Rate Of Reabsorption Research Articles

NLRP3 inhibition improves maternal hypertension, inflammation, and vascular dysfunction in response to placental ischemia.

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder with end-organ damage that presents after 20 wk of gestation. PE pathophysiology often includes vascular dysfunction and increased inflammation that continues to damage patient health even after PE resolves. Currently, there is no cure for PE beyond delivery of the fetal-placental unit. Previous clinical studies have identified elevated placental NLRP3 expression in patients with PE and suggest NLRP3 as a potential therapeutic target. In this study, we examined the effect of NLRP3 inhibition on PE pathophysiology in the reduced uterine perfusion pressure (RUPP) model rat using MCC950 (20 mg/kg/day) or esomeprazole (3.5 mg/kg/day). We hypothesized that increased NLRP3 in response to placental ischemia impairs anti-inflammatory IL-33 signaling to induce T-helper 17 cell (TH17) and cytolytic NK cell (cNK) activation, which is known to mediate oxidative stress and vascular dysfunction leading to maternal HTN and intrauterine growth restriction. RUPP rats had significantly higher placental NLRP3 expression, maternal blood pressure, fetal reabsorption rate, vascular resistance, oxidative stress, cNKs and TH17s, and decreased IL-33 compared with normal pregnant (NP) rats. NLRP3 inhibition, with either treatment, significantly reduced placental NLRP3 expression, maternal blood pressure, fetal reabsorption rates, vascular resistance, oxidative stress, cNK, and TH17 populations in RUPP rats. Based on our findings, NLRP3 inhibition reduces PE pathophysiology and esomeprazole may be a potential therapeutic for PE treatment.

Influence of mineralized and demineralized xenograft bone on the repair of intraoral bone defect in rats.

Introduction: Mineralized bovine bone grafts have been widely used as substitutes for bone losses in dental clinics. Studies have shown that exposing the organic components of the bone matrix at surgical sites accelerates bone deposition. Objective: The present study evaluated the bone repair progress of an intraoral bone defect in rats after grafting with mineralized (MBB) and demineralized bovine bone (DBB). Materials and Methods: An intraoral bone defect was created after extraction of the right maxillary first molar, drilling the area of the alveoli of the four distal roots using a diamond tip. The defect was filled with the MBB or DBB graft. Grafting effects were evaluated after 1, 7, 14, 21, and 49 days, using radiographic and histological data. Results: After 14 days, all groups showed full mucosa epithelialization at the surgical site. Radiographic data showed an improvement in bone deposition in defects grafted with the organic matrix. This data was confirmed by histological analysis. A higher level of bone maturation of the neoformed trabeculae and a faster reabsorption rate were also observed to be a feature of the DBB graft. Conclusion: The present in vivo data revealed that the DBB graft may represent an alternative to mineralized biomaterials.

Sex differences of burosumab in children with X-linked hypophosphataemic rickets.

The severity of X-linked hypophosphataemic rickets (XLH) may be affected by genotype and sex. However, burosumab, a fully humanized monoclonal antibody against fibroblast growth factor 23, has the same pediatric dose recommendation for both sexes (0.8mg/kg every 2weeks). In a retrospective cohort study, we describe the burosumab response differences by sex in children with XLH. We treated 10 children (5 females, mean age at initiation 4.2 ± 3.5years) with XLH with burosumab. Initial mean serum phosphate was 0.69 ± 0.18mmol/L in males and 0.86 ± 0.22mmol/L in females (p = 0.108). The mean ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) was 0.55 ± 0.11mmol/L in males and 0.76 ± 0.23mmol/L in females (p = 0.06). The mean starting dose of burosumab was 0.83 ± 0.19mg/kg subcutaneously every 14days (males: 0.79 ± 0.19mg/kg; females: 0.87 ± 0.21mg/kg, n.s.). Two weeks after starting burosumab, serum phosphate differed significantly between males (0.90 ± 0.21mmol/L) and females (1.27 ± 0.25mmol/L) (p = 0.018). All males required a dose increase to try to normalize serum phosphate. On day 140 after starting, the average dose in males increased further to 1.24 ± 0.41mg/kg to achieve a phosphate of 0.87 ± 0.11mmol/L while females had a normal phosphate and alkaline phosphatase on the starting dose. After a mean of 458 ± 79days, the mean burosumab dose/kg in males was 1.68 ± 0.61mg/kg, mean serum phosphate was 1.08 ± 0.23mmol/L, mean TmP/GFR was 1.01 ± 0.20, mean alkaline phosphatase had normalized to 303.6 ± 40.7U/L, and mean 1.25(OH)2 vitamin D level was 186.4 ± 16.6nmol/L. Our findings may suggest a sex difference in response to burosumab in XLH patients. Our data suggest that males may require higher doses.

Stoichiometric Characteristics of Leaf, Litter and Soil during Vegetation Succession in Maolan National Nature Reserve, Guizhou, China

Carbon (C), nitrogen (N), phosphorus (P) and potassium (K) are the main nutrient elements widely found in soil, litter and leaves, and their stoichiometric ratios are important indicators of ecosystem functions. However, there is little research on the effects that nutrient cycle and vegetation succession have on leaf, litter and soil nutrients and stoichiometric ratios, especially in the fragile karst areas. To reveal the nutrient cycling characteristics and ecosystem stability mechanism during vegetation succession, leaf, litter and soil samples were collected from the herbaceous community (HC), shrub community (SC), secondary forest community (SF) and primary forest community (PF) in a typical karst area at growth and senescence phases. The results showed that the nutrient contents and stoichiometric ratios of leaf, litter and soil in the main layers of each community were significantly different at the growth and senescence phase. The utilization efficiency of N in the leaves of the main layers of each succession community first decreased and then increased at different growth stages, and the utilization efficiency of P increased but the reabsorption rates of N and P showed a continuous decreasing trend. In addition, there was a significant allometric relationship between N and P contents in plant leaves during the growth phase. More importantly, the internal stability of N content in plant leaves was higher than the P content, suggesting that vegetation succession significantly affected leaf, litter and soil nutrient contents and their stoichiometric ratios in our study region. The strength of the relationship between them reflects the inheritance and co–variation of nutrient content to a certain extent, and the differences in the strategies that different species in the community use to adapt to the fragile karst environment. This study concludes that plants in the karst region mainly improve their P utilization efficiency to adapt to low phosphorus stress in soil and ensure the normal physiological and biochemical responses in the process of vegetation succession.

Design and Modeling of Bioreactor Utilizing Electrophoresis and Di-Electrophoresis Techniques for Regenerating Reabsorption Function of Human Kidney PCT in Microfluidics Environment.

The need for innovation in medical device technology is immense; especially to replace dialysis techniques the necessity is extremely high. Available techniques that promised to replace dialysis have not yet geared up to the marketization level. The utilization of live kidney cells makes these devices costly, delicate, and unreliable. This paper aims to design a bioreactor to mimic the reabsorption function of the kidney that is fully artificial and highly controllable, which can be one step forward to the emerging Kidney-on-Chip (KOC) technology. The additional benefit of the proposed design is that it utilizes size-dependent reabsorption along with charge-dependent reabsorption phenomena to make it more compatible with human kidney function. The electrophoresis (EP), and di-electrophoresis (DEP) techniques are utilized to mimic the reabsorption function in this report. The structure utilized in the present design exactly replicates the proximal convoluted tubule (PCT) dimensions and functions as well. The whole setup is implemented in the COMSOL Multiphysics FEM benchmark tool for simulation, and analysis with appropriate boundary conditions. The device when excited by an electric field, Electrophoresis has produced a maximum velocity of 1.07 m/s for DC excitation and di-electrophoresis has produced a maximum flow velocity of 1.23 m/s, where both the offset voltages are the same (0.7 V). The flow velocity obtained utilizing both EP and DEP produced a reabsorption rate of 50-58% depending on the voltage applied and dimensions considered which is close to 60% reabsorption rate of the normal human kidney PCT. In accordance with the outcomes produced, the di-electrophoresis technique proved to be more efficient in realizing bioreactor as compared to electrophoresis. The novelty of the present work lies in the creation of a simulation environment, rigorous analysis, and optimization of the bioreactor supported by compact mathematical model.

Sealing the Cranial Base Access After Endonasal Endoscopic Approach: Reabsorption Rate of Fat Graft in the “3FTechnique”

Sealing the Cranial Base Access After Endonasal Endoscopic Approach: Reabsorption Rate of Fat Graft in the “3FTechnique”

Renal and Vascular Effects of Combined SGLT2 and Angiotensin-Converting Enzyme Inhibition.

Background:The cardiorenal effects of sodium-glucose cotransporter 2 inhibition (empagliflozin 25 mg QD) combined with angiotensin-converting enzyme inhibition (ramipril 10 mg QD) were assessed in this mechanistic study in patients with type 1 diabetes with potential renal hyperfiltration.Methods:Thirty patients (out of 31 randomized) completed this double-blind, placebo-controlled, crossover trial. Recruitment was stopped early because of an unexpectedly low proportion of patients with hyperfiltration. Measurements were obtained after each of the 6 treatment phases over 19 weeks: (1) baseline without treatment, (2) 4-week run-in with ramipril treatment alone, (3) 4-week combined empagliflozin-ramipril treatment, (4) a 4-week washout, (5) 4-week combined placebo-ramipril treatment, and (6) 1-week follow-up. The primary end point was glomerular filtration rate (GFR) after combination treatment with empagliflozin-ramipril compared with placebo-ramipril. GFR was corrected for ramipril treatment alone before randomization. At the end of study phase, the following outcomes were measured under clamped euglycemia (4 to 6 mmol/L): inulin (GFR) and para-aminohippurate (effective renal plasma flow) clearances, tubular sodium handling, ambulatory blood pressure, arterial stiffness, heart rate variability, noninvasive cardiac output monitoring, plasma and urine biochemistry, markers of the renin-angiotensin-aldosterone system, and oxidative stress.Results:Combination treatment with empagliflozin-ramipril resulted in an 8 mL/min/1.73 m2 lower GFR compared with placebo-ramipril treatment (P=0.0061) without significant changes to effective renal plasma flow. GFR decrease was accompanied by a 21.3 mL/min lower absolute proximal fluid reabsorption rate (P=0.0092), a 3.1 mmol/min lower absolute proximal sodium reabsorption rate (P=0.0056), and a 194 ng/mmol creatinine lower urinary 8-isoprostane level (P=0.0084) relative to placebo-ramipril combination treatment. Sodium-glucose cotransporter 2 inhibitor/angiotensin-converting enzyme inhibitor combination treatment resulted in additive blood pressure–lowering effects (clinic systolic blood pressure lower by 4 mm Hg [P=0.0112]; diastolic blood pressure lower by 3 mm Hg [P=0.0032]) in conjunction with a 94.5 dynes × sex/cm5 lower total peripheral resistance (P=0.0368). There were no significant changes observed to ambulatory blood pressure, arterial stiffness, heart rate variability, or cardiac output with the addition of empagliflozin.Conclusions:Adding sodium-glucose cotransporter 2 inhibitor treatment to angiotensin-converting enzyme inhibitor resulted in an expected GFR dip, suppression of oxidative stress markers, additive declines in blood pressure and total peripheral resistance. These changes are consistent with a protective physiologic profile characterized by the lowering of intraglomerular pressure and related cardiorenal risk when adding a sodium-glucose cotransporter 2 inhibitor to conservative therapy.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02632747.

20-OR: The Renal and Vascular Effects of Combined SGLT2 and Angiotensin Converting Enzyme Inhibition

The goal of this mechanistic trial was to determine the kidney and cardiovascular effects of combined treatment with an SGLT2i (empagliflozin 25mg QD) and an ACEi (ramipril 10mg QD) for 4 weeks in patients at risk of renal hyperfiltration. In this randomized, double-blind, placebo-controlled, cross-over trial, measurements were obtained following each of the 4 treatment phases: 1) no treatment, 2) 4-week ramipril treatment alone, 3) 4-week empagliflozin-ramipril combination treatment, and 4) 4-week placebo-ramipril combination treatment. The primary endpoint was GFR after empagliflozin-ramipril treatment compared to placebo-ramipril. At the end of each study phase the following measurements were performed under clamped euglycemia (4-6 mmol/L) : inulin (GFR) and paraaminohippurate (effective renal plasma flow, ERPF) clearances, tubular sodium handling, ambulatory blood pressure, arterial stiffness, heart rate variability, non-invasive cardiac output monitoring, plasma and urine biochemistry. Empagliflozin-ramipril treatment resulted in an 8ml/min/1.73m2 lower GFR (p=0.0061) , lower absolute proximal fluid reabsorption rate (p=0.0092) , lower absolute proximal sodium reabsorption rate (p=0.0056) , and lower urinary 8-isoprostane (p=0.0084) relative to placebo-ramipril treatment. Empagliflozin-ramipril treatment resulted in additive blood pressure lowering effects (SBP p=0.0112; DBP p=0.0032) and a lower total peripheral resistance (p=0.0368) . There were no other significant changes observed with the addition of empagliflozin. SGLT2i-ACEi combination treatment resulted in an expected GFR “dip”, suppression of oxidative stress markers, and additive declines in blood pressure and total peripheral resistance in this mechanistic study. These changes are consistent with a protective physiological profile characterized by the lowering of intraglomerular pressure and related cardiorenal risk when adding an SGLT2i to conservative therapy. Disclosure Y. Lytvyn: None. K. Kimura: Employee; 3Boehringer Ingelheim Canada Ltd./Ltée. N. Peter: Employee; Boehringer Ingelheim Pharma GmbH & Co.KG. V.S. Lai: Advisory Panel; Baxter. J. Tse: None. L. Cham: None. B.A. Perkins: Advisory Panel; Abbott Diabetes, Insulet Corporation, Sanofi. Board Member; Novo Nordisk. Research Support; BMO Bank of Montreal, Novo Nordisk. Other Relationship; Abbott Diabetes, Insulet Corporation, Medtronic, Novo Nordisk. N. Soleymanlou: Employee; Boehringer Ingelheim Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc. D. Cherney: Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk, Mitsubishi Tanabe Pharma Corporation, Sanofi. Funding Boehringer Ingelheim and CIHR, Diabetes Canada and the Heart and Stroke Richard Lewar Centre of Excellence and the Heart and Stroke Foundation of Canada

Long follow-up of Multiple Recurrent Calcific Masses–A rare case report of Hyperphosphatemic Familial Tumoral Calcinosis

Hyperphosphatemic familial tumoral calcinosis (HFTC) is an autosomal recessive benign condition of dysregulated phosphate metabolism (biallelic mutation in GLANT3, KLOTHO or FGF23) due to deficiency or resistance of intact fibroblast growth factor 23 resulting in deposition of large amount of ectopic calcium salts in periarticular soft tissues. We present a 21-year male with multiple recurrent masses around both hips, feet, left knee, and left elbow. His serum inorganic phosphate levels and ratio of renal tubular reabsorption rate of phosphate to corrected glomerular filtration rate were markedly elevated. Medical treatment to lower serum phosphate levels by placing him on tablet sevelamer hydrochloride and acetazolamide and surgical excision of the periarticular masses lead to disease remission. At 4 years follow up he has no recurrence and his functional scores (SF 36 and Harris Hip Score) have tremendously improved. Tumoral calcinosis, though rare must be kept in mind as a differential in abnormal calcific masses and with good radiological and laboratory support can be diagnosed early.

NLRP3 Inhibition Improves Maternal Blood Pressure, Inflammation, and Vascular Function During Placental Ischemia

Preeclampsia (PE) is a pregnancy, hypertensive disorder with end‐organ damage, that develops after 20 weeks of gestation. PE pathophysiology often includes vascular dysfunction and increased inflammation that continues to damage patient health even after their PE resolves. Currently, there are no treatments for PE beyond delivery of the fetal‐placental unit. Previous clinical studies have identified elevated NLRP3 expression in PE placentas and suggest NLRP3 as a potential therapeutic target. In this study, we examined the effects of NLRP3 inhibition on PE pathophysiology in the reduced uterine perfusion pressure (RUPP) rat using MCC950 (20 mg/kg/day) or esomeprazole (3.5 mg/kg/day). We hypothesized that increased NLRP3 in response to placental ischemia impairs anti‐inflammatory IL‐33 signaling to induce T‐helper17 cell (TH17) and cytolytic NK cell (cNK) activation, which is known to mediate oxidative stress and vascular dysfunction causing maternal HTN and intrauterine growth restriction. RUPP rats had significantly higher placental NLRP3 expression, maternal blood pressure, fetal reabsorption rate, vascular resistance, oxidative stress, cNKs and TH17s, and decreased IL‐33 compared to normal pregnant (NP) rats. NLRP3 inhibition, with either treatment, significantly reduced placental NLRP3 expression, maternal blood pressure, fetal reabsorption rates, vascular resistance, oxidative stress, cNK and TH17 populations in RUPP rats. Based on our findings, NLRP3 inhibition reduces PE pathophysiology and esomeprazole may be a potential therapeutic for PE treatment.

X-linked hypophosphatemic rickets: Description of seven new variants in patients followed up in reference hospitals in Rio de Janeiro.

BackgroundX‐linked hypophosphatemic rickets (XLHR) is a rare genetic disease, often delayed in diagnosis due to the low degree of suspicion and limited access to sophisticated diagnostic tools that confirm the diagnosis, such as genetic testing.MethodsThrough a cross‐sectional and observational study, 26 patients with a previously presumptive diagnosis of X‐linked hypophosphatemic rickets (based on clinical history, laboratory findings, and physical examination), were followed for approximately 12 months. During 12 months of follow‐up, only 16 patients underwent genetic testing and enrolled in the study. Previous data were analyzed, such as clinical history (e.g., gender, current age, age of clinical diagnosis, age of admission to hospital, family history, and previous orthopedic surgery), physical exam, imaging tests (e.g., radiological changes) and laboratory tests (e.g., tubular maximum reabsorption rate of phosphate to glomerular filtration rate, alkaline phosphatase, and phosphate levels) at the time of the patient’s admission to IEDE and UFRJ, to corroborate and substantiate our research. These data were extracted from the medical records of the patients.ResultsAmong the 16 patients analyzed by molecular biology techniques, the new generation sequencing (NGS), using DNA samples from oral swabs, we obtained seven variants never previously described, which were verified by Sanger sequencing. Among the seven variants never previously described, the most common coding impact was the nonsense mutation. We found two frameshift, one intronic splicing variant, three nonsense, and one deletion splice junction loss. Among patients with new mutations who presented data in the medical record, 100% showed a reduction in TmP/GFR (average of 1.98 mg/dl), the most sensitive laboratory parameter at the time of diagnosis, as well as serum phosphorus (100% had hypophosphatemia on arrival at the referral hospitals––average of 2.4 mg/dl and median 2.3 mg/dl). We also performed NGS on three mothers of the patients with identified mutations. Among these mothers, only one tested negative for the mutation and no family history was reported as well. This mother had serum phosphate of 3.5 mg/dl (normal range: 2.5–4.5 mg/dl) at the time of genetic test collection. The others had a positive test, low serum phosphorus at the time of the molecular test, in addition to a positive family history.ConclusionThis study describes seven new variants in the PHEX gene and aims to increase the knowledge of the scientific community about the types of mutations involving this gene, increasing information on the genetic basis of this condition, enabling future considerations about genotype–phenotype correlation, in addition to diagnosis accurate and early.

A new moisture control method: Analysis of dynamic changes of temperature and moisture in coal particles during drying

The vapor–solid double split moving bed dryer compared to other dryer achieves the purpose of uniform drying of particles and higher drying efficiency. Aiming at theoretical blind spots and technical errors in this technology, a small drying device with stirring was set up in the laboratory to simulate the interface update of coal in the moving heating surface, and the dynamic changes of temperature and moisture during the drying period. Then the changes of coal particle characteristics after drying was tested and analyzed to evaluate the effect of these changes and storage conditions on water re-absorption during dry coal storage. The results indicate that interface update, drying temperature and particle size were three main factors that affect the drying rate of coal. The higher drying temperature will cause the shrinkage and collapse of the macropores and mesopores, this reduces the water re-absorption rate of dry coal during later storage in bunker. The reasonable stirring speed can not only meet the interface renewal rate of coal heating surface, but also protect the structure of large particles from being destroyed. Finally, the increase of ambient temperature and partial pressure of water vapor also can reduce the water re-absorption.

Analytical study of creeping flow of Maxwell fluid in a permeable slit with linear re-absorption

This research presents the analytical study of the creeping flow of a Maxwell fluid in a permeable slit under the effect of linear reabsorption. Analysis of fluid leakage on the slit wall is carried out with the help of the law of conservation of momentum in the rectangular coordinates. The mathematical model in the form of the system of nonlinear partial differential equations is solved by the recursive approach explaining the hydrodynamic aspects of creeping Maxwell fluid flow. The expressions for the velocity field, hydrostatic pressure, stream function, leakage flux, and fractional reabsorption on the boundary of the slit are obtained from the mathematical model. Graphical analysis is also established to demonstrate the effects of emerging parameters due to linear reabsorption on slit boundary and relaxation time. It is analyzed that the horizontal and vertical velocity decelerates by the growing values of the relaxation parameter, but the reabsorption rate gives an increasing effect on the shear stress, volume flow rate, and vertical velocity. This analytical study will help the bioengineers in designing the medical tools with the required pressure and flow rate, therefore the application of this model for the hemodialyzer is also important.

Enhanced plasma persistence of ceftriaxone following single intramuscular injection with prior oral dosing of a mammary protective commercial herbal drug as complementary therapy

BackgroundThe herbal drug (Fibrosin®) is often used as supportive therapy with intramuscular ceftriaxone injection for treatment of mastitis in field condition. MethodA single oral dose of Fibrosin® (1.9 g) was given 1 h prior to single intramuscular injection of ceftriaxone at 50 mg kg−1 in 3 apparently healthy male and 3 female goats. Plasma and urine samples were collected at predetermined time intervals and ceftriaxone/ceftizoxime was analyzed by HPLC. Ceftriaxone persisted for 3 h in plasma of Fibrosin® treated healthy goats. ResultsCeftriaxone showed a distinct reabsorption phase in its dispositional profile. Mean t½ K (distribution half-life) following absorption phase and t½ K′ (elimination half-life) following re-absorption phase were 0.091±0.01 and 0.43±0.03 h respectively with a reabsorption half-life (t½Ka′) of 0.18±0.003 h. Ceftriaxone at a lower concentration (67.91±9.42 μg mL−1) was recovered at 24 h post dosing from urine. The reabsorption rate constant was 3.86±0.10 h−1 that suggested rapid intestinal reabsorption. ConclusionRapid intestinal absorption of ceftriaxone indicated shorter persistence in the intestine and it also exhibited enhanced plasma persistence which may help to preserve beneficial intestinal bacteria as well as prevention of antimicrobial resistance development in the intestine for which the herbal drug may be used as a supportive therapy with intramuscular injection of ceftriaxone.

Assessment of Photon Recycling in Perovskite Solar Cells by Fully Coupled Optoelectronic Simulation

An optical dyadic Green's function framework to describe the transverse electromagnetic fields in a planar perovskite solar-cell stack is coupled to an electronic drift-diffusion model for rigorous treatment of photon recycling in the wave-optics regime for a realistic photovoltaic device. The optical model provides the local reabsorption rate as well as a detailed-balance compatible radiative prefactor, which are used in the electronic model to achieve a self-consistent solution that yields the full optoelectronic device characteristics. The presented approach provides detailed insights into the impact of photon recycling on device performance under different regimes of charge transport and recombination and can help identify the various electronic and optical losses for nonideal, realistic devices. The global efficiency of photon recycling is quantified by defining quantum efficiencies of reabsorbed radiation, while the local efficiency can furthermore be quantified by defining an effective local radiative prefactor. The model introduced here can be used to guide the design of future devices that exploit the full potential of photon recycling.

ヒトiPS細胞由来の近位尿細管細胞を用いたMPSにおけるP-gpとSGLT2の輸送能評価

Proximal tubule plays an important role in reabsorption of nutrients and excretion of drugs. Such reabsorption and excretion processes are mediated by proteins known as transporters in the proximal tubule cells. To evaluate the transport of nutrients and xenobiotics in vitro, proximal tubule microphysiological systems (MPS) have been developed. However, conventional proximal tubule MPS employ cells derived from experimental animals or cells immortalized by genetic modification. Apparently, the expression levels of transporters are insufficient in these cells. In this study, we prepared MPS employing proximal tubular cells isolated from kidney organoids generated from iPS cells. In this MPS, we quantitatively evaluated the transport of SGLT2, which is responsible for glucose reabsorption, and P-gp, which is responsible for drug excretion. As a result, compared to MPS using immortalized cells, MPS using iPS cell-derived cells showed an approximately 1.6-fold improvement in the transport capacity. This indicates that we were able to produce an MPS that better reproduced reabsorption and excretion rates in vivo.

Transient Type 3 Renal Tubular Acidosis during Cyclic Vomiting Syndrome

Type 3 renal tubular acidosis is a pathological condition characterized by the simultaneous occurrence of distal renal tubular acidosis, which causes urinary acidification disorders, and proximal renal tubular acidosis, which causes impaired reabsorption of bicarbonate ions. Type 3 renal tubular acidosis is considered rare. A 5-year-old boy was admitted to our hospital because of frequent vomiting, poor vitality, and fever. He was diagnosed with cyclic vomiting syndrome. Type 3 renal tubular acidosis was also diagnosed because of severe mixed metabolic acidosis with impaired urinary acidification, a low tubular phosphorus reabsorption rate with hypophosphatemia, low-molecular-weight proteinuria, pan-aminoaciduria, and glucosuria. Fluid infusion was performed. On the second day of hospitalization, the vomiting disappeared and the patient was able to eat and drink. He was discharged on the eighth day of hospitalization. The laboratory test abnormalities associated with the renal tubular acidosis gradually improved, and testing at discharge on the eighth day of admission showed no metabolic acidosis, hypophosphatemia, low-molecular-weight proteinuria, or glucosuria. These findings suggested that the type 3 renal tubular acidosis was transient. Severe metabolic acidosis was observed in this patient because of both normal anion gap metabolic acidosis due to type 3 renal tubular acidosis and anion gap metabolic acidosis due to cyclic vomiting syndrome. Although type 3 tubular acidosis is rare, the resultant metabolic acidosis worsens when combined with a disease that causes metabolic acidosis. Type 3 tubular acidosis should be ruled out when severe metabolic acidosis is present.

Effects of Drugs Reabsorption Time Delays for a Pharmacokinetics Model in Humans

A three-compartmental delay model is formulated to describe the pharmacokinetics of drugs subjected to both intravenous and oral doses with reabsorptions by the central compartment. Model dynamics are analyzed rigorously, and two equilibrium points are obtained to be locally asymptotically stable under certain conditions. Time delays used as lags in reabsorption of drugs by central compartment from other two compartments caused rebounds or peaks and fluctuations in the time profiles for amounts of drug in all the compartments. Sensitivity analysis revealed that elimination rates decrease the amounts in all compartments. Furthermore, reabsorption rates cause superimposition at the initial phases of the drug amount profiles; subsequently, the quantities decrease in compartment one and increase in compartments two and three, respectively.

Different Effects of Empagliflozin on Markers of Mineral-Bone Metabolism in Diabetic and Non-Diabetic Patients with Stage 3 Chronic Kidney Disease.

Background and objectives: Treatment with sodium–glucose co-transporter 2 (SGLT2) inhibitors decrease tubular reabsorption of phosphate, which may explain the reduction of bone mineral density and an excess of bone fractures observed in some studies with this class of drugs. Since an increased risk of bone fractures may also be a result of diabetes itself, our study aimed to compare the effect of empagliflozin on the markers of mineral-bone metabolism between diabetic (DKD) and non-diabetic (ND-CKD) patients with stage 3 chronic kidney disease (CKD). Materials and Methods: Forty-two patients with stage 3 CKD and A2 albuminuria, including 18 with DKD and 24 ND-CKD, were investigated. All subjects received 10 mg empagliflozin for 7 days. Serum calcium, phosphate, parathormone (PTH), calcitriol, bone alkaline phosphatase (BAP), FGF-23 and urine calcium, phosphate, albumin and the renal tubular maximum reabsorption rate of phosphate to the glomerular filtration rate (TmP-GFR) were measured before and after empagliflozin administration. Differences in biomarkers response to empagliflozin between DKD and ND-CKD were the main measures of outcome. Results: There was a significant increase of PTH, FGF-23 and phosphate in DKD but not in ND-CKD whereas BAP and TmP/GFR did not change in either group. The reduction of albuminuria was only significant in ND-CKD. Conclusions: The effect of SGLT2 inhibitor on serum mineral and bone markers and on albuminuria in patients with CKD may be differently modified by the presence of diabetes mellitus.

Computational analysis of an axisymmetric flow of Jeffrey fluid in a permeable micro channel

This study presents the computational analysis of axisymmetric flow of Jeffrey fluid in a permeable micro channel with linear reabsorption. Mathematical formulation of complex problem has been carried out in cylindrical coordinates due to the axisymmetric flow. The nonlinear set of partial differential equations is solved by the recursive approach and hydrodynamic aspects of axisymmetric flow of Jeffery fluid are explained in detail. Results are achieved for axial and radial velocity, hydrostatic pressure, stream function, leakage flux, and fractional reabsorption on the boundary. Numerical analysis has also been carried out to demonstrate the effects of emerging parameters due to linear reabsorption on the boundary of micro channel and relaxation time due to Jeffrey fluid parameters. The findings of the study suggest that axisymmetric flow decelerates by the growing values of relaxation time but the reabsorption rate gives the increasing effect on shear stress, volume flow rate, and transverse velocity. This study is useful for bioengineers to design the medical tools required for the flow of bio fluids.