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In recent years, the knowledge of the physiological and pathophysiological roles of the renin-angiotensin system (RAS) in glucose metabolism has advanced significantly. It is now well-established that blockade of the angiotensin AT1 receptor (AT1R) improves insulin sensitivity. Activation of the AT2 receptor (AT2R) and the MAS receptor are significant contributors to this beneficial effect. Elevated availability of angiotensin (Ang) II) for interaction with the AT2R and increased Ang-(1-7) formation during AT1R blockade mediate these effects. The ongoing development of selective AT2R agonists, such as compound 21 and the novel Ang III peptidomimetics, has significantly advanced the exploration of the role of AT2R in metabolism and its potential as a therapeutic target. These agents show promise, particularly when RAS inhibition is contraindicated. Additionally, other RAS peptides, including Ang IV, des-Asp-Ang I, Ang-(1-9), and alamandine, hold therapeutic capability for addressing metabolic disturbances linked to type 2 diabetes. The possibility of AT2R heteromerization with either AT1R or MAS receptor offers an exciting area for future research, particularly concerning therapeutic strategies to improve glycemic control. This review focuses on therapeutic opportunities to improve insulin sensitivity, taking advantage of the protective arm of the RAS.
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P53 Phase separation is crucial towards amyloid aggregation and p63 and p73 have enhanced expression in tumors. This study examines the phase behaviors of p53, p63, and p73. Here we show that unlike the DNA-binding domain of p53 (p53C), the p63C and p73C undergo phase separation, but do not form amyloids under physiological temperatures. Wild-type and mutant p53C form droplets at 4°C and aggregates at 37 °C with amyloid properties. Mutant p53C promotes amyloid-like states in p63C and p73C, recruiting them into membraneless organelles. Amyloid conversion is supported by thioflavin T and Congo red binding, increased light scattering, and circular dichroism. Full-length mutant p53 and p63C (or p73C) co-transfection shows reduced fluorescence recovery after photobleaching. Heparin inhibits the prion-like aggregation of p63C and p73C induced by p53C. These findings highlight the role of p53 in initiating amyloid aggregation in p63 and p73, opening avenues for targeting prion-like conversion in cancer therapy.
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Leptospirosis is a disease caused by the bacteria of the Leptospira genus, which can usually be acquired by humans through contact with urine from infected animals; it is also possible for this urine to contaminate soils and bodies of water. The disease can have deadly consequences in some extreme cases. Fortunately, until now, patients with leptospirosis have responded adequately to treatment with doxycycline and azithromycin, and no cases of antibiotic resistance have been reported. However, with the extensive use of such medications, more bacteria, such as Staphylococci and Enterococci, are becoming resistant. The purpose of this study is to determine the presence of genes related to antibiotic resistance in the Leptospira genus using bioinformatic tools, which have not been undertaken in the past. Whole genomes from the 69 described Leptospira species were downloaded from NCBI's GeneBank and analyzed using CARD (The Comprehensive Antibiotic Resistant Database) and RAST (Rapid Annotations using Subsystem Technology). After a detailed genomic search, 12 genes associated with four mechanisms were found: resistance to beta-lactamases, vancomycin, aminoglycoside adenylyltransferases, as well as multiple drug efflux pumps. Some of these genes are highly polymorphic among different species, and some of them are present in multiple copies in the same species. In conclusion, this study provides evidence of the presence of genes related to antibiotic resistance in the genomes of some species of the genus Leptospira, and it is the starting point for future experimental evaluation to determine whether these genes are transcriptionally active in some species and serovars.
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Endometritis is the leading cause of mare subfertility. Most mares respond to standard therapy, but alternative therapies have been developed for mares failing to respond. This study aimed to investigate a commercially available, yet unassessed, product labeled as a uterine sanitizer to determine the in vitro antimicrobial activity against microorganisms associated with endometritis and its in vitro stability to dilute antibiotics. In experiment 1, the microdilution broth technique and antimicrobial effects were assessed against Escherichia sp, Staphylococcus sp., Klebsiella sp., Pseudomonas sp., and Candida sp. Percentage inhibition was calculated by comparing the optical density. The minimum inhibitory concentration (MIC) 100% was determined using the resazurin dye technique. MIC 50% and 90% were determined using a dose-response non-linear regression. In experiment 2, the uterine sanitizer was used to dilute commonly used antibiotics achieving a final volume of 90 mL at 5°C, 21°C, and 37°C. The pH was measured at 0, 1, 3, 6, and 24 h after dilution. The uterine sanitizer had inhibitory properties against all microorganisms; Escherichia sp. being the most susceptible, and Pseudomonas sp. the most resistant. The uterine sanitizer had an acidic pH=4; however, when combined with the antibiotics, the pH of the antibiotic remained unchanged with the different temperatures and did not precipitate. In conclusion, the uterine sanitizer showed antimicrobial effects against endometritis-causing microorganisms. The dilution of antibiotics in the uterine sanitizer was stable and this association could potentiate the antimicrobial effects. Uterine sanitizer's safety and clinical efficacy in vivo remain to be tested.
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Antibacterianos , Bacterias , Endometritis , Enfermedades de los Caballos , Pruebas de Sensibilidad Microbiana , Femenino , Animales , Endometritis/tratamiento farmacológico , Endometritis/microbiología , Endometritis/veterinaria , Caballos , Antibacterianos/farmacología , Antibacterianos/química , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/microbiología , Bacterias/efectos de los fármacos , Estabilidad de MedicamentosRESUMEN
Background: Tuberous sclerosis complex is a genetic neurocutaneous autosomal dominant syndrome, characterized by the development of multiple benign tumors (hamartomas) affecting various systems. Heart-benign tumors that result from the complex are called cardiac rhabdomyomas. Unlike hamartomas that occur in other organs, cardiac rhabdomyomas are most prevalent in infants and very young children with tuberous sclerosis complex. We present a case of a young adult with tuberous sclerosis who had an unusually late diagnosis of cardiac rhabdomyomas. Case report: A 22-year-old male patient of Afro-descendant, diagnosed with tuberous sclerosis complex in childhood, presented with refractory epilepsy and was treated only with lacosamide. The patient came to medical consultation due to a recent history of episodic, persistent chest pain in the sternal region, associated with physical effort. Echocardiography revealed a non-dilated left ventricle, with several rounded masses of high echogenicity without pedicles at the apical level, the largest measuring 14 × 11 mm, consistent with cardiac rhabdomyomas. Conclusion: Cardiac rhabdomyomas rarely develop in adulthood for individuals with tuberous sclerosis. These late-onset cases can exhibit various symptoms, from simple to complex presentations. Regular clinical checkups are essential for adults with tuberous sclerosis complex.
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Scoliosis is the most prevalent type of spinal deformity, with a 2-3% prevalence in the general population. Moreover, surgery for scoliotic deformity may result in severe blood loss and, consequently, the need for blood transfusions, thereby increasing surgical morbidity and the rate of complications. Several antifibrinolytic drugs, such as tranexamic acid, have been regarded as safe and effective options for reducing blood loss. Therefore, the present study aimed to analyse the effectiveness of this drug for controlling bleeding when used intraoperatively and in the first 48 h after surgery. A prospective randomized study of a cohort of patients included in a mass event for scoliosis treatment using PSF was performed. Twenty-eight patients were analysed and divided into two groups: 14 patients were selected for intraoperative and postoperative use of tranexamic acid (TXA), and the other 14 were selected only during the intraoperative period. The drainage bleeding rate, length of hospital stay, number of transfused blood units, and rate of adverse clinical effects were compared. All the patients involved had similar numbers of fusion levels addressed and similar scoliosis profiles. The postoperative bleeding rate through the drain did not significantly differ between the two groups (p > 0.05). There was no significant difference in the number of transfused blood units between the groups (p = 0.473); however, in absolute numbers, patients in the control group received more transfusions. The length of hospital stay was fairly similar between the groups, with no statistically significant difference. Furthermore, the groups had similar adverse effects (p = 0.440), with the exception of nausea and vomiting, which were twice as common in the TXA group postoperatively than in the control group. No significant differences were found in the use of TXA during the first 48 postoperative hours or in postoperative outcomes.
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Antifibrinolíticos , Pérdida de Sangre Quirúrgica , Escoliosis , Fusión Vertebral , Ácido Tranexámico , Humanos , Ácido Tranexámico/uso terapéutico , Escoliosis/cirugía , Femenino , Fusión Vertebral/métodos , Fusión Vertebral/efectos adversos , Masculino , Antifibrinolíticos/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Adolescente , Estudios Prospectivos , Adulto , Transfusión Sanguínea/estadística & datos numéricos , Resultado del Tratamiento , Periodo Posoperatorio , Tiempo de Internación , Adulto Joven , Hemorragia Posoperatoria/epidemiologíaRESUMEN
N-heterocyclic compounds are important molecular scaffolds in the search for new drugs, since most drugs contain heterocyclic moieties in their molecular structure, and some of these classes of heterocycles are able to provide ligands for two or more biological targets. Ketene dithioacetals are important building blocks in organic synthesis and are widely used in the synthesis of N-heterocyclic compounds. In this work, we used double vinylic substitution reactions on ketene dithioacetals to synthesize a small library of heterocyclic derivatives and evaluated their cytotoxic activity in breast and ovarian cancer cells, identifying two benzoxazoles with good potency and selectivity. In silico predictions indicate that the two most active derivatives exhibit physicochemical properties within the range of drug-like compounds and showed potential to interact with HDAC8 and ERK1 cancer-related targets.
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Antineoplásicos , Etilenos , Compuestos Heterocíclicos , Cetonas , Humanos , Línea Celular Tumoral , Etilenos/química , Etilenos/farmacología , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Cetonas/química , Cetonas/farmacología , Cetonas/síntesis química , Relación Estructura-Actividad , Histona Desacetilasas/metabolismo , Simulación del Acoplamiento Molecular , Ensayos de Selección de Medicamentos Antitumorales , Acetales/química , Acetales/farmacología , Acetales/síntesis química , Proteínas RepresorasRESUMEN
PURPOSE: To conduct an independent assessment of inter- and intraobserver agreement for the META score as a tool for differentiating osteoporotic vertebral fractures and multiple myeloma vertebral fractures. METHODS: This is a retrospective observational study. The magnetic resonance imaging analysis was made by two independent spinal surgeons. We designated a Subjective assessment, in which the surgeon should establish a diagnostic classification for each vertebral fracture based on personal experience: secondary to osteoporosis, categorized as a benign vertebral fracture (BVF), or attributed to multiple myeloma, categorized a malign vertebral fracture (MVF). After a 90-day interval, both surgeons repeated the evaluations. For the next step, the observers should establish a diagnosis between BVF and MVF according to the META score system, and both observers repeated the evaluations after a 90-day interval. The intra and interobserver reliability of the Subjective evaluation was studied using the kappa (κ) test. Then, the META evaluations were paralleled using the intraclass correlation coefficient (ICC). RESULTS: A total of 220 patients who had the potential to participate in the study were initially enrolled, but after applying the exclusion criteria, 44 patients were included. Thirty-three patients had BVF, and 12 patients presented MVF. Interobserver agreement for both Subjective evaluations moments (initial and 90-days interval) found a slight agreement for both moments (0.35 and 0.40 respectively). Kappa test for both META evaluations moments (initial and 90-days interval) found a moderate interobserver agreement for both moments (0.54 and 0.48 respectively). It was observed that the ICC calculated for the Initial evaluation using META score was 0.680 and that in the 90-days interval was 0.726, indicating regular to good agreement. Kappa test for intraobserver agreements for the Subjective evaluation presented moderate agreement for both Surgeons. On the other side, Kappa test for intraobserver agreements for the META evaluation presented substantial agreement for both Surgeons. The Intraclass Correlation Coefficient of the META score found presented an almost perfect agreement for both Surgeons. CONCLUSION: Intra and interobserver agreement for both surgeons were unsatisfactory. The lack of consistent reproducibility by the same observer discourages and disfavors the routine use of the META score in clinical decision making, when potentially cases of multiple myeloma may be present.
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Mieloma Múltiple , Variaciones Dependientes del Observador , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiología , Anciano , Femenino , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/diagnóstico , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Diagnóstico Diferencial , Anciano de 80 o más Años , Imagen por Resonancia Magnética , Reproducibilidad de los ResultadosRESUMEN
Estrone (E1) constitutes the primary component in oral conjugated equine estrogens (CEEs) and serves as the principal estrogen precursor in the female circulation in the post-menopause. E1 induces endothelium-dependent vasodilation and activate PI3K/NO/cGMP signaling. To assess whether E1 mitigates vascular dysfunction associated with postmenopause and explore the underlying mechanisms, we examined the vascular effects of E1 in ovariectomized (OVX) rats, a postmenopausal experimental model. Blood pressure was measured using tail-cuff plethysmography, and aortic rings were isolated to assess responses to phenylephrine, acetylcholine (ACh), and sodium nitroprusside. Responses to ACh in rings pre-incubated with superoxide dismutase (SOD), catalase (CAT), or apocynin were also evaluated. Protein expression of SOD, CAT, NOX1, NOX2, and NOX4 was determined by Western blotting. E1 treatment resulted in decreased body weight and retroperitoneal fat, increased uterine weight, and prevented elevated blood pressure in the OVX group. Furthermore, E1 improved endothelium-dependent ACh vasodilation, activated compensatory antioxidant mechanisms - i.e. increased SOD and CAT antioxidant enzymes activity, and decreased NOX4 expression. This, in turn, helped prevent oxidative stress and endothelial dysfunction in OVX rats. Additionally, E1 treatment reversed the increased total LDL cholesterol observed in the OVX group. The findings underscore protective effects of E1 on the cardiovascular system, counteracting OVX-related oxidative stress and endothelial dysfunction in Wistar rats. E1 exhibits promising therapeutic benefits for managing cardiovascular health, particularly in postmenopausal conditions.
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Endotelio Vascular , Estrona , NADPH Oxidasa 4 , Ovariectomía , Ratas Wistar , Especies Reactivas de Oxígeno , Vasodilatación , Animales , Femenino , NADPH Oxidasa 4/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Vasodilatación/efectos de los fármacos , Estrona/farmacología , Presión Sanguínea/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , RatasRESUMEN
BACKGROUND: Experiential avoidance (EA) is a psychological mechanism associated with several mental health disorders and is regarded as a relevant target by third-generation cognitive behavioral therapies. It has been mainly assessed through self-report questionnaires, and the AAQ-II is the most used tool. Its psychometric evidence has been mostly tested through the classical test theory (CTT) and very scarcely assessed through Item Response Theory (IRT). METHODS: We used the Graded Response Model to examine its psychometric properties in Spanish-speaking university students (n = 1503; women = 995 (66.2%), mean age = 19.29, SD = 2.45). We tested whether the empirical data fit the model's predictions and estimated the dispersion of persons and items along the experiential avoidance continuum. Moreover, we examined category probability curves to identify the response probability of each answer. Likewise, an item-person map was made where the measurement of persons and items, both on the same scale and along the experiential avoidance continuum, could be observed jointly. Finally, we tested the gender invariance of the scale. RESULTS: We found that the values of the individuals and the items were in the established range to be considered an adequate measure of EA. Additionally, we observed high discrimination indices for all items. The current version with seven answer options could not be optimal and should be tested in future studies. Finally, we found evidence of differential functioning by gender in one of the seven items of the instrument. CONCLUSIONS: Our results indicate that the AAQ-II is a suitable tool for measuring EA and accurately classifying and differentiating EA levels in university students.
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Estudiantes , Humanos , Femenino , Adulto Joven , Adulto , Psicometría , Chile , Universidades , Encuestas y CuestionariosRESUMEN
BACKGROUND: Information is scarce regarding the economic burden of respiratory syncytial virus (RSV) disease in low-resource settings. This study aimed to estimate the cost per episode of hospital admissions due to RSV severe disease in Argentina. METHODS: This is a prospective cohort study that collected information regarding 256 infants under 12 months of age with acute lower respiratory tract infection (ALRTI) due to RSV in two public hospitals of Buenos Aires between 2014 and 2016. Information on healthcare resource use was collected from the patient's report and its associated costs were estimated based on the financial database and account records of the hospitals. We estimated the total cost per hospitalization due to RSV using the health system perspective. The costs were estimated in US dollars as of December 2022 (1 US dollar = 170 Argentine pesos). RESULTS: The mean costs per RSV hospitalization in infants was US$587.79 (95% confidence interval [CI] $535.24 - $640.33). The mean costs associated with pediatric intensive care unit (PICU) admission more than doubled from those at regular pediatric wards ($1,556.81 [95% CI $512.21 - $2,601.40] versus $556.53 [95% CI $514.59 - $598.48]). CONCLUSIONS: This study shows the direct economic impact of acute severe RSV infection on the public health system in Argentina. The estimates obtained from this study could be used to inform cost-effectiveness analyses of new preventive RSV interventions being developed.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Lactante , Humanos , Niño , Estudios Prospectivos , Argentina/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Hospitalización , Infecciones del Sistema Respiratorio/epidemiología , Costo de EnfermedadRESUMEN
Boar seminal plasma (SP) proteins were associated with differences on sperm resistance to cooling at 17°C. However, information about seminal plasma proteins in boars classified by capacity of semen preservation and in vivo fertility remains lacking. Thus, the objective was to evaluate the SP proteome in boars classified by capacity of semen preservation and putative biomarkers for fertility. The ejaculates from high-preservation (HP) showed higher progressive motility during all 5 days than the low-preservation (LP) boars. There was no difference for farrowing rate between ejaculates from LP (89.7%) and HP boars (88.4%). The LP boars presented lower total piglets born (14.0 ± 0.2) than HP (14.8 ± 0.2; p < 0.01). A total of 257 proteins were identified, where 184 were present in both classes of boar, and 41 and 32 were identified only in LP and HP boars, respectively. Nine proteins were differently expressed: five were more abundant in HP (SPMI, ZPBP1, FN1, HPX, and C3) and four in LP boars (B2M, COL1A1, NKX3-2, and MPZL1). The HP boars had an increased abundance of SP proteins related to sperm resistance and fecundation process which explains the better TPB. LP boars had a higher abundance of SP proteins associated with impaired spermatogenesis.
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Preservación de Semen , Semen , Porcinos , Animales , Masculino , Semen/metabolismo , Preservación de Semen/veterinaria , Proteómica , Inseminación Artificial , Espermatozoides , Fertilidad , Análisis de Semen , Proteínas de Plasma Seminal/metabolismo , Motilidad EspermáticaRESUMEN
This study aimed to assess the suitability of egg yolk (EY) supplementation to a tris-citric acid-based extender on cryosurvival of guinea pig (Cavia porcellus) epididymal spermatozoa. Two synthetic-based extenders, tris-citric acid-glucose plus 20% EY (TCG-EY) and tris-citric acid-fructose (TCF) both with 5% glycerol, were compared. Thirty-two epididymides were recovered from 16 adult guinea pig males by gonadectomy, and then the sperm samples were retrieved by retrograde flushing using TCG-EY and TCF extenders for left or right epididymis, respectively. TCG-EY and TCF sperm samples were frozen in static liquid nitrogen vapors through a two-step cooling procedure. Before freezing, the percentage of progressive sperm motility and sperm with intact plasma and acrosome membranes from TCG-EY sperm samples were higher (p < 0.05) than those diluted with TCF. Post-thaw sperm kinematic variables and membrane integrity were drastically reduced (p < 0.001) compared with prefreezing samples, regardless of extender type. The post-thaw plasmatic and acrosome membrane integrity from TCG-EY sperm samples was higher (p < 0.05) than those from TCF samples. Except for the length, the morphometric head dimensions of sperm diluted with TCG-EY or TCF did not vary (p > 0.05) after the freezing-thawing process compared with the prefreezing samples. In conclusion, despite greater cell cryoinjury with both extenders, the EY supplementation exerted greater cell membrane protection before and after the freezing-thawing process. This research shows an in-depth analysis of guinea pig sperm cryopreservation; however, more studies are recommended.
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Yema de Huevo , Preservación de Semen , Masculino , Cobayas , Animales , Porcinos , Epidídimo , Ácido Cítrico/farmacología , Motilidad Espermática , Semen , Espermatozoides , Criopreservación/métodos , Preservación de Semen/métodos , Crioprotectores/farmacologíaRESUMEN
There is currently innumerable evidence showing that the lunar cycle affects various reproductive aspects in farm animals. However, there is very little information on the effect of the lunar cycle on productive traits in these species. A retrospective study was conducted (2015-2018) to evaluate the influence of the lunar cycle on some reproductive and productive traits in a guinea pig (Cavia porcellus) production system in the southern Andean region of Ecuador. A total of 7352 productive and reproductive records of guinea pig females housed in 3 m2 cages with a breeding male were analyzed. The following variables were considered: offspring sex ratio, litter size per cage, number of weaned guinea pigs, mortality, individual and litter weaning weight of guinea pigs, and calving frequency. The lunar cycle was split into eight periods of ~3.7-d length each. Data were analyzed by logistic regression and general linear model, and means were compared by the least mean squares method of the SAS. The offspring sex ratio was not correlated to the lunar cycle. The lunar cycle at mating and calving influenced the litter size per cage, number of weaned, and mortality of guinea pigs. The individual and litter-weaning weights were influenced by the lunar cycle at calving. The frequency of calving was greater around the new and full moon than in the remaining periods of the lunar cycle. In conclusion, the lunar cycle influenced several productive and reproductive traits in guinea pigs, such as litter size, mortality, number of pups weaned, and individual and litter weaning weights. This valuable information may have practical applications in management of guinea pig production systems.
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Ritmo Circadiano , Luna , Embarazo , Femenino , Cobayas , Animales , Masculino , Estudios Retrospectivos , Reproducción , Tamaño de la CamadaRESUMEN
BACKGROUND: Leptospirosis is a zoonosis of worldwide incidence, with a broad spectrum of health risk factors. AIM: The objective was to determine risk factors associated with acute human leptospirosis and to explore predictive variables of risk to human leptospirosis. METHODS: The study was carried out in the Department of Córdoba, in the north of Colombia. We conducted a longitudinal prospective descriptive study with non-probabilistic sampling, which included 339 patients suspected of leptospirosis. Positive cases were confirmed by MAT and PCR. The determination of social and environmental risk factors was done with a survey on epidemiological and environmental variables to establish an association between cases of leptospirosis and risk factors as well as predictive variables. RESULTS: We found 19.8% (67/339) cases of acute leptospirosis, and the seroprevalence was 27.1% (92/339). The most frequent serogroups were Sejroe, Australis, Pomona, Batavie, Pyrogenes and Grippotyphosa. We identified the following risk factors: age between 10 and 19 years (OR = 2.571; 95% CI); pig ownership (OR = 2.019; 95% CI); bathing or recreational activities in lake/lagoon (OR = 3.85; 95% CI) and in dams (OR = 3.0; 95% CI); floodings 30 days before the onset of symptoms (OR = 2.019; 95% CI), and a mean temperature of 28°C (p 0.044; 95%CI). As significant predictor variables, we identified age (10-19 years), bathing or recreational activities in the lake/lagoon, and flooding 30 days before symptoms were again evidenced. This region presents classic risk factors (pig ownership) and emerging environmental risk factors (recreational practice or bathing in a lake/lagoon and flooding 30 days before the onset of symptoms), and demographic factors such as young age (10-19 years). CONCLUSIONS: These factors are also predictors of human cases of acute leptospirosis and provide contextual information on environmental and public health that should be considered for epidemiological surveillance in this endemic area.
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Leptospira , Leptospirosis , Enfermedades de los Porcinos , Humanos , Animales , Porcinos , Colombia/epidemiología , Estudios Seroepidemiológicos , Leptospirosis/epidemiología , Leptospirosis/veterinaria , Factores de Riesgo , Región del Caribe , Anticuerpos AntibacterianosRESUMEN
OBJECTIVE: To assess the outcomes of several rodent animal models for studying tooth extraction-related medication-related osteonecrosis of the jaw (MRONJ). DESIGN: After a search of the databases, 2004 articles were located, and 118 corroborated the inclusion factors (in vivo studies in rodents evaluating tooth extraction as a risk factor for the development of MRONJ). RESULTS: Numerous studies attempting to establish an optimal protocol to induce MRONJ were found. Zoledronic acid (ZA) was the most used drug, followed by alendronate (ALN). Even when ZA did not lead to the development of MRONJ, its effect compromised the homeostasis of the bone and soft tissue. The association of other risk factors (dexamethasone, diabetes, and tooth-related inflammatory dental disease) besides tooth extraction also played a role in the development of MRONJ. In addition, studies demonstrated a relationship between cumulative dose and MRONJ. CONCLUSIONS: Both ZA and ALN can lead to MRONJ in rodents when equivalent human doses (in osteoporosis or cancer treatment) are used. Local oral risk factors and tooth-related inflammatory dental disease increase the incidence of MRONJ in a tooth extraction-related rodent model.
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Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Animales , Humanos , Difosfonatos/efectos adversos , Conservadores de la Densidad Ósea/efectos adversos , Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Roedores , Ácido Zoledrónico/efectos adversos , Extracción Dental/efectos adversos , Modelos Animales , Alendronato/efectos adversosRESUMEN
The angiotensin II type 2 (AT2) receptor has a role in promoting insulin sensitivity. However, the mechanisms underlying the AT2 receptor-induced facilitation of insulin are still not completely understood. Therefore, we investigated whether acute in vivo administration of AT2 receptor agonist compound 21 (C21) could activate insulin signaling molecules in insulin-target tissues. We report that, in male C57BL/6 mice, an acute (5 min, 0.25 mg/kg; i.v.) injection of C21 induces the phosphorylation of Akt and ERK1/2 at activating residues (Ser473 and Thr202/Tyr204, respectively) in both epididymal white adipose tissue (WAT) and heart tissue. In WAT, the extent of phosphorylation (p) of Akt and ERK1/2 induced by C21 was approximately 65% of the level detected after a bolus injection of a dose of insulin known to induce maximal activation of the insulin receptor (IR). In the heart, C21 stimulated p-Akt to a lesser extent than in WAT and stimulated p-ERK1/2 to similar levels to those attained by insulin administration. C21 did not modify p-IR levels in either tissue. We conclude that in vivo injection of the AT2 receptor agonist C21 activates Akt and ERK1/2 through a mechanism that does not involve the IR, indicating the participation of these enzymes in AT2R-mediated signaling.
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Insulinas , Proteínas Proto-Oncogénicas c-akt , Ratones , Animales , Masculino , Fosforilación , Sistema de Señalización de MAP Quinasas , Ratones Endogámicos C57BL , Tejido Adiposo/metabolismo , Receptor de Angiotensina Tipo 2/metabolismoRESUMEN
We develop a continuum framework applicable to solid-state hydrogen storage, cell biology and other scenarios where the diffusion of a single constituent within a bulk region is coupled via adsorption/desorption to reactions and diffusion on the boundary of the region. We formulate content balances for all relevant constituents and develop thermodynamically consistent constitutive equations. The latter encompass two classes of kinetics for adsorption/desorption and chemical reactions-fast and Marcelin-De Donder, and the second class includes mass action kinetics as a special case. We apply the framework to derive a system consisting of the standard diffusion equation in bulk and FitzHugh-Nagumo type surface reaction-diffusion system of equations on the boundary. We also study the linear stability of a homogeneous steady state in a spherical region and establish sufficient conditions for the occurrence of instabilities driven by surface diffusion. These findings are verified through numerical simulations which reveal that instabilities driven by diffusion lead to the emergence of steady-state spatial patterns from random initial conditions and that bulk diffusion can suppress spatial patterns, in which case temporal oscillations can ensue. We include an extension of our framework that accounts for mechanochemical coupling when the bulk region is occupied by a deformable solid. This article is part of the theme issue 'Foundational issues, analysis and geometry in continuum mechanics'.