Ideal Features of Topical Antibiotic Therapy for the Treatment of Impetigo: An Italian Expert Consensus Report.

Background: A group of Italian experts in impetigo medical care sought to define 10 statements to describe the ideal characteristics of the best local antibiotic treatments, and to provide relevant information re- garding their appropriate use and prescription that should be considered in clinical practice for impetigo management. Objective: A group of Italian experts in impetigo medical care sought to define 10 statements to describe the ideal characteristics of the best local antibiotic treatments, and to provide relevant information regarding their appropriate use and prescription that should be considered in clinical practice for impetigo management. Methods: A consensus on ideal features of antibiotic therapy for the treatment of impetigo was appraised by an online Delphi-based method, based on a panel of 61 infectious disease specialists, pediatricians, and dermatologists coordinated by a scientific committee of 5 experts specializing in impetigo management. Results: Full or very high consensus was reached on the 10 statements identified to describe the characteristics of the best hypothetic antibiotic therapy for impetigo together with indications for appropriate antibiotics use. Conclusions: Several criteria have to be considered when selecting topical antibacterial therapy for impetigo. Beyond efficacy and safety, antimicrobial susceptibility and pharmacological characteristics of the agent are essential points. Formulation of the antimicrobial product is fundamental, as well as patient and caregiver preference, to facilitate therapeutic adherence, to achieve the infection control, and to obtain the best benefit from treatment (Curr Ther Res Clin Exp. 2023; 84:XXXXXX).

Environmental Risk Assessment of Drugs in Tropical Freshwaters Using Ceriodaphnia silvestrii as Test Organism.

In this study we evaluated the acute (immobility/mortality) and chronic (survival and reproduction) effects of the drugs caffeine, diclofenac sodium salt, ketoprofen, paracetamol and salicylic acid on the cladoceran Ceriodaphnia silvestrii. The environmental risks of these substances for tropical freshwaters were estimated from the risk quotient MEC/PNEC. Sensitivity in acute exposures varied up on the drug as follows: salicylic acid (EC50 = 69.15 mg L- 1) < caffeine (EC50 = 45.94 mg L- 1) < paracetamol (EC50 = 34.49 mg L- 1) < ketoprofen (EC50 = 24.84 mg L- 1) < diclofenac sodium salt (EC50 = 14.59 mg L- 1). Chronic toxicity data showed negative effects of the drugs on reproduction. Paracetamol and salicylic acid caused reduction in fecundity in concentrations starting from 10 mg L- 1 and 35 mg L- 1, respectively. Ketoprofen caused total inhibition at 5 mg L- 1. MEC/PNEC values were relatively low for all drugs. The risk was estimated as low or insignificant, except for caffeine, whose MEC/PNEC value was greater than 1 (moderate risk).

Real-life isoniazid and rifampicin plasma concentrations in children: a tool for therapeutic drug monitoring of tuberculosis.

BACKGROUND: Low plasma levels of first-line antitubercular drugs can be counted among the main causes of poor response to antitubercular therapy, and therapeutic drug monitoring has been proposed as a method to promote tailored treatments for both child and adult patients. The main aim of the study was to evaluate serum concentrations of isoniazid (INH) and rifampicin (RIF) and to investigate reasons for sub-therapeutic plasma concentrations in order to fix dosages. METHODS: Children with TB were prospectively enrolled from January to August 2019. Two venous blood samples were collected (the first at least 15 days after the beginning of antitubercular treatment, and the second between 1 and 8 weeks later). Plasma concentrations were determined by a validated high-performance liquid chromatography method. RESULTS: In all, 45 children were included. Seventy blood samples for INH plasma concentration were collected between 120 and 240 min after drug intake. Adjusting for dose (mg/kg/day) and time of INH administration, when considering three different age groups (≤ 2 years, 2-12 years, > 12 years), a statistically significant lower INH plasma concentration was observed in younger children compared to the older age groups in the multivariate analysis (p < 0.001 and p < 0.001). A total of 68 blood samples were evaluated for RIF concentrations. Both for INH and RIF a statistically significant lower plasma concentration was also observed in adolescents (p < 0.001). Fifteen children (15/45, 33%) presented drug concentrations under the referral therapeutic range. CONCLUSIONS: Based on our findings, monitoring patients' drug plasma concentrations in children under 2 years of age and in adolescents can make treatment more patient-tailored.

Fosfomycin Trometamol versus Comparator Antibiotics for the Treatment of Acute Uncomplicated Urinary Tract Infections in Women: A Systematic Review and Meta-Analysis.

PURPOSE: We performed a systematic review and meta-analysis to compare the effectiveness and safety profile of fosfomycin vs comparator antibiotics in women with acute uncomplicated cystitis. MATERIALS AND METHODS: Relevant databases were searched using methods recommended by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. We assessed the risk of bias and confounders. The study primary end point was clinical or microbiological success, defined as complete (cure) and/or incomplete resolution of symptoms at the end of treatment (improvement) and/or microbiological eradication. RESULTS: After screening 539 articles 15 were included which recruited a total of 2,295 adult female patients. Of the studies 14 were used for microbiological eradication analysis. We used 11 of the 15 articles in a total of 1,976 patients for clinical resolution and 11 in a total of 1,816 patients for safety outcome analysis. No difference was found for clinical resolution in all comparators combined in 11 randomized controlled trials in a total of 1,976 patients (OR 1.16, 95% CI 0.91-1.49, p=0.13). No difference was found for microbiological eradication in 14 randomized controlled trials in a total of 2,052 patients (OR 1.03, 95% CI 0.83-1.30, p=0.09) or for safety outcome in 11 randomized controlled trials in a total of 1,816 patients (OR 1.17, 95% CI 0.86-1.58, p=0.33). Most adverse effects reported for fosfomycin were transient and single dose therapy seems to have resulted in better patient compliance. CONCLUSIONS: Single dose oral fosfomycin trometamol is equal to comparator regimens in terms of clinical and microbiological effectiveness and safety in women with microbiologically confirmed and/or clinically suspected, acute uncomplicated cystitis. It is associated with high patient compliance.

Clindamycin as unique antibiotic choice in Hidradenitis Suppurativa.

The rifampicin (RF)-clindamycin (CL) combination is recommended as first line therapy in moderate to severe Hidradenitis Suppurativa (HS) by European S1 guidelines. Although prolonged use of RF should be discouraged, there are currently few alternatives to this combination therapy. The aim of the present study was to assess retrospectively the efficacy of oral CL monotherapy in patients diagnosed with HS. In the period January 2017-May 2018, 31 HS patients who received a 300 mg b.i.d. oral dose of CL were studied retrospectively. Efficacy of the treatment was evaluated by comparing the main HS severity scores (Sartorius score modified by Revuz, Hidradenitis Suppurativa Physician Global Assessment [HS-PGA] and International Hidradenitis Suppurativa Severity Score System [IHS4]) before (W0) and after (W12) CL oral therapy. CL efficacy was demonstrated by the extreme and significant reduction of all three disease severity parameters during the 12-week period (p ≤ .01). There was also a statistically significant change in the mean visual analogue scale for pain. The present study demonstrates the efficacy of oral CL monotherapy as RF-sparing regimen alternative to RF-CL combination in a selected group of patients.

Voriconazole treatment in adults and children with hematological diseases: can it be used without measurement of plasma concentration?

Indication and timing of trough plasma-voriconazole (VCZ)-concentration (t-PVC) measurement during VCZ treatment is a debated issue. Patterns of t-PVC were prospectively evaluated in pediatric (50 courses) and adult (95 courses) hematologic patients. Efficacy patterns were defined: adequate, t-PVC always ≥1 mcg/ml; borderline, at least one t-PVC measurement <1 mcg/ml but median value of the measurements ≥1 mcg/ml; inadequate, median value of the measurements <1 mcg/ml. Toxicity patterns were defined: favorable, t-PVC always ≤5 mcg/ml; borderline, one or more t-PVC measurements >5 mcg/ml but median value of the measurements ≤5 mcg/ml; unfavorable, median value of the measurements >5 mcg/ml. In children and adults the mean t-PVCs were higher during intravenous treatments. The t-PVC efficacy pattern was adequate, borderline and inadequate in 48%, 12%, and 40% of courses, respectively, in children, and in 66.3%, 16.8%, and 16.8% of courses, respectively, in adults. Adequate efficacy pattern was more frequent in children with body weight above the median (≥25 kg) (OR 4.8; P = .011) and in adults with active hematological disease receiving intravenous therapy (OR 3.93; P = .006). Favorable toxicity pattern was more frequent in children receiving VCZ daily dosage below the median (<14 mg/kg) (OR 4.18; P = .027) and in adults with body weight below the median (<68 kg) (OR 0.22; P = .004). T-PVC measurement is generally needed, however, a non t-PVC guided approach may be considered in heavier adults receiving intravenous VCZ. The risk of supratherapeutic levels does not seem an absolute indication for t-PVC monitoring.

Changes in ceftriaxone pharmacokinetics/pharmacodynamics during the early phase of sepsis: a prospective, experimental study in the rat.

BACKGROUND: Sepsis is characterized by the loss of the perm-selectivity properties of the glomerular filtration barrier (GFB) with consequent albuminuria. We examined whether the pharmacokinetics-pharmacodynamics (PK/PD) of ceftriaxone (CTX), an extensively protein-bound 3rd generation cephalosporin, is altered during early sepsis and whether an increase in urinary loss of bound-CTX, due to GFB alteration, can occur in this condition. METHODS: A prospective, experimental, randomized study was carried out in adult male Sprague-Dawley rats. Sepsis was induced by cecal ligation and puncture (CLP). Rats were divided into two groups: Sham-operated and CLP. CTX (100 mg i.p., equivalent to 1 g dose in humans) was administered in order to measure plasma and lung CTX concentrations at several time-points: baseline and 1, 2, 4 and 6 h after administration. CTX was measured by High Performance Liquid Chromatography (HPLC). The morphological status of the sialic components of the GFB barrier was assessed by lectin histo-chemistry. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA >90%) for 80 and 100% of Tfree > minimum inhibitory concentration (MIC) for 80 and 100% of dosing interval. MEASUREMENTS AND MAIN RESULTS: After CLP, sepsis developed in rats as documented by the growth of polymicrobial flora in the peritoneal fluid (≤1 × 101 CFU in sham rats vs 5 × 104-1 × 105 CFU in CLP rats). CTX plasma concentrations were higher in CLP than in sham rats at 2 and 4 h after administration (difference at 2 h was 47.3, p = 0.012; difference at 4 h was 24.94, p = 0.004), while lung penetration tended to be lower. An increased urinary elimination of protein-bound CTX occurred (553 ± 689 vs 149 ± 128 mg/L, p < 0.05; % of bound/total CTX 22 ± 6 in septic rats vs 11 ± 4 in sham rats, p < 0.01) and it was associated with loss of the GFB sialic components. According to Monte Carlo simulation a PTA > 90% for 100% of the dosing interval was reached neither for sham nor CLP rats using MIC = 1 mg/L, the clinical breakpoint for Enterobacteriacee. CONCLUSIONS: Sepsis causes changes in the PK of CTX and an alteration in the sialic components of the GFB, with consequent loss of protein-bound CTX. Among factors that can affect drug pharmacokinetics during the early phases of sepsis, urinary loss of both free and albumin-bound antimicrobials should be considered.

Posaconazole oral suspension primary prophylaxis in acute leukemia and allogeneic stem cell transplant patients: can it be used without measurement of plasma concentration?

Posaconazole oral suspension (PCZ-susp) can display a variable degree of inter and intra-individual absorption. However, there is no agreement on the need of plasma-posaconazole-concentration (PPC) monitoring as a routine practice in patients receiving PCZ-susp. In this prospective, multicenter study we evaluated the variability of PPCs in hematologic patients receiving PCZ-susp prophylaxis with the aim to define conditions at different risk of subtherapeutic PPCs. Overall, 103 acute leukemia (AL) patients submitted to intensive chemotherapy (115 courses) and 46 allogeneic stem cell transplant (allo-SCT) recipients (47 courses) receiving PCZ-susp prophylaxis were considered. The adequacy of PPC pattern after the steady state (≥day 7 of treatment) in courses with two or more PPC measurements was defined as follows: inadequate pattern: PPC < 0.5 mcg/ml at least once; borderline pattern: PPC always ≥0.5mcg/ml but < 0.7 mcg/ml at least once; adequate pattern: PPC always ≥0.7 mcg/ml. The PPC pattern was evaluable in 83 and 37 AL and allo-SCT patients, respectively. It was adequate, borderline and inadequate in 63.9%, 14.5%, and 21.7% of courses, respectively, in AL, and in 62.2%, 10.8%, and 27.0% of courses, respectively, in allo-SCT. In both groups, an inadequate PPC pattern was associated with the development of diarrhea. In absence of diarrhea, the probability of an inadequate PPC pattern was 11.9% in AL and 17.2% in allo-SCT patients. PCZ-susp might be used without stringent need of PPC monitoring in patients without diarrhea.

Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review.

BACKGROUND: Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected in critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy (CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter changes observed in critically ill septic patients with AKI, who are on CRRT. METHOD: Citations published on PubMed up to January 2016 were systematically reviewed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. All authors assessed the methodological quality of the studies and consensus was used to ensure studies met inclusion criteria. In-vivo studies in adult patients with AKI treated with linezolid and on CRRT were considered eligible for the analysis only if operational settings of the CRRT machine, membrane type, linezolid blood concentrations and main PK-PD parameters were all clearly reported. RESULTS: Among 68 potentially relevant articles, only 9 were considered eligible for the analysis. Across these, 53 treatments were identified among the 49 patients included (46 treated with high-flux and 3 with high cut-off membranes). Continuous veno-venous hemofiltration (CVVH) was the most frequent treatment performed amongst the studies. The extracorporeal clearance values of linezolid across the different modalities were 1.2-2.3 L/h for CVVH, 0.9-2.2 L/h for hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD parameters was reported. The optimal area under the curve/minimum inhibitory concentration (AUC/MIC) ratio was reached for pathogens with an MIC of 4 mg/L in one study only. CONCLUSIONS: Wide variability in linezolid PK/PD parameters has been observed across critically ill septic patients with AKI treated with CRRT. Particular attention should be paid to linezolid therapy in order to avoid antibiotic failure in these patients. Strategies to improve the effectiveness of this antimicrobial therapy (such as routine use of target drug monitoring, increased posology or extended infusion) should be carefully evaluated, both in clinical and research settings.

Simplified equations using two concentrations to calculate area under the curve for antimicrobials with concentration-dependent pharmacodynamics: daptomycin as a motivating example.

The effects of several antimicrobial agents are predicted by the ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC). Peak (Cp) and trough (Ct) concentrations are often measured clinically as surrogates of AUC because actual computation of AUC from 1 or 2 samples requires sophisticated mathematical methods. Given that the effects of daptomycin are predicted by AUC/MIC, our objective was to compare simple equation calculated AUC based on Cp and Ct to model integrated AUC. A standard population pharmacokinetic model was used to simulate 5,000 daptomycin concentration-time profiles after 5 doses of 6 mg/kg of body weight/day (0.5-h infusions). The AUC for the 24-h period was computed by integration and by equations with 110 Cp-Ct combination pairs. The Cp time points were in 15-min increments between 0.5 h and 3 h and Ct in 15-min increments within an hour of the end of the dosing interval for each dose. The precision and bias of the calculated AUC relative to the integrated AUC were determined to identify Cp-Ct pairs associated with the lowest bias and highest precision. The equations were further validated using two daptomycin concentration-time data sets from healthy volunteers and critically ill patients. The precision and bias of calculated AUC were based primarily on Cp, and use of a daptomycin Cp 1.5 h to 3 h from the start of infusion was associated with a bias of <10% and an R(2) of >0.95. Data from the healthy volunteers and critically ill patients also demonstrated declining bias with use of Cp ≥ 1.5 h from the start of infusion with relatively good precision. Simplified equations using a daptomycin Cp approximately 2 h from the start of infusion and a Ct within an hour of the end of the dosing interval should yield precise and unbiased estimates of daptomycin AUC.

Drug repositioning: auranofin as a prospective antimicrobial agent for the treatment of severe staphylococcal infections.

Auranofin, (AF), a gold(I) complex in clinical use for the therapy of rheumatoid arthritis, is reported here to produce remarkable bactericidal effects in vitro against Staphylococcus sp. Noticeably, a similar antimicrobial action and potency are also noticed toward a few methicillin-resistant Staphylococcus aureus strains but not toward Escherichia coli. The time and concentration dependencies of the antimicrobial actions of AF have been characterized through recording time kill curves, and a concentration dependent profile highlighted. Overall, the present results point out that auranofin might be quickly and successfully repurposed for the treatment of severe bacterial infections due to resistant Staphylococci.

Considerations for higher doses of daptomycin in critically ill patients with methicillin-resistant Staphylococcus aureus bacteremia.

BACKGROUND: Higher daptomycin doses are advocated for select methicillin-resistant Staphylococcus aureus (MRSA)-related infections, but the probabilities of target attainment (PTA) and toxicity of these doses have not been characterized in critically ill patients. METHODS: We evaluated the plasma pharmacokinetics (PK) and clinical outcomes of a cohort of critically ill patients treated with daptomycin 6-8 mg/kg/day for primarily Staphylococcus species-related infections. Daptomycin concentrations were measured intensively over the initial 96-hour dosing period. Data were modeled by population PK analyses, and Monte Carlo simulation was used to estimate the probabilities of effect and toxicity with standard and alternate dosing regimens. RESULTS: Fifty patients with a mean (SD) age of 69.7 (12.2) years, weight 74.5 (20.3) kg, and creatinine clearance 56.8 (38.2) mL/minute were enrolled with measurements of 12 (2.2) daptomycin samples per patient. Significantly lower daptomycin exposures were observed despite comparable doses in a subset of patients (n = 13) with augmented clearance (CL). No covariates of CL were identified, but this subset was significantly more likely to be in severe sepsis or septic shock, have higher Sequential Organ Failure Assessment scores, and MRSA bacteremia. In-hospital mortality was significantly higher (30.7% vs 10.8%) in patients with augmented daptomycin CL. Use of an empiric fixed dose of 750 mg of daptomycin is predicted to achieve a comparable PTA with a lower probability of toxicity as compared to the use of 10 mg/kg in critically ill patients. CONCLUSIONS: A reappraisal of current daptomycin dosing recommendations is needed to improve the PTA and reduce toxicity among critically ill patients.

Prospective phase II single-center study of the safety of a single very high dose of liposomal amphotericin B for antifungal prophylaxis in patients with acute myeloid leukemia.

Some preclinical and pharmacokinetic studies suggested the variable safety and the potential efficacy of an antifungal prophylaxis with a single high dose of liposomal amphotericin B (L-AmB) in high-risk patients. An open-label, prospective study was conducted with 48 adults receiving induction chemotherapy for acute myeloid leukemia (AML). Patients received a single infusion of 15 mg/kg of body weight L-AmB and, eventually, a second dose after 15 days of persistent neutropenia. The primary objective was tolerability and safety. Efficacy was also evaluated as a secondary endpoint. A pharmacokinetic study was performed with 34 patients in order to evaluate any association of plasma L-AmB levels with toxicity and efficacy. Overall, only 6 patients (12.5%) reported Common Toxicity Criteria (CTC) grade 3 hypokalemia, which was corrected with potassium supplementation in all cases, and no patient developed clinically relevant nephrotoxicity. Mild infusion-related adverse events occurred after 6 of 53 (11.3%) total infusions, with permanent drug discontinuation in only one case. Proven invasive fungal disease (IFD) was diagnosed in 4 (8.3%) patients. The mean AmB plasma levels at 6 h, 24 h, and 7 days after L-AmB administration were 160, 49.5, and 1 mg/liter, respectively. The plasma AmB levels were higher than the mean values of the overall population in 3 patients who developed CTC grade 3 hypokalemia and did not significantly differ from the mean values of the overall population in 3 patients who developed IFD. Our experience demonstrates the feasibility and safety of a single 15-mg/kg L-AmB dose as antifungal prophylaxis in AML patients undergoing induction chemotherapy.

Variability of pharmacokinetic parameters in patients receiving different dosages of daptomycin: is therapeutic drug monitoring necessary?

Pharmacokinetic studies of daptomycin in septic patients indicate that pharmacokinetic parameters may be altered. The purpose of this clinical investigation is to determine the pharmacokinetics of daptomycin in a population of hospitalized patients with clinically significant gram-positive infections and receiving daptomycin. Daptomycin was measured using an isocratic HPLC technique. Thirty-five patients suffering from gram-positive severe infections and receiving daptomycin were included in the study. Patients were divided into two groups, depending on the dose of daptomycin received: group A, including 24 patients receiving 6 mg/kg/day daptomycin and group B, 11 patients receiving 8 mg/kg/day. Patients receiving a daptomycin dosage of 8 mg/kg/day had significantly higher values of mean C max and AUC0-24. Each group was further divided into three subgroups, according to the creatinine clearance (CrCl) values: (1) patients with a CrCl >80 ml/min, (2) patients with CrCl ranging between 80 and 40 ml/min, and (3) patients with CrCl <40 ml/min. Compared to patients with normal renal function, those with CrCl <40 ml/min had higher mean values of minimum concentration (C min) (p < 0.001), AUC0-24 (p = 0.03), and prolonged plasma half-time (p < 0.001). These differences were present both in patients receiving 6 and those with 8 mg/kg/day. However, in each of the three subgroups with different degrees of renal function a marked variability of pharmacokinetics parameters was observed. The factors associated with increased mortality were an infection acquired in the ICU, hypoalbuminemia, and AUC/MIC <666. The marked variability that characterizes daptomycin pharmacokinetics in these patients suggest the monitoring of the main pharmacokinetic parameters in this clinical setting.

Rediscovering the value of fosfomycin trometamol in the era of antimicrobial resistance: A systematic review and expert opinion.

The worldwide prevalence of uncomplicated lower urinary tract infections (uUTIs) caused by multidrug-resistant Escherichia coli is increasing. To address this emergency, international guidelines recommend reducing administration of fluoroquinolones, in the context of growing resistance and the long-lasting and potentially disabling side effects of these drugs. The favoured drug to replace fluoroquinolones is fosfomycin trometamol (FT), a well-known derivate of phosphonic acid with broad-spectrum activity against Gram-negative and Gram-positive bacteria, including multidrug-resistant (MDR) strains. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) recently reduced the susceptibility breakpoint for E. coli from 32 mg/L to 8 mg/L regarding FT used for uUTIs. This might lead to increased appropriate use of oral fosfomycin target therapy against E. coli and other microorganisms, and may be associated with a high likelihood of success. For species such as Klebsiella spp, particularly MDR strains, the absence of clinical breakpoints might lead to reduced use of oral fosfomycin, particularly if minimum inhibitory concentration is not available. To address this issue, this review presents an overview of the preclinical evidence on the activity of FT, and a systematic review of the clinical activity of FT in uUTIs in women, and in the prevention of infectious complications after prostate biopsy. The findings indicate that the safety and microbiological and clinical effectiveness of a single oral dose of FT are similar to that for comparator regimens with longer treatment schedules in women with uUTI, and FT can be considered a viable alternative to fluoroquinolones for antimicrobial prophylaxis in prostate biopsy. These observations and a broad clinical experience support the empirical use of FT for treating uUTI and indicate that FT is a promising candidate to effectively counteract antibiotic-resistant uUTIs throughout Europe.

Glutathione: Pharmacological aspects and implications for clinical use in non-alcoholic fatty liver disease.

Glutathione is a tripeptide synthesized at cytosolic level, that exists in cells in a reduced form (thiol-reduced-GSH-) and in an oxidized form (disulfide-oxidized). The antioxidant function of GSH has led to speculation about its therapeutic role in numerous chronic diseases characterized by altered redox balance and reduced GSH levels, including, for instance, neurodegenerative disorders, cancer, and chronic liver diseases. Among these latter, non-alcoholic fatty liver disease (NAFLD), characterized by lipid accumulation in hepatocytes, in the absence of alcohol abuse or other steatogenic factors, is one of the most prevalent. The umbrella term NAFLD includes the pure liver fat accumulation, the so-called hepatic steatosis or non-alcoholic fatty liver, and the progressive form with inflammation, also known as non-alcoholic steatohepatitis, which is related to the increase in oxidative stress and reactive oxygen species, eventually leading to liver fibrosis. Although the pathogenetic role of oxidative stress in these diseases is well established, there is still limited evidence on the therapeutic role of GSH in such conditions. Hence, the aim of this review is to depict the current molecular and pharmacological knowledge on glutathione, focusing on the available studies related to its therapeutic activity in NAFLD.

Field and laboratory studies to assess the effects of Vertimec(®) 18EC on Daphnia similis.

The present study aimed to evaluate the interactions of the pesticide Vertimec(®) 18EC in aquatic ecosystems. In this respect, soil plots were contaminated with Vertimec(®) 18EC at the concentration indicated for strawberry crops (0.125L of solution m(-2)). After the contamination, torrential rainfall was simulated and the surface runoff was collected and transferred to mesocosm tanks in five treatments, run in triplicate: (1) control-C; (2) runoff from an uncontaminated plot-UR; (3) runoff from the plot contaminated with Vertimec(®) 18EC-CR; (4) direct application of Vertimec(®) 18EC in the water-V and (5) water samples gathered randomly to verify whether there was contamination between the mesocosms-RS. Water samples from these tanks were also submitted to ecotoxicological tests with Daphnia similis and analyses to evaluate the limnological characteristics, in five collection periods over 10 days (240h). Physical and chemical differences were observed in the water samples, mainly related to increased turbidity, suspended solids and nutrients (nitrogen and phosphate forms). Acute toxicity was observed for the direct application treatment for the entire experimental period, and in some periods for the CR treatment (from 48h to 168h). The results obtained suggest that the pesticide did not fully degrade during the study period (10 days) in the direct application treatment, demonstrating that the presence of other substances in the commercial formulation contribute to the maintenance of toxicity. This represents a potential risk for aquatic ecosystems in areas adjacent to where the chemical is applied.