Degradation of cytostatics methotrexate and cytarabine through physico-chemical and advanced oxidative processes: influence of pH and combined processes on the treatment efficiency.

Environmental release of wastewater that contains cytostatic drugs can cause genotoxic impact, since these drugs act directly on the genetic material of aquatic organisms. Thus, the aim of this study was to evaluate the removal of the cytostatic drugs cytarabine (CTR) and methotrexate (MTX) using different physico-chemical methods individually (i.e. US, O3, H2O2 and UV) and combined (i.e. O3/US, US/H2O2, O3/H2O2 and O3/US/H2O2) under different pH conditions (4, 7 and 10). In the degradation tests, the efficiency of the methods applied was found to be dependent on the pH of the solution, with the degradation of CTR being better at pH 4 and MTX at pH 7 and pH 10. The US, H2O2 and US + H2O2 methods were the least efficient in degrading CTR and MTX under the pH conditions tested. The highest MTX degradation rate after 16 min of treatment at pH 7 was achieved by the O3 + H2O2 method (97.05% - C/C0 = 0.0295). For CTR, the highest degradation rate after 16 min of treatment was achieved by the O3 process (99.70% - C/C0 = 0.0030) at pH 4. In conclusion, most of the treatment methods tested for the degradation of CTR and MTX are effective. Notably, ozonolysis is an efficient process applied alone. Also, in combination with other methods (US + O3, O3 + H2O2 and O3 + H2O2 + US) it increases the degradation performance, showing a rapid removal rate of 70-94% in less than 4 min of treatment.

Efficacy of postoperative analgesia with duloxetine in posthemorrhoidectomy pain: a prospective, randomized, double-blind and placebo-controlled trial.

BACKGROUND: To evaluate the effect of duloxetine when added to a multimodal analgesia regimen on posthemorrhoidectomy pain, opioid consumption, and side effects. METHODS: Prospective, randomized, double-blind placebo-controlled trial. This study included 62 patients who underwent hemorrhoidectomy. The patients were randomly assigned to receive oral duloxetine 60 mg or placebo 2 h before and 24 h after surgery. The primary outcomes were pain intensity - measured on an 11-point visual analog pain scale - and cumulative morphine consumption at 12, 24, and 48 postoperative hours. RESULTS: Fifty-two patients completed the study (25 in the duloxetine group and 27 in the placebo group). Pain scores did not differ between duloxetine and placebo: 4.5; 3.0 - 7.0 vs. 5.0; 3.5 - 7.0, p = 0.68 at 12 h, 3.0; 2.0 - 5.0 vs. 3.0; 2.0 - 5.0, p = 0.56 at 24 h, and 2.5; 1.75 - 3.75 vs. 1.5; 0.5 - 3, p = 0.08 at 48 h. Further, cumulative morphine consumption did not differ between the duloxetine and placebo groups: 4; 1.25 - 10.75 mg vs. 7; 1.0 - 12.0 mg, p = 0.68 at 12 h, 9.5; 2.0 - 17.5 mg vs. 8.0; 4.0 - 18.0 mg; p = 0.80 at 24 h, and 11.0; 2.0 - 27.0 mg vs. 10; 4.0 - 24.0 mg, p = 0.78 at 48 h. Side effects did not differ between the groups. CONCLUSIONS: Compared with placebo, duloxetine did not decrease pain intensity or morphine consumption during the first 48 h postoperatively. TRIAL REGISTRATION: The study was retrospectively registered on the Brazilian Clinical Trials Registry (identifier: RBR-9pdgms, registration date: 08/10/2020).

The effects of a short-term perioperative duloxetine treatment on post-colectomy pain: A randomized, controlled clinical trial.

STUDY OBJECTIVE: To test the hypothesis that duloxetine reduces postoperative morphine consumption and pain intensity in patients undergoing major colonic surgeries. DESIGN: Single-center, prospective, double-blinded, randomized, controlled trial. SETTING: Tertiary university hospital, from December 2019 to September 2021. PATIENTS: Sixty 18-85 years old, ASA I - III patients undergoing elective open major colonic surgeries were randomly allocated into duloxetine (duloxetine) or placebo (placebo) groups (n = 30 per group). INTERVENTIONS: Duloxetine 60 mg or placebo was administered orally 2 h before and 24 h after surgery. MEASUREMENTS: PCA morphine consumption, surgical pain at rest, and movement measured on 10-cm visual analog scales (VAS), Ramsay sedation scores, and the incidence of adverse effects potentially associated with duloxetine were assessed at patients' admission to the post-anesthesia care unit (PACU), 6, 24, and 48 h postoperatively (PO). MAIN RESULTS: After adjusting for age, BMI, ASA physical status, education level, and incision type, no differences were found between groups in PCA morphine consumption 24 PO h (duloxetine = 5.44 ± 2.06 mg; placebo = 10.33 ± 2.06 mg, p = 0.62) or 48 h PO (duloxetine = 9.18 ± 2.06 mg, placebo = 12.93 ± 2.06, p = 1). Pain at rest also did not differ between groups at 24 h PO (duloxetine = 1.76 ± 0.67 cm; placebo = 1 ± 0.67 cm, p = 1) or at 48 h PO (duloxetine = 0.84 ± 0.67 cm; placebo = 0.49 ± 0.67 cm, p = 1). Similarly, groups did not differ regarding pain on movement at 24 h PO (duloxetine = 2.09 ± 0.68 cm; placebo = 1.80 ± 0.68, p = 1) or at 48 h PO (duloxetine = 1.16 ± 0.68 cm; placebo = 0.88 ± 0.68 cm, p = 1). Sedation scores and adverse effects also did not differ between groups. CONCLUSION: Under this study's conditions, short-term duloxetine did not reduce total opioid consumption or pain intensity during the initial 48 h following major colon surgery.

Using basic parameters to evaluate adsorption potential of alternative materials: example of amoxicillin adsorption by activated carbon produced from termite bio-waste.

The minimum set of parameters that can be used to assess the adsorption capacity of activated carbon (AC) produced from termite bio-waste was determined. Three types of AC were prepared: AC600 at 600 °C, MAC600 at the same temperature and impregnated with FeCl3, and AC800 at 800 °C. The influence of the solution pH on the adsorption, adsorption kinetics, isotherms and thermodynamic parameters was considered to characterize the amoxicillin (AMX) adsorption process. The AC materials had surface areas (m2 g-1) of approximately 248.8 for AC600, 501.6 for AC800 and 269.5 for MAC600, with point of zero charge (pHPZC) values of 8.3, 7.5 and 1.7, respectively. A time period of 30 min was chosen for the adsorption kinetics, which was best represented by the pseudo-first-order model for AC600, the intraparticle diffusion model for AC800 and the pseudo-second-order model for MAC600. Regarding the isotherms, a maximum adsorption of 23.4 mg g-1 was found for AC800. In general, the thermodynamic parameters demonstrated a non-spontaneous process. It seems that the medium conditions, the adsorbate and adsorbent characteristics, and the Gibbs free energy are the most important parameters to be considered in a preliminary assessment of the adsorption efficiency of specific adsorbent/adsorbate pairs.

Genetic material present in hospital wastewaters: Evaluation of the efficiency of DNA denaturation by ozonolysis and ozonolysis/sonolysis treatments.

Hospital wastewater treatments must ensure that all genetic material is destroyed, since nuclear and extra-nuclear DNA can show antimicrobial resistance and contain recombinant genes, which promote vertical and/or horizontal gene transfer, amplifying the current problem of the emergence of antibiotic-resistant microorganisms. In this study, we investigated whether ozonolysis or ozonolysis/sonolysis in combination can denature genetic material, i.e., destroy the integrity of DNA molecules, present in hospital wastewaters. To achieve this goal, hospital wastewaters were treated by ozonolysis or ozonolysis/sonolysis in combination (at 70 and 100 W L(-1)) and both raw and treated wastewaters were analyzed in terms of disinfection and DNA denaturation efficiency quantified by viable cell counts and by agarose gel electrophoresis. In the ozonolysis treatment, the agarose gel electrophoresis technique showed that the ozone-treated samples contained DNA molecules, while combined ozonolysis/sonolysis destroyed the DNA in a power density-dependent manner (64% at 70 W L(-1) and 81% at 100 W L(-1)). Care must be taken by environmental managers to distinguish disinfection processes from DNA denaturation processes, since these two terms are not synonymous.

Individuals with hematological malignancies before undergoing chemotherapy present oxidative stress parameters and acute phase proteins correlated with nutritional status.

Hematological malignancies present abnormal blood cells that may have altered functions. This study aimed to evaluate nutritional status, acute phase proteins, parameters of cell's functionality, and oxidative stress of patients with hematological malignancies, providing a representation of these variables at diagnosis, comparisons between leukemias and lymphomas and establishing correlations. Nutritional status, C-reactive protein (CRP), albumin, phagocytic capacity and superoxide anion production of mononuclear cells, lipid peroxidation and catalase activity in plasma were evaluated in 16 untreated subjects. Main diagnosis was acute leukemia (n = 9) and median body mass index (BMI) indicated overweight (25.6 kg/m(2)). Median albumin was below (3.2 g/dL) and CRP above (37.45 mg/L) the reference values. Albumin was inversely correlated with BMI (r = -0.53). Most patients were overweight before the beginning of treatment and had a high CRP/albumin ratio, which may indicate a nutrition inflammatory risk. BMI values correlated positively with lipid peroxidation and catalase activity. A strong correlation between catalase activity and lipid peroxidation was found (r = 0.75). Besides the elevated BMI, these patients also have elevated CRP values and unexpected relations between nutritional status and albumin, reinforcing the need for nutritional counseling during the course of chemotherapy, especially considering the correlations between oxidative stress parameters and nutritional status evidenced here.

A comparison between ozonolysis and sonolysis/ozonolysis treatments for the degradation of the cytostatic drugs methotrexate and doxorubicin: Kinetic and efficiency approaches.

Cytostatics are a major class of chemotherapy drugs with great potential to cause genotoxic and/or mutagenic effects in all organisms. Currently, hospital wastewater treatment systems (HWTS) are not able to remove these compounds and they are discharged to the environment. Thus, the objective of this study was to investigate the oxidative degradation of the cytostatic drugs doxorubicin (DOXO) [(8s,10s)-10-(4-amino-5-hydroxy-6-methyl-tetrahydro-2h-pyran-2-yloxy)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione] and methotrexate (METHO) {N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid} by ozonolysis alone and using a combined sonolysis/ozonolysis process on bench-scale at different pH values. Besides determining the degradation efficiency, a kinetic approach was applied to determine the reaction order and rate constants for different oxidative processes carried out at pH 7.0, which is the normal pH of hospital wastewater. The results showed that the removal efficiency of these compounds is pH-dependent. A combination of sonolysis and ozonolysis processes is more efficient than the ozonolysis process alone for the degradation of doxorubicin at all pH values, while methotrexate can easily be degraded by ozonolysis alone or sonolysis/ozonolysis methodologies at any pH.

Effect of fructose-1,6-bisphosphate on the nephrotoxicity induced by cisplatin in rats.

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer, but its clinical use is frequently limited by nephrotoxicity. The study presented here attempted to evaluate the effect of fructose-1,6-bisphosphate in the cisplatin-induced nephrotoxicity in rats. The drugs were administered intraperitoneally as a single dose: sodium chloride 0.9%, cisplatin (6 mg/kg), fructose-1,6-bisphosphate (500 mg/kg), and cisplatin plus fructose-1,6-bisphosphate (6 and 500 mg/kg, respectively). The use of cisplatin resulted in significant elevation of serum creatinine and urea. The group that received cisplatin plus fructose-1,6-bisphosphate presented a significantly lower level of creatinine and urea compared to the cisplatin group. Acute tubular necrosis was demonstrated in the animals that received cisplatin and a less severe one in the cisplatin plus fructose-1,6-bisphosphate group. Fructose-1,6-bisphosphate has a protective effect over renal function and renal parenchyma in a rat experimental model of cisplatin-induced nephrotoxicity. The anti-inflammatory effect of fructose-1,6-bisphosphate confirms its protective effect in cases of cellular injury.

Ocurrence of blaSPM-1 and blaIMP-1 genes of metallo-beta-lactamases in clinical isolates of Pseudomonas aeruginosa from three universitary hospitals in the city of Porto Alegre, Brazil

We described the ocurrence of metallo-beta-lactamases (MBL) genes blaSPM-1 and blaIMP-1 in clinical isolates of Pseudomonas aeruginosa resistant to imipenem and/or ceftazidime obtained from three universitary hospitals in the city of Porto Alegre, Brazil. The MBL production was screened by phenotypic test and the genes were detected by PCR.

Descrevemos a ocorrência dos genes de metalo-beta-lactamases (MBL) blaSPM-1 e blaIMP-1 em isolados clínicos de Pseudomonas aeruginosa resistentes ao imipenem e/ou ceftazidima obtidos em três hospitais universitários de Porto Alegre, Brasil. A produção de MBL foi observada através de técnica fenotípica e os genes foram detectados pelo método de PCR.

Risk factors for nosocomial infections due to Pseudomonas aeruginosa producing metallo-beta-lactamase in two tertiary-care teaching hospitals.

OBJECTIVES: To assess risk factors for nosocomial infections due to Pseudomonas aeruginosa producing metallo-beta-lactamase (MBL-PA) in two teaching hospitals where horizontal dissemination has been demonstrated. METHODS: A case-control study was performed in both hospitals (assigned as hospital 1 and 2). Cases were patients with MBL-PA infections and controls were those with non-MBL-PA infections. Multivariate analysis was performed to identify independent risk factors. RESULTS: A total of 86 cases and 212 controls were included in the study. A logistic regression model showed that exposure to beta-lactams [odds ratio (OR) 3.21; 95% confidence interval (CI) 1.74-5.93] or fluoroquinolones (OR 3.50; 95% CI 1.46-8.37) was associated with MBL-PA infections. Other independent risk factors were neurological disease (OR 3.00; 95% CI 1.61-5.58), urinary tract infection (OR 2.48; 95% CI 1.21-5.09) and renal failure (OR 2.29; 95% CI 1.13-4.65). Admission to hospital 1 (OR 5.97; 95% CI 3.45-14.09) and intensive care unit stay (OR 2.07; 95% CI 1.46-3.96) were also associated with increased risk for MBL-PA infections. CONCLUSIONS: beta-Lactam exposure is an important risk factor for MBL-PA infections even in a setting where patient-to-patient transmission plays a major role in the spread of the isolates. Other risk factors deserve further investigation, particularly exposure to fluoroquinolones.

Outbreak of carbapenem-resistant Pseudomonas aeruginosa producing SPM-1 metallo-{beta}-lactamase in a teaching hospital in southern Brazil.

OBJECTIVES: To describe the first nosocomial outbreak of Pseudomonas aeruginosa producing SPM-1 metallo-beta-lactamase (MBL) in southern Brazil. PATIENTS AND METHODS: From January to October 2004, carbapenem-resistant P. aeruginosa (CRPA) were recovered from hospitalized patients. Mortality, site of infection/colonization, patient location and susceptibility profiles were analysed. A sample of CRPA was screened for MBL production, evaluated for the presence of bla(SPM-1), bla(IMP-1) and bla(VIM-2) genes by PCR and submitted for molecular typing by DNA macrorestriction. RESULTS: A total of 135 CRPA (one isolate per patient) were recovered. Two major antibiotic susceptibility profiles comprised 63.7% of the isolates (susceptibility to polymyxin B and aztreonam, and susceptibility only to polymyxin B). Thirty-five CRPA were screened for MBL production (10 isolates from April, June and July, and 25 from September and October) and 27 (77.1%) proved to be positive for MBL production. Twenty-one of the 24 CRPA tested carried the bla(SPM-1) gene. The mortality of patients with CRPA was 48.1% and no variable was associated with death. Molecular typing revealed the presence of a clone with four related subtypes among the bla(SPM-1)-positive CRPA. CONCLUSIONS: The prevalence of MBL production by CRPA is high and horizontal transmission is a major determinant for the spread of SPM-1 CRPA among patients in this institution. As infection control measures failed to control the spread of CRPA, continuous surveillance for MBL production is warranted.

Intravenous toxicity of fructose-1,6-bisphosphate in rats.

Fructose-1,6-bisphosphate (FBP) is a bisphosphorilated sugar with a protective action against events that lead to cellular damage. The toxicity of the drug was assessed when administered intravenously in Wistar rats in doses of between 250 and 4000 mg/kg. Ionic calcium, total calcium, inorganic serum phosphate and the electrocardiographic profile of these animals were assessed. The lethal dose (LD(50)) was established by means of PROBIT processing. There was no reduction in the levels of total calcium, with the administration of increased doses of FBP, although there was a significant reduction in the levels of ionic calcium in those groups that received 250 mg/kg and over. The serum phosphate showed a significant statistical increase in those groups that received 750 mg/kg and over. The LD(50) obtained in 24 h was 1068 mg/kg. Though it was not possible to elucidate the toxic mechanism of FBP, the electrocardiogram (ECG) showed that all the rats died of cardiac arrest.

Prevalência de enteroparasitos em moradores de vilas periféricas de Porto Alegre, RS / Survey of intestinal parasites among inhabitants of Porto Alegre Metropolitan area

Realizou-se um trabalho integrado de pesquisa e extensão comunitária com o objetivo de determinar a prevalência das enteroparasitoses na vila Fátima (Mato Sampaio), Campo da Tuca e Vila dos Papeleiros, vilas periféricas de Porto Alegre. este estudo foi realizado durante os anos de 1999 e 2002 em uma população de 594 pessoas, todas residentes nestas vilas. As amostras fecais foram examinadas pela técnica de Hoffman, Pons e Janer. O maior percentual geral de infecção obtido para nematóides foi de 39,5% (235) para Ascaris lumbricoides e, entre os protozoários, a Giardia lamblia com 18,0% (107). As altas taxas de enteroparasitoses entre crianças e adultos jovens moradores destas vilas mostrou o baixo nível sócio-econômico, a falta de escolaridade e a inexistência de saneamento básico.

O antígeno prostático específico e sua importância na decisão clínica no câncer de próstata / The prostatic specific antigen and its importance in the clinical decision in the prostate cancer

O câncer de próstata (CaP) representa um problema de saúde pública de proporções cada vez mais importantes. É uma das neoplasias mais frequentes nos homens e representa uma das principais causas de morte na população. A busca de métodos diagnósticos para as neoplasias é um constante objetivo clínico laboratorial. Exame físico, métodos de imagem e dosagens laboratoriais compreendem o conjunto de auxílio diagnóstico no CaP. O antígeno prostático específico (PSA) é produzido pelo tecido prostático normal, bem como, em casos de Hiperplasia Prostática Benigna (HPB) e no CaP. Sua dosagem constitui importante método laboratorial na prática médica, uma vez que se apresenta com grande valor no rastreamento, diagnóstico e acompanhamento dos casos de CaP. O entendimento do seu papel pelo farmacêutico-bioquímico, bem como, a interação com a equipe clínica mostra-se promissor para influenciar as decisões diagnóstico-terapêuticas.

Prostate cancer represents a public health concern whose proportions are becoming increasingly important. It is one of the most common neoplasia among men and it represents one of the main causes of death in the population. The search for diagnostic methods for this neoplasia has been a constant laboratory clinic target. Physical checking, imaging methods and laboratory dosages compose the range of diagnostic support when dealing with prostate cancer...