Administration Of Salt Research Articles

Features of beta cell differentiation during the development of type 2 diabetes mellitus

Type 2 diabetes mellitus is characterized by a mild inflammatory reaction in the pancreas, which affects the structure and function of the pancreatic islets: the number of β-cells decreases and the number of α-cells increases. The work examined the features of β-cell differentiation in the development of experimental type 2 diabetes mellitus and while reducing the inflammatory process. Biochemical, histological methods, enzyme-linked immunosorbent assay, immunohistochemical methods were used using primary antibodies to insulin, glucagon, proliferation marker Ki-67 and secondary antibodies labeled with fluorescent dyes. Streptozotocin and nicotinamide were used to model type 2 diabetes mellitus, and the sodium salt of 5-amino-2,3-dihydrophthalazine-1,4-dione was used to reduce the inflammatory response. Previous studies have shown that it changes the macrophage phenotype from proinflammatory M1 to anti-inflammatory M2. In type 2 diabetes mellitus, against the background of a decrease in the number of macrophages with the CD163 marker and the concentration of the cytokine TGF-β1, which have an anti-inflammatory effect, in the pancreatic islets, a decrease in the number of β-cells and their functional activity was observed, while the content of α-cells synthesizing glucagon increased. After administration of the sodium salt of 5-amino-2,3-dihydrophthalazine-1,4-dione, the opposite picture was observed in the pancreatic islets: against the background of an increase in the number of CD163+ macrophages and the content of TGF-β1, the number of β cells increased and the number of α cells decreased-cells. The increase in the number of insulin-synthesizing cells was not accompanied by their mitotic activity. It is likely that a decrease in the number of CD163+ macrophages and the level of the antiinflammatory cytokine TGF-β1 in the islets are factors contributing to changes in the cell microenvironment and, as a consequence, the differentiation of β-cells into α-cells. On the contrary, an increase in the number of CD163+ macrophages and TGF-β1 against the background of administration of the sodium salt of 5-amino-2,3-dihydrophthalazine-1,4-dione presumably promotes reverse differentiation of α-cells into β-cells and restoration of insulin synthesis pancreas. Targeted effects on the microenvironment of cells in the pancreatic islet in type 2 diabetes mellitus may be a new approach to treating the disease.

Metabolic effects of a submaximal dose of pink salt and monosodium glutamate in experimental rats

Background & objectivesPink salt and monosodium glutamate (MSG) are two typical food additives used in cooking to enhance flavour. However, excessive use of them has been associated to a variety of metabolic problems, including weight gain and hyperglycemia. The current study aimed to assess the metabolic changes caused by submaximal dosages of MSG and pink salt in experimental rats. MethodsTwenty-four 120–150 g Wister rats of both sexes were divided into three groups: control, pink salt-treated (0.8 g/kg daily for three weeks), and MSG-treated (3.6 g/kg daily for three weeks). The body weight, amount of food and water consumed, and blood glucose levels of animals were measured and recorded as indicators of their metabolic changes. Furthermore, after salt treatments at intervals such as week 1, week 2, and week 3, the survival rate and general toxicity manifestations were determined. The results were statistically analysed using one-way ANOVA, with p < 0.05 being considered significant. ResultsThe study found that the group given a submaximal dose of MSG gained significantly more weight (p < 0.05), consumed more food and water, and had higher blood glucose levels than the control. Ninety percent of the MSG therapy group survived by the end of the third week, however, they suffered from negative effects like abdominal distention, respiratory problems, ptosis, and subcutaneous swelling. On the other hand, the consumption of food and drink was significantly (p < 0.05) increased upon the administration of pink salt. Only little changes were observed in the body weight, blood sugar levels, and general features (such as subcutaneous swelling, change in bowel colour, and loose stools). Additionally, it was shown that the survival rate remained unchanged, particularly after week 3. ConclusionAccording to study findings, MSG may induce metabolic issues, increasing the chance of death. While there was no discernible metabolic aberration linked to pink salt. Further research is required to fully understand the mechanism and consequences of these taste enhancers on the host system before pink salt can be deemed safe.

Acamprosate reduces ethanol intake in the rat by a combined action of different drug components

Alcohol misuse accounts for a sizeable proportion of the global burden of disease, and Campral® (acamprosate; calcium-bis-(N-acetylhomotaurinate)) is widely used as relapse prevention therapy. The mechanism underlying its effect has in some studies been attributed to the calcium moiety and not to the N-acetylhomotaurine part of the compound. We recently suggested that the dopamine elevating effect of acamprosate is mediated both by N-acetylhomotaurine and calcium in a glycine receptor dependent manner. Here we aimed to explore, by means of in vivo microdialysis, if our previous study using local administration was functionally relevant and if systemic administration of the sodium salt of N-acetylhomotaurine (sodium acamprosate; 200 mg/kg, i.p.) enhanced the effects of calcium chloride (CaCl2; 73.5 mg/kg, i.p.) on nucleus accumbens (nAc) dopamine and/or taurine levels in male Wistar rats. In addition, we investigated the impact of regular acamprosate and the combination of CaCl2 and N-acetylhomotaurine on the alcohol deprivation effect (ADE). Finally, we assessed if N-acetylhomotaurine potentiates the ethanol-intake reducing effect of CaCl2 in a two-bottle choice voluntary ethanol consumption model followed by an ADE paradigm. Systemic administration of regular acamprosate, sodium acamprosate and CaCl2 all trended to increase nAc dopamine whereas the combination of CaCl2 and sodium acamprosate produced a significant increase. Sodium acamprosate elevated extracellular taurine levels without additional effects of CaCl2. Ethanol intake was significantly reduced by systemic administration of CaCl2 without additional effects of the combination of CaCl2 and sodium acamprosate. Both acamprosate and CaCl2 combined with sodium acamprosate blocked the ADE following acute treatment. The data presented suggest that CaCl2 and N-acetylhomotaurine act in concert on a neurochemical level, but calcium appears to have the predominant effect on ethanol intake.

From Colonial India to Semi-Colonial Republican China: Imaginaries and Realities of Civil Service and State-Building in Salt Administration, 1912–45

This article studies the Sino-Foreign Salt Inspectorate, which was imposed upon a weak Chinese government by an international consortium from 1913 till 1949. The founder of the Salt Inspectorate was Sir Richard Dane, a high-level civil servant in the Indian Civil Service with long experience in salt tax administration in India. This article charts the development of the Salt Inspectorate, considering how it maintained its organisational integrity in a hostile policy environment through core strategies of simplification, bureaucratisation and insulation. The Salt Inspectorate stands as an exemplar of liberal imperial order in its replication of the Indian Civil Service and classic British liberal ideals of political economy, operating in the midst of a dangerous policy environment of civil war, rising nationalism and foreign invasion.

Salt, Sovereignty and Law in Colonial India: The Case of Rajputana Salt in the Late Nineteenth Century

This article explores salt as a substance that lay at the heart of discussions around sovereignty, jurisdiction, criminality and control. Tracing salt administration in late nineteenth-century Rajputana, it argues that the colonial state significantly altered existing local contexts of power and control in the princely states where the salt sources lay. It explores how the colonial state, while maintaining a façade of ‘indirect rule’, created jurisdictional spaces for itself within the princely states. In the process, local and regional salt production and the trade circuits of Rajputana were subsumed in the making of an expansive colonial enterprise.

Effect of Exogenous Acute β-Hydroxybutyrate Administration on Different Modalities of Exercise Performance in Healthy Rats.

A ketone body (β-hydroxybutyrate [β-HB]) is used as an energy source in the peripheral tissues. However, the effects of acute β-HB supplementation on different modalities of exercise performance remain unclear. This study aimed to assess the effects of acute β-HB administration on the exercise performance of rats. In study 1, Sprague-Dawley rats were randomly divided into six groups: endurance exercise (EE + PL and EE + KE), resistance exercise (RE + PL and RE + KE), and high-intensity intermittent exercise (HIIE + PL and HIIE + KE) with placebo (PL) or β-HB salt (KE) administration. In study 2, metabolome analysis using capillary electrophoresis mass spectrometry was performed to profile the effects of β-HB salt administration on HIIE-induced metabolic responses in the skeletal and heart muscles. The maximal carrying capacity (rest for 3 min after each ladder climb, while carrying heavy weights until the rats could not climb) in the RE + KE group was higher than that in the RE + PL group. The maximum number of HIIE sessions (a 20-s swimming session with a 10-s rest between sessions, while bearing a weight equivalent to 16% of body weight) in the HIIE + KE group was higher than that in the HIIE + PL group. However, there was no significant difference in the time to exhaustion at 30 m·min -1 between the EE + PL and the EE + KE groups. Metabolome analysis showed that the overall tricarboxylic acid cycle and creatine phosphate levels in the skeletal muscle were higher in the HIIE + KE group than those in the HIIE + PL group. These results indicate that acute β-HB salt administration may accelerate HIIE and RE performance, and the changes in metabolic responses in the skeletal muscle after β-HB salt administration may be involved in the enhancement of HIIE performance.

Researches on Salt Archaeology and Salt History in Roman Dacia

Even if the researches on salt exploitation and salt administration in Roman Dacia are scarce and the results are far from offering a coherent image on this economic activity, there are however some works which are important for this stage of our approach. These works are treating the aforementioned issues from historical, ethnographic and archaeological perspectives, both in synchronic and diachronic way. I shall briefly present the most important researches and their results.

AW-APSH-2: “MINERALOCORTICOID RECEPTOR (MR)-ASSOCIATED HYPERTENSION” IN “GREEDY ORGAN HYPOTHESIS”

Spironolactone has been used for more than 60 years. Eplerenone is MR-specific MRB and esaxerenone possesses non-steroidal structure with high affinity and specificity to MR and exhibits long half-life. We conducted a double-blind phase III study of esaxerenone compared with eplerenone in patients with essential hypertension in 2020. Esaxerenone 2.5 mg elicited comparable hypotensive effect to eplerenone 50 mg and 5 mg exhibited significantly stronger effect than 2.5 mg. We also investigated the efficacy of dosage-escalation of esaxerenone added to a RAS inhibitor in hypertensive patients with type 2 diabetes (DM) (HbA1c:6.8%) and albuminuria (212 mg/gCr). 5 mg esaxerenone induced 20/8mmHg blood pressure reduction and reduced albumin excretion significantly. Interestingly, in these studies, esaxerenone exerted similar hypotensive action in the patients with RAS inhibitors, compared to the groups without them. This observation indicates that MR can be activated being independent of renin-angiotensin-aldosterone system. In 2012, we proposed the concept of “MR-associated hypertension”, hypertension caused by over-activation of MR with wide range of plasma aldosterone level. Primary aldosteronism is the typical example of MR-associated hypertension, but even in low plasma aldosterone concentration state, such as obesity, DM, CKD, MR can be over-activated. There are several postulated mechanisms of over-activation of MR. Increased expression of MR, increased sensitivity of MR and MR protein stabilization. We are interested in the activation of MR by salt and sugar themselves. We focus on MR expressed in the intestine for sodium absorption. Administration of DOCA and high salt induced up-regulation of epithelial sodium channel, ENaC, the target molecule of MR. And intestine specific knock-out of MR mice exhibited blunted increase of blood pressure by DOCA and high salt loading. We also demonstrated that high sugar induces MR protein stabilization by PKC activation, O-GlcNac modification or EGFR-ERK activation. More recently, in relation to excessive salt and sugar intake and occurrence of non-communicable diseases (NCDs), including hypertension, we have proposed “Greedy Organ Hypothesis”. Excessive intake of salt and sugar are sensed by the kidney and the intestines, and these organs up-regulate SGLT, sodium-glucose co-transporters and come to absorb salt and sugar greedily. Excessive salt intake through SGLT2 makes the kidney greedy to induce hypertension/CKD. Excessive food intake through SGLT1 make the intestines greedy to induce obesity/DM. Furthermore, there is “crossing” relationships between “greedy organs” and NCDs. Greedy kidney and intestines over-activate MR and induce MR-associated hypertension. Therefore, MRB are effective to alleviate Greedy Organs and to suppress NCDs.

PS-B05-2: ANALYSIS OF SHORT-TERM CARDIOVASCULAR AND RENAL DISORDERS IN MICE WITH CARDIO-RENAL DAMAGES

Chronic kidney disease (CKD) and cardiovascular disease (CVD) coexist often and pose a risk for disease progression. In recent years, a concept of “cardio-renal syndrome” has been proposed, in which disruption of cardio-renal homeostasis causes mutual harm. The renin-angiotensin system, sympathetic nervous system, and inflammation are involved in the cardiorenal axis, but the details of underlying molecular mechanisms have not been elucidated. We have previously reported that a heart failure model (ANS mice) subjected to simultaneous angiotensin II (A), unilateral nephrectomy (N), and salt (S) administration developed cardiac dysfunction, renal dysfunction, and proteinuria at 4 weeks post-treatment and may serve as a model for cardio-renal coupling pathophysiology. In the present study, we analyzed renal and cardiovascular lesions in ANS mice at week 1 of treatment. Interestingly, ANS mice exhibited cardio-renal lesions including cardiac fibrosis, aortic atherosclerosis, proteinuria, and tubular damage even at the short intervention period of 1 week (under submission). These results indicate that the ANS mice may be a useful tool for the analysis of the early pathophysiology of cardio-renal syndrome.

An Efficient UPLC-MS/MS Method for the Determination of Pyrroloquinoline Quinone in Rat Plasma and Its Application to a Toxicokinetic Study.

Pyrroloquinoline quinone (PQQ) is a powerful antioxidant coenzyme existing in diet, benefiting growth, development, cognition function, and the repair of damaged organs. However, a method for detecting PQQ in vivo was rarely described, limiting the research on the bioanalysis and metabolic properties of PQQ. In this study, a novel, simple, and efficient ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to quantify the concentration of PQQ in rat plasma. Detection through mass spectrometry was operated by multiple reaction monitoring (MRM) in negative electrospray ionization mode with ion transitions m/z 328.99→197.05 for PQQ and m/z 280.04→195.04 for the internal standard. The calibration curves were linear up to 10,000 ng/mL, with a lower limit of quantitation of 10 ng/mL. Inter-run and intra-run precision ranged from 1.79% to 10.73% and accuracy ranged from -7.73% to 7.30%. The method was successfully applied to a toxicokinetic study in Sprague-Dawley rats after the oral administration of PQQ disodium salt at doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg. The toxicokinetic parameters were subsequently analyzed, which may provide valuable references for the toxicokinetic properties and safety evaluation of PQQ.

Antihypertensive Effects of Aqueous Extract of Ricinodendron heudelotii (Baill.) Pierre (Euphorbiaceae) in Wistar Rat.

Ricinodendron heudelotii stem bark is commonly used in Cameroonian traditional medicine to treat cardiovascular diseases such as hypertension. The present study was designed to investigate the antihypertensive and antioxidant properties of the aqueous extract of Ricinodendron heudelotii in salt-induced hypertensive rats. Analysis by HPLC-ESI-Q-TOF-MS was used to identify various chemical components of the extract. A total of thirty rats were used for each test. High-salt hypertension was induced in rats by oral administration of NaCl for 12 weeks. Mean blood pressure (MBP) and heart rate (HR) were monitored by noninvasive methods. Oral administration of Ricinodendron heudelotii significantly (p < 0.01) reduced the increase of mean blood pressure (23.12%, 26.14%, and 24.34%) and heart rate (31.19%, 31.09%, and 26.98%), respectively, at the doses of 40, 20, and 6 mg/kg, compared to the hypertensive group. All the doses tested significantly reduced or/and ameliorated biochemical and oxidative stress parameters. Histological analysis showed that Ricinodendron heudelotii restored renal disorders induced by the administration of salt. The aqueous extract of Ricinodendron heudelotii exerts a cardioprotective effect, and the antihypertensive activity seems associated with an improvement in antioxidant status. Overall, the results justify and support the traditional use of Ricinodendron heudelotii.

State finance, merchant stake, and foreign interests: The certificate system in the Chinese salt administration, 1912–1949

The certificate system was a tax farming system that originated in the imperial era. During the Republic of China (1912–1949) the practice largely continued, despite being much criticised. Aiming to explore how and why the system was able to survive until the late 1940s, this article addresses three related issues: the role of the foreign-managed Chief Inspectorate of Salt Revenue in the Chinese state finance, the fiscal relationship between the central and provisional/local governments, and the interactions between the state and salt merchants. These factors contextualise the resistance of salt merchants against the abolition of the certificate system. The Chinese state did not abolish the system due to a concern about possible disruptions to salt revenues. During the wartime Japanese occupation (1937–1945), the concern became irrelevant, with the collapse of the prewar salt transport and revenue collection-remittance. After the war ended, the state simply ruled out a revival of the system.

Effects of Ketone Salt Supplementation on Blood Health Parameters in Adults Diagnosed with Post-traumatic Stress Disorder

ObjectivesThe purpose of this study was to determine if ketone salt administration for six-weeks alters blood health parameters, specifically variables from the comprehensive metabolic panel and complete blood count test, in adults diagnosed with post-traumatic stress disorder (PTSD). MethodsThis clinical trial consisted of a randomized, double-blinded, placebo-controlled design. Participants included males and females between the ages of 18–65 diagnosed with PTSD. Participants were randomized to either consume a control or ketone salt supplement twice a day for 6-weeks. Blood samples via a venous blood draw were collected before and after the six-week supplementation period. Blood analyses included a comprehensive metabolic panel and a complete blood count test. A series of 2 × 2 mixed ANOVAs (time: pre- and post-intervention; group: control or ketone salt) were used to analyze the collected data for each of the dependent variables. ResultsOf the 16 subjects that finished the study, 12 had complete pre- and post- comprehensive metabolic panel and complete blood count test results. There were main effects of group for the variables aspartate aminotransferase, alanine transaminase, and mean corpuscular volume, which were significantly greater in the control group than in the ketone group (p < .05 for each). However, no significant interaction effect between group and time for any of the dependent variables was observed (p > .05 in all cases). The results demonstrate that the control and ketone salt supplements did not alter any of the variables in the comprehensive metabolic panel or complete blood count test when compared from baseline to post-six-week supplementation. ConclusionsBeta-hydroxybutyrate, a ketone body, may reduce anxiety and other sympathetic driven measures associated with PTSD, however, it is important to ensure ketone supplements to do not cause adverse effects in this populations before implementing them for possible therapeutic effects. The findings from this pilot study suggest that prolonged ketone salt supplementation may be further examined as a therapeutic option as it did not result in negative blood health outcomes. Funding SourcesPruvit Ventures, Inc. and the College of Education at Augusta University financially supported this study.

Plasma concentrations of diclazuril following oral administration of diclazuril and diclazuril sodium salt to cattle.

Diclazuril is a triazine-based antiprotozoal agent widely used in veterinary practice that may have clinical application in the treatment of bovine protozoal diseases. The present study reports on the bioavailability, pharmacokinetics, and metabolism of diclazuril and diclazuril sodium salt in cattle following administration of diclazuril suspended in water and by direct application of diclazuril sodium salt to the oral mucosa. Compared with diclazuril itself, the sodium salt formulation of diclazuril applied to the oral mucosa was rapidly and reliably absorbed. Plasma concentrations of diclazuril peaked at around 8 h after oral-mucosal administration of diclazuril sodium salt. On the contrary, application of diclazuril itself orally resulted in delayed and variable absorption. The mean bioavailability of diclazuril as pure powder was 42.5% relative to diclazuril sodium salt indicating approximately 2.5-fold increase in bioavailability of diclazuril as a sodium salt relative to diclazuril as a pure compound in cattle. The present study also reports finding of a previously unreported diclazuril metabolite at high concentrations in plasma especially after oral administration of diclazuril. Further studies, including synthesis and characterization of the novel described metabolite, are required to accurately determine aspects of the metabolism of diclazuril in cattle.

Resveratrol and regular exercise may attenuate hypertension-induced cardiac dysfunction through modulation of cellular stress responses

AimsHypertension is one of the major causes of cardiac damage. In this study, the effects of resveratrol supplementation and regular exercise on hypertension-induced cellular stress responses of myocardium were compared. Main methodsHypertension was induced in male Wistar rats by deoxycorticosterone-acetate + salt administration for 12 weeks. Resveratrol and regular exercise were applied for the last six weeks. In addition to biochemical and molecular examinations, isoprenaline, phenylephrine and, acetylcholine-mediated contractions and sinus rate were recorded in the isolated cardiac tissues. Key findingsResveratrol and regular exercise reduced systolic blood pressure in hypertensive rats. The altered adrenergic and cholinergic responses of the right atrium and left papillary muscles in hypertension were separately improved by resveratrol and regular exercise. Resveratrol and regular exercise decreased plasma and cardiac total antioxidant capacity and, augmented the expression of antioxidant genes in hypertensive rats. While regular exercise restored the increase in p-PERK expression associated with endoplasmic reticulum stress and decrease in mitophagic marker PINK1 expression, resveratrol only ameliorated PINK1 expression in hypertensive rats. Resveratrol and exercise training suppressed hypertension-induced NLRP3 inflammasome activation by reversing the increase in NLRP3, p-NF-κB expression and the mature-IL-1β/pro-IL-1β and cleaved-caspase-1/pro-caspase-1 ratio. Resveratrol and exercise enhanced mRNA expression of caspase-3, bax, and bcl-2 involved in the apoptotic pathway, but attenuated phosphorylation of stress-related mitogenic proteins p38 and JNK induced by hypertension. SignificanceOur study demonstrated the protective effect of resveratrol and exercise on hypertension-induced cardiac dysfunction by modulating cellular stress responses including oxidative stress, ER stress, mitophagy, NLRP3 inflammasome-mediated inflammation, and mitogenic activation.

Calcium Chloride Requirement and Postreperfusion Rebound During Massive Transfusion in Liver Transplantation

The administration of citrated blood products during massive transfusion requires calcium salt administration to prevent citrate toxicity and to maintain ionized calcium values. The literature does not provide adequate guidance for the amount of calcium required during massive transfusions during liver transplantation. This study was conducted to provide guidance on calcium salt replacement during a massive transfusion in liver transplant patients, with a focus on the phase of transplantation during which citrate metabolism was minimal. An observational retrospective chart review. An academic single-institution study of hospitalized patients. One hundred thirty-two patients after liver transplantation. The study authors observed documented measurements of ionized calcium and observed the ratio of calcium salts to citrated bank blood products in patients undergoing liver transplantation with complete data sets. They also observed the effect of continuous venovenous hemofiltration on the distribution of ionized calcium values. Prereperfusion, an average of 1.09 g CaCl2/L of citrated blood was administered to maintain ionized calcium in the normal range. Postreperfusion, less CaCl2 was administered, and a rebound of ionized calcium occurred. Prereperfusion, continuous venovenous hemofiltration reduced the number of ionized calcium values outside of 2 standard deviations, meaning fewer values were critically low. With massive transfusions up to 67 liters (approximately 13 blood volumes), 1.09 g CaCl2/L citrated blood maintained ionized calcium in the normal range in the absence of citrate metabolism. This ratio may have value in empiric treatment when ionized calcium measurements are unavailable, and massive transfusion rates exceed metabolic capacity.

Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity.

Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters. Several studies have suggested that GABA supplements can reduce blood pressure and modulate the renal immune system in vitro and in vivo. In the present study, we investigated the effect of GABA-enriched salt as an alternative to traditional salt on aggravated renal injury by high salt intake in cisplatin-induced nephrotoxicity mice. High salt intake accelerated the increase of biomarkers, such as blood urea nitrogen and serum creatinine levels for renal injury in cisplatin-induced nephrotoxicity mice. However, oral administration of GABA-contained salt notably suppressed serum BUN and creatinine levels. The efficacy of GABA salt was superior to lacto GABA salt and postbiotics GABA salt. Furthermore, GABA-enriched salt markedly restored histological symptoms of nephrotoxicity including renal hypertrophy, tubular dilation, hemorrhage, and collagen deposition aggravated by salt over-loading in cisplatin-exposed mice. Among them, GABA salt showed a higher protective effect against cisplatin-induced renal histological changes than lacto GABA salt and postbiotics GABA salt. In addition, administration of high salt significantly enhanced expression levels of apoptosis and inflammatory mediators in cisplatin-induced nephrotoxicity mice, while GABA-enriched salt greatly down-regulated the expression of these mediators. Taken together, these results demonstrate the protective effect of GABA against damage caused by high salt intake in cisplatin-induced renal toxicity. Its mechanism may be due to the suppression of hematological and biochemical toxicity, apoptosis, and inflammation. In conclusion, although the protective efficacy of GABA salt on renal injury is different depending on the sterilization and filtration process after fermentation with L. brevis BJ20 and L. plantarum BJ21, our findings suggest that GABA-enriched salt has a beneficial effect against immoderate high salt intake-mediated kidney injury in patients with cisplatin-induced nephrotoxicity.

URINARY EXCRETION OF PLUTONIUM IN MAYAK WORKERS DURING AND AFTER CA-DTPA ADMINISTRATION.

Chelation therapy is sometimes used after potential exposures to plutonium to increase urinary excretion of the radionuclide to improve the accuracy of bioassay measurements. The purpose of this report is to describe the enhancement of urinary excretion of plutonium during and after the administration of the trisodium salt of calcium diethylenetriaminepentaacetate (Ca-DTPA) daily for 3d to a group of male and female plutonium workers from the Mayak Production Association in Ozyorsk, Russia. One-hundred and two cases (18 females and 84 males) were selected where urinary contents of plutonium, prior to chelation, exceeded the detection threshold. Daily urine collections were obtained during the 3d of Ca-DTPA treatments. In addition, 58 of these cases had urine bioassays at 1-45d after chelation. The daily enhancement over baseline values excretion of plutonium was found to be 50.4×/1.4 (geometric mean and geometric standard deviation); 58.9×/1.2; 72.9×/1.4 in the first, second and third days of Ca-DTPA administration. The mean enhancement for the 3-d period was 60.1×/1.7. The rate of plutonium excretion from 1 to 45d after chelation decreased with a half-period of 3.9d and the chelation enhancement factor (Кenh-i) is described by the function Кenh-i=(0.79±0.24)+(42.9±1.2)×e-(0.18±0.01)×day.

Secreted protein acidic and rich in cysteine (SPARC) and a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) increments by the renin-angiotensin system induce renal fibrosis in deoxycorticosterone acetate-salt hypertensive rats

Secreted protein acidic and rich in cysteine (SPARC), an extracellular matrix (ECM) protein, was recently shown to induce collagen deposition through the production of a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) in the aging heart. ADAMTS1 regulates ECM turnover by degrading ECM components, and its excessive activation contributes to various pathological states, including fibrosis. The present study investigated the pathophysiological regulation and role of SPARC and ADAMTS1 in renal fibrosis using uninephrectomized rats treated with deoxycorticosterone acetate (DOCA, 40 mg/kg/week, subcutaneously) and salt (1% in drinking water). The administration of DOCA and salt gradually and significantly elevated systolic blood pressure during the 3-week treatment period, induced proteinuria, decreased creatinine clearance, and increased NADPH oxidase-derived superoxide production, malondialdehyde concentrations, and monocyte chemoattractant protein-1 and osteopontin expression in the kidneys. Glomerulosclerosis, fibrillar collagen deposition, and transforming growth factor-β expression increased in a time-dependent manner, and SPARC and ADAMTS1 expression showed a similar pattern to these changes. The angiotensin II type-1 receptor blocker losartan suppressed the overexpression of SPARC and ADAMTS1, and an in vitro exposure to angiotensin II induced the production of both SPARC and ADAMTS1 in renal fibroblast NRK-49F cells. Knockdown of the SPARC gene with small interfering RNA reduced all forms (the 110-kDa latent and 87- and 65-kDa bioactive forms) of ADAMTS1 expression as well as collagen production. These results suggest that SPARC is induced by the renin-angiotensin system and may be a fibrogenic factor, at least in part, by producing ADAMTS1 in hypertensive renal disease.

Sodium butyrate inhibits colitis-associated colorectal cancer through preventing the gut microbiota dysbiosis and reducing the expression of NLRP3 and IL-1β

• Sodium butyrate (NaB) ameliorated colitis and colitis associated cancer induced by AOM/DSS in mice. • NaB attenuated colon inflammation induced by AOM/DSS through inhibiting NLRP3 inflammasome. • NaB protected mice from AOM/DSS-induced CAC by improving colon inflammation and regulating gut microbiota dysbiosis. Sodium butyrate (NaB) is a by-product of dietary fiber that has an anti-tumor effect on colorectal cancer (CRC). The aim of this study was to explore the effect of NaB on tumor and colitis using a colitis-associated colorectal cancer (CAC) model. CAC model was induced in mice by administration of azoxymethane (AOM) and dextran sulfate sodium salt (DSS). 0.1 M NaB in drinking water, or intraperitoneal injection of NaB (1 g/kg body weight) was given during the study period. NLRP3 inflammasome-related molecules were detected. The composition and taxonomy of colorectal microbiota were analyzed. NaB increased spleen index decreased by AOM/DSS. NaB attenuated tumors by reducing tumor load and tumor size in AOM/DSS-induced mice. NaB protected mice from CAC by improving colitis and inhibiting expression of NLRP3 and IL-1β. NaB regulated gut microbiota dysbiosis induced by AOM/DSS. In conclusion, NaB inhibited CAC by ameliorating the gut microbiota dysbiosis and inhibiting colitis.