Investigation of Antiproliferative Effects of Combinations of White and Black Garlic Extracts with 5-Fluorouracil (5-FU) on Caco-2 Colorectal Adenocarcinoma Cells.

Garlic is rich in bioactive compounds that are effective against colon cancer cells. This study tests the antioxidant and antiproliferative effects of cold-extracted white and black garlic extracts. Black garlic extracted in water (SSU) exhibits the highest antioxidant activity, phenolic content, and flavonoid content, while black garlic extracted in ethanol (SET) shows the lowest values. Caspase-3 activity is notably higher in the white garlic extracted in methanol (BME), white garlic extracted in methanol combines with 5-FU, black garlic extracted in ethanol (SET), black garlic extracted in ethanol combines with 5-fluorouracil (5-FU), and 5-FU treatments compare to the control group (p > 0.05). BME+5-FU displays the highest caspase-8 activity (p < 0.05). A decrease in NF-κB levels is observed in the SET+5-FU group (p>0.05), while COX-2 activities decrease in the BME, SET+5-FU, SET, and 5-FU groups (p>0.05). Wound healing increases in the BME, BME+5-FU, SET+5-FU, and 5-FU groups (p < 0.05). In conclusion, aqueous black garlic extract may exhibit pro-oxidant activity despite its high antioxidant capacity. It is worth noting that exposure to heat-treated food and increased sugar content may lead to heightened inflammation and adverse health effects. This study is the first to combine garlic with chemo-preventive drugs like 5-FU in Caco-2 cells.

Comparison of recent anaphylaxis diagnostic criteria in real life: Can more patients be diagnosed as having anaphylaxis?

Introduction: In 2020, World Allergy Organization (WAO) updated their diagnostic criteria for anaphylaxis, which differed as a result from the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria which were still used in the 2021 update of the European Academy of Allergy and Clinical Immunology (EAACI) anaphylaxis guideline. Our aim was to evaluate and to compare both diagnostic criteria and attempt to identify factors affecting severity of anaphylaxis. Methods: The medical records of the patients who were evaluated with suspected anaphylaxis at 3 medical centers in Türkiye between 2014 and 2021, and underwent a detailed diagnostic work-up, were analyzed retrospectively. Diagnosis of anaphylaxis was evaluated based on the WAO 2020 and EAACI 2021 and NIAID/FAAN diagnostic criteria. The severity of anaphylaxis was determined according to the WAO systemic allergic reaction grading system. Grade 5 anaphylaxis was defined as having respiratory failure, collapse/hypotension, loss of consciousness. Patients' demographic and clinical characteristics were further analyzed depending on the severity of the reaction. Results: One thousand and six patients were evaluated and 232 patients without a convincing diagnosis of anaphylaxis were excluded from the study. The remaining 774 patients (70.6% female, median [Inter quartile range (IQR) 25-75] age: 42 [33-52]) were included for further examination. Anaphylaxis was diagnosed in 729 (94.2%) patients meeting both criteria whereas 35 patients (4.5%) with isolated laryngeal involvement and 10 (1.3%) patients with isolated respiratory involvement were only diagnosed according to the WAO 2020 criteria. Twenty-three patients (3.0%) had a diagnosis of indolent systemic mastocytosis. Mastocytosis was related to grade 5 anaphylaxis [p = 0.022, OR (CI) = 2.9 (1.1-7.6)]. Venom allergy was a risk factor for grade 5 anaphylaxis among those for whom an eliciting allergen could be determined [p = 0.03, OR (CI) = 2.7 (1.1-6.8)]. For drug induced anaphylaxis, parenteral route of drug administration and proton pump inhibitor (PPI) allergy were considered as risk factors for grade 5 anaphylaxis [p < 0.001, OR (CI) = 6.5 (2.5-17.0); p = 0.011, OR (CI) = 10.3 (1.6-63.3)]. Conclusion: This multicenter study demonstrated that both criteria identified the majority of patients with anaphylaxis, but the WAO 2020 diagnostic criteria identified an additional 6%. Hymenoptera stings, PPI allergy, parenteral drug administration, and underlying mastocytosis were associated with more severe episodes.

Impact of mental health on disease activity in mastocytosis during COVID-19 pandemic.

BACKGROUND: Mast cell-related symptoms might be influenced by mental health status in mastocytosis. In this study, we aimed to investigate the influence of mental health problems developed during the COVID-19 pandemic on the course of mastocytosis. METHODS: Mental health status in 60 adult patients with mastocytosis was prospectively evaluated with the total Depression-Anxiety-Stress Scale (tDASS-21) and Fear of COVID-19 Scale (FCV-19S) in the lockdown period (LP) and the return to normal period (RTNP) during the pandemic. The disease course was assessed from emergency and outpatient medical reports, including Scoring Mastocytosis (SCORMA) index and serum baseline tryptase levels, by telephone interviews and clinical visits. RESULTS: The mean FCV-19S and median tDASS-21 scores were significantly higher in LP than RTNP (p < 0.001) and there was a positive correlation between FCV-19S and tDASS-21 in LP (r = 0.820, p < 0.001) and in RTNP (r = 0.572 p= <0.001). Disease-related symptoms including skin lesions, flushing and anaphylaxis attacks increased in 22 patients in LP, and in this group, mean FCV-19S and median tDASS-21 were higher than those without symptom exacerbation (p < 0.001). During the study period, four (6.7%) patients who experienced COVID-19 recovered without any requirement for hospitalization and had not experienced symptom exacerbation. CONCLUSIONS: Fear of COVID-19 can be a reason for mental health changes, including depression, anxiety and stress which may further increase mast cell-related symptoms. Therefore, psychological support is important to control the severity of mast cell-related symptoms in mastocytosis during a pandemic.

Paucigranulocytic asthma: Do sputum macrophages matter?

Background: Although paucigranulocytic asthma (PGA) is the most common phenotype of stable asthma, its features have not been adequately studied. In this study, we aimed to display the characteristics of PGA. Method: A total of 116 non-smoking adult patients with asthma (80% women; mean ± standard deviation age, 39 ± 12.9 years) admitted to three tertiary centers were included. Their demographic and clinical features, allergy status, biochemical results, scores of Asthma Control Test (ACT), spirometry, and exhaled nitric oxide (FeNO) measurements were obtained. Induced sputum cytometry was performed. Results: Four phenotypes, according to induced sputum cell counts, were detected: eosinophilic asthma (EA) (22.4%), mixed granulocytic asthma (MGA) (6.9%), neutrophilic (NA) (7.8%), and PGA (62.9%). In the sputum, macrophages were higher in the PGA group compared with the other groups (PGA versus NA and PGA versus MGA, p < 0.001; and PGA versus EA, p =0 .030). The atopy rate between phenotypes was the same. Although the forced expiratory volume in the first second of expiration (FEV1) was similar in four groups, the ratio of FEV1 to the forced vital capacity ratio was higher (p = 0.013) and FEV1 reversibility was lower in the patients with PGA than the corresponding values in other phenotypes (p = 0.015). Low reversibility was comparable both in patients with PGA who were inhaled corticosteroid (ICS) naive and in patients on ICS treatment. Although insignificant, the FeNO values and blood eosinophil counts were higher in the MGA and EA groups, whereas these were the lowest in the PGA group. The uncontrolled asthma ratio was low in PGA (16%), whereas it was 11% for NA, 25% for MG, and 23% in EA. Conclusion: Macrophages are predominant in sputum of patients with PGA. Besides a lower uncontrolled asthma ratio, lower FEV1 reversibility is a prominent characteristic of this phenotype.

Prevalence of atopy and allergic rhinitis in patients with adult non-cystic fibrosis bronchiectasis

Background/aim: Non-cystic fibrosis bronchiectasis (non-CF BR) is common in developing countries.Limited data are available regarding the impact of atopy, and no data are available regarding allergic rhinitis in patients with adult bronchiectasis.The aim of this study was to evaluate the prevalence of atopy and allergic rhinitis in the clinical conditions of patients with BR. Materials and methods: The study enrolled 101 patients who were diagnosed with non-CF BR using high-resolution computed chest tomography. Allergic rhinitis (AR) was defined by skin prick test (SPT) positivity and the presence of any nasal symptoms (watery runny nose, nasal obstruction, nasal itching, and sneezing). Results: The mean age of patients was 48 ± 15 years (range 18­82); 55 (54.5%) patients were female. SPT positivity was detected in 37 (36.6%) cases. AR was detected in 32 (31.7%) patients with non-CF BR. AR was related to dyspnea (P = 0.04) and number of admissions to an emergency department in the previous year (P = 0.01). Forced expiratory volume in 1 s and forced vital capacity in patients with and without AR were different (P = 0.01 and P = 0.01, respectively). AR was correlated with number of admissions to an emergency department in the last year (r = 0.417, P = 0.005). Conclusion: We concluded that atopy was detected in more than one-third of adult non-CF BR patients. This study demonstrated that non-CF BR patients might have AR; it might be important to be aware of nasal symptoms in non-CF BR patients.

Evaluation of the Potential Risk Factors for Drug-Induced Anaphylaxis in Adult Patients.

AIM: To investigate the potential risk factors in patients who have experienced anaphylaxis from drugs. METHOD: The study included 281 adult patients (median age 40 years; 76.5% female) who experienced immediate types of hypersensitivity reaction to a drug. The patients were divided into an anaphylaxis group and a nonanaphylaxis group. The anaphylaxis group was diagnosed according to the criteria of the World Allergy Organization. Skin testing with culprit drugs was performed. In the nonanaphylaxis group, drug provocation tests were performed with culprit drugs, including aspirin or diclofenac, to determine nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Atopy was determined by skin prick tests with the common inhalant allergens. Patients' demographics, clinical features, and baseline tryptase and total IgE levels were compared between the 2 groups. RESULTS: The median interval between the last reaction in the patient's history and the study evaluation was 7 months (range 1-120 months). In 52.3% of the patients, reactions were defined as anaphylaxis. The most common culprit drugs were NSAIDs (56.9%) and ß-lactams (34.7%). The culprit drugs were used parenterally in 13.2% of the patients. 34.9% of the patients had comorbid diseases and 24.6% used additional drugs, the most common being antihypertensives (10%). Atopy was determined in 28.8% and 28.1% of the patients were smokers. The median serum level of baseline tryptase and total IgE was 3.5 µg/L and 77 kU/L, respectively. In 46.3% of the patients, skin tests with culprit drugs were positive and the positivity ratio was higher in the anaphylaxis group (p = 0.002). Anapyhlaxis was more common in patients who were: hypertensive, atopic, using angio-tensin-converting enzyme inhibitors/angiotensin receptor blockers, and received the culprit drug parenterally (p = 0.034, p = 0.04, p = 0.03, p = 0.035, p = 0.013, and p < 0.001). In the multivariate analysis, it was observed that the parenteral usage of the drug and the presence of atopy were significantly higher in the anaphylaxis group (p < 0.001, odds ratio [OR] = 20.05, confidence interval [CI] 4.75-88.64; p = 0.012, OR = 2.1, CI 1.17-3.74). Age, smoking, family history, and serum levels of baseline tryptase and total IgE did not differ between groups. CONCLUSION: The parenteral route and atopy increase the risk of drug-induced anaphylaxis. IgE-mediated sensitivity to the culprit drug seems to facilitate anaphylaxis.

Oral nickel exposure may induce Type I hypersensitivity reaction in nickel-sensitized subjects.

BACKGROUND: Little is known about the clinical and immunological changes in the nickel allergic patients with systemic symptoms. We aimed to evaluate T helper cell responses of patients with different clinical presentations due to nickel. METHODS: Patients having various allergic symptoms and positive patch test results to nickel and 20 controls underwent skin prick tests with nickel. IL-10, IL-4, IL-5 and IFN-gamma were measured in the culture supernatants of PBMC stimulated by nickel during lymphocyte proliferation test (LTT). RESULTS: 69 patients (56 female, mean age: 49.2 ± 13.1), 97% having nickel containing dental devices and 20 controls (8 female, mean age 34.9 ± 12.06) were evaluated. Skin prick tests with nickel were positive in 70% of the patients (p<0.001), being significantly higher in the patients with urticaria/angioedema (p=0.02). The LTT stimulation index (p<0.0001), IL-4 (p=0.002), IFN-gamma (p=0.01), IL-5 (p=0.04) and IL-10 (p=0.003) were higher in the patient group. LTT stimulation index, IL-4 and IL-10 were significantly elevated in patients having urticaria, angioedema and respiratory symptoms when compared to those who had only oral symptoms or systemic dermatitis (p=0.004, p=0.002 and p=0.01, respectively). CONCLUSION: This study suggests the presence of Type I hypersensitivity in addition to a Type IV immune reaction in patients with chronic systemic symptoms related to nickel. Nickel containing dental alloys and oral nickel intake seem to trigger systemic symptoms in previously nickel sensitized patients.

A practical and successful desensitization protocol for immediate hypersensitivity reactions to iron salts.

Orally administered iron salts (OAS) are widely used in the management of iron deficiency anemia and hypersensitivity reactions to OAS are not common. If an offending drug is the sole option or is significantly more effective than its alternatives, it can be readministered by desensitization. The oral desensitization protocols for iron published so far concern either desensitization that was completed only over a long period or did not attain the recommended therapeutic dose. We aimed to develop a more effective protocol. We report here on 2 patients who experienced hypersensitivity reactions to OAS. After confirming the diagnosis, both patients were desensitized to oral ferrous (II) glycine sulfate complex according to a 2-day desensitization protocol. A commercial suspension of oral ferrous glycine sulfate, which contains 4 mg of elemental iron in 1 ml, was preferred. We started with a dose as low as 0.1 ml from a 1/100 dilution (0.004 mg elemental iron) of the original suspension and reached the maximum effective dose in 2 days. Both patients were successfully desensitized and they went on to complete the 6-month iron treatment without any adverse effects. Although hypersensitvity reactions to iron are not common, there is no alternative for iron administration. Therefore, desensitization has to be the choice. This easy desensitization protocol seems to be a promising option.