Antileukemic activity of sulfoxide nutraceutical allicin against THP-1 cells is associated with premature phosphatidylserine exposure in human erythrocytes.

BACKGROUND: Allicin (ACN), a sulfoxide in freshly crushed garlic, is known for its diverse bioactive properties. Among the most notable effects of ACN is its antitumor activity against a wide array of cancer types. Thus, ACN may be a promising anticancer therapeutic. Nevertheless, chemotherapy-induced anemia is a major obstacle in cancer management with a prevalence of up to 70%. Although the pathophysiology behind it remains elusive, a number of medications known to cause anemia in patients have been shown to induce premature programmed cell death in red blood cells (RBCs) known as eryptosis. This study, thus, investigates the anticancer potential of ACN against THP-1 monocytic leukemia cells, its toxic effects on human RBCs, and delineate the underlying biochemical mechanisms. METHODS: Cytotoxicity was detected using the MTT assay, while hemoglobin leakage was used as a surrogate for hemolysis which was photometrically measured. Major eryptotic events were examined using flow cytometry with fluorescent probes. Phosphatidylserine (PS) exposure was detected by Annexin-V-FITC, cytosolic calcium with Fluo4/AM, and reactive oxygen species with H2DCFDA. RESULTS: Our results show that ACN induces hemolysis in a dose-dependent fashion, which is significantly abrogated in absence of extracellular calcium. Moreover, ACN stimulates PS exposure, intracellular calcium overload, and oxidative stress. Using small-molecule inhibitors, we demonstrate that the pro-eryptotic activity of ACN is ameliorated in presence of zVAD(OMe)-FMK, SB203580, and D4476. CONCLUSION: ACN possesses both hemolytic and eryptotic properties mediated through elevated intracellular calcium levels, oxidative stress, caspase, p38 MAPK, and CK1α.

Clinical and hematological features among ß-thalassemia major patients in Jazan region: A hospital-based study.

CONTEXT: Beta-thalassemia is a prevalent hereditary blood disorder in Saudi Arabia. Various clinical manifestations and hematological abnormalities are common among these patients. AIMS: To evaluate the clinical manifestations and hematological parameters of ß-thalassemia patients in Jazan, Saudi Arabia. SETTINGS AND DESIGN: This is a cross-sectional study conducted in Jazan region, Saudi Arabia. METHODS AND MATERIALS: We included 36 ß-Thalassemia major patients who admitted to PMNH during the period from February 1, 2016 to December 31, 2017. Clinical features were obtained via physical examination. The hematological parameters were obtained from the patients' medical records. STATISTICAL ANALYSIS USED: Descriptive and inferential statistics were conducted using SPSS. Continuous data was evaluated using independent sample t-test and Chi-square was used to evaluate categorical variables. P < 0.05 indicated statistical significance. RESULTS: Mean age was 18.56 ± 6.89 years. Males were 23 (63.9%). About 41.4% of patients were underweight. Exposing of the upper teeth was the most prominent feature (n = 19, 59.4%). The majority of patients were splenectomized (62.1%). About two-thirds have moderate anemia. More than half of the patients (58.8%) had high WBCs counts and 35.3% had a high platelet count, especially among those who underwent splenectomy. Approximately, two-thirds had a ferritin level higher than 2500 ng/ml. O+ blood group was the most frequent blood group among the patients (n = 15, 46.9%). CONCLUSIONS: Deteriorated clinical and hematological parameters in our study justify the need for more efforts for regular evaluation and follow-up of the ßTM patients and reevaluation of the management protocols to be improved or modified.

Screening for glucose-6-phosphate dehydrogenase deficiency in neonates: a comparison between cord and peripheral blood samples.

BACKGROUND: The use of cord blood in the neonatal screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency is being done with increasing frequency but has yet to be adequately evaluated against the use of peripheral blood sample which is usually employed for confirmation. We sought to determine the incidence and gender distribution of G6PD deficiency, and compare the results of cord against peripheral blood in identifying G6PD DEFICIENCY neonates using quantitative enzyme activity assay. METHODS: We carried out a retrospective and cross-sectional study employing review of primary hospital data of neonates born in a tertiary care center from January to December 2008. RESULTS: Among the 8139 neonates with cord blood G6PD assays, an overall incidence of 2% for G6PD deficiency was computed. 79% of these were males and 21% were females with significantly more deficient males (p < .001). Gender-specific incidence was 3.06% for males and 0.85% for females. A subgroup analysis comparing cord and peripheral blood samples (n = 1253) showed a significantly higher mean G6PD value for peripheral than cord blood (15.12 ± 4.52 U/g and 14.52 ± 4.43 U/g, respectively, p = 0.0008). However, the proportion of G6PD deficient neonates did not significantly differ in the two groups (p = 0.79). Sensitivity of cord blood in screening for G6PD deficiency, using peripheral G6PD assay as a gold standard was 98.6% with a NPV of 99.5%. CONCLUSION: There was no difference between cord and peripheral blood samples in discriminating between G6PD deficient and non-deficient neonates. A significantly higher mean peripheral G6PD assay reinforces the use of cord blood for neonatal screening since it has substantially low false negative results.

Lifelong prophylaxis in a large cohort of adult patients with severe haemophilia: a beneficial effect on orthopaedic outcome and quality of life.

BACKGROUND: In the 1950s, Sweden initiated prophylaxis as a lifelong treatment for haemophilia. It was the first country to do so. OBJECTIVES: To describe and evaluate dosing and outcome of prophylactic treatment in a large cohort of adult people with severe haemophilia who have been using prophylaxis most of their lives. METHODS: Eighty-one patients born between 1932 and1992 were divided into two groups (Group A started prophylaxis at the age of ≤ 3 yr; Group B at three or more years of age) and evaluated retrospectively. Outcome was evaluated using the Hemophilia Joint Health Score (HJHS) and SF-36, a measure of quality of life. RESULTS: The median number of joint bleeds per year was 0 in both study groups; however, the annual number of joint bleeds during the final 3 yr of observation was higher in group B than in group A (P < 0.006). Twenty-five of 30 patients in group A and 27/51 patients in group B had no joint bleeds in that period. Group A had significantly better joint outcomes than group B. Patients in group A experienced better physical and social health than those in group B. CONCLUSIONS: This follow-up has provided for the first time more extensive and detailed information regarding the practice of prophylactic treatment in a large cohort of adults with severe haemophilia. The present study confirms that early start of prophylaxis continuing throughout the lifespan has been successful in virtually eliminating joint bleeds, preserving a close to normal joint status, and keeping patients healthy and able to live normal lives.