Circulating CD4+ CD25 high FoxP3+ T cells vary in different clinical forms of leprosy

Background CD4⁺ CD25^highFoxP3⁺ regulatory T cells (T‐regs) were reported to increase in chronic infections. We aimed at studying their frequency in leprosy to investigate their role during Mycobacterium leprae infection. Methods Using flow cytometry, the frequency and FoxP3 expression of circulating T‐regs was assessed in 38 leprosy patients and 38 healthy controls. Patients were divided into; group I tuberculoid (TT), group II borderline cases [borderline tuberculoid (BT), borderline (BB), and borderline lepromatous (BL)], group III lepromatous (LL), and group IV erythema nodosum leprosum (ENL). Results Mean T‐regs% and FoxP3 expression were significantly elevated in patients (particularly TT) compared to controls (3.8 ± 2.5% vs. 2.5 ± 0.8% and 78.8 ± 56.2% vs. 55.8 ± 15.7%, respectively) (P < 0.05). Comparing the four disease groups, T‐regs% was significantly different (median 5.3% in group I, 3.4% in group II, 2.8% in group III, and 1.2% in group IV; P = 0.005). FoxP3% on T‐regs was not significantly different between them [median 71.5% in TT, 62.3% in borderline categories, 67.75% in LL, and 85.75% in ENL; P = 0.149). Notably FoxP3 expression was significantly higher in ENL than controls (P = 0.011). Conclusion The frequency and suppressive marker of circulating T‐regs are elevated in TT patients. Patients with LL and ENL express significantly lower frequency of T‐regs and higher FoxP3 expression (in ENL), consistent with disease progression and immune hyper‐activation in these disease categories. Thus, rather than being detrimental to immunity, intact T‐regs activity may be beneficial to leprosy patients.     

Cumulative administrations of gadolinium-based contrast agents: risks of accumulation and toxicity of linear vs macrocyclic agents

Abstract

Ever since gadolinium was found to deposit in the brain of patients with normal kidney function by Kanda et al. in 2014, several studies have been conducted to evaluate its effect on the patients’ health. However, conflicting results were obtained regarding imaging in gadolinium retention. These finding were attributed to the chelating structure of the administered gadolinium-based contrast agent (GBCA): linear agents were found to accumulate in the dentate nucleus (DN) and the globus pallidus (GP) of subjects even after one dose. There are some contradictory results when assessing macrocyclic agents. In the following article, we review the basis of GBCAs characteristics and their side effects, as well as, the MRI studies that assessed the accumulation of gadolinium in the brain. Based on the results of several studies, in 2017, the European Medicine Agency requested the suspension of the marketing authorizations for three linear GBCAs: gadodiamide (Omniscan®), gadoversetamide (Optimark®) and gadopentate dimeglimine (Magnevist®) and limited the use of gadoxetate disodium (Primovist/Eovist®) and gadobenate dimeglumine (MultiHance®) to hepatic uptake for imaging poorly vascularized hepatic lesions. Accordingly, the FDA did not restrict GBCA use, but will continue to study their safety and urged clinicians to use these agents sparingly. All macrocyclic GBCAs continued however to be used as no available valid evidence linked them to brain gadolinium retention. Regardless of possible accumulation in the brain, there is no evidence to-date that gadolinium retention leads to any disease or disorders in subjects with normal renal function. Further investigations with long-term follow-up are needed.     

A new isoflavone from Blepharis ciliaris of an Egyptian origin

A phytochemical study of the aerial parts of Blepharis ciliaris (L.) B.L. Burtt. led to the isolation of one new isoflavone glycoside caffeic acid ester: genistein-7-O-(6″-O-E-caffeoyl-β-d-glucopyranoside) (4), along with seven known compounds: methyl veratrate (1), methyl vanillate (2), protocatechuic acid (3), naringenin-7-O-(3″-acetyl-6″-E-p-coumaroyl-β-d-glucopyranoside) (5), naringenin-7-O-(6″-E-p-coumaroyl-β-d-glucopyranoside) (6), apigenin-7-O-(6″-E-p-coumaroyl-β-d-glucopyranoside) (7), and acteoside (8). Their structures were established on the basis of detailed analyses of physical, chemical, and spectral data. Compounds 1, 2, 3, 6, and 8 were isolated for the first time from this plant. The antioxidant activity of the different extracts as well as for some of the isolated compounds was evaluated.     

Diagnostic Evaluation of Urinary Angiogenin (ANG) and Clusterin (CLU) as Biomarker for Bladder Cancer

Bladder carcinoma is an important worldwide health problem. Both cystoscopy and urine cytology used in detecting bladder cancer suffer from drawbacks where cystoscopy is an invasive method and urine cytology shows low sensitivity in low grade tumors. This study validates easier and less time-consuming techniques to evaluate the value of combined use of angiogenin and clusterin in comparison and combination with voided urine cytology in the detection of bladder cancer patients. This study includes malignant (bladder cancer patients, n?=?50), benign (n?=?20) and healthy (n?=?20) groups. The studied groups were subjected to cystoscopic examination, detection of bilharzial antibodies, urine cytology, and estimation of urinary angiogenin and clusterin by ELISA. The overall sensitivity and specificity were 66 and 75 % for angiogenin, 70 and 82.5 % for clusterin and 46 and 80 % for voided urine cytology. Combined sensitivity of voided urine cytology with the two studied biomarkers was 88 % which is higher than the combined sensitivity of both markers alone (82 %) and that of the cytology with each marker (76 and 80 %) for angiogenin and clusterin respectively. In conclusion, combined use of the cytology with the studied biomarkers can improve the sensitivity for detecting bladder cancer, and may be very useful in monitoring the effectiveness of antiangiogenic and apoptotic therapies in bladder cancer.