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

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

Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies

Heavy chain-only antibodies (HCAbs) do not associate with light chains and their VH regions are functional as single domains, forming the smallest active antibody fragment. These VH regions are ideal building blocks for a variety of antibody-based biologics because they tolerate fusion to other molecules and may also be attached in series to construct multispecific antibodies without the need for protein engineering to ensure proper heavy and light chain pairing. Production of human HCAbs has been impeded by the fact that natural human VH regions require light chain association and display poor biophysical characteristics when expressed in the absence of light chains. Here, we present an innovative platform for the rapid development of diverse sets of human HCAbs that have been selected in vivo. Our unique approach combines antibody repertoire analysis with immunization of transgenic rats, called UniRats, that produce chimeric HCAbs with fully human VH domains in response to an antigen challenge. UniRats express HCAbs from large transgenic loci representing the entire productive human heavy chain V(D)J repertoire, mount robust immune responses to a wide array of antigens, exhibit diverse V gene usage and generate large panels of stable, high affinity, antigen-specific molecules

IDDM and early infant feeding : Sardinian case-control study

OBJECTIVE - To further investigate the association between the type of feeding in infancy and the development of IDDM. RESEARCH DESIGN AND METHODS - We have carried out a case-control study in the area of Sassari (northern Sardinia, Italy), which is characterized by an ethnically homogenous population at high risk of IDDM. The study subjects comprised 100 IDDM patients and 100 control subjects, matched for sex and age and selected from children admitted at the Department of Pediatrics of the University of Sassari. Diabetic children (53 boys, 47 girls) had been diagnosed between 1983 and 1994, and their age at diagnosis ranged between 1 and 15 years. Information on feeding patterns during the Ist year of life was collected through questionnaires administered to the mothers. The questionnaire was designed to evaluate the duration of complete or partial breast-feeding and the age at which dietary products containing cows milk were introduced into the diet. RESULTS - A larger proportion of the diabetic children rather than the control children had been breast-fed, and the risk of IDDM among children who had not been breast-fed was below unity (adds ratio [OR] 0.41; 95% CI 0.19-0.91). No clear difference was observed between diabetic and control subjects in the duration of breast-feeding (medians: 3 and 2 months, respectively, even if, overall, the data suggested a slight increase in the risk of IDDM with longer duration of breast-feeding (OR 1.10; 95% CI 0.99-1.22 per month). Although a larger proportion of control children rather than diabetic children had been given cow's milk-derived formula and solid food before the age of 3 months, there was no time-risk relationship. CONCLUSIONS - Our data do not support the existence of a protective effect of breast-feeding on the risk of IDDM, nor do the data indicate that early exposure to cow's milk and daily products has any influence on the development of IDDM in a high-risk population

High prevalence of lactose absorbers in Northern Sardinian patients with type 1 and type 2 diabetes mellitus

Background: Increased intestinal lactase activity has been shown to occur in alloxan and streptozotocin diabetic rats. Objective: The objective of this study was to determine whether increased intestinal lactase activity is present in humans with diabetes mellitus. Design: We assessed the capacity to digest lactose by measuring breath-hydrogen production after oral administration of lactose in 50 patients with type I diabetes, 50 patients with type 2 diabetes, and 50 healthy control subjects from Sassari, Sardinia, Italy, a population characterized by a low prevalence of lactase persistence (lactose absorbers). Results: Fourteen percent of control subjects were lactose absorbers, compared with 48% of patients with type 1 diabetes and 52% of patients with type 2 diabetes (P < 0.005). The odds ratio of lactase persistence in patients with type 1 diabetes was 5.3 (95% CE: 2.0, 14.0) and in patients with type 2 diabetes was 5.5 (95% CT: 2.1, 14.5). Conclusions: Diabetes is associated with increased intestinal lactase activity in humans. Consequently, there is a seater exposure to glucose and galactose in diabetic patients with high lactose consumption. This may explain the association between diabetes and the risk of cataract

Model Evaluation

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Nonhepatic origin of notothenioid antifreeze reveals pancreatic synthesis as common mechanism in polar fish freezing avoidance

Phylogenetically diverse polar and subpolar marine teleost fishes have evolved antifreeze proteins (AFPs) or antifreeze glycoproteins (AFGPs) to avoid inoculative freezing by internalized ice. For over three decades since the first fish antifreeze (AF) protein was discovered, many studies of teleost freezing avoidance showed hepatic AF synthesis and distribution within the circulation as pivotal in preventing the blood, and therefore the fish, from freezing. We have uncovered an important twist to this long-held paradigm: the complete absence of liver synthesis of AFGPs in any life stage of the Antarctic notothenioids, indicating that the liver plays no role in the freezing avoidance in these fishes. Instead, we found the exocrine pancreas to be the major site of AFGP synthesis and secretion in all life stages, and that pancreatic AFGPs enter the intestinal lumen via the pancreatic duct to prevent ingested ice from nucleating the hyposmotic intestinal fluids. AFGPs appear to remain undegraded in the intestinal milieu, and the composition and relative abundance of intestinal AFGP isoforms are nearly identical to serum AFGPs. Thus, the reabsorption of intact pancreas-derived intestinal AFGPs, and not the liver, is the likely source of circulatory AFGPs in notothenioid fishes. We examined diverse northern fish taxa and Antarctic eelpouts with hepatic synthesis of bloodborne AF and found that they also express secreted pancreatic AF of their respective types. The evolutionary convergence of this functional physiology underscores the hitherto largely unrecognized importance of intestinal freezing prevention in polar teleost freezing avoidance, especially in the chronically icy Antarctic waters

Structural accreditation of healthcare facilities: comparison of the requirements by Italian Presidential Decree 14/01/1997 and regional regulations. A proposal for updating the minimum environmental units at national level A proposal for updating the minimum environmental units at national level

Background and aim. The Decree of the President of the Italian Republic 14/01/1997 is the reference norm related to the accreditation of public and private healthcare structures. This guideline establishes the minimum structural, technological and organizational requirements that each structure operating in the Italian territory must comply with. Methods. In occasion of the project work for the postgraduate training course in healthcare management by ALTEMS School, a team of researchers conducted a survey on the state of updating of the minimum structural requirements indicated in the norm-in particular those relating to hospital facilities- with those adopted by the individual regions through the analysis of the most up-to-date regional regulations. Results. Precisely starting from the comparison of regional references and from the regulations on the subject of structural accreditation which suggest strategic environmental units and which address some key-aspects relating to the contemporary design of healing environments (i.e. semi-intensive care units, hybrid operating theatres, etc.), the outcome of the project work is to define a proposal to update the national reference document, also in the light of the currently changing needs in terms of hospital design. Conclusions. The research aims to become a starting milestone for future investigations. The team investigated – in this first phase – the functional areas listed in the norm, and the next step aims to extend the analysis also to the innovative functions (i.e. buffer spaces, hybrid operating theatres, sub-intensive care units, etc.) and/or introduced only the last years which have only been regulated in some regions