RESUMEN
Heavy metal-rich environments can promote the selection of metal-resistance genes (MRGs) in bacteria, often leading to the simultaneous selection of antibiotic-resistance genes (ARGs) through a process known as co-selection. To comprehensively evaluate the biological pollutants at electronic-waste (e-waste) recycling facilities, air, soil, and river samples were collected at four distinct Swiss e-waste recycling facilities and analyzed for ARGs, MRGs, mobile genetic elements (MGEs), endotoxins, and bacterial species, with correlations drawn to heavy metal occurrence. To our knowledge, the present work marks the first attempt to quantify these bio-pollutants in the air of e-waste recycling facilities, that might pose a significant health risk to workers. Although ARG and MRG's profiles varied among the different sample types, intl1 consistently exhibited high relative abundance rates, identifying it as the predominant MGE across all sample types and facilities. These findings underscore its pivol role in driving diverse bacterial adaptations to extreme heavy metal exposure by selection and dissemination of ARGs and MRGs. All air samples exhibited consistent profiles of ARGs and MRGs, with blaTEM emerging as the predominant ARG, alongside pbrT and nccA as the most prevalent MRGs. However, one facility, engaged in batteries recycling and characterized by exceptionally high concentrations of heavy metals, showcased a more diverse resistance gene profile, suggesting that bacteria in this environment required more complex resistance mechanisms to cope with extreme metal exposure. Furthermore, this study unveiled a strong association between gram-negative bacteria and ARGs and less with MRGs. Overall, this research emphasizes the critical importance of studying biological pollutants in the air of e-waste recycling facilities to inform robust safety measures and mitigate the risk of resistance gene dissemination among workers. These findings establish a solid foundation for further investigations into the complex interplay among heavy metal exposure, bacterial adaptation, and resistance patterns in such distinctive ecosystems.
Asunto(s)
Residuos Electrónicos , Contaminantes Ambientales , Metales Pesados , Humanos , Antibacterianos/farmacología , Genes Bacterianos , Ecosistema , Bacterias/genética , Metales Pesados/toxicidadRESUMEN
In this work, new films containing composite materials based on blends of thermoplastic polymers of the polyurethane (TPU) and polyolefin (TPO) type, in the absence and presence of BaTiO3 nanoparticles (NPs) with the size smaller 100 nm, were prepared. The vibrational properties of the free films depending on the weight ratio of the two thermoplastic polymers were studied. Our results demonstrate that these films are optically active, with strong, broad, and adjustable photoluminescence by varying the amount of TPU. The crystalline structure of BaTiO3 and the influence of thermoplastic polymers on the crystallization process of these inorganic NPs were determined by X-ray diffraction (XRD) studies. The vibrational changes induced in the thermoplastic polymer's matrix of the BaTiO3 NPs were showcased by Raman scattering and FTIR spectroscopy. The incorporation of BaTiO3 NPs in the matrix of thermoplastic elastomers revealed the shift dependence of the photoluminescence (PL) band depending on the BaTiO3 NP concentration, which was capable of covering a wide visible spectral range. The dependencies of the dielectric relaxation phenomena with the weight of BaTiO3 NPs in thermoplastic polymers blends were also demonstrated.
RESUMEN
Aging is associated with progressive loss of physiological integrity, leading to impaired physical and mental functions as well as increased morbidity and mortality. With advancing age, the immune system is no longer able to adequately control autoimmunity, infections, or cancer. The abilities of the elderly to slow down undesirable effects of aging may depend on the genetic background, lifestyle, geographic region, and other presently unknown factors. Although most aspects of the immunity are constantly declining in relation to age, some features are retained, while e.g. the ability to produce high levels of cytokines, response to pathogens by increased inflammation, and imbalanced proteolytic activity are found in the elderly, and might eventually cause harm. In this context, it is important to differentiate between the effect of immunosenescence that is contributing to this decline and adaptations of the immune system that can be quickly reversed if necessary.
Asunto(s)
Inmunosenescencia , Linfocitos/citología , Animales , Citocinas/metabolismo , Humanos , Sistema Inmunológico/fisiología , Inflamación/patologíaRESUMEN
Functional columns of primary auditory cortex (AI) are arranged in layers, each composed of highly connected fine-scale networks. The basic response properties and interactions within these local subnetworks have only begun to be assessed. We examined the functional diversity of neurons within the laminar microarchitecture of cat AI to determine the relationship of spectrotemporal processing between neighboring neurons. Neuronal activity was recorded across the cortical layers while presenting a dynamically modulated broadband noise. Spectrotemporal receptive fields (STRFs) and their nonlinear input/output functions (nonlinearities) were constructed for each neuron and compared for pairs of neurons simultaneously recorded at the same contact site. Properties of these local neuron pairs showed greater similarity than non-paired neurons within the same column for all considered parameters including firing rate, envelope-phase precision, preferred spectral and temporal modulation frequency, as well as for the threshold and transition of the response nonlinearity. This higher functional similarity of paired versus non-paired neurons was most apparent in infragranular neuron pairs, and less for local supragranular and granular pairs. The functional similarity of local paired neurons for firing rate, best temporal modulation frequency and two nonlinearity aspects was laminar dependent, with infragranular local pair-wise differences larger than for granular or supragranular layers. Synchronous spiking events between pairs of neurons revealed that simultaneous 'Bicellular' spikes, in addition to carrying higher stimulus information than non-synchronized spikes, encoded faster modulation frequencies. Bicellular functional differences to the best matched of the paired neurons could be substantial. Bicellular nonlinearities showed that synchronous spikes act to transmit stimulus information with higher fidelity and precision than non-synchronous spikes of the individual neurons, thus, likely enhancing stimulus feature selectivity in their target neurons. Overall, the well-correlated and temporally precise processing within local subnetworks of cat AI showed laminar-dependent functional diversity in spectrotemporal processing, despite high intra-columnar congruity in frequency preference.
Asunto(s)
Corteza Auditiva/fisiología , Vías Auditivas/fisiología , Percepción Auditiva/fisiología , Red Nerviosa/fisiología , Neuronas/fisiología , Estimulación Acústica , Potenciales de Acción/fisiología , Animales , Corteza Auditiva/citología , Gatos , Análisis de Fourier , Técnicas In Vitro , Modelos Neurológicos , Dinámicas no Lineales , Psicoacústica , Factores de TiempoRESUMEN
This integrative study examined the morphological and genetic affinities of three endemic barbel species from Italy (brook barbel Barbus caninus, Italian barbel Barbus plebejus and horse barbel Barbus tyberinus) and of putative hybrid specimens to their species of origin. Two of the species frequently occur together with the non-native barbel Barbus barbus. DNA barcoding indicates that mitochondrial (mt) haplotypes often do not match the species expected from morphology. Linear distance measurements and meristics are not informative for discrimination of the species and putative hybrids, but a discriminant analysis of principal components (DAPC) of geometric landmark data produces reassignments largely in congruence with mt and nuclear genetic data. Cyto-nuclear conflicts confirm the presence of hybridization in B. plebejus and B. tyberinus and identify additional introgressed specimens. A comparison between mixed genotypes and their morphology-based assignment reveals no predictable pattern. The finding that most individuals of the morphologically similar B. plebejus and B. tyberinus have very high assignment probabilities to their respective species suggests that the presented approach may serve as a valuable tool to distinguish morphologically very similar taxa.
Asunto(s)
Cyprinidae/anatomía & histología , Cyprinidae/genética , Hibridación Genética , Animales , Cyprinidae/clasificación , Complejo IV de Transporte de Electrones/genética , Genotipo , Haplotipos , Italia , Filogenia , Especificidad de la EspecieRESUMEN
BACKGROUND: To dissect the intricate workings of neural circuits, it is essential to gain precise control over subsets of neurons while retaining the ability to monitor larger-scale circuit dynamics. This requires the ability to both evoke and record neural activity simultaneously with high spatial and temporal resolution. NEW METHOD: In this paper we present approaches that address this need by combining micro-electrocorticography (µECoG) with optogenetics in ways that avoid photovoltaic artifacts. RESULTS: We demonstrate that variations of this approach are broadly applicable across three commonly studied mammalian species - mouse, rat, and macaque monkey - and that the recorded µECoG signal shows complex spectral and spatio-temporal patterns in response to optical stimulation. COMPARISON WITH EXISTING METHODS: While optogenetics provides the ability to excite or inhibit neural subpopulations in a targeted fashion, large-scale recording of resulting neural activity remains challenging. Recent advances in optical physiology, such as genetically encoded Ca(2+) indicators, are promising but currently do not allow simultaneous recordings from extended cortical areas due to limitations in optical imaging hardware. CONCLUSIONS: We demonstrate techniques for the large-scale simultaneous interrogation of cortical circuits in three commonly used mammalian species.
Asunto(s)
Electrocorticografía/métodos , Optogenética/métodos , Animales , Artefactos , Percepción Auditiva/fisiología , Corteza Cerebral/fisiología , Diseño Asistido por Computadora , Impedancia Eléctrica , Electrocorticografía/instrumentación , Electrodos Implantados , Diseño de Equipo , Potenciales Evocados/fisiología , Macaca mulatta , Masculino , Ratones Transgénicos , Inhibición Neural/fisiología , Neuronas/fisiología , Optogenética/instrumentación , Estimulación Luminosa/métodos , Ratas Long-Evans , Compuestos de EstañoRESUMEN
CD-1 mice were exposed to baseline gasoline vapor condensate (BGVC) alone or to vapors of gasoline blended with methyl tertiary butyl ether (G/MTBE). Inhalation exposures were 6h/d on GD 5-17 at levels of 0, 2000, 10,000, and 20,000mg/m(3). Dams were evaluated for evidence of maternal toxicity, and fetuses were weighed, sexed, and evaluated for external, visceral, and skeletal anomalies. Exposure to 20,000mg/m(3) of BGVC produced slight reductions in maternal body weight/gain and decreased fetal body weight. G/MTBE exposure did not produce statistically significant maternal or developmental effects; however, two uncommon ventral wall closure defects occurred: gastroschisis (1 fetus at 10,000mg/m(3)) and ectopia cordis (1 fetus at 2000mg/m(3); 2 fetuses/1 litter at 10,000mg/m(3)). A second study (G/MTBE-2) evaluated similar exposure levels on GD 5-16 and an additional group exposed to 30,000mg/m(3) from GD 5-10. An increased incidence of cleft palate was observed at 30,000mg/m(3) G/MTBE. No ectopia cordis occurred in the replicate study, but a single observation of gastroschisis was observed at 30,000mg/m(3). The no observed adverse effect levels for maternal/developmental toxicity in the BGVC study were 10,000/2000mg/m(3), 20,000/20,000 for the G/MTBE study, and 10,000/20,000 for the G/MTBE-2 study.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Desarrollo Fetal/efectos de los fármacos , Gasolina/toxicidad , Animales , Femenino , Inhalación , Masculino , Ratones , Medición de Riesgo , Pruebas de ToxicidadRESUMEN
A Type III Built-up Roofing Asphalt (BURA) fume condensate was evaluated for subchronic systemic toxicity and reproductive/developmental toxicity screening in Wistar rats, by OECD protocol 422 and OECD cytogenetic protocol 474. Animals were exposed by nose-only inhalation to target concentrations of 30, 100 and 300 mg/m³ total hydrocarbons (actual concentrations, 30.0, 100.1 and 297.3 mg/m³). The study was performed to assess potential hazards from asphalt fumes to which humans could be exposed during application. No adverse effects were seen for spermology, reproductive or developmental parameters or early postnatal development of offspring from day 1 to 4 postpartum. BURA fume condensate did not induce any significant increases in micronucleus frequency in polychromatic erythrocytes of rat bone marrow nor was neurobehavioral toxicity observed at any dose. Systemic effects were slight and seen at doses above those measured at work sites. The systemic NOAEC of 100 mg/m³ for males was based on decreased body weight gain, food consumption and increased absolute and relative lung wet weight correlated with slight histological changes in the lung, primarily adaptive in nature at 300 mg/m³. The female NOAEC of 30 mg/m³ was based on a statistically significant increase in relative wet lung weight at higher doses, correlated with slight histopathologic effects in the lungs at the highest dose. However, no increase in relative lung weight was seen in breeding females at 100 mg/m³.
Asunto(s)
Hidrocarburos/administración & dosificación , Hidrocarburos/toxicidad , Exposición por Inhalación , Pulmón/efectos de los fármacos , Reproducción/efectos de los fármacos , Administración por Inhalación , Administración Intranasal , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Análisis Citogenético/métodos , Esquema de Medicación , Evaluación Preclínica de Medicamentos/métodos , Monitoreo del Ambiente/métodos , Femenino , Exposición por Inhalación/efectos adversos , Pulmón/crecimiento & desarrollo , Masculino , Embarazo , Ratas , Ratas Wistar , Reproducción/fisiologíaRESUMEN
Neurons in the center of cat primary auditory cortex (AI) respond to a narrow range of sound frequencies and the preferred frequencies in local neuron clusters are closely aligned in this central narrow bandwidth region (cNB). Response preferences to other input parameters, such as sound intensity and binaural interaction, vary within cNB; however, the source of this variability is unknown. Here we examined whether input to the cNB could arise from multiple, anatomically independent subregions in the ventral nucleus of the medial geniculate body (MGBv). Retrograde tracers injected into cNB labeled discontinuous clusters of neurons in the superior (sMGBv) and inferior (iMGBv) halves of the MGBv. Most labeled neurons were in the sMGBv and their density was greater, iMGBv somata were significantly larger. These findings suggest that cNB projection neurons in superior and iMGBv have distinct anatomic and possibly physiologic organization.
Asunto(s)
Corteza Auditiva/citología , Vías Auditivas/citología , Mapeo Encefálico , Neuronas/citología , Tálamo/citología , Estimulación Acústica , Animales , GatosRESUMEN
Noncoplanar polychlorinated biphenyls (PCBs) are widely dispersed in human environment and tissues. Here, an exemplar noncoplanar PCB was fed to rat dams during gestation and throughout three subsequent nursing weeks. Although the hearing sensitivity and brainstem auditory responses of pups were normal, exposure resulted in the abnormal development of the primary auditory cortex (A1). A1 was irregularly shaped and marked by internal nonresponsive zones, its topographic organization was grossly abnormal or reversed in about half of the exposed pups, the balance of neuronal inhibition to excitation for A1 neurons was disturbed, and the critical period plasticity that underlies normal postnatal auditory system development was significantly altered. These findings demonstrate that developmental exposure to this class of environmental contaminant alters cortical development. It is proposed that exposure to noncoplanar PCBs may contribute to common developmental disorders, especially in populations with heritable imbalances in neurotransmitter systems that regulate the ratio of inhibition and excitation in the brain. We conclude that the health implications associated with exposure to noncoplanar PCBs in human populations merit a more careful examination.
Asunto(s)
Corteza Auditiva/efectos de los fármacos , Exposición Materna , Plasticidad Neuronal/efectos de los fármacos , Bifenilos Policlorados/farmacología , Animales , Electrofisiología , Femenino , Audición/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Sensibilidad y EspecificidadRESUMEN
The developmental toxicity of toluene was evaluated via whole body inhalation exposure, in pregnant Sprague Dawley rats exposed to toluene (99.9% pure) from gestation day (GD) 6-15 inclusive, 6h/day, at concentrations of 0, 250, 750, 1500 and 3000ppm (0, 938, 2812, 5625 and 11250mg/m(3)). Doses were selected from a preliminary study performed over a range of concentrations from 0 to 5000ppm, in which maternal and fetal toxicity were observed at 2000ppm and above. This study has been cited in various regulatory documents and is presented here to allow greater accessibility to results and conclusions. Toluene induced clinical signs in pregnant dams (ataxia, hyper-responsivity, increased water intake, decreased food consumption) at 3000ppm, ataxia and hyper-responsivity at 1500ppm, and reduced maternal body weight gain at 1500 during the exposure period only and at 3000ppm from initiation of exposure to GD20. At Caesarean section on GD20, no adverse effects on implantation, number and viability of fetuses, or fetal sex distribution were observed. Litter weight and mean fetal weight was reduced at 3000ppm and mean fetal weight was reduced at 1500ppm. Instances of reduced or unossified skeletal elements occurred at the same dose levels. Mean fetal weight was also reduced at 250ppm but not at 750ppm. Extensive statistical analysis of fetal body weight data support the conclusion that there is no toxicologically significant dose-related effect on fetal body weight at or below 750ppm. Low incidences (Asunto(s)
Anomalías Inducidas por Medicamentos
, Contaminantes Atmosféricos/toxicidad
, Huesos/anomalías
, Peso Fetal/efectos de los fármacos
, Exposición por Inhalación
, Organogénesis/efectos de los fármacos
, Reproducción/efectos de los fármacos
, Tolueno/toxicidad
, Contaminantes Atmosféricos/química
, Animales
, Peso Corporal/efectos de los fármacos
, Relación Dosis-Respuesta a Droga
, Ingestión de Líquidos/efectos de los fármacos
, Ingestión de Alimentos/efectos de los fármacos
, Femenino
, Reabsorción del Feto/inducido químicamente
, Edad Gestacional
, Masculino
, Actividad Motora/efectos de los fármacos
, Nivel sin Efectos Adversos Observados
, Embarazo
, Ratas
, Ratas Sprague-Dawley
, Medición de Riesgo
, Tolueno/química
, Volatilización
RESUMEN
Intensity-tuned auditory cortex neurons have spike rates that are nonmonotonic functions of sound intensity: their spike rate initially increases and peaks as sound intensity is increased, then decreases as sound intensity is further increased. They are either "unbalanced," receiving disproportionally large synaptic inhibition at high sound intensities; or "balanced," receiving intensity-tuned synaptic excitation and identically tuned synaptic inhibition which neither creates enhances nor creates intensity-tuning. It has remained unknown if the synaptic inhibition received by unbalanced neurons enhances intensity-tuning already present in the synaptic excitation, or if it creates intensity-tuning that is not present in the synaptic excitation. Here we show, using in vivo whole cell recordings in pentobarbital-anesthetized rats, that in some unbalanced intensity-tuned auditory cortex neurons synaptic inhibition enhances the intensity-tuning; while in others it actually creates the intensity-tuning. The lack of balance between synaptic excitation and inhibition was not always apparent in their peak amplitudes, but could sometimes be revealed only by considering their relative timing. Since synaptic inhibition is essentially cortical in origin, the unbalanced neurons in which inhibition creates intensity-tuning provide examples of auditory feature-selectivity arising de novo at the auditory cortex.
Asunto(s)
Corteza Auditiva/citología , Inhibición Neural/fisiología , Neuronas/fisiología , Sinapsis/fisiología , Estimulación Acústica/métodos , Animales , Conducta Animal , Condicionamiento Operante/fisiología , Relación Dosis-Respuesta en la Radiación , Femenino , Técnicas In Vitro , Potenciales de la Membrana/fisiología , Potenciales de la Membrana/efectos de la radiación , Técnicas de Placa-Clamp/métodos , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/fisiología , Tiempo de Reacción/efectos de la radiación , Factores de TiempoRESUMEN
Combined physiological and connectional studies show significant non-topographic extrinsic projections to frequency-specific domains in the cat auditory cortex. These frequency-mismatched loci in the thalamus, ipsilateral cortex, and commissural system complement the predicted topographic and tonotopic projections. Two tonotopic areas, the primary auditory cortex (AI) and the anterior auditory field (AAF), were electrophysiologically characterized by their frequency organization. Next, either cholera toxin beta subunit or cholera toxin beta subunit gold conjugate was injected into frequency-matched locations in each area to reveal the projection pattern from the thalamus and cortex. Most retrograde labeling was found at tonotopically appropriate locations within a 1 mm-wide strip in the thalamus and a 2-3 mm-wide expanse of cortex (approximately 85%). However, approximately 13-30% of the neurons originated from frequency-mismatched locations far from their predicted positions in thalamic nuclei and cortical areas, respectively. We propose that these heterotopic projections satisfy at least three criteria that may be necessary to support the magnitude and character of plastic changes in physiological studies. First, they are found in the thalamus, ipsilateral and commissural cortex; since this reorganization could arise from any of these routes and may involve each, such projections ought to occur in them. Second, they originate from nuclei and areas with or without tonotopy; it is likely that plasticity is not exclusively shaped by spectral influences and not limited to cochleotopic regions. Finally, the projections are appropriate in magnitude and sign to plausibly support such rearrangements; given the rapidity of some aspects of plastic changes, they should be mediated by substantial existing connections. Alternative roles for these heterotopic projections are also considered.
Asunto(s)
Corteza Auditiva/fisiología , Vías Auditivas/fisiología , Mapeo Encefálico , Animales , Corteza Auditiva/anatomía & histología , Vías Auditivas/anatomía & histología , Gatos , Toxina del Cólera/metabolismo , Relación Dosis-Respuesta en la Radiación , Estimulación Eléctrica/métodos , Femenino , Lateralidad Funcional/fisiología , Masculino , Redes Neurales de la Computación , Tálamo/anatomía & histología , Tálamo/fisiologíaRESUMEN
Amplitude modulation (AM) is a temporal feature of most natural acoustic signals. A long psychophysical tradition has shown that AM is important in a variety of perceptual tasks, over a range of time scales. Technical possibilities in stimulus synthesis have reinvigorated this field and brought the modulation dimension back into focus. We address the question whether specialized neural mechanisms exist to extract AM information, and thus whether consideration of the modulation domain is essential in understanding the neural architecture of the auditory system. The available evidence suggests that this is the case. Peripheral neural structures not only transmit envelope information in the form of neural activity synchronized to the modulation waveform but are often tuned so that they only respond over a limited range of modulation frequencies. Ascending the auditory neuraxis, AM tuning persists but increasingly takes the form of tuning in average firing rate, rather than synchronization, to modulation frequency. There is a decrease in the highest modulation frequencies that influence the neural response, either in average rate or synchronization, as one records at higher and higher levels along the neuraxis. In parallel, there is an increasing tolerance of modulation tuning for other stimulus parameters such as sound pressure level, modulation depth, and type of carrier. At several anatomical levels, consideration of modulation response properties assists the prediction of neural responses to complex natural stimuli. Finally, some evidence exists for a topographic ordering of neurons according to modulation tuning. The picture that emerges is that temporal modulations are a critical stimulus attribute that assists us in the detection, discrimination, identification, parsing, and localization of acoustic sources and that this wide-ranging role is reflected in dedicated physiological properties at different anatomical levels.
Asunto(s)
Percepción Auditiva/fisiología , Encéfalo/fisiología , Neuronas/fisiología , Sonido , Animales , HumanosRESUMEN
The reproductive toxicity of toluene was evaluated in a 2-generation test in which male and female Sprague-Dawley rats, parental (F0) and first generation (F1), were exposed to toluene via whole body inhalation, 6 h/day, 7 days/week for 80 days premating and 15 days of mating at concentrations of 0, 100, 500 and 2000 ppm (0, 375, 1875 and 7500 mg/m(3)). Toluene was administered at 2000 ppm to both sexes, or to females or males only to be mated with untreated partners. Pregnant females at all dose levels were exposed from gestation day (GD) 1-20 and lactation day (LD) 5-21. At LD5, females were removed from their litters for daily exposure and returned when 6 h of exposure was completed. F1 pups selected to produce the F2 generation were treated for 80 days beginning immediately after weaning (LD21) and initially mated at a minimum of 100 days of age. F2 pups were not exposed to toluene by inhalation. Toluene exposure did not induce adverse effects on fertility, reproductive performance, or maternal/pup behaviors during the lactation period in males and females of the parental or first generation, but did inhibit growth in F1 and F2 offspring in the 2000 ppm (both sexes treated) and 2000 ppm (females only treated) groups. Caesarean section of selected 2000 ppm (both sexes treated) dams at GD20 showed reduced fetal body weight and skeletal variations. Exposure to toluene caused decreased pup weights throughout lactation in F1 and F2 2000 ppm (both sexes treated), and 2000 ppm (females only treated) groups. Exposure at 2000 ppm to male parents only did not induce similar weight inhibition in offspring. The toluene offspring NOAEL is 500 ppm in groups in which maternal animals were exposed, and 2000 ppm for male only treated groups.
Asunto(s)
Reproducción/efectos de los fármacos , Tolueno/toxicidad , Anomalías Inducidas por Medicamentos/epidemiología , Anomalías Inducidas por Medicamentos/patología , Animales , Peso al Nacer/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Fertilidad/efectos de los fármacos , Feto/patología , Gases , Lactancia/efectos de los fármacos , Masculino , Embarazo , Ratas , Sobrevida , Aumento de Peso/efectos de los fármacosRESUMEN
The clinical course of inflammatory bowel disease (IBD) in dogs is characterized by spontaneous exacerbations and remissions, which makes assessment of disease burden difficult. The objectives of this study were to develop a scoring system for evaluation of canine IBD activity and to validate this scoring method by correlating it to objective laboratory and histologic indices of intestinal inflammation. Fifty-eight dogs with IBD were evaluated prospectively and compared to 9 disease-free control dogs. Clinical disease activity was quantified by a simple scoring system, the canine IBD activity index (CIBDAI), and compared to serum concentrations of C-reactive protein (CRP), haptoglobin (HAP), alpha-acid glycoprotein (AGP), and serum amyloid A (SAA), as well as histology scores derived from endoscopic biopsy specimens. Forty-six dogs were available for a reevaluation of the CIBDAI, CRP HAP, and AGP, and 34 dogs had repeat analysis of SAA performed after medical therapy. Serum concentrations of CRP were significantly (P < .02) increased in dogs with CIBDAI scores > or = 5 (mild disease activity or greater) compared to controls. Among IBD dogs, the CIBDAI showed good correlation (r = 0.82, P < .0001) to both histology and HAP scores, but CRP also was a strong co-correlate of disease activity. The IBD dogs showed significantly (P < .0001) decreased CIBDAI and CRP values but significantly (P < .0001) increased HAP concentrations after medical therapy compared to pretreatment values. We conclude that the CIBDAI is a reliable measure of inflammatory activity in canine IBD and that CRP is suitable for laboratory evaluation of the effect of therapy in these patients.
Asunto(s)
Enfermedades de los Perros/diagnóstico , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/veterinaria , Envejecimiento , Animales , Antiinfecciosos/uso terapéutico , Antiinflamatorios/uso terapéutico , Dieta , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/patología , Perros , Quimioterapia Combinada , Femenino , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Masculino , Metronidazol/uso terapéutico , Prednisona/uso terapéutico , Ranitidina/uso terapéutico , Sulfasalazina/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVES: Current manufacture of intravenous immunoglobulin (Gamimune N) uses four cold-ethanol precipitation steps and solvent-detergent treatment. Our objective was to design a new manufacturing process to maximize immunoglobulin G (IgG) purity, achieve robust viral safety, preserve all the biological activities of antibody and avoid unnecessary protein loss. MATERIALS AND METHODS: The new process combines multiple functions in single steps. Caprylate is added to precipitate non-IgG proteins and to inactivate enveloped viruses. Two successive anion-exchange columns are used to purify IgG and remove caprylate. The new product, IGIV-C (Gamunex, 10%) is formulated with glycine at 100 mg/ml IgG, pH 4.25. Vials are incubated for 21 days at 23-27 degrees C in a final virus-inactivation step. RESULTS: Compared with the process for production of Gamimune N, that for IGIV-C requires a shorter production time, achieves more robust virus inactivation, increases IGIV yield from plasma, improves physiological IgG subclass distribution (resulting in higher levels of IgG4), and improves purity, with lower levels of IgA (40 microg/ml), IgM (< 2 microg/ml) and albumin (< 20 microg/ml). Antibody binding, opsonization and protective activities are similar. CONCLUSIONS: Compared with the current commercial process, the new IGIV-C manufacturing process produces a more highly purified preparation that contains slightly higher levels of IgG4 and retains antibody activities required for clinical efficacy.
Asunto(s)
Desinfección/métodos , Inmunoglobulinas Intravenosas/normas , Virus/aislamiento & purificación , Animales , Infecciones Bacterianas/tratamiento farmacológico , Caprilatos/farmacología , Precipitación Química , Cromatografía , Desinfección/normas , Contaminación de Medicamentos/prevención & control , Industria Farmacéutica/métodos , Industria Farmacéutica/normas , Humanos , Inmunoglobulinas Intravenosas/análisis , Inmunoglobulinas Intravenosas/farmacología , Ratones , Tasa de Supervivencia , Virosis/prevención & control , Virosis/transmisiónRESUMEN
Vitamin D-dependent rickets type 2 in a four-month-old cat A 4-month-old male domestic shorthair cat was examined because of lethargy, vomiting, diarrhea, muscle tremors, and mydriasis. Laboratory evaluation revealed hypocalcemia, hyperphosphatemia, and high intact parathormone and calcitriol concentrations. Findings were compatible with a diagnosis of vitamin D-dependent rickets type 2. Treatment consisted of oral administration of calcium and calcitriol supplements. During the subsequent 18 months, the cat remained clinically normal. Treatment with oral calcium supplements was eventually discontinued, and the cat was able to maintain serum calcium concentrations within reference limits.
Asunto(s)
Calcitriol/sangre , Enfermedades de los Gatos/metabolismo , Hiperparatiroidismo Secundario/veterinaria , Hipocalcemia/veterinaria , Raquitismo/veterinaria , Vitamina D/metabolismo , Animales , Calcitriol/administración & dosificación , Calcio/administración & dosificación , Calcio/sangre , Enfermedades de los Gatos/sangre , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/etiología , Hipocalcemia/sangre , Hipocalcemia/tratamiento farmacológico , Hipocalcemia/etiología , Masculino , Raquitismo/complicaciones , Raquitismo/tratamiento farmacológico , Raquitismo/metabolismo , Vitamina D/administración & dosificaciónRESUMEN
One of the brain's fundamental tasks is to construct and transform representations of an animal's environment, yet few studies describe how individual neurons accomplish this. Our results from correlated pairs in the auditory thalamocortical system show that cortical excitatory receptive field regions can be directly inherited from thalamus, constructed from smaller inputs, and assembled by the cooperative activity of neuronal ensembles. The prevalence of functional thalamocortical connectivity is strictly governed by tonotopy, but connection strength is not. Finally, spectral and temporal modulation preferences in cortex may differ dramatically from the thalamic input. Our observations reveal a radical reconstruction of response properties from auditory thalamus to cortex, and illustrate how some properties are propagated with great fidelity while others are significantly transformed or generated intracortically.
Asunto(s)
Corteza Auditiva/citología , Corteza Auditiva/fisiología , Cuerpos Geniculados/citología , Cuerpos Geniculados/fisiología , Estimulación Acústica , Potenciales de Acción/fisiología , Anestésicos Disociativos , Animales , Vías Auditivas/citología , Vías Auditivas/fisiología , Gatos , Electrofisiología , Ketamina , Inhibición Neural/fisiologíaRESUMEN
Action potentials are a universal currency for fast information transfer in the nervous system, yet few studies address how some spikes carry more information than others. We focused on the transformation of sensory representations in the lemniscal (high-fidelity) auditory thalamocortical network. While stimulating with a complex sound, we recorded simultaneously from functionally connected cell pairs in the ventral medial geniculate body and primary auditory cortex. Thalamic action potentials that immediately preceded or potentially caused a cortical spike were more selective than the average thalamic spike for spectrotemporal stimulus features. This net improvement of thalamic signaling indicates that for some thalamic cells, spikes are not propagated through cortex independently but interact with other inputs onto the same target cell. We then developed a method to identify the spectrotemporal nature of these interactions and found that they could be cooperative or antagonistic to the average receptive field of the thalamic cell. The degree of cooperativity with the thalamic cell determined the increase in feature selectivity for potentially causal thalamic spikes. We therefore show how some thalamic spikes carry more receptive field information than average and how other inputs cooperate to constrain the information communicated through a cortical cell.