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1.
Sci Rep ; 13(1): 157, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599863

RESUMO

Ringworm is a worldwide distributed contagious disease infecting both man and animals that constitute an economic, zoonotic, and health problem concern all over the world. During the last decade, attention has been directed to vaccination as an ideal approach to the control of such diseases. In the present study, non-adjuvanted polyvalent vaccines were prepared from locally isolated hot and virulent dermatophyte species, namely Trichophyton verrucosum (T. verrucosum), Trichophyton mentagrophytes (T. mentagrophytes), and Microsporum canis (M. canis) were immunologically evaluated. The prepared vaccine evaluation was focused on the aspects of immunogenicity and protective efficacy using guinea pigs. Both in its living or inactivated forms, the vaccine-induced significant humoral and cell-mediated immune responses and achieve proper protection of guinea pigs against challenging infections with homologous and heterologous dermatophyte strains. On the other hand, investigations on dermatophyte exo-keratinases showed that it was better produced and more expressed in a mineral-based medium containing pure keratin (3 g/L) than in the same medium with human hair supplementation (2.6 g/L). The maximum dermatophyte productivity of exo-keratinases was found to be between 18 and 21 days post-incubation. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), two fractions with molecular weights of 40 kDa (fraction I) and 28 kDa (fraction II) have been identified in the culture filtrate of the three involved dermatophyte species. Both fractions demonstrated keratinolytic activity. The specific activity of the isolated keratinases (number of Keratinase units (KU)/mg protein) was stronger in fraction I, where it reached 18.75, 15.38, and 14 KU/mg protein as compared to 12.9, 8.74, and 12 KU/mg protein in fraction II of T. verrucosum, T. mentagrophytes, and M. canis, respectively. The dermatophyte exo-keratinases proved to be immunogenic as they stimulated high keratinase-specific antibody titers and induced strong delayed skin hypersensitivity reactions in vaccinated animals. Anti-keratinase-specific IgG was detected in sera of guinea pigs immunized with the inactivated or living polyvalent dermatophyte vaccines by a homemade enzyme-linked immunosorbent assay (ELISA) using dermatophyte exo-keratinases as coating antigen. The intradermal injection of dermatophyte exo-keratinases induced specific delayed skin reactions in guinea pigs immunized with the inactivated or the living polyvalent dermatophyte vaccines. The intradermal injection of dermatophyte exo-keratinases in the control non-sensitized guinea pigs was associated with itching, swelling, and bloody scar formation, however, no skin indurations were formed. The development of those post-exo-keratinases injection reactions in the control non-sensitized apparently healthy guinea pigs group, suggests an exo-keratinases possible role in the pathogenesis of dermatophytosis.


Assuntos
Arthrodermataceae , Dermatomicoses , Masculino , Humanos , Animais , Cobaias , Dermatomicoses/prevenção & controle , Dermatomicoses/patologia , Vacinas Combinadas , Microsporum
2.
PLoS One ; 18(1): e0279111, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36652495

RESUMO

OBJECTIVE: To investigate the effects of scleral collagen cross-linking (SXL) using riboflavin and ultraviolet A (UVA) light on the scleral thickness of different regions and expression of matrix metalloproteinase 2 (MMP-2) and membrane-type MMP-1 (MT1-MMP) in guinea pigs with lens-induced myopia. METHODS: Forty-eight 4-week-old guinea pigs were assigned to three groups (n = 16 per group): SXL group, lens-induced myopia (LIM) group, and control group. The sclera of the right eye of the guinea pig in the SXL group was surgically exposed, riboflavin was dropped on the treatment area for 10 minutes before the 30-minute UVA irradiation. The same surgical procedure was performed in the LIM group without UVA irradiation. The -10.00 D lenses were then placed on the right eyes of guinea pigs in the SXL and LIM groups for six weeks. The control group received no treatment. The left eyes were untreated in all groups. The ocular axial length (AXL) and refraction were measured at 4 weeks and 10 weeks of age. 10-week-old guinea pigs were sacrificed, and the right eyes were enucleated and evenly divided for preparation of hematoxylin and eosin (HE) stained sections, quantitative real-time polymerase chain reaction (qPCR) and western blotting. The scleral thickness of different regions was measured on HE stained sections. The temporal half of the sclera was harvested to measure the expression of MMP-2 and MT1-MMP by qPCR and western blotting. RESULTS: The AXL was significantly shorter, and the degree of myopic refraction was significantly lower in the SXL group than those in the LIM group at 10 weeks of age. The scleral thickness of the cross-linked area was significantly greater in the SXL group than that of the corresponding area in the LIM group, while the scleral thickness of the untreated nasal side was not significantly different between the SXL group and the LIM group. The expression of MMP-2 and MT1-MMP of the cross-linked sclera was significantly downregulated compared with that of the corresponding area in the LIM group. CONCLUSION: Riboflavin/UVA SXL could slow myopia progression and thicken the cross-linked sclera in guinea pigs, which might be related to the downregulation of MMP-2 and MT1-MMP expression during the scleral remodeling process.


Assuntos
Miopia , Esclera , Cobaias , Animais , Esclera/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Miopia/tratamento farmacológico , Miopia/metabolismo , Riboflavina/farmacologia , Riboflavina/metabolismo , Colágeno/metabolismo , Modelos Animais de Doenças
3.
Physiol Rep ; 11(1): e15567, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36636780

RESUMO

The speed of pellet propulsion through the isolated guinea pig distal colon in vitro significantly exceeds in vivo measurements, suggesting a role for inhibitory mechanisms from sources outside the gut. The aim of this study was to investigate the effects of sympathetic nerve stimulation on three different neurogenic motor behaviors of the distal colon: transient neural events (TNEs), colonic motor complexes (CMCs), and pellet propulsion. To do this, segments of guinea pig distal colon with intact connections to the inferior mesenteric ganglion (IMG) were set up in organ baths allowing for simultaneous extracellular suction electrode recordings from smooth muscle, video recordings for diameter mapping, and intraluminal manometry. Electrical stimulation (1-20 Hz) of colonic nerves surrounding the inferior mesenteric artery caused a statistically significant, frequency-dependent inhibition of TNEs, as well as single pellet propulsion, from frequencies of 5 Hz and greater. Significant inhibition of CMCs required stimulation frequencies of 10 Hz and greater. Phentolamine (3.6 µM) abolished effects of colonic nerve stimulation, consistent with a sympathetic noradrenergic mechanism. Sympathetic inhibition was constrained to regions with intact extrinsic nerve pathways, allowing normal motor behaviors to continue without modulation in adjacent extrinsically denervated regions of the same colonic segments. The results demonstrate differential sensitivities to sympathetic input among distinct neurogenic motor behaviors of the colon. Together with findings indicating CMCs activate colo-colonic sympathetic reflexes through the IMG, these results raise the possibility that CMCs may paradoxically facilitate suppression of pellet movement in vivo, through peripheral sympathetic reflex circuits.


Assuntos
Gânglios Simpáticos , Sistema Nervoso Simpático , Cobaias , Animais , Gânglios Simpáticos/fisiologia , Reflexo/fisiologia , Colo/inervação , Atividade Motora , Estimulação Elétrica
4.
Eur J Med Res ; 28(1): 26, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639782

RESUMO

BACKGROUND: Aldosterone relieves transcriptional repression of epithelial sodium channel (ENaC) by inhibiting Dot1a and Af9 expression and their interaction with ENaC promoter in various tissues. Expressions of ENaC and Af9 in inner ear have been identified. However, it is not known how Dot1l is regulated by aldosterone in inner ear. METHODS: Twenty-eight adult guinea pigs were randomly divided into the control group and treatment group. Aldosterone 1 mg/kg/d was injected intraperitoneally in the treatment group and saline in the control group for 7 days. Animals were killed 1 month later following auditory brainstem response examination. Histomorphology of cochlea was detected with hematoxylin-eosin staining, and Dot1l expression was examined with immunohistochemistry and Western blot. RESULTS: There was no significant difference in ABR thresholds before and after injection of aldosterone or saline in either group. Endolymphatic hydrops was found in 75% of animals in the treatment group. Dot1l was found in both groups in the stria vascularis, Reissner's membrane, spiral limbus, organ of Corti and spiral ligament. Dot1l expression in the treatment group was decreased by aldosterone. CONCLUSIONS: Dot1l in guinea pig cochlea is inhibited by aldosterone with induction of endolymphatic hydrops. Dot1l may be closely related to endolymph regulation by aldosterone and to pathogenesis of Meniere's disease.


Assuntos
Hidropisia Endolinfática , Doença de Meniere , Cobaias , Animais , Aldosterona/farmacologia , Aldosterona/metabolismo , Cóclea/metabolismo , Cóclea/patologia , Hidropisia Endolinfática/etiologia , Hidropisia Endolinfática/metabolismo , Hidropisia Endolinfática/patologia , Doença de Meniere/complicações , Doença de Meniere/metabolismo , Doença de Meniere/patologia
5.
BMC Vet Res ; 19(1): 12, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658593

RESUMO

Macrodontia is the enlargement of tooth dimensions of different ethologies. This work aims to show a histological evaluation of macrodontic teeth in guinea pigs. The material was obtained from animals postmortem. Ninety structural changes derived from 24 guinea pigs were evaluated. All teeth used in the study showed macrodontic changes. The samples were decalcified, dehydrated and embedded in paraffin. Material was cut in the transverse and longitudinal planes in relation to the alveolar bone. Histological evaluation included apical bud cells, pulp cavity cells, periodontium, dentin, enamel, cementum and alveolar bone tissue. Individual elements were evaluated with respect to their morphology and distribution. Moreover, the arrangement of the individual hard tooth structures was assessed on the teeth. No atypia was found among the cells that make up the apical bud, pulp or periodontal cavity. Displacement of periodontal cells or odontoblasts towards the pulp cavity as well as disorganization of the cell system in the pulp cavity were observed. Changes in the dentine ligaments and the reconstruction of the alveolar bone were also observed in areas where dentine and cement systems were affected. Dental slides were observed and showed that the enamel is also involved in structural remodelling of the pulp cavity. The histological assessment revealed that structural changes in macrodontic teeth involve the rearrangement of typical tooth tissues.


Assuntos
Dente , Cobaias , Animais , Bochecha , Dente/anatomia & histologia , Osso e Ossos , Polpa Dentária
6.
Nat Commun ; 14(1): 366, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690629

RESUMO

Sensory neurons of the dorsal root ganglion (DRG) are critical for maintaining tissue homeostasis by sensing and initiating responses to stimuli. While most preclinical studies of DRGs are conducted in rodents, much less is known about the mechanisms of sensory perception in primates. We generated a transcriptome atlas of mouse, guinea pig, cynomolgus monkey, and human DRGs by implementing a common laboratory workflow and multiple data-integration approaches to generate high-resolution cross-species mappings of sensory neuron subtypes. Using our atlas, we identified conserved core modules highlighting subtype-specific biological processes related to inflammatory response. We also identified divergent expression of key genes involved in DRG function, suggesting species-specific adaptations specifically in nociceptors that likely point to divergent function of nociceptors. Among these, we validated that TAFA4, a member of the druggable genome, was expressed in distinct populations of DRG neurons across species, highlighting species-specific programs that are critical for therapeutic development.


Assuntos
Gânglios Espinais , Transcriptoma , Camundongos , Humanos , Animais , Cobaias , Gânglios Espinais/metabolismo , Macaca fascicularis , Nociceptores/metabolismo , Células Receptoras Sensoriais/metabolismo , Sensação , Citocinas/metabolismo
7.
Biol Pharm Bull ; 46(1): 133-137, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36596522

RESUMO

The negative inotropic effects of nine Vaughan Williams class I antiarrhythmic drugs were examined in guinea pig ventricular tissue preparations. The drugs decreased the contractile force of papillary muscles with different potencies: the potency order was propafenone > aprindine > cibenzoline > flecainide > ranolazine > disopyramide > pilsicainide > mexiletine > GS-458967. The potency of drugs correlated with the reported IC50 values to block the L-type Ca2+ channel rather than the Na+ channel. The effects of drugs were roughly the same when examined under a high extracellular K+ solution, which inactivates the Na+ channel. Furthermore, the attenuation of the extracellular Ca2+-induced positive inotropy was strong with propafenone, moderate with cibenzoline, and weak with pilsicainide. These results indicate that the negative inotropic effects of class I antiarrhythmic drugs can be largely explained by their blockade of the L-type Ca2+ channel.


Assuntos
Antiarrítmicos , Propafenona , Cobaias , Animais , Antiarrítmicos/farmacologia , Propafenona/farmacologia , Miocárdio , Lidocaína/farmacologia , Músculos Papilares
8.
J Vis Exp ; (191)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36688548

RESUMO

Noise exposure is a leading cause of sensorineural hearing loss. Animal models of noise-induced hearing loss have generated mechanistic insight into the underlying anatomical and physiological pathologies of hearing loss. However, relating behavioral deficits observed in humans with hearing loss to behavioral deficits in animal models remains challenging. Here, pupillometry is proposed as a method that will enable the direct comparison of animal and human behavioral data. The method is based on a modified oddball paradigm - habituating the subject to the repeated presentation of a stimulus and intermittently presenting a deviant stimulus that varies in some parametric fashion from the repeated stimulus. The fundamental premise is that if the change between the repeated and deviant stimulus is detected by the subject, it will trigger a pupil dilation response that is larger than that elicited by the repeated stimulus. This approach is demonstrated using a vocalization categorization task in guinea pigs, an animal model widely used in auditory research, including in hearing loss studies. By presenting vocalizations from one vocalization category as standard stimuli and a second category as oddball stimuli embedded in noise at various signal-to-noise ratios, it is demonstrated that the magnitude of pupil dilation in response to the oddball category varies monotonically with the signal-to-noise ratio. Growth curve analyses can then be used to characterize the time course and statistical significance of these pupil dilation responses. In this protocol, detailed procedures for acclimating guinea pigs to the setup, conducting pupillometry, and evaluating/analyzing data are described. Although this technique is demonstrated in normal-hearing guinea pigs in this protocol, the method may be used to assess the sensory effects of various forms of hearing loss within each subject. These effects may then be correlated with concurrent electrophysiological measures and post-hoc anatomical observations.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva , Humanos , Cobaias , Animais , Ruído , Sensação
9.
Viruses ; 15(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36680259

RESUMO

Genital herpes (GH) has become one of the most common sexually transmitted diseases worldwide, and it is spreading rapidly in developing countries. Approximately 90% of GH cases are caused by HSV-2. Therapeutic HSV-2 vaccines are intended for people already infected with HSV-2 with the goal of reducing clinical recurrences and recurrent virus shedding. In our previous work, we evaluated recombinant adenovirus-based vaccines, including rAd-gD2ΔUL25, rAd-ΔUL25, and rAd-gD2, for their potency as prophylactic vaccines. In this study, we evaluated these three vaccines as therapeutic vaccines against acute and recurrent diseases in intravaginal challenged guinea pigs. Compared with the control groups, the recombinant vaccine rAd-gD2ΔUL25 induced a higher titer of the binding antibody, and rAd-gD2 + rAd-ΔUL25 induced a higher titer of the neutralizing antibody. Both rAd-gD2ΔUL25 and rAd-gD2 + rAd-ΔUL25 vaccines significantly enhanced the survival rate by 50% compared to rAd-gD2 and reduced viral replication in the genital tract and recurrent genital skin disease. Our findings provide a new perspective for HSV-2 therapeutic vaccine research and provide a new technique to curtail the increasing spread of HSV-2.


Assuntos
Infecções por Adenoviridae , Vacinas contra Adenovirus , Herpes Genital , Vacinas contra o Vírus do Herpes Simples , Cobaias , Animais , Herpesvirus Humano 2/genética , Adenoviridae/genética , Proteínas do Envelope Viral/genética , Herpes Genital/prevenção & controle , Vacinas Sintéticas/genética , Anticorpos Antivirais
10.
J Prev Alzheimers Dis ; 10(1): 34-40, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36641608

RESUMO

BACKGROUND: Recruitment to dementia prevention clinical trials is challenging, and participants are not representative of US adults at risk. A better understanding of the general public's interest in dementia prevention research participation is needed to inform future recruitment strategies. OBJECTIVE: To examine US adults' characteristics associated with self-reported likelihood to participate in dementia prevention clinical trials. DESIGN: We conducted a cross-sectional survey using the October 2018 wave of the University of Michigan National Poll on Healthy Aging. SETTING: The National Poll on Healthy Aging is a nationally representative survey of adults using KnowledgePanel (Ipsos Public Affairs LLC), a probability-based panel of the civilian, noninstitutionalized US population. PARTICIPANTS: We analyzed data from 1,028 respondents, ages 50 to 64 years, who completed a web survey module on brain health. MEASUREMENTS: We used logistic regression models to examine associations between sociodemographic and dementia-related factors (e.g., family history) and self-reported likelihood to participate in a dementia prevention clinical trial of a new medicine ("very" or "somewhat likely" vs. "not likely" survey responses). Among respondents not likely to participate, we examined frequency of reasons endorsed for this decision, stratified by age, sex, and race and ethnicity. RESULTS: Of the 1,028 respondents, half were female, 68% Non-Hispanic White, 13% Hispanic, and 12% Non-Hispanic Black. Twelve percent of respondents reported being very likely to participate in a dementia prevention trial, 32% somewhat likely, and 56% not likely. Factors associated with higher likelihood to participate were higher perceived risk of dementia [OR, 2.17 (95% CI, 1.61, 2.93)], a positive family history of dementia [OR, 1.75 (95% CI, 1.27, 2.43)], and having discussed dementia prevention with a doctor [OR, 2.20 (95% CI, 1.10, 4.42)]. There were no differences in likelihood to participate by sociodemographic characteristics. Among 570 respondents not likely to participate, 39% said they did not want to be a guinea pig, 23% thought dementia would not affect them, 22% thought there would be too high a chance for harm, 15% indicated study participation would take too much time, and 5% reported fear of learning information about oneself. There were no differences across age, sex, and racial and ethnic groups. CONCLUSIONS: In this study, perceived risk of dementia, family history, and discussion of prevention with a doctor were associated with likelihood to participate in a dementia prevention clinical trial, whereas sociodemographic factors including race and ethnicity were not. Findings suggest that recruitment interventions focused on increasing knowledge of dementia risk and prevention trials and involving healthcare providers may be effective tools to improve enrollment rates, regardless of target community.


Assuntos
Demência , Envelhecimento Saudável , Humanos , Feminino , Animais , Cobaias , Masculino , Estudos Transversais , Etnicidade , Probabilidade , Demência/prevenção & controle
12.
Theriogenology ; 198: 231-240, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36621132

RESUMO

Guinea pig in vitro fertilization (IVF) are poorly developed due to the limited accessibility to oocytes and the lack of an efficient method of sperm capacitation. Thus, we aimed to evaluate different capacitation protocols that we validated through sperm analysis and using heterologous (He) IVF with zona-intact bovine oocytes. Spermatozoa of guinea pigs were collected and processed separately by 4 different protocols: A) Spermatozoa were obtained by flushing the lumen of one cauda epididymis and incubated in a minimal culture medium (MCM); B) One epididymis was placed in a prewarmed of M2 medium and gently minced with fine scissors. Spermatozoa were incubated in a modified human tubal fluid medium (HTF). In both protocols, the spermatozoa were capacitated at 37 °C under an atmosphere of 5% CO2 for 2 h. In the protocols C and D, the spermatozoa were collected by flushing the lumen of the cauda epididymis and selected by commercial density gradient Bovipure® (Nidacon Laboratories AB, Göthenborg, Sweden), according to the manufacturer's instructions. Then for Protocol C) spermatozoa were incubated in MCM medium supplemented with 10 mg/mL heparin (MCM-Hep); while for Protocol D) spermatozoa were incubated in FERT medium supplemented 10 mg/mL heparin (FERT-Hep). Incubation of C and D protocols were performed at 38.5 °C under an atmosphere of 5% CO2 for 2 h. Capacitation protocols C and D showed a higher percentage of viability, total and hyperactive-like motility, and acrosome reaction compared to protocols A and B. For this reason, protocols C and D were used for further He-IVF analysis. Guinea pig sperm and matured zona-intact bovine oocytes were co-incubated at 5% CO2 and 38.5 °C. Sperm-oocyte interaction was assessed at 2.5 h post-insemination (hpi) and pronuclear formation (PrF) were evaluated at 18, 20, 22, 24 and 26 hpi, while the cleavage rate was evaluated at 48 hpi. In protocol D, PrF was significantly higher than in protocol C (P ≤ 0.05) at every time point evaluated. Also, the cleavage rate at 48 hpi was higher (P ≤ 0.05) in He-IVF protocol D (69.8 ± 1.7%) compared to He-IVF protocol C (49.1 ± 1.1%). In conclusion, we determined the most adequate sperm capacitation conditions for guinea pig that allow zona-intact bovine oocyte penetration and lead to hybrid embryo formation, suggesting that these conditions could be optimal to develop IVF in guinea pigs.


Assuntos
Dióxido de Carbono , Zona Pelúcida , Humanos , Cobaias , Animais , Masculino , Bovinos , Sêmen , Espermatozoides , Interações Espermatozoide-Óvulo , Fertilização In Vitro/veterinária , Capacitação Espermática , Heparina
13.
Cytokine ; 162: 156104, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36493630

RESUMO

AIMS: Cigarette smoke often induces pulmonary and systemic inflammation. In animal models, mesenchymal stem cells (MSC) tend to ameliorate these effects. We aimed to explore the local and systemic expression of cytokines in guinea pigs chronically exposed to cigarette smoke, and their modifications by MSC. MAIN METHODS: Concentrations of IL-1ß, IL-6, IL-8, IL-12, TNF-α, INF-É£, TSG-6, MMP-9, TIMP-1, and/or TIMP-2 in serum and bronchoalveolar lavage (BALF) from animals exposed to tobacco smoke (20 cigarettes/day, 5 days/week for 10 weeks) were determined, and mRNA expression of some of them was measured in lung tissue. Intratracheal instillation of allogeneic bone marrow MSC (5x106 cells in 1 ml) was done at week 2. KEY FINDINGS: After cigarette smoke, IL-6 and IFN-γ increased in serum and BALF, while IL-1ß and IL-12 decreased in serum, and TSG-6 and TIMP-2 increased in BALF. IL-1ß had a paradoxical increase in BALF. MSC had an almost null effect in unexposed animals. The intratracheal administration of MSC in guinea pigs exposed to cigarette smoke was associated with a statistically significant decrease of IL-12 and TSG-6 in serum, as well as a decrease of IL-1ß and IFN-γ and an increase in TIMP-1 in BALF. Concerning mRNA expression in lung tissue, cigarette smoke did not modify the relative amount of the studied transcripts, but even so, MSC decreased the IL-12 mRNA and increased the TIMP-1 mRNA. SIGNIFICANCE: A single intratracheal instillation of MSC reduces the pulmonary and systemic proinflammatory pattern induced by chronic exposure to cigarette smoke in guinea pigs. TRIAL REGISTRATION: Not applicable.


Assuntos
Fumar Cigarros , Células-Tronco Mesenquimais , Cobaias , Animais , Citocinas/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2 , Interleucina-6/farmacologia , Fumar Cigarros/efeitos adversos , Pulmão/metabolismo , Interleucina-12/farmacologia , RNA Mensageiro , Células-Tronco Mesenquimais/metabolismo , Líquido da Lavagem Broncoalveolar
14.
J Ethnopharmacol ; 303: 116026, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36503031

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Wei-Qiang-Wei Powder (SWQ) is a formulated traditional Tibetan medicine preparation that has been used clinically to treat liver and gallbladder diseases for centuries. Previous work has confirmed its clinical effectiveness, however, the specific mechanism of SWQ is still unknown. AIM OF THE STUDY: This study aims to explore the anti-inflammatory effect of SWQ on cholecystitis and its possible mechanism. MATERIALS AND METHODS: The main chemical components of SWQ were analyzed by HPLC. The network pharmacology database was used to screen and construct the network of the main components and molecular targets of SWQ, and to predict the molecular pathways of its core targets. Cholecystitis guinea pig model and LPS stimulated cultured human gallbladder epithelial cells (HGBEC) were used, as in vivo and in vitro methods respectively, to study the anti-cholecystitis activity of SWQ. Specifically, gallbladder wall thickness, hematoxylin-eosin (H&E) staining, and liver function indexes were used to evaluate the anti-inflammatory activities of SWQ in cholecystitis; qRT-PCR and ELISA were used to detect the changes of the production of inflammatory cytokines; Western blot analysis was used to analyze the effects of SWQ on phosphorylation of P38, ERK1/2, JNK and AKT. RESULTS: SWQ decreased the indexes of ALT, AST, TBA, CHOL, DBIL in serum and TBIL, TC and Ca2+ in bile, and alleviated the wall thickness of gallbladder and hepatobiliary fibrosis in LCA-induced guinea pigs. In addition, SWQ attenuated the expression and production of TNF-α, IL-6, IL-1ß, COX-2 both in liver and gallbladder. Moreover, SWQ reversed the up-regulation of p-P38, p-ERK1/2, and p-JNK in animals with cholecystitis and LPS-induced HGBEC. Furthermore, mechanistic studies indicated that SWQ inhibited the activation of ERK1/2, thereby decreasing the expression of TNF-α, IL-6, IL-1ß and phosphorylation P38 and JNK. CONCLUSION: In summary, our research showed that SWQ relieves gallbladder inflammation by inhibiting the MAPK pathway.


Assuntos
Colecistite , Sistema de Sinalização das MAP Quinases , Humanos , Animais , Cobaias , Citocinas/metabolismo , Medicina Tradicional Tibetana , Pós , Fator de Necrose Tumoral alfa/metabolismo , Lipopolissacarídeos/farmacologia , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
15.
Schweiz Arch Tierheilkd ; 165(1): 59-63, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36562747

RESUMO

INTRODUCTION: In a guinea pig herd with 26 breeding animals, several individuals of all age categories died (16/26) after three animals had been newly introduced from another herd. Furthermore, the population suffered of apathy, anorexia, severe weight loss and conjunctivitis, as well as abortions and stillbirths. At the same time, the owner experienced a SARS-CoV-2 infection with pneumonia, which was confirmed by taking a PCR test. Chlamydia caviae was detected from the conjunctiva and vagina/uterus in one juvenile animal together with an intestinal Cryptosporidium wrairi infection. Oocysts were found histologically in the small intestine, which was confirmed by PCR. C. wairi is a parasite adapted to guinea pigs with zoonotic potential, which causes diarrhoea with frequent deaths in larger guinea pig herds. C. caviae is also a zoonotic pathogen and often the cause of conjunctivitis, pneumonia and abortions in guinea pigs and can lead to upper respiratory tract disease, conjunctivitis but also severe pneumonia in humans. The increased death cases and the clinical signs could be traced back to an infection with Cryptosporidium wrairi, complicated by a co-infection of C. caviae. We suspect that the abortions were caused by C. caviae, but since the population was treated with various antibiotics effective against chlamydial infections, it was no longer possible to verify this by PCR testing. Unfortunately, more animals succumbed and finally only two animals of the originally 26 were left. With this case report, we would like to point out to veterinarians that guinea pigs can be an important source of zoonotic infections for various pathogens, especially since they are popular pets and often come into close contact with children where hygiene might not always be strictly followed.


INTRODUCTION: Dans un groupe de cobayes de 26 animaux reproducteurs, plusieurs individus de toutes les catégories d'âge sont morts (16/26) après l'introduction de trois animaux provenant d'un autre groupe. En outre, la population a souffert d'apathie, d'anorexie, de perte de poids sévère et de conjonctivite ainsi que d'avortements et de mortinatalité. La présence de Chlamydia caviae a pu être détectée dans la conjonctive et le vagin/utérus d'un animal juvénile, ainsi qu'une infection intestinale à Cryptosporidium wrairi. Des oocystes ont été trouvés histologiquement dans l'intestin grêle, ce qui a été confirmé par PCR. C. wairi est un parasite adapté aux cobayes avec un potentiel zoonotique, qui provoque des diarrhées avec des morts fréquentes dans les grands groupes de cobayes. C. caviae est également un agent pathogène zoonotique et est souvent à l'origine de conjonctivites, de pneumonies et d'avortements chez les cobayes ; il peut entraîner des maladies des voies respiratoires supérieures, des conjonctivites mais aussi des pneumonies graves chez l'homme. L'augmentation des cas de décès et les signes cliniques pourraient être attribués à une infection par Cryptosporidium wrairi, compliquée par une co-infection par C. caviae. Nous soupçonnons que les avortements ont été causés par C. caviae, mais comme la population a été traitée avec divers antibiotiques efficaces contre les infections à chlamydia, il n'était plus possible de le vérifier par des tests PCR. Malheureusement, d'autres animaux ont succombé et il ne restait finalement que deux animaux sur les 26 d'origine. Avec ce rapport de cas, nous aimerions attirer l'attention des vétérinaires sur le fait que les cochons d'Inde peuvent être une source importante d'infections zoonotiques pour divers pathogènes, d'autant plus qu'il s'agit d'animaux de compagnie populaires qui sont souvent en contact étroit avec des enfants avec lesquels l'hygiène n'est pas toujours strictement respectée.


Assuntos
Infecções por Chlamydia , Conjuntivite , Criptosporidiose , Cobaias , Animais , Feminino , Humanos , Conjuntivite/epidemiologia , Conjuntivite/microbiologia , Conjuntivite/parasitologia , Conjuntivite/veterinária , Criptosporidiose/epidemiologia , Cryptosporidium , Surtos de Doenças/veterinária , Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/veterinária , Zoonoses/epidemiologia , Zoonoses/microbiologia , Zoonoses/parasitologia
16.
Eur J Pharm Biopharm ; 182: 128-140, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36549398

RESUMO

The role of inorganic nanoparticles in our society is increasing every day, from its use in sunscreens to their introduction in analytical laboratories, pharmacy, medicine, agricultural and other uses. Therefore, in order to establish precautions as well as correct handling of this type of material by operators, it is important to determine the ability of these compounds to travel through the different layers of the skin and to study their possible toxicological effects. In this sense, several authors have studied the ability of inorganic nanoparticles to penetrate the skin barrier by diverse methodologies in in vivo and in vitro modes. In the first case, most of the studies have been performed with animal skins that can imitate the human one (porcine, mouse and guinea pigs, among others), although human skin from surgery have been also explored. However, the use of animals is a common model that should be avoided in the following years due to ethical issues. In this sense, the use of in vitro methodologies is also usually selected to study the dermal absorption of nanoparticles through the skin. Nevertheless, most of the studies are performed with authentic animal skins, instead of the use of synthetic skins that imitate the permeability of our skin system, which has been scarcely studied. In addition, most of the literature is focused in achieving high-transdermal uptake to use nanoparticles (not only inorganic) as carriers for drugs, but little efforts have been done in the study of their inherent percutaneous absorption and toxicity. For these reasons, this review covers the current state-of-the-art of dermal absorption of inorganic nanoparticles in skin and their possible toxicity taking into account that people can be in contact with these nanomaterials in daily life, work or other places. In this sense, the observed results showed that the nanoparticles rarely reach the blood circulatory system, and no big toxicological effects were commonly found when in vivo and actual skin was used. In addition, similar results were found when synthetic skins were used, demonstrating the possibility of avoiding animals in these studies. In any case, more studies covering the dermal absorption of nanoparticles should be performed to have a better understanding of how nanoparticles can affect our health.


Assuntos
Nanopartículas , Nanoestruturas , Humanos , Animais , Camundongos , Cobaias , Absorção Cutânea , Pele/metabolismo , Administração Cutânea , Nanopartículas/toxicidade
17.
Am J Physiol Heart Circ Physiol ; 324(1): H141-H154, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36487188

RESUMO

Highlighting the importance of sex as a biological variable, we recently reported sex differences in guinea pig in vivo electrocardiogram (ECG) measurements. However, substantial inconsistencies exist in this animal model, with conflicting reports of sex-specific differences in cardiac electrophysiology observed in vivo and in vitro. Herein, we evaluated whether sexual dimorphism persists in ex vivo preparations, using an isolated intact heart preparation. Pseudo-ECG recordings were collected in conjunction with dual optical mapping of transmembrane voltage and intracellular calcium from Langendorff-perfused hearts. In contrast to our in vivo results, we did not observe sex-specific differences in ECG parameters collected from isolated hearts. Furthermore, we observed significant age-specific differences in action potential duration (APD) and Ca2+ transient duration (CaD) during both normal sinus rhythm (NSR) and in response to dynamic pacing but only a modest sex-specific difference in CaD30. Similarly, the alternans fluctuation coefficient, conduction velocity during sinus rhythm or in response to pacing, and electrophysiology parameters (atrioventricular nodal effective refractory period, Wenckebach cycle length) were comparable between males and females. Results of our study suggest that the observed sex-specific differences in in vivo ECG parameters from guinea pigs are diminished in ex vivo isolated heart preparations, although age-specific patterns are prevalent. To assess sex as a biological variable in cardiac electrophysiology, a comprehensive approach may be necessary using both in vitro measurements from cardiomyocyte or intact heart preparations with secondary follow-up in vivo studies.NEW & NOTEWORTHY We evaluated whether the guinea pig heart has intrinsic sex-specific differences in cardiac electrophysiology. Although we observed sex-specific differences in in vivo ECGs, these differences did not persist ex vivo. Using a whole heart model, we observed similar APD, CaD, conduction velocity, and alternans susceptibility in males and females. We conclude that sex-specific differences in guinea pig cardiac electrophysiology are likely influenced by the in vivo environment and less dependent on the intrinsic electrical properties of the heart.


Assuntos
Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco , Cobaias , Feminino , Animais , Masculino , Coração/fisiologia , Eletrocardiografia , Miócitos Cardíacos/fisiologia , Arritmias Cardíacas , Potenciais de Ação
18.
Antiviral Res ; 210: 105496, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36567020

RESUMO

Development of lethal models of Ebola virus disease has been achieved by the serial passage of virus isolates from human cases in mice and guinea pigs. Use of mice infected with non-adapted virus has been limited due to the absence of overt clinical disease. In recent years, newly recognized sequelae identified in human cases has highlighted the importance of continued investigations of non-lethal infection both in humans and animal models. Here, we revisit the use of rodent-adapted and non-adapted Ebola virus (EBOV) in mice to investigate infection tolerance and future utility of these models in pathogenesis and therapeutic intervention studies. We found that like non-adapted wild-type EBOV, guinea pig-adapted EBOV resulted in widespread tissue infection, variably associated with tissue pathology, and alterations in clinical and immunological analytes in the absence of overt disease. Notably, infection with either non-lethal variant did not greatly differ from lethal mouse-adapted EBOV until near the time end-point criteria are reached in these mice. These data support future investigations of pathogenesis, convalescence, and sequelae in mouse models of virus tolerance.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Cobaias , Humanos , Animais , Camundongos , Ebolavirus/genética , Modelos Animais de Doenças
19.
Antiviral Res ; 210: 105493, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36567023

RESUMO

Ebola virus (EBOV) is a member of the filoviridae family, which are comprised of negative sense, enveloped RNA hemorrhagic fever viruses that can cause severe disease and high lethality rates. These viruses require BSL-4 containment laboratories for study. Early studies of EBOV pathogenesis relied heavily on the use of nonhuman primates, which are expensive and cumbersome to handle in large numbers. Guinea pig models were also developed, but even to this day limited reagents are available in this model. In 1998, Mike Bray and colleagues developed a mouse-adapted EBOV (maEBOV) that caused lethality in adult immunocompetent mice. This model had significant advantages, including being inexpensive, allowing for higher animal numbers for statistical analysis, availability of reagents for studying pathogenesis, and availability of a vast array of genetically modified strains. The model has been used to test vaccines, therapeutic drugs, EBOV mutants, and pathogenesis, and its importance is demonstrated by the hundreds of citations referencing the original publication. This review will cover the history of the maEBOV model and its use in filovirus research.


Assuntos
Ebolavirus , Infecções por Filoviridae , Doença pelo Vírus Ebola , Animais , Camundongos , Cobaias , Ebolavirus/genética , Modelos Animais de Doenças
20.
Hear Res ; 428: 108667, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36566642

RESUMO

The startle reflex (SR), a robust, motor response elicited by an intense auditory, visual, or somatosensory stimulus has been widely used as a tool to assess psychophysiology in humans and animals for almost a century in diverse fields such as schizophrenia, bipolar disorder, hearing loss, and tinnitus. Previously, SR waveforms have been ignored, or assessed with basic statistical techniques and/or simple template matching paradigms. This has led to considerable variability in SR studies from different laboratories, and species. In an effort to standardize SR assessment methods, we developed a machine learning algorithm and workflow to automatically classify SR waveforms in virtually any animal model including mice, rats, guinea pigs, and gerbils obtained with various paradigms and modalities from several laboratories. The universal features common to SR waveforms of various species and paradigms are examined and discussed in the context of each animal model. The procedure describes common results using the SR across species and how to fully implement the open-source R implementation. Since SR is widely used to investigate toxicological or pharmaceutical efficacy, a detailed and universal SR waveform classification protocol should be developed to aid in standardizing SR assessment procedures across different laboratories and species. This machine learning-based method will improve data reliability and translatability between labs that use the startle reflex paradigm.


Assuntos
Reflexo de Sobressalto , Zumbido , Humanos , Ratos , Camundongos , Animais , Cobaias , Reflexo de Sobressalto/fisiologia , Estimulação Acústica/métodos , Reprodutibilidade dos Testes , Modelos Animais de Doenças , Gerbillinae
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