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At least 19 recordsLinked to original sources
PubMed2026

PIP3 antagonist as a molecular regulator in MSC-derived cardiomyocytes: Potential in vitro therapeutic implications for conotruncal heart defects.

Conotruncal heart defects (CTDs) account for approximately one-third of all congenital heart defects. Elevated levels of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) may contribute to CTD pathogenesis. PIP3 plays a pivotal role in mechanotransduction-based biological processes and remodeling of cardiac cytoskeletal proteins. Here, we aimed to evaluate the efficacy of the 322PESB derivative compound as a molecular regulator that antagonizes PIP3 binding pleckstrin homology (PH) domain of the Akt protein using mesenchymal stem cell-derived cardiomyocyte. Human adipose-derived MSCs (Ad-MSCs) were isolated. Immunophenotypic features of the hAd-MSCs were characterized according to minimal criteria of the international society for cellular therapy (ISCT) including immunophenotyping and trilineage differentiation potential. Subsequently, the differentiated hAd-MSCs were cultured in cardiomyogenesis-inducing medium. Successfully differentiated cardiomyocytes were assessed by measuring the expression levels of cardiomyocyte-specific genes using RT-qPCR. PIP3-primed cardiomyocytes were treated with 10 and 30 μmol/L of a 322PESB derivative molecule. The results showed a typical MSCs with high expression levels of CD73 (77.55%), CD90 (87.59%) and CD105 (91.88%) and that was accompanied by low expression levels of CD34 (0.59%) and CD45 (1.78%). After 21 days of MSC culture, cardiomyocyte-like cells with prominent striations were observed. Subsequent confirmation by RT-qPCR quantification of ADRB1 and MLC2a expression levels showed an average increase of 2.9-fold and 2.1-fold, respectively, in induced cardiomyocytes. Compared with the untreated control, PIP3 ELISA assay showed a significant increase in PIP3 levels in PIP3(10 nmol/L)-primed cardiomyocytes treated with 10 and 30 μmol/L of the 322PESB molecule derivative by 485.804 and 3564.164 ng/mL, respectively. In this study, we conducted the first promising molecular regulator with potential therapeutic implications for CTD patients. Further functional animal model and clinical phase studies are recommended.

Cardiomyocyte↗
PubMed1978

Association of atrioventricular valve atresia with single ventricle, truncus arteriosus communis and transposition. A basic reorientation in the approach to the definition of congenital heart defects.

A heart specimen is presented which showed a rare combination of atrioventricular valve atresia with single ventricle, truncus arteriosus communis with an anteriorly placed trunk, ie transposition. Because of the problems involved in the classification of this heart, the types of single ventricle are revised with particular attention to the rare cases of atrioventricular valve atresia and single ventricle reported in the literature. Also the rare type of truncus arteriosus communis with truncoatrioventricular valve discontinuity is excluded from the so-called transposition complexes, and properly classified as a form of truncus. The literal meaning of transposition is stressed and it is urged to approach congenital heart defects in a purely anatomic sense with definition of each segment as accurately as possible. Thus the present confusion in terminology and further plethora of new terms are avoided.

Child↗
PubMed1978

Surgery for congenital heart disease in Ibadan. I: Non-cyanotic heart defects.

Congenital heart disease represents about 5% of all cardiovascular diseases in Nigeria today. Its incidence has increased in the last decade because of improved neonatal care, increased awareness and clinical acumen of physicians, better diagnostic tools and the introduction of newer techniques in cardiac catheterization. It is now possible to make the diagnosis with certainty and to define the extent of the pathology thus making it possible to select the appropriate surgical therapy for these children. This article reviews the commonest types of noncyanotic heart disease, the indications for surgery and the types of surgical procedures available in Nigeria today. The simple extracardiac defects, such as patent ductus arteriosus and coarctation of the aorta can be corrected with little or no mortality, but the more complex intracardiac defects can only be palliated pending the introduction of open heart surgery in Nigeria.

Aortic Coarctation↗
PubMed1975

[Oxygen transport in the blood of children with congenital heart defects].

In 55 children with congenital heart defects (aged 6 months and older), hematocrit, hemoglobin concentration, acid-base status, oxygen pressure, oxygen saturation, and 2,3-DPG content of erythrocytes were determined in blood taken from the vena cava superior. The data were correlated with each other as well as with parameters obtained during cardiac catheterization. Whereas an increased hematocrit was seen only at a difference in arteriovenous oxygen saturation of more than 30%, or a central venous saturation below 65%, a close correlation between 2,3-DPG concentration in erythrocytes and these parameters was obtained already in the normal range (r = 0.79, and r = 0.78, respectively). A relatively close correlation was also found between 2,3-DPG concentration and half-maximal oxygen saturation pressure (T50 value; r equals 0.73), and the T50 values and the central venous oxygen saturation (r equals 0.61), respectively. Because of the shift to the right of the O2-binding curve the functional oxygen transport capacity was increased by an average 15% in children with acyanotic heart defects (mean T50 value of 31.6 mm Hg), and by 40% in children with cyanotic heart defects (mean T50 value of 34.6 mm Hg), as compared to healthy children (mean T50 value of 28.1 mm Hg). A marked influence on the position of the O2-binding curve and hence on oxygen release of the blood in the periphery is therefore exerted by the 2,3-DPG concentration, whose effect was about twice that of the Bohr effect in the pH range measured.

Biological Transport↗
PubMed1978

Maximal exercise capacity of children with heart defects.

Maximal treadmill tests following the Bruce protocol were performed by 830 children with heart defects and the endurance times compared with normal values from 327 children seen in the same clinic because of normal murmurs and from 388 normal children randomly selected and tested in the schools. When values in the normal clinic children were used as the reference, only 21 percent of the patients with heart defects had endurance times below the 10th percentile line. This line was 14 percent higher in the normal school children, and 47 percent of the patient group had values below the 10th percentile when values in the school children were used as the reference. Maximal heart rate in children with heart defects was almost always in the normal range (180 to 210 beats/min) except in patients with cyanosis or severe valve disease and, when encouraged to continue exercising, even these children had a mean maximal heart rate of 175 beats/min. When comparing the exercise capacity of children with heart defects with that of normal children, the source of the normal children is important; body build needs to be considered, as well as physical activity habits. Clinic patients without heart defects probably serve as a better normal control group than children obtained from the school system. Maximal exercise tests do not necessarily distinguish between children with mild or severe heart disease. Only children with lesions causing cyanosis or children with obviously severe disease have consistent reductions in exercise capacity.

Adolescent↗
PubMed1979

[Pre- and postoperative erythrocyte volume distribution curves in children with cyanotic heart defects].

The behaviour of the volume distribution curves (VVK) of red blood cells in children with cyanosed organic heart defect is reported by taking preoperative and postoperative observations as a basis. MCV determined from the volume distribution curve amounts to 80.3 micron3. If the volume distribution curves of the preoperative patient group are compared with the postoperative patient group (4 months) by means of the criteria DSmax, DS, inclination and dispersion, no significant changes can be identified. Therefore, shifting maturity divisions cannot be assumed in children with cyanosed organic heart defects, even in those with a preoperative hypoxia of a high degree.

Adolescent↗
PubMed1978

Risk factors in surgical correction of congenital heart defects in early childhood.

The technique of surface-induced hypothermia, circulatory arrest and limited extracorporeal circulation was used in the surgical correction of congenital heart defects in 125 young children. Hospital mortality was 18% and no death could be attributed to the surgical technique. An analysis of risk factors demonstrated that successful corrective surgery was not significantly related to age, body weight or pulmonary vascular obstructive disease. In transposition of the great arteries, the presence of a ventricular septal defect was associated with an increased mortality. Emergency operations performed because of severe hypoxaemia carried a high mortality, especially in patients with tetralogy of Fallot.

Child↗
PubMed1975

[Congenital heart defects in persons of advanced and old age].

The article presents data on 7 sectional observations on congenital heart defects in elderly and old persons (57 to 75 years). An open oval window with the functioning valve was detected in 6 cases, completely non-obliterated oval window--in one case. The correct diagnosis had not been made when the patients were alive. This can be easily explained due to the difficulties of diagnosing, since no clinical manifestations of the defect were noted for a long time. In all cases death was caused by chronic cardiovascular insufficiency.

Age Factors↗
PubMed1979

[Pathologic diagnosis of certain congenital heart defects].

Morphometrical examinations of 265 normally formed hearts collected at autopsies of infants under 2 years of age were used as a control of the heart weight and size of the pulmonary trunk and aorta. The time of anatomical closing of the arterial duct and oval window were established. Comparisons of the results of morphometry of normal and 173 malformed hearts with the tabulated data were used to develop objective criteria for pathological diagnosis of congenital heart diseases: open arterial duct and centrally located defect of the interatrial septum in infants dying within the first two months of life. The criteria for the detection of marginal forms of stenosis of the pulmonary trunk ostium and isolated coarctation of the aortal isthmus were established.

Age Factors↗