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1.
JAMA ; 331(10): 866-877, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470381

RESUMO

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.


Assuntos
Glucocorticoides , Antagonistas dos Receptores Histamínicos , Rinite Alérgica , Humanos , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Cetirizina/uso terapêutico , Fluticasona/administração & dosagem , Fluticasona/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Imunoglobulina E/imunologia , Furoato de Mometasona/administração & dosagem , Furoato de Mometasona/uso terapêutico , Cloridrato de Olopatadina/administração & dosagem , Cloridrato de Olopatadina/uso terapêutico , Prurido/etiologia , Rinite Alérgica/complicações , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Rinite Alérgica/terapia , Rinorreia/etiologia , Espirro , Triancinolona/administração & dosagem , Triancinolona/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Rinite/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/uso terapêutico , Administração Intranasal
3.
Int J Med Sci ; 20(13): 1671-1678, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928871

RESUMO

Histamine receptor-1 (H1) antagonists like levocetirizine are frequently used nowadays to treat rhinitis patients who experience rhinorrhea and sneezing. The trachea may be affected by the H1 antagonist when it is used to treat nasal symptoms, either orally or through inhalation. The purpose of this study was to ascertain in vitro effects of levocetirizine on isolated tracheal smooth muscle. As a parasympathetic mimetic, methacholine (10-6 M) causes contractions in tracheal smooth muscle, which is how we tested effectiveness of levocetirizine on isolated rat tracheal smooth muscle. We also tested the drug's impact on electrically induced tracheal smooth muscle contractions. The impact of menthol (either before or after) on the contraction brought on by 10-6 M methacholine was also investigated. According to the results, the addition of levocetirizine at concentrations of 10-5 M or more caused a slight relaxation in response to methacholine's 10-6 M contraction. Levocetirizine could prevent spike contraction brought on by electrical field stimulation (EFS). As the concentration rose, it alone had a neglect effect on the trachea's basal tension. Before menthol was applied, levocetirizine might have also inhibited the function of the cold receptor. According to this study, levocetirizine might potentially impede the parasympathetic function of the trachea. If levocetirizine was used prior to menthol addition, it also reduced the function of cold receptors.


Assuntos
Cetirizina , Mentol , Ratos , Humanos , Animais , Cloreto de Metacolina/farmacologia , Mentol/farmacologia , Cetirizina/farmacologia , Cetirizina/uso terapêutico , Músculo Liso/fisiologia , Contração Muscular , Traqueia/fisiologia
4.
Front Endocrinol (Lausanne) ; 14: 1068925, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36843581

RESUMO

Severe burns induce a catecholamine surge, causing severe damage to the organism and raising the possibility of multisystem organ failure. Few strategies are generally acceptable to reduce catecholamine surge and organ injury post-burn. We have previously shown that histamine can amplify the catecholamine surge. In addition, promethazine, a first-generation histamine H1 receptor antagonist, alleviates catecholamine surge and organ injury after severe burns in rats. However, evidence is lacking on whether promethazine benefits patients after severe burns. Currently, sedation and analgesia (such as midazolam and fentanyl) are commonly required for patients after severe burns. It remains unclear if patients after severe burns derive clinical benefit from histamine H1 receptor antagonists combined with sedation and analgesia. This study investigates the therapeutic effect of promethazine on patients after severe burns. Moreover, we test the therapeutic effect of cetirizine, a second-generation histamine H1 receptor antagonist, combined with sedation and analgesia in rats after severe burns. We find that promethazine-pethidine treatment shows a tendency for a lower level of total bilirubin than midazolam-fentanyl in patients 7-day after severe burn. Our study confirms that cetirizine combined with midazolam and fentanyl reduces catecholamine surge and liver and lung damage after severe burns in rats; the effects are better than midazolam and fentanyl treatment. In summary, for the first time, we suggest that histamine H1 receptor antagonist has the potential clinical value of reducing liver injury in patients after severe burns. In addition, we reveal that cetirizine combined with midazolam and fentanyl may be an ideal strategy for treating severe burns.


Assuntos
Antagonistas dos Receptores Histamínicos H1 , Prometazina , Ratos , Animais , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/farmacologia , Prometazina/farmacologia , Cetirizina/uso terapêutico , Cetirizina/farmacologia , Midazolam/uso terapêutico , Dor/tratamento farmacológico , Histamina/farmacologia , Fentanila
5.
Arch Dermatol Res ; 315(5): 1293-1304, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36571611

RESUMO

Androgenetic alopecia (AGA) is the most common cause of hair loss in both genders with a higher psychological impact on females. Currently, topical minoxidil is the only FDA-approved treatment for female AGA and it needs life-long application and causes side effects. Cetirizine is an antihistamine that may be effective in hair loss treatment. This study aimed to compare the efficacy and safety of topical cetirizine with minoxidil (group 1) versus topical minoxidil with placebo (group 2) in female patients with AGA. This was a double-blind, randomized, controlled, parallel study conducted at Dermatology Clinic, Cairo University Teaching Hospital (Kasr- Al- Ainy), Egypt. Sixty-six patients with female AGA, aged 20-50 years, Sinclair (II-IV), were randomly assigned to one of the 2 groups for 24 weeks. The trichoscopic parameters, patients' self-assessment, side effects and global photographic assessment were evaluated. There was a statistically significant change from baseline in frontal and vertex terminal and vellus hair density (P < 0.0005) with a significant increase in vertex hair shaft thickness and average number of hairs per follicular unit in group 1 (P < 0.05). Patients reported significantly better scores in patient self-assessment in group 1 (P < 0.05). Side effects were not significantly different between groups (P > 0.05). Topical cetirizine increases hair shaft thickness and results in a higher clinical improvement from patients' perspective with a good safety profile (NCT04481412, study start date: July 2020).


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Minoxidil , Feminino , Humanos , Masculino , Cetirizina/farmacologia , Cetirizina/uso terapêutico , Administração Tópica , Alopecia/tratamento farmacológico , Cabelo
6.
Cutan Ocul Toxicol ; 42(1): 8-11, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36469932

RESUMO

BACKGROUND: Literature on the effects of second-generation H1-antihistamines on angiogenesis is limited. OBJECTIVES: To investigate the effects of cetirizine, desloratadine, and rupatadine (second-generation H1-antihistamines commonly used in dermatology clinics) on angiogenesis in an in vivo chick chorioallantoic membrane (CAM) model. METHODS: The study was approved by the local ethics committee on animal experimentation. Forty fertilized specific pathogen free eggs were incubated and kept under appropriate temperature and humidity control. Drug solutions were prepared in identical concentrations by dissolving powders in phosphate-buffered saline (PBS). On the third day of the incubation, a small window was opened on the CAM and 0.1 mL desloratadine (1.5 µg/0.1 mL) in the first group, 0.1 mL cetirizine (1.5 µg/0.1 mL) in the second group, 0.1 mL rupatadine in the third group (1.5 µg/0.1 mL), and PBS (0.1 mL) in the fourth group were administered by injection. On the eighth day of incubation, the vascular structures of the CAMs were macroscopically examined and standard digital photographs were taken. The digital images were analyzed and data including mean vessel density, thickness, and number were compared between groups. p < 0.05 was considered statistically significant. RESULTS: Vessel densities were similar in the desloratadine, cetirizine, and control groups, whereas they were significantly less in the rupatadine group (p = 0.01). Furthermore, the rupatadine group had significantly lower vessel thickness and number compared with the other groups (p < 0.05 for both). CONCLUSIONS: Rupatadine showed anti-angiogenic effects in the chick CAM model, compared with desloratadine and cetirizine. The anti-angiogenic effect of rupatadine could be due to its platelet-activating factor (PAF) receptor inhibition. Thus, rupatadine could be a treatment agent in pathological processes in which angiogenesis is responsible. Further studies with larger series are needed to clarify this potential.


Assuntos
Cetirizina , Antagonistas não Sedativos dos Receptores H1 da Histamina , Animais , Cetirizina/farmacologia , Cetirizina/uso terapêutico , Membrana Corioalantoide , Galinhas
7.
Phytomedicine ; 107: 154426, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36116201

RESUMO

BACKGROUND: Shufeng Jiedu capsule (SFJDC) has been widely used as a conventional Chinese pharmaceutical agent for various upper respiratory infections, including acute lung injury, acute respiratory distress syndrome and allergic rhinitis (AR). However, its mechanism in AR remains unclear. PURPOSE: The present study aimed to decipher the antiallergic inflammatory effect of SFJDC in an AR model with olfactory dysfunction. Specifically, we wanted to explore whether SFJDC can improve the olfactory abnormality in AR mice and reduce the levels of inflammatory factors in the olfactory epithelium (OE) and olfactory bulb (OB). METHODS: To address the above issues, we constructed an AR model using C57BL/6 mice, which were sensitised and challenged with ovalbumin (OVA) by intraperitoneal injection. SFJDC (0.045 or 0.18 g/kg) was delivered by gavage administration 1 h prior to the intraperitoneal injection of OVA. The control mice received saline alone. Then, the animals were assessed according to the presence of nasal symptoms and nasal inflammation, and a buried food test was used to evaluate olfactory function. The levels of proteins involved in the AMPK/mTOR autophagy pathway in the OE and OB were investigated by western blotting and fluorescence staining. RESULTS: After OVA induction of AR and drug administration, we found that SFJDC significantly ameliorated the nasal symptoms and allergic inflammatory reaction of the nasal mucosa superior to cetirizine. A behavioural test indicated that the mice with AR had olfactory dysfunction, and SFJDC can ameliorate this behavior deficiency. Meanwhile, SFJDC clearly reduced the neuroinflammation level in OE tissue. In addition, SFJDC increased p-mTOR and decreased p-AMPK, beclin1, LC3 and cleaved caspase-3 levels in the OE. CONCLUSIONS: In addition to antibacterial and antiviral activities, SFJDC has marked anti-inflammatory effects in AR mice. Its mechanism of action in the nasal cavity involves inhibition of upregulated anti-inflammatory cytokines, modulation of autophagy and apoptosis levels and regulation of autophagy through the AMPK/mTOR pathway in the OE tissue of AR mice. Hence, SFJDC is a promising drug for AR, and clinical trials should further validate the therapeutic impact of SFJDC on AR with olfactory dysfunction.


Assuntos
Antialérgicos , Medicamentos de Ervas Chinesas , Transtornos do Olfato , Rinite Alérgica , Proteínas Quinases Ativadas por AMP , Animais , Antialérgicos/farmacologia , Antialérgicos/uso terapêutico , Antibacterianos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Autofagia , Proteína Beclina-1 , Caspase 3 , Cetirizina/uso terapêutico , Citocinas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transtornos do Olfato/tratamento farmacológico , Ovalbumina , Rinite Alérgica/tratamento farmacológico , Serina-Treonina Quinases TOR
8.
J Transl Med ; 20(1): 436, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36180872

RESUMO

BACKGROUND: The clinical observation showed a potential additive effect of anti-PD-1 agents and cetirizine in patients with advanced melanoma. METHODS: Clinical outcomes of concomitant cetirizine/anti-PD-1 treatment of patients with stage IIIb-IV melanoma were retrospectively collected, and a transcriptomic analysis was performed on blood samples obtained at baseline and after 3 months of treatment. RESULTS: Patients treated with cetirizine concomitantly with an anti-PD-1 agent had significantly longer progression-free survival (PFS; mean PFS: 28 vs 15 months, HR 0.46, 95% CI: 0.28-0.76; p = 0.0023) and OS (mean OS was 36 vs 23 months, HR 0.48, 95% CI: 0.29-0.78; p = 0.0032) in comparison with those not receiving cetirizine. The concomitant treatment was significantly associated with ORR and DCR (p < 0.05). The expression of FCGR1A/CD64, a specific marker of macrophages, was increased after the treatment in comparison with baseline in blood samples from patients receiving cetirizine, but not in those receiving only the anti-PD1, and positively correlated with the expression of genes linked to the interferon pathway such as CCL8 (rho = 0.32; p = 0.0111), IFIT1 (rho = 0.29; p = 0.0229), IFIT3 (rho = 0.57; p < 0.0001), IFI27 (rho = 0.42; p = 0.008), MX1 (rho = 0.26; p = 0.0383) and RSAD2 (rho = 0.43; p = 0.0005). CONCLUSIONS: This retrospective study suggests that M1 macrophage polarization may be induced by cetirizine through the interferon-gamma pathway. This effect may synergize with the immunotherapy of advanced melanoma with anti-PD-1 agents.


Assuntos
Melanoma , Receptor de Morte Celular Programada 1 , Cetirizina/farmacologia , Cetirizina/uso terapêutico , Humanos , Interferon gama/uso terapêutico , Macrófagos/metabolismo , Melanoma/genética , Estudos Retrospectivos
9.
Drug Des Devel Ther ; 16: 2509-2515, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35959421

RESUMO

Objective: Infantile eczema (IE), a common pediatric allergic skin disease caused by multiple inherent and external factors, is common in infants and young children, with skin lesions and itching as the main clinical manifestations. At present, its pathological mechanism has not been thoroughly clarified, but scholars believe that it is related to the joint action of various internal and external factors. This research aims to investigate the influences of bifid triple viable capsules plus cetirizine (CTZ) on gut microbiota (GMB) and immunity in children with eczema. Methods: The complete clinical data of 162 cases of IE presented between July 2019 and July 2020 to the First Hospital of Shanxi Medical University were retrospectively analyzed. Children treated by CTZ alone were assigned to the control group (n = 81) and those by CTZ plus bifid triple viable capsules were included in the observation group (n = 81). Therapeutic efficacy, adverse reactions (ARs), disease recurrence, as well as changes in GMB, inflammatory factors (IFs) and immunoglobulins (Igs) were observed. Results: The observation group was observed with a higher overall response rate and increased fecal Lactobacillus, Escherichia coli (E. coli) and Bifidobacterium counts after treatment versus the control group. After treatment, reduced IgG and IgM, as well as IFs, were found in both groups, with lower levels in the observation group. A lower incidence of ARs was determined in the observation group. Conclusion: With high efficacy for the treatment of IE, bifid triple viable capsules plus CTZ can validly regulate the GMB of children, improve their immune function and clinical symptoms, and reduce the disease recurrence rate, which is worthy of clinical promotion.


Assuntos
Dermatite Atópica , Eczema , Microbioma Gastrointestinal , Cetirizina/uso terapêutico , Criança , Pré-Escolar , Dermatite Atópica/tratamento farmacológico , Eczema/induzido quimicamente , Escherichia coli , Humanos , Imunidade , Lactente , Estudos Retrospectivos
10.
J Assoc Physicians India ; 70(6): 11-12, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35702846

RESUMO

BACKGROUND: Allergic rhinitis (AR) is associated with disturbed sleep and subsequent functioning, and an impaired quality of life (QoL). The symptoms of AR exhibit prominent circadian variations, with symptoms being more common at the night-time or early morning. Addressing these allergy-related sleep issues, impaired QoL, and circadian variation in symptoms is important from the patient perspective and should be considered in the management of AR. OBJECTIVE: To review the efficacy of cetirizine, a second-generation antihistamine and selective H1-receptor antagonist, in relation to improvement in the QoL of the patients, addressing the sleep disturbances and circadian variations in the symptoms of AR in clinical practice, and establishing its role as a contemporary antihistamine for the management of AR compared to newer antihistamines. METHODS: Systematic literature review of the databases such as PubMed/MEDLINE, Google Scholar, and the Cochrane Central Register of Controlled Trials from 1990 to 2020. RESULTS: The symptoms of AR exhibited a circadian variation, with symptoms being worse during the night and early morning. The patients with AR encountered several sleep-related symptoms, including poor sleep quality, daytime somnolence, fatigue, and impaired productivity and QoL. Impaired QoL in AR was related to the disease severity. Administration of cetirizine at bedtime provides effective control of sleep impairment and symptoms of AR, besides improving the QoL. The efficacy of cetirizine has been demonstrated to be superior or comparable to the newer second-generation antihistamines. Cetirizine exhibits a tolerability profile comparable to the newer antihistamines. CONCLUSION: With long years of clinical experience and a good tolerability profile, cetirizine represents a valuable therapeutic option for the management of AR, even 30 years after its introduction. Cetirizine is included in the National List of Essential Medicines of India for the management of allergic disorders in view of its established efficacy and safety profile as well as being a cost-effective option.


Assuntos
Antagonistas não Sedativos dos Receptores H1 da Histamina , Rinite Alérgica , Cetirizina/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Humanos , Qualidade de Vida , Rinite Alérgica/tratamento farmacológico
11.
ACS Appl Mater Interfaces ; 14(26): 29639-29649, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35749729

RESUMO

Allergic rhinitis (AR) is a chronic inflammatory reaction by immunoglobulin E (IgE) mediators after individual contact with allergens. It affects 10-40% of the world's population and reduces the quality of life. Long-term symptoms of rhinitis can cause inflammation to spread and trigger asthma, which can harm human health. Herein, we develop a Smart PeptIde defeNse (SPIN) web technique, which in situ constructs a peptide web, trapping IgE against AR. Two candidate SPINs, SPIN-1 and SPIN-2, are designed with different IgE-binding sequences. The SPIN-1 or SPIN-2 is able to bind to IgE and transform from nanoparticles into entangled nanofibers. In turn, the web of SPIN-1 or SPIN-2 acts as a long-term trap of IgE to prevent the IgE from binding to mast cells. SPIN-1 or SPIN-2 (10 mg/kg) is able to treat AR model Balb/c mice with high efficiency and reduced symptoms of rhinitis and inflammatory factors, even better than a first-line clinical drug, cetirizine (10 mg/kg). For example, the amount of IL-4 released in the AR group (185.5 ± 6.8 pg/mL) is significantly reduced after the treatment with SPIN-1 (70.4 ± 14.1 pg/mL), SPIN-2 (86.0 ± 9.3 pg/mL), or cetirizine (112.8 ± 19.3 pg/mL). More importantly, compared with the cetirizine group (1 day), the SPIN-1 or SPIN-2 group shows long-term therapeutic effects (1 week). The SPIN web technique shows the great potential for blocking IgE binding to mast cells in vivo, attenuating AR or other allergic reactions.


Assuntos
Rinite Alérgica , Rinite , Animais , Cetirizina/uso terapêutico , Imunoglobulina E/uso terapêutico , Camundongos , Peptídeos/uso terapêutico , Qualidade de Vida , Rinite Alérgica/tratamento farmacológico
12.
Environ Sci Pollut Res Int ; 29(29): 43984-44002, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35122640

RESUMO

Antihistamines (ANTs) are medicines to treat allergic diseases. They have been frequently detected in the natural water environment, posing potential threats to the ecological environment and human health. In this study, the degradation of three common antihistamines, loratadine, fexofenadine, and cetirizine, was estimated under different oxidation methods (NaClO, UV, and UV-NaClO). The results showed that UV-NaClO had the highest degree of degradation on the drugs under most conditions: 100% degradation for fexofenadine within 20 s at pH 7 and 10. Under UV irradiation, the degradation efficiencies of the three drugs during 150 s were all above 77% at a pH of 7. The drugs' removal by NaClO was much lower than that of the previous two methods. In addition, this study explored the contribution rates of active oxygen species in the photolysis process. Among them, the contribution of 1O2 to the fexofenadine and cetirizine removal rate reached 70%. Different aqueous matrices (HCO3-, NO3-, and humic acid) had varying degrees of influence on the degradation. Acute toxicity tests and ultraviolet scans of the degradation products showed that the drugs were not completely mineralized, and the toxicities of the intermediates were even higher than those of the parent drugs. There were 9, 8, and 10 chloride oxidation products of loratadine, fexofenadine, and cetirizine, respectively, and 8 photolysis products of cetirizine were identified. For cetirizine, it was found that there were three identical intermediates produced by photodegradation and NaClO oxidation.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Cetirizina/uso terapêutico , Antagonistas dos Receptores Histamínicos , Humanos , Cinética , Loratadina/uso terapêutico , Fotólise , Raios Ultravioleta , Água , Poluentes Químicos da Água/análise , Purificação da Água/métodos
13.
Int Immunopharmacol ; 103: 108412, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34942461

RESUMO

Levocetirizine, a third-generation antihistamine, and montelukast, a leukotriene receptor antagonist, exhibit remarkable synergistic anti-inflammatory activity across a spectrum of signaling proteins, cell adhesion molecules, and leukocytes. By targeting cellular protein activity, they are uniquely positioned to treat the symptoms of COVID-19. Clinical data to date with an associated six-month follow-up, suggests the combination therapy may prevent the progression of the disease from mild to moderate to severe, as well as prevent/treat many of the aspects of 'Long COVID,' thereby cost effectively reducing both morbidity and mortality. To investigate patient outcomes, 53 consecutive COVID-19 test (+) cases (ages 3-90) from a well-established, single-center practice in Boston, Massachusetts, between March - November 2020, were treated with levocetirizine and montelukast in addition to then existing protocols [2]. The data set was retrospectively reviewed. Thirty-four cases were considered mild (64%), 17 moderate (32%), and 2 (4%) severe. Several patients presented with significant comorbidities (obesity: n = 22, 41%; diabetes: n = 10, 19%; hypertension: n = 24, 45%). Among the cohort there were no exclusions, no intubations, and no deaths. The pilot study in Massachusetts encompassed the first COVID-19 wave which peaked on April 23, 2020 as well as the ascending portion of the second wave in the fall. During this period the average weekly COVID-19 case mortality rate (confirmed deaths/confirmed cases) varied considerably between 1 and 7.5% [37]. FDA has approved a multicenter, randomized, placebo-controlled, Phase 2 clinical trial design, replete with electronic diaries and laboratory metrics to explore scientific questions not addressed herein.


Assuntos
Acetatos/uso terapêutico , Tratamento Farmacológico da COVID-19 , Cetirizina/uso terapêutico , Ciclopropanos/uso terapêutico , Antagonistas não Sedativos dos Receptores H1 da Histamina/uso terapêutico , Antagonistas de Leucotrienos/uso terapêutico , Quinolinas/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Sulfetos/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Am J Physiol Renal Physiol ; 321(4): F466-F479, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34423679

RESUMO

Intraurethral inoculation of mice with uropathogenic Escherichia coli (CP1) results in prostate inflammation, fibrosis, and urinary dysfunction, recapitulating some but not all of the pathognomonic clinical features associated with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). In both patients with LUTS and CP1-infected mice, we observed increased numbers and activation of mast cells and elevated levels of prostate fibrosis. Therapeutic inhibition of mast cells using a combination of a mast cell stabilizer, cromolyn sodium, and the histamine 1 receptor antagonist cetirizine di-hydrochloride in the mouse model resulted in reduced mast cell activation in the prostate and significant alleviation of urinary dysfunction. Treated mice showed reduced prostate fibrosis, less infiltration of immune cells, and decreased inflammation. In addition, as opposed to symptomatic CP1-infected mice, treated mice showed reduced myosin light chain-2 phosphorylation, a marker of prostate smooth muscle contraction. These results show that mast cells play a critical role in the pathophysiology of urinary dysfunction and may be an important therapeutic target for men with BPH/LUTS.NEW & NOTEWORTHY LUTS-associated benign prostatic hyperplasia is derived from a combination of immune activation, extracellular matrix remodeling, hyperplasia, and smooth muscle cell contraction in prostates of men. Using a mouse model, we describe the importance of mast cells in regulating these multiple facets involved in the pathophysiology of LUTS. Mast cell inhibition alleviates both pathology and urinary dysfunction in this model, suggesting the potential for mast cell inhibition as a therapeutic that prevents and reverses pathology and associated symptomology.


Assuntos
Fibrose/patologia , Mastócitos/fisiologia , Miócitos de Músculo Liso/patologia , Doenças Prostáticas/patologia , Animais , Antialérgicos/uso terapêutico , Cetirizina/uso terapêutico , Cromolina Sódica/uso terapêutico , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/patologia , Fibrose/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/metabolismo , Próstata/metabolismo , Próstata/patologia , Doenças Prostáticas/metabolismo , Micção
16.
Ann Allergy Asthma Immunol ; 127(4): 488-495.e5, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34186172

RESUMO

BACKGROUND: Birch pollen is a prevalent aeroallergen during the springtime allergy season. In field studies, variable allergen exposure and environmental factors can affect data quality while environmental exposure units (EEUs) deliver controlled, standardized, and reproducible allergen exposures. OBJECTIVE: To inform study design for EEU trials evaluating antiallergic therapies. METHODS: In this prospective study, 76 participants with birch allergy experienced 3 exposures to birch pollen: (1) an out-of-season EEU challenge (two 3-hour sessions on consecutive days); (2) a natural seasonal exposure; and (3) an in-season EEU challenge (3-hour exposure for 2 weeks after birch pollen season initiation). RESULTS: The total nasal symptom score, total ocular symptom score, and total symptom score (TSS = total nasal symptom score plus total ocular symptom score) were assessed every 30 minutes and daily during EEU and natural exposures. A high association between TSSs and day 2 of the out-of-season and in-season EEU challenges was noted, with a good association between the maximum TSS during the natural and in-season EEU challenges, and natural season and day 2 of the out-of-season EEU challenge (P < .001 for all). Participants had higher maximum change from the baseline TSS during day 2 of the out-of-season EEU challenge (12.4) vs the following: (1) first day (9.8); (2) in-season EEU challenge (8.4); and (3) natural seasonal exposure (7.6) (P < .001 for all). CONCLUSION: A strong association was seen between the presence of allergy symptoms and exposure to birch pollen in the EEU (maximum change in symptom scores during day 2) and in the field. A hybrid trial design may be useful to demonstrate the clinical efficacy of novel antiallergic therapies requiring fewer participants and shorter timelines and expediting treatment availability.


Assuntos
Antialérgicos/uso terapêutico , Betula/imunologia , Exposição Ambiental/efeitos adversos , Pólen/imunologia , Rinite Alérgica Sazonal/tratamento farmacológico , Adulto , Alérgenos/administração & dosagem , Alérgenos/imunologia , Cetirizina/uso terapêutico , Feminino , Humanos , Masculino , Furoato de Mometasona/uso terapêutico , Cloridrato de Olopatadina/uso terapêutico , Estudos Prospectivos , Rinite Alérgica Sazonal/imunologia , Estações do Ano , Índice de Gravidade de Doença
18.
J Pharm Pharm Sci ; 24: 191-199, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33909554

RESUMO

PURPOSE: Prostaglandins play a pivotal role in modulating hair growth cycle. Prostaglandin F2α and prostaglandin E have stimulating and prostaglandin D has inhibitory effects on hair follicle. Cetirizine inhibits release of prostaglandin D2 and stimulates the release of prostaglandin E2. In the present study, the efficacy and safety of twice daily application of topical cetirizine 1% versus minoxidil 5% solutions for 16 weeks were compared in male androgenetic alopecia (AGA). METHODS: Forty men, aged 18 to 49 years, were randomly divided into two equal groups to apply either cetirizine 1% or minoxidil 5% solutions. The study was divided into two phases, a 16-week treatment phase either with cetirizine or minoxidil (anagen phase), followed by an 8-week drug-free (telogen phase) with a follow-up when patients used placebo. Efficacy outcomes included the change in total hair density, vellus and terminal hair density, hair diameter and the percentage of hair in anagen and telogen phases from baseline in 16 and 24 weeks. RESULTS: After 16 weeks, we observed a significant increase in total and vellus hair density in both minoxidil and cetirizine groups, but the improvement was much higher in the minoxidil group. The percentage of hair in the anagen phase also increased in both groups after 16 weeks of treatment, but then diminished after 8 weeks of placebo consumption. No significant adverse reactions associated with the administration of cetirizine solution were reported. CONCLUSION: Cetirizine 1% solution was effective in hair growth without any complications for treatment of male AGA.


Assuntos
Alopecia/tratamento farmacológico , Cetirizina/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Minoxidil/uso terapêutico , Administração Tópica , Adulto , Humanos , Masculino , Minoxidil/efeitos adversos , Método Simples-Cego , Soluções , Resultado do Tratamento , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-33580925

RESUMO

Darier disease (DD) is a rare type of inherited keratinizing disorder with no definitive therapeutic approach. The objective of this study is to provide a detailed literature review of all the available treatment modalities of Darier disease, including those that are both surgical and non surgical, to compare their efficacies and to propose a novel therapeutic approach. A complete search of the literature for all articles describing the different treatments of Darier disease, with no restrictions on patients' ages, gender or nationalities, was performed with the use of PubMed. A total of 68 articles were included in the study: 3 prospective studies, 44 case reports/case series and 21 letters/correspondences/clinical images. The treatments described were topical, oral or physical. Retinoids (isotretinoin, tazarotene and adapalene) and fluorouracil were the two most effective topical treatments. Oral retinoids were the most effective oral therapy and were prescribed in the cases of generalized Darier disease. For localized and resistant skin lesions, physical therapies including surgical excision, dermabrasion and CO2 laser ablation were the first line choices. Limitations of this article include the inability to verify the accuracy of the published data, the relatively small sample size, the absence of randomized controlled clinical trials and possible unidentified confounding factors in various studies. In every therapeutic approach to Darier disease, consideration of patient comorbidities, disease distribution, severity and treatment accessibility is essential. Large and randomized clinical trials are necessary for the comparison of the efficacy and the safety of all the treatments of Darier disease and settling a consensus for management.


Assuntos
Doença de Darier/terapia , Administração Tópica , Algoritmos , Toxinas Botulínicas , Cetirizina/uso terapêutico , Ciclosporina/uso terapêutico , Dermabrasão , Diclofenaco/uso terapêutico , Di-Hidroxicolecalciferóis/uso terapêutico , Doxiciclina/uso terapêutico , Combinação de Medicamentos , Eletrocirurgia , Etinilestradiol/uso terapêutico , Ácidos Graxos/uso terapêutico , Fluoruracila/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Lasers , Levanogestrel/uso terapêutico , Cloreto de Magnésio/uso terapêutico , Naltrexona/uso terapêutico , Fotoquimioterapia , Retinoides/uso terapêutico , Tacrolimo/uso terapêutico
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