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Micronutrients
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
Chloride is found in the form of anion (Cl-) in all organisms and combines with cations like sodium (Na+) or potassium (K+) to form a salt such as sodium chloride (NaCl) or potassium chloride (KCl). After sodium, chloride is the most abundant mineral in the body. Chloride is the principal extracellular and intracellular anion (Cl−) in the body, where it represents 60–70% of the total negative ion content (6, 8, 15–16). Chloride is vital for maintenance of serum electrical neutrality, muscular activity, osmotic pressure, electrolyte balance, acid-base status, renal function, regulation of body fluids (fluid homeostasis), and hydrochloric acid (HCl) production in the gastrointestinal tract (6, 8, 15–16). In addition, it is an essential component for the assessment of many pathological conditions. It maintains the electrical balance in the nervous system and is involved in intracellular and extracellular transport (8, 15–16).
Battlefield Chemical Inhalation Injury
Published in Jacob Loke, Pathophysiology and Treatment of Inhalation Injuries, 2020
The formula for chlorine (Cl) is Cl2; density 2.5; specific gravity 1.41; boiling point -34.1°C. Chlorine appears as a greenish yellow gas with an acrid, pungent, characteristic odor. Since the odor threshold is substantially below the toxic limit, this substance is considered to have good warning properties. With chronic and repeated exposure, however, some threshold adaptation occurs (Beck, 1959). A progressive olfactory inhibition has been described. This progressive loss of sensitivity is thought to be the reason that chlorine workers suffer more frequent and more severe exposures in the later months and years of their work history, ostensibly because of the “warning” threshold of their olfactory sensitivity (Laciak and Sipa, 1958).
Anion Gap and Stewart's Strong Ion Difference
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Effect of SIDa on water dissociation (Figure 50.1): Decreased SIDa (i.e. <40 mEq/L). Water dissociates to release more H+ than OH− to restore electroneutrality (by Law of electroneutrality). Hence since H+ > OH−, metabolic acidosis results. For example, high serum Cl− from infusions of large volumes of normal saline causes metabolic acidosis. Similarly, decreased Na+ (hyponatraemia) results in metabolic acidosis.Increased SIDa (i.e. >44 mEq/L). Water dissociates to release more OH– ions than H+ions to restore electroneutrality, and results in metabolic alkalosis. This occurs in hypernatraemia following an infusion of sodium bicarbonate or in hypochloraemia following vomiting of large volumes of gastric juice in a patient with gastric outlet obstruction or those treated with loop diuretics.
Study of FA12 peptide-modified PEGylated liposomal doxorubicin (PLD) as an effective ligand to target Muc1 in mice bearing C26 colon carcinoma: in silico, in vitro, and in vivo study
Published in Expert Opinion on Drug Delivery, 2022
Atefeh Biabangard, Ahmad Asoodeh, Mahmoud Reza Jaafari, Mohammad Mashreghi
The best docking complexes regarding binding energy among all peptides were selected for further MD simulations. Simulations were performed using the GROMACS 5.1.1 package [29] with the GROMOS96 43a1 force field. First of all, the peptide-protein complex was embedded into a cubic box of TIP3P water, which extended to a10 Å between the protein and the box edge. The chloride ion (Cl−) was added to neutralize the system. The particle mesh Ewald (PME) method [30] and SHAKE algorithm [31] were used during the simulation. In all directions, periodic boundary conditions were applied. Initially, the system was subjected to energy minimization using the steepest descent technique, which was set to a maximum of 1000 kJ/(mol∙nm). After 50,000 steps minimization, the system was equilibrated during 100 ps under a constant volume ensemble (NVT) with a position restraint on all water oxygen. The time step for the simulation was set to 2 fs. Afterward, constant pressure simulations (NPT) were run for 1 ns and maintained at 300 K and a pressure of 1 bar. Finally, the productive MD simulations (without positional constraints) of 100 ns were performed on the whole system (T = 300 K and P = 1 bar). All covalent bonds to hydrogen atoms were constrained using the default linear constraint solver (LINCS) algorithm [32].
A Novel Class of On-Treatment Cancer Immunotherapy Biomarker: Trough Levels of Antibody Therapeutics in Peripheral Blood
Published in Immunological Investigations, 2022
Yoshinobu Koguchi, William L. Redmond
In this review, we frequently use two related but distinct concepts in PK terminology: 1) Trough concentration, which is the concentration of a drug in the blood immediately before the next dose is administered (Figure 2) (Merry and Flexner 2008). When an mAb is administered in a multiple-dosing regimen, each successive dosage is administered before the preceding dose is eliminated. Accumulation of the mAb results in a higher peripheral drug concentration, which eventually plateaus where the same maximum and minimum (trough levels) concentrations are reproduced repeatedly. This state is called a steady state. In contrast, the state following administration of the first dosage is called the initial state (Figure 2); and then 2) Clearance (CL), which is an index of the ability of the body to eliminate a drug. Rather than describing the amount of drug eliminated, CL describes the volume of plasma from which a drug would be totally removed per unit time and is inversely related to half-life (Bardal et al. 2011). Therefore, low CL results in high systemic exposure (high trough levels), while high CL results in low systemic exposure (low trough levels) (Figure 3). Below, we will summarize how CL, exposure, and trough level of mAbs differ between responders and non-responders. We will also discuss the implications of varying PK using a concept of various exposure-response (E-R) relationships.
Oral, intranasal, and intravenous abuse potential of serdexmethylphenidate, a novel prodrug of d-methylphenidate
Published in Current Medical Research and Opinion, 2022
Megan J. Shram, Beatrice Setnik, Lynn Webster, Sven Guenther, Travis C. Mickle, Rene Braeckman, Jaroslaw Kanski, Andrea Martin, Debra Kelsh, Bradley D. Vince, Andrew C. Barrett
Serdexmethylphenidate (SDX) (see Figure 1 for chemical structure) is an extended-duration prodrug of d-MPH that was developed, in part, to produce lower abuse-related effects than d-MPH hydrochloride (HCl) when administered via oral and non-oral routes. SDX is approved as a combination product, SDX/d-MPH (70/30 molar ratio) capsules (AZSTARYS [Schedule II]), for the treatment of ADHD; the IR component was included to achieve faster d-MPH exposures following oral administration and thus efficacy earlier in the dosing interval. SDX is currently under investigation as a single-entity product for the treatment of various CNS-related conditions. Intact SDX chloride (Cl) is pharmacologically inactive until converted to active d-MPH, a process likely occurring primarily in the lower intestinal tract28. Preclinical studies in several animal species were suggestive of low relative abuse potential insofar as: (1) oral administration of SDX Cl yielded a slow onset and relatively long duration of d-MPH exposure, and (2) IV administration of SDX Cl resulted in very low plasma concentrations of d-MPH relative to d-MPH HCl administration29. The objective of the 3 studies described here was to evaluate the human abuse potential of SDX Cl following oral, IN, and IV administration. These studies were conducted as a part of the overall abuse potential assessment to inform a scheduling decision for SDX under the Controlled Substances Act.