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Transplant International : Official... 2023Normothermic machine perfusion (NMP) has reshaped organ preservation in recent years. In this preclinical study, prolonged normothermic perfusions of discarded human...
Normothermic machine perfusion (NMP) has reshaped organ preservation in recent years. In this preclinical study, prolonged normothermic perfusions of discarded human kidney grafts were performed in order to investigate perfusion dynamics and identify potential quality and assessment indicators. Five human discarded kidney grafts were perfused normothermically (37°C) for 48 h using the Kidney Assist device with a red-blood-cell based perfusate with urine recirculation. Perfusion dynamics, perfusate and urine composition as well as injury markers were measured and analyzed. Donor age ranged from 41 to 68 years. All but one kidney were from brain dead donors. Perfusions were performed successfully for 48 h with all discarded kidneys. Median arterial flow ranged from 405 to 841 mL/min. All kidneys excreted urine until the end of perfusion (median 0.43 mL/min at the end of perfusion). While sodium levels were consistently lower in urine compared to perfusate samples, this was only seen for chloride and potassium in kidney KTX 2. Lactate, AST, LDH as well as pro-inflammatory cytokines increased over time, especially in kidneys KTX 3 and 4. normothermic perfusion is able to identify patterns of perfusion, biological function, and changes in inflammatory markers in heterogenous discarded kidney grafts.
Topics: Humans; Adult; Middle Aged; Aged; Kidney; Kidney Transplantation; Perfusion; Organ Preservation; Extracorporeal Circulation
PubMed: 37901298
DOI: 10.3389/ti.2023.11804 -
Frontiers in Public Health 2023Empowerment lifestyle programs are needed to reduce the risk of hypertension. Our study compared the effectiveness of two empowerment-based approaches toward blood... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Empowerment lifestyle programs are needed to reduce the risk of hypertension. Our study compared the effectiveness of two empowerment-based approaches toward blood pressure (BP) reduction: salt reduction-specific program vs. healthy lifestyle general program.
METHODS
Three hundred and eleven adults (median age of 44 years, IQR 34-54 years) were randomly assigned to a salt reduction ( = 147) or a healthy lifestyle program ( = 164). The outcome measures were urinary sodium (Na) and potassium (K) excretion, systolic (SBP) and diastolic (DBP) blood pressure, weight, and waist circumference.
RESULTS
There were no significant differences in primary and secondary outcomes between the two program groups. When comparing each program to baseline, the program focused on salt reduction was effective in lowering BP following a 12-week intervention with a mean change of -2.5 mm Hg in SBP (95% CI, -4.1 to -0.8) and - 2.7 mm Hg in DBP (95% CI, -3.8 to -1.5) in the intention-to-treat (ITT) analysis. In the complete-case (CC) analysis, the mean change was -2.1 mm Hg in SBP (95% CI, -3.7 to -0.5) and - 2.3 mm Hg in DBP (95% CI, -3.4 to -1.1). This effect increases in subjects with high-normal BP or hypertension [SBP - 7.9 mm Hg (95% CI, -12.5 to -3.3); DBP - 7.3 mm Hg (95% CI, -10.2 to -4.4)]. The healthy lifestyle group also exhibited BP improvements after 12 weeks; however, the changes were less pronounced compared to the salt reduction group and were observed only for DBP [mean change of -1.5 mm Hg (95% CI, -2.6 to -0.4) in ITT analysis and - 1.4 mm Hg (95% CI, -2.4 to -0.3) in CC analysis, relative to baseline]. Overall, improvements in Na/K ratio, weight, and Mediterranean diet adherence resulted in clinically significant SBP decreases. Importantly, BP reduction is attributed to improved dietary quality, rather than being solely linked to changes in the Na/K ratio.
CONCLUSION
Salt-focused programs are effective public health tools mainly in managing individuals at high risk of hypertension. Nevertheless, in general, empowerment-based approaches are important strategies for lowering BP, by promoting health literacy that culminates in adherence to the Mediterranean diet and weight reduction.
Topics: Adult; Humans; Middle Aged; Blood Pressure; Hypertension; Sodium Chloride, Dietary; Outcome Assessment, Health Care
PubMed: 38026295
DOI: 10.3389/fpubh.2023.1277355 -
Environmental Toxicology and Chemistry May 2024The ASTM International standard test method for freshwater mussels (E2455-13) recommends 4-week toxicity testing with juveniles to evaluate chronic effects on survival...
The ASTM International standard test method for freshwater mussels (E2455-13) recommends 4-week toxicity testing with juveniles to evaluate chronic effects on survival and growth. However, concerns remain that the method may not adequately address the sensitivity of mussels to longer term exposures (>4 weeks), particularly in relation to potential reproductive impairments. No standard method directly evaluates toxicant effects on mussel reproduction. The objectives of the present study were to (1) evaluate toxicity endpoints related to reproduction in fatmucket (Lampsilis siliquoidea) using two common reference toxicants, potassium chloride (KCl) and nickel (Ni); (2) evaluate the survival and growth of juvenile fatmucket in standard 4-week and longer term (12-week) KCl and Ni tests following a method refined from the standard method; and (3) compare the sensitivity of the reproductive endpoints with the endpoints obtained from the juvenile mussel tests. Reproductive toxicity tests were conducted by first exposing female fatmucket brooding mature larvae (glochidia) to five test concentrations of KCl and Ni for 6 weeks. Subsamples of the glochidia were then removed from the adults to determine three reproductive endpoints: (1) the viability of brooded glochidia; (2) the viability of free glochidia in a 24-h exposure to the same toxicant concentrations as their mother; and (3) the success of glochidia parasitism on host fish. Mean viability of brooded glochidia was significantly reduced in the high KCl concentration (26 mg K/L) relative to the control, with a 20% effect concentration (EC20) of 14 mg K/L, but there were no significant differences between the control and any Ni treatment (EC20 > 95 µg Ni/L). The EC20s for viability of free glochidia after the additional 24-h exposure and parasitism success were similar to the EC20s of brooded glochidia. The EC20s based on the most sensitive biomass endpoint in the 4-week juvenile tests were 15 mg K/L and 91 µg Ni/L, similar to or greater than the EC20s from the reproductive KCl and Ni tests, respectively. When exposure duration in the juvenile tests was extended from 4 to 12 weeks, the EC20s decreased by more than 50% in the KCl test but by only 8% in the Ni test. Overall, these results indicate that a standard 4-week test with juvenile mussels can prove effective for estimating effects in chronic exposures with different life stages although a longer term 12-week exposure with juvenile mussels may reveal higher sensitivity of mussels to some toxicants, such as KCl. Environ Toxicol Chem 2024;43:1097-1111. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Topics: Animals; Nickel; Reproduction; Water Pollutants, Chemical; Potassium Chloride; Female; Bivalvia; Unionidae
PubMed: 38488680
DOI: 10.1002/etc.5843 -
Dietary sodium restriction reduces blood pressure in patients with treatment resistant hypertension.BMC Nephrology Sep 2023Patients with treatment resistant hypertension (TRH) are at particular risk of cardiovascular disease. Life style modification, including sodium restriction, is an...
PURPOSE
Patients with treatment resistant hypertension (TRH) are at particular risk of cardiovascular disease. Life style modification, including sodium restriction, is an important part of the treatment of these patients. We aimed to analyse if self-performed dietary sodium restriction could be implemented in patients with TRH and to evaluate the effect of this intervention on blood pressure (BP). Moreover, we aimed to examine if mechanisms involving nitric oxide, body water content and BNP, renal function and handling of sodium were involved in the effect on nocturnal and 24-h BP. Also, measurement of erythrocyte sodium sensitivity was included as a possible predictor for the effect of sodium restriction on BP levels.
PATIENTS AND METHODS
TRH patients were included for this interventional four week study: two weeks on usual diet and two weeks on self-performed sodium restricted diet with supplementary handed out sodium-free bread. At the end of each period, 24-h BP and 24-h urine collections (sodium, potassium, ENaC) were performed, blood samples (BNP, NOx, salt blood test) were drawn, and bio impedance measurements were made.
RESULTS
Fifteen patients, 11 males, with a mean age of 59 years were included. After sodium restriction, urinary sodium excretion decreased from 186 (70) to 91 [51] mmol/24-h, and all but one reduced sodium excretion. Nocturnal and 24-h systolic BP were significantly reduced (- 8 and - 10 mmHg, respectively, p < 0.05). NOx increased, BNP and extracellular water content decreased, all significantly. Change in NOx correlated to the change in 24-h systolic BP. BP response after sodium restriction was not related to sodium sensitivity examined by salt blood test.
CONCLUSION
Self-performed dietary sodium restriction was feasible in a population of patients with TRH, and BP was significantly reduced. Increased NOx synthesis may be involved in the BP lowering effect of sodium restriction.
TRIAL REGISTRATION
The study was registered in Clinical trials with ID: NCT06022133.
Topics: Male; Humans; Middle Aged; Sodium, Dietary; Sodium; Blood Pressure; Hypertension; Sodium Chloride, Dietary; Sodium Chloride
PubMed: 37726656
DOI: 10.1186/s12882-023-03333-9 -
Frontiers in Pharmacology 2023Despite improvements in treatment, lung cancer is still a major health problem worldwide. Among lung cancer subtypes, the most frequent is represented by adenocarcinoma... (Review)
Review
Despite improvements in treatment, lung cancer is still a major health problem worldwide. Among lung cancer subtypes, the most frequent is represented by adenocarcinoma (belonging to the Non-Small Cell Lung Cancer class) although the most challenging and harder to treat is represented by Small Cell Lung Cancer, that occurs at lower frequency but has the worst prognosis. For these reasons, the standard of care for these patients is represented by a combination of surgery, radiation therapy and chemotherapy. In this view, searching for novel biomarkers that might help both in diagnosis and therapy is mandatory. In the last 30 years it was demonstrated that different families of ion channels are overexpressed in both lung cancer cell lines and primary tumours. The altered ion channel profile may be advantageous for diagnostic and therapeutic purposes since most of them are localised on the plasma membrane thus their detection is quite easy, as well as their block with specific drugs and antibodies. This review focuses on ion channels (Potassium, Sodium, Calcium, Chloride, Anion and Nicotinic Acetylcholine receptors) in lung cancer (both Non-Small Cell Lung Cancer and Small Cell Lung Cancer) and recapitulate the up-to-date knowledge about their role and clinical relevance for a potential use in the clinical setting, for lung cancer diagnosis and therapy.
PubMed: 37942486
DOI: 10.3389/fphar.2023.1283623 -
Molecules (Basel, Switzerland) Sep 2023Sodium chloride (NaCl) is a commonly used additive in minimally processed fish-based products. The addition of NaCl to fish products and packaging in a modified...
Sodium chloride (NaCl) is a commonly used additive in minimally processed fish-based products. The addition of NaCl to fish products and packaging in a modified atmosphere is usually efficient with regard to limiting the occurrence of the aquatic environmental pathogen Given the negative effects of excess NaCl in the diet, there is a growing demand to reduce NaCl in food products with safer substituents, but the knowledge of their impact on antibiotic resistant is limited. This study aimed to evaluate the physiological and transcriptome characteristics of NT06 isolated from fish and to determine the effect of selected concentrations of alternative NaCl compounds (KCl/NaL/NaC) on the NT06 virulence phenotype and genotype. In the study, among the isolated microorganisms, NT06 showed the highest antibiotic resistance (to ampicillin, ceftriaxone, nalidixic acid, and norfloxacin) and the ability to grow at 4 °C. The Comprehensive Antibiotic Resistance Database (CARD) and the Virulence Factor Database (VFDB) revealed the presence of 24 and 134 gene products assigned to AMR and VF in the NT06 transcriptome, respectively. KCl, KCl/NaL and KCl/NaL/NaC inhibited pyocyanin biosynthesis, elastase activity, and protease activity from 40 to 77%. The above virulence phenotypic observations were confirmed via RT-qPCR analyses, which showed that all tested AMR and VF genes were the most downregulated due to KCl/NaL/NaC treatment. In conclusion, this study provides insight into the potential AMR and VF among foodborne and the possible impairment of those features by KCl, NaL, and NaC, which exert synergistic effects and can be used in minimally processed fish-based products.
Topics: Animals; Virulence; Anti-Bacterial Agents; Pseudomonas aeruginosa; Sodium Citrate; Sodium Lactate; Potassium Chloride; Sodium Chloride; Drug Resistance, Bacterial; Virulence Factors; Pseudomonas Infections
PubMed: 37764430
DOI: 10.3390/molecules28186654 -
American Journal of Kidney Diseases :... Apr 2024
Topics: Humans; Potassium; Hypertension; Sodium Chloride, Dietary; Sodium Chloride; Blood Pressure
PubMed: 38081406
DOI: 10.1053/j.ajkd.2023.12.001 -
European Heart Journal Aug 2023
Topics: Humans; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Metolazone; Heart Failure
PubMed: 37572039
DOI: 10.1093/eurheartj/ehad463 -
Seminars in Interventional Radiology Aug 2023Interstitial ectopic pregnancy involves the interstitial portion of the fallopian tube and is among the most hazardous of all ectopic pregnancies, with the highest risk... (Review)
Review
Interstitial ectopic pregnancy involves the interstitial portion of the fallopian tube and is among the most hazardous of all ectopic pregnancies, with the highest risk of uterine rupture and maternal mortality. Unlike tubal ectopic pregnancy, management of interstitial pregnancy is not well standardized. Systemic methotrexate (MTX) and surgical resection are the primary treatment options; however, failure rates and risk of bleeding remain high. Alternative minimally invasive techniques have been described-including uterine artery embolization (UAE) and local injection of MTX or potassium chloride-and may confer improved success rates. We report a case of a high-risk 28-year-old female with an interstitial ectopic pregnancy successfully treated with combined local injection of MTX plus UAE. We describe our technique and the unique medical management in the setting of a known bleeding disorder.
PubMed: 37575342
DOI: 10.1055/s-0043-1770712 -
Current Rheumatology Reviews Apr 2024Osteoarthritis (OA) is becoming a major medical burden worldwide due to changing lifestyles and aging populations. Osteoarthritis is a disease characterized by a variety...
BACKGROUND
Osteoarthritis (OA) is becoming a major medical burden worldwide due to changing lifestyles and aging populations. Osteoarthritis is a disease characterized by a variety of anatomic and physiological changes to joints, including cartilage degradation, bone remodeling, and the formation of osteophytes. These changes cause pain, stiffness, swelling, and limitations in joint function. Glucosamine serves as a fundamental constituent for cartilage, the resilient connective tissue responsible for cushioning joints. Glucosamine Sulphate Potassium Chloride (GSPC) supplementation is widely employed to mitigate symptoms linked to osteoarthritis, a degenerative joint disorder hallmarked by cartilage degradation.
AIM
Palliative care aims at minimizing pain and disability and improving function, performance, and quality of life. In this study, the emulgel formulation of GSPC was developed and checked for its potential.
OBJECTIVE
Currently, OA does not have a definitive treatment. Since conventional dosage forms cannot deliver the active drug content at a predefined target site in a predictable manner throughout the treatment period, a new carrier system is always required. Considering their reduced size, targeting potential, and site specificity, nanocarrier-based approaches could hold an answer to shortcomings associated with conventional routes. Thus, the objective of the current study was to formulate and characterize glucosamine sulphate potassium chloride-loaded emulgel for the treatment of osteoarthritis.
METHODS
Microemulsion of glucosamine sulphate potassium chloride was formulated using a spontaneous emulsification method comprising of oleic acid (oil phase), Tween 80, Tween 20 (surfactant) and PEG 400, Span 80 (co-surfactant), and distilled water (aqueous phase). The microemulsions were evaluated for surface morphology, globule size, poly-dispersibility index (PDI), zeta potential, and viscosity, and the final batch of microemulsions was selected.
RESULT
The optimized microemulsion contained 35% co-surfactant (propylene glycol), 20% surfactant (Tween 20), and 15% oil (oleic acid) and glucosamine sulphate potassium chloride in a dose of 60 mg, which has sufficient drug loading capacity with a droplet size of 182 nm for optimized formulation. The optimized microemulsion formulation was added to gel prepared by Carbopol 934 in a 1:1 (w/w) ratio, leading to the formulation of glucosamine sulphate potassium chloride- containing emulgel. The prepared emulgel was further evaluated for viscosity, drug content, pH, and in-vitro drug release. Emulgel formulation (F6) showed 88% drug release after 6 hours, and it followed the Higuchi model.
CONCLUSION
Glucosamine Sulphate Potassium Chloride (GSPC) is used in the treatment of OA by increasing the production of proteoglycans, which can cause the cartilage to break down. Emulgel formulation (F3) showed 75.41% drug release, and formulation (F6) showed 88% drug release after 6 h. Therefore, it may be concluded that an emulgel of GSPC can be used as a controlled-release dosage form of the drug for local application in OA.
PubMed: 38584559
DOI: 10.2174/0115733971291114240326042453