RESUMO
OBJECTIVES: The Fueguians are descendants of the first settlers of America, a 'relict' isolated geographically for 10,000 years. We compared their cranial variation with other Americans, and samples from Asia and Australia to know whether the modern extinct Fueguians can be considered Paleoamericans or not. MATERIALS AND METHODS: Herein we study 176 Fuego-Patagonian skulls, the largest cranial sample to be studied, refined and well documented, using CVA, and the D2 of Mahalanobis. The affinities between populations and sexual dimorphism were jointly studied. RESULTS: Terrestrial hunters (Selknam) have a different cranial morphology from sea canoeists (Yamana, Alakaluf) particularly with regard to cranial size and robustness. In the American context, there are extreme differences between the canoeists of Santa Cruz (California) and the Eskimos and canoeists of Fuego-Patagonia in terms of cranial size, prognathism and development of the frontal region. Fueguian canoeists are cranially closer to the Californian ones than to their Fueguian neighbors, the Selknam. Our results favor the hypothesis of two different flows for the origin of the first populators of Tierra del Fuego. DISCUSSION: We concluded that the robusticity of some Fuegians (Selknam) might be the result of an allometric pattern of overall robusticity expression well as a result of epigenetics or differential reproduction (Larsen, 2015:264) or hypothetical endocrine changes (Bernal et al. in Am J Hum Biol 2006;18:748-765). When compared with three Australian-Melanesian series, the group comprising Amerindians, Ainu, and Eskimos clusters together as they are all extremely different from the former in terms of both cranial size and shape.
Assuntos
Etnicidade/estatística & dados numéricos , Indígenas Sul-Americanos/estatística & dados numéricos , Crânio/anatomia & histologia , Adulto , Antropologia Física , Cefalometria , Chile , Feminino , Humanos , Masculino , Caracteres Sexuais , Crânio/patologia , População BrancaRESUMO
The Peruvian Andes presents a climate suitable for many species of sandfly that are known vectors of leishmaniasis or bartonellosis, including Lutzomyia peruensis (Diptera: Psychodidae), among others. In the present study, occurrences data for Lu. peruensis were compiled from several items in the scientific literature from Peru published between 1927 and 2015. Based on these data, ecological niche models were constructed to predict spatial distributions using three algorithms [Support vector machine (SVM), the Genetic Algorithm for Rule-set Prediction (GARP) and Maximum Entropy (MaxEnt)]. In addition, the environmental requirements of Lu. peruensis and three niche characteristics were modelled in the context of future climate change scenarios: (a) potential changes in niche breadth; (b) shifts in the direction and magnitude of niche centroids, and (c) shifts in elevation range. The model identified areas that included environments suitable for Lu. peruensis in most regions of Peru (45.77%) and an average altitude of 3289 m a.s.l. Under climate change scenarios, a decrease in the distribution areas of Lu. peruensis was observed for all representative concentration pathways. However, the centroid of the species' ecological niche showed a northwest direction in all climate change scenarios. The information generated in this study may help health authorities responsible for the supervision of strategies to control leishmaniasis to coordinate, plan and implement appropriate strategies for each area of risk, taking into account the geographic distribution and potential dispersal of Lu. peruensis.
Assuntos
Mudança Climática , Ecossistema , Insetos Vetores/fisiologia , Leishmaniose/transmissão , Psychodidae/fisiologia , Distribuição Animal , Animais , Leishmania/fisiologia , Leishmaniose/parasitologia , Modelos Biológicos , PeruRESUMO
It is generally accepted that chromosomal inversions have been key elements in adaptation and speciation processes. In this context, Drosophila subobscura has been, and still is, an excellent model species due to its rich chromosomal polymorphism. In this species, many analyses from natural populations have demonstrated the adaptive potential of individual inversions (and their overlapped combinations, the so-called arrangements). However, little information is available on the evolutionary role of combinations generated by inversions located in homologous and nonhomologous chromosomes. The aim of this research was to ascertain whether these combinations are also a target for natural selection. For this objective, we have studied the inversion composition of homologous and nonhomologous chromosomes from a D. subobscura sample collected in a well-studied population, Mount Avala (Serbia). No significant deviation from H-W expectations was detected, and when comparing particular karyotypic combinations, likelihood ratios close to 1 were obtained. Thus, it seems that for each pair of homologous chromosomes inversions no deviation from randomness was detected. Finally, no linkage disequilibrium was observed between inversions located in different chromosomes of the karyotype. For all these reasons, it can be assumed that, at the cytological level, the individual inversions rather than their combinations in different chromosomes are the main target of selection.
Assuntos
Inversão Cromossômica , Drosophila/genética , Genética Populacional , Seleção Genética , Animais , Cromossomos de Insetos , Polimorfismo Genético , SérviaRESUMO
Autism is a severe neurodevelopmental disorder, the aetiology of which remains mainly unknown. Family and twin studies provide strong evidence that genetic factors have a major role in the aetiology of this disease. Recently, whole exome sequencing (WES) efforts have focused mainly on rare de novo variants in singleton families. Although these studies have provided pioneering insights, de novo variants probably explain only a small proportion of the autism risk variance. In this study, we performed exome sequencing of 10 autism multiplex families with the aim of investigating the role of rare variants that are coinherited in the affected sibs. The pool of variants selected in our study is enriched with genes involved in neuronal functions or previously reported in psychiatric disorders, as shown by Gene Ontology analysis and by browsing the Neurocarta database. Our data suggest that rare truncating heterozygous variants have a predominant role in the aetiology of autism. Using a multiple linear regression model, we found that the burden of truncating mutations correlates with a lower non-verbal intelligence quotient (NVIQ). Also, the number of truncating mutations that were transmitted to the affected sibs was significantly higher (twofold) than those not transmitted. Protein-protein interaction analysis performed with our list of mutated genes revealed that the postsynaptic YWHAZ is the most interconnected node of the network. Among the genes found disrupted in our study, there is evidence suggesting that YWHAZ and also the X-linked DRP2 may be considered as novel autism candidate genes.
Assuntos
Proteínas 14-3-3/genética , Transtorno Autístico/genética , Exoma/genética , Predisposição Genética para Doença/genética , Heterozigoto , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação/genética , Proteínas do Tecido Nervoso/genética , Criança , Pré-Escolar , Bases de Dados Genéticas , Feminino , Humanos , Inteligência/genética , Masculino , Mapas de Interação de Proteínas/genética , Adulto JovemRESUMO
To study whether inversions (or arrangements) by themselves or karyotypes are the main global warming adaptive target of natural selection, two Drosophila subobscura Serbian populations (Apatin and Petnica) were re-analyzed using different statistical approaches. Both populations were sampled in an approximately 15 years period: Apatin in 1994 and 2008 + 2009 and Petnica in 1995 and 2010. For all chromosomes, the four collections studied were in Hardy-Weinberg equilibrium. Thus, it seems that inversions (or arrangements) combined at random to constitute populations' karyotypes. However, there were differences in karyotypic frequencies along the years, although they were significant only for Apatin population. It is possible to conclude that inversions (or arrangements) are likely the target of natural selection, because they presented long-term changes, but combine at random to generate the corresponding karyotypic combinations. As a consequence, the frequencies of karyotypes also change along time.
Assuntos
Inversão Cromossômica , Drosophila/genética , Polimorfismo Genético , Animais , Cromossomos de Insetos/genética , Ligação Genética , Cariótipo , Seleção GenéticaRESUMO
Systemic antimicrobial treatments are commonly prescribed to dogs with acute diarrhoea, while nutraceuticals (prebiotics, probiotics, and synbiotics) are frequently administered as an alternative treatment. The aim of this systematic review and meta-analysis was to assess the effectiveness of antimicrobials and nutraceutical preparations for treatment of canine acute diarrhoea (CAD). The results of this study will be used to create evidence-based treatment guidelines. PICOs (population, intervention, comparator, and outcome) were generated by a multidisciplinary expert panel taking into account opinions from stakeholders (general practitioners and dog owners). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty of the evidence. The systematic search yielded six randomised controlled trials (RCT) for antimicrobial treatment and six RCTs for nutraceutical treatment meeting the eligibility criteria. Categories of disease severity (mild, moderate, and severe) were created based on the presence of systemic signs and response to fluid therapy. Outcomes included duration of diarrhoea, duration of hospitalization, progression of disease, mortality, and adverse effects. High certainty evidence showed that antimicrobial treatment did not have a clinically relevant effect on any outcome in dogs with mild or moderate disease. Certainty of evidence was low for dogs with severe disease. Nutraceutical products did not show a clinically significant effect in shortening the duration of diarrhoea (based on very low to moderate certainty evidence). No adverse effects were reported in any of the studies.
Assuntos
Anti-Infecciosos , Probióticos , Cães , Animais , Diarreia/tratamento farmacológico , Diarreia/veterinária , Hidratação/veterináriaRESUMO
Acute diarrhoea is a common presentation in dogs, and a common reason for antimicrobial prescription and nutraceutical use. This evidence-based guideline provides recommendations for antimicrobial and probiotic treatment of canine acute diarrhoea (CAD). A multidisciplinary panel developed the recommendations by adhering to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The opinions of stakeholders (general veterinary practitioners and dog owners) were collected and incorporated to ensure the applicability of this guideline. Four strong recommendations informed by high certainty evidence, and three conditional recommendations informed by very low or low certainty evidence, were drafted by the panel, along with an ungraded section on diagnostic work-up of dogs with acute diarrhoea. The ENOVAT guidelines initiative encourages national or regional guideline makers to use the evidence presented in this document, and the supporting systematic review, to draft national or local guidance documents.
RESUMO
Lethal chromosomal frequencies were obtained from three Drosophila subobscura samples from the Mt. Avala (Serbia) population in September 2003 (0.218), June 2004 (0.204) and September 2004 (0.250). These values and those from other Balkan populations studied previously (Petnica, Kamariste, Zanjic and Djerdap) were used to analyze the possible effect of population, year, month and altitude above sea level on lethal chromosomal frequencies. According to ANOVAS no effect were observed. Furthermore, the lethal frequencies of the Balkan populations did not vary according to latitude. This is probably due to the relative proximity and high gene flow between these populations. From a joint study of all the Palearctic D. subobscura populations so far analyzed, it can be deduced that the Balkan populations are located in the central area of the species distribution. Finally, it seems that lethal chromosomal frequencies are a consequence of the genetic structure of the populations.
Assuntos
Cromossomos de Insetos/genética , Drosophila/genética , Genes Letais/genética , Animais , Inversão Cromossômica/genética , Frequência do Gene/genética , Montenegro , Polimorfismo Genético , SérviaRESUMO
The Base Excision Repair (BER) pathway is a highly conserved DNA repair system targeting chemical base modifications that arise from oxidation, deamination and alkylation reactions. BER features lesion-specific DNA glycosylases (DGs) which recognize and excise modified or inappropriate DNA bases to produce apurinic/apyrimidinic (AP) sites and coordinate AP-site hand-off to subsequent BER pathway enzymes. The DG superfamilies identified have evolved independently to cope with a wide variety of nucleobase chemical modifications. Most DG superfamilies recognize a distinct set of structurally related lesions. In contrast, the Helix-hairpin-Helix (HhH) DG superfamily has the remarkable ability to act upon structurally diverse sets of base modifications. The versatility in substrate recognition of the HhH-DG superfamily has been shaped by motif and domain acquisitions during evolution. In this paper, we review the structural features and catalytic mechanisms of the HhH-DG superfamily and draw a hypothetical reconstruction of the evolutionary path where these DGs developed diverse and unique enzymatic features.
Assuntos
DNA Glicosilases , DNA/metabolismo , Dano ao DNA , DNA Glicosilases/metabolismo , Reparo do DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismoRESUMO
Organ transplantation represents one of the medical fields with the largest impact and advances. Liver transplantation constitutes a constant challenge in finding viable options to maintain or recover an adequate function when faced with end-stage liver failure. Critical review of the literature was conducted in specific topics on liver transplantation and development in Mexico. We focused our review on medical and surgical topics such as liver procurement from a related living donor, liver transplantation options for patients with liver cancer, especially hepatocellular carcinoma and cholangiocarcinoma, as well as on cellular and molecular biology aspects, such as xenotransplantation and hepatocyte transplantation.
Assuntos
Transplante de Células , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Humanos , Doadores VivosRESUMO
Paval, a solid waste stream from the aluminum industry, is used as a pore generation agent in geopolymers. Paval was mixed with coal combustion fly ash, as a geopolymeric precursor, and activated with alkaline solution with the aim of obtaining porous geopolymers to be used as noise barriers. Both geopolymeric and pore generation reactions happen simultaneously. Aluminum from Paval can react with water and OH¯ from the geopolymerization activating solution, producing hydrogen. The hydrogen gas released generates a highly porous material. The influence of the fly ash-paval proportion and the setting temperature on open porosity, compressive strength and noise-absorbing properties were evaluated. To better understand these influences, the setting time, volume expansion and mineral composition were also studied. The obtained results showed that a higher Paval content (fly ash-Paval ratio 50:50) and setting temperature (70⯰C) produced a lower setting time and higher volume expansion, increasing the open porosity and improving acoustic properties, but reducing the compressive strength. The material manufactured under these conditions showed similar amorphous phase content to the non-porous geopolymers made without Paval. On the other hand, the obtained materials did not raise environmental concerns in a normalised leaching test.
Assuntos
Alumínio , Polímeros , Carvão Mineral , Cinza de Carvão , PorosidadeRESUMO
Microarray technology is increasingly being applied in biological and medical research to address a wide range of problems. Cluster analysis has proven to be a very useful tool for investigating the structure of microarray data. This paper presents a program for clustering microarray data, which is based on the so call path-distance. The algorithm gives in each step a partition in two clusters and no prior assumptions on the structure of clusters are required. It assigns each object (gene or sample) to only one cluster and gives the global optimum for the function that quantifies the adequacy of a given partition of the sample into k clusters. The program was tested on experimental data sets, showing the robustness of the algorithm.
Assuntos
Algoritmos , Caenorhabditis elegans/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Software , Animais , Caenorhabditis elegans/genéticaRESUMO
Forty-six dogs with pituitary-dependent hyperadrenocorticism were treated with mitotane by the non-selective adrenocorticolysis protocol and 40 were treated twice a day with trilostane. The treatment groups were compared by chi-squared tests, and survival data were analysed using Kaplan-Meier survival plots and a Cox proportional hazard method. The non-selective adrenocorticolysis protocol was very effective (89 per cent), its toxicity was moderate (24 per cent) and there were fewer recurrences (29 per cent) than reported with the classical selective adrenocorticolysis protocol (58 per cent). In a multivariate model, age and bodyweight at diagnosis were significantly negatively correlated with survival time. The median survival time of the dogs treated with trilostane twice a day (900 days) was longer (P=0.05) than that of the dogs treated with mitotane (720 days).
Assuntos
Hiperfunção Adrenocortical/veterinária , Antineoplásicos Hormonais/uso terapêutico , Di-Hidrotestosterona/análogos & derivados , Doenças do Cão/tratamento farmacológico , Mitotano/uso terapêutico , Hiperfunção Adrenocortical/tratamento farmacológico , Hiperfunção Adrenocortical/mortalidade , Fatores Etários , Animais , Antineoplásicos Hormonais/efeitos adversos , Peso Corporal/fisiologia , Di-Hidrotestosterona/efeitos adversos , Di-Hidrotestosterona/uso terapêutico , Doenças do Cão/mortalidade , Cães , Feminino , Estimativa de Kaplan-Meier , Masculino , Mitotano/efeitos adversos , Modelos de Riscos Proporcionais , Resultado do TratamentoRESUMO
Molecular epidemiological studies revealed that the epicenter of the HIV pandemic was Kinshasa, the capital city of the Democratic Republic of the Congo (DRC) in Central Africa. All known subtypes and numerous complex recombinant strains co-circulate in the DRC. Moreover, high intra-subtype diversity has been also documented. During two previous surveys on HIV-1 antiretroviral drug resistance in the DRC, we identified two divergent subtype C lineages in the protease and partial reverse transcriptase gene regions. We sequenced eight near full-length genomes and classified them using bootscanning and likelihood-based phylogenetic analyses. Four strains are more closely related to subtype C although within the range of inter sub-subtype distances. However, these strains also have small unclassified fragments and thus were named CRF92_C2U. Another strain is a unique recombinant of CRF92_C2U with an additional small unclassified fragment and a small divergent subtype A fragment. The three remaining strains represent a complex mosaic named CRF93_cpx. CRF93_cpx have two fragments of divergent subtype C sequences, which are not conventional subtype C nor the above described C2, and multiple divergent subtype A-like fragments. We then inferred the time-scaled evolutionary history of subtype C following a Bayesian approach and a partitioned analysis using major genomic regions. CRF92_C2U and CRF93_cpx had the most recent common ancestor with conventional subtype C around 1932 and 1928, respectively. A Bayesian demographic reconstruction corroborated that the subtype C transition to a faster phase of exponential growth occurred during the 1950s. Our analysis showed considerable differences between the newly discovered early-divergent strains and the conventional subtype C and therefore suggested that this virus has been diverging in humans for several decades before the HIV/M diversity boom in the 1950s.
RESUMO
Resumen Introducción: El personal de otorrinolaringología presenta una elevada exposición al virus SARS-CoV-2, debido a los procedimientos que lleva a cabo. Es fundamental tomar las medidas de protección adecuadas. Determinar la seroprevalencia nos dará un mejor panorama sobre la exposición, contagios y efectividad de medidas de protección adoptadas. Objetivo: Determinar la prevalencia de resultados serológicos positivos en personal médico que presta servicio en la Cátedra de Otorrinolaringología de marzo del 2020 a marzo de 2021. Material y Método: Estudio observacional, descriptivo, corte transversal, retrospectivo con asociación cruzada. Muestreo no probabilístico de casos consecutivos. La población total fue de 38 médicos del Servicio de Otorrinolaringología del Hospital de Clínicas. Resultados: La media de edades fue 37,4 años, 63,5% refirió haber atendido a paciente conocido portador de COVID-19. Un 42% refirió no haber cumplido con todas las medidas de protección personal, mientras que un 23,7% de los sujetos de estudio dio positivo para IgG, interpretándose como infección previa por COVID-19. Conclusión: Más de las dos terceras partes de los médicos refirió dar consulta a paciente COVID-19 positivo. Casi la cuarta parte de los médicos resultó ser positivo para COVID-19 según la prueba de serología anti-N. No se halló asociación entre consulta ni cirugía a pacientes portadores de COVID-19 y el contagio al personal médico.
Abstract Introduction: Otolaryngology personnel have a high exposure to SARS-CoV-2 virus due to the procedures they perform. It is essential to take appropriate protective measures. Determining seroprevalence will give us a better picture of exposure, contagion and effectiveness of protective measures adopted. Aim: To determine the prevalence of positive serological results in medical staff serving in the otolaryngology department from March 2020 to March 2021. Material and Method: Observational, descriptive, cross-sectional, retrospective, retrospective study with cross-association. Non-probability sampling of consecutive cases. The total population was 38 physicians of the Otolaryngology Service of the Hospital de Clinicas. Results: The mean age was 37.4. 63.5% reported having seen a patient known to be a COVID-19 carrier, while 42% reported not having complied with all personal protection measures. A 23.68% of the study subjects tested positive for IgG, interpreting previous COVID-19 infection. Conclusion: More than two-thirds of the physicians referred to giving consultation to COVID-19 positive patients. Almost a quarter of the physicians were positive for COVID-19 according to the Anti-N serology test. No association was found between consultation or surgery of patients with COVID-19 and infection of medical personnel.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Imunoglobulina G/análise , Imunoglobulina M/análise , Estudos Soroepidemiológicos , Pessoal de Saúde/estatística & dados numéricos , Otorrinolaringologistas/estatística & dados numéricos , COVID-19/imunologia , Paraguai/epidemiologia , Medidas de Segurança , Prevalência , Estudos Retrospectivos , Proteção Pessoal , Teste Sorológico para COVID-19 , SARS-CoV-2/imunologiaRESUMO
BACKGROUND: Levosulpiride is a 5HT4 agonist/D2 antagonist prokinetic agent used to improve gastric emptying in patients with functional dyspepsia or gastroparesis. The aim of this study was to characterize its effect on the main in vitro motility patterns in the human fundus, antrum, and jejunum. METHODS: Circular muscle strips from human stomach (antrum and fundus) and jejunum, obtained from 46 patients undergoing bariatric surgery, were studied using organ baths. Enteric motor neurons (EMNs) were stimulated by electrical field stimulation (EFS). KEY RESULTS: Levosulpiride, caused an increase in the EFS-induced cholinergic contractions in the gastric antrum (+37 ± 15.18% at 100 µM, pEC50 = 4.46 ± 0.14; p < 0.05, n = 8) and jejunum (+45.4 ± 22.03% at 100 µM, pEC50 = 3.78 ± 6.81; p < 0.05, n = 5), but not in the gastric fundus. It also caused a slight decrease in tone and frequency of spontaneous contractions in the jejunum, but did not have any major effect on tone or spontaneous contractions in the stomach. It did not have any effect on EFS-induced relaxations mediated by nitric oxide (NO) in the stomach (antrum and fundus) and by NO and ATP in the jejunum. CONCLUSIONS & INFERENCES: Our results suggest that the prokinetic effects of levosulpiride in humans are mainly due to the facilitation of the release of acetylcholine by enteric motor neurons in the gastric antrum and the jejunum.
Assuntos
Fundo Gástrico/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Jejuno/efeitos dos fármacos , Antro Pilórico/efeitos dos fármacos , Agonistas do Receptor 5-HT4 de Serotonina/farmacologia , Sulpirida/análogos & derivados , Adulto , Relação Dose-Resposta a Droga , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Esvaziamento Gástrico/fisiologia , Fundo Gástrico/fisiologia , Humanos , Jejuno/fisiologia , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Antro Pilórico/fisiologia , Sulpirida/farmacologiaRESUMO
Cyclooxygenase-2 (Cox-2) enzyme participates in different steps of the carcinogenetic process and in canine mammary tumours (CMTs), a high expression of Cox-2 is associated with malignancy and tumour angiogenesis. The objectives of the study were to evaluate the disease-free survival (DFS) and overall survival (OS) of a Cox-2 inhibitor as adjuvant therapy in dogs with highly malignant (HM)-CMTs and compare it with that of dogs treated with chemotherapy and with control dogs. Twenty-eight dogs were prospectively included. After surgery, dogs were alternatively allocated into two treatment groups (chemotherapy with mitoxantrone n=8; Cox-2 inhibitor, firocoxib n=7). Control group (n=13) included dogs whose owners rejected adjuvant therapy. All dogs were followed up for two years or until death. The DFS was significantly higher in dogs that received adjuvant treatment (mitoxantrone or firocoxib) (P=0.030) than in control dogs. Dogs on firocoxib treatment had significantly higher DFS (P=0.015) and OS (P=0.048) than control dogs. The DFS and OS of dogs on mitoxantrone treatment were not statistically different from controls. In conclusion, this study supports the use of firocoxib for the treatment of HM-CMTs. Further studies are needed to compare the efficacy of chemotherapy drugs versus Cox-2 inhibitors as adjuvant treatment in these cases.
Assuntos
Antineoplásicos/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Doenças do Cão/tratamento farmacológico , Neoplasias Mamárias Animais/tratamento farmacológico , 4-Butirolactona/análogos & derivados , 4-Butirolactona/uso terapêutico , Animais , Estudos de Casos e Controles , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/veterinária , Doenças do Cão/patologia , Cães , Feminino , Neoplasias Mamárias Animais/patologia , Mitoxantrona/uso terapêutico , Estudos Prospectivos , Sulfonas/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Local release of mast cell proteases during gastrointestinal surgery is associated with the inhibition of motility and postoperative ileus (POI). We determined whether activation of intramuscular mast cell affects the motor patterns of the human ileum and colon and whether proteases are involved. METHODS: Motor response of ileal and colonic circular muscle strips was measured in organ bath. Mast cell degranulation was induced by compound 48/80 (c48/80; 25-675 µg/mL). Motor response was quantified as tone, rhythmic phasic contractions (RPCs) and contractions to electric field stimulation (EFS; 40 Hz), and bethanechol-evoked contractions. Ketotifen (10(-6) mol/L) and a protease inhibitor cocktail (P8340) were used to evaluate the role of mast cell mediators. KEY RESULTS: (a) c48/80 impaired the spontaneous and the electrically evoked motor response in small bowel and colonic strips (sigmoid colon EC50 : 460.0 µg/mL for RPCs and 8.9 µg/mL for electrically evoked contraction amplitudes) and bethanechol-evoked contractions. (b) Preincubation with ketotifen (10(-6) mol/L, 1 h) prevented the impairment of RPCs and EFS-evoked contractions in the sigmoid colon and ileum but not in the right colon. (c) Preincubation with P8340 also prevented the impairment of contractions in the sigmoid colon but not in the ileum or the right colon. CONCLUSIONS & INFERENCES: Mast cell degranulation by c48/80 inhibits the spontaneous and the nerve-mediated motor response in the human ileum and colon. The effect is partially mediated by mast cell proteases and could be relevant in the pathophysiology of POI.
Assuntos
Degranulação Celular , Colo Sigmoide/fisiologia , Íleo/fisiologia , Mastócitos/fisiologia , p-Metoxi-N-metilfenetilamina/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo Sigmoide/efeitos dos fármacos , Feminino , Humanos , Íleo/efeitos dos fármacos , Íleus/complicações , Íleus/fisiopatologia , Técnicas In Vitro , Cetotifeno/farmacologia , Masculino , Mastócitos/efeitos dos fármacos , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Complicações Pós-Operatórias , Inibidores de Proteases/farmacologiaRESUMO
This paper presents an experimental analysis on a new board composed of gypsum and fly ashes from coal combustion, which are mutually compatible. Physical and mechanical properties, sound absorption coefficient, thermal properties and leaching test have been obtained. The mechanical properties showed similar values to other commercial products. As far as the acoustic insulation characteristics are concerned, sound absorption coefficients of 0.3 and 0.8 were found. The board presents a low thermal conductivity and a fire resistance higher than 50 min (for 4 cm of thickness). The leaching of trace elements was below the leaching limit values. These boards can be considered as suitable to be used in building applications as partitions.
Assuntos
Sulfato de Cálcio/análise , Cinza de Carvão/análise , Carvão Mineral , Materiais de Construção/análise , IncineraçãoRESUMO
BACKGROUND: Colonic samples from asymptomatic diverticulosis (DS) patients presented enhanced electrical field stimulation (EFS)-contractions, in an earlier study of ours, suggesting increased endogenous responses. The aim of this study was to explore changes in excitatory neuromuscular transmission and to assess the pharmacodynamics of spasmolytic agents in DS. METHODS: Circular muscle strips from sigmoid colon of DS patients (n = 30; 69.5 ± 14.8 years) and controls (n = 32; 64.7 ± 16.2 years) were studied using organ baths to evaluate the direct effect of excitatory agonists (carbachol, neurokinin A [NKA] and substance P [SP]), and the effect of antagonists (atropine and NK2 antagonist GR94800) and spasmolytic drugs (otilonium bromide [OB] and N-butyl-hyoscine) on the contractions induced by EFS-stimulation of excitatory motorneurons. qRT-PCR was also performed to compare mRNA expression of M2 , M3 , NK2 receptors and L-type calcium channels. KEY RESULTS: Contractions to carbachol (Emax : 663.7 ± 305.6% control vs 2698.0 ± 439.5% DS; p < 0.0005) and NKA (Emax : 387.8 ± 35.6% vs 1102.0 ± 190.1%; p < 0.0005) were higher in DS group, without differences for SP. Higher potency for DS patients was observed in the concentration-response curves for atropine (pIC50 = 8.56 ± 0.15 control vs pIC50 = 9.95 ± 0.18 DS group; p < 0.005) and slightly higher for GR94800 (pIC50 = 7.21 ± 0.18 control vs pIC50 = 7.97 ± 0.32 group; p < 0.0001). Lower efficacy (Emax ) and potency (pIC50 ) was observed for spasmolytic drugs in DS, whereas no differences were found regarding the relative expression of the receptors evaluated between groups. CONCLUSIONS & INFERENCES: The greater response to cholinergic and tachykinergic agonists and greater potency for muscarinic and NK2 antagonists observed in DS might play a role in the spasticity found in diverticular disease.