Non HLA genetic markers association with type-1 diabetes mellitus

The currently available data identified IDDM1 and IDDM2 as 2 susceptibility loci for type 1 diabetes (T1D). The major histocompatibility complex (MHC)/HLA region referred to as IDDM1 contains several 100 genes known to have a great influence on T1D risk. Within IDDM2, a minisatellite variable number of tandem repeats (VNTR) locus in the insulin gene (INS) promoter region is likely to represent the etiologic polymorphism. The aim of the present work was to study the association between genotypes and susceptibility to T1D among Egyptian diabetic children and their family members. Twenty-five nuclear Egyptian families with 27 children having T1D, aged 3–14 years, their nondiabetic 44 sibs, aged 3–15 years and their parents were included in our study. All studied children were subjected to: detailed history and family pedigree. Thorough clinical examination and anthropometric measurements. Laboratory work up of diabetes including random blood sugar (RBS) and HbA1C. Molecular genetics of INS was studied in four steps; nucleic acid purification, amplification, sequencing and haplotyping using flanking single nucleotide  polymorphisms (SNPs) as surrogate markers for minisatellite alleles identification. Analysis of variant repeat distribution among Egyptian families combined with flanking haplotypes revealed that all our diabetic children had class I alleles of INS; 9 had class IC+, 9 had classID+ and 9 had class ID, while all non-diabetic family members had class III alleles of INS. Therefore the three class I alleles were considered to be equally predisposing to T1D, while class III alleles are dominantly protective. There was significant positive correlations between body massindex (BMI) and both HbA1C and AST liver enzyme among diabetic children with class IC+ but not other alleles; indicating that they need close monitoring of their diabetic control and liver functions beside following specific dietary regimens. It can be concluded that all class I alleles (IC+, ID+ and ID) are equally important susceptibility factors for T1D among Egyptian children, while class III alleles (IIIA and IIIB) are dominantlyprotective. It is concluded also that our diabetic children with class IC+ are an especially endangered subgroup of diabetics. Genotyping for INS-VNTR alleles is recommended for diabetic children as an important step of diagnostic and follow up regimens and for their non-diabetic familymembers for family counseling and early identification of potential diabetics. Further studies of INS-VNTR alleles and HLA haplotypes all over Egypt are recommended to define the Egyptian susceptibility loci for T1D and their relations to the clinical and laboratory findings as an importantnational programs

Validated spectrophotometric methods for determination of Alendronate sodium in tablets through nucleophilic aromatic substitution reactions

<p>Abstract</p> <p>Background</p> <p>Alendronate (ALD) is a member of the bisphosphonate family which is used for the treatment of osteoporosis, bone metastasis, Paget's disease, hypocalcaemia associated with malignancy and other conditions that feature bone fragility. ALD is a non-chromophoric compound so its determination by conventional spectrophotometric methods is not possible. So two derivatization reactions were proposed for determination of ALD through the reaction with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and 2,4-dinitrofluorobenzene (DNFB) as chromogenic derivatizing reagents.</p> <p>Results</p> <p>Three simple and sensitive spectrophotometric methods are described for the determination of ALD. Method I is based on the reaction of ALD with NBD-Cl. Method II involved heat-catalyzed derivatization of ALD with DNFB, while, Method III is based on micellar-catalyzed reaction of the studied drug with DNFB at room temperature. The reactions products were measured at 472, 378 and 374 nm, for methods I, II and III, respectively. Beer's law was obeyed over the concentration ranges of 1.0-20.0, 4.0-40.0 and 1.5-30.0 μg/mL with lower limits of detection of 0.09, 1.06 and 0.06 μg/mL for Methods I, II and III, respectively. The proposed methods were applied for quantitation of the studied drug in its pure form with mean percentage recoveries of 100.47 ± 1.12, 100.17 ± 1.21 and 99.23 ± 1.26 for Methods I, II and III, respectively. Moreover the proposed methods were successfully applied for determination of ALD in different tablets. Proposals of the reactions pathways have been postulated.</p> <p>Conclusion</p> <p>The proposed spectrophotometric methods provided sensitive, specific and inexpensive analytical procedures for determination of the non-chromophoric drug alendronate either per se or in its tablet dosage forms without interference from common excipients.</p> <p>Graphical abstract</p> <p><display-formula><graphic file="1752-153X-6-25-i3.gif"/></display-formula></p

Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children &lt;18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p&lt;0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p&lt;0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p&lt;0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Freshwater Snail Distribution Related to Physicochemical Parameters and Aquatic Macrophytes in Giza and Kafr El-Shiekh Governorates, Egypt

A field work was conducted to study the density of the freshwater snail in relation to the vegetation cover as well as the physical and chemical properties in different watercourses. Two sites were selected in Giza governorate while, three sites were selected at Kafr El-Shiekh governorate. Water temperature, conductivity, total hardness, and pH were measured in the selected sites as well as bisphenol A (BPA) levels. Snail sampling was carried out and all types of macrophytes found in each site were collected, identified and coverage. Nine snails species namely Biomphalaria alexandrina, Physa acuta, Planorbis planorbis, Lymnaea natalensis, Bulinus truncates, Bellamya unicolor, Melanoides tuberculata, Helisoma duryi and Lanistes carinatus were identifi ed. B. alexandrina was the most enumeration of snail species. The percentage of total snail species (75.47 %) was recorded at 28 °C as compared to 5.86 % recorded at 34 °C. Five species of aquatic vegetation were identifi ed, two of them correlated positively and signifi cantly with various snail species. Sites in which snails associated with macrophytes were characterized with higher ranges of chemicals, dissolved oxygen, and conductivity. In conclusion, the most important of the associating vegetation was L. gibba which correlated with B. alexandrina and served as an indicator plant.</p

Factors Affecting Lethality of Bisphenol a on Biomphalaria alexandrina Snails

The present study was undertaken to investigate the influence of some environmental factors including temperature, water vegetation, bed mud and pH on LC50, LC90 and LT50 of bisphenol A (BPA) on the snail host of Schistosoma mansoni, Biomphalaria alexandrina. Effects of exposure to the sublethal concentrations of BPA on some biological aspects of the snails and on the cercarial output form S. mansoni infected snails were studied. Results showed that temperature, water vegetation, bed mud and pH markedly affected the lethality of BPA. The biological parameters of B. alexandrina including survival rate, egg hatchability and egg laying capacity were greatly affected by exposure to BPA and the response was dose dependent. Regarding the possible effect of BPA on transmission of schistosomiasis, results showed that exposure to different concentration of BPA for 7 days before miracidial infection caused the death of all the snails before reaching the patent period while, no cercarial output was recorded from snails exposed to BPA for 24 hrs till their death. In conclusion, our results showed that the environmental characteristics may alter the biological impacts of BPA and the exposure of snail to BPA may affect the transmission of schistosomiasis.</p