Effect of Alstonia Boonei Stem Bark Extracts on the Activity of Liver Maker Enzymes in Rats Induced by Ccl4

بحثت هذه الدراسة في نتائج لحاء جذع ألستونيا بوناي على إنزيمات الكبد بعد تحريض فئران ويستار البيضاء باستخدام رباعي كلوريد الكربون (CCl4). تمت مقارنة تأثير المستخلصات النباتية مع سيليمارين - وهو دواء شائع الاستخدام لعلاج اضطراب خلايا الكبد المزمن. تم استخلاص العينة النباتية مع الإيثانول. تم إجراء دراسة السمية الحادة للمستخلص على ثمانية عشر فأر من Wistar ، بينما تم التضحية بـ 30 جرذاً لفحص إنزيمات الكبد. تم تقسيم الجرذان إلى ست مجموعات: كل مجموعة بها خمسة فئران ، و culster 1 بمثابة مجموعة تحكم وأعطيت 2 مل / كجم من وزن الجسم - ماء مقطر ؛ المجموعات 2-6 كانت مستحثه من CCl. لم يتم علاج المجموعة 2 ولكنها كانت بمثابة عنصر تحكم سلبي بينما أعطيت المجموعة 3 0.025 مل أو 25 كجم / كجم من وزن الجسم من سيليمارين ، والذي كان دواءً عاديًا ومساعدًا كعنصر تحكم عادي. تم إعطاء الجرذان في المجموعات 4-6 - 100 و 200 و 500 ملغم / كغم على التوالي من مستخلص الإيثانول لمدة أربعة عشر يومًا. أظهرت نتائج السمية الحادة لمستخلص A. boonei التحصين النسبي نتيجة عدم حدوث موت أو استجابات عدائية بعد 24 ساعة من إعطاء المستخلص. زيادة كبيرة (P 0.05) في عمل ALT بعد إعطاء 500 مجم / كجم يثبت أن السمية الأقل كانت جرعة أكبر. عند جرعة منخفضة من المستخلص ، يشير الارتفاع غير الهام (p 0.05) في تأثير AST إلى أن المستخلص كان غير ضار إلى حد ما مع عدم وجود سمية كبدية عند تناول الأدوية المنخفضة. يشير الانخفاض الكبير في تأثير الفوسفاتيز القلوي في المجموعة 3 من الفئران المستحدثة باستخدام CCl4 والمُعطاة مع Silymarin ، جنبًا إلى جنب مع المجموعات 4 - 6 التي تم تحفيزها باستخدام CCl4 وتم إعطاؤها بجرعات متدرجة من مستخلص لحاء جذع A. boonei ، مما يشير إلى وجود خصائص واقية للكبد.This study investigated the outcome of Alstonia boonei stem bark on liver enzymes after inducing the Wistar albino rats with carbon tetrachloride (CCl4). This effect of plant extract was compared with silymarin – a drug commonly used for the treatment of chronic hepatocyte disorder. The plant sample was extracted with ethanol; acute toxicity study of the extract was performed on eighteen Wistar mice, while 30 rats were sacrificed for liver enzymes assay. The rats were divided into six clusters: each cluster has five rats, culster 1 served as control and was given 2 mL/kg b.w - distilled water; clusters 2 – 6 were CCl4 induced. Cluster 2 was untreated but served as the negative control while cluster 3 was given 0.025 mL or 25kg/kg B.W of Silymarin, which was a regular medicine and aided as the ordinary control. Rats in clusters 4 – 6 were administered - 100, 200 and 500 mg/kg, respectively of ethanol extract for fourteen days. The acute toxicity results of A. boonei extract showed relative fortification due to no death or adversarial responses after 24 hours of the extract administration. A substantial (P ≥ 0.05) surge in ALT action after administering 500 mg/kg proves lesser toxicity was greater dosage. At low dosage of the extract, a non-significant (p ≥ 0.05) rise in AST action specifies that the extract was moderately harmless with no hepatotoxic magnitude at low medication. The substantial reduction of alkaline phosphatase action in cluster 3 rats induced with CCl4 and given with Silymarin, together with clusters 4 – 6 that were CCl4 induced and administered with graded doses of A. boonei stem bark extract suggest hepatoprotective properties

Application of extreme value distribution for assigning optimum fractions to distributions with boundary parameters: an eucalyptus plantations case study

The search for an optimum value to constrain boundary parameters in distribution models can be (and is) laborious and time-consuming. The accuracy of a distribution fit depends on the predetermined values of the boundary parameters. In this study, we applied the extreme value distributions derived from the generalized extreme value (GEV) in assigning the optimum constant to a distribution with boundary parameters. GEV subfamily (type 1), Gumbel’s distribution, was used to generate constant values which were used as a fraction of the minimum and maximum diameter and height data. The effectiveness of these values was established using five distribution models: logit-logistic (LL), Burr XII, Dagum, Kumaraswamy, and Johnson’s SB distributions. The distributions were fitted with maximum accuracy to the diameter and height data collected on 90 Eucalyptus camaldulensis Dehn sample plots. Model assessment was based on negative log-likelihood (-ΛΛ), Kolmogorov-Smirnov (K-S), Cramér-von Mises (W2), Reynold’s error index (EI), and mean square error (MSE). The result showed that the performance of the distributions was improved, especially for the height distribution, compared to other constant values. Gumbel’s distribution can be applied whenever (where) a boundary constraint is to be imposed on the location and scale parameters of the distribution models

Artemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia

As effective therapies for relapse and refractory B-cell acute lymphoblastic leukemia (B-ALL) remain problematic, novel therapeutic strategies are needed. Artemis is a key endonuclease in V(D)J recombination and nonhomologous end joining (NHEJ) of DNA double-strand break (DSB) repair. Inhibition of Artemis would cause chromosome breaks during maturation of RAG-expressing T- and B-cells. Though this would block generation of new B- and T-cells temporarily, it could be oncologically beneficial for reducing the proliferation of B-ALL and T-ALL cells by causing chromosome breaks in these RAG-expressing tumor cells. Currently, pharmacological inhibition is not available for Artemis. According to gene expression analyses from 207 children with high-risk pre-B acute lymphoblastic leukemias high Artemis expression is correlated with poor outcome. Therefore, we evaluated four compounds (827171, 827032, 826941, and 825226), previously generated from a large Artemis targeted drug screen. A biochemical assay using a purified Artemis:DNA-PKcs complex shows that the Artemis inhibitors 827171, 827032, 826941, 825226 have nanomolar IC50 values for Artemis inhibition. We compared these 4 compounds to a DNA-PK inhibitor (AZD7648) in three patient-derived B-ALL cell lines (LAX56, BLQ5 and LAX7R) and in two mature B-cell lines (3301015 and 5680001) as controls. We found that pharmacological Artemis inhibition substantially decreases proliferation of B-ALL cell lines while normal mature B-cell lines are not markedly affected. Inhibition of DNA-PKcs (which regulates Artemis) using the DNA-PK inhibitor AZD7648 had minor effects on these same primary patient-derived ALL lines, indicating that inhibition of V(D)J hairpin opening requires direct inhibition of Artemis, rather than indirect suppression of the kinase that regulates Artemis. Our data provides a basis for further evaluation of pharmacological Artemis inhibition of proliferation of B- and T-ALL

Comprehensive Assessment of Maize Aflatoxin Levels in Eastern Kenya, 2005–2007

Background: Aflatoxin, a potent fungal toxin, contaminates 25% of crops worldwide. Since 2004, 477 aflatoxin poisonings associated with eating contaminated maize have been documented in Eastern Kenya, with a case-fatality rate of 40%

The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of the transcription factor ERG

The ERG (ETS-related gene) transcription factor is linked to various types of cancer, including leukemia. However, the specific ERG domains and co-factors contributing to leukemogenesis are poorly understood. Drug targeting a transcription factor such as ERG is challenging. Our study reveals the critical role of a conserved amino acid, proline, at position 199, located at the 3' end of the PNT (pointed) domain, in ERG's ability to induce leukemia. P199 is necessary for ERG to promote self-renewal, prevent myeloid differentiation in hematopoietic progenitor cells, and initiate leukemia in mouse models. Here we show that P199 facilitates ERG's interaction with the NCoR-HDAC3 co-repressor complex. Inhibiting HDAC3 reduces the growth of ERG-dependent leukemic and prostate cancer cells, indicating that the interaction between ERG and the NCoR-HDAC3 co-repressor complex is crucial for its oncogenic activity. Thus, targeting this interaction may offer a potential therapeutic intervention

Younger age at onset and sex predict celiac disease in children and adolescents with type 1 diabetes: an Italian multicenter study

OBJECTIVE— To estimate the prevalence of biopsy-confirmed celiac disease in Italian children and adolescents with type 1 diabetes and to assess whether age at onset of type 1 diabetes is independently associated with diagnosis of celiac disease. RESEARCH DESIGNANDMETHODS— The study group was a clinic-based cohort of children and adolescents with type 1 diabetes cared for in 25 Italian centers for childhood diabetes. Yearly screening for celiac disease was performed using IgA/IgG anti-gliadin and IgA anti-endomysium antibodies. RESULTS— Of the 4,322 children and adolescents (age 11.8 4.2 years) identified with type 1 diabetes, biopsy-confirmed celiac disease was diagnosed in 292 (prevalence 6.8%, 95% confidence interval [CI] 6.0 –7.6), with a higher risk seen in girls than in boys (odds ratio [OR] 1.93, 1.51–2.47). In 89% of these, diabetes was diagnosed before celiac disease. In logistic regression analyses, being younger at onset of diabetes, being female, and having a diagnosis of a thyroid disorder were independently associated with the risk of having diabetes and celiac disease. In comparison with subjects who were older than 9 years at onset of diabetes, subjects who were younger than 4 years at onset had an OR of 3.27 (2.20–4.85). CONCLUSIONS— We have provided evidence that 1) the prevalence of biopsy-confirmed celiac disease in children and adolescents with type 1 diabetes is high (6.8%); 2) the risk of having both diseases is threefold higher in children diagnosed with type 1 diabetes at age 4 years than in those age 9 years; and 3) girls have a higher risk of having both diseases than boys