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1.
Mediators Inflamm ; 2022: 2222270, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060927

RESUMO

Airway inflammation in asthma is managed with anti-inflammatory steroids such as dexamethasone (DEX). However, about 20% of asthmatics do not respond to this therapy and are classified as steroid-resistant. Currently, no effective therapy is available for steroid-resistant asthma. This work therefore evaluated the effect of a plant sterol, stigmasterol (STIG), and stigmasterol-dexamethasone combination (STIG+DEX) in LPS-ovalbumin-induced steroid-resistant asthma in Guinea pigs. To do this, the effect of drugs on inflammatory features such as airway hyperreactivity and histopathology of lung tissue was evaluated. Additionally, the possible pathway of drug action was assessed by measuring events such neutrophil levels, oxidative and nitrative stress, and histone deacetylase 2 (HDAC2) and interleukin 17 (IL-17) levels. STIG alone did not affect inflammatory features, although it caused some changes in the molecular events associated with steroid-resistant asthma. However, STIG+DEX caused significant modulation of inflammatory features by protecting against destruction of lung tissue. The modulation of inflammatory features was associated with significant inhibition of neutrophilia and oxidative and nitrative stress, decrease in HDAC2, and increase in IL-17 levels that are usually associated with steroid-resistant asthma. Our findings show that although STIG and DEX individually do not protect against steroid-resistant asthma, their coadministration results in significant modulation of inflammatory features and the associated molecular events that lead to steroid-resistant asthma.


Assuntos
Asma , Estigmasterol , Animais , Asma/tratamento farmacológico , Asma/metabolismo , Dexametasona/uso terapêutico , Resistência a Medicamentos , Cobaias , Interleucina-17/uso terapêutico , Esteroides/farmacologia
2.
J Exp Anal Behav ; 118(2): 292-301, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36121599

RESUMO

To investigate the utility of ramps as enrichment and as a method for establishing demand for commodities, the latency to climb a ramp of increasing slope to obtain food was measured in four guinea pigs. The average height where guinea pigs failed to climb was 29.1 cm (slope 14.2 degrees). In addition, the increasing slope altered climbing behavior; when climbing speed was tested using the same slope for all trials within a single session, the guinea pigs maintained their climbing speed as the gradient increased across sessions. In comparison, when the slope was increased with each successful climb within a session, climbing speed was not maintained. Installing the maximum slope climbed can promote increased exercise and foraging but avoid physical harm or barriers to resources. Furthermore, these results indicate that climbing, a simple behavior with measurable differences as a function of slope and thus, effort, could be used as a method for testing the demand for commodities, such as food type or enrichment items, to be included in the husbandry of guinea pigs to improve welfare of the small cavy.


Assuntos
Cobaias , Locomoção , Animais , Cobaias/fisiologia
3.
Vet Clin North Am Exot Anim Pract ; 25(3): 631-661, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36122944

RESUMO

Endocrine disease in exotic species is less common than in small animals. Nevertheless, the diagnostic principles used in small animals can be adapted to evaluate endocrine disease in many of the exotic species although species-specific aspects need to be considered. This article covers important diseases such as thyroid dysfunction in reptiles and birds, hyperthyroidism in guinea pigs, and hyperadrenocorticism in ferrets. Glucose metabolism in neoplasms affecting normal physiology, such as insulinoma in ferrets and gastric neuroendocrine carcinoma in bearded dragons, is discussed. Calcium abnormalities, including metabolic bone disease in reptiles and hypocalcemia in birds, are also covered.


Assuntos
Animais Exóticos , Doenças do Sistema Endócrino , Animais , Aves , Cálcio , Doenças do Sistema Endócrino/veterinária , Furões , Glucose , Cobaias
4.
Biomed Res Int ; 2022: 6193876, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36132076

RESUMO

Objective: The effects of TGF-ß2 on mechanical properties of sclerotic desmocytes isolated from healthy and myopic guinea pigs were investigated in order to further understand the pathogenesis of myopia. To study the effect of TGF-ß2 on the mechanical properties of posterior scleral fibroblasts in experimental myopia. Methods: A lens-induced myopia (LIM) animal model was developed in 12 guinea pigs, with the opposite eye serving as a self-control (SC). Five untreated guinea pigs served as normal controls. Lenses were removed 30 days after model onset. Primary scleral fibroblasts were isolated and passaged twice and then treated with vehicle control or 1, 10, or 100 ng/mL TGF-ß2. After 24 h, micropipette aspiration was used to investigate the viscoelastic properties of the cells. Results: Scleral fibroblasts from LIM exhibited significantly higher equilibrium moduli and apparent viscosities relative to SC without TGF-ß2 treatment. Treatment of LIM or SC scleral fibroblasts with 1 or 10 ng/mL TGF-ß2 led to significantly different (p < 0.05) equilibrium moduli and apparent viscosities compared with vehicle control, whereas no significant differences were observed upon treatment with 100 ng/mL TGF-ß2. LIM cells treated with 1 and 10 ng/mL TGF-ß2 exhibited lower equilibrium moduli and apparent viscosities compared with similarly treated SC cells, but LIM cells and SC cells treated with 100 ng/mL TGF-ß2 had similar mechanical properties. Conclusions: The addition of 1 and 10 ng/mL TGF-ß2 can lower the equilibrium modulus and apparent viscosity of scleral fibroblasts in the normal eye.


Assuntos
Miopia , Fator de Crescimento Transformador beta2 , Animais , Modelos Animais de Doenças , Fibroblastos , Cobaias , Miopia/patologia , Esclera
5.
J Virol ; 96(17): e0083122, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36000848

RESUMO

The guinea pig is the only small animal model for congenital cytomegalovirus (CMV) but requires species-specific guinea pig cytomegalovirus (GPCMV). Infection of epithelial cells and trophoblasts by GPCMV requires the viral glycoprotein pentamer complex (PC) and endocytic entry because of the absence of platelet-derived growth factor receptor alpha (PDGFRA). Endothelial cells represent an important cell type for infection, dissemination in the host, and disease but have been poorly evaluated for GPCMV. Novel endothelial cell lines were established from animal vascular systems, including aorta (EndoC) and placental umbilical cord vein (GPUVEC). Cell lines were characterized for endothelial cell protein markers (PECAM1, vWF, and FLI1) and evaluated for GPCMV infection. Only PC-positive virus was capable of infecting endothelial cells. Individual knockout mutants for unique PC components (GP129, GP131, and GP133) were unable to infect endothelial cells without impacting fibroblast infection. Ectopic expression of PDGFRA in EndoC cells enabled GPCMV(PC-) infection via direct cell entry independent of the PC. Neutralizing antibodies to the essential viral gB glycoprotein were insufficient to prevent endothelial cell infection, which also required antibodies to gH/gL and the PC. Endothelial cell infection was also dependent upon viral tegument pp65 protein (GP83) to counteract the IFI16/cGAS-STING innate immune pathway, similar to epithelial cell infection. GPCMV endothelial cells were lytically (EndoC) or persistently (GPUVEC) infected dependent on tissue origin. The ability to establish a persistent infection in the umbilical cord could potentially enable sustained and more significant infection of the fetus in utero. Overall, results demonstrate the importance of this translationally relevant model for CMV research. IMPORTANCE Congenital CMV is a leading cause of cognitive impairment and deafness in newborns, and a vaccine is a high priority. The only small animal model for congenital CMV is the guinea pig and guinea pig cytomegalovirus (GPCMV) encoding functional HCMV homolog viral glycoprotein complexes necessary for cell entry that are neutralizing-antibody vaccine targets. Endothelial cells are important in HCMV for human disease and viral dissemination. GPCMV endothelial cell infection requires the viral pentamer complex (PC), which further increases the importance of this complex as a vaccine target, as antibodies to the immunodominant and essential viral glycoprotein gB fail to prevent endothelial cell infection. GPCMV endothelial cell infection established either a fully lytic or a persistent infection, depending on tissue origin. The potential for persistent infection in the umbilical cord potentially enables sustained infection of the fetus in utero, likely increasing the severity of congenital disease.


Assuntos
Infecções por Citomegalovirus , Roseolovirus , Animais , Anticorpos Neutralizantes , Células Endoteliais/metabolismo , Feminino , Cobaias , Humanos , Recém-Nascido , Infecção Persistente , Placenta , Gravidez , Proteínas do Envelope Viral/metabolismo
6.
J Parasitol ; 108(4): 395-402, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-36027573

RESUMO

Using microscopy and/or immunodiagnosis, the authors analyzed 284 fecal samples from the Brazilian rock cavy, Kerodon rupestris, that were collected between 1984 and 2015 in Serra da Capivara National Park for the presence of helminths and protozoa. Fourteen morphospecies of helminth eggs of the following taxa were found: Trematoda, Nematoda, Strongylidae, Lagochilascaris sp., Strongylida, Trichuris (2 species), Oxyuridae (3 species), Ancylostomatidae (2 species), and Ascarididae (2 species), along with 3 protozoan taxa: Coccidia, Cryptosporidium sp., and Balantidium sp. During the last 30 yr, the population of K. rupestris has increased in the region as a consequence of the creation and management of the National Park, and data from this study show a concurrent increase in the diversity of intestinal parasites in this host, including new reports. Some of these species have zoonotic potential, which suggests that K. rupestris may be in contact with domestic farm animals and/or human feces. These results show the importance of integrating different diagnostic approaches for the identification of protozoa in the region and indicate that further methods need to be employed to increase recovery. This work highlights the usefulness of parasite studies in assessing the health of ecosystems, especially in protected areas, which should be considered by park managers and health agencies.


Assuntos
Criptosporidiose , Cryptosporidium , Helmintos , Parasitos , Animais , Brasil , Ecossistema , Fezes , Cobaias , Humanos , Roedores
7.
Virus Res ; 319: 198884, 2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-35931226

RESUMO

Japanese encephalitis virus (JEV) is a single-stranded positive-sense RNA virus belonging to the Flaviviridae family. The JEV is the leading cause of viral encephalitis in children and the elderly which is spread by mosquitoes. JEV infection has been established in different animal models such as mouse, hamster, guinea pig, swine, rat, monkey, rabbit by using the different routes of inoculations. Here, we have shown that the alpha/beta and gamma -receptor deficient AG129 mouse induces fatal encephalitis in both young and aged old mice, when challenged with high titer JEV Indian clinical isolate by both intraperitoneal and intradermal route. The JEV infected AG129 mouse have shown neurological symptoms, JEV-induced pathological features and supported high level viral replication. Additionally, administration of JEV in AG129 mice resulted in the induction of severe peripheral vascular permeability, which is a major hall mark of Dengue infection but not shown in JEV. Taken together, our results demonstrate interferon α/ß and γ receptors knock out AG129 mouse does not need adaptation of JEV clinical isolates and could be is a promising JEV challenge mouse model by mimicking the natural intradermal route of administration for rapid screening of novel antivirals and vaccines.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Vírus da Encefalite Japonesa (Subgrupo) , Encefalite Japonesa , Animais , Vírus da Encefalite Japonesa (Espécie)/genética , Cobaias , Camundongos , Camundongos Knockout , Coelhos , Ratos , Receptores de Interferon/genética , Vasodilatação
8.
BMC Vet Res ; 18(1): 317, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978428

RESUMO

BACKGROUND: Bacterial corneal infections are common and potentially blinding diseases in all species. As antibiotic resistance is a growing concern, alternative treatment methods are an important focus of research. Photoactivated chromophore for keratitis-corneal crosslinking (PACK-CXL) is a promising oxygen radical-mediated alternative to antibiotic treatment. The main goal of this study was to assess the anti-bactericidal efficacy on clinical bacterial isolates of the current standard and an accelerated PACK-CXL treatment protocol delivering the same energy dose (5.4 J/cm2). METHODS: Clinical bacterial isolates from 11 dogs, five horses, one cat and one guinea pig were cultured, brought into suspension with 0.1% riboflavin and subsequently irradiated. Irradiation was performed with a 365 nm UVA light source for 30 min at 3mW/cm2 (standard protocol) or for 5 min at 18mW/cm2 (accelerated protocol), respectively. After treatment, the samples were cultured and colony forming units (CFU's) were counted and the weighted average mean of CFU's per µl was calculated. Results were statistically compared between treated and control samples using a linear mixed effects model. RESULTS: Both PACK-CXL protocols demonstrated a significant bactericidal effect on all tested isolates when compared to untreated controls. No efficacy difference between the two PACK-CXL protocols was observed. CONCLUSION: The accelerated PACK-CXL protocol can be recommended for empirical use in the treatment of bacterial corneal infections in veterinary patients while awaiting culture results. This will facilitate immediate treatment, the delivery of higher fluence PACK-CXL treatment within a reasonable time, and minimize the required anesthetic time or even obviate the need for general anesthesia.


Assuntos
Infecções Bacterianas , Doenças do Cão , Infecções Oculares Bacterianas , Doenças dos Cavalos , Ceratite , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/veterinária , Colágeno/uso terapêutico , Reagentes de Ligações Cruzadas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Cães , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/veterinária , Cobaias , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Ceratite/tratamento farmacológico , Ceratite/veterinária , Animais de Estimação , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/farmacologia , Riboflavina/uso terapêutico , Raios Ultravioleta
9.
Virus Res ; 320: 198899, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36030927

RESUMO

Infectious bovine rhinotracheitis (IBR) is caused by Bovine herpesvirus type 1 (BoHV-1), which seriously threatens the global cattle industry. Only vaccination to improve immunity is the most direct and effective means to prevent IBR. Attempts are being made to use subunit vaccines, deleted or recombinant viral vaccines to reduce or eradicate IBR. For investigating the immunological characteristics of glycoprotein B subunit vaccine in pattern animal guinea pigs, the partial glycoprotein B (gB) of BoHV-1 with dominant antigenic characteristic was selected. A recombinant prokaryotic expression vector pET-32a-gB with the truncated gB gene was constructed, expressed, identified and the purified proteins were used to immunize guinea pigs. The immune effect of the subunit vaccine was assessed by monitoring clinical symptoms, viral load, antibody secretion, and histopathological changes. The results indicated that guinea pigs immunized with the gB subunit vaccine produced high levels of anti-gB antibodies and virus-neutralizing antibodies. The gB subunit vaccine significantly reduced viral shedding and lung tissue damage after IBRV challenge. The animals inoculated the gB subunit vaccine also had less virus reactivation. Its protective effect on viral shedding and tissue damage was similar to that of inactivated BoHV-1 vaccine. This work is a proof-of-concept study of subunit vaccine-induced protection against BoHV-1. And it is expected to be a candidate vaccine for the prevention of IBR.


Assuntos
Herpesvirus Bovino 1 , Rinotraqueíte Infecciosa Bovina , Vacinas Virais , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Bovinos , Cobaias , Herpesvirus Bovino 1/genética , Rinotraqueíte Infecciosa Bovina/prevenção & controle , Vacinas de Produtos Inativados , Vacinas de Subunidades/genética , Vacinas Virais/genética
10.
Cutan Ocul Toxicol ; 41(3): 264-270, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36037101

RESUMO

Purpose: Of the several selenized yeasts authorised for use as feed additives in the EU, Saccharomyces cerevisiae CNCM I-3060 inactivated' (Sel-Plex®), was the first to be approved for use, in 2006. The additive has a concentration of selenium between 2000 and 2400 mg/kg and a selenomethionine content greater than 63%. Previous toxicological and safety studies have shown Sel-Plex® to be safe for use for target animal species, consumers, users and the environment. A new formulation of Sel-Plex® was recently developed however, with a minimum selenium content of 3000 mg/kg. The increase in selenium in this product, Sel-Plex® 3000, presented the need to assess the risk for workers and users and to establish if there would be any eye and/or skin irritancy and skin sensitisation effects associated with the product. The purpose of this paper is to present the methodology and results of the user safety skin and eye studies performed on Sel-Plex® 3000.Materials & Methods: In vitro skin and eye models were used to assess skin and eye irritancy, while skin sensitisation was examined using an in vivo method. The acute eye irritation was evaluated using a Reconstructed human Cornea-like Epithelium (RhCE) model, which followed the OECD guideline 492. The skin irritation was assessed based on its ability to induce cell death in a commercial reconstructed human epidermis (RhE) model (EPISKIN™) according to the OECD Guideline No. 439. The skin sensitising potential was evaluated in the Guinea pig in line with OECD Guideline 406, and measured the extent and degree of skin reaction to a challenge exposure following previous topical exposure of a substance on the skin.Results: The skin and eye irritation test results showed that Sel-Plex® 3000 was a non-irritant in both cases. The skin sensitisation study showed that the additive did not generate a sensitisation response in the guinea pig and should not be considered a skin sensitiser.Conclusion: These results indicate that Sel-Plex® 3000 is safe to use for workers in an industrial setting when handling the product and the studies may be further used to support regulatory compliance in respective markets.


Assuntos
Selênio , Dermatopatias , Animais , Epiderme , Cobaias , Humanos , Irritantes , Saccharomyces cerevisiae , Selênio/farmacologia
11.
Elife ; 112022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35916367

RESUMO

Human and animal EEG data demonstrate that focal seizures start with low-voltage fast activity, evolve into rhythmic burst discharges and are followed by a period of suppressed background activity. This suggests that processes with dynamics in the range of tens of seconds govern focal seizure evolution. We investigate the processes associated with seizure dynamics by complementing the Hodgkin-Huxley mathematical model with the physical laws that dictate ion movement and maintain ionic gradients. Our biophysically realistic computational model closely replicates the electrographic pattern of a typical human focal seizure characterized by low voltage fast activity onset, tonic phase, clonic phase and postictal suppression. Our study demonstrates, for the first time in silico, the potential mechanism of seizure initiation by inhibitory interneurons via the initial build-up of extracellular K+ due to intense interneuronal spiking. The model also identifies ionic mechanisms that may underlie a key feature in seizure dynamics, that is, progressive slowing down of ictal discharges towards the end of seizure. Our model prediction of specific scaling of inter-burst intervals is confirmed by seizure data recorded in the whole guinea pig brain in vitro and in humans, suggesting that the observed termination pattern may hold across different species. Our results emphasize ionic dynamics as elementary processes behind seizure generation and indicate targets for new therapeutic strategies.


Assuntos
Eletroencefalografia , Convulsões , Animais , Encéfalo , Eletroencefalografia/métodos , Retroalimentação , Cobaias , Humanos , Interneurônios
12.
Int J Mol Sci ; 23(15)2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35955743

RESUMO

Glycoprotein (GP) VI is the major platelet collagen receptor and a promising anti-thrombotic target. This was first demonstrated in mice using the rat monoclonal antibody JAQ1, which completely blocks the Collagen-Related Peptide (CRP)-binding site on mouse GPVI and efficiently inhibits mouse platelet adhesion, activation and aggregation on collagen. Here, we show for the first time that JAQ1 cross-reacts with human GPVI (huGPVI), but not with GPVI in other tested species, including rat, rabbit, guinea pig, swine, and dog. We further demonstrate that JAQ1 differently modulates mouse and human GPVI function. Similar to its effects on mouse GPVI (mGPVI), JAQ1 inhibits CRP-induced activation in human platelets, whereas, in stark contrast to mouse GPVI, it does not inhibit the adhesion, activation or aggregate formation of human platelets on collagen, but causes instead an increased response. This effect was also seen with platelets from newly generated human GPVI knockin mice (hGP6tg/tg). These results indicate that the binding of JAQ1 to a structurally conserved epitope in GPVI differently affects its function in human and mouse platelets.


Assuntos
Adesividade Plaquetária , Glicoproteínas da Membrana de Plaquetas , Animais , Plaquetas/metabolismo , Colágeno/metabolismo , Cães , Epitopos/metabolismo , Cobaias , Humanos , Camundongos , Ativação Plaquetária , Agregação Plaquetária , Glicoproteínas da Membrana de Plaquetas/metabolismo , Coelhos , Ratos
13.
Mem Inst Oswaldo Cruz ; 117: e220065, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35920504

RESUMO

BACKGROUND: Leishmania (Mundinia) enriettii is a species commonly found in the guinea pig, Cavia porcellus. Although it is a dermotropic species, there is still an uncertainty regarding its ability to visceralise during Leishmania life cycle. OBJECTIVE: Here, we investigated the ability of L. enriettii (strain L88) to visceralise in lungs, trachea, spleen, and liver of C. porcellus, its natural vertebrate host. METHODS: Animals were infected sub-cutaneously in the nose and followed for 12 weeks using histological (hematoxilin-eosin) and molecular tools (polymerase chain reaction-restriction fragment length polymorphism - PCR-RFLP). To isolate parasite from C. porcellus, animals were experimentally infected for viscera removal and PCR typing targeting hsp70 gene. FINDINGS: Histological analysis revealed intense and diffuse inflammation with the presence of amastigotes in the trachea, lung, and spleen up to 12 weeks post-infection (PI). Molecular analysis of paraffin-embedded tissues detected parasite DNA in the trachea and spleen between the 4th and 8th weeks PI. At the 12th PI, no parasite DNA was detected in any of the organs. To confirm that the spleen could serve as a temporary site for L. enriettii, we performed additional in vivo experiments. During 6th week PI, the parasite was isolated from the spleen confirming previous histopathological and PCR observations. MAIN CONCLUSION: Leishmania enriettii (strain L88) was able to visceralise in the trachea, lung, and spleen of C. porcellus.


Assuntos
Leishmania enriettii , Leishmania , Animais , Cobaias , Leishmania/genética , Pulmão , Baço , Traqueia
14.
Front Public Health ; 10: 907157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910918

RESUMO

Inhalation studies involving laboratory rats exposed to poorly soluble particles (PSLTs), such as carbon black and titanium dioxide, among others, have led to the development of lung cancer in conditions characterized as lung overload. Lung overload has been described as a physiological state in which pulmonary clearance is impaired, particles are not effectively removed from the lungs and chronic inflammation develops, ultimately leading to tumor growth. Since lung tumors have not occurred under similar states of lung overload in other laboratory animal species, such as mice, hamsters and guinea pigs, the relevance of the rat as a model for human risk assessment has presented regulatory challenges. It has been suggested that coal workers' pneumoconiosis may reflect a human example of apparent "lung overload" of poorly soluble particles. In turn, studies of risk of lung cancer in coal miners may offer a valuable perspective for understanding the significance of rat inhalation studies of PSLTs on humans. This report addresses whether coal can be considered a PSLT based on its composition in contrast to carbon black and titanium dioxide. We also review cohort mortality studies and case-control studies of coal workers. We conclude that coal differs substantially from carbon black and titanium dioxide in its structure and composition. Carbon black, a manufactured product, is virtually pure carbon (upwards of 98%); TiO2 is also a manufactured product. Coal contains carcinogens such as crystalline silica, beryllium, cadmium and iron, among others; in addition, coal mining activities tend to occur in the presence of operating machinery in which diesel exhaust particles, a Type I Human carcinogen, may be present in the occupational environment. As a result of its composition and the environment in which coal mining occurs, it is scientifically inappropriate to consider coal a PSLT. Despite coal not being similar to carbon black or TiO2, through the use of a weight of evidence approach-considered the preferred method when evaluating disparate studies to assess risk- studies of coal-mine workers do not indicate a consistent increase in lung cancer risk. Slight elevations in SMR cannot lead to a reliable conclusion about an increased risk due to limitations in exposure assessment and control of inherent biases in case-control studies, most notably confounding and recall bias. In conclusion, the weight of the scientific literature suggests that coal mine dust is not a PSLT, and it does not increase lung cancer risk.


Assuntos
Neoplasias Pulmonares , Mineradores , Animais , Carvão Mineral/efeitos adversos , Cricetinae , Poeira , Cobaias , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/patologia , Camundongos , Ratos , Fuligem/toxicidade
15.
Invest Ophthalmol Vis Sci ; 63(9): 25, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-36006019

RESUMO

Purpose: To identify key retinal pigment epithelium (RPE) genes linked to the induction of myopia in guinea pigs. Methods: To induce myopia, two-week-old pigmented guinea pigs (New Zealand strain, n = 5) wore -10 diopter (D) rigid gas-permeable contact lenses (CLs), for one day; fellow eyes were left without CLs and served as controls. Spherical equivalent refractive errors (SE) and axial length (AL) were measured at baseline and one day after initiation of CL wear. RNA sequencing was applied to RPE collected from both treated and fellow (control) eyes after one day of CL-wear to identify related gene expression changes. Additional RPE-RNA samples from treated and fellow eyes were subjected to quantitative real-time PCR (qRT-PCR) analysis for validation purposes. Results: The CLs induced myopia. The change from baseline values in SE was significantly different (P = 0.016), whereas there was no significant difference in the change in AL (P = 0.10). RNA sequencing revealed significant interocular differences in the expression in RPE of 13 genes: eight genes were significantly upregulated in treated eyes relative to their fellows, and five genes, including bone morphogenetic protein 2 (Bmp2), were significantly downregulated. The latter result was also confirmed by qRT-PCR. Additional analysis of differentially expressed genes revealed significant enrichment for bone morphogenetic protein (BMP) and TGF-ß signaling pathways. Conclusions: The results of this RPE gene expression study provide further supporting evidence for an important role of BMP2 in eye growth regulation, here from a guinea pig myopia model.


Assuntos
Lentes de Contato , Miopia , Animais , Lentes de Contato/efeitos adversos , Modelos Animais de Doenças , Cobaias , Miopia/genética , Miopia/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Pigmentos da Retina/metabolismo , Transcriptoma
16.
Am J Physiol Gastrointest Liver Physiol ; 323(4): G341-G347, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36044672

RESUMO

Live calcium imaging is often used as a proxy for electrophysiological measurements and has been a valuable tool that allows simultaneous analysis of neuronal activity in multiple cells at the population level. In the enteric nervous system, there are two main electrophysiological classes of neurons, after-hyperpolarizing (AH)- and synaptic (S)-neurons, which have been shown to have different calcium handling mechanisms. However, they are rarely considered separately in calcium imaging experiments. A handful of studies have shown that in guinea pig, a calcium transient will accompany a single action potential in AH-neurons, but multiple action potentials are required to generate a calcium transient in S-neurons. How this translates to different modes of cellular depolarization and whether this is consistent across species is unknown. In this study, we used simultaneous whole-cell patch-clamp electrophysiology together with calcium imaging to investigate how enteric neurons respond to different modes of depolarization. Using both traditional (4 Hz) and also high-speed (1,000 Hz) imaging techniques, we found that single action potentials elicit calcium transients in both AH-neurons and S-neurons. Subthreshold membrane depolarizations were also able to elicit calcium transients, although calcium responses were generally amplified if an action potential was present. Furthermore, we identified that responses to nicotinic acetylcholine receptor stimulation can be used to distinguish between AH- and S-neurons in calcium imaging.NEW & NOTEWORTHY Live calcium imaging is an important tool for investigating enteric nervous system (ENS) function. Previous studies have shown that multiple action potentials are needed to generate a calcium response in S-neurons, which has important implications for the interpretation of calcium imaging data. Here, we show that in mouse myenteric neurons, calcium transients are elicited by single action potentials in both AH- and S-neurons. In addition, nicotinic acetylcholine receptor stimulation can be used to distinguish between these two classes.


Assuntos
Plexo Mientérico , Receptores Nicotínicos , Potenciais de Ação/fisiologia , Animais , Cálcio , Eletrofisiologia , Cobaias , Humanos , Camundongos , Neurônios/fisiologia
17.
Phytomedicine ; 105: 154372, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35932609

RESUMO

BACKGROUND: Huanglian ointment exhibits clinical efficacy for repairing skin barriers and inhibiting skin inflammation, and has been used to ameliorate eczema for many years. However, the active components and mechanism of Huanglian ointment have not yet been elucidated. PURPOSE: This study aimed to demonstrate the main active components and molecular mechanisms of Huanglian ointment for the treatment of eczema. METHODS: The main active components of Huanglian ointment were identified by gas chromatography-mass spectrometry. Network pharmacology approach and molecular docking techniques to predict the potential molecular mechanisms of Huanglian ointment alleviating eczema. Furthermore, Biostir-AD®-induced guinea pigs and tumor necrosis α (TNF-α)/interferon γ (IFN-γ)-induced HaCaT cells were employed to investigate the effectiveness and mechanisms of Huanglian ointment using histopathological staining, enzyme-linked immunosorbent assay, MTT assay, and western blot analysis. RESULTS: Fourteen chemistry components were identified in Huanglian ointment. In total, 78 intersecting gene targets were identified between Huanglian ointment and eczema, including Jun, inflammatory regulators, and chemokine factors. Intersecting gene targets were enriched for cytokine and chemokine receptor binding, and inflammatory related signaling pathways. The molecular docking results showed that the identified components had a stable binding conformation with core targets. In vivo experiments showed that Huanglian ointment markedly ameliorated eczema-like skin lesions, restored histopathological morphology, and decreased levels of TNF-α, IFN-γ, and interleukin 6. Moreover, Huanglian ointment effectively protected HaCaT cells against TNF-α/IFN-γ-induced cell death and overproduction of thymus- and activation-regulated chemokine, macrophage-derived chemokine, and regulated upon activation normal T cell-expressed and secreted factor. Subsequently, we found that Huanglian ointment repaired skin barriers by affecting c-Jun, JunB, and filaggrin expression, and suppressed inflammatory response by inhibiting AGE-RAGE signaling pathway, both in vivo and in vitro. CONCLUSION: Our results demonstrated that Huanglian ointment repaired skin barriers and inhibited inflammation by maintaining the balance of c-Jun and JunB, and suppressing AGE-RAGE signaling pathway, thereby relieving eczema. These findings providing a molecular basis for treatment of eczema by Huanglian ointment.


Assuntos
Eczema , Queratinócitos , Animais , Quimiocinas , Medicamentos de Ervas Chinesas , Cobaias , Inflamação , Interferon gama , Simulação de Acoplamento Molecular , Pomadas , Transdução de Sinais , Fator de Necrose Tumoral alfa
18.
Einstein (Sao Paulo) ; 20: eRC6881, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35792760

RESUMO

Dermatophytoses are fungal infections affecting the skin and cutaneous annexes. This clinical case report describes a 7-year-old girl with Kerion celsi, a severe manifestation of Tinea capitis. The patient presented with painful edematous crusty scalp lesions and alopecia, which required surgical debridement and long-term antifungal treatment. Culture of samples collected from scalp and arm skin lesions (patient and patient's mother respectively) were positive for Trichophyton mentagrophytes. The family owned a pet guinea pig. This particular dermatophytosis is easily transmitted from guinea pigs to humans, with some studies showing up to 34.9% prevalence of Trichophyton mentagrophytes infection in these animals.


Assuntos
Tinha do Couro Cabeludo , Tinha , Alopecia/diagnóstico por imagem , Alopecia/tratamento farmacológico , Animais , Antifúngicos , Cobaias , Humanos , Pele/diagnóstico por imagem , Pele/patologia , Tinha/tratamento farmacológico , Tinha/microbiologia , Tinha/patologia , Tinha do Couro Cabeludo/diagnóstico por imagem , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/epidemiologia
19.
Pharmacol Res Perspect ; 10(4): e00982, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35822549

RESUMO

Non-selective cation channels in urinary bladder smooth muscle (UBSM) are thought to mediate increases in cellular excitability and contractility. For transient receptor potential melastatin type-4 (TRPM4) channels, the evidence primarily relies on the inhibitor 9-phenanthrol, which exhibits pharmacological limitations. Recently, 4-chloro-2-[2-(2-chloro-phenoxy)-acetylamino]-benzoic acid (CBA) has been discovered as a novel TRPM4 channel blocker. We examined how, in comparison to 9-phenanthrol, CBA affects the excitability of freshly isolated guinea pig UBSM cells and the contractility of UBSM strips. Additionally, non-selective TRPM4 channel inhibitor flufenamic acid (FFA) and potentiator BTP2 (also known as YM-58483) were studied in UBSM cells. Unlike robust inhibition for 9-phenanthrol already known, CBA (up to 100 µM) displayed either no or a very weak reduction (<20%) in spontaneous phasic, 20 mM KCl-induced, and electrical field stimulated contractions. For 300 µM CBA, reductions were higher except for an increase in the frequency of KCl-induced contractions. In UBSM cells, examined under amphotericin B-perforated patch-clamp, CBA (30 µM) did not affect the membrane potential (I = 0) or voltage step-induced whole-cell cation currents, sensitive to 9-phenanthrol. The currents were not inhibited by FFA (100 µM), increased by BTP2 (10 µM), nor enhanced under a strongly depolarizing holding voltage of -16 or + 6 mV (vs. -74 mV). None of the three compounds affected the cell capacitance, unlike 9-phenanthrol. In summary, the novel inhibitor CBA and nonselective FFA did not mimic the inhibitory properties of 9-phenanthrol on UBSM function. These results suggest that TRPM4 channels, although expressed in UBSM, play a distinct role rather than direct regulation of excitability and contractility.


Assuntos
Contração Muscular , Bexiga Urinária , Animais , Ácido Benzoico/farmacologia , Cátions/farmacologia , Cobaias , Músculo Liso , Fenantrenos
20.
Biologicals ; 78: 10-16, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35786353

RESUMO

We have obtained an attenuated rabies virus CTN181-3. In this paper, we make a comprehensive studies on CTN181-3. CTN181-3 showed no pathogenicity by i. c. or o. i. inoculation in 3-week-old mice, lower pathogenic in 2-week-old mice, and no virulence by o. i. inoculation in 8-week-old golden hamsters. CTN181-3 showed high immunogenicity, which produced high level neutralizing antibodies, 100% sero-conversation and >5.0 IU/ml GMT by one dose i. m. or o. i. vaccination in mice and golden hamsters. Cellular immune response by one dose i. m. or o. i. inoculation was detected. Especially in PEP, reduced dose of vaccination resulted in 50% (one dose) and 100% (2 doses) protections in golden hamsters. Molecular basis of the attenuation indicated that eight substitutions compared to its parental virus strain CTN-1, among them the two substitutions at the G276 (Leu→Val) and L1496 (Met→Trp) were the critical attenuated site. The phenotypic and genotypic characteristics of CTN181-3 were highly stable, no reversion was occurred when the virus was multiple passaged in suckling mice brains, guinea pig submandibular glands or BSR/Vero cell cultures. The gene homology compared to the Chinese rabies isolates showed much higher than rabies vaccine strains used in China, suggesting CTN181-3 is a promising and suitable oral rabies vaccine candidate strain.


Assuntos
Vacinas Antirrábicas , Vírus da Raiva , Raiva , Animais , Anticorpos Antivirais , Chlorocebus aethiops , Cricetinae , Cobaias , Mesocricetus , Camundongos , Raiva/prevenção & controle , Vírus da Raiva/genética , Células Vero
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