Effect of Switching the Histamine-1 Receptor Antagonist Clemastine to Cetirizine in Paclitaxel Premedication Regimens: The H1-Switch Study.

PURPOSE: Premedication, including a histamine-1 receptor (H1) antagonist, is recommended to all patients treated with paclitaxel chemotherapy to reduce the incidence of hypersensitivity reactions (HSRs). However, the scientific basis for this premedication is not robust, which provides opportunities for optimization. Substitution of intravenously administered first-generation H1 antagonist for orally administered second-generation H1 antagonist could reduce side effects, and improve efficiency and sustainability. This study investigates the efficacy and safety of substituting intravenous clemastine for oral cetirizine as prophylaxis for paclitaxel-induced HSRs. METHODS: This single-center, prospective, noninferiority study compares a historic cohort receiving a premedication regimen with intravenous clemastine to a prospective cohort receiving oral cetirizine. Primary end point of the study is HSR grade ≥3. The difference in incidence was calculated together with the 90% CI. We determined that the two-sided 90% CI of HSR grade ≥3 incidence in the oral cetirizine cohort should not be more than 4% higher (ie, the noninferiority margin) compared with the intravenous clemastine cohort. RESULTS: Two hundred and twelve patients were included in the oral cetirizine cohort (June 2022 and May 2023) and 183 in the intravenous clemastine cohort. HSR grade ≥3 incidence was 1.6% (n = 3) in the intravenous clemastine cohort and 0.5% (n = 1) in the oral cetirizine cohort, resulting in a difference of -1.2% (90% CI, -3.4 to 1.1). CONCLUSION: Premedication containing oral cetirizine is as safe as premedication containing intravenous clemastine in preventing paclitaxel-induced HSR grade ≥3. These findings could contribute to optimization of care for patients and improve efficiency and sustainability.

Effectiveness of Postburn Pruritus Treatment and Improvement of Insomnia-A Randomized Trial.

Postburn pruritus is difficult to assess and treat. Antihistamines used in its treatment provide little relief. Identification of the itch neuronal pathway has inspired new alternatives, including gabapentin, for its management. The study compared the effectiveness of cetirizine, gabapentin, and a combination of gabapentin and cetirizine in treating postburn pruritus. Burn patients were randomly assigned to treatment with Cetirizine (n = 23), Gabapentin (n = 23), or Cetirizine plus Gabapentin (n = 23). A baseline assessment of the intensity or the severity of pruritus was evaluated, after which treatment commenced with standard doses of the 3 study regimens. Quality of sleep was assessed at baseline (day 0) and repeated on day 3, day 7, and day 14. Approximately 97% of participants presented with moderate or severe itch; 69% with acute itch; and the majority (94.2%) experienced pruritus between the first and fourth weeks. Gabapentin reduced itch by 92.9% in 14 days compared to cetirizine's 61.8%. The combined effect of cetirizine and gabapentin was comparable using gabapentin alone. When the itch became protracted over 6 weeks, the effectiveness of cetirizine in controlling itch worsened. It reduced itch intensity by only 37.7%, whilst gabapentin did so at 89.4%. Itch intensity correlated positively with insomnia, and controlling itch intensity improved sleep. Gabapentin was more effective for the treatment of postburn pruritus than cetirizine. Controlling itch intensity improved sleep. In acute and moderate itch, low-dose gabapentin could be added if cetirizine is the drug intended for its treatment.

Comparing the Risk of Infusion-Related Reactions and Tolerability in Patients Given Cetirizine or Diphenhydramine Prior to Ocrelizumab Infusion (PRECEPT).

Background: Ocrelizumab is an effective medication for multiple sclerosis. However, infusion-related reactions (IRRs) are a concern for patients and may lead to discontinuation of ocrelizumab. To minimize IRRs, pre-medications are administered. However, from our experience, these medications, especially diphenhydramine, can cause marked drowsiness. The primary objective of this study was to evaluate whether cetirizine is non-inferior to diphenhydramine in limiting the proportion and severity of reactions from ocrelizumab infusions. Methods: Twenty participants were serially randomized in a 1:1 ratio to receive 10 mg of cetirizine or 25 mg of diphenhydramine orally prior to their first three ocrelizumab infusions. Results: The rate of IRRs in this study was similar across both treatment groups with no increase in the risk of severity, and no grade 3 IRRs. Further, patients receiving cetirizine experienced a reduction in fatigue. While there was not a significant difference in global satisfaction, this score increased over time in the cetirizine arm while it remained unchanged in the diphenhydramine arm. Conclusions: Overall, our results suggest that cetirizine does not increase the risk of infusion-related reactions compared to diphenhydramine.

Reporte de caso de dengue clásico a predominio de sintomatología dermatológica en el marco de la epidemia en la provincia de Misiones 2023-2024 / Case of classic dengue with predominance of dermatologic symptoms in the 2023-2024 epidemic in the province of Misiones

Se presenta un caso femenino de dengue clásico (DC) en el marco de la epidemia 2023-2024 en la provincia de Misiones, con predominio de síntomas dermatológicos de exantemas máculo papulosos, habonosos y eritrodérmicos sobre los síntomas sindrómicos cardinales. Las lesiones presentan componente humoral y de extravasación, sin diátesis ni componentes purpúricos apreciables, presentando una rápida y efectiva evolución al eritema y la normalización con tratamiento antihistamínico y corticoide parenteral. De la misma manera se evalúan alteraciones analíticas hematológicas y hepáticas de gran magnitud, con escasa repercusión clínica, que se mensuran en función del riesgo relativo al dengue hemorrágico (DH) y el pronóstico de la paciente. (AU)

A female case of classic dengue (DC) is presented in the context of the 2023-2024 epidemic in the province of Misiones, with a predominance of dermatologic symptoms of maculopapular, hives, and erythrodermic rashes overlapping the cardinal syndromic symptoms. The lesions have a humoral and extravasation component, without any significant diathesis or purpuric components, showing rapid and effective progression to erythema and normalization with antihistamine and parenteral corticosteroid treatment. Similarly, hematologic and hepatic analytical alterations of great magnitude are evaluated, with little clinical impact, measured in terms of relative risk for hemorrhagic dengue (HD) and the prognosis of the patient. (AU)

Allergic Rhinitis: A Review.

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.

Efficacy of levocetirizine in isolated rat tracheal smooth muscle.

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.

Histamine H1 receptor antagonist attenuates catecholamine surge and organ injury after severe burns.

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.

Comparison between topical cetirizine with minoxidil versus topical placebo with minoxidil in female androgenetic alopecia: a randomized, double-blind, placebo-controlled study.

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).

Effects of second-generation H1-antihistamine drugs on angiogenesis in in vivo chick chorioallantoic membrane model.

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.

Concomitant medication of cetirizine in advanced melanoma could enhance anti-PD-1 efficacy by promoting M1 macrophages polarization.

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.

Shufeng Jiedu capsule ameliorates olfactory dysfunction via the AMPK/mTOR autophagy pathway in a mouse model of allergic rhinitis.

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.

Influences of Bifid Triple Viable Capsules Plus Cetirizine on Gut Microbiota and Immune Function in Children with Eczema.

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.

Improving the Quality of Life in the Management of Allergic Rhinitis: New Perspective on Cetirizine.

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.

Smart Peptide Defense Web In Situ Connects for Continuous Interception of IgE against Allergic Rhinitis.

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.

Analysis of degradation and pathways of three common antihistamine drugs by NaClO, UV, and UV-NaClO methods.

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.

Levocetirizine and montelukast in the COVID-19 treatment paradigm.

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.

Urticaria and edema in a 2-year-old boy.

The absence of blisters, the presence of mild systemic symptoms, and the patient's age guided the diagnosis.

Mast cell function in prostate inflammation, fibrosis, and smooth muscle cell dysfunction.

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.