Predictability of expansion movements performed by clear aligners in mixed dentition in both arches: a retrospective study on digital casts.

BACKGROUND: to evaluate the predictability of expansion achieved in patients in early mixed dentition treated with Clear Aligners (CA), analyzing the efficiency of the expansion at the end of the first set of aligners and at the end of the therapy in the upper and lower arch. METHODS: 36 patients (20 F, 16 M; mean age 8.3 ± 1.5 years) were selected retrospectively from the Department of Orthodontics of the Hospital of Rome "Tor Vergata". All subjects were treated with CA with no other auxiliaries than attachments. For each patient a standardized sequential expansion protocol was planned for both arches. Digital dental casts were created at three observation periods from an intraoral scanner: prior to treatment (T0), at the end of the first set of aligners (T1), at the end of treatment (T2). The 3D models in planned position determined by the first Clincheck (CC) were obtained for comparison with T1 and T2. Six linear transversal measurements were used to evaluate the dimensional changes and the predictability of expansion movements, comparing T1-CC and T2-CC. RESULTS: a statistically significant increase within the pre-treatment and the final outcomes for all the variables examined was found. In the upper arch, the greatest level of predictability was detected at the level of the first (46.44%) and second deciduous molar width (44.95%) at T1. The analysis of T2-CC changes showed a significant increase in the percentage of predictability of expansion at the level of the first permanent molars, at mesial (54.86%) and distal (58.92%) width. In the lower arch, a higher percentage of predictability than the upper arch was reported at T1-CC and T2-CC, with the greatest values at the level of second (T1-CC: 48.70%; T2-CC: 75.32%) and first deciduous molar width (T1-CC: 45.71%; T2-CC: 72.75%). CONCLUSIONS: CA can induce significant transversal increments. The predictability of expansion is variable, but it did not exceed the 50% during the first set of aligners. It was necessary to apply refinement set to achieve a good predictability for expansion of about 70%. The expansion in the lower arch was observed to be more predictable than in the upper arch.

Experimental validation of mechanical oscillating IPR system.

BACKGROUND: Interproximal enamel reduction (IPR) is a clinical procedure which involves reduction and anatomic recontouring of interproximal surfaces of enamel as a method of gaining space. The biological effects related to this clinical procedure have long been discussed. Thus, the aim of this study was to evaluate the enamel reduction efficiency and the effects on enamel surfaces of the oscillating mechanical system for interproximal enamel reduction (IPR). METHODS: Fifteen complete oscillating IPR sequences included one opener (0.1 mm), two metallic strips for active IPR phase (0.2 and 0.3 mm), three resin strips for active and initial polishing phases (0.4 and 0.5 mm), and one resin strip for polishing phase (0.15 mm). Sequences were selected and tested on fifteen freshly extracted teeth by means of tribological tests with alternative dry-sliding motion (Linear Reciprocating Tribometer; C.S.M. Instruments, Peseaux, Switzerland). A 3D analysis of treated surfaces was performed by using a TayMap software. Then, enamel surfaces were qualitatively evaluated before and after the tribological analysis, with a FEI Quanta 200 (FEI, Hillsboro, OR, USA) in high vacuum at 30.00 kV. Images were acquired at a 30×, 100× and 300× magnification. RESULTS: Minimum surface irregularities were observed on all treated enamel surfaces when compared with untreated ones. The 3D analysis showed a uniform wear pattern after tribological tests. Meanwhile, the SEM analysis revealed smooth and regular wear lines on treated surfaces after the entire mechanical IPR sequence. The macroscopic irregularities illustrated can be considered similar to those of untreated surfaces. CONCLUSIONS: The adoption of a standardized oscillating IPR sequence allows an efficient reduction of the interproximal enamel, leaving regular and harmonious surfaces. Adequate polishing procedures should always be performed at the end of active IPR phases in order to guarantee a good long-term prognosis and proper respect of biological structures.

Effectiveness of Nutritional Supplements for Attenuating the Side Effects of SARS-CoV-2 Vaccines.

Supplementation is known to enhance the immune response and reduce infection. Therefore, the association between immune nutrients and vaccine side effects needs to be investigated. Our aim was to analyze the relationship between vaccination side effects and supplement intake among the Italian population. The study included a questionnaire asking for personal data, anthropometric information, COVID-19 infection and immunity response, and COVID-19 vaccination and supplementation. The survey was conducted from 8 February to 15 June 2022. In the study, 776 respondents were included, aged between 18 and 86 (71.3% females). We observed a statistically significant correlation between supplement consumption and side effects at the end of the vaccination cycle (p = 0.000), which was also confirmed by logistic regression (p = 0.02). Significant associations were observed between supplement intake and side effects of diarrhea and nausea at the end of the vaccination cycle (p = 0.001; p = 0.04, respectively). Significant associations were observed between side effects and omega-3 and mineral supplementation at the start of the vaccination cycle (p = 0.02; p = 0.001, respectively), and between side effects and vitamin supplementation at the end of the vaccination cycle (p = 0.005). In conclusion, our study shows a positive impact of supplementation on vaccination response, increasing host immune defenses, and reducing side effects.

Evaluation of the Upper Arch Morphological Changes after Two Different Protocols of Expansion in Early Mixed Dentition: Rapid Maxillary Expansion and Invisalign® First System.

Background: The objective of this retrospective study was to analyze the morphological changes of the upper arch after two protocols of expansion, the Invisalign® First system and rapid maxillary expansion (RME), in mixed dentition by means of geometric morphometric analysis (GMM). Methods: Digital dental casts of 32 children treated either with RME (RME group: 17 subjects; mean age 8.1 years) or the First system (First group: subjects; mean age 8.4 years) were collected. For both the RG and FG, pre-(T1) and post-treatment(T2) digital models were created. A total of 14 landmarks were digitized and GMM was applied. Procrustes analysis and principal component analysis (PCA) were performed. Results: The PC1 resulting from the T2-T1 comparison in the RG g showed statistically significant morphological changes in the posterior region of the upper arch shape, without significant variations in the anterior region. The comparison of the T2-T1 changes in the FG showed an increase in the transverse dimension at the level of the canine and the first deciduous molar widths, with morphological variation in the anterior region due to frontal teeth alignment. Conclusions: The First system induced shape modifications of the upper arch during expansion in contrast to RME. The FG presented an improvement in the maxillary arch shape, while the RG maintained the initial triangular shape.

Dento-skeletal response to three different protocols of rapid maxillary expansion in hyperdivergent growing subjects: a longitudinal retrospective study.

BACKGROUND: The aim of this study was to evaluate the dento-skeletal response in hyperdivergent growing patients comparing Rapid Maxillary Expansion (RME) using three different protocols. MATERIALS AND METHODS: Three groups of hyperdivergent subjects treated with RME were analyzed. In 41 patients (23F, 18M) the RME was bonded on the maxillary deciduous second molars (E-RME group); in 40 patients (24F, 16M) the RME was bonded on the first permanent maxillary molars (6-RME group); in 45 patients (26F,19M) the RME was bonded on the first permanent maxillary molars with a removable mandibular Bite-Block (6-RME/BB group). Lateral cephalograms and dental casts were scanned and digitally measured before treatment (T1), at the appliance removal (T2) and at least 1 year after the appliance removal (T3). The comparison was made within the same group and between the groups. Statistical comparisons were assessed with analysis of variance multi-comparison test (*P = 0.05). RESULTS: A significant increase of upper molars buccal tipping was observed in 6-RME group when compared with E-RME and 6-RME/BB groups in the short-term (T2-T1) and long-term (T3-T1); a significant intercanine width increase was observed in E-RME group at the same times. No significant differences in dentoalveolar variables were observed comparing E-RME group versus 6-RME/BB group. CONCLUSIONS: The E-RME protocol allows for a greater skeletal expansion and produces a lower buccal tipping of the first permanent upper molars. The use of the BB in 6-RME/BB group shows a similar attitude to the E-RME protocol then can be considered an effective therapeutic alternative.

Land-use impacts on benthic macroinvertebrate assemblages in pampean streams (Argentina).

In recent decades agriculture has intensified in the Argentine Pampa, and pesticide application has also increased. Livestock fields, although being progressively replaced by crops, are still commonly interspersed with crop fields. The objective of the present work is to assess the effects of land use on the benthic invertebrate assemblages of streams in the main Argentine agricultural region. Two areas were sampled during the 2011/12 growing season (November-March): Arrecifes, a homogeneous intensively cultivated area, and La Plata, a heterogeneous area of mixed livestock pasture, cropland and biological reserve. Nutrient concentrations in water were significantly higher in the streams surrounded by cropland. Measured pesticides in stream sediments were those most commonly used in crop production: chlorpyrifos, cypermethrin, lambda-cyhalothrin, endosulfan and its degradation product endosulfan sulfate. Detection frequency and pesticide concentrations were generally higher in streams surrounded by cropland than in streams surrounded by pasture or reserve. Macroinvertebrate assemblages were significantly different in streams with different land uses. Palaemonidae (Decapoda) and Caenidae (Ephemeroptera) were the taxa best represented in the reserve. Hyalellidae (Amphipoda) and Hirudinea were dominant at the streams surrounded by livestock fields. Within the streams surrounded by croplands, Oligochaeta and Hirudinea were best represented in La Plata while Chironomidae, Gastropoda and Oligochaeta were dominant at Arrecifes. Present evidence suggests that agrochemical applications contribute, in combination with other environmental variables, to the observed differences in macroinvertebrate assemblages in streams of different land use.

Land use effect on invertebrate assemblages in Pampasic streams (Buenos Aires, Argentina).

Agriculture and livestock may contribute to water quality degradation in adjacent waterbodies and produce changes in the resident invertebrate composition. The objective of the present study was to assess land use effects on the stream invertebrate assemblages in rural areas of the Argentine Pampa. The four sampling events were performed at six sites in four streams of the Pampa plain; two streams were sampled inside a biosphere reserve, and another one was surrounded by extensive livestock fields. The fourth stream was sampled at three sites; the upstream site was adjacent to agricultural plots, the following site was adjacent to an intensive livestock plot and the downstream site was adjacent to extensive breeding cattle plots. Higher pesticide concentrations were found at the site adjacent to agricultural plots and higher nutrient concentrations at the sites adjacent to agricultural and intensive breeding cattle plots. The invertebrate fauna were also different at these sites. Multivariate analysis showed a relationship between nutrient concentrations and taxonomic composition. Amphipoda (Hyalella curvispina) was the dominant group in the reserve and extensive breeding cattle sites, but was not present in the agricultural site. Also, Chironomidae were absent from the agricultural site while present at other sites. Gasteropoda (Biomphalaria peregrina), Zygoptera, and Hirudinea were dominant at the most impacted agricultural and intensive breeding cattle sites.

Insecticide concentrations in stream sediments of soy production regions of South America.

Concentrations of 17 insecticides were measured in sediments collected from 53 streams in soy production regions of South America (Argentina in 2011-2014, Paraguay and Brazil in 2013) during peak application periods. Although environmental regulations are quite different in each country, commonly used insecticides were detected at high frequencies in all regions. Maximum concentrations (and detection frequencies) for each sampling event ranged from: 1.2-7.4 ng/g dw chlorpyrifos (56-100%); 0.9-8.3 ng/g dw cypermethrin (20-100%); 0.42-16.6 ng/g dw lambda-cyhalothrin (60-100%); and, 0.49-2.1 ng/g dw endosulfan (13-100%). Other pyrethroids were detected less frequently. Banned organochlorines were most frequently detected in Brazil. In all countries, cypermethrin and/or lambda-cyhalothrin toxic units (TUs), based on Hyalella azteca LC50 bioassays, were occasionally>0.5 (indicating likely acute toxicity), while TUs for other insecticides were <0.5. All samples with total insecticide TU>1 were collected from streams with riparian buffer width<20 m. A multiple regression analysis that included five landscape and habitat predictor variables for the Brazilian streams examined indicated that buffer width was the most important predictor variable in explaining total insecticide TU values. While Brazil and Paraguay require forested stream buffers, there were no such regulations in the Argentine pampas, where buffer widths were smaller. Multiple insecticides were found in almost all stream sediment samples in intensive soy production regions, with pyrethroids most often occurring at acutely toxic concentrations, and the greatest potential for insecticide toxicity occurring in streams with minimum buffer width<20 m.

Acute Toxicity of Endosulfan to the Non-target Organisms Hyalella curvispina and Cnesterodon decemmaculatus.

Pesticide consumption in Argentina has steadily increased over the last two decades, while one of these compounds, namely endosulfan, is commonly found in environmental samples. Also the fish Cnesterodon decemmaculatus and the amphipod Hyalella curvispina are widely distributed in agricultural areas of southern South America. The aim of the present contribution was therefore to determine the acute toxicity of endosulfan to both organisms, and compare it with species sensitivity distributions (SSD) and measured field concentrations. The 48 h-LC50 (with 95 % confidence limits) were 1.8 (1.6-2.1) µg/L for C. decemmaculatus and 16.4 (15.1-17.7) µg/L for H. curvispina. C. decemmaculatus was more sensitive than 74 % of fish based on the SSD. Endosulfan concentrations in stream water reported in the literature were often higher than the C. decemmaculatus LC50. It may hence be concluded that C. decemmaculatus is a suitable sentinel organism for ecotoxicological risk assessment in South America.

Acetaldehyde content and oxidative stress in the deleterious effects of alcohol drinking on rat uterine horn.

After alcohol exposure through a standard Lieber and De Carli diet for 28 days, a severe atrophy in the rat uteirne horn was observed, accompanied by significant alterations in its epithelial cells. Microsomal pathway of acetaldehyde production was slightly increased. Hydroxyl radicals were detected in the cytosolic fraction, and this was attributed to participation of xanthine oxidoreductase. They were also observed in the microsomal fraction in the presence of NADPH generating system. No generation of 1-hydroxyethyl was evidenced. The t-butylhydroperoxide-induced chemiluminescence analysis of uterine horn homogenates revealed a significant increase in the chemiluminiscence emission due to ethanol exposure. In the animals repeatedly exposed to alcohol, sulfhydryl content from uterine horn proteins was decreased, but no significant changes were observed in the protein carbonyl content from the same samples. Minor but significant decreasing changes were observed in the GSH content accompanied by a tendency to decrease in the GSH/GSSG ratio. A highly significant finding was the diminished activity content of glutathione peroxidase. Results suggest that acetaldehyde accumulation plus the oxidative stress may play an additional effect to the alcohol-promoted hormonal changes in the uterus reported by others after chronic exposure to alcohol.

Metodología UV para la determinación de los antichagásicos Nifurtimox y Benznidazol en sangre / UV methodology for determination of antichagasic drugs Nifurtimox and Benznidazol in blood / Metodologia UV para a determinação dos antichagásicos Nifurtimox e Benznidazol em sangue

El Mal de Chagas es una enfermedad parasitaria endémica en América del Sur y Central. Existen dos fármacos disponibles para el tratamiento médico de la enfermedad, el Nifurtimox (Nfx) y el Benznidazol (Bz). No existen protocolos estandarizados, validados y accesibles en laboratorios regionales para determinar niveles de los antichagásicos en sangre. En este trabajo se presenta un método espectrofotométrico para la determinación de Nfx y Bz en sangre. Los metabolitos en sangre se extraen con columnas Extrelut®. Los extractos se evaporan, se redisuelven en mezclas de metanol/agua y se analizan espectrofotométricamente a 400 nm y a 320 nm para Nfx y Bz, respectivamente. Se cuantifica comparando con soluciones estándar de Nfx o Bz en el solvente. La metodología utilizada fue validada entre 0,5 y 50 ug/mL de sangre para Nfx y entre 0,5 y 100 ug/mL de sangre para Bz. La exactitud, precisión, linealidad y robustez del método fueron satisfactorias. Se aplicó el procedimiento determinando concentraciones sanguíneas post administración de ambos fármacos a ratas.

Chagas' Disease is an endemic parasitic disease in South and Central America. There are two drugs available for medical treatment of the disease, Nifurtimox (Nfx) and Benznidazol (Bz). There are no standardized or accessible protocols in regional laboratorios to determine the levels of antichagasic drugs in blood. A spectrophotometric method for Nfx and Bz determination in blood is presented in the present work. Blood metabolites are extracted through Extrelut® columns. Extracts are evaporated, redissolved in metanol/water mixanalysed by spectrophotometry at 400 nm and 320 nm for Nfx and Bz, respectively. They are quantified comparing with standard Nfx or Bz solutions in the solvent. The methodology used was validated between 0.5 and 50 jg/mL of blood for Nfx, and between 0.5 and 100 jg/mL of blood for Bz. The accuracy, precision, lineality and robustness of the method were satisfactory. The procedure was applied determining blood concentrations after administration of both drugs to rats.

O Mal de Chagas é uma doenga parasitaria endémica na América do Sul e Central. Existem dois fármacos disponíveis para o tratamento médico da doença, o Nifurtimox (Nfx) e o Benznidazol (Bz). Não existem protocolos padronizados, validados e acessíveis em laboratorios regionais para determinarem níveis dos antichagásicos em sangue. Neste trabalho se apresenta um método espectrofotométrico para a determinação de Nfx e Bz em sangue. Os metabólitos em sangue são extraídos com colunas Extrelut®. Os extratos se evaporam, são redissolvidos em misturas de metanol/água e se analisam espectrofotometricamente a 400 nm e a 320 nm para Nfx e Bz, respectivamente. São quantificados comparando com soluções padrão de Nfx ou Bz no solvente. A metodologia utilizada foi validada entre 0,5 e 50 μg/mL de sangue para Nfx e entre 0,5 e 100 μg/mL de sangue para Bz. A exatidão, precisao, linearidade e robustez do método foram satisfatórias. Aplicouse o procedimento determinando concentrações sanguíneas pós- administragao de ambos os fármacos em ratos.

Benzonidazole levels in blood vary with age in rats.

Benznidazole (Bz) exhibits toxic side effects in animal studies and clinical use. Reductive metabolism of Bz in liver microsomes modulates the duration of its chemotherapeutic effect and its toxicity. The rate of this metabolism depends on age and is less intense in newborns and youngsters than in adults. In the present study, we determined Bz blood levels in rats of different ages that received Bz intragastrically (100 mg/kg). We developed and validated a high-pressure liquid chromatography with UV detector method for determination of Bz levels in whole blood. Bz levels were significantly higher and persisted for longer periods of time in the blood of young rats when compared to that of adult animals.

Benznidazole levels in blood vary with age in rats

Benznidazole (Bz) exhibits toxic side effects in animal studies and clinical use. Reductive metabolism of Bz in liver microsomes modulates the duration of its chemotherapeutic effect and its toxicity. The rate of this metabolism depends on age and is less intense in newborns and youngsters than in adults. In the present study, we determined Bz blood levels in rats of different ages that received Bz intragastrically (100 mg/kg). We developed and validated a high-pressure liquid chromatography with UV detector method for determination of Bz levels in whole blood. Bz levels were significantly higher and persisted for longer periods of time in the blood of young rats when compared to that of adult animals.

Further studies on the potential contribution of acetaldehyde accumulation and oxidative stress in rat mammary tissue in the alcohol drinking promotion of breast cancer.

There is available evidence supporting a positive association between alcohol intake and risk of breast cancer. However, there is limited information regarding possible mechanisms for this effect. Past studies from our laboratory suggest that acetaldehyde accumulation in mammary tissue after alcohol intake may be of particular relevance and that cytosolic and microsomal in situ bioactivation of ethanol to acetaldehyde and free radicals and the resulting stimulation of oxidative stress could be a significant early event related to tumor promotion. In the present studies repetitive alcohol drinking for 28 days was found to produce significant decreases in the mammary tissue content of GSH and alpha tocopherol and in glutathione S-transferase or glutathione reductase activities. In contrast, glutathione peroxidase activity was slightly increased. Malondialdehyde determinations did not show the occurrence of lipid peroxidation while the xylenol orange procedure gave positive results. The mammary microsomal metabolism of ethanol to acetaldehyde was not induced after an acute dose of ethanol or acetone able to induce the activity of its liver counterpart. The cytosolic pathway of alcohol metabolism instead was significantly enhanced by these two treatments. No increased generation of comet images was found either in mammary tissue or in liver under the experimental conditions tested. Results suggest that, while acetaldehyde accumulation in mammary tissue could be a critical event resulting from increasing production of acetaldehyde in situ plus an additional amount of it arriving via blood, other factors such as poor handling of the accumulated acetaldehyde could be also relevant.

Diallyl disulfide prevention of cis-Diamminedichloroplatinum-induced nephrotoxicity and leukopenia in rats: potential adjuvant effects.

Cisplatin (CisPt) is an effective chemotherapeutic agent against several human cancers, but it produces important nephrotoxicity, leukopenia, and mortality. In this work, we report initial results on the potential ability of diallyl disulfide (DADS) to block these toxicities without compromising chemotherapy. Male Sprague Dawley rats were used (control, DADS, CisPt, and CisPt/DADS). CisPt was administered sc as a single dose (10.5 mg/kg) in saline. DADS was given daily intragastrically in olive oil (292.5 mg/kg) 1 h before CisPt administration the first day and 146.25 mg/kg during the next 3 days. The animals were sacrificed at the fifth day after CisPt administration. DADS significantly decreased CisPt-induced nephrotoxicity as evaluated by histology and by seric urea (CisPt: 11.05 +/- 3.59; CisPt/DADS: 6.53 +/- 1.74) and creatinine (CisPt: 24.74 +/- 3.03; CisPt/DADS: 14.83 +/- 2.07). DADS also decreased leukopenia (CisPt: 13.5% and CisPt/DADS: 43.4% respect the control), and mortality (CisPt: 50%; CisPt/DADS: 29%). DADS showed ability to interact with reactive oxygen species (H(2)O(2), hydroperoxides, OH*) and with iron. DADS treatment does not change Platinum levels in kidney (CisPt: 15.2 +/- 5.1; CisPt/DADS: 13.9 +/- 4.5). Because DADS is known to inhibit cellular replication and to promote apoptosis of tumor cells, results suggest that DADS merit to be tested as a potential coadjuvant of CisPt chemotherapy in tumor-bearing animals.

Nifurtimox nitroreductase activity in different cellular fractions from male rat pancreas. Biochemical and ultrastructural alterations.

Nifurtimox (Nfx) is a nitroheterocyclic drug used in the treatment of Chagas' disease. It has serious side effects which frequently force to interrupt the treatment. Nfx toxicity has been linked to its nitroreduction to a nitroanion radical with a subsequent redox cycling which generate reactive oxygen species. We analyzed the ability of Sprague Dawley male rat pancreas to nitroreduce Nfx and whether this drug may cause deleterious effects in this organ. The microsomal fraction exhibited Nfx nitroreductase activity in the presence of NADPH under anaerobic atmosphere, which was fully inhibited under air but not altered when N2 was replaced by pure CO. The cytosol nitroreduced Nfx in the presence of hypoxanthine under N2; it was inhibited by allopurinol and negligible in aerobiosis. Nfx reached pancreatic tissue at 1, 3 or 6 h after intragastric administration (100 mg/kg). Six hours after drug administration, a significant increase in t-buthylhydroperoxide promoted chemiluminiscence was detected. Pancreatic protein sulfhydryl content significantly decreased at either 1, 3 or 6 h after Nfx administration. No changes in either protein carbonyl or in lipid hydroperoxides were observable. Ultrastructural alterations were observed in the endoplasmic reticulum and nuclei from acinar cells and in the insulin-containing granules from the pancreas. However, the seric amylase levels were not changed, but the blood glucose levels were slightly but significantly increased 24 h after Nfx administration. These studies might suggest that Nfx treatment could impose an increased risk to patients exposed to other insults provoking oxidative stress or having preexisting pathologies in the pancreas.

Ethanol-induced oxidative stress and acetaldehyde formation in rat mammary tissue: potential factors involved in alcohol drinking promotion of breast cancer.

Recent studies from our laboratory provided evidence that part of the carcinogenic effects of ethanol consumption might be related to its in situ metabolism at cytosolic and microsomal levels, to the mutagen acetaldehyde and to hydroxyl and 1-hydroxyethyl radicals. In this work, we report on our experiments where Sprague-Dawley female rats were exposed to the standard Lieber & De Carli diet for 28 days. We observed: the induction of the (xanthineoxidoreductase mediated) cytosolic and microsomal (lipoxygenase mediated) pathways of ethanol metabolism; promotion of oxidative stress as shown by increased formation of lipid hydroperoxides; delay in the t-butylhydroperoxide induced chemiluminiscence, and a significant decrease in protein sulfhydryls. In addition, the epithelial cells showed ultrastructural alterations consisting of markedly irregular nuclei, with frequent invaginations at the level of the nuclear envelope, condensation of chromatin around the inner nuclear membrane, and marked dilatation of the nuclear pores showing filamentous material exiting to the cytoplasm. In conclusion, the presence in mammary epithelial cells of cytosolic and microsomal pathways of ethanol bioactivation to carcinogenic and to tumorigenic metabolites might play a role in alcohol promotion of breast cancer.

Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet.

In previous studies from our laboratory, the presence in highly purified liver nuclei of metabolic pathways for processing ethanol (EtOH), N-nitrosodimethylamine (NDMA), carbon tetrachloride and chloroform was reported. All these chemicals are known to be metabolized in liver microsomes, via cytochrome P450 2E1 (CYP2E)-mediated processes. In the present work we checked whether rat liver nuclei from rats chronically drinking an alcohol-containing liquid diet exhibited an enhanced ability to metabolize chemicals known to require CYP2E1 participation for given metabolic transformations. The nicotinamide adenosine dinucleotide phosphate (NADPH)-requiring metabolism of p-nitrophenol to p-nitrocathecol; the activation of carbon tetrachloride to trichloromethyl radicals, covalently binding to proteins; and the ring hydroxylation of aniline and o-toluidine were studied. Comparison of the obtained nuclear activities against the one present in the microsomal counterpart, and their respective response to the EtOH inductive effect after repetitive exposure to it, was studied. The obtained results showed that rat liver nuclei exhibited less p-nitrophenol hydroxylase activity than microsomes, but it was inducible by repetitive alcohol drinking to equivalent levels of those of microsomes from control animals. Nuclei exhibited the ability to activate CCl4, which was significantly enhanced by alcohol drinking. Aniline was ring hydroxylated in liver microsomes but not in nuclei from either control or EtOH-treated animals. In contrast, nuclei and microsomes metabolized o-toluidine to ring hydroxylated products. They are considered less toxic in nature but other authors reported a genotoxic effect for one of them. The production of the ring hydroxylated metabolites was enhanced by repetitive EtOH drinking. Results suggest that nuclear metabolism of xenobiotics might be relevant for either activations or detoxications mediated by CYP2E1 and that repetitive exposure to EtOH might significantly modulate those processes.

Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus.

Benznidazole (Bz) is a drug used in the chemotherapy of the acute and intermediate phases of Chagas' disease (American Trypanosomiasis), an endemic parasitic disease afflicting more than 16 million people in Latin America. Serious toxic side effects of Bz have been reported in treated human beings and in experimental animals. Bz toxicity would be linked to its nitroreductive bioactivation to reactive intermediates and to the corresponding amine known to occur in vivo and mediated by different enzymatic systems. In the present study the presence of Bz nitroreductases in rat esophagus and the occurrence of Bz induced esophageal cell injury are described. Already 1 and 3 h after an intragastric Bz administration to Sprague-Dawley male rats (240-260 g body weight) at a dose of 100 mg/kg esophageal levels of the drug were 66.4+/-4.0 and 149.2+/-14.3 nmol per g tissue, respectively. The esophageal mucosa homogenates exhibited Bz nitroreductase activity attributable to the participation of cytochrome P450 reductase and xanthine oxidoreductase (XOR). The ultrastructural observation of esophageal tissue from Bz treated animals 24 h after its administration evidenced: detachment and conglomeration of polyribosomes, reduction in the presence of desmosomes and of the amount of bacteria on its surface. The potential significance of these alterations is not fully clear at present. However, these deleterious effects might be additive or synergistic with those induced by the evolution of the disease.