activates purinergic receptors, leading to an increase in intracellular Ca2+ (Cai2+) and the opening of CaCCs. Data from docking simulations suggest that the protonation state of ATP influences its affnity for purinergic receptors, therefore we tested the hypothesis that ASL pH influences the effcacy of ATP to activate CaCCs in airway epithelia. In saline solutions buffered with 5 mM ATP, titration experiments revealed a pKa of ~6.9 at 37°C. Thus, ATP exists in its protonated ATP3− and deprotonated ATP4− in ASL that can range from pH 6 to pH 7.5. To determine the effect of pH on ATP-stimulated Cl− secretion through CaCCs, we measured Cl− secretion across CF epithelia generated by several ATP concentrations with apical pH-6.00, -6.70, and -7.40 solutions. As pH became alkaline, the EC50 for the relationship between [ATP] and Cl− secretion decreased. Using the Henderson-Hasselbalch equation and the pKa for ATP, we determined the relationship between ATP4− and Cl− secretion. This analysis revealed that regardless of apical pH values, the relationship between [ATP4−] and Cl− secretion aligned to a single experimental fit. These data suggest that pH regulates the CaCC response by deprotonating ATP. To examine the pH dependence of purinergic receptor activation, we measured ATP-induced Cai2+ responses in acutely dissociated human airway epithelial cells loaded with FURA-2 and perfused with pH-7.40 or -6.50 solutions. Separate experiments measuring intracellular pH in pH-7.40 or 6.50 solutions informed Kd values for FURA-2 experiments. With an [ATP] that induces similar levels of Cl− secretion from pH 6.00 to pH 7.40 (100 μM ATP), we observed similar Cai2+ responses for pH-7.40 and -6.50 solutions. However, when we repeated the experiment with an [ATP] that induces pH-sensitive Cl− secretion (10 μM ATP), we observed larger Ca2+ responses with pH-7.40 solutions than with pH-6.50 solutions. These data indicate that pH influences purinergic receptor activation near the pKa of ATP, a finding consistent with ATP4− activating purinergic receptors. These data have implications in CF and airway inflammation. In CF, decreased CFTR-mediated HCO−3 secretion acidifies the ASL, thus a large portion of ATP will exist in the protonated ATP3− species requiring a higher total [ATP] to open CaCCs. Inflammatory cytokines that cause airway inflammation increase the ASL pH, therefore a larger portion of ATP will exist in the deprotonated ATP4− species requiring less total [ATP] to open CaCCs. Cystic Fibrosis Foundation Research Development Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Bicarbonate assay comparison of ezymatic method and Henderson Hasselbalch method

Bicarbonate assay comparison of ezymatic method and Henderson Hasselbalch method

A versatile look-up algorithm for mapping pH values and magnesium ion content using 31P MRSI.

31P MRSI allows for the non-invasive mapping of pH and magnesium ion content (Mg) in vivo, by translating the chemical shifts of inorganic phosphate and adenosine-5'-triphosphate (ATP) to pH and Mg via suitable calibration equations, such as the modified Henderson-Hasselbalch equation. However, the required constants in these calibration equations are typically only determined for physiological conditions, posing a particular challenge for their application to diseased tissue, where the biochemical conditions might change manyfold. In this article, we propose a multi-parametric look-up algorithm aiming at the condition-independent determination of pH and Mg by employing multiple quantifiable 31P spectral properties simultaneously. To generate entries for an initial look-up table, measurements from 114 model solutions prepared with varying chemical properties were made at 9.4 T. The number of look-up table entries was increased by inter- and extrapolation using a multi-dimensional function developed based on the Hill equation. The assignment of biochemical parameters, that is, pH and Mg, is realized using probability distributions incorporating specific measurement uncertainties on the quantified spectral parameters, allowing for an estimation of most plausible output values. As proof of concept, we applied a version of the look-up algorithm employing only the chemical shifts of γ- and β-ATP for the determination of pH and Mg to in vivo 3D 31P MRSI data acquired at 7 T from (i) the lower leg muscles of healthy volunteers and (ii) the brains of patients with glioblastoma. The resulting volumetric maps showed plausible values for pH and Mg, partly revealing differences from maps generated using the conventional calibration equations.

Abstract B014: The number analysis of digital data in Nature’s ecosystem: The unified general dynamics theory of “Unity of One” and its fractional distribution, action and interaction principle, and algorithms for computerized translational informatics

Abstract Nature’s ecosystem is governed by the physical and chemical principle of the mass-action law (MAL). The conventional classical specific aimed observation/statistics-based scientific R&D is considered a “Bottom-Up” approach. Here, this author introduces a new mathematical approach that established the MAL-unified general dynamics theory-based “Top-Down” algorithms of scientific translational, computerized simulation for Econo-green R&D. The new math approach evoked the general system analysis with sequential, pattern, combinatorial analysis, and mathematical induction and deduction, which is distinct from the aim-specific derivation of Michaelis-Menten, Henderson-Hasselbalch, Hill, Scatchard, and Langmuir theoretical equations. In short, the unified MAL-based biodynamics, pharmacodynamics, and bio-informatics (BD/PD/BI) include three general equations/algorithms for Unity of One Theory (UOT): (i) For action, the median-effect equation (MEE), also called the doctrine of the median (DOM), where the median-effect dose (Dm) is the universal reference of action potency and the dynamic-order (m) common-link in which m=1, >1, <1 indicates hyperbolic, sigmoidal and flat sigmoidal, respectively for dose-effect curves (DEC); (ii) For interaction, the combination-index equation (CIE), in which CI=1, <1, and >1 quantitatively indicates additive-effect, synergism, and antagonism, respectively; (iii) For the consequence of interaction, the dose-reduction index equation (DRIE), in which DRI=1, >1 and <1, digitally defines no-dose-reduction, favorable, and not favorable dose-reduction, respectively. The linearization of DECs with the MEE plot (MEP) led to the minimum two dose-data points theory (MTDPT), which provides efficient, cost-effective, Econo-green scientific R&D in biomedical sciences such as in molecules, cells, tissues, organs, whole body, and clinical protocol design and data analysis/simulation in the general R&D, in which 2 becomes 4, 3 become 5, and 4 becomes 6 dose-data points. The automatically added default two data points in the algorithm are dose zero and Dm-dose in all dynamic studies, designs, and dynamic simulations. The most important feature of the MAL-dynamics and informatics theory is that all mathematical terms of MEE, CIE, and DRIE are dimensionless relativity ratios, thus ensuring universal applicability regardless of units, physical states, and mechanisms. As of September 11, 2023, the MAL-BD/PD/CI/BI theory, algorithm, and computer software have been cited in over 1,550 scientific journals and 1,188 patents, indicating broad applications in scientific R&D and patent discovery. These citations encompass biomedical, agricultural, environmental, marine, physical, and food sciences. The effectors can be nanoparticles, molecules, chemicals, biologicals, radiation, UV, microwave, thermal, and photo effects, or their mix. Relevant details are available at HTTPS://www.combosyn.com; DOI:10.1016/j.jbc.2023.103419, and dx.doi.org/10.1124/jpet.122.185320. Citation Format: Ting-Chao Chou. The number analysis of digital data in Nature’s ecosystem: The unified general dynamics theory of “Unity of One” and its fractional distribution, action and interaction principle, and algorithms for computerized translational informatics [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B014.

PHASE CONCENTRATION EQUILIBRIUM DURING DRYING COLLOID CAPILLARY-POROUS MATERIAL - PEA

In this work, we studied experimentally the phase concentration equilibrium during drying of a colloidal capillary-porous material - peas. The studies were carried out by a static (exsicator) method using saturated aqueous solutions of mineral salts, with the help of which certain relative air humidity was created in the desiccators. To establish equilibrium, the samples were kept in desiccators for one month. The values of relative air humidity over salt solutions at the corresponding temperatures were found from the well-known Schneider diagram. Moisture desorption isotherms were determined, for which high-moisture pea samples were placed in exsicators. The experiments were carried out at three temperatures: 30, 40 and 50 °C. According to the measurement data, moisture desorption isotherms were constructed in the coordinates "relative air humidity - equilibrium moisture content of the material." The resulting desorption isotherms were described by the Henderson equation, for which the values of the coefficients of this equation were found and their statistical evaluation was given. The data on the balance of peas were compared with similar data for other plant colloidal capillary-porous materials: vegetables (carrot and beet cuts), grain crops (rye, wheat and corn grains), and vegetable seeds. A significant influence of the type of culture on the equilibrium moisture content of the material during drying is shown, while the intraspecific influence on the equilibrium moisture content is less important. The obtained data on moisture desorption isotherms during drying can be used for engineering calculations of the kinetics of drying pea grain and for choosing the temperature and humidity conditions for its storage after drying.

Abstract LB_B20: The Unity Theory of One: The dynamic algorithm of mass action law for drug and biosimilar digital evaluation/simulation in molecules, cells, and organs, regardless of units, physical states, and mechanisms

Abstract Mathematical analysis of mass-action law (MAL) of the intermediate-forming system analysis led to the general median-effect equation (MEE) for action dynamics that determines potency (Dm, median-effect dose, and dynamic order [m, the shape of dose-effect-curve (DEC) where m=1, >1, <1 indicate hyperbolic, sigmoidal and flat sigmoidal, respectively]; the combination index equation (CIE) for interaction that quantifies synergism (CI<1), additive effect (CI=1) and antagonism (CI>1); and the dose-reduction index equation (DRIE) for interaction consequences, where DRI=1, >1 and <1 indicate no dose-reduction, favorable dose-reduction, and unfavorable dose-reduction. All terms of MEE, CIE, and DRIE are dimensionless relativity ratios, thus ensuring the general applicability of MAL. Therefore, the MAL biodynamics, pharmacodynamics, and bioinformatics (MAL-BD/PD/BI) is the top-down fundamental theory-based R&D, which approach is different from the classical observation/statistics-based bottom-up R&D. The MEE, CIE, and DRIE all center on “One” (the Unity Theory of One) (UTO), which are not feasible to derive from the classical specific-aimed derivations, such as Michaelis-Menten, Henderson-Hasselbalch, Hill, Scatchard, and Langmuir equations. The most important extensions and utilities of AML-MEE/CIE are the linearization of DECs with the median-effect plot (MEP) that led to the Minimum Two-dose Data Point Theory (MTDPT), which automatically adds two default data points to DECs (Do, dose-zero, and Dm, the universal reference point and the dynamic-orders common link). Thus, 2 becomes 4, 3 becomes 5, and 4 becomes 6 doses. This discovery allows digital quantitative, simple, efficient, cost-effective, Econo-Green biomedical R&D and drug evaluation of unified regulatory guidance. This MAL-theoretical approach is particularly beneficial in animal studies, clinical trial protocol design, and computerized analysis/simulation. The MAL-theoretical approach (MEE and CIE) was introduced by Chou and Talalay (1984), then by a Review article by Chou (2006) and a Perspective article (2006). Based on the bibliometrics by Web of Science and Google Scholar, as of August 26, 2023, these three articles have been cited 8,020, 5,194, and 5,129 times in 1,523, 1,242, and 1,157 journals internationally. The MAL-BD/PD/CI/BI is an Econo-green complementary alternative to traditional bottom-up studies. The MAL dynamics and informatics have been cited by 1,184 patents and by thousands of research grants sponsored by international governmental institutions, including USA (NIH, NCI, NCATS, NSF, and FDA), EU (Euro. Reginal Develop. Fund), China (Natl Key R&D), Japan (Soc. of Promotion of Sci), Korea (Natl. Sci. Foundation), Germany (Deutsch Fortungsgemeinschaft), France (INSERM), England (MRC), etc. The MAL-BD/PD/CI BI dynamics and informatics provide a new avenue for efficient and cost-effective translational and precision medicine and beyond, including environmental, agricultural, marine, material, biophysical, radiation, and food sciences. Citation Format: Ting-Chao Chou. The Unity Theory of One: The dynamic algorithm of mass action law for drug and biosimilar digital evaluation/simulation in molecules, cells, and organs, regardless of units, physical states, and mechanisms [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_B20.

Simulated warming decreases acidity of forest topsoil under Norway spruce (Picea abies (L.) H.Karst.) stands in the Western Carpathians

Global warming is affecting the montane forests of the temperate zone, causing a number of changes in all elements of the ecosystem, including the soil. Norway spruce forests, weakened by ongoing decay over several decades, are likely particularly sensitive to climate-induced changes. The response of soil cation exchange capacity components of spruce stands to warming is not well understood. We have assumed that warming will cause significant changes in pH, disrupting ion-exchange relationships in the soil. To the best of our knowledge, the present study is the first devoted to examining the mechanisms of soil pH change in temperate forest under the influence of warming. The forest in-situ experiment, simulating the soil warming for 578 days, was performed. Laboratory analyses included measurements of pH, and concentrations of carbon and exchangeable forms of calcium, potassium, magnesium, sodium, and aluminum. Shortly after the beginning of simulated warming (84 days), we observed a significant increase in the pH of the topsoil horizons. On average, in the warmed organic (O) horizon, the pH increased by 0.21, and in the mineral (A) horizon by 0.29 pH units. Based on previous studies, the pH increase was most likely triggered by an increase in ammonium-nitrogen content in the warmed soil. Using the Henderson–Hasselbalch equation to model the pH revealed that, in the O horizon, the pH increase is a result of the presence of weaker organic acids, less able to release hydrogen ions during dissociation. In the A horizon, the increase in pH was explained by an increase in abundance of aluminum ions, probably migrating upward from deeper soil layers. We consider that the ion-exchange mechanisms described here will contribute to an improved understanding of the complex processes of spruce forest dieback in the context of climate warming.

Characterization of physiochemical parameters & their effect on microbial content of smokeless tobacco products marketed in north India.

Smokeless tobacco (SLT) product consumption has profound public health implications for its users. The p H and moisture of SLTs determine the bioavailability of nicotine, the microbial structure dynamics and the amount of microbial conversion of tobacco alkaloids to carcinogenic tobacco-specific nitrosamines. This study aimed to characterize and compare the p H, moisture and alkaloid content of various SLT products. Thirty-seven SLT samples including khaini , snus, moist snuff, gul , pan masala , zarda , Mainpuri kapoori and qiwam were collected from the retail market around the National Capital Region in north India and their p H, moisture, nicotine and alkaloid content were measured. The p H and total nicotine were used to calculate the amount of free nicotine, the readily absorbed form, for each product by applying the Henderson-Hasselbalch equation. The investigation showed that the SLTs varied drastically in their p H (5.36 to 10.27), moisture content (4.7 to 51.7%) and alkaloid content (0.82 to 35.87 mg/g). The p H and free nicotine levels of a product were found to be positively correlated, and the highest free nicotine content was reported in snus samples. Further, the moisture content was seen to impact the bacterial and fungal diversity in these samples. Studies to detect the presence of pathogenic microbiological genera as well as potentially toxic constituents are warranted. The use of SLTs as an alternative to cigarette smoking should be discouraged, and cessation programmes must call attention to their detrimental effects and emphasize on benefits of quitting SLT consumption.

Student exploration of the Henderson-Hasselbach equation and pH readings to determine the pK a value of 4,4′-trimethylenedipiperidine (TMDP)

Abstract This educatory experiment uses an inexpensive pH meter to determine an approximate negative logarithm of the acid dissociation constant (pK a ) value of 4,4′-trimethylenedipiperidine (TMDP). Using a pH meter and statistical data analysis by Excel tool presents an excellent opportunity to deepen student engagement with the Henderson-Hasselbalch equation and acid/base dissociation constant (K a /K b ). Furthermore, students understand the importance determination of K a /K b and its relationship with the concentration and strength of acid/base. Four different concentrations of TMDP aqueous solutions were prepared and a series of pH readings were collected using a calibrated pH meter. Some statistical parameters were calculated and analyzed using the statistical program in Excel. Finally, students identified an unknown pK a for TMDP and compared their obtained value with a predicted pK a using software like ChemAxon. The experiment is inexpensive, safe, simple, and clean, and less experienced students can perform it. In addition, all pH recordings can be readily accessible for analysis and descriptive statistics by the Excel formula.

Growth/no-growth models of propionic and sorbic acid for bread and cake moulds

Propionic and sorbic acid are very effective weak-organic acid preservatives in bakery products. Their pH-dependent antifungal activity, the role of undissociated acid and the importance of the aqueous phase was studied. Besides looking for new natural preservation techniques the gain of further knowledge on their activity is still highly relevant to tackle the problem of food waste. In this study, the susceptibility of spoilage moulds for propionic (PA) and sorbic acid (SA) was tested in-vitro and in bread and cake. Aspergillus niger, Aspergillus montevidensis, Aspergillus ruber, Cladosporium ramotenellum, Penicillium brevicompactum and Penicillium roqueforti were subjected to PA and SA, both through macrodilution on malt extract agar (MEA) plates with adjusted aw (0.93, 0.95, 0.97), pH (5, 5.5, 6.0), acid (max. 2000 mg/L MEA), and through validation in wheat bread (max. 2901 mg PA/kg) and (lemon) cake (max. 1988 mg SA/kg). The undissociated acid concentrations (CHA) were estimated using either the Henderson-Hasselbalch (HH) equation or two modified HH equations. The influence of the food matrix (liquid oil, water, pH, aw), partitioning coefficient of the acids and spoilage fungi were evaluated and results were compared with in-vitro predictive models. In bread, the regular HH eq. proved to have good predictive power of CHA, whereas in cake a modified HH eq. (model 2) had better performance due to the inclusion of potential loss of CHA in the oil phase of complex food systems. The minimal inhibitory concentration (MIC) of PA in bread, after 30 days, was higher than 2901 mg/kg bread due to the strong resistance of P. brevicompactum, P. roqueforti and A. montevidensis. MIC of SA in lemon cake was 1429 mg SA/kg (pH 5.2), whereas in standard cake with pH 7.2, the max. level of 1988 mg SA/kg was insufficient for postponing mould growth to 30 days. The pH of cake had no influence on MIC of SA against A. niger and A. rubrum, whereas this effect was seen for C. ramotenellum, P. brevicompactum and P. roqueforti.

ACID-BASE PROPERTIES OF PHOSPHORYLATED CRUMB RUBBER

Phosphorylation of crumb rubber was carried out by the reaction of oxidative chlorophosphorylation and hydrolysis of the obtained modifier. The modified crumb rubber was studied by potentiometric titration using the method of various samples. The ionization constants of phosphorylated crumb rubber were calculated using the Henderson-Hasselbach equation

Extraction, physicochemical characterization, functionality, and excipient ability of corn fiber gum-starch isolate from corn milling industry waste

Corn processing industries generate an extensive fibrous byproduct consisting of corn fiber gum (CFG) and residual starch (S). The present study hypothesized that CFG and S could be isolated as a single crosslinked conjugate. The isolated CFG-S conjugate was acidic, with a pKa value of 11.49, and a swelling index of 99.60%. Henderson–Hasselbalch equation predicted negligible ionization throughout the gastrointestinal pH range. The DSC thermogram highlights glass transition and temperature-specific structure stabilization through the exothermic crystallization domain. FTIR, SEM & XRD confirmed the structural conjugation and integrity of the conjugate. Tablets containing Venlafaxine hydrochloride as a model drug were prepared using CFG-S (14 and 57%) as excipient by wet granulation method. Percentage cumulative drug release with low concentration was up to 99.67175 ± 0.09 % in 5 h whereas with high concentration, it was extended to 12 h (P < 0.05). Korsemayer-Peppas release exponent indicates zero order (R2 = 0.9935) kinetics with super case-II anomalous transport showing diffusion and erosion as drug release mechanisms. The results confirmed that CFG-S isolate could act as a good binding agent at low concentrations and release extending cross-linked matrix former at a higher concentration for release retardant excipient.