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1.
Toxicol Lett ; 320: 109-112, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31778775

RESUMO

BACKGROUND: Since 2016 an increase has been observed in the availability of new synthetic opioids (NSO) in Europe. Cyclopropylfentanyl is a very potent and selective µ-opioid agonist, which was reported for the first time in August 2017 in Europe. METHODS: The case was included in a prospective observational study of patients treated in emergency departments after the intake of novel psychoactive substances (NPS). Clinical features were acquired using a structured questionnaire for physicians. Serum and/or urine samples of ED patients were analyzed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) screening methods for NPS. CASE REPORT: Within 10 min after intranasal intake of fentanyl, a 25-year-old male developed nausea, profuse sweating and dyspnoe. Because soon afterwards coma and respiratory insufficiency was noticed, the patient was admitted to hospital. After administration of naloxone (0.8 mg) breathing stabilized. However, the patient displayed recurrent decreases of oxygen saturation for 12 h. The intake of cyclopropylfentanyl was analytically confirmed. CONCLUSION: The constantly growing diversity of NSO still poses a high risk for drug users and can be a challenging task for clinicians and forensic toxicologists. Clinicians treating opioid overdoses should be aware of the potentially long lasting respiratory depression induced by fentanyl analogs.


Assuntos
Analgésicos Opioides/envenenamento , Overdose de Drogas/diagnóstico , Fentanila/análogos & derivados , Transtornos Relacionados ao Uso de Opioides , Detecção do Abuso de Substâncias/métodos , Administração Intranasal , Adulto , Aerossóis , Analgésicos Opioides/administração & dosagem , Cromatografia Líquida de Alta Pressão , Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/fisiopatologia , Fentanila/administração & dosagem , Fentanila/envenenamento , Humanos , Masculino , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Resultado do Tratamento
2.
Quintessence Int ; 51(2): 162-167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31538149

RESUMO

OBJECTIVE: Intranasal midazolam (INM) is an increasingly popular agent for sedation in the emergency department and outside the hospital in physician, imaging, and dental offices, to facilitate diagnostic and minor surgical procedures and avoid the need for an operating room and general anesthesia. The use of INM has been commonly associated with a burning sensation of the nasal mucosa. Despite its significance, this subject has received little adequate research focus. The objective of the current study was to evaluate the effectiveness of topical lidocaine in relieving pain related to INM administration. METHOD AND MATERIALS: This was a blinded, randomized placebo-controlled trial. Sixty-three uncooperative children undergoing dental treatment, aged 4 to 11 years, were randomly assigned to one of three groups to receive the drug nasally via a precalibrated spray as per the following assignments: group A received 0.5 mg/kg midazolam, group B received lidocaine 2% prior to 0.5 mg/kg midazolam, and group C received saline 0.9% (placebo), 0.5 mg/kg. Children were asked to record the degree of pain using the Wong-Baker faces scale. Parental acceptance was also rated. RESULTS: Topical lidocaine prior to INM administration reduced the burning sensation in the nasal mucosa and improved the drug acceptance. The median score of pain was 8, 1, and 4 in groups A, B, and C, respectively. The differences among the three groups were statistically significant (P > .05). The children's acceptance and parents' future acceptance regarding the intranasal drug administration was significantly higher in group B. CONCLUSION: INM administration results in burning sensation in the nasal mucosa with high levels of pain. Using topical lidocaine 2% counteracted the burning sensation and achieved a higher acceptance rate and lower pain scores.


Assuntos
Lidocaína , Midazolam , Administração Intranasal , Criança , Pré-Escolar , Método Duplo-Cego , Humanos , Dor
3.
Vestn Otorinolaringol ; 84(5): 61-67, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31793529

RESUMO

The aim of the study was proof of efficacy and safety of the drug Frinozol nasal spray in patients with acute respiratory infection (acute rhinitis). PATIENTS AND METHODS: A randomized open-label study with active control included 134 ambulatory patients: men and women aged 18 to 65 years with acute upper respiratory tract infection (acute rhinitis) lasting no more than 48 hours before inclusion into the study. Patients were randomized in two groups: group 1 took Frinozol nasal spray 2 sprays per each nostril three times a day for 7 days, subjects randomized to the group 2 took Vibrocil at the same dose and treatment regimen. The primary efficacy endpoint in the study was assessment of the dynamics of symptoms such as nasal congestion, rhinorrhea, itching in the nose and hyposmia using 10 cm VAS in 1 day after the start of treatment compared to the baseline. Secondary endpoints included assessment of the dynamics of nasal symptoms after 7 days of treatment, changes in the values of the Congestion Quantifier 5, CQ-5 questionnaire and evaluation of the effectiveness by the investigator. Safety analysis was carried out throughout the study and included the assessment of adverse events, laboratory data, vital signs, ECG assessment. RESULTS: According to the results of the study and comparative analysis of the primary (assessment of the dynamics of nasal symptoms on a 10 cm visual analogue scale 1 day after the start of treatment) and secondary efficacy endpoints as well as a comprehensive safety analysis, it can be concluded that the study drug is not inferior to the reference drug. Thus, the new combination Frinozol nasal spray is an effective and safe treatment for patients with acute respiratory infections.


Assuntos
Sprays Nasais , Fenilefrina/uso terapêutico , Infecções Respiratórias , Administração Intranasal , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Sr Care Pharm ; 34(10): 669-673, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31818352

RESUMO

This report describes a case of persistent rhinorrhea caused by donepezil and successfully treated with azelastine in an 84-year-old male treated with donepezil for Alzheimer's disease (AD) who experienced excessive rhinorrhea. After initiation of donepezil for AD the patient showed increased discomfort with rhinorrhea. A trial with an oral second-generation antihistamine provided no benefit. Azelastine 0.1% nasal spray was initiated and successfully reduced the rhinorrhea. A less-oftenreported side effect of donepezil that may impact patients is rhinorrhea, also described as rhinitis or nasopharyngitis.
Cholinergic mechanisms of rhinorrhea have been previously described in the condition of vasomotor rhinitis and are not allergy-mediated though symptomatology overlaps. Azelastine is a histamine H1 antagonist indicated for vasomotor rhinitis. To our knowledge there are no previous descriptions in the literature that recommend azelastine to manage symptoms of rhinorrhea caused by treatments for AD. The adverse side effect of rhinorrhea, resulting from treatment with donepezil, can be disregarded as allergy symptoms. Instead, a trial of azelastine 0.1% nasal spray, one spray each nostril daily then titrated up to two sprays in each nostril twice daily as tolerated, may be warranted. Patients and caregivers should be aware of epistaxis as a potential side effect of azelastine, especially for patients on antithrombotic therapy.


Assuntos
Doença de Alzheimer , Doenças Nasais/induzido quimicamente , Administração Intranasal , Idoso de 80 Anos ou mais , Doença de Alzheimer/tratamento farmacológico , Antagonistas dos Receptores Histamínicos H1 não Sedativos , Humanos , Masculino , Rinite Alérgica Sazonal
6.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4800-4805, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872585

RESUMO

Due to the increasing incidence of central nervous system diseases,especially the increasing incidence and mortality of stroke,brain-targeted drug delivery has attached more and more attention. Nasal administration,as one of the ways of brain-targeted administration,can effectively make the drug delivered to the brain in a targeted way after by passing the blood-brain barrier,providing a new idea for the treatment of central nervous system diseases. Therefore,it is a promising administration way. In recent years,the treatment of encephalopathy by nasal administration of traditional Chinese medicine has become a hot topic in the research of traditional Chinese medicine. Ischemic stroke is one of the most important diseases endangering human health. Nasal administration has a history of thousands of years in treatment of stroke. Modern medical research has proved that there is a subtle connection between the nasal cavity and the brain,and the complex and ingenious structure of the nasal cavity provides the possibility for drugs delivery to the brain through the nose. Drug administration through nasal cavity has obvious advantages in treatment of central nervous system diseases represented by ischemic stroke. Nasal administration is characterized by non-invasion,low infection,rapid absorption and brain targeting. The author will expound the theoretical basis of brain targeting of nasal administration from the aspects of anatomy and physiology,and summarize the transport pathway of drugs through the nose into the brain,the in vitro and in vivo experimental research basis of the " nose-brain"pathway,and the clinical nasal administration of traditional Chinese medicine to prevent cerebral ischemia. It provides a reference for better research of drugs to prevent and treat cerebral ischemia injury through the " nose-brain"pathway and lays a foundation for further research of the " nose-brain" pathway.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Medicina Tradicional Chinesa , Preparações Farmacêuticas , Administração Intranasal , Encéfalo , Sistemas de Liberação de Medicamentos , Humanos , Mucosa Nasal
8.
Vet Microbiol ; 237: 108401, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31585639

RESUMO

Influenza results in significant economic loss in the swine industry each year. A broadly protective swine influenza vaccine would have the dual benefit of protecting pigs from influenza A viruses (IAVs) and limiting their possible zoonotic transmission to humans. In this study, we developed polyanhydride nanoparticles-based swine influenza vaccine (KAg + CpG-nanovaccine) co-encapsulating inacticated/killed soluble antigen (KAg) and Toll-like receptor (TLR)-9 agonist (CpG-ODN). The immunogenicity and protective efficacy of KAg + CpG-nanovaccine was compared with KAg vaccine containing five-times greater quantity of antigens following heterologous virus challenge. Prime-boost intranasally delivered KAg + CpG-nanovaccine induced significantly higher levels of cross-reactive antigen-specific IgA antibody responses in the nasal cavity, greater lymphoproliferative response in peripheral blood mononuclear cells (PBMCs), and higher IFN-γ secretion during antigen-induced recall responses of PBMCs and tracheobronchial lymph nodes cells compared to those immunized with KAg alone. Importantly, KAg + CpG-nanovaccine provided better protective efficacy through a significant reduction in influenza-induced fever, 16-fold reduction of nasal virus shedding and 80-fold reduction in lung virus titers compared to those immunized with soluble KAg. Our results indicated that CpG-ODN-adjuvanted polyanhydride nanovaccine can induce higher mucosal antibody and cellular immune responses in pigs; and provide better protection as compared with intranasally delivered soluble KAg.


Assuntos
Vacinas contra Influenza/imunologia , Oligodesoxirribonucleotídeos/farmacologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/prevenção & controle , Adjuvantes Imunológicos , Administração Intranasal , Animais , Anticorpos Antivirais , Antígenos Virais/imunologia , Feminino , Imunidade nas Mucosas , Imunoglobulina A/imunologia , Interferon gama/metabolismo , Leucócitos Mononucleares , Masculino , Nanoestruturas , Oligodesoxirribonucleotídeos/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Polianidridos , Suínos , Vacinas de Produtos Inativados/imunologia
9.
Laryngoscope ; 129(10): 2210-2215, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31566760

RESUMO

OBJECTIVES/HYPOTHESIS: The objective of this study was to report for the first time on the results of submucosal injections of bevacizumab used in conjunction with cyanoacrylate glue sclerotherapy in hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: Retrospective analytic chart review. METHODS: We performed a chart review that included all patients with HHT treated with intranasal bevacizumab and cyanoacrylate glue for refractory epistaxis at Lariboisiere University Hospital from 2013 with a minimum follow-up of 6 months. We injected 100 mg (25 mg/mL) of bevacizumab diluted in 2 mL of serum at the base of the telangiectasias, and sclerotherapy with an injection of cyanoacrylate glue was used adjunctively. Treatment efficacy was based on changes in Epistaxis Severity Scores (ESS) and the Bergler-Sadick Scale. Quality of life and patient satisfaction were evaluated using the Cantril Self-Anchoring Ladder (CL) and Likert scale, respectively. RESULTS: Thirty-one patients were included, with a mean follow-up of 26.6 months. The average ESS score significantly decreased from 7.82 to 3.89 (P < .05). The Bergler-Sadick score significantly improved (P < .05) following the treatment, including the frequency (from 2.74 to 1.64) and the quantity (from 2.54 to 1.51) scales. Quality of life was significantly improved (P < .05) using the CL score (from 4.16 to 7.22). The Likert satisfaction scale related to the treatment efficacy was high, with an average of 7.03 out of 10. No complications were noted. CONCLUSIONS: Submucosal injections of bevacizumab in conjunction with cyanoacrylate glue sclerotherapy significantly reduced epistaxis and improved the quality of life in HHT. Prospective comparative studies are needed to further evaluate the significance of this treatment modality. LEVEL OF EVIDENCE: 3b Laryngoscope, 129:2210-2215, 2019.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Cianoacrilatos/administração & dosagem , Epistaxe/tratamento farmacológico , Adesivo Tecidual de Fibrina/administração & dosagem , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Administração Intranasal , Adulto , Idoso , Idoso de 80 Anos ou mais , Epistaxe/etiologia , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Telangiectasia Hemorrágica Hereditária/complicações , Resultado do Tratamento
10.
Int J Nanomedicine ; 14: 8179-8193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632026

RESUMO

Background: Chlamydia psittaci is a zoonotic bacteria closely associated with psittacosis/ornithosis. Vaccination has been recognized as the best way to inhibit the spread of C. psittaci due to the majority ignored of infections. The optimal Chlamydia vaccine was obstructed by the defect of single immunization route and the lack of availability of nontoxic and valid adjuvants. Methods: In this study, we developed a novel immunization strategy, simultaneous (SIM) intramuscular (IM) and intranasal (IN) administration of a C. psittaci antigens (Ags) adjuvanted with chitosan nanoparticles (CNPs). And SIM-CNPs-Ags were used to determine the different types of immune response and the protective role in vivo. Results: CNPs-Ags with zeta-potential values of 13.12 mV and of 276.1 nm showed excellent stability and optimal size for crossing the mucosal barrier with high 71.7% encapsulation efficiency. SIM-CPN-Ags mediated stronger humoral and mucosal responses by producing meaningfully high levels of IgG and secretory IgA (sIgA) antibodies. The SIM route also led to Ags-specific T-cell responses and increased IFN-γ, IL-2, TNF-α and IL-17A in the splenocyte supernatants. Following respiratory infection with C. psittaci, we found that SIM immunization remarkably reduced bacterial load and the degree of inflammation in the infected lungs and made for a lower level of IFN-γ, TNF-α and IL-6. Furthermore, SIM vaccination with CNPs-Ags had obviously inhibited C. psittaci disseminating to various organs in vivo. Conclusion: SIM immunization with CNPs-adjuvanted C. psittaci Ags may present a novel strategy for the development of a vaccine against the C. psittaci infection.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Quitosana/administração & dosagem , Chlamydophila psittaci/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Nanopartículas/administração & dosagem , Administração Intranasal , Animais , Antígenos de Bactérias/imunologia , Citocinas/metabolismo , Feminino , Imunidade Humoral , Imunidade nas Mucosas , Imunoglobulina G/metabolismo , Injeções Intramusculares , Pulmão/patologia , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Tamanho da Partícula , Psitacose , Baço/imunologia , Baço/microbiologia , Linfócitos T/imunologia , Vacinação
11.
Eur J Pharm Biopharm ; 144: 91-100, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31521715

RESUMO

We have previously demonstrated that the ester conjugation of zidovudine (AZT) with ursodeoxycholic acid (UDCA) allows to obtain a prodrug (U-AZT) which eludes the active efflux transporters (AET). This allows the prodrug to more efficiently permeates and remains in murine macrophages than the parent compound. Here we demonstrate that U-AZT can be formulated, by a nanoprecipitation method, as nanoparticle cores coated by bile acid salt (taurocholate or ursodeoxycholate) corona, without any other excipients. The U-AZT nanoparticles appeared spherical with a mean diameter of ∼200 nm and a zeta potential of ∼-55 mV. During the incubation (5 h) in fetal bovine serum, the ursodeoxycholate-coated nanoparticle size did not change. Differently, taurocholate-coated particle size was firstly reduced and then increased up to 800 µm, thus suggesting the high aptitude of these nanoparticles to interact with serum proteins. The in vitro uptake of taurocholate coated particles by murine macrophages was strongly higher than that of ursodeoxycholate-coated particles or free U-AZT (∼500% and ∼7000%, respectively). AZT was also detected in macrophages following the prodrug uptake, with the greatest amounts observed after the taurocholate-coated nanoparticle incubation. As macrophages in the subarachnoid spaces of cerebrospinal fluid (CSF) constitute one of the most unreachable HIV sanctuaries in the body, we also tested the ability of taurocholate-coated nanoparticles (i.e., nanoparticles highly internalized by macrophages) to reach them after their nasal administration in the presence or absence of chitosan. The results indicate that chitosan allowed to obtain a relatively high uptake (up to 4 µg/ml) of U-AZT in CSF. Taking into account that chitosan may promote the direct brain nanoparticle uptake, these findings can be considered an initial step toward the in vivo targeting of the subarachnoid macrophages by U-AZT prodrug.


Assuntos
Ácidos e Sais Biliares/química , Encéfalo/metabolismo , Macrófagos/efeitos dos fármacos , Nanopartículas/química , Mucosa Nasal/metabolismo , Pró-Fármacos/farmacologia , Zidovudina/farmacologia , Administração Intranasal , Animais , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Quitosana/química , Portadores de Fármacos/química , Excipientes/química , Camundongos , Nariz , Tamanho da Partícula , Ácido Ursodesoxicólico/química
12.
Lett Appl Microbiol ; 69(5): 366-372, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31508837

RESUMO

We evaluate the efficacy of recombinant DNA vaccine ABA392 against haemorrhagic septicaemia infection through intranasal administration route by targeting the mucosal immunity. The DNA vaccine was constructed and subjected to animal study using the Sprague Dawley (SD) rat. The study was divided into two major parts: (i) active and (ii) passive immunization studies, involving 30 animals for each part. Each group was then divided into five test groups: two test samples G1 and G2 with 50 and 100 µg ml-1 purified DNA vaccine; one positive control G5 with 106  CFU per ml formalin-killed PMB2; and two negative controls, G3 and G4 with normal saline and pVAX1 vector. Both studies were conducted for the determination of immunogenicity by total white blood cell count (TWBC), indirect ELISA and histopathological changes for the presence of the bronchus-associated lymphoid tissue (BALT). Our findings demonstrate that TWBC, IgA and IgG increased after each of the three vaccination regimes: groups G1, G2 and G5. Test samples G1 and G2 showed significant differences (P < 0·05) compared to the negative controls, G3 and G4, but no significant differences from the positive control G5. Groups G1, G2 and G5 showed more formation of BALT compared to the negative controls, G3 and G4. Our results show that intranasal inoculation of recombinant DNA vaccine ABA392 can provoke mucosal immunity which makes it a potential prophylactic against HS. SIGNIFICANCE AND IMPACT OF THE STUDY: New approach of combating haemorrhagic septicaemia disease among bovines by recombinant DNA vaccine is crucial to overcome the loss of edible products from the infected bovines. DNA vaccine can potentially serve as a better immunogen which would elicit both cellular and humoral immunity, and it is also stable for its molecular reproduction. This research report demonstrates an effective yet simple way of administering the DNA vaccine via the intranasal route in rats, to provoke the mucosal immunity through the development of immunoglobulins IgA, IgG and bronchus-associated lymphoid tissue which guard as the first-line defence at the host's mucosal lining.


Assuntos
Vacinas Bacterianas/administração & dosagem , Doenças dos Bovinos/prevenção & controle , Septicemia Hemorrágica/veterinária , Pasteurella multocida/imunologia , Vacinas de DNA/administração & dosagem , Administração Intranasal , Animais , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/genética , Vacinas Bacterianas/imunologia , Bovinos , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/microbiologia , DNA Recombinante/administração & dosagem , DNA Recombinante/genética , DNA Recombinante/imunologia , Ensaio de Imunoadsorção Enzimática , Septicemia Hemorrágica/imunologia , Septicemia Hemorrágica/microbiologia , Septicemia Hemorrágica/prevenção & controle , Imunização Passiva , Masculino , Pasteurella multocida/genética , Ratos , Ratos Sprague-Dawley , Vacinas de DNA/genética , Vacinas de DNA/imunologia
14.
PLoS Pathog ; 15(9): e1008036, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525249

RESUMO

Cytomegalovirus (CMV) is a ubiquitous ß-herpesvirus that establishes life-long latent infection in a high percentage of the population worldwide. CMV induces the strongest and most durable CD8+ T cell response known in human clinical medicine. Due to its unique properties, the virus represents a promising candidate vaccine vector for the induction of persistent cellular immunity. To take advantage of this, we constructed a recombinant murine CMV (MCMV) expressing an MHC-I restricted epitope from influenza A virus (IAV) H1N1 within the immediate early 2 (ie2) gene. Only mice that were immunized intranasally (i.n.) were capable of controlling IAV infection, despite the greater potency of the intraperitoneally (i.p.) vaccination in inducing a systemic IAV-specific CD8+ T cell response. The protective capacity of the i.n. immunization was associated with its ability to induce IAV-specific tissue-resident memory CD8+ T (CD8TRM) cells in the lungs. Our data demonstrate that the protective effect exerted by the i.n. immunization was critically mediated by antigen-specific CD8+ T cells. CD8TRM cells promoted the induction of IFNγ and chemokines that facilitate the recruitment of antigen-specific CD8+ T cells to the lungs. Overall, our results showed that locally applied MCMV vectors could induce mucosal immunity at sites of entry, providing superior immune protection against respiratory infections.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Imunidade nas Mucosas , Vacinas contra Influenza/imunologia , Muromegalovirus/imunologia , Administração Intranasal , Sequência de Aminoácidos , Animais , Linhagem Celular , Quimiocinas/biossíntese , Epitopos de Linfócito T/administração & dosagem , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Feminino , Produtos do Gene env/administração & dosagem , Produtos do Gene env/genética , Produtos do Gene env/imunologia , Vetores Genéticos , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Pulmão/imunologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Muromegalovirus/genética , Células NIH 3T3 , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/virologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
15.
Infect Immun ; 87(12)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31501249

RESUMO

Coxiella burnetii, the etiological agent of Q fever, is a Gram-negative bacterium transmitted to humans by inhalation of contaminated aerosols. Acute Q fever is often self-limiting, presenting as a febrile illness that can result in atypical pneumonia. In some cases, Q fever becomes chronic, leading to endocarditis that can be life threatening. The formalin-inactivated whole-cell vaccine (WCV) confers long-term protection but has significant side effects when administered to presensitized individuals. Designing new vaccines against C. burnetii remains a challenge and requires the use of clinically relevant modes of transmission in appropriate animal models. We have developed a safe and reproducible C. burnetii aerosol challenge in three different animal models to evaluate the effects of pulmonary acquired infection. Using a MicroSprayer aerosolizer, BL/6 mice and Hartley guinea pigs were infected intratracheally with C. burnetii Nine Mile phase I (NMI) and demonstrated susceptibility as determined by measuring bacterial growth in the lungs and subsequent dissemination to the spleen. Histological analysis of lung tissue showed significant pathology associated with disease, which was more severe in guinea pigs. Infection using large-particle aerosol (LPA) delivery was further confirmed in nonhuman primates, which developed fever and pneumonia. We also demonstrate that vaccinating mice and guinea pigs with WCV prior to LPA challenge is capable of eliciting protective immunity that significantly reduces splenomegaly and the bacterial burden in spleen and lung tissues. These data suggest that these models can have appreciable value in using the LPA delivery system to study pulmonary Q fever pathogenesis as well as designing vaccine countermeasures to C. burnetii aerosol transmission.


Assuntos
Vacinas Bacterianas/imunologia , Coxiella burnetii/imunologia , Pulmão/microbiologia , Febre Q/veterinária , Vacinas de Produtos Inativados/imunologia , Administração Intranasal , Animais , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/administração & dosagem , Modelos Animais de Doenças , Feminino , Cobaias , Pulmão/imunologia , Macaca mulatta , Camundongos , Camundongos Endogâmicos C57BL , Febre Q/imunologia , Febre Q/prevenção & controle , Baço/imunologia , Baço/microbiologia , Vacinas de Produtos Inativados/administração & dosagem
16.
AAPS PharmSciTech ; 20(7): 299, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31482286

RESUMO

The integrity of the nasal epithelium plays a crucial role in the airway defence mechanism. The nasal epithelium may be injured as a result of a large number of factors leading to nose bleeds, also known as epistaxis. However, local measures commonly used to treat epistaxis and improve wound healing present several side effects and patient discomfort. Hence, this study aims to address some of these drawbacks by developing a new formulation for nasal epithelial wound healing. Chitosan, a biodegradable and biocompatible polymer, was used to develop a thermosensitive nasal formulation for the delivery of tranexamic acid (TXA), one of the most effective pharmacological options to control bleeding with cost and tolerability advantages. The in situ gelation properties of the formulation upon administration in the nasal cavity were investigated in terms of gelation time and temperature. It was found that the developed formulation can undergo rapid liquid-to-gel phase change within approximately 5 min at 32°C, which is well within the human nasal cavity temperature range. The spray pattern, deposition and droplet size generated by the nasal spray was also characterised and were found to be suitable for nasal drug delivery. It was also observed that the in situ gelation of the formulation prevent nasal runoff, while the majority of drug deposited mainly in the anterior part of the nose with no lung deposition. The developed formulation was shown to be safe on human nasal epithelium and demonstrated six times faster wound closure compared to the control TXA solution.


Assuntos
Quitosana/administração & dosagem , Modelos Biológicos , Sprays Nasais , Ácido Tranexâmico/administração & dosagem , Cicatrização/efeitos dos fármacos , Administração Intranasal , Quitosana/química , Quitosana/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Géis , Humanos , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Temperatura Ambiente , Ácido Tranexâmico/química , Ácido Tranexâmico/metabolismo , Cicatrização/fisiologia
17.
AAPS PharmSciTech ; 20(7): 301, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31485857

RESUMO

Huperzine A (hup A), extracted from the Chinese medicinal plant Huperzia serrata, is a reversible and highly selective second-generation acetylcholine esterase (AchE) inhibitor for treating Alzheimer's disease (AD), but it suffers from low bioavailability in the brain. This study aimed to develop a nasal temperature and pH dual-responsive in situ gel delivery system based on microemulsion of hup A (hup A-M-TPISG). The optimal formulation was obtained by central composite design and response surface methodology. The optimized mucoadhesive formulation, hup A-M-TPISG, was composed of pluronic F127 (20.80%), pluronic F68 (2.8%), and chitosan (0.88%) as the gel matrix, which could gelatinize under physiological conditions (29-34°C, pH 6.5) because of its temperature and pH responsiveness. The optimized hup A-M-TPISG formulation was further evaluated by in vitro release and in vivo pharmacokinetic studies via microdialysis. The in vitro release study showed continuous and steady drug release from hup A-M-TPISG, which was in accordance with the first-order model. Moreover, the pharmacokinetic results revealed that the optimized formulation for nasal administration, with convenient administration and improved patient compliance, could achieve similar brain-targeting properties as intravenous administration. In conclusion, the hup A-M-TPISG for intranasal administration, as an effective and safe vehicle, could enhance the absorption of hup A in vivo and would be a promising noninvasive alternative for partially improving brain-targeting therapy.


Assuntos
Alcaloides/administração & dosagem , Inibidores da Colinesterase/administração & dosagem , Sistemas de Liberação de Medicamentos , Sesquiterpenos/administração & dosagem , Administração Intranasal , Alcaloides/química , Alcaloides/farmacocinética , Animais , Encéfalo/efeitos dos fármacos , Composição de Medicamentos , Emulsões , Géis , Concentração de Íons de Hidrogênio , Masculino , Ratos , Ratos Sprague-Dawley , Sesquiterpenos/química , Sesquiterpenos/farmacocinética , Temperatura Ambiente
18.
Vet J ; 251: 105346, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31492384

RESUMO

The aim of this study was to compare the sedative and cardiovascular effects of dexmedetomidine (DEX) administrated via intranasal (IN) and intramuscular (IM) routes. This masked, randomised, crossover study used six male beagle dogs, receiving 0.02 mg/kg dexmedetomidine either IN (DEX-IN) or IM (DEX-IM), and an equal volume of saline by the alternative route. Dexmedetomidine plasma concentration was measured before (TB) and at time points (T) 2, 5, 10, 15, 30, 45, 60, 90 and 120 min after drug administration (T0). Physiological variables, sedation scores and sedation times were recorded until recovery. Echocardiography was performed at TB and between T20-T40. Repeated data over time were analysed using a Scheirer-Ray-Hare test. Other data were compared using a Wilcoxon or Student's t test. Times from T0 to sternal position and from lateral to sternal position were longer for DEX-IN than DEX-IM (P = 0.018 and P = 0.009, respectively). Time from sternal to standing position was shorter for DEX-IN than DEX-IM (P = 0.03). Dexmedetomidine plasma concentrations were significantly lower for DEX-IN than DEX-IM from T10 to T120. Heart rate was significantly lower for DEX-IM than DEX-IN from T5 to T20. Echocardiography showed a decrease in systolic function and calculated cardiac output in DEX-IM as compared to baseline. The DEX concentration-sedation curve for DEX-IN as compared to DEX-IM was leftward shifted, whereas the IN and IM DEX concentration-variation-in-heart-rate curves overlapped. Although reaching lower plasma concentrations, IN dexmedetomidine produced similar sedation to IM dexmedetomidine without affecting cardiovascular function.


Assuntos
Administração Intranasal/veterinária , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacocinética , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacocinética , Injeções Intramusculares/veterinária , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Estudos Cross-Over , Dexmedetomidina/sangue , Cães , Ecocardiografia/veterinária , Frequência Cardíaca/efeitos dos fármacos , Masculino , Distribuição Aleatória
19.
Int. arch. otorhinolaryngol. (Impr.) ; 23(3): 325-330, July-Sept. 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1040031

RESUMO

Abstract Introduction Oral antihistamines and intranasal corticosteroids have been shown to be effective and safe for the treatment of allergic rhinitis; however, the evidence suggests a level of superiority of corticosteroids, so they should be preferred over the former. Objective To know the prescription profile of two second generation antihistamines (cetirizine and levocetirizine) and two nasal corticosteroids (mometasone and furoateciclesonide) in a cohort of patients with allergic rhinitis, and to compare the clinical outcomes obtained. Methods A cohort study was carried including patients with allergic rhinitis treated with cetirizine, levocetirizine, mometasone furoate or ciclesonide. The improvement was evaluated with the total nasal symptoms score (TNSS). This scale yields results between 0 and 12. Zero indicates absence of symptoms. Results A total of 314 patients completed 12 weeks of follow-up. Seventy-five percent were treated with antihistamines, 20% with corticosteroids, and 5% with a combination of the above. The TNSS median for corticosteroid was 2.5 points; for antihistamines, its was 5 points, and for combination, it was 4 points. We found differences between corticosteroids and antihistamines. Conclusion The prescription percentage of second generation oral antihistamines is higher than that of intranasal corticosteroids. However, patients with allergic rhinitis treated with the second option obtained better control of symptoms.


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Corticosteroides/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Prescrições de Medicamentos , Administração Intranasal , Estudos de Coortes , Resultado do Tratamento , Cetirizina/uso terapêutico , Corticosteroides/administração & dosagem , Colômbia , Furoato de Mometasona/uso terapêutico
20.
Drug Deliv ; 26(1): 831-840, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401887

RESUMO

Formulations for nasal drug delivery often rely on water sorption to adhere to the mucosa, which also causes a higher water gradient over the tissue and subsequent dehydration. The primary aim of this study was therefore to evaluate mucosal response to dehydration and resolve the hypothesis that mucoadhesion achieved through water sorption could also be a constraint for drug absorption via the nasal route. The effect of altering water activity of the vehicle on Xylometazoline HCl and 51Cr-EDTA uptake was studied separately ex vivo using flow through diffusion cells and excised porcine mucosa. We have shown that a modest increase in the water gradient over mucosa induces a substantial decrease in drug uptake for both Xylometazoline HCl and 51Cr-EDTA. A similar result was obtained when comparing two different vehicles on the market; Nasoferm® (Nordic Drugs, Sweden) and BLOX4® (Bioglan, Sweden). Mucoadhesion based on water sorption can slow down drug uptake in the nasal cavity. However, a clinical study is required to determine whether prolonged duration of the vehicle in situ or preventing dehydration of the mucosa is the most important factor for improving bioavailability.


Assuntos
Transporte Biológico/fisiologia , Desidratação/metabolismo , Desidratação/fisiopatologia , Mucosa Nasal/metabolismo , Preparações Farmacêuticas/metabolismo , Administração Intranasal/métodos , Animais , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos/métodos , Excipientes/química , Suínos
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