13949 research outputs found
Sort by
C-type Natriuretic Peptide Over Expression in Chondrocytes Prevents Growth Delay in Murine Arthritis
No full textIntroduction:
C-type natriuretic peptide (CNP) signaling pathway is a major contributor to post-natal skeletal growth in humans. CNP signaling pathway controls the endochondral bone growth by its inhibitory effects over FGFR3-induced mitogen-activated protein kinase (MAPK) Erk1/2 activity at the Raf-1 level. It is unknown whether this pathway is affected during chronic inflammatory diseases or whether its excess may rescue the growth delay secondary to the inflammatory arthritis. In this study, using a mouse model for arthritis and a transgenic mouse that over express CNP in cartilage with longitudinal overgrowth we investigated the potential therapeutic role of CNP signaling in growth delay due to chronic inflammatory arthritis.
Methods:
We developed a transgenic mouse that over expressed CNP in chondrocytes and analyzed its longitudinal bone growth pattern. Then we analyzed and the mouse model of rheumatoid arthritis that develop arthritis at a juvenile age (K/BxN TCR mice) for its longitudinal bone growth. By crossing the two transgenic mice we obtained mice that developed arthritis and over expressed CNP in cartilage. Both arthritic and CNP over expressing mice growth patterns were characterized using in vivo/ex vivo anatomic and histologic measurements. The degree of arthritis was analyzed using a scoring system. Using primary chondrocytes isolated from the newborn mice gene and protein expression of molecules CNP signaling pathway were analyzed by RT-PCR and western blotting. Primary chondrocytes were treated with proinflammatory cytokines in order to check the response of CNP signaling system to inflammatory stimuli. Statistical analysis was performed between transgenic and non-transgenic mice and chondrocyte cultures using student’s t-test. Correlations between the measurements were performed using Pearson’s correlation matrices.
Results:
K/BxN TCR mice with arthritis shows that significant longitudinal growth delay by 13 weeks (n=88, females, p=0.001, males, p=0.001). Growth delay of K/BxN TCR mice correlate with severity of arthritis. Histologic evaluation of proximal tibia growth plates in K/BxN TCR mice showed diminished chondrocyte proliferation (BrDU percent uptake) and decreased matrix synthesis (evidenced by narrowed hypertrophic chondrocyte zone and decreased proteoglycan staining) starting with significantly narrow growth plates by 6-week-age (p<0.01). Mice that over expressed CNP in cartilage developed significant longitudinal overgrowth after 6 weeks (n=24, p<0.01). We then mated K/BxN TCR mice with and transgenic mice that over express CNP. Offspring transgenic for CNP and developed arthritis with K/BxN TCR background (n=11) showed no evidence for histopathologic or anatomic growth delay (n=14) (p<0.01). Clinical and histopathologic findings of arthritis were found to be less severe in K/BxN TCR mouse with CNP over expression. Expression of matrix molecules, collagen II, X, aggrecan and NPR2 (receptor to CNP) genes and matrix metalloproteinases (MMP) -3, -9, -13 gene and protein were found significantly higher in the primary chondrocyte cultures isolated from CNP transgenic mice in vitro. Exposure of these chondrocyte cultures to TNF-α, and IL-1β in vitro further enhanced both gene and protein expression of MMP-3, -9, -13, NPR2 and phopshorylation of MAPK p38..
Conclusion:
Our results demonstrate that CNP over expression can prevent the endochondral growth delay in K/BxN TCR mice with arthritis. The cartilage protective effect of CNP signaling is due to its effects of chondrocyte proliferation and matrix synthesis. CNP or its downstream effecting molecules may represent novel therapeutic agents to prevent growth retardation and may protect joint cartilage homeostasis during systemic inflammatory diseases such as that noted in juvenile idiopathic arthritis (JIA)
الاستدامة في العمران الإسلامي
No full textتعتبر الاستدامة من المصطلحات الحديثه التي استخدمت على نطاق واسع وعلى كافة
الأصعدة الاقتصادية والاجتماعية والبيئية وحتى السياسية، وحيث كانت قضايا البيئة
والعمران هي المحرك الأساس لهذا الفكر، فقد ظهرت على مدى السنوات الماضية
العديد من المحاولات لتقنين وتأطير هذا الفكر، على شكل أدلة ومعايير، وهو ماحاول
البحث التعامل معه بدافعي الاكتشاف والتأصيل؛ ولذلك تم بحث المفهوم باسمه
الشمولي "الاستدامة"، ثم الانتقال إلى مفهوم أصغر وأقرب لعملنا المعماري، وهو
"العمارة المستدامة"، وتم بحثه والاطلاع على بعض المشروعات المعمارية التي
طبقت هذا المفهوم.
بعد ذلك تم الانتقال إلى دائرة أصغر وأدق، وهي تشريح لأحد أشهر وأهم الأدلة
والتي قننت مفهوم الاستدامة العمرانية، بل ،( LEED والمعايير العالمية (معايير ليد
فرضته كقانون في كثير من دول العالم، حتى وصل الإلزام بتطبيقه لبعض دولنا
الخليجية، وبذلك تحقق جزء مهم من أهداف البحث، وهو استكشاف مايهمنا من مفهوم
الاستدامة.
ولكون البحث يهدف إلى تأصيل مفهوم الاستدامة في العمران الإسلامي، فقد تم
اختبار "معايير ليد" مع مفاهيم وأساليب "العمارة الاسلامية".
ورغم صعوبة إجراء الاختبار بين مستويين مختلفين من البيانات؛ الأول منها محدد
التفاصيل في ٧٠ عنصرا، هي عناصر ليد، مغرق في التقنية الحديثة، بينما الآخر-
الاستدامة في العمران الاسلامي- عبارة عن مفاهيم وتطبيقات تحقق الاستدامة
ويتناول العموميات، ومفرق في عدد كبير من الكتب والدراسات، إلا أن إجراء هذا
الاختبار قد أثبت أن العمران الإسلامي قد تعاطى مع قضايا الاستدامة بكل اقتدار،
وغطى معظم جوانبها
Crestal Bone Level Alterations and Osseointegration After Implant Placement With or Without Surgical Flap Reflection. A Study in Beagle Dogs
No full textMaster's Thesis for Department of Periodontics and Community DentistryAim: This study aimed to evaluate the changes in crestal bone level following implant placement with the flapped and two flapless techniques and to study the effect of the flapless surgery on osseointegration in beagle dogs.
Materials and methods: Ten beagle dogs, 1-2 years of age, each with an average weight of 8 to 15 kg and with full dentition, were included in the study. Bilateral mandibular second and third premolars were extracted. A three-month healing period followed. Thirty Straumann® Dental Implant System, SLActive® surface: 8 mm long, 3.3 mm diameter, standard plus, narrow neck implants were placed in the mandible. Each animal received three dental implants randomly assigned to one side of the mandible. One side received two fixtures while the other side received one. The dental implants were placed using one of the following three surgical approaches: the flapped surgical approach (Group 1), the tissue punch flapless surgical approach (Group 2) and the direct flapless surgical approach (Group 3). Three months following the fixtures placement, the dogs were sacrificed with an overdose of ketamine 10%, 8-10 mg/kg intramuscularly (IM) and 1-3 mg/kg IM xylazine 2%.
Histomorphometric analysis was used to measure the changes in the crestal bone level while histological analysis measured the bone implant contact (BIC). Finally, microcomputerized tomography was used to quantify the bone volume around the implants in the three treatment groups.
Results: Three months following implant placement, three dental implants from the flapless surgical approach Group 2 were clinically mobile and one implant from the direct flapless approach group 3 was lost. The bone volume percentage was 55.1% for Group 1, 51.4% for Group 2 and 53.6% for Group 3 with no statistically significant differences between the groups (p = 0.4475). The first bone contact values were 3420±762.5 μm in Group 1, 5357±1771.9 μm in Group 2 and 3842±459.5 μm in Group 3. Statistical testing of the first bone contact measurements indicated that the bone made its first contact with the implant surface at a significantly lower level when implanted with the procedure in Group 2 when compared with the other two groups (p = 0.0023); there was no significant difference between Groups 1 and 3. Bone-Implant contact was 70.1±12.6 in Group 1, 48.0±23.7 in Group 2 and 72.8±13.1 in Group 3. Statistical testing of the first bone contact measurements indicated that the implants in Groups 1 and 3 revealed a significantly higher amount of bone-implant contact compared with the implants in Group 2 (p = 0.0074), while no difference was present between Groups 1 and 3.
Conclusions: There were no statistically significant differences in the bone volume surrounding the dental implants in the three groups. There were no statistically significant differences between Groups 1 and 3 regarding the BIC and crestal bone resorption. The tissue punch flapless surgical technique had significantly less BIC and more crestal bone resorption than the other two groups
The relevance of reticulocyte hemoglobin content measurement in assessing functional iron Deficiency
No full textThe diagnosis of iron deficiency or functional iron deficiency (FID) is considered to be mostly challenging in patients with acute or chronic inflammatory conditions, because most of the biochemical parameters for iron metabolism (such as ferritin and transferrin saturation) are influenced by acute inflammatory response. For that a recently introduced method to quantify reticulocyte haemoglobin content (CHr), looks to add to the battery of tests for the determination of body ‘iron status’ and could provide additional information for FID in patients suffering from anaemia of chronic diseases (ACD) and chronic renal failure(CRF).
Subjects and Methods: The aims of this study were to estimate the value of the CHr in normal adult population, and compare the levels with conventional iron indices. This study included 60 normal healthy age matching control, 100 patients with iron deficiency, 60 patients with ACD and 100 patients with CRF before the start of dialysis. The methods employed for the blood examinations in the laboratory were as follows: CBC including CHr, microscopic blood film examination, erythrocyte sedimentation rate, colorimetric method for serum iron,
iron binding capacity(TIBC), and estimation of transferrin saturation(TAST), serum ferritin(SF), and C-reactive protein(CRP).
Result: The results showed that the normal range for CHr in healthy adult subject was with mean of 30.93 ± 1.3 pg pg and a range of 28.8-33.1pg. There was a high significant correlation between CHr and haematological parameters (and with biochemical parameters of iron status were high in three different group of patients. On the other hand, there was weak correlation between CHr and ferritin in ACD and CRF groups. There was also an inverse correlation between CHr and CRP in both ACD and CRF patients. This finding indicates that CHr value, unlike SF, is independent of the inflammatory processes and remains a true indicator of the body iron status. Conclusion: CHr was a useful parameter for the diagnosis of simple iron deficiency or FID in patients suffering from ACD and anaemia associated with CRF on haemodialysis and treated with r-HuEPO
C-Type natriuretic peptide overexpression protects mice against post-ovariectomy osteoporosis.
No full textC-type natriuretic peptide (CNP) signaling pathway has been shown to regulate endochondral bone growth and has been proposed to promote bone formation through regulation of osteoblast function. A transgenic mouse (CNPcol2a1TG) that over-expresses CNP by a Col2a1 promoter and enhancer was generated resulting in increased trabeculation in the subchondral bone. We hypothesized that CNPcol2a1TG female mice might resist to bone loss due to estrogen deficiency post-ovariectomy (OVX) and rescue post menopausal osteoporosis.
CNPcol2a1TG female and wild type were ovariectomized and sham operated at 1.5 month of age to induce post menopausal osteoporosis. CNPcol2a1TG and wild type littermate mice were analysed in vivo and in vitro using methods of skeletal staining, x-rays, micro-CT and using serologic measures of bone remodeling. Primary chondrocyte and osteoblast cultures isolated from rib cartilage and calvarium of newborn CNPcol2a1TG and wild type littermates were analysed for mRNA and protein expressions of molecules that play roles in bone remodeling.
The serum osteocalcin levels of CNPcol2a1TG mice both OVX and sham operated were significantly high as compared to wild-type OVX and sham operated littermates. Micro-CT analysis of the thoracic spine (6-7) of overictomized mice showed increased cortical and trabecular bone mineral content, in CNPcol2a1TG which remained higher even after OVX as compared to wild type sham and ovx littermates. Average trabecular thickness and connectivity in CNPcol2a1TG mice was highest compared to OVX CNPcol2a1TG, wild type sham, ovx.
Quantitative RT-PCR suggested a possible regulatory effect of CNP in bone remodelling. Furthermore, ratio of OPG and RANKL was higher in the transgenic mice suggesting suppression of osteoclastogenesis in the transgenic mice compared to wild type. In conclusion, these results suggest that CNP might have a therapeutic role in post menopausal osteoporosis by affecting the bone mineralization and trabeculation
Over Expression of CNP Enhances the Formation of Long Bone Exostoses in Ext1+/- mice
No full textMultiple hereditary exostoses (MHE) is an autosomal dominant skeletal disorder caused by heterozygous loss-of-function mutations in either EXT1 or EXT2. Exostosis in patients with EXT mutations occurs at diverse skeletal sites and can undergo malignant degeneration. The exostosis in EXT1 heterozygous (EXT1+/-) mice predominantly affect the ribs and do not become malignant.
In this study EXT1+/- mice were bred to transgenic mice that over-express C-type natriuretic peptide under the control of the type II collagen promoter/enhancer (CNPcol2a1TG). The purpose of this study was to determine whether CNP over expression would enhance the EXT1+/- phenotype. By itself, CNP over-expression causes skeletal overgrowth, but does not produce exostoses. EXT1+/- and CNPcol2a1TG mice were mated and 27 offspring were followed for up to 8 months. Non-rib exostoses were detected clinically and/or radiographically, and they were examined histologically following sacrifice.
Eight of the 27 offspring developed non-rib exostoses and these 8 offspring were both EXT1+/- and CNPcol2a1TG positive (EXC). Of the remaining 19 mice in which we did not observe long bone or vertebral exostoses, 9 were CNPcol2a1TG, 4 were EXT1+/-, and 6 were entirely wild-type. The histological appearance of each exostosis was similar to that of human exostotic lesions.
Western blots using antibodies towards NPR2 and MMP13 showed an increase in CNPcol2a1TG and EXC mice as compared to their non-transgenic littermates. There was an increase in the phosphorylated form of P38 and JNK in the EXC transgenic mice when compared to EXT and CNP mice. CNP over expression in EXT+/- mice provided the necessary environment for EXT1 haploinsufficiency for exositosis formation. EXT haploinsufficient and CNP over expressing mice provides us a new murine model to study MH
Low serum levels of NT-proCNP in children with poly-articular onset juvenile rheumatoid arthritis.
No full textChildren with juvenile rheumatoid arthritis (JRA) develop longitudinal growth delay. Increased levels of proinflammatory cytokines (IL-6, TNF-α) in serum and in synovial fluid have been blamed for suppressing the local and/or systemic growth factors that regulate endochondral bone growth. Aside from growth hormone signaling pathway, it is unknown whether other growth factors that regulate the endochondral bone growth are affected in JRA.
C-type natriuretic peptide (CNP) has been recently described as an essential paracrine factor for normal endochondral bone growth. Serum level of N-terminal pro-peptide of CNP (NT-proCNP) has been suggested to be a marker for endochondral bone growth. In this study, we aimed to investigate whether CNP signaling is affected during active juvenile inflammatory arthritis in children by measuring the serum NT-proCNP levels during active disease and investigated whether serum NT-proCNP levels correlated with the serum IL-6 and TNF-alpha levels.
Clinical and laboratory data was collected from children diagnosed with juvenile rheumatoid arthritis (JRA) according to ACR criteria (n=18, 9 pauci-articular, 8 poly-articular, and 1 systemic onset JRA). Concurrent clinical and laboratory data were collected from patients during their enrollment in the study as a part of their routine care. Pro-inflammatory cytokine levels and the NT-proCNP levels were measured using ELISA. Z-scores of NT-proCNP levels for each patient were calculated using NT-proCNP levels of age matched healthy children. Statistical analysis software was used (SAS 9.2) to calculate the correlations between the z-scores, cytokines and laboratory data.
All patients with JRA had low NT-proCNP z-scores compared to age matched controls. Poly- and systemic JRA patient’s z-scores were significantly lower. IL-6 levels showed negative correlation with the z-scores in children with poly-JRA (r= -0.67, p=0.06). When stratified for gender, correlation of z-scores with IL-6 level became significant (r=-0.99, p=0.034). Sedimentation levels correlated with TNF-α levels in poly-JRA patients (r=0.91, p=0.003), but TNF-α levels correlation with NT-proCNP z-scores did not reach statistical significance. Seven of eight poly-JRA patients were under treatment with Methotrexate (20mg/m2) and five were also treated with oral prednisone (>0.5mg/kg/d). The mean z-scores of NT-proCNP in patients who used prednisone (n=5) were not different than those who did not use prednisone (n=3).
Serum NT-proCNP levels of children with JRA are lower than age matched controls. In poly-articular onset JRA patients, the serum levels of IL-6 show negative correlation with z-scores of NT-proCNP. In addition to ongoing systemic inflammation, patients with poly-JRA were also being treated with medications such as methotrexate and prednisone which might lower the NT-proCNP levels. Further studies with larger JRA patient population are necessary to further delineate the disruption of CNP signaling during JRA. Serum NT-proCNP levels could be a biomarker for endochondral bone growth in children with JRA
معايير اختيار مواقع المباني المدرسية في المملكة العربية السعودية (حالة دراسية: منطقة القصيم)
No full textتطرق البحث إلى الإجابة عن تساؤلات مشكلة الدراسة الرئيسية، والتي تتركز على بحث مدى
ملاءمة المعايير والأسس التخطيطية المتبعة عند اختيار مواقع المنشآت التعليمية للمتطلبات التعليمية
للمراحل التعليمية المختلفة، وخاصة الابتدائية والمتوسطة، ومدى مناسبتها للاحتياجات المستقبلية،
وذلك من خلال دراسة حالة منطقة القصيم بوصفها مثا ً لا للمناطق الصحراوية.
ويهدف البحث إلى تطوير حد أدنى من معايير اختيار مواقع المباني المدرسية في المملكة العربية
السعودية، والتي يجب استخدامها مستقب ً لا في تقييم واختيار المواقع المناسبة لإقامة المباني المدرسية.
واتبع البحث المنهجية الوصفية التحليلية والتي اعتمدت على مراجعة الدراسات السابقة للوصول إلى
معايير يتم تطبيقها، مع تقييم مدى تحقيق هذه المعايير على بعض المواقع التي تم استخدامها وذلك من
خلال المسح الميداني لبعض المدارس القائمة.
وقد خلص البحث إلى نتيجتين رئيستين، الأولى: وضع منهجية علمية يتم استخدامها عند اختيار
المواقع المناسبة لإقامة منشأة تعليمية، وذلك من خلال تحديد مواقع العجز في الخدمة، والمواقع
المعروضة ومساحاا ليتم الاستفادة منها جميعًا، ومن ثم تقييمها لتحديد المواقع المناسبة. الثانية:
التوصل إلى مذكرة لتقييم المواقع المقترحة بوصفها منشآت تعليمية، اشتملت على كافة المعايير التي
. يتم من خلالها تقييم تلك المواقع والأوزان النسبية المقترحة له
نشأة وأعمال شعبة الأبحاث العربية في شركة ( أمرامكو )
No full textيتناول البحث جانباُ من تاريخ شركة الزيت العربية الأمريكية ( أرامكو ) من خلال تسليط الضوء على إحدى إداراتها المهمة وهي " شعبة الأبحاث العربية " المعنية بتقديم الدراسات الجغرافية والتاريخية والثقافية عن الجزيرة العربية والخليج العربي، لمسئولي الشركة وصانعي القرار فيها ومن مهامها متابعة الأحداث السياسية والاقتصادية في العالم العربي ومنطقة الشرق الأوسط عامة، ورصدها، وتحليل مضامينها واستشراف تأثيرها على سير أعمال الشركة، بدأ البحث بتمهيد تناول فيه ظاهرة " مراكز التفكير " في الولايات المتحدة، بداياتها، وأهدافها، وأهميتها في توفير المعلومات لصانع القرار في المؤسسة الأمريكية سواء في القطاع العام أو القطاع الخاص، منذ أواخر القرن التاسع عشر ، واستمرت هذه الظاهرة في الانتشار خاص بعد الحرب العالمية الثانية وتعاظم نفوذها إلى الوقت الحاضر مما جعل ثقافة توفير المعلومات من جهات متخصصة معنية بهذه المهمة وقديم الخبرات والاستشارات لتضع بذلك خيارات المتعددة أمام المسئول وصاحب القرار في المؤسسة، وأصبحت مراكز الأبحاث – تحت أسماء عديدة – جهازاً أساسياً في قطاعات الإدارة الأمريكية الرسمية وقد عملت القطاعات الخاصة من شركات وغيرها، على إنشاء تلك المراكز التي تقوم بعمل الدراسات في مجال اهتمام الشركة وتقديم الرأي والمشورة، ومن ذلك شرك ( أرامكو ) التي كانت " شعبة الأبحاث العربية " تقوم بهذه المهمة بدرجة كبيرة وقد تناول البحث في ثنايا فصوله تاريخ نشأت شعبة الأبحاث في أرامكو وأعمالها خلال الفترة 1946م/1956م مبيناً الأسباب التي دفعت الشركة إلى تأسيسها وعرض لمهامها، والجهات التي تعمل في إطارها
Assessment of the Haematological changes Post-haemodialysis Among Saudi Renal Failure Patients
No full textRenal failure is a situation in which the kidney fails to function
adequately. There are two forms of renal failure: acute and chronic renal failure. End-
Stage Renal Disease is the final stage of chronic renal failure were in there is a
progressive, irreversible deterioration in renal function and function is substituted by
renal replacement therapy, haemodialysis (HD), peritoneal dialysis (PD), or
transplantation. During HD, patients’ blood comes in direct contact with the dialysis
membrane non physiological environment which may elicit a series of changes in the
blood cells and in haemostasis.
The aim of this present study was to assess the changes in various
hematological parameters that may occur in renal failure patients post-HD, to
determine the differences between various hematological parameters that occur in
renal failure patients pre and post–HD compared to a control group. The possible
effect of dialysis duration on hematological parameters that may occur in renal failure
patients was also investigated. The resulting data from these studies might help the
clinicians to initiate precautions before and after a dialysis session.
The study included a healthy control group of 60, consisting of 30 males and
30 females. The control group was age, sex and race matched with the patients group
of 100 renal failure patients undergoing HD, and consisting of 61 males and 39
females. Blood samples from these patients were collected before and after dialysis
sessions. The samples were tested for complete blood count, differential count,
prothrombin time (PT) ,activated partial thromboplastin time (APTT) and fibrinogen.
The results of the present study revealed that the most of the hematological
parameters measured in HD patients, pre- or post-HD were either elevated or lowered
when compared to a Control group. Furthermore it was noticed that most of the
hematological parameters increased after HD session. More significantly PT, APTT
and fibrinogen were found to increase post-HD while there was a concurrent decrease
of platelets counts. A significant positive correlation was noticed between the time
period the patients have been on dialysis and each of fibrinogen, APTT and PT levels.
However there was a significant negative correlation between the time period the
patients have been on dialysis and platelets count. Therefore, it is recommended that
all patients be screened appropriately before and after dialysis to avoid complications