scholarly journals Correlation between renal distribution of leptospires during the acute phase and chronic renal dysfunction in a hamster model of infection with Leptospira interrogans

2021 ◽  
Vol 15 (6) ◽  
pp. e0009410
Author(s):  
Tsukasa Maruoka ◽  
Yasuhiko Nikaido ◽  
Satoshi Miyahara ◽  
Eisuke Katafuchi ◽  
Yoshinori Inamasu ◽  
...  

Background Leptospirosis has been described as a biphasic disease consisting of hematogenous dissemination to major organs in the acute phase and asymptomatic renal colonization in the chronic phase. Several observational studies have suggested an association between leptospirosis and chronic kidney disease (CKD). We investigated the dynamics of leptospires and histopathological changes in the kidney to understand the relationship between them, and also investigated the extent of renal dysfunction in the acute and chronic phases of leptospirosis using a hamster model. Findings Hamsters (n = 68) were subcutaneously infected with 1 × 104 cells of the Leptospira interrogans serovar Manilae strain UP-MMC-SM. A total of 53 infected hamsters developed fatal acute leptospirosis, and the remaining 15 hamsters recovered from the acute phase, 13 of which showed Leptospira colonization in the kidneys in the chronic phase. Five asymptomatic hamsters also had renal colonization in the chronic phase. Immunofluorescence staining showed that leptospires were locally distributed in the renal interstitium in the early acute phase and then spread continuously into the surrounding interstitium. The kidneys of the surviving hamsters in the chronic phase showed patchy lesions of atrophic tubules, a finding of chronic tubulointerstitial nephritis, which were substantially consistent with the distribution of leptospires in the renal interstitium. The degree of atrophic tubules in kidney sections correlated statistically with the serum creatinine level in the chronic phase (rs = 0.78, p = 0.01). Conclusion Subcutaneous infection with pathogenic leptospires could cause acute death or chronic leptospirosis in hamsters after surviving the acute phase. We suggest that the renal distribution of leptospires during the acute phase probably affected the extent of tubular atrophy, leading to CKD.

2020 ◽  
Vol 319 (4) ◽  
pp. F579-F591
Author(s):  
Noriyuki Yamashita ◽  
Tetsuro Kusaba ◽  
Tomohiro Nakata ◽  
Aya Tomita ◽  
Tomoharu Ida ◽  
...  

Tubular atrophy is a common pathological feature of kidney fibrosis. Although fibroblasts play a predominant role in tissue fibrosis, the role of repairing tubular epithelia in tubular atrophy is unclear. We demonstrated the essential role of focal adhesion kinase (FAK)-mediated intratubular epithelial-mesenchymal transition (EMT) in the pathogenesis of tubular atrophy after severe ischemia-reperfusion injury (IRI). Actively proliferating tubular epithelia undergoing intratubular EMT were noted in the acute phase of severe IRI, resulting in tubular atrophy in the chronic phase, reflecting failed tubular repair. Furthermore, FAK was phosphorylated in the tubular epithelia in the acute phase of severe IRI, and its inhibition ameliorated both tubular atrophy and interstitial fibrosis in the chronic phase after injury. In vivo clonal analysis of single-labeled proximal tubular epithelial cells after IRI using proximal tubule reporter mice revealed substantial clonal expansion after IRI, reflecting active epithelial proliferation during repair. The majority of these proliferating epithelia were located in atrophic and nonfunctional tubules, and FAK inhibition was sufficient to prevent tubular atrophy. In vitro, transforming growth factor-β induced FAK phosphorylation and an EMT phenotype, which was also prevented by FAK inhibition. In an in vitro tubular epithelia gel contraction assay, transforming growth factor-β treatment accelerated gel contraction, which was suppressed by FAK inhibition. In conclusion, injury-induced intratubular EMT is closely related to tubular atrophy in a FAK-dependent manner.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Oscar Acosta ◽  
Luis Solano ◽  
Jorge Escobar ◽  
Miguel Fernandez ◽  
Carlos Solano ◽  
...  

Carrion’s disease (CD), is a human bartonellosis, that is, endemic in the Andes of Peru, Ecuador, and Colombia.Bartonella bacilliformis, a native hemotrophic bacteria, is the causative agent of CD, and the interaction with the host could have produced changes in the gene frequencies of erythrocyte antigens. The goal here is to investigate the relationship between allele frequencies of blood group systems MNS, Diego, and Duffy and the clinical phases of CD, within a genetic context. In this associative and analytical study, 76 individuals from Bagua Grande, the province of Utcubamba, and the department of Amazonas in Peru, were enrolled. Forty of them resided in Tomocho-Collicate-Vista Hermosa area (high prevalence of cases in chronic phase, verrucous, or eruptive phase, without previous acute phase). Thirty-six individuals were from the area of Miraflores (high prevalence of cases in acute phase only) and were evaluated for blood group systems MNS, Diego, and Duffy. This study constitutes one of the first attempts at evaluating the genetic factors and clinical phases of CD. No significant statistical differences(P>0.05)between allele frequencies of blood groups MNS, Diego, and Duffy and the prevalence of chronic and acute phases were detected in the two areas of Amazonas, Peru.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maiko Kokubu ◽  
Masaru Matsui ◽  
Takayuki Uemura ◽  
Katsuhiko Morimoto ◽  
Masahiro Eriguchi ◽  
...  

Abstract Peritonitis is a critical complication of peritoneal dialysis (PD). Investigators have reported the risk of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) versus automated peritoneal dialysis (APD), but the available evidence is predominantly based on observational studies which failed to report on the connection type. Our understanding of the relationship between peritonitis risk and PD modality thus remained insufficient. We studied 285 participants who began PD treatment between 1997 and 2014 at three hospitals in Nara Prefecture in Japan. We matched 106 APD patients with 106 CAPD patients based on their propensity scores. The primary outcome was time to first episode of peritonitis within 3 years after PD commencement. In total, PD peritonitis occurred in 64 patients during the study period. Patients initiated on APD had a lower risk of peritonitis than did those initiated on CAPD in both the unadjusted and adjusted models. The hazard ratio (HR) and 95% confidence interval (CI) for the primary endpoint were 0.30 (0.17–0.53) in the fully adjusted model including connection type. In the matched cohort, APD patients had a significantly lower risk of peritonitis than did CAPD patients (log-rank: p < 0.001, HR 0.32, 95% CI 0.16–0.59). The weighting-adjusted analysis of the inverse probability of treatment yielded a similar result (HR 0.35, 95% CI 0.18–0.67). In conclusion, patients initiated on APD at PD commencement had a reduced risk of peritonitis compared with those initiated on CAPD, suggesting APD may be preferable for prevention of peritonitis among PD patients.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kenji Shoda ◽  
Yukiko Enomoto ◽  
Yusuke Egashira ◽  
Takamasa Kinoshita ◽  
Daisuke Mizutani ◽  
...  

Abstract Background Dual antiplatelet therapy (DAPT) is necessary for stent assisted coiling. However, long term use of DAPT has a potential risk of hemorrhagic events. We aimed to examine the relationship between clopidogrel reactivity and complications. Methods Patients who underwent stent assisted coiling for unruptured aneurysms or previously treated aneurysms and received periprocedural DAPT in our institution between August 2011 to March 2020 were included. Platelet reactivity for clopidogrel was measured by VerifyNow assay system, and we defined the cut off value of P2Y12 Reaction Units (PRU) at 208 and classified patients as hypo-responders (PRU≧208) or responders (PRU<208). The rates of hemorrhagic and thrombotic events within 30 days (acute phase) and 30 days after the procedure (delayed phase) were compared between the two groups. Furthermore, changes in hemoglobin levels were measured before and after the procedure and at chronic stages (1 to 6 months thereafter). Results From 61 patients included in this study, 36 patients were hypo-responders and 25 patients were responders. Hemorrhagic events occurred 8.0% only in responders in the acute phase (p = 0.16), and 2.78% in hypo-responders and 20.0% in responders in the delayed phase (p = 0.037). Changes in hemoglobin levels before and after the procedure were 1.22 g/dl in hypo-responders and 1.74 g/dl in responders (p = 0.032) while before the procedure and chronic stages they were 0.39 g/dl in hypo-responders and 1.39 g/dl in responders (p <  0.01). Thrombotic events were not significantly different between the two groups. Conclusion Long term use of DAPT after stent assisted coiling is related to hemorrhagic events in the delayed phase. Preventing for hemorrhagic events, the duration of DAPT should be carefully considered in clopidogrel responders.


Author(s):  
Junfan Fang ◽  
Junying Du ◽  
Xuaner Xiang ◽  
Xiaomei Shao ◽  
Xiaofeng He ◽  
...  
Keyword(s):  

2021 ◽  
pp. 1-12
Author(s):  
Jia Zhou ◽  
Dingkun Wang ◽  
Bingong Li ◽  
Xuelian Li ◽  
Xingjun Lai ◽  
...  

<b><i>Introduction:</i></b> Trimethylamine N-oxide (TMAO) is a metabolite produced by gut bacteria. Although increased TMAO levels have been linked to hypertension (HTN) and chronic kidney disease (CKD) with poor prognosis, no clinical studies have directly addressed the relationship between them. In this study, we investigated the relationship between TMAO and renal dysfunction in hypertensive patients. <b><i>Methods:</i></b> We included healthy controls (<i>n</i> = 50), hypertensive patients (<i>n</i> = 46), and hypertensive patients with renal dysfunction (<i>n</i> = 143). Their blood pressure values were taken as the highest measured blood pressure. Renal function was evaluated using the estimated glomerular filtration rate. Plasma TMAO levels were measured using high-performance liquid chromatography tandem mass spectrometry. <b><i>Results:</i></b> We found significant differences in plasma TMAO levels among the 3 groups (<i>p</i> &#x3c; 0.01). The plasma TMAO of patients with HTN was significantly higher than that of healthy people, and the plasma TMAO of patients with HTN complicated by renal dysfunction was significantly higher than either of the other groups. Patients in the highest TMAO quartile were at a higher risk of developing CKD stage 5 than those in the lowest quartile. In the receiver operating characteristic curve, the area under the curve of TMAO combined with β 2-macroglobulin for predicting renal dysfunction in patients with HTN was 0.85 (95% confidence interval 0.80–0.90). <b><i>Conclusion:</i></b> An elevated TMAO level reflects higher levels of HTN and more severe renal dysfunction. TMAO, combined with β 2-macroglobulin levels, may assist in diagnosing CKD in hypertensive patients. Plasma TMAO has predictive value for early kidney disease in hypertensive patients.


2021 ◽  
pp. 1-7
Author(s):  
Alastair J. Flint ◽  
Kathleen S. Bingham ◽  
Nicholas H. Neufeld ◽  
George S. Alexopoulos ◽  
Benoit H. Mulsant ◽  
...  

Abstract Background Little is known about the relationship between psychomotor disturbance (PMD) and treatment outcome of psychotic depression. This study examined the association between PMD and subsequent remission and relapse of treated psychotic depression. Methods Two hundred and sixty-nine men and women aged 18–85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission or near-remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine (n = 64) with sertraline plus placebo (n = 62). PMD was measured with the psychiatrist-rated sign-based CORE at acute phase baseline and at RCT baseline. Spearman's correlations and logistic regression analyses were used to analyze the association between CORE total score at acute phase baseline and remission/near-remission and CORE total score at RCT baseline and relapse. Results Higher CORE total score at acute phase baseline was associated with lower frequency of remission/near-remission. Higher CORE total score at RCT baseline was associated with higher frequency of relapse, in the RCT sample as a whole, as well as in each of the two randomized groups. Conclusions PMD is associated with poorer outcome of psychotic depression treated with sertraline plus olanzapine. Future research needs to examine the neurobiology of PMD in psychotic depression in relation to treatment outcome.


2000 ◽  
Vol 19 (6) ◽  
pp. 27-37 ◽  
Author(s):  
Janet Pinelli

Purpose: To determine the relationship between family coping and resources and family adjustment and parental stress in the acute phase of the NICU experience.Design: Correlational study based on the Resiliency Model of Family Stress, Adjustment, and Adaptation. Main study instruments included the State Anxiety scale of the State-Trait Anxiety Inventory, the Family Inventory of Resources for Management, the Family Crisis Oriented Personal Evaluation Scales, and the General Functioning subscale of the McMaster Family Assessment Device.Sample: Data collected from 124 mother and father pairs within two to four days of their infant’s admission to the NICU.Main Outcome Variables: Family adjustment and parental stress.Results: Adequate resources were more strongly related to positive adjustment and decreased stress than were either coping or being a first-time parent. The relationships among the variables were generally the same for both parents. Mothers utilized more coping strategies than did fathers.Practice Recommendations: Families with limited resources should be identified early to facilitate their adjustment to the NICU.


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