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BACKGROUND: GPP is a rare, chronic, neutrophilic skin disease, with limited real-world data characterizing patients with flares and the impact of flares on disease progression and morbidity. OBJECTIVE: Describe the clinical characteristics of patients with GPP, comorbidities, disease epidemiology and frequency and severity of flares, and compare patients with GPP with a matched severe psoriasis population. METHODS: In this population-based real-world cohort study an algorithm was developed to identify patients with GPP flares. Three cohorts were identified using the Système National des Données de Santé (SNDS) database covering almost the entire French population; a prevalent cohort (2010-2018), an incident cohort (2012-2015). A severe psoriasis cohort was compared with the GPP incident cohort using propensity score matching. RESULTS: The prevalent and incident cohorts comprised 4195 and 1842 patients, respectively. In both cohorts, mean age was 58 years; 53% were male. Comorbidities were significantly more common in the incident cohort versus matched psoriasis cohort, respectively, including hypertension (44% vs. 26%), ischaemic heart disease (26% vs. 18%) and hyperlipidaemia (25% vs. 15%). In the incident cohort, the flare rate was 0.1 flares/person-year and 0.4 flares/person-year among the 569 out of 1842 patients hospitalized with flares. These patients had a mean (±SD) stay of 11.6 ± 10.4 days; 25% were admitted to the intensive care unit. In 2017, the cumulative incidence and cumulative GPP age-sex standardized prevalence were 7.1 and 45.2 per million, respectively. CONCLUSIONS: Patients with GPP had a distinct comorbidity profile compared to patients with severe psoriasis, and GPP flares were associated with long hospitalizations.
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Psoríase , Humanos , Psoríase/epidemiologia , França/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Bases de Dados Factuais , Comorbidade , Incidência , Prevalência , Índice de Gravidade de Doença , Estudos de Coortes , Hospitalização/estatística & dados numéricos , Adulto Jovem , Hipertensão/epidemiologia , AdolescenteRESUMO
In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.
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Nanopartículas , Neoplasias , Humanos , Lipossomos/uso terapêutico , Portadores de Fármacos/química , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológicoRESUMO
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.
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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 BroncoalveolarRESUMO
One of the main functions of infrared thermography (IRT) consists in detecting temperature changes in organisms caused by variations in surface blood circulation. IRT is a useful tool that has been used mainly as a diagnostic method for various stress-causing pathologies, though recent suggestions indicate that it can be used to assess the block quality of certain body regions. In the field of anaesthesiology, IRT has been applied to brachial and epidural blocks, while in algology, changes in surface blood circulation associated with sympathetic activity have been investigated. Thermography has also been employed to complement pain level scales based on the facial expressions of patients in critical condition, or after surgery. In addition, it has been used as a tool in research designed to evaluate different surgical procedures in human medicine, as in the case of surgical burrs for placing dental implants, where IRT helps assess the degree of heating associated with bone devascularisation, reduction in vascular perfusion as a consequence of stroke, and changes in the autonomous nervous system, or the degree of vascular changes in flaps applied to burn patients. In veterinary medicine, thermography has brought several benefits for animals in terms of evaluating lesions, diseases, and surgical procedures. The aim of this review is to evaluate how IRT can be used as a tool in surgical procedures, cases of vascular change, and pain monitoring in veterinary medicine with an emphasis on small animals.
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Hemodinâmica , Dor/diagnóstico , Termografia/métodos , Animais , Humanos , Raios Infravermelhos , Microcirculação , Dor/veterinária , Temperatura Cutânea , Termografia/instrumentação , Termografia/veterinária , Medicina Veterinária/métodosRESUMO
AIM OF THE STUDY: Long-term exposure to cigarette smoke generates chronic obstructive pulmonary disease (COPD) in guinea pigs, but a comprehensive evaluation of changes in lung function, as assessed by barometric whole body plethysmography (WBP), is lacking. MATERIALS AND METHODS: Female guinea pigs were exposed to the smoke of 20 cigarettes/day, 5 days/week, during 10 weeks (COPD group, n = 8), and were compared with unexposed female guinea pigs of the same age (control group, n = 8). WBP was performed in both groups, followed by lung histology. RESULTS: At the end of the exposure period, guinea pigs in the COPD group had higher respiratory frequency, while duty cycle (Ti/Ttot) was unaffected. There was a trend toward minute ventilation (MV) and expiratory flow at the mid-tidal volume (EF50) to be higher in the COPD group. Enhanced pause (Penh) was lower, while time of braking (TB) and time to PEF relative to Te (Rpef) were higher in the COPD group. All guinea pigs exposed to tobacco smoke developed emphysematous lesions in their lungs and gained less body weight than controls. CONCLUSIONS: In this COPD model, exposure to cigarette smoke produced changes in WBP characterized by a shallow breathing pattern with decreased Penh and a trend toward increasing EF50 (probably due to decreased elastic recoil), increased TB (suggesting dynamic laryngeal narrowing), and a trend of increasing MV (probably due to a higher metabolic rate). Many of these functional changes resemble those observed in patients with COPD and corroborate the suitability of this guinea pig model for the study of COPD.
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Pletismografia/métodos , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumaça/efeitos adversos , Animais , Modelos Animais de Doenças , Feminino , Cobaias , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ventilação Pulmonar , Respiração , Testes de Função Respiratória , Volume de Ventilação Pulmonar , Produtos do TabacoRESUMO
Granulomatous amoebic encephalitis (GAE) is a chronic, difficult to resolve infection caused by amphizoic amoebae of the genus Acanthamoeba, which in most cases occurs in immunosuppressed persons or with chronic diseases such as diabetes. In this study, we describe the early events of A. culbertsoni infection of GAE in diabetic mice model. Diabetes was induced in male BALB/c mice, with a dose of streptozotocin (130 mg/kg). Healthy and diabetic mice were inoculated via intranasal with 1 × 106 trophozoites of A. culbertsoni. Then were sacrificed and fixed by perfusion at 24, 48, 72 and 96 h post-inoculation, the brains and nasopharyngeal meatus were processed to immunohistochemical analysis. Invasion of trophozoites in diabetic mice was significantly greater with respect to inoculated healthy mice. Trophozoites and scarce cysts were immunolocalized in respiratory epithelial adjacent bone tissue, olfactory nerve packets, Schwann cells and the epineurium base since early 24 h post-inoculation. After 48 h, trophozoites were observed in the respiratory epithelium, white matter of the brain, subcortical central cortex and nasopharyngeal associated lymphoid tissue (NALT). At 72 h, cysts and trophozoites were immunolocalized in the olfactory bulb with the presence of a low inflammatory infiltrate characterized by polymorphonuclear cells. Scarce amoebae were observed in the granular layer of the cerebellum without evidence of inflammation or tissue damage. No amoebas were observed at 96 h after inoculation, suggesting penetration to other tissues at this time. In line with this, no inflammatory infiltrate was observed in the surrounding tissues where the amoebae were immunolocalized, which could contribute to the rapid spread of infection, particularly in diabetic mice. All data suggest that trophozoites invade the tissues by separating the superficial cells, penetrating between the junctions without causing cytolytic effect in the adjacent cells and subsequently reaching the CNS, importantly, diabetes increases the susceptibility to amoebae infection, which could favor the GAE development.
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Acanthamoeba/patogenicidade , Amebíase/etiologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Encefalite/parasitologia , Acanthamoeba/fisiologia , Animais , Encéfalo/parasitologia , Encéfalo/patologia , Cerebelo/parasitologia , Cerebelo/patologia , Suscetibilidade a Doenças , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nasofaringe/parasitologia , Nasofaringe/patologia , Bulbo Olfatório/parasitologia , Bulbo Olfatório/patologia , Inoculações Seriadas , Trofozoítos , VirulênciaRESUMO
This study was developed in order to describe the early morphological events observed during the invasion of two pathogenic strains of Acanthamoeba (genotype T4); A. castellanii and A. culbertsoni, at the olfactory meatus and cerebral, pulmonary, renal, hepatic and splenic tissues levels, an in vivo invasion study. Histological and immunohistochemical description of the events at 24, 48, 72, and 96 h postintranasal inoculations of BALB/c mice was performed. A. castellanii showed a higher invasion rate than A. culbertsoni, which was only able to reach lung and brain tissue in the in vivo model. The current study supports previous evidence of lack of inflammatory response during the early stages of infection. Acanthamoeba invasion of the CNS and other organs is a slow and contact-dependent process. The early morphological events during the invasion of amoebae include the penetration of trophozoites into different epithelia: olfactory, respiratory, alveolar space, and renal tubule, which resemble the process of amoebae invasion described in corneal tissue. The data suggest that after reaching the nasal epithelium, trophozoites continued invasion, separating and lifting the most superficial cells, then migrating and penetrating between the cell junctions without causing a cytolytic effect on adjacent cells. These results reaffirm the idea that contact-dependent mechanisms are relevant for amoebae of Acanthamoeba genus regardless of the invasion site.
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Acanthamoeba/patogenicidade , Amebíase/patologia , Sistema Nervoso Central/parasitologia , Túbulos Renais/parasitologia , Mucosa Nasal/parasitologia , Mucosa Respiratória/parasitologia , Trofozoítos/metabolismo , Animais , Córnea/parasitologia , Modelos Animais de Doenças , Genótipo , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB CRESUMO
OBJECTIVES: This study aimed to assess the association between the appearance of intussusception in children and medication intake in the immediately preceding period (2-15 days). METHODS: A case-crossover design was used. We selected cases of children admitted with a diagnosis of intussusception (International Classification of Diseases, Ninth Revision, 860) to the major hospitals in the city of Valencia, Spain, from 2006 to 2009. We then estimated the association between the episode of intussusception and the intake of prescription medication during the preceding 2, 7, and 15 days (case period) and for the same time window 1, 2, 3, and 4 months prior (control period). Data on previous drug administration were obtained from the Pharmaceutical Service Manager System. RESULTS: A total of 95 cases (65.3% boys and 34.7% girls) were selected; 76.6% were younger than the age of 2 years. The association between intussusception and prior drug use varied depending on the exposure window: 15-day odds ratio (OR), 1.45 (95% confidence interval [95% CI], 0.86-2.43); 7-day OR, 1.46 (95% CI, 0.80-2.67); and 2-day OR, 2.26 (95% CI, 1.10-4.64). These associations were greater for children aged younger than 2 years and were usually due to the recent administration (preceding 2 days) of antibiotics (OR, 8.00; 95% CI, 1.47-43.7). CONCLUSIONS: Intussusception was more common among boys aged younger than 2 years. A positive and significant association was observed when drugs were administered 2 to 7 days before the onset of symptoms in children younger than the age of 2 years.
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Antibacterianos/efeitos adversos , Intussuscepção/induzido quimicamente , Pré-Escolar , Estudos Cross-Over , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Intussuscepção/diagnóstico , Intussuscepção/epidemiologia , Masculino , Estudos Retrospectivos , Espanha/epidemiologia , Centros de Atenção TerciáriaRESUMO
Treatment of fatty acid oxidation disorders is based on dietary, pharmacological and metabolic decompensation measures. It is essential to provide the patient with sufficient glucose to prevent lipolysis and to avoid the use of fatty acids as fuel as far as possible. Dietary management consists of preventing periods of fasting and restricting fat intake by increasing carbohydrate intake, while maintaining an adequate and uninterrupted caloric intake. In long-chain deficits, long-chain triglyceride restriction should be 10% of total energy, with linoleic acid and linolenic acid intake of 3-4% and 0.5-1% (5/1-10/1 ratio), with medium-chain triglyceride supplementation at 10-25% of total energy (total MCT+LCT ratio = 20-35%). Trihepatnoin is a new therapeutic option with a good safety and efficacy profile. Patients at risk of rhabdomyolysis should ingest MCT or carbohydrates or a combination of both 20 min before exercise. In medium- and short-chain deficits, dietary modifications are not advised (except during exacerbations), with MCT contraindicated and slow sugars recommended 20 min before any significant physical exertion. Parents should be alerted to the need to increase the amount and frequency of carbohydrate intake in stressful situations. The main measure in emergency hospital treatment is the administration of IV glucose. The use of carnitine remains controversial and new therapeutic options are under investigation.
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Ácidos Graxos , Humanos , Ácidos Graxos/administração & dosagem , Oxirredução , Carboidratos da Dieta/administração & dosagem , Erros Inatos do Metabolismo Lipídico/dietoterapia , Triglicerídeos/sangue , Carnitina/administração & dosagem , Suplementos Nutricionais , RabdomióliseRESUMO
A solitary extraosseous plasmacytoma is a rare type of plasma cell neoplasm. Its occurrence in the stomach is particularly unusual and can easily be mistaken for more common types of tumors. We describe a case involving a solitary extraosseous plasmacytoma in a patient who experienced weight loss as the sole symptom. Initially, the condition was misdiagnosed as gastric adenocarcinoma based on endoscopic biopsy results, leading to a gastrectomy after neoadjuvant chemotherapy. Subsequent examination of the pathological specimen revealed the presence of plasma cell neoplasia alongside a gastric adenocarcinoma in situ.
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BACKGROUND: Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus (T2DM), that is, patients who have insulin resistance, obesity, and other cardiovascular risk factors, suggesting that the presence of glutamic acid decarboxylase (anti-GAD65), islet antigen 2 (anti-IA2), and zinc transporter 8 (anti-Zn8T) antibodies could have deleterious effects on beta cell function, causing failure and earlier requirement for insulin treatment. AIM: To evaluate anti-GAD65, anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of T2DM. METHODS: This was a case-control study in patients with clinically diagnosed with T2DM (68 cases and 64 controls with and without early insulin dependence respectively), male and female, aged 12-18 years. Somatometry, blood pressure, glucose, insulin, C-peptide, glycated hemoglobin A1c, and lipid profiles were assessed. ELISA was used to measure anti-GAD65, anti-IA2, and anti-Zn8T antibodies. Descriptive statistics, Pearson's χ 2 test, Student's t test, and logistic regression was performed. P < 0.05 was considered statistically significant. RESULTS: There were 132 patients (53.8% female), with a mean age was 15.9 ± 1.3 years, and there was a disease evolution time of 4.49 ± 0.88 years. The presence of anti-GAD65, anti-IA2, and anti-Zn8T positivity was found in 29.5%, 18.2%, and 15.9%, respectively. Dividing the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity: anti-GAD65 odds ratio (OR): 2.42 (1.112-5.303, P = 0.026); anti-IA2: OR: 1.55 (0.859-2.818, P = 0.105); and anti-Zn8T: OR: 7.32 (2.039-26.279, P = 0.002). CONCLUSION: Anti-GAD65 positivity was high in our study. Anti-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype, leading to an increased risk of early insulin dependence.
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The cow-calf bonding is a process that must be developed within the first six hours after calving. Both the buffalo dam and the newborn calf receive a series of sensory cues during calving, including olfactory, tactile, auditory, and visual stimuli. These inputs are processed in the brain to develop an exclusive bond where the dam provides selective care to the filial newborn. The limbic system, sensory cortices, and maternal-related hormones such as oxytocin mediate this process. Due to the complex integration of the maternal response towards the newborn, this paper aims to review the development of the cow-calf bonding process in water buffalo (Bubalus bubalis) via the olfactory, tactile, auditory, and visual stimuli. It will also discuss the neuroendocrine factors motivating buffalo cows to care for the calf using examples in other ruminant species where dam-newborn bonding has been extensively studied.
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The negative effects of pain are a constant concern in the surgical management of animals, leading to the search for new drugs or more effective analgesic protocols to control this negative emotion. This study aimed to evaluate the nociceptive response of cannabidiol (CBD) alone and in combination with meloxicam using infrared pupillometry in female dogs undergoing elective ovariohysterectomy (OVH) under isoflurane anesthesia. A total of 60 female dogs of different breeds were included. These dogs were randomly assigned to four study groups according to the treatment: Control Group (G0: n = 15) receiving saline solution; group premedicated with meloxicam at a dose of 0.2 mg Kg-1 IV (GMelox: n = 15). Postoperatively this drug was used at 0.1 mg Kg-1 IV every 24 h; the CBD-treated Group (GCBD: n = 15) at a dose of 2 mg Kg-1 orally in the preoperative. Postoperatively was administrated every 12 h; and the Group premedicated with the combination of meloxicam and CBD (GMelox/CBD: n = 15) Meloxicam at a dose of 0.2 mg Kg-1 IV preoperatively, and 0.1 mg Kg-1 IV during the postoperative. CBD at a dose of 2 mg Kg-1 orally in the preoperative, and every 12 h in the postoperative. Treatments were administered for 48 postoperative hours. After OVH, the pupillary neurologic index, pupillary size, minimum diameter (MIN), percentage change, constriction latency (Lat), constriction velocity, and maximum constriction velocity were recorded as pupillometric variables in both eyes during events (E): Baseline (30 min before drug administration), E30 min, E1h, E2h, E3h, E4h, E8h, E12h, E24h, and E48h. The Short-Form of the Glasgow Composite Measure Pain Scale (GCMPS-SF) was used to assess pain during the same events. Overall, it was observed that the pupillometric variables Size, MIN., and Lat. were significantly higher in G0 compared to the other groups during E30 min, E1h, and E2h (p = 0.03), indicating greater pupil dilation in G0 animals. Additionally, no statistically significant differences were observed in GCMPS-SF between GMelox, GCBD, and GMelox/CBD during the postoperative period (p > 0.05). In contrast, the scores were statistically different compared to G0 (p = 0.00001), where all animals in this group received rescue analgesia at 2 h post-surgery. According to pupillometry and scores on the GCMPS-SF scale, it was observed that monotherapy with cannabidiol provides a similar analgesic effect to meloxicam alone or in combination with cannabidiol to manage acute pain in dogs. Similarly, these findings suggest that infrared pupillometry could be a tool for recognizing acute pain in dogs.
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The present review has two objectives, the first is to investigate the differences in temperament between Bos indicus and Bos taurus breeds and determining the effects on production due to positive treatment and to compare this with negative HAR, by using the Five Domain Model as framework. The second objective is to discuss potential strategies to achieve better HAR when working with Bos indicus cattle. Bos indicus are more reactive and temperamental than Bos taurus cattle. When human animal relationships (HAR) are evaluated, Bos indicus cattle may react with greater intensity. They may be more likely to develop a negative emotional state, especially in extensively raised Bos indicus cattle that are handled only a few times each year. Bos indicus cattle can have positive emotional states when they have frequent positive interactions with people. Interactions with people, both positive and negative, would be in the fourth Domain of the Five Domains model. Cattle that are more reactive during handling may also have lower weight gain, even when they have abundant feed. This would be in the first Domain of Nutrition. When cattle are handled in races and corrals, injuries may be more likely to occur. Injuries and bruises would be in the third Domain of Health. Injuries could be caused by either poor handling practices by people or poor handling facilities. Yelling or electric prod use would be examples of poor HAR. Second Environmental Domain issues may be broken facilities or slick, slippery floors that are associated with falls.
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Over the last decade, scientists have shifted their focus to the development of smart carriers for the delivery of chemotherapeutics in order to overcome the problems associated with traditional chemotherapy, such as poor aqueous solubility and bioavailability, low selectivity and targeting specificity, off-target drug side effects, and damage to surrounding healthy tissues. Nanofiber-based drug delivery systems have recently emerged as a promising drug delivery system in cancer therapy owing to their unique structural and functional properties, including tunable interconnected porosity, a high surface-to-volume ratio associated with high entrapment efficiency and drug loading capacity, and high mass transport properties, which allow for controlled and targeted drug delivery. In addition, they are biocompatible, biodegradable, and capable of surface functionalization, allowing for target-specific delivery and drug release. One of the most common fiber production methods is electrospinning, even though the relatively two-dimensional (2D) tightly packed fiber structures and low production rates have limited its performance. Forcespinning is an alternative spinning technology that generates high-throughput, continuous polymeric nanofibers with 3D structures. Unlike electrospinning, forcespinning generates fibers by centrifugal forces rather than electrostatic forces, resulting in significantly higher fiber production. The functionalization of nanocarriers on nanofibers can result in smart nanofibers with anticancer capabilities that can be activated by external stimuli, such as light. This review addresses current trends and potential applications of light-responsive and dual-stimuli-responsive electro- and forcespun smart nanofibers in cancer therapy, with a particular emphasis on functionalizing nanofiber surfaces and developing nano-in-nanofiber emerging delivery systems for dual-controlled drug release and high-precision tumor targeting. In addition, the progress and prospective diagnostic and therapeutic applications of light-responsive and dual-stimuli-responsive smart nanofibers are discussed in the context of combination cancer therapy.
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Several types of enrichment can be used to improve animal welfare. This review summarizes the literature on the use of mechanical brushes, tactile udder stimulation, music, and visual stimuli as enrichment methods for dairy cows. Mechanical brushes and tactile stimulation of the udder have been shown to have a positive effect on milk yield and overall behavioral repertoire, enhancing natural behavior. Classical music reduces stress levels and has similarly been associated with increased milk yield. A slow or moderate tempo (70 to 100 bpm) at frequencies below 70 dB is recommended to have this positive effect. Evidence on the impacts of other types of enrichment, such as visual stimulation through mirrors, pictures, and color lights, or the use of olfactory stimuli, is equivocal and requires further study.
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Infrared Thermography (IRT) has become an assistance tool in medicine and is used to noninvasively evaluate heat elimination during and after inflammatory processes or during the recovery period. However, its application in veterinary patients undergoing physiotherapy is a field that requires deep research. This review aims to analyze the application of IRT in the monitoring of animal physiotherapy, using the thermal changes that are present in patients undergoing gait or lameness issues (e.g., inflammation, pain, increased local temperature) as a neurobiological basis. Rehabilitation techniques such as acupuncture, physical therapies, thermotherapy, photo-biomodulation, and electrostimulation have been reported to have an anti-inflammatory effect that decreases the amount of local heat production, which is heat that can be recorded with IRT. Therefore, IRT could be used as a complementary tool to evaluate the effectiveness of the therapy, and it is suggested that further studies evaluate the accuracy, sensibility, and sensitivity of IRT.
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Parkinson's disease is the second most prevalent neurodegenerative disease in the world. Its treatment is limited so far to the management of parkinsonian symptoms with L-DOPA (LD). The long-term use of LD is limited by the development of L-DOPA-induced dyskinesias and dystonia. However, recent studies have suggested that pharmacological targeting of the endocannabinoid system may potentially provide a valuable therapeutic tool to suppress these motor alterations. In the present study, we have explored the behavioral (L-DOPA-induced dyskinesias severity) and cytological (substantia nigra compacta neurons and striatum neuropil preservation) effects of the oral coadministration of LD and rimonabant, a selective antagonist of CB1 receptors, in the 6-hydroxydopamine rat model of Parkinson's disease. Oral coadministration of LD (30 mg/kg) and rimonabant (1 mg/kg) significantly decreased abnormal involuntary movements and dystonia, possibly through the conservation of some functional tyrosine hydroxylase-immunoreactive dopaminergic cells, which in turn translates into a well-preserved neuropil of a less denervated striatum. Our results provide anatomical evidence that long-term coadministration of LD with cannabinoid antagonist-based therapy may not only alleviate specific motor symptoms but also delay/arrest the degeneration of striatal and substantia nigra compacta cells.
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Antagonistas de Receptores de Canabinoides/uso terapêutico , Di-Hidroxifenilalanina/administração & dosagem , Di-Hidroxifenilalanina/uso terapêutico , Discinesia Induzida por Medicamentos/tratamento farmacológico , Degeneração Neural/patologia , Transtornos Parkinsonianos/tratamento farmacológico , Piperidinas/uso terapêutico , Pirazóis/uso terapêutico , Administração Oral , Animais , Antagonistas de Receptores de Canabinoides/farmacologia , Corpo Estriado/citologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/ultraestrutura , Di-Hidroxifenilalanina/farmacologia , Modelos Animais de Doenças , Dopaminérgicos/administração & dosagem , Dopaminérgicos/farmacologia , Dopaminérgicos/uso terapêutico , Quimioterapia Combinada , Masculino , Degeneração Neural/tratamento farmacológico , Neurópilo/citologia , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , Piperidinas/administração & dosagem , Piperidinas/farmacologia , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Ratos , Rimonabanto , Substância Negra/citologia , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Several contractile mediators involved in the antigen-induced airway obstruction have been identified, but the role of 5-HT (5-hydroxytryptamine or serotonin) has been scantily investigated. In this work, the potential role of 5-HT in the allergic bronchoconstriction was evaluated through a pharmacological approach and plasma 5-HT measurement in blood samples from the right and left ventricles of anesthetized guinea-pigs. Intravenous 5-HT caused a dose-dependent increase of the lung resistance in anesthetized, nonsensitized guinea pigs. Likewise, in sensitized animals the antigenic challenge with ovalbumin also caused a transient bronchoconstriction (356 ± 60% the basal value), which was largely inhibited by the blockade of serotonergic receptors with methiothepin plus tropisetron (134 ± 10%, P = .007). Sensitized animals tended to have plasma 5-HT concentrations higher than nonsensitized controls, and shortly after the peak of the allergic bronchoconstriction the 5-HT levels in the left ventricle (blood flowing out from lungs) tended to be higher than in the right ventricle (blood entering the lungs), although data dispersion precluded the obtaining of statistical significance. Interestingly, the degree of bronchoconstriction highly correlated with the concentrations of 5-HT found in the left ventricle and measured either in platelet-rich plasma (r = 0.97 P = .007) or platelet-poor plasma (r = 0.97, P = .006). After the obstructive response subsided these correlations were lost, but now the degree of bronchoconstriction turned to be correlated with 5-HT concentration in platelet concentrate (r = 0.76, P = .03). In conclusion, our results suggested that 5-HT is actively released from lungs during the antigenic challenge and that this autacoid is involved in the generation of the airway obstruction.
Assuntos
Alérgenos/efeitos adversos , Broncoconstrição/fisiologia , Ovalbumina/efeitos adversos , Serotonina/sangue , Alérgenos/farmacologia , Animais , Broncoconstrição/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Cobaias , Ventrículos do Coração/fisiopatologia , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Ovalbumina/farmacologiaRESUMO
Practically all organs of the respiratory system are under the control of the autonomic nervous system. Double vegetative innervation, sympathetic and parasympathetic, contributes to the regulation of airway smooth muscle tone, and modulates secretion from the submucosal glands. Nevertheless, more than 20 years ago, the classical view of excitatory cholinergic and inhibitory adrenergic innervation changed considerably when the existence was proved of the non-adrenergic non-cholinergic system (NANC), which is able to produce both effects. Several purines and peptides have been postulated as neurotransmitters of this system, and some of them coexist with the acetylcholine or norepinephrine; for example, vasoactive intestinal peptide (VIP) on cholinergic nerves and neuropeptide Y in the adrenergic nerves. The aim of this paper is to describe the anatomo-physiological aspects of the airways' autonomic innervation and the possible implication of a neural mechanism that contributes in the development of the symptomatology in respiratory diseases.