Frequency of toll-like receptor 4 variants and association with treatment response in children with primary immune thrombocytopenia.

OBJECTIVES: To investigate the frequency of toll-like receptor 4 (TLR4) variants c.896A>G (p.Asp299Gly) and c.1196C>T (p.Thr399Ile) among Egyptian children with primary immune thrombocytopenia (pITP), and their association with disease course and response to treatment. METHODS: A case-control study that included 80 children with pITP and 50 age- and sex-matched healthy controls. TLR4 c.896A>G and c.1196C>T variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Patients were classified according to their response to treatment after 3 months as responders and nonresponders. RESULTS: Compared with controls, children with pITP had significantly higher minor allele frequencies of TLR4 p.Asp299Gly (16.25% vs. 6%, odds ratio [OR] 3.04, 95% confidence interval [CI]: 1.16-9.36, p = .014) and p.Thr399Ile (20% vs. 4%, OR 6, 95% CI: 2.02-24.01, p < .001). The presence of p.Asp299Gly variant was significantly associated with chronic ITP (OR 7.78, 95% CI: 2.04-35.69, p < .001) and non-response to therapy with steroid (OR 11.67, 95% CI: 1.32-104.08, p = .012), but not thrombopoietin-receptor agonist (OR 1.67, 95% CI: 0.35-8.19, p = .464). Likewise, having p.Thr399Ile variant was significantly associated with chronic ITP (OR 5.14, 95% CI: 1.6-17.4, p = .002) and non-response to therapy with steroid (OR 6.1, 95% CI: 1.01-49.06, p = .046) but not thrombopoietin-receptor agonist (OR 1.57, 95% CI: 0.33-7.58, p = .515). CONCLUSION: The presence of TLR4 p.Asp299Gly or p.Thr399Ile variant may be associated with ITP predisposition, chronicity, and non-response to upfront steroid therapy. These findings enhance our understanding of the complex pathophysiology of pITP with potentially important clinical implications.

The Antidiabetic Effects and Modes of Action of the Balanites aegyptiaca Fruit and Seed Aqueous Extracts in NA/STZ-Induced Diabetic Rats.

Diabetes mellitus (DM) is a chronic metabolic disorder that threatens human health. Medicinal plants have been a source of wide varieties of pharmacologically active constituents and used extensively as crude extracts or as pure compounds for treating various disease conditions. Thus, the aim of this study is to assess the anti-hyperglycemic and anti-hyperlipidemic effects and the modes of action of the aqueous extracts of the fruits and seeds of Balanites aegyptiaca (B. aegyptiaca) in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. Gas chromatography-mass spectrometry analysis indicated that 3,4,6-tri-O-methyl-d-glucose and 9,12-octadecadienoic acid (Z,Z)- were the major components of the B. aegyptiaca fruit and seed extracts, respectively. A single intraperitoneal injection of STZ (60 mg/kg body weight (b.w.)) 15 min after intraperitoneal NA injection (60 mg/kg b.w.) was administered to induce type 2 DM. After induction was established, the diabetic rats were treated with the B. aegyptiaca fruit and seed aqueous extracts (200 mg/kg b.w./day) via oral gavage for 4 weeks. As a result of the treatments with the B. aegyptiaca fruit and seed extracts, the treated diabetic-treated rats exhibited a significant improvement in the deleterious effects on oral glucose tolerance; serum insulin, and C-peptide levels; liver glycogen content; liver glucose-6-phosphatase and glycogen phosphorylase activities; serum lipid profile; serum free fatty acid level; liver lipid peroxidation; glutathione content and anti-oxidant enzyme (glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase) activities; and the mRNA expression of the adipose tissue expression of the insulin receptor ß-subunit. Moreover, the treatment with fruit and seed extracts also produced a remarkable improvement of the pancreatic islet architecture and integrity and increased the islet size and islet cell number. In conclusion, the B. aegyptiaca fruit and seed aqueous extracts exhibit potential anti-hyperglycemic and anti-hyperlipidemic effects, which may be mediated by increasing the serum insulin levels, decreasing insulin resistance, and enhancing the anti-oxidant defense system in diabetic rats.

Clinical and immunological assessment of children with ataxia telangiectasia attending Sohag university hospital in Upper Egypt.

Ataxia Telangiectasia (AT) is a very rare autosomal recessive primary immune deficiency (PID) disease that affects 1 in 10,000-40,000 new births per year in the world. It is caused by biallelic mutations in ataxia telangiectasia mutated (ATM) gene and characterized by a progressive cerebellar ataxia. The clinical profile of AT children in Upper Egypt in missing. Herein, we evaluated the clinical characteristics and immunological profiles of patients with AT attending Sohag University Hospital. This was a cross-sectional study, included 21 AT patients attending the Neurological and Immunological Units, Pediatric Department, Sohag University Hospital, starting April 2018 to the end of March 2019. AT represented 20.5% of all PID patients attending the hospital. The most common type of humoral immune deficiency in patients with AT was specific IgA deficiency (52.3%) followed by hypogammaglobulinemia (23.8%). Recurrent sinopulmonary infection with different degrees of severity was the common immunological problem. The most common neurological manifestations in our studied patients, other than the ataxia, were language delay and eye movement abnormalities followed by developmental delay and head nodding. None of our patients had developed malignancy till the end of the study.

Ischemic Pressure vs Postisometric Relaxation for Treatment of Rhomboid Latent Myofascial Trigger Points: A Randomized, Blinded Clinical Trial.

OBJECTIVE: The purpose of this study was to investigate the effects of ischemic pressure (IP) vs postisometric relaxation (PIR) on rhomboid-muscle latent trigger points (LTrPs). METHODS: Forty-five participants with rhomboid-muscle LTrPs were randomly assigned into 3 groups and received 3 weeks of treatment-group A: IP and traditional treatment (infrared radiation, ultrasonic therapy, and transcutaneous electrical nerve stimulation); group B: PIR and traditional treatment; and group C: traditional treatment. Shoulder pain and disability, neck pain and disability, and pressure pain threshold (PPT) of 3 points on each side were measured before and after treatment. RESULTS: Multivariate analysis of variance indicated a statistically significant Group × Time interaction (P = .005). The PPT for the right lower point was increased in group A more than in groups B or C. Neck pain was reduced in group B more than in group C. Moreover, shoulder and neck disability were reduced in both groups A and B more than in group C. The PPTs of the left lower and middle points were increased in group B compared with groups A and C. The PPT of the left upper point was increased in group A more than in group C. There were significant changes in all outcomes in the 2 experimental groups (P < .05). No changes were found in the control group except in pain intensity, shoulder disability, and PPT of the left lower point. CONCLUSION: This study found that IP may be more effective than PIR regarding PPT, but both techniques showed changes in the treatment of rhomboid-muscle LTrPs.

Antidiabetic Potency, Antioxidant Effects, and Mode of Actions of Citrus reticulata Fruit Peel Hydroethanolic Extract, Hesperidin, and Quercetin in Nicotinamide/Streptozotocin-Induced Wistar Diabetic Rats.

This study is aimed at assessing the antihyperglycemic, antihyperlipidemic, and antioxidant effects of Citrus reticulata (C. reticulata) fruit peel hydroethanolic extract and two flavonoids, hesperidin and quercetin, in nicotinamide (NA)/streptozotocin- (STZ-) induced type 2 diabetic rats. In addition, GC-MS and HPLC-MS analyses of the extract were performed and the results indicated the presence of multiple flavonoids including hesperidin, quercetin, naringin, and polymethoxylated flavones (nobiletin and tangeretin). To achieve the aim of the study, diabetic rats with NA/STZ-induced T2DM were orally treated with C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin at a dose of 100 mg/kg b.w./day for four weeks. The treatments with C. reticulata fruit peel extract, hesperidin, and quercetin significantly ameliorated the impaired oral glucose tolerance; the elevated serum fructosamine level; the diminished serum insulin and C-peptide levels; the altered HOMA-IR, HOMA-IS, and HOMA-ß cell function; the decreased liver glycogen content; the increased liver glucose-6-phosphatase and glycogen phosphorylase activities; the deleteriously affected serum lipid profile; the elevated serum AST and ALT activities; and the raised serum creatinine and urea levels in the diabetic rats. The treatments also produced remarkable improvement in the antioxidant defense system manifested by a decrease in the elevated liver lipid peroxidation and an increase in the lowered glutathione content and GPx, GST, and SOD activities. Furthermore, the three treatments enhanced the mRNA expression of GLUT-4 and the insulin receptor ß-subunit, but only quercetin produced a significant increase in the expression of adiponectin in adipose tissue of diabetic rats. In conclusion, C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin have potent antidiabetic effects which may be mediated through their insulinotropic effects and insulin-sensitizing actions. In addition, the alleviation of the antioxidant defense system by the extract, hesperidin, and naringin may have an important action to enhance the antidiabetic actions and to improve liver and kidney functions in NA/STZ-induced diabetic rats.

Improvement of 6-gingerol production in ginger rhizomes (Zingiber officinale Roscoe) plants by mutation breeding using gamma irradiation.

Ginger (Zingiber officinale Roscoe) is a valuable culinary and medicinal plant. The compound 6-gingerol is the main gingerol in ginger rhizomes and it possesses interesting pharmacological and physiological properties. Mutation breeding involved using low doses of gamma radiation (5-30 Gy) to increase the genetic variability in ginger rhizomes (M1 generation). Ginger plants selected from the next generation (M2) were characterized and subjected to quantitative analysis for 6-gingerol content using HPLC of ginger extracts. M2 offspring from a parent ginger rhizome irradiated with 20 Gy was found to have a high 6-gingerol content (38.4 ± 0.01 mg/g methanol extract in comparison to 22.1 ± 0.03 mg/g methanol extract in non-irradiated control samples). Radiation induced genetic variability was also probed and confirmed using RAPD-PCR analysis. This research demonstrates the potential for ginger improvement and to our knowledge is the first to report the use of gamma radiation in breeding ginger plants with enhanced 6-gingerol content.

Does vitamin D status correlate with insulin resistance in obese prediabetic patients? An Egyptian multicenter study.

BACKGROUND: The link between Vitamin-D deficiency and type 2 diabetes (T2D) is well-established. Since prediabetic obese populations have the greatest risk to develop to T2D, it was important in our study to examine serum 25(OH) D3 concentration among prediabetic obese patients and to evaluate the correlation between serum level of vitamin D and BMI, FBS, HOMA IR and HbA1c among prediabetes patients. METHODS: A multicenter case control study was carried out among 101 prediabetic persons & 50 controls, after obtaining consent from subjects and clearance from institutional ethics committee. Serum vitamin D level, Plasma levels of glycosylated hemoglobin (HbA1c) and fasting insulin levels were measured by ELISA in both groups enrolled in the study. RESULTS: The prevalence of vitamin-D deficiency/insufficiency was (73.3%) (n = 74) among 101 prediabetic obese individuals. Also, A significant inverse correlation was observed between vitamin D levels & body mass index(r = - 0.28, P = 0.004); fasting blood sugar (r = - 0.22, P = 0.002); HOMA insulin resistance (r = - 0.25 P = 0.01); HbA1C (r = - 0.2, P= 0.004). CONCLUSIONS: High prevalence of vitamin D deficiency exists among obese prediabetic individuals and there is significant inverse correlation between BMI, FBS, HOMA IR, HbA1c and vitamin D level.

Expression of S-adenosyl methionine decarboxylase gene for polyamine accumulation in Egyptian cotton Giza 88 and Giza 90.

Developing drought tolerance in Egyptian cotton varieties is a strategic goal considering the need to expand cotton cultivated area and water scarcity in the Nile valley. In the present study, increasing levels of polyamine accumulation via expressing S-adenosyl methionine decarboxylase (SAMDC) gene was the main goal. SAMDC cDNA isolated from Saccharomyces cerevisiae isolate was isolated and genetically engineered into Egyptian cotton varieties Giza 88 as an extra long staple and Giza 90 as a long staple by means of particle bombardment through meristem transformation.T(0) transgenic plants were screened using basta herbicide (200 mg/l). RT- PCR analysis was used to confirm gene expression while gene integration was confirmed by Southern blot analysis. Control plants from Giza 88 and Giza 90 were subjected to drought regime using different concentrations of PEG 6000 (2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 17%, and 20%) for 9 hrs to record drought stress symptoms and determine the potential concentration level for inducing polyamine accumulation. 17% of PEG 6000 was considered the sublethal concentration showing drought stress symptoms and therefore was used as potential stress concentration for estimating the level for spermine accumulation in both control and transgenic Giza varieties. T(1) transgenic plants grown under induced drought stress regime were tested positive for gene integration and expression and subjected to HPLC analysis to determine levels of spermine as polyamine accumulated compound in response to drought stress regime. Elevated spermine accumulation in Egyptian cotton varieties Giza 88 and Giza 90, were compared as non transgenic plants grown under same induced drought conditions with T(1) transgenic plants using reverse-phase HPLC analysis. Elevated spermine accumulation expressing SAMDC gene reflect main cause for increasing drought tolerance in both transgenic varieties.