MAPK11 (p38ß) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study.

Background and purpose: MAPKs are among the most relevant signalling pathways involved in coordinating cell responses to different stimuli. This group includes p38MAPKs, constituted by 4 different proteins with a high sequence homology: MAPK14 (p38α), MAPK11 (p38ß), MAPK12 (p38γ) and MAPK13 (p38δ). Despite their high similarity, each member shows unique expression patterns and even exclusive functions. Thus, analysing protein-specific functions of MAPK members is necessary to unequivocally uncover the roles of this signalling pathway. Here, we investigate the possible role of MAPK11 in the cell response to ionizing radiation (IR). Materials and methods: We developed MAPK11/14 knockdown through shRNA and CRISPR interference gene perturbation approaches and analysed the downstream effects on cell responses to ionizing radiation in A549, HCT-116 and MCF-7 cancer cell lines. Specifically, we assessed IR toxicity by clonogenic assays; DNA damage response activity by immunocytochemistry; apoptosis and cell cycle by flow cytometry (Annexin V and propidium iodide, respectively); DNA repair by comet assay; and senescence induction by both X-Gal staining and gene expression of senescence-associated genes by RT-qPCR. Results: Our findings demonstrate a critical role of MAPK11 in the cellular response to IR by controlling the associated senescent phenotype, and without observable effects on DNA damage response, apoptosis, cell cycle or DNA damage repair. Conclusion: Our results highlight MAPK11 as a novel mediator of the cellular response to ionizing radiation through the control exerted onto IR-associated senescence.

Adequacy of antibiotic prophylaxis and incidence of surgical site infections in neck surgery.

Health care-related infections are frequent and among them surgical site infection (SSI) are the most frequent in hospitals. The objective was to evaluate the adequacy of antibiotic prophylaxis in patients undergoing neck surgery and its relationship with the incidence of surgical site infection (SSI). Prospective cohort study. The adequacy of antibiotic prophylaxis in patients undergoing neck surgery was evaluated. Antibiotic prophylaxis was considered adequate when it conformed to all items of the protocol (antibiotic used, time of administration, administration route, dose and duration). The cumulative incidence of SSI was calculated, and the relationship between SSI and antibiotic prophylaxis adequacy was determined using adjusted relative risk (RR). Antibiotic prophylaxis was administered in 63 patients and was adequate in 85.7% (95% CI 75.0-92.3) of them. The cumulative incidence of SSI was 6.4% (95% CI 3.4-11.8). There was no significant relationship between antibiotic prophylaxis inadequacy and the incidence of SSI (RR = 2.4, 95% CI 0.6-10.6). Adequacy of antibiotic prophylaxis was high and it did not affect the incidence of SSIs.

[Evaluation of compliance with the antibiotic prophylaxis protocol in hysterectomy. Prospective cohort study]. / Evaluación de la adecuación al protocolo de profilaxis antibiótica en histerectomías. Estudio de cohortes prospectivo.

OBJECTIVE: Health care-related infections are a public health problem, among them surgical site infection (SSI) are the most frequent in hospitals. The objetive of this study was to assess the effect of the compliance to antibiotic prophylaxis protocol on the incidence of surgical site infection in hysterectomized patients. METHODS: A prospective cohort study was carried out between October 2009 and December 2018. The incidence of SSI was studied after a maximum period of 30 days from the moment of surgery. The degree of adequacy of antibiotic prophylaxis in hysterectomy and the effect of its inadequacy on the incidence of infection was evaluated using relative risk (RR) adjusted with a logistic regression model. RESULTS: A total of 1,025 interventions were studied in 1,022 women. The cumulative incidence of SSI was 2,1% (n = 22). The most frequent etiology of infection was Escherichia coli (23.1%) and Proteus mirabilis (23.1%). Antibiotic prophylaxis was indicated in 1,014 interventions (98.9%) being administered in 1,009 of them (99.5%). The adherence to the protocol was 92,5%. The main cause of non-compliance was the time of onset (40.9%), followed by the choice of the antibiotic (35.2%). The effect of inadequate prophylaxis on the incidence of infection was RR = 0.9; 95% CI 0.2-3.9; p> 0.05. CONCLUSIONS: The adequacy of antibiotic prophylaxis was very high, with a low incidence of surgical site infection. No association was found between adequacy of prophylaxis and incidence of infection in hysterectomy. The continuous improvement of epidemiological surveillance in gynecology should be emphasized.

Resistance profile and molecular characterization of pyrethroid resistance in a Rhipicephalus microplus strain from Colombia.

Intensive use of chemical acaricides for the control of cattle ticks (Rhipicephalus microplus) has led to the development of multiple acaricide resistance in Colombia. The present study aimed to characterize, using toxicological bioassays and molecular biology techniques, the resistance profile of a tick strain isolated from the Arauca state, Northeast Colombia. Commercial acaricides were used in adult immersion tests to determine its in vitro efficacies. Deltamethrin showed very low activity (4-7.3%), a mixture of cypermethrin and chlorpyrifos had intermediate efficacy (64-75.2%), and ethion presented the highest activity (88.5-100%). A colony (Arauquita strain) was established and larval immersion tests confirmed high resistance level to deltamethrin (241-fold) and susceptibility to ivermectin. A quantitative polymerase chain reaction-high resolution melt technique was used to identify single nucleotide polymorphisms (SNPs) in the para-sodium channel gene. All of the genotyped individuals were mutant, presenting one (n = 7), two (n = 7) or three (n = 9) SNPs previously associated with pyrethroid resistance. Sequencing revealed a novel mutation (F712L), that was found for the first time in R. microplus ticks from South America. This is the first description of mutations associated with pyrethroid resistance in R. microplus from Colombia. The acaricide resistance pattern found in the Arauquita strain is similar to other parts of Colombia.

Epidemiological survey and risk factor analysis on Eimeria infections in calves and young cattle up to 1 year old in Colombia.

A large-scale cross-sectional epidemiological study was conducted to evaluate prevalence, species diversity, and associated risk factors of Eimeria infections in 55 cattle farms across seven states of Colombia, including subtropical and tropical regions. In total, 1333 fecal samples from young animals (< 1 year of age) were examined at a single sampling date from August 2016 to December 2016. Flotation and McMaster techniques were conducted for parasitological investigation. Excreted Eimeria oocysts were allowed to sporulate in vitro and thereafter identified to species level based on morphological and morphometric characteristics. The overall Eimeria prevalence was 75.5% (1006/1333), with no difference observed between age categories. In total, 13 different Eimeria species were identified. The most prevalent species was E. bovis (33.5%), followed by E. auburnensis (12.5%) and E. zuernii (11.9%). Analysis of extrinsic associated risk factors revealed the floor type, feeding system, watering system, and herd size as significant (p < 0.05) risk factors for Eimeria spp. infections. Based on these data, it can be assumed that bovine coccidiosis infections occur ubiquitously in the country and might play an important role especially in its subclinical form by affecting production parameters in conventional cattle management systems.

Molecular detection of Marek's disease virus in feather and blood samples from young laying hens in Colombia.

Marek's disease virus (MDV) is an immunosuppressive pathogen that can cause low production efficiency and high mortality rates in chickens. There is no current information on the MDV serotypes and pathotypes circulating in vaccinated commercial farms in Colombia where the birds are vaccinated in the incubator with Gallid herpesvirus (GaHV-2) and Meleagrid herpesvirus 1 (MeHV-1). Based on that, the main focus of this study was to understand the MDV's infection dynamics for the three known serotypes and to detect wild-virus pathogenic strains in 4-layer poultry farms in Antioquia. Samples of blood, feathers and spleens were collected from three randomly chosen animals according to age category: 1, 15, 30, 60, 90, and 120 days. Quantitative real-time PCR (qPCR) that differentiates between the three serotypes of MDV was used to assess viral loads over time, and phylogenetic analysis of the Meq oncogene was done to compare the strains of MDV with those of known pathogenicity. Meleagrid herpesvirus 1 (MeHV-1) was detected in all blood and feather follicle samples with an average number of genome copies (per 10,000 cells) of 31.44 in blood as expected as a result of vaccination. GaHV-2 was also detected in almost 100% of the blood and feather follicle samples throughout all defined age categories, with an average of 10.65 genome copies in blood samples. Gallid herpesvirus 3 (GaHV-3) was detected in 72% of blood and 84.61% of feather samples, with less than 1 copy per 10,000 cells. Based on the number of 132 bp repeats of the BamHI-H and BamHI-D regions in pooled feather samples, there were 70% (8/25) of attenuated MDV and 30% (17/25) of virulent MDV strains circulating in the farms. Virus isolation was performed successfully from every farm. In conclusion, different strains of MDV are circulating for up to 120 days in layers in Antioquia-Colombia and could be of major impact in poultry health. Keywords: Marek's disease virus (MDV); Antioquia-Colombia; qPCR; PCR; Meq gene phylogeny.

[Evaluation of compliance with the antibiotic prophylaxis protocol in breast surgery and its effect on the incidence of surgical infection]. / Evaluación de la adecuación al protocolo de profilaxis antibiótica en cirugía de mama y su efecto sobre la incidencia de infección quirúrgica.

BACKGROUND: Antibiotic prophylaxis is one of the most effective ways to avoid surgical site infection (SSI). The present study evaluates compliance with the antibiotic prophylaxis protocol and the effect of non-compliance on the incidence of SSI in breast surgery. METHODS: A prospective cohort study was carried out from July 2008 to July 2018. It assessed the degree of compliance with antibiotic prophylaxis in breast surgery and the causes of non-compliance: choice of antibiotic, route of administration, time of onset, dose and duration. The incidence of SSI was studied during the 30 days after intervention (90 in the case of implants or prostheses). Relative risk (RR) was used to assess the effect of inadequate prophylaxis. RESULTS: We studied 1,328 interventions in 1,212 women. The cumulative incidence of SSI was 1.7% (n=22) and the most common etiology was Staphylococcus aureus (47.1%). Overall antibiotic prophylaxis protocol compliance was 95.3%, (including the 568 interventions where it was not indicated). The principle causes of non-compliance were the time of onset (46.8%) and choice of antibiotic (40.3%). Non-compliance significantly increased both incidence of SSI (8.1 vs 1.3%, p=0,003) and its risk (RR=6.5, CI95% 2.3-18.1). CONCLUSIONS: The overall protocol compliance rate was very high. Non-compliance with prophylaxis protocol at least doubled the risk of SSI in breast surgery.

[Hand hygiene compliance with hydroalcoholic solutions in medical students. Cross-sectional study]. / Adherencia a la higiene de manos con soluciones hidroalcohólicas en estudiantes de medicina. Estudio descriptivo transversal.

OBJECTIVE: To assess hand hygiene compliance covertly in medical students in a university teaching hospital. METHODS: Cross-sectional study. Hand hygiene compliance in medical students was assessed in the units of Neonatology, Paediatrics, Neurology and Orthopaedic surgery. The five moments were covertly observed so as the hand rub technique. Hand hygiene compliance was described with the compliance percentages of the five moments. RESULTS: We studied 456 opportunities of hand hygiene. Global compliance was 44.3%. The most registered unit was Orthopaedic surgery (59.6%). According to the different moments, global compliance was better "after touching a patient" (60.2%). The unit with the highest hand hygiene compliance was Neonatology (60%). Hand hygiene compliance was better in the different hospitalisation units (50%) than in the office rooms (33%) (P<0.05) and the mean duration of hand hygiene was 22 seconds. CONCLUSIONS: Most of the moments were registered in the unit of Orthopaedic surgery and the moment with the highest hand hygiene compliance was "after touching a patient". The most hand hygiene compliance percentage was observed in Neonatology. Hand hygiene compliance was moderate, and it could and must be improved.

Characterization of hadron production in γ−A photonuclear interactions of ultra-peripheral collisions / Caracterización de la producción de hadrones en interacciones fotonucleares γ−A de colisiones ultraperiféricas

Abstract A methodology for the simulation of ultra-peripheral collisions, specifically ultra-relativistic heavy ion 197Au-197Au and p-208Pb collisions, is developed. First, the fluxes of virtual photons as a function of the photon energy and the impact parameter are obtained using the Method of Weizsäcker-Williams. Then, the processes induced by photons in photon-hadron collisions γ+Au, γ+p and γ+Pb are simulated, neglecting the photon-photon contribution. The model is implemented in the code CRISP (Collaboration Rio-Sao Paulo), specifically designed for simulations of the nuclear environment. Cross-section, differential cross-section, multiplicity, invariant mass spectrum, angular distribution and p T distribution in 197Au-197Au and p-208Pb collisions are obtained, and a comparison with experimental data is accomplished in order to validate the model.

Resumen Una metodología para la simulación de colisiones ultraperiféricas, específicamente colisiones ultrarelativistas de iones pesados 197Au-197Au y p-208Pb es desarrollada. Primero, los flujos de fotones virtuales como función de la energía del fotón y el parámetro de impacto son obtenidos, usando el Método de Weizsäcker-Williams. Luego, los procesos inducidos por fotones en colisiones fotón-hadrón γ+Au, γ+p y γ+Pb son simulados, despreciando la contribución fotón-fotón. El modelo es implementado en el código CRISP (Colaboración Rio-Sao Paulo), específicamente diseñado para simulaciones del ambiente nuclear. La sección eficaz, sección eficaz diferencial, multiplicidad, espectro de masa invariante y distribución de p T son obtenidas, y se realiza una comparación con resultados experimentales, con el objetivo de validar el modelo.

Abundance of Harpy and Crested Eagles from a reservoir-impact area in the Low- and Mid-Xingu River.

In the Brazilian Amazon, two monospecific genera, the Harpy Eagle and Crested Eagle have low densities and are classified by IUCN as Near Threatened due to habitat loss, deforestation, habitat degradation and hunting. In this study, we evaluate occurrence of these large raptors using the environmental surveys database from Belo Monte Hydroelectric Power Plant. Integrating the dataset from two methods, we plotted a distribution map along the Xingu River, including records over a 276-km stretch of river. Terrestrial surveys (RAPELD method) were more efficient for detecting large raptors than standardized aquatic surveys, although the latter were complementary in areas without modules. About 53% of the records were obtained during activities of wildlife rescue/flushing, vegetation suppression or in transit. Between 2012 and 2014, four Harpy Eagles were removed from the wild; two shooting victims, one injured by collision with power lines and one hit by a vehicle. Also, seven nests were mapped. The mean distance between Harpy Eagle records was 15 km along the river channel, with a mean of 20 km between nests near the channel, which allowed us to estimate 20 possible pairs using the alluvial forest, riverine forest and forest fragments. Territories of another ten pairs will probably be affected by inundation of the Volta Grande channel, which is far from the main river. The average distance between Crested Eagle records was 16 km along the river channel. The only nest found was 1.3 km away from a Harpy Eagle nest. The remnant forests are under threat of being replaced by cattle pastures, so we recommend that permanently protected riparian vegetation borders (APP) be guaranteed, and that forest fragments within 5 km of the river be conserved to maintain eagle populations.

Abundance of Harpy and Crested Eagles from a reservoir-impact area in the Low- and Mid-Xingu River / Abundância de Gavião-real e Gavião-real falso numa área sob impacto de reservatório no Baixo e Médio rio Xingu

In the Brazilian Amazon, two monospecific genera, the Harpy Eagle and Crested Eagle have low densities and are classified by IUCN as Near Threatened due to habitat loss, deforestation, habitat degradation and hunting. In this study, we evaluate occurrence of these large raptors using the environmental surveys database from Belo Monte Hydroelectric Power Plant. Integrating the dataset from two methods, we plotted a distribution map along the Xingu River, including records over a 276-km stretch of river. Terrestrial surveys (RAPELD method) were more efficient for detecting large raptors than standardized aquatic surveys, although the latter were complementary in areas without modules. About 53% of the records were obtained during activities of wildlife rescue/flushing, vegetation suppression or in transit. Between 2012 and 2014, four Harpy Eagles were removed from the wild; two shooting victims, one injured by collision with power lines and one hit by a vehicle. Also, seven nests were mapped. The mean distance between Harpy Eagle records was 15 km along the river channel, with a mean of 20 km between nests near the channel, which allowed us to estimate 20 possible pairs using the alluvial forest, riverine forest and forest fragments. Territories of another ten pairs will probably be affected by inundation of the Volta Grande channel, which is far from the main river. The average distance between Crested Eagle records was 16 km along the river channel. The only nest found was 1.3 km away from a Harpy Eagle nest. The remnant forests are under threat of being replaced by cattle pastures, so we recommend that permanently protected riparian vegetation borders (APP) be guaranteed, and that forest fragments within 5 km of the river be conserved to maintain eagle populations.

Na Amazônia brasileira dois gêneros mono-específicos, Harpia e Morphnus, caracterizam-se por baixa densidade e estão classificados pelo IUCN como Quase Ameaçados, porém ocorrem sobre grande parte do território nacional, suas principais ameaças são a fragmentação florestal, a degradação de hábitat e a caça. Neste estudo avaliamos a abundância destas duas grandes aves de rapina utilizando a base de dados dos programas ambientais da UHE Belo Monte, integrando-se dois métodos para construir um mapa de distribuição ao longo de 245 km do rio Xingu. Os levantamentos terrestres pelo método RAPELD mostraram-se mais eficientes para os registros de grandes águias quando comparado aos esforços padronizados aquáticos, entretanto estes foram complementares na ausência de módulos. Cinquenta e tres por cento foram registros ocasionais durante a supressão da vegetação, afugentamento ou deslocamento. Entre 2012-2014 quatro harpias foram removidas da natureza, dois indivíduos alvo de disparos, uma por colisão com rede elétrica, e outra por atropelamento. Sete ninhos mapeados, a distância média entre os registros de harpia na calha e margens do rio foi de 15 km, 20 km distância média entre ninhos, o que permitiu estimar um total de 20 casais utilizando as florestas aluviais em uma distancia de 270 km, incluindo matas ciliares e os fragmentos fora da margem do rio. Estimamos que territórios de outros 10 casais usando a Volta Grande longe do rio principal também serão afetados pela inundação. A distância média entre os registros de Morphnus foi 16 km ao longo do rio, o único ninho mapeado estava distante 1.3 km do ninho de Harpia. Estes fragmentos florestais estão sendo substituídos por pastagens, ressaltando-se a importância da manutenção das áreas de preservação permanentes (APP) e a proteção destes fragmentos em diversos formatos de áreas de proteção, para diminuir a degradação dos mesmos e garantir a manutenção das populações destes grandes predadores na região do rio Xingu.

Interaction between PARP-1 and HIF-2α in the hypoxic response.

Hypoxia-inducible factors (HIFs) mediate the transcriptional adaptation of hypoxic cells. The extensive transcriptional programm regulated by HIFs involves the induction of genes controlling angiogenesis, cellular metabolism, cell growth, metastasis, apoptosis, extracellular matrix remodeling and others. HIF is a heterodimer of HIF-α and HIF-ß subunits. In addition to HIF-1α, HIF-2α has evolved as an isoform that contributes differently to the hypoxic adaptation by performing non-redundant functions. Poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein involved in the control of DNA repair and gene transcription by modulating chromatin structure and acting as part of gene-specific enhancer/promoter-binding complexes. Previous results have shown that PARP-1 regulates HIF-1 activity. In this study, we focused on the cross-talk between HIF-2α and PARP-1. By using different approaches to suppress PARP-1, we show that HIF-2α mRNA expression, protein levels and HIF-2-dependent gene expression, such as ANGPTL4 and erythropoietin (EPO), are regulated by PARP-1. This regulation occurs at both the transcriptional and post-trancriptional level. We also show a complex formation between HIF-2α with PARP-1. This complex is sensitive to PARP inhibition and seems to protect against the von Hippel-Lindau-dependent HIF-2α degradation. Finally, we show that parp-1(-/-) mice display a significant reduction in the circulating hypoxia-induced EPO levels, number of red cells and hemoglobin concentration. Altogether, these results reveal a complex functional interaction between PARP-1 and the HIF system and suggest that PARP-1 is involved in the fine tuning of the HIF-mediated hypoxic response in vivo.

Early maximum extent of paleoglaciers from Mediterranean mountains during the last glaciation.

Mountain glaciers respond directly to changes in precipitation and temperature, thus their margin extent is a high-sensitivity climate proxy. Here, we present a robust (10)Be chronology for the glacier maximum areal extent of central Spain paleoglaciers dated at 26.1 ± 1.3 ka BP. These glaciers reached their maximum extent several thousand years earlier than those from central Europe due to the increased precipitation within a cold period between 25 to 29 ka BP, as confirmed by a local speleothem record. These paleoclimate conditions impacted the maximum extent of mountain glaciers along the western and central Mediterranean region. The cause and timing of the enhanced precipitation implies a southward shift of the North Atlantic Polar Front followed by storm tracks in response to changes in insolation via orbital parameters modulation. Thus, these mountain paleoglaciers from the Mediterranean region record an ocean-continent climate interaction triggered by external forcing.

[Prognostic factors in hypertrophic pyloric stenosis]. / Factores pronósticos en la estenosis hipertrófica de píloro.

INTRODUCTION: Although the surgical treatment of hypertrophic pyloric stenosis is well established, its management and main complication after surgery, postoperative vomits, are subject to constant revisions. In this study, we sought a prognostic factor that indicates the occurrence of this complication. METHODS: We analyzed different parameters listed in the medical histories of 169 patients treated at a tertiary hospital between 2000 and 2009, both inclusive, ruling out those who suffered some type of complication (n = 17) and those who followed a different pattern of reintroduction of feeding (n = 43). RESULTS: The decrease in the time interval between surgery and the first shot does not influence the outcome of patients. However, we found a negative correlation between the chlorine level in blood measured by the number of postoperative vomits. The time required to reach a correct tolerance, influenced by the degree of metabolic disorder, does influence both the number of vomits and the time required to achieve a proper tolerance. Other parameters analyzed, such as surgical time and ultrasound measurements of the pyloric olive, do not seem to influence the postoperative course of patients. CONCLUSION: Just the degree of metabolic disturbance and blood levels of chlorine seem to influence postoperative outcome, detected by the time required to reach a correct tolerance and the number of postoperative vomits.

[Esophageal obstruction caused by dietary fiber from Plantago ovata, a complication preventable by adequate information]. / Obstrucción esofágica por la fibra dietética Plantago ovata, una complicación prevenible mediante la información.

INTRODUCTION: Plantago ovata (PO) is widely used as a dietary fiber in the treatment of constipation. A case of esophageal obstruction due to PO is presented. Other published cases are reviewed, and possible risk factors and prevention are discussed. CASE REPORT: A 41-year-old woman felt chest pain and regurgitation immediately after swallowing a tablespoonful of PO in granules. She kept the granules in her mouth for a few seconds before swallowing them with 250 ml of water. Flexible endoscopy revealed a brown-black consistent mass blocking the inferior esophagus. A mild hiatus hernia was subsequently discovered. DISCUSSION: All the cases found through an unlimited Medline search using key words Plantago, Psyllium, mucilage, bezoars and esophagus, were taking PO in granules. Most of the cases took the granules with insufficient liquid, and some had previous obstructive esophageal disease. PO in powder probably presents a lower risk of esophageal obstruction.

Porcine circovirus type 2 (PCV-2) coinfections in US field cases of postweaning multisystemic wasting syndrome (PMWS).

The prevalence of different pathogens detected in combination with porcine circovirus type 2 (PCV-2) was studied retrospectively in field cases of postweaning multisystemic wasting syndrome (PMWS) diagnosed at the Iowa State University Veterinary Diagnostic Laboratory, Ames, Iowa, between January 2000, and September 2001. The presence of PCV-2 antigen in lymphoid tissues and/or lung, demonstrated by immunohistochemistry, together with moderate to severe lymphoid depletion and/or granulomatous lymphadenitis, was used as the criteria for the diagnosis of PMWS. A total of 484 cases fulfilled these criteria. Most of the cases (294/369) of PMWS occurred in pigs between the ages of 8 and 18 weeks, with a peak at 10 weeks of age. Porcine reproductive and respiratory syndrome virus was detected in 51.9% of the cases, Mycoplasma hyopneumoniae in 35.5%, bacterial septicemia in 14.0%, bacterial pneumonia in 7.6%, swine influenza virus in 5.4%, and PCV-2 alone in 1.9%. In cases with bacterial septicemia the most frequently isolated pathogen was Streptococcus suis. In cases with bacterial pneumonia, Pasteurella multocida was the most prevalent.

Type II and type III monodeiodinase activities in the skin of untreated and propylthiouracil-treated cashmere goats.

The presence or absence of types I, II and III iodothyronine monodeiodinase enzymes (MDI, MDII and MDIII) and their levels of activity in the skin of goats, which were orally dosed for 60 days with 0, 1.1, 2.2, 4.4, 8.8, 17.5, or 35 mg(-1)kg liveweight day(-1)of the anti-thyroid, enzyme-inhibiting drug, propylthiouracil (PTU), were determined. Contrary to our earlier report that PTU did not influence skin MDII activity, the currect more thorough investigation (in terms of numbers of observations and the efficiency of the enzyme extraction procedure) indicated that doses of 1.1.to 17.5 mg kg(-1)liveweight induced a 2 to 3 fold increase (P = 0.01) in MDII activity. However, in three of the four goats treated with 35 mg kg(-1)group, activity was similar to that of control animals. There were no significant differences between treatments in MDIII activity but there was a trend towards lower levels of activity in the goats dosed with 17.5 and 35 mg kg(-1). It is concluded that there is significant MDII and MDIII activity in the skin of goats and that although there is none of the PTU -sensitive MDI enzyme, synthesis of T3 within the skin could nevertheless be modified through increases in MDII activity induced by lower T4 concentrations in the circulation caused by PTU. Changes in pattern of fibre moult induced by treatment with low doses of MD-inhibiting drugs may therefore be achieved through this effect. Since MDII and MDIII enzyme activity may be reduced by high doses of PTU, prolonged treatment with high doses of PTU may have adverse effects on skin tissue.

Novobiocin inhibits both UDP-glucuronosyltransferase and cytochrome P450-mediated enzyme activities in pig liver microsomes.

The effects of novobiocin (range 0.0125-2 mmol/L) on the hydroxylation of testosterone, the N-demethylation of erythromycin, and the glucuronidation of alpha-naphthol and paracetamol were studied using pig hepatic microsomes, pooled from five animals. The final concentrations of these substrates in the incubation mixtures were selected to meet Vmax conditions. Novobiocin caused a concentration-dependent inhibition of the glucuronidation of paracetamol; the formation of alpha-naphthol-glucuronide was reduced to a lesser degree. These results confirm and extend earlier findings in laboratory animal species that novobiocin inhibits UDP-glucuronosyltransferases (UDPGTs). Moreover, novobiocin strongly inhibited 6 beta-hydroxylation of testosterone. The microsomal N-demethylation of erythromycin and hydroxylation of testosterone at the 15 alpha position were less affected by novobiocin. These results suggest that novobiocin inhibits not only UDPGTs, but also cytochrome P450 (CYP) enzyme activities, probably those belonging to the CYP3A subfamily. More research is needed to reveal which CYPs and UDPGTs are affected by novobiocin in vivo, in order to improve the understanding the probably the predictability of potential drug interactions with this antibiotic.

Ibuprofen, aspirin and acetaminophen toxicosis and treatment in dogs and cats.

Toxicosis to 3 commonly available analgesics--ibuprofen, aspirin and acetaminophen--occurs in dogs and cats after acute ingestion or repetitive administration of therapeutic or excessive doses. Whereas in acute exposure, where the clinical course of an overdose to all 3 drugs is predictable in relation to the amount ingested, in chronic exposure to therapeutic doses of aspirin and ibuprofen, the development of gastric ulcers and analgesic nephropathy is unpredictable. Ibuprofen is not recommended for prolonged treatment in dogs and cats due to the likelihood of ulcer formation. Although gastric mucosal adaptation usually occurs with repeated therapeutic doses of aspirin, some individuals nevertheless develop gastric ulcers; simultaneous administration of the prostaglandin analogue misoprostol can reduce the risk. Following acute ingestion of aspirin or ibuprofen, treatment is essentially symptomatic and supportive following early decontamination procedures. Gastrointestinal protectants and i.v. fluids with sodium bicarbonate are generally recommended. Acetaminophen toxicosis is usually associated with single acute ingestion, and the primary target organs affected are the liver and the red blood cells in dogs and cats respectively. Because signs can progress rapidly with acute acetaminophen overdose, administration of N-acetylcysteine is always recommended, even when the history is unclear. This report summarizes the common clinical presentations of dogs and cats exposed to therapeutic or excessive doses of ibuprofen, aspirin or acetaminophen, and describes the treatment procedures advised by the ASPCA-National Animal Poison Control Center.