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1.
Yakugaku Zasshi ; 144(5): 577-584, 2024.
Article in Japanese | MEDLINE | ID: mdl-38692934

ABSTRACT

We conducted a multicenter survey of emergency room nurses to obtain information that would be useful for the establishment of pharmacist services in emergency rooms. Notably, 199 valid responses were obtained from 12 hospitals. The most common expectation from pharmacists in the emergency room was "drug management" (70.9%), followed by "providing information to physicians regarding the patient's medication history" (59.3%), and "auditing of dosage and interaction" (57.3%). The working arrangements that the survey respondents wanted regarding pharmacists in emergency rooms were: 24 h pharmacist (41.7% wanted this arrangement), day-shift pharmacist (24.6% wanted this arrangement), 24 h on-call (17.1% wanted this arrangement), day-shift on-call (5.0% wanted this arrangement), telephone support (11.1% wanted this arrangement), and 0.5% said that there was no need for pharmacists. In the analysis of factors affecting nurse satisfaction, day-shift pharmacist was a significant factor. We hope that the results of this survey will be used as a guide for the development of emergency room pharmacist services tailored to the unique characteristics and actual working conditions of each hospital.


Subject(s)
Emergency Service, Hospital , Pharmacists , Pharmacy Service, Hospital , Surveys and Questionnaires , Humans , Japan , Nurses , Adult , Female , Male , Professional Role , Middle Aged
2.
J Exp Bot ; 75(9): 2664-2681, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38452239

ABSTRACT

Plants accumulate high concentrations of ascorbate, commonly in their leaves, as a redox buffer. While ascorbate levels have increased during plant evolution, the mechanisms behind this phenomenon are unclear. Moreover, has the increase in ascorbate concentration been achieved without imposing any detrimental effects on the plants? In this review, we focus on potential transitions in two regulatory mechanisms related to ascorbate biosynthesis and the availability of cellular dehydroascorbate (DHA) during plant evolution. The first transition might be that the trigger for the transcriptional induction of VTC2, which encodes the rate-limiting enzyme in ascorbate biosynthesis, has shifted from oxidative stress (in green algae) to light/photosynthesis (in land plants), probably enabling the continuous accumulation of ascorbate under illumination. This could serve as a preventive system against the unpredictable occurrence of oxidative stress. The second transition might be that DHA-degrading enzymes, which protect cells from the highly reactive DHA in green algae and mosses, have been lost in ferns or flowering plants. Instead, flowering plants may have increased glutathione concentrations to reinforce the DHA reduction capacity, possibly allowing ascorbate accumulation and avoiding the toxicity of DHA. These potential transitions may have contributed to strategies for plants' safe and effective accumulation of ascorbate.


Subject(s)
Ascorbic Acid , Biological Evolution , Plants , Ascorbic Acid/metabolism , Plants/metabolism , Oxidative Stress
3.
Int J Mol Sci ; 25(2)2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38255818

ABSTRACT

Renal biopsy is the gold standard for making the final diagnosis and for predicting the progression of renal disease, but monitoring disease status by performing biopsies repeatedly is impossible because it is an invasive procedure. Urine tests are non-invasive and may reflect the general condition of the whole kidney better than renal biopsy results. We therefore investigated the diagnostic value of extensive urinary sediment analysis by immunofluorescence staining for markers expressed on kidney-derived cells (cytokeratin: marker for tubular epithelial cells, synaptopodin: marker for podocytes, claudin1: marker for parietal epithelial cells, CD68: marker for macrophages (MΦ), neutrophil elastase: marker for neutrophils). We further examined the expression levels of the mRNAs for these markers by real-time reverse transcription polymerase chain reaction. We also examined the levels of mRNAs associated with the M1 (iNOS, IL-6) and M2 (CD163, CD204, CD206, IL-10) MΦ phenotypes. Evaluated markers were compared with clinical and histological findings for the assessment of renal diseases. Claudin1- and CD68-positive cell counts in urinary sediments were higher in patients with glomerular crescents (especially cellular crescents) than in patients without crescents. The relative levels of mRNA for CD68 and the M2 MΦ markers (CD163, CD204, CD206, and IL-10) in urinary sediments were also higher in patients with glomerular crescents. These data suggest that immunofluorescence staining for claudin1 and CD68 in urinary sediments and the relative levels of mRNA for CD68 and M2 MΦ markers in urinary sediments are useful for evaluating the state of glomerular diseases.


Subject(s)
Kidney Diseases , Urinary Tract , Humans , Interleukin-10 , Kidney , Fluorescent Antibody Technique
4.
SSM Popul Health ; 24: 101539, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37927815

ABSTRACT

Introduction: Noncommunicable diseases (NCDs) have become a significant global problem. Health behaviors are associated with NCDs, and characterizing populations using a public health approach can help provide specific interventions according to their characteristics. This study aims to examine the formation of clusters of health behavior combinations in the Japanese working population at risk of NCDs, taking into account the influences of age and gender, using latent class analysis. Methods: Participants were individuals at risk for NCDs but had not previously been diagnosed with any. Latent class analysis (LCA) was used to study clustering based on basic characteristics and health behaviors. All statistical analyses were conducted using R (Version 4.0.4) and the "poLCA" package (Version 1.6.0). Results: This study included 12,168 participants. LCA compared models with one to six latent classes. The five-class model was determined to be the most appropriate based on Bayesian Information Criterion, Akaike Information Criterion, and G^2 values, as well as distinguishable cluster characteristics. Cluster 1: "having healthy lifestyles but disliking hospitals"; Cluster 2: "women with healthy lifestyle behaviors"; Cluster 3: "general population"; Cluster 4: "middle-aged group in need of lifestyle improvement"; Cluster 5: "a group receiving treatment for lifestyle-related diseases." Conclusions: This study reveals discernible health behavior patterns in a sample of the Japanese population using large real-world data, suggesting the effectiveness of distinct approaches when considering a population approach to public health.

5.
CEN Case Rep ; 12(4): 378-383, 2023 11.
Article in English | MEDLINE | ID: mdl-36856751

ABSTRACT

A 48-year-old woman presented with hyperreninemic hypertension and renal dysfunction and was diagnosed with hydronephrosis-related Page kidney. The pathophysiology was "renal tamponade", in which the kidney was compressed by the renal pelvis and Gerota's fascia, resulting in intrarenal microvascular ischemia. Ureteral stent placement promptly improved the hyperreninemic hypertension and renal dysfunction, and additional perirenal fluid drainage gradually improved these conditions. These observations indicated the following three points. First, renal compression-induced renin-angiotensin-aldosterone system upregulation plays an important role in the pathogenesis of Page kidney. Second, physicians should consider perirenal fluid drainage as a therapeutic option in addition to ureteral stenting in patients with hydronephrosis-related Page kidney. Third, bilateral perirenal subcapsular hematomas in this case could be caused by hydronephrosis. Hydronephrosis-induced intrarenal pressure elevation possibly caused chronic perirenal subcapsular hemorrhage at the vulnerable sites of the renal cortex and peeling of the renal capsule from the cortex, resulting in the bilateral massive subcapsular hematomas and Page kidney.


Subject(s)
Hydronephrosis , Hypertension, Renal , Hypertension , Female , Humans , Middle Aged , Kidney/pathology , Hypertension, Renal/complications , Hydronephrosis/diagnosis , Hydronephrosis/etiology , Hypertension/etiology , Hematoma/diagnosis , Hematoma/etiology
6.
J Ultrason ; 22(91): e240-e244, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36483785

ABSTRACT

Aim of the study: Seromas are rarely reported as complications of autologous arteriovenous fistula creation. Case description: An 89-year-old woman was hospitalized for hemodialysis and underwent an autologous arteriovenous fistula creation in the forearm. During cephalic vein expansion using a heparinized saline solution, leakage occurred. A suture was placed to control the leakage, and a Penrose drain was inserted. Serosanguineous drainage ceased on postoperative day two; however, a seroma occurred approximately two weeks after the surgery. Follow-up ultrasonography revealed no growth tendency; therefore, excision and aspiration were unnecessary. Conclusion: This seroma was associated with postoperative dead space, surgical technique, and patient clinical status. Sufficient preoperative ultrasonographic vascular mapping is required to avoid inappropriate handling of veins and prevent seroma formation. Postoperative ultrasonographic follow-up is recommended due to the future risk of fistula dysfunction and infection associated with seroma enlargement, which may necessitate surgical seroma excision.

7.
Circ Rep ; 4(7): 322-329, 2022 Jul 08.
Article in English | MEDLINE | ID: mdl-35860354

ABSTRACT

Background: The overlap of multiple lifestyle-related diseases increases the risk of vascular diseases. This study investigated the effects of a mobile health (mHealth)-based disease management program on blood pressure and the safety of this program in people with multiple lifestyle-related diseases at risk of developing vascular disease. Methods and Results: This retrospective observational study was conducted using secondary data collected by PREVENT Inc. People with a full history of hypertension, diabetes, and dyslipidemia and who participated in a 6-month mHealth-based disease management program were included in the study. The primary outcome was blood pressure. Adverse events during the program were investigated to evaluate safety. In total, 125 participants (mean [±SD] age 55.3±6.2 years) were examined. Systolic and diastolic blood pressure were significantly lower after the intervention than at baseline (systolic blood pressure, 128.0±12.3 vs. 131.9±12.7 mmHg [P<0.001]; diastolic blood pressure, 81.2±9.3 vs. 83.6±8.9 mmHg; P=0.003). No serious adverse events occurred during the program. Conclusions: The present results indicate that the mHealth-based disease management program may reduce blood pressure in people with multiple lifestyle-related diseases at risk of developing vascular disease and that the program is safe. These findings will help shape future health instructions using mHealth-based interventions.

8.
Biopharm Drug Dispos ; 43(3): 108-116, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35508086

ABSTRACT

Acetaminophen (APAP)-induced liver injury (AILI) is the most common cause of acute liver failure. Although the mechanisms that trigger AILI are well known, it is less understood how to halt AILI progression and facilitate liver recovery. Therefore, it is necessary to understand the pathophysiology of APAP hepatotoxicity in patients and to examine predictive/preventive markers. In a clinical study, we had a case in which aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels increased in a patient with a low ratio of APAP glucuronide concentration (AP-G)/APAP plasma concentration. Then a reverse translational study was conducted for clarifying this clinical question. The relationship between plasma AP-G/APAP concentration ratio and the levels of AST and ALT was examined by in vivo and in vitro experiments. In in vivo experiments, 10-week-old rats showed lower UGT activity, lower AP-G/APAP concentration ratios, and higher AST and ALT levels than 5-week-old rats. This suggests an inverse correlation between the AP-G/APAP concentration ratio and the AST, ALT levels in APAP-treated rats. Furthermore, as a result of the in vitro experiment, it was confirmed that the cell viability decreased when the AP-G/APAP concentration ratio in the culture medium decreased. Since the decrease in the plasma AP-G/APAP concentration ratio appears earlier than the increase of AST and ALT levels, the ratio might be a presymptomatic marker of AILI. When APAP is used for a long time, it is recommended to perform therapeutic drug monitoring of the AP-G/APAP concentration ratio, which is a predictive/preventive marker of AILI.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Chemical and Drug Induced Liver Injury , Acetaminophen/adverse effects , Acetaminophen/analogs & derivatives , Acetaminophen/pharmacokinetics , Acetaminophen/toxicity , Alanine Transaminase , Animals , Chemical and Drug Induced Liver Injury/etiology , Humans , Liver , Rats
9.
Intern Med ; 61(14): 2233-2237, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35283374

ABSTRACT

Capnocytophaga species are among the typical zoonotic pathogens causing infections following direct contact with animals. Recently, a putative novel species of zoonotic Capnocytophaga, Capnocytophaga stomatis, was reported. We herein report the first case of bacteremia caused by C. stomatis. A woman in her 80s with multiple myeloma who was receiving bortezomib and dexamethasone therapy was admitted to our hospital with a 2-day history of a fever and right calf redness. She was often licked by her cat. On a blood culture, thin, Gram-negative rods were detected, which were identified as C. stomatis by whole-genome sequencing. The patient was successfully treated with ampicillin-sulbactam treatment. Our case highlights the pathogenic potential of the putative novel Capnocytophaga, C. stomatis, in immunocompromised hosts.


Subject(s)
Bacteremia , Bites and Stings , Gram-Negative Bacterial Infections , Multiple Myeloma , Animals , Bacteremia/complications , Bacteremia/drug therapy , Capnocytophaga , Female , Gram-Negative Bacterial Infections/complications , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/drug therapy , Humans , Multiple Myeloma/complications
10.
Cancer Med ; 10(20): 7174-7183, 2021 10.
Article in English | MEDLINE | ID: mdl-34505396

ABSTRACT

BACKGROUND: The incidence and risk factors of severe anaphylaxis by intravenous anti-cancer drugs are unclear, whereas those of milder reactions have been reported. STUDY DESIGN: Electronic medical charts of cancer patients who have undergone intravenous chemotherapy between January 2013 and October 2020 in a university hospital were retrospectively reviewed. Non-epithelial malignancies were also included in the analysis. "Severe anaphylaxis" was judged using Brown's criteria: typical presentation of anaphylaxis and one or more of hypoxia, shock, and neurologic compromise. (UMIN000042887). RESULTS: Among 5584 patients (2964 males [53.1%], 2620 females [46.9%], median age 66 years), 88,200 person-day anti-cancer drug administrations were performed intravenously, and 27 severe anaphylaxes were observed. The causative drugs included carboplatin (14 cases), paclitaxel (9 cases), and cisplatin, docetaxel, trastuzumab, and cetuximab (1 case each). The person-based lifetime incidence of severe anaphylaxis for patients who received at least one intravenous chemotherapy was 0.48% (27/5584, 95% confidence interval (CI) 0.30%-0.67%) and the administration-based incidence was 0.031% (27/88,200, 95% CI 0.019%-0.043%). Among 124 patients who received at least 10 carboplatin administrations, 10 patients experienced carboplatin-induced severe anaphylaxis (10/124, 8.1%, 95% CI 3.0%-13.1%). Carboplatin caused severe anaphylaxis after at least 9-min interval since the drip started. Thirteen out of 14 patients experienced carboplatin-induced severe anaphylaxis within a 75-day interval from the previous treatment. Paclitaxel infusion caused severe anaphylaxis after a median of 5 min after the first drip of the day at a life-long incidence of 0.93% (9/968, 95% CI 0.27%-1.59%). CONCLUSION: We elucidated the high-risk settings of chemotherapy-induced severe anaphylaxis.


Subject(s)
Anaphylaxis/chemically induced , Antineoplastic Agents/adverse effects , Administration, Intravenous , Aged , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors
11.
Endosc Int Open ; 9(5): E674-E683, 2021 May.
Article in English | MEDLINE | ID: mdl-33937507

ABSTRACT

Background and study aims There has been little evidence assessing the prevalence of musculoskeletal disorders (MSDs) among endoscopists performing recent diagnostic and therapeutic endoscopic procedures requiring prolonged procedural times. We evaluated the prevalence and identified the risk factors for developing MSDs, focusing on procedural time. Methods An electronic survey of endoscopists (n = 213) employed at the Nagoya University Hospital and its affiliated hospitals was developed by a multidisciplinary group.  Results Of the 110 endoscopists (51.6 %) who responded to the survey, eighty-seven endoscopists (79.1 %) had experienced endoscopy-related MSDs during the previous 1 year, and 49 endoscopists (44.5 %) had experienced these MSDs during the previous week. Nineteen endoscopists (17.3 %) reported absence from work due to severe MSDs. The most frequent sites of MSDs were neck, low back, and shoulders. Logistic regression analyses showed that longer upper endoscopic submucosal dissection ESD, (odds ratio: 5.7; 95 %CI: 1.3-25.0), lower ESD (odds ratio 4.9; 95 %CI: 1.1-22.0), and lower gastrointestinal treatment (odds ratio: 5.6; 95 %CI: 2.3-13.3) were significantly associated with the development of MSDs in the low back area. Moreover, longer lower ESD (odds ratio: 5.0; 95 % CI: 1.2-20.2) was a risk factor for symptoms in the left shoulder. Conclusion This study suggests a correlation between the volume of therapeutic endoscopic procedures including ESD and the risk of MSDs mainly low back area and left shoulder. Managing monthly total endoscopic time, in light of organizational ergonomics, could contribute to minimizing such risks of endoscopy-related MSDs.

12.
Intern Med ; 60(21): 3453-3458, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34024856

ABSTRACT

A 73-year-old woman with atrial fibrillation treated with rivaroxaban was hospitalized for nephrotic syndrome. After discontinuation of rivaroxaban to lower the risk of hemorrhagic events, a renal biopsy was performed. Rivaroxaban was scheduled to resume a week after the biopsy to prevent renal hemorrhaging. However, she developed acute brachial arterial embolic occlusion and mural thrombosis in the abdominal aorta before resuming rivaroxaban. If immune-mediated renal diseases are suspected in anticoagulated patients at a risk of thrombotic events, physicians should consider initiating glucocorticoid therapy without a renal biopsy in order to avoid hemorrhagic and thrombotic events.


Subject(s)
Atrial Fibrillation , Nephrotic Syndrome , Aged , Anticoagulants/adverse effects , Biopsy , Factor Xa Inhibitors/adverse effects , Female , Humans , Nephrotic Syndrome/drug therapy , Rivaroxaban/adverse effects
13.
J Occup Health ; 62(1): e12159, 2020 Jan.
Article in English | MEDLINE | ID: mdl-32845553

ABSTRACT

OBJECTIVE: To examine whether the self-monitoring interventions of a mobile health app reduce sedentary behavior in the short and long terms. METHOD: We designed a double-blind randomized control trial. Participants were selected from among the staff of a medical institution and registrants of an online research firm. Forty-nine participants were randomly assigned to either a control group (n = 25) or an intervention group (n = 24). The control group was given only the latest information about sedentary behavior, and the intervention was provided real-time feedback for self-monitoring in addition to the information. These interventions provided for 5 weeks (to measure the short-term effect) and 13 weeks (to measure the long-term effect) via the smartphone app. Measurements were as follows: subjective total sedentary time (SST), objective total sedentary time (OST), mean sedentary bout duration (MSB), and the number of sedentary breaks (SB). Only SST was measured by self-report based on the standardized International Physical Activity Questionnaire and others were measured with the smartphone. RESULTS: No significant results were observed in the short term. In the long term, while no significant results were also observed in objective sedentary behavior (OST, MSB, SB), the significant differences were observed in subjective sedentary behavior (SST, ßint  - ßctrl between baseline and 9/13 weeks; 1.73 and 1.50 h/d, respectively). CONCLUSIONS: Real-time feedback for self-monitoring with smartphone did not significantly affect objective sedentary behavior. However, providing only information about sedentary behavior to users with smartphones may make misperception on the amount of their subjective sedentary behavior.


Subject(s)
Health Behavior , Mobile Applications , Monitoring, Ambulatory , Sedentary Behavior , Smartphone , Adult , Double-Blind Method , Female , Humans , Male , Middle Aged
14.
J Occup Health ; 62(1): e12089, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31599046

ABSTRACT

OBJECTIVE: Recent attention has been focused on sedentary behavior (SB) affecting health outcomes, but the characteristics of indicators reflecting SB remain to be identified. This cross-sectional study aims to identify the characteristics of indicators of SB, focusing on the examination of correlations, reliability, and validity of sedentary variables assessed by the smartphone app. METHOD: Objectively measured data of SB of eligible 46 Japanese workers obtained from smartphones were used. We assessed the characteristics of current indicators being used with a 10-minute or 30-minute thresholds, in addition to the conventional indicators of total sedentary time, mean sedentary bout duration, and total number of sedentary bouts. They were evaluated from three perspectives: (a) association among the indicators, (b) reliability of the indicators, and (c) criterion validity. RESULTS: Total sedentary time under 10 minutes (U10) and U30 had negative associations with Total sedentary time (r = -.47 and -.21 respectively). The correlation between Mean sedentary bout duration and Total number of sedentary bouts was -.84, whereas between Mean sedentary bout duration 10, 30 and Total number of sedentary bouts were -.54 and -.21, respectively. The intraclass correlation coefficients of almost all indicators were around .80. Mean sedentary bout duration, Mean sedentary bout duration 10, Total number of sedentary bouts, Total sedentary time 30, U30 and U10 have significant differences between three BMI groups. CONCLUSION: This study comprehensively revealed the rationale of advantage in the current indicator being used with a 10-minute or 30-minute threshold, rather than the conventional total amount of SB.


Subject(s)
Mobile Applications , Sedentary Behavior , Smartphone , Accelerometry , Adult , Cross-Sectional Studies , Female , Humans , Japan , Male , Middle Aged , Reproducibility of Results , Time Factors
15.
Medicine (Baltimore) ; 96(40): e8216, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28984775

ABSTRACT

RATIONALE: TAFRO syndrome is a systemic inflammatory disease characterized by a constellation of symptoms: Thrombocytopenia, Anasarca, MyeloFibrosis, Renal dysfunction, and Organomegaly. Progressive renal insufficiency is a predominant symptom; however, the mechanism of acute kidney injury (AKI) remains unclear, probably because severe thrombocytopenia prevents kidney biopsy. We report a rare case of TAFRO syndrome with histologically confirmed renal involvement. PATIENTS CONCERNS: A 70-year-old man developed fever, anasarca, AKI, thrombocytopenia, and hepatosplenomegaly. DIAGNOSES: Plasma vascular endothelial growth factor and serum interleukin-6 levels were significantly elevated. The diagnosis of TAFRO syndrome was made based on his clinical and laboratory findings. Kidney biopsy was performed for the evaluation of AKI and provided a diagnosis of membranoproliferative glomerulonephritis-like lesions due to endothelial injury. Glomerular capillary lumens were extremely narrowed or occluded by endothelial swelling, and marked widening of the subendothelial space by electron-lucent material resulted in mesangiolysis and a double-contoured glomerular basement membrane with no immune complex deposits. INTERVENTIONS AND OUTCOMES: The patient required temporary hemodialysis due to oliguric AKI, but steroid therapy rapidly improved renal function. LESSONS: Typically, patients with progressive renal involvement in TAFRO syndrome rapidly develop oliguric or anuric AKI. This report suggests that the reduction of glomerular perfusion by glomerular endothelial injury might be a primary factor in the progressive AKI of TAFRO syndrome. Our case and the literature review indicate that steroid and/or biological therapies result in highly favorable renal outcomes in patients with progressive AKI in TAFRO syndrome.


Subject(s)
Edema/diagnosis , Hypertrophy/diagnosis , Kidney Diseases/diagnosis , Primary Myelofibrosis/diagnosis , Thrombocytopenia/diagnosis , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Aged , Disease Progression , Edema/pathology , Humans , Hypertrophy/pathology , Interleukin-6/blood , Kidney/pathology , Kidney Diseases/pathology , Male , Primary Myelofibrosis/pathology , Syndrome , Thrombocytopenia/pathology , Vascular Endothelial Growth Factor A/blood
16.
Jpn J Infect Dis ; 70(5): 586-589, 2017 Sep 25.
Article in English | MEDLINE | ID: mdl-28367888

ABSTRACT

Outbreaks of Zika virus (ZIKV) infection in tropical and subtropical regions are a cause of worldwide concern and represent a public health emergency. ZIKV was isolated from a 17-year-old patient with fever and maculopapular rash. The patient returned to Japan from the Republic of Fiji in late April 2016. The complete genome sequence of the ZIKV isolate (ZIKV/Hu/S36/Chiba/2016), which might be the first strain to be isolated in Japan, was identified and reported.


Subject(s)
Travel-Related Illness , Zika Virus Infection/diagnosis , Zika Virus Infection/pathology , Zika Virus/isolation & purification , Adolescent , Asian People , Fiji , Humans , Male , Whole Genome Sequencing , Zika Virus/genetics
17.
J Nephrol ; 29(1): 53-62, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25971850

ABSTRACT

BACKGROUND: Plasmin has recently been reported to be associated with renal fibrosis in experimental models, but its role in human renal diseases is unclear. METHODS: Fifty-seven patients with IgA nephropathy (IgAN) were evaluated retrospectively. Plasmin in their renal biopsy tissues was assessed by in situ zymography using a plasmin-sensitive synthetic peptide, and the relationships between patients' histologic or clinical parameters and their renal plasmin activity [assessed semiquantitatively by calculating the positively stained percentage of the total tubulointerstitial (TI) area] were evaluated. RESULTS: Plasmin activity was observed almost exclusively in the TI space (mainly in the interstitium and partly in the tubular epithelial cells) and was significantly stronger in patients with TI lesion (tubular atrophy/interstitial fibrosis and tubulointerstitial inflammation) than in those without TI lesion. It was significantly and positively correlated with the global glomerulosclerosis rate and significantly and negatively correlated with estimated glomerular filtration rate not only at the time of renal biopsy but also at the end of the follow-up period. Double stainings for plasmin activity and inflammatory cells, cytokeratin, or α-smooth muscle actin (α-SMA) in selected patients revealed TI infiltration of inflammatory cells, attenuated tubular epithelial expression of cytokeratin, and augmented interstitial expression of α-SMA close to upregulated plasmin activity in the TI space. CONCLUSIONS: These data suggest that TI plasmin is associated with TI inflammation leading to renal fibrosis, and can cause the decline in renal function seen in patients with IgAN. Reducing plasmin in situ may therefore be a promising therapeutic approach slowing renal fibrogenesis and improving renal function.


Subject(s)
Epithelial Cells/chemistry , Fibrinolysin/analysis , Glomerulonephritis, IGA/metabolism , Kidney Tubules/chemistry , Actins/analysis , Adolescent , Adult , Aged , Biomarkers/analysis , Biopsy , Disease Progression , Epithelial Cells/pathology , Female , Fibrosis , Fluorescent Antibody Technique , Glomerular Filtration Rate , Glomerulonephritis, IGA/pathology , Glomerulonephritis, IGA/physiopathology , Humans , Keratins/analysis , Kidney Tubules/pathology , Kidney Tubules/physiopathology , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Young Adult
18.
Hypertens Res ; 37(11): 976-83, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24965172

ABSTRACT

The expression and effects of ß-adrenergic receptors (ß-ARs) on the neurons of the bulbospinal rostral ventrolateral medulla (RVLM) have been limitedly examined to date. The objective of this study was to examine the expression of ß1- and ß2-ARs on the bulbospinal RVLM neurons electrophysiologically and histologically. To directly investigate whether RVLM neurons display sensitivity to metoprolol (a ß1-AR antagonist), dobutamine (a ß1-AR agonist), butoxamine (a ß2-AR antagonist), and salbutamol (a ß2-AR agonist), we examined changes in the membrane potentials of the bulbospinal RVLM neurons using the whole-cell patch-clamp technique during superfusion of these drugs. During metoprolol superfusion, 16 of the 20 RVLM neurons were hyperpolarized, and 5 of the 6 RVLM neurons were depolarized during dobutamine superfusion. During butoxamine superfusion, 11 of the 16 RVLM neurons were depolarized, and all of the 8 RVLM neurons were hyperpolarized during salbutamol superfusion. These results suggest the expression of ß1- and ß2-ARs on the RVLM neurons. To determine the presence of ß1- and ß2-ARs histologically, immunofluorescence examination was performed. Five metoprolol-hyperpolarized neurons were examined for ß1-AR and tyrosine hydroxylase (TH) immunoreactivity. All of the neurons displayed ß1-AR immunoreactivity, whereas three of the neurons displayed TH immunoreactivity. All of the five RVLM neurons that became depolarized during metoprolol superfusion and hyperpolarized during butoxamine superfusion displayed ß1- and ß2-AR immunoreactivity. Our findings suggest that ß1-AR antagonists or ß2-AR agonists may decrease blood pressure through decreasing the activity of the bulbospinal RVLM neurons.


Subject(s)
Medulla Oblongata/metabolism , Neurons/metabolism , Receptors, Adrenergic, beta-1/biosynthesis , Receptors, Adrenergic, beta-2/biosynthesis , Spinal Nerves/metabolism , Adrenergic beta-1 Receptor Agonists/pharmacology , Adrenergic beta-1 Receptor Antagonists/pharmacology , Adrenergic beta-2 Receptor Agonists/pharmacology , Adrenergic beta-2 Receptor Antagonists/pharmacology , Animals , In Vitro Techniques , Medulla Oblongata/cytology , Patch-Clamp Techniques , Rats , Rats, Wistar , Receptors, Adrenergic, beta-1/drug effects , Receptors, Adrenergic, beta-2/drug effects , Spinal Nerves/cytology
19.
Clin Nephrol ; 82(1): 62-7, 2014 Jul.
Article in English | MEDLINE | ID: mdl-23442257

ABSTRACT

We report a case in which renal biopsies were performed 4 years apart in a woman with a prolonged human parvovirus B19 (HPB19) infection. When she was 29 years old the first biopsy, performed because of microscopic hematuria and mild proteinuria, showed endocapillary and mesangial proliferative glomerulonephritis in light microscopy as well as deposits of immunoglobulins (Igs) and complement C3 on capillary walls. Mesangial, intramembranous, and subepithelial hump-like electron dense deposits were seen in electron microscopy. The principal differential diagnoses, acute poststreptococcal glomerulonephritis and lupus nephritis, were unlikely, and her serological positivity for IgM antibody for HPB19 made us diagnose acute glomerulonephritis associated with HPB19 infection. The second biopsy, performed 4 years later because of persistent proteinuria and prolonged positivity for IgM antibody for HPB19, showed membranoproliferative glomerulonephritis (MPGN) with mesangial interposition and with thickening and double contours of glomerular basement membrane. In tissues obtained in both biopsies, HPB19 DNA was detected by polymerase chain reaction. HPB19 infection has been widely known to cause various glomerular diseases. This case reveals that acute endocapillary proliferative glomerulonephritis can change into MPGN during prolonged HPB19 infection.


Subject(s)
Glomerulonephritis, Membranoproliferative/virology , Kidney/virology , Parvoviridae Infections/complications , Parvovirus B19, Human/isolation & purification , Adult , Antibodies, Viral/blood , Biopsy , DNA, Viral/isolation & purification , Diagnosis, Differential , Disease Progression , Female , Glomerulonephritis, Membranoproliferative/diagnosis , Glomerulonephritis, Membranoproliferative/immunology , Humans , Immunoglobulin M/blood , Kidney/immunology , Kidney/pathology , Parvoviridae Infections/diagnosis , Parvoviridae Infections/virology , Parvovirus B19, Human/genetics , Parvovirus B19, Human/immunology , Predictive Value of Tests , Time Factors
20.
Nephrol Dial Transplant ; 28(12): 3004-13, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24081865

ABSTRACT

BACKGROUND: The therapeutic effect of tonsillectomy for immunoglobulin A nephropathy (IgAN) has been widely recognized, but the mechanism by which tonsillar immunity leads to glomerulonephritis has been unclear. We investigated subtypes and localization of dendritic cells (DCs) in tonsils and looked for relationships between the tonsillar DCs and the clinical features and renal histological changes of patients with IgAN. METHODS: We examined tonsils from 33 IgAN patients, using as control tonsillar specimens from subjects without glomerulonephritis. Five distinct markers of DCs (CD303, CD1c, CD209, CD208 and CD1a) were analyzed by immunohistochemistry and flow cytometry. The mRNA levels of these DC markers were evaluated using real-time polymerase chain reaction. The clinical data and histological results obtained evaluating renal biopsy tissues were statistically compared with immunological data. RESULTS: Of the five subtypes of DCs, CD208(+) DCs were significantly increased in the tonsils of IgAN patients compared with that of controls. Furthermore, the number of CD208(+) DCs in the tonsils was positively and linearly correlated with the proportion of crescentic glomeruli in renal biopsy tissues and with the urinary protein level. Only few CD208(+) cells, however, were found in the kidney biopsy specimens of IgAN patients. CONCLUSIONS: These observations suggest that increased CD208(+) DCs in tonsils may play a directive role in the pathogenesis of IgAN. The present results support the therapeutic significance of tonsillectomy for IgAN patients.


Subject(s)
Dendritic Cells/immunology , Glomerulonephritis, IGA/immunology , Lysosomal Membrane Proteins/metabolism , Neoplasm Proteins/metabolism , Palatine Tonsil/immunology , Adult , Blotting, Western , Case-Control Studies , Dendritic Cells/metabolism , Dendritic Cells/pathology , Female , Flow Cytometry , Glomerulonephritis, IGA/metabolism , Glomerulonephritis, IGA/surgery , Humans , Immunoenzyme Techniques , Kidney/immunology , Kidney/metabolism , Kidney/pathology , Male , Palatine Tonsil/metabolism , Palatine Tonsil/pathology , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tonsillectomy
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