Upregulation of utrophin A is an attractive therapeutic strategy for treating Duchenne muscular dystrophy (DMD). Over the years, several studies revealed that utrophin A is regulated by multiple transcriptional and post-transcriptional mechanisms, and that pharmacological modulation of these pathways stimulates utrophin A expression in dystrophic muscle. In particular, we recently showed that activation of p38 signaling causes an increase in the levels of utrophin A mRNAs and protein by decreasing the functional availability of the destabilizing RNA-binding protein called K-homology splicing regulatory protein, thereby resulting in increases in the stability of existing mRNAs. Here, we treated 6-week-old mdx mice for 4 weeks with the clinically used anticoagulant drug heparin known to activate p38 mitogen-activated protein kinase, and determined the impact of this pharmacological intervention on the dystrophic phenotype. Our results show that heparin treatment of mdx mice caused a significant ∼1.5- to 3-fold increase in utrophin A expression in diaphragm, extensor digitorum longus and tibialis anterior (TA) muscles. In agreement with these findings, heparin-treated diaphragm and TA muscle fibers showed an accumulation of utrophin A and β-dystroglycan along their sarcolemma and displayed improved morphology and structural integrity. Moreover, combinatorial drug treatment using both heparin and 5-amino-4-imidazolecarboxamide riboside (AICAR), the latter targeting 5' adenosine monophosphate-activated protein kinase and the transcriptional activation of utrophin A, caused an additive effect on utrophin A expression in dystrophic muscle. These findings establish that heparin is a relevant therapeutic agent for treating DMD, and illustrate that combinatorial treatment of heparin with AICAR may serve as an effective strategy to further increase utrophin A expression in dystrophic muscle via activation of distinct signaling pathways.
ORIGINAL PROF-3471 ABSTRACT… Background: In 1939 Rh antigen was discovered by Levine and Stetson. Rh system antigens are very immunogenic, they can produce significant Hemolytic Disease of the fetus and Newborn as well as hemolytic transfusion reactions. There are numerous variants of D, the most common subtypes are Weak D and Partial D, now called as abnormal D antigens. The incidence of Rh negativity worldwide varies between 3%-25% and that of weak D antigen ranges from 0.2%-1%. Objectives: To find out the frequency of Rh negativity and weak D antigen among the donors coming to the blood bank of The Children's Hospital & Institute of Child Health, Lahore and to review the clinical significance of weak D antigen in transfusion perspective especially its role in alloimmunization caused by Weak D antigen when transfused to Rh negative individuals. Study Design: Cross-sectional study. Setting: The Children's Hospital and Institute of Child Health, Lahore. Period: 1 st Jan 2015 to 31st May, 2015. Materials and Methods: 6320 healthy donors were randomly selected. All samples were grouped for ABO and Rh-D factor by immediate spin tube technique. All samples found Rh negative, were further processed for weak D antigen with monoclonal anti D sera by using indirect Coomb's technique. The presence of macroscopic or microscopic agglutination was recorded as Rh positive. In case there was no agglutination the mixture was washed 4 times with normal saline. After the last wash, saline was decanted and 2 drops of monoclonal, polyvalent anti human globulin was added. Macroscopic and microscopic agglutination was looked for and any agglutination at this stage was recorded as weak D antigen. Positive control (check cells i.e. washed O positive cells with diluted anti D) and negative control (washed O positive cells) were always put. Results: Among the 6320 healthy donors, 1224(19.4%) were Rh-D negative and 5096(80.6%) were Rh-D positive. Of the 1224 Rh D negative samples, 3 (0.2%) samples found positive for weak D antigen. Conclusion: The frequency of Rh negative blood group was 0.2% among the healthy donors at The Children's Hospital and ICH, Lahore. Although the frequency is low but it's proven by literature that weak D antigen can produce alloimmunization if transfused to Rh-D negative subjects. At the same time the cases of hemolytic reactions reported previously with Weak D antigen have been scarce.
Background: In 1939 Rh antigen was discovered by Levine and Stetson. Rhsystem antigens are very immunogenic, they can produce significant Hemolytic Disease of thefetus and Newborn as well as hemolytic transfusion reactions. There are numerous variants ofD, the most common subtypes are Weak D and Partial D, now called as abnormal D antigens.The incidence of Rh negativity worldwide varies between 3%-25% and that of weak D antigenranges from 0.2%-1%. Objectives: To find out the frequency of Rh negativity and weak Dantigen among the donors coming to the blood bank of The Children’s Hospital & Institute ofChild Health, Lahore and to review the clinical significance of weak D antigen in transfusionperspective especially its role in alloimmunization caused by Weak D antigen when transfusedto Rh negative individuals. Study Design: Cross- sectional study. Setting: The Children’sHospital and Institute of Child Health, Lahore. Period: 1st Jan 2015 to 31st May, 2015. Materialsand Methods: 6320 healthy donors were randomly selected. All samples were grouped forABO and Rh-D factor by immediate spin tube technique. All samples found Rh negative, werefurther processed for weak D antigen with monoclonal anti D sera by using indirect Coomb’stechnique. The presence of macroscopic or microscopic agglutination was recorded as Rhpositive. In case there was no agglutination the mixture was washed 4 times with normalsaline. After the last wash, saline was decanted and 2 drops of monoclonal, polyvalent antihuman globulin was added. Macroscopic and microscopic agglutination was looked for andany agglutination at this stage was recorded as weak D antigen. Positive control (check cellsi.e. washed O positive cells with diluted anti D) and negative control (washed O positive cells)were always put. Results: Among the 6320 healthy donors, 1224(19.4%) were Rh-D negativeand 5096(80.6%) were Rh-D positive. Of the 1224 Rh D negative samples, 3 (0.2%) samplesfound positive for weak D antigen. Conclusion: The frequency of Rh negative blood groupwas 0.2% among the healthy donors at The Children’s Hospital and ICH, Lahore. Although thefrequency is low but it’s proven by literature that weak D antigen can produce alloimmunizationif transfused to Rh-D negative subjects. At the same time the cases of hemolytic reactionsreported previously with Weak D antigen have been scarce.
The participation of women in blood donation process has been scarce equallyin low & high resourced countries. Every year 3.5 million blood donations are collected inPakistan with very little percentage of females donating blood. Objective: The objective of thestudy was to assess the knowledge, attitude and beliefs of female attendants accompanyingthe patients. Study Design: Cross-sectional study. Setting: The Children’s Hospital & Instituteof Child Health, Lahore, regarding blood donation. Period: 1st June to 31st December, 2015.Material & Methods: 306 females of age 16-50 years accompanying a patient in the hospitalwere randomly selected. After taking informed consent, a self-designed questionnaire validatedby Kappa Statistics program was distributed to the participants. Data was analyzed by usingSPSS 22. Results: The mean age of female attendants was 29.57 years. 31.7% had neverreceived any education. Only 12.7% had donated blood before. 93.8% had the idea that ablood transfusion is a lifesaving procedure but only half of them knew the common bloodgroups. 87.3% knew that both males and females can donate blood but 75.5% thought thatmales are better donors than females. There was a lack of knowledge about certain importantfacts including transfusion transmissible infections, donation frequency, duration and volumeof blood collected during a single session. Majority females were of the view that they are toofragile to donate blood and severe and prolonged anemia can develop after donating blood.Conclusion: There is a need to develop effective interventions for the education & motivationof potential female donors towards blood donation in order to increase the donor turnover rate.
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