The effect of long-term (30 days) exposure to PCZ (0.2, 50, and 500
μg
l
−1) on intestine-related biochemical markers in rainbow trout was investigated. Multiple biomarkers were measured, including ...digestive enzymes (proteolytic enzymes and amylase), antioxidant responses (TBARS, CP, SOD, CAT, GR and GPx) and energy metabolic parameters (RNA/DNA ratio, Na
+-K
+-ATPase). Exposure to 500
μg
l
−1 PCZ led to significantly inhibited (
p
<
0.01) proteolytic enzyme and amylase activity. Activities of the antioxidant enzymes SOD, CAT, and GPx gradually increased at lower PCZ concentrations (0.2 and 50
μg
l
−1). At the highest concentration (500
μg
l
−1), oxidative stress was apparent as significant higher (
p
<
0.05) lipid peroxidation and protein carbonyls, associated with an inhibition of antioxidant enzymes activity. Moreover, energy metabolic parameters (RNA/DNA ratio, Na
+-K
+-ATPase) were significantly inhibited (
p
<
0.01) in the intestines of fish exposed to 500
μg
l
−1 PCZ, compared with controls. We suggest that long-term exposure to PCZ could result in several responses in intestine-related biochemical markers, which potentially could be used as indicators for monitoring residual PCZ present in the aquatic environment.
Thrombotic microangiopathy (TMA) significantly affects kidney graft survival, but its pathophysiology remains poorly understood.
In this multicenter, retrospective, case-control paired study designed ...to control for donor-associated risks, we assessed the recipients' risk factors for de novo TMA development and its effects on graft survival. The study group consists of patients with TMA found in case biopsies from 2000 to 2019 (n = 93), and the control group consists of recipients of paired kidney grafts (n = 93). Graft follow-up was initiated at the time of TMA diagnosis and at the same time in the corresponding paired kidney graft.
The TMA group displayed higher peak panel-reactive antibodies, more frequent retransplantation status, and longer cold ischemia time in univariable analysis. In the multivariable regression model, longer cold ischemia times (odds ratio, 1.18; 95% confidence interval CI, 1.01-1.39;
= 0.043) and higher peak pretransplant panel-reactive antibodies (odds ratio, 1.03; 95% CI, 1.01-1.06;
= 0.005) were found to be associated with increased risk of de novo TMA. The risk of graft failure was higher in the TMA group at 5 y (hazard ratio HR, 3.99; 95% CI, 2.04-7.84;
< 0.0001). Concomitant rejection significantly affected graft prognosis at 5 y (HR, 6.36; 95% CI, 2.92-13.87;
< 0.001). De novo TMA associated with the active antibody-mediated rejection was associated with higher risk of graft failure at 5 y (HR, 3.43; 95% CI, 1.69-6.98;
< 0.001) compared with other TMA.
Longer cold ischemia and allosensitization play a role in de novo TMA development, whereas TMA as a part of active antibody-mediated rejection was associated with the highest risk for premature graft loss.
The effects of Nexide (a.i. gamma-cyhalothrin 60 g L - 1 ) on cumulative mortality, growth indices, and ontogenetic development of embryos and larvae of common carp (Cyprinus carpio L.) were studied. ...Levels of oxidative stress parameters glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), glutathione-S-transferase (GST), and lipid peroxidation were determined. Eggs of newly fertilised common carp were exposed to Nexide at concentrations 5, 25, 50, 100, and 250 μg L - 1 (0.3, 1.5, 3, 6, and 15 μg L - 1 gamma-cyhalothrin). All organisms exposed to concentrations higher than 50 μg L - 1 died soon after hatching; at 25 μg L - 1 , 95% mortality was recorded. Larvae exposed to 5 μg L - 1 showed significantly lower growth and retarded ontogenetic development compared to control. Histological examination of the livers of larvae from the exposed group revealed dystrophic changes. The value of detoxification enzyme GST of organisms from the exposed group was significantly higher compared to the control and the value of defensive enzyme GPx was significantly lower compared to the control. The results of our investigation confirmed that contamination of aquatic environment by pesticides containing cyhalothrin may impair growth and development of early life stages of carp and cause disbalance of defensive enzymes.
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccination may fail to sufficiently protect transplant recipients against coronavirus disease 2019 (COVID‐19). We retrospectively ...evaluated COVID‐19 in kidney transplant recipients (n = 226) after BNT162b2 mRNA vaccine administration. The control group consisted of unvaccinated patients (n = 194) during the previous pandemic wave. We measured anti‐spike protein immunoglobulin G (IgG) levels and cellular responses, using enzyme‐linked immunosorbent spot assay, in a prospective cohort after vaccination (n = 31) and recovery from COVID‐19 (n = 19). COVID‐19 was diagnosed in 37 (16%) vaccinated and 43 (22%) unvaccinated patients. COVID‐19 severity was similar in both groups, with patients exhibiting a comparable need for hospitalization (41% vs. 40%, p = 1.000) and mortality (14% vs. 9%, p = .726). Short posttransplant periods were associated with COVID‐19 after vaccination (p < .001). Only 5 (16%) patients achieved positive SARS‐CoV‐2 IgG after vaccination, and 17 (89%, p < .001) recovered from COVID‐19 (median IgG levels, 0.6 vs. 52.5 AU/ml, p < .001). A cellular response following vaccination was present in the majority (n = 22, 71%), with an increase in interleukin 2 secreting T cells (p < .001). Despite detectable T cell immunity after mRNA vaccination, kidney transplant recipients remained at a high risk of severe COVID‐19. Humoral responses induced by vaccination were significantly lower than that after COVID‐19.
A two‐dose SARS‐CoV‐2 mRNA vaccination schedule does not induce sufficient humoral response in the majority of kidney transplant recipients who therefore remain at high risk of severe COVID‐19, comparable to unvaccinated patients.
Polyomavirus BK (BKV) is the cause of polyomavirus‐associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its ...prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio HR = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.
A post hoc analysis of two randomized trials evaluating CMV prevention strategies in kidney transplant recipients suggests an association between valganciclovir prophylaxis and an increased risk of polyomavirus BK viremia and polyomavirus‐associated nephropathy compared to other modalities, such as high‐dose valacyclovir prophylaxis or a pre‐emptive therapy approach. See the editorial by Pape on page 2401.
The effects of Diazinon 60 EC (organophosphate insecticide, active substance diazinon) on mortality, growth rate, early ontogenetic rate, and occurrence of malformations was studied in embryos and ...larvae of tench, Tinca tinca (L.). The exposure of fish to 0, 10, 100, 1,000, and 3,000 μg dm⁻³ of Diazinon 60 EC was initiated 24 h after fertilization of eggs and concluded 32 days later. At the highest concentration tested (3,000 μg dm⁻³), total mortality was observed within the first 15 days of exposure. A concentration of 1,000 μg dm⁻³ caused high incidence of malformations, decrease in growth rate and ontogenetic development slowed down. A concentration of 100 μg dm⁻³ mildly decreased growth rate, but at 10 μg dm⁻³ no changes compared to the control were observed. Thus, Diazion 60 EC at the concentration of 10 μg dm⁻³ is not dangerous for the embryos and larvae of tench.
Abstract
Background
Polyomavirus BK (BKV) infection of the renal allograft causes destructive tissue injury with inflammation and subsequent fibrosis.
Methods
Using a prospective cohort of patients ...after kidney transplantation performed between 2003 and 2012, we investigated the role of BKV viraemia in the development and progression of interstitial fibrosis and tubular atrophy (IFTA). The primary outcome was moderate-to-severe IFTA assessed by protocol biopsy at 36 months.
Results
A total of 207 consecutive recipients were enrolled. Of these, 57 (28%) developed BKV viraemia with 10 (5%) cases of polyomavirus-associated nephropathy (PVAN). Transient (<3 months) BKV viraemia occurred in 70% of patients, and persistent (≥3 months) BKV viraemia in 30%. A high viral load (≥10 000 copies/mL) was detected in 18% and a low viral load (<10 000 copies/mL) in 61%, while the viral load could not be determined in 21%. Moderate-to-severe IFTA was significantly increased in high 71%; odds ratio (OR) = 12.1; 95% confidence interval (CI) 1.62–90.0; P = 0.015 or persistent BKV viraemia (67%; OR = 6.33; 95% CI 1.19–33.7; P = 0.031) with corresponding rise in ‘interstitial fibrosis + tubular atrophy’ scores. Only patients with transient low BKV viraemia showed similar incidence and progression of IFTA to the no-BKV group. Persistent low BKV viraemia was uncommon yet the progression of fibrosis was significant. Only recipients with PVAN experienced inferior graft survival at 5 years.
Conclusions
These data suggest that only transient low BKV viraemia does not negatively affect the progression of allograft fibrosis in contrast to excessive risk of severe fibrosis after high or persistent BKV viraemia.
Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined the optimal CMV prevention strategy to avoid ...indirect effects of the virus. In this randomized trial involving 140 kidney transplant recipients, incidence of acute rejection at 12 months was not lower with valganciclovir prophylaxis (for at least 3 months) compared with preemptive therapy initiated after detection of CMV DNA in whole blood. However, prophylaxis was associated with a lower risk of subclinical rejection at 3 months. Although both regimens were effective in preventing CMV disease, the incidence of CMV DNAemia (including episodes with higher viral loads) was significantly higher with preemptive therapy. Further research with long-term follow-up is warranted to better compare the two approaches.
The optimal regimen for preventing cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in reducing indirect CMV effects, has not been defined.
This open-label, single-center, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy included kidney transplant recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative recipients with transplants from seronegative donors, we randomized 140 participants 1:1 to receive valganciclovir prophylaxis (900 mg, daily for 3 or 6 months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor) or preemptive therapy (valganciclovir, 900 mg, twice daily) that was initiated after detection of CMV DNA in whole blood (≥1000 IU/ml) and stopped after two consecutive negative tests (preemptive therapy patients received weekly CMV PCR tests for 4 months). The primary outcome was the incidence of biopsy-confirmed acute rejection at 12 months. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia.
The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 versus 23%, 16/70), but the difference was not statistically significant. Subclinical rejection at 3 months was lower in the prophylaxis group (13% versus 29%, P = 0.027). Both regimens prevented CMV disease (in 4% of patients in both groups). Compared with prophylaxis, preemptive therapy resulted in significantly higher rates of CMV DNAemia (44% versus 75%, P < 0.001) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/ml), but significantly lower valganciclovir exposure and neutropenia.
Among kidney transplant recipients, the use of valganciclovir prophylaxis did not result in a significantly lower incidence of acute rejection compared with the use of preemptive therapy.
Optimizing Valganciclovir Efficacy in Renal Transplantation (OVERT Study), ACTRN12613000554763 .
Haematological parameters of 2-year-old carp (Cyprinus carpio L.) were assessed to study the protective effect of chloride on the health of fish exposed to elevated nitrite concentrations. Four ...groups of carp were exposed to different concentrations of nitrite and chloride for 96 h (group E1: 67 mg L(-1) NO2(-), 11 mg L(-1) Cl(-); group E2: 67 mg L(-1) NO2(-), 100 mg L(-1) Cl(-); group E3: 0 mg L(-1) superoxide, 100 mg L(-1) Cl(-) and group C: 0 mg L(-1) NO2(-), 11 mg L(-1) Cl(-)). The main haematological response of carp to an acute exposure to nitrite (group E1) was a significant decrease (P<0.05) in haemoglobin concentrations (53.40 +/- 6.61 g L(-1)), haematocrit (0.21 +/- 0.02 LL(-1)), erythrocyte count (1.13 +/- 0.12 TL(-1)), leucocyte count (7.1 +/- 4.19 GL(-1)) and lymphocyte count (5.28 +/- 2.51 GL(-1)), and a significant increase in methaemoglobin concentration (90.50 +/- 4.38%, P<0.01) and mean corpuscular haemoglobin concentration (0.27 +/- 0.2 LL(-1), P<0.05). At higher chloride concentrations (group E2), a lower nitrite toxicity was observed. In group E2 carp, methaemoglobin made up 38.32 +/- 13.30%. Erythrocytes in carp exposed to nitrite showed qualitative changes. Compared with the control group C, group E1 carp showed a significantly higher number (P<0.05) of elongated erythrocytes, with the nucleus located at one cell pole (0.519 +/- 0.388 TL(-1)). All erythrocytes of group E1 carp had remarkably clear cytoplasms compared with the cytoplasm in the control group C. The biochemical values found were comparable with those found in controls. The main histological lesions were found in the gills of carp exposed to nitrite and consisted of hyperplasia and an elevated number of chloride cells.
The aim of the study was to evaluate the use of leeches of the genus Erpobdella as a means of assessing polychlorinated biphenyl contamination of watercourses. The River Skalice, heavily contaminated ...with PCBs, was selected as a model. The source of contamination was a road gravel processing factory in Rožmitál pod Třemšínem from which an estimated 1 metric ton of PCBs leaked in 1986. Levels of PCB were measured in leeches collected between 1992 to 2003 from 11 sites covering about 50 km of the river (the first sampling site upstream to the source of contamination and 10 sites downstream). The PCB indicator congeners IUPA no. 28, 52, 101, 118, 138, 153, and 180 were measured. Levels were highest at the four sampling sites nearest the source of pollution. The highest values of PCB congeners were found in 1992. PCB content decreased from 1992 to 2003 and with distance from the source. The study indicated that leeches of the genus Erpobdella are a suitable bioindicator of contamination in the surface layer of river sediments.
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