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Biomedical subjects

K Baysal

Publications and source records attributed to K Baysal.

At least 19 recordsLinked to original sources

Electrocardiographic findings after 5-HT3 receptor antagonists and chemotherapy in children with cancer.

BACKGROUND: The antiemetic efficacy of serotonin-type 3 (5-HT3) receptor antagonists has been found to be superior to older antiemetic drugs in cancer patients. Following the administration of these agents, changes in ECG parameters and increased or decreased heart rates have been demonstrated, but there is no sufficient data in children with cancer who are treated with cytotoxic agents. The objective of this study is to evaluate the ECG changes after administration of 5-HT3 receptor antagonists and chemotherapeutic agents in children with cancer. PROCEDURE: Thirty-eight patients with an age range between 2 and 19 years receiving chemotherapy for solid tumors were included in the study. The patients received 5-HT3 receptor antagonists 30 min before antineoplastic agents in 83 chemotherapy days. Antiemetic therapy consisted of ondansetron in 43 and granisetron in 40 chemotherapy days. Twelve-leads ECGs were obtained four times at the first day of each chemotherapy: just before 30, 90 min, and 24 hr after 5-HT3 receptor antagonists were given. Rate, rhythm, PR interval, QRS duration, ST segment, the shortest (QTca) and the longest (QTcb) QTc intervals with QTc dispersion (QTcd) were all evaluated. RESULTS: We found a significant shortening of the PR interval and QRS complex durations in the granisetron group at 90th min and at 24th hr, respectively. Also, granisetron infusion caused a significant prolongation of the QTca interval at 90 min. CONCLUSION: Although we observed minor ECG changes after 5-HT3 receptor antagonists and chemotherapy, neither dangerous rhythm disturbances nor serious ECG changes were seen.

Adolescent↗

A thoracal spinal cord teratoma associated with Taussig-Bing anomaly in a newborn.

BACKGROUND: Teratomas are the most common type of childhood germ cell tumor, arising in both ovary and extragonadal locations. From 40% to 50% of the extragonadal teratomas occur in the sacrococcygeal region. Teratomas in the head, neck, brain, mediastinum, abdominal, and spinal cord locations are seen less frequently. Congenital anomalies are observed up to 26% of the cases with teratoma. METHODS: A 2-day-old newborn was admitted to the hospital because of a mass in the interscapular region. She was evaluated for this and other anomalies. The mass was excised totally, and histopathologic evaluation was done. RESULTS: Histopathologic examination of the mass revealed a mature teratoma. In addition, the child had a Taussig-Bing anomaly of the heart. CONCLUSIONS: This appears to be the first report of the association between congenital thoracic spinal cord teratoma and Taussig-Bing anomaly, a specific type of transposition of the great arteries.

Double Outlet Right Ventricle↗

Activation of ERK by Ca2+ store depletion in rat liver epithelial cells.

In rat liver epithelial (WB) cells, Ca2+ pool depletion induced by two independent methods resulted in activation of extracellular signal-regulated protein kinase (ERK). In the first method, Ca2+ pool depletion by thapsigargin increased the activity of ERK, even when rise in cytosolic Ca2+ was blocked with the Ca2+ chelator BAPTA-AM. For the second method, addition of extracellular EGTA at a concentration shown to deplete intracellular Ca2+ pools also increased ERK activity. In each instance, ERK activation, as measured by an immunocomplex kinase assay, was greatly reduced by the tyrosine kinase inhibitor genistein, suggesting that Ca2+ store depletion increased ERK activity through a tyrosine kinase pathway. The intracellular Ca2+-releasing agent thapsigargin increased Fyn activity, which was unaffected by BAPTA-AM pretreatment, suggesting that Fyn activity was unaffected by increased cytosolic free Ca2+. Furthermore, depletion of intracellular Ca2+ with EGTA caused inactivation of protein phosphatase 2A and protein tyrosine phosphatases. ANG II-induced activations of Fyn, Raf-1, and ERK were augmented in cells pretreated with BAPTA-AM, but ANG II-induced expression of the dual-specificity phosphatase mitogen-activated protein kinase phosphatase-1 was blocked by BAPTA-AM pretreatment. Together these results indicate that ERK activity is regulated by the balance of phosphorylation vs. dephosphorylation reactions in intact cells and that the amount of Ca2+ stored in intracellular pools plays an important role in this regulation.

Angiotensin II↗

Correlation between sustained c-Jun N-terminal protein kinase activation and apoptosis induced by tumor necrosis factor-alpha in rat mesangial cells.

Rat mesangial cells are normally resistant to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. In this report we show that the cells can be made susceptible to the apoptotic effect of TNF-alpha when pretreated with actinomycin D, cycloheximide, or vanadate. c-Jun N-terminal protein kinase (JNK) has been thought to mediate apoptotic processes elicited by some stimuli, but its involvement in TNF-alpha-induced apoptosis has been controversial. JNK activation was investigated under conditions where the mesangial cells were either resistant or susceptible to TNF-alpha-induced apoptosis. TNF-alpha alone stimulated a single transient JNK activity peak. However, when the cells were pretreated with actinomycin D or cycloheximide, TNF-alpha stimulated a second sustained JNK activity peak. When the cells were pretreated with the phosphatase inhibitor vanadate, TNF-alpha-induced JNK activation was greatly prolonged. In all three cases, a sustained JNK activation was associated with the initiation of apoptosis. Our data suggest that a sustained activation of JNK induced by these reagents may be associated with blocking the expression of a phosphatase that inactivates JNK. Further studies reveal that the expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) was induced by TNF-alpha, indicating that MKP-1 may be involved in protecting the cells from apoptosis by preventing a prolonged activation of JNK under normal conditions. Additional studies showed that extracellular signal-regulated protein kinase activation stimulated by TNF-alpha was unlikely to contribute to the resistance of mesangial cells to TNF-alpha cytotoxicity.

Animals↗

Cardiac involvement due to Salmonella typhi infections in children.

Sixty-six patients with Salmonella typhi infections were evaluated in terms of cardiological events in the Department of Pediatrics of Ondokuz Mayis University Hospital for a period of 14 years. Cardiac involvement is described in three cases of typhoid fever during that time. One patient had myocarditis only but another two cases had myocarditis and pericarditis. In addition to antibiotic therapy, pericardiocentesis and pericardiectomy were used. We present three cases of myocarditis caused by Salmonella typhi infections.

Adolescent↗

On the relationship between matrix free Mg2+ concentration and total Mg2+ in heart mitochondria.

The matrix free magnesium ion concentration, [Mg2+]m, estimated using the fluorescent probe furaptra, averaged 0.67 mM in 15 preparations of beef heart mitochondria containing an average of 21 nmol total Mg2+ per mg protein. [Mg2+]m was compared with total Mg2+ during respiration-dependent uptake and efflux of Mg2+ and during osmotic swelling. In the absence of external Pi these mitochondria contain about 32 nmol/mg non-diffusible Mg-binding sites with an apparent Kd of 0.34 mM. [Mg2+]m depends on both the size of the total Mg2+ pool and the ability of matrix anions to provide Mg-ligands. Pi interacts strongly with Mg2+ to decrease [Mg2+]m and, in the absence of external Mg2+, promotes respiration-dependent Mg2+ efflux and a decrease in [Mg2+]m to very low levels. The uptake of Pi by respiring mitochondria converts delta pH to membrane potential (delta psi) and provides additional Mg-binding sites. This permits large accumulations of Mg2+ and Pi with little change in [Mg2+]m. Nigericin also converts delta pH to delta psi in respiring mitochondria and induces a large and rapid increase in both total Mg2+ and [Mg2+]m. Mersalyl increases the permeability of the mitochondrial membrane to cations and this also induces a marked increase in both total Mg2+ and [Mg2+]m. These results suggest that mitochondria take up Mg2+ by electrophoretic flux through membrane leak pathways, rather than via a specific Mg2+ transporter. Mitochondria swollen by respiration dependent uptake of potassium phosphate show decreased [Mg2+]m, whereas those swollen to the same extent in potassium acetate do not. This suggests that [Mg2+]m is well-buffered during osmotic volume changes unless there is also a change in ligand availability.

Animals↗

On the use of fluorescent probes to estimate free Mg2+ in the matrix of heart mitochondria.

The fluorescent probe furaptra shows increases and decreases in the concentration of free magnesium ion, [Mg2+], in the mitochondrial matrix with changes in total Mg2+ and ligand availability. The factors involved in the calibration of these fluorescence changes in terms of absolute [Mg2+] have been investigated. The affinity of furaptra for Mg2+ is highly dependent on both temperature and ionic strength. The Kd for Mg-furaptra in solution in 100 mM KCl was found to be 2.1 +/- 0.1 mM at 25 degrees C. The use of this Kd to calculate matrix [Mg2+] is more reliable than in situ Kd measurements because ionophores, such as BrA23187 and ionomycin, do not equilibrate external Mg2+ with the matrix in an acceptable way. Furaptra is present at high concentrations (up to 500 microM) in the matrix when introduced by hydrolysis of the acetoxymethyl ester. However, absorbance spectra of aqueous solutions show no evidence of dimerization of the probe or other changes in properties at these concentrations. Fluorescence intensity at 340 nmex is strongly attenuated for matrix-sequestered furaptra, mag-fura-5, and mag-indo-1. This appears to result in part from preferential binding of the Mg-probe to mitochondrial proteins. The fluorescence of uncomplexed furaptra at 375-380 nmex seems unaffected by protein binding, however, and changes in intensity in this region of the spectrum can be used in conjunction with the Kd found in aqueous solution to estimate matrix [Mg2+]. The presence of secondary equilibria, such as protein binding, and possible changes in ionic strength may undermine exact quantitation by this method. However, values for matrix [Mg2+] obtained in this way (0.5 to 0.7 mM) correspond well to estimates by other available methods and each of these methods suffers from comparable uncertainties.

Animals↗

The incidence and significance of increased backscatter in myocardial ultrasonography of patients on hemodialysis.

Ultrasonic backscatter is substantially modified by pathologic changes in myocardium. To define the incidence and significance of increased backscatter in myocardial ultrasonography of patients on chronic hemodialysis, 41 patients (aged 9-63 years) and 20 healthy controls were studied with conventional two-dimensional and M-mode echocardiography and with analysis of integrated backscatter. Increased histogram values were found in all patients especially in those whose two-dimensional echocardiographic examinations revealed mitral annular calcification (n = 3), aortic valve calcification (n = 2) and aortic plus mitral annular calcification (n = 1). It was concluded that ultrasonographic-integrated backscatter may be a useful method for early identification of cardiac calcification in uremic patients.

Adolescent↗

The sodium-calcium antiport of heart mitochondria is not electroneutral.

Heart mitochondria contain a nNa+/Ca2+ antiport that participates in the regulation of matrix [Ca2+]. Based largely on a single study (Brand, M. D. (1985) Biochem. J. 229, 161-166), there has been a consensus that this antiport promotes the electroneutral exchange of two Na+ for one Ca2+. However, a recent study in our laboratory (Baysal, K., Jung, D. W., Gunter, K. K., Gunter, T. P., and Brierley, G. P. (1994) Am. J. Physiol. 266, C800-C808) has shown that the Na(+)-dependent efflux of Ca2+ from heart mitochondria has more energy available to it than can be supplied by a passive 2Na+/Ca2+ exchange. We have therefore re-examined Brand's protocols using fluorescent probes to monitor matrix pH and free [Ca2+]. Respiring heart mitochondria, suspended in KCl and treated with ruthenium red to block Ca2+ influx, extrude Ca2+ and establish a large [Ca2+]out:[Ca2+]matrix gradient. The extrusion of Ca2+ under these conditions is Na(+)-dependent and diltiazem-sensitive and can be attributed to the nNa+/Ca2+ antiport. Addition of nigericin increases the membrane potential (delta psi) and decreases delta pH to 0.1 or less, but has virtually no effect on the magnitude of the [Ca2+] gradient. Under these conditions a gradient maintained by electroneutral 2Na+/Ca2+ antiport should be abolished because the mitochondrial Na+/H+ antiport keeps the [Na+] gradient equivalent to the [H+] gradient. The [Ca2+] gradient is abolished, however, when an uncoupler is added to dissipate delta psi or when the exogenous electroneutral antiport BrA23187 is added. In addition, [Ca2+] influx via the nNa+/Ca2+ antiport in nonrespiring mitochondria is enhanced when delta psi is abolished. These results are consistent with Ca2+ extrusion by an electrophoretic antiport that can respond to delta psi but not with an electroneutral antiport.

Animals↗

The role of thymosin F5 on anemia in hypercholesterolemic rabbits.

New Zealand White rabbits were made hypercholesterolemic by feeding a high cholesterol diet (20 g/kg diet) for 3 months. Plasma cholesterol concentrations were monitored as a function of time. At the end of 3 months, the plasma lipid levels, the whole blood, erythrocyte and haemoglobin-bound 2,3-DPG levels and leucocyte counts increased, whereas erythrocyte counts, hematocrit and haemoglobin levels decreased significantly in hypercholesterolemic rabbits. At the end of 3 months, the rabbits in the experimental group were divided into two groups. The first group was fed a standard diet for 21 days. The second group received 0.5 mg/kg thymosin F5 injection i.p. every other day for 21 days. After this period, the plasma lipid levels, the whole blood, erythrocyte and haemoglobin-bound 2,3-DPG levels, erythrocyte and leucocyte counts, hematocrit and haemoglobin levels were measured. Rabbits fed diets supplemented with thymosin F5 had markedly lower plasma lipid levels, erythrocyte counts, hematocrit and haemoglobin levels and enhanced leucocyte counts, but did not have significantly less whole blood, erythrocyte and haemoglobin-bound 2,3-DPG levels. We conclude that thymosin F5 has lipid-lowering effects in hypercholesterolemic rabbits. The data further suggest that effects of thymosin F5 on haematological parameters are due to the cholesterol decrease and not to the direct regulatory mechanism.

2,3-Diphosphoglycerate↗

Cation transport systems in mitochondria: Na+ and K+ uniports and exchangers.

It is now well established that mitochondria contain three antiporters that transport monovalent cations. A latent, allosterically regulated K+/H+ antiport appears to serve as a cation-extruding device that helps maintain mitochondrial volume homeostasis. An apparently unregulated Na+/H+ antiport keeps matrix [Na+] low and the Na(+)-gradient equal to the H(+)-gradient. A Na+/Ca2+ antiport provides a Ca(2+)-extruding mechanism that permits the mitochondrion to regulate matrix [Ca2+] by balancing Ca2+ efflux against influx on the Ca(2+)-uniport. All three antiports have well-defined physiological roles and their molecular properties and regulatory features are now being determined. Mitochondria also contain monovalent cation uniports, such as the recently described ATP- and glibenclamide-sensitive K+ channel and ruthenium red-sensitive uniports for Na+ and K+. A physiological role of such uniports has not been established and their properties are just beginning to be defined.

Animals↗

Na(+)-dependent Ca2+ efflux mechanism of heart mitochondria is not a passive Ca2+/2Na+ exchanger.

Net Ca2+ flux across the inner membrane of respiring heart mitochondria was evaluated under conditions in which virtually all Ca2+ movement can be attributed to the Na+/Ca2+ antiport. If this antiport promotes a passive electroneutral exchange of Ca2+ for 2Na+, the Ca2+ gradient should be equal to the square of the Na+ gradient at equilibrium. Because the mitochondrial Na+/H+ antiport equilibrates the Na+ and H+ gradients, the Ca2+ gradient should also equal the square of the H+ gradient. In a series of > 20 determinations at different matrix [Ca2+], different delta pH, and varying membrane potential, it was found that Ca2+ is transported out of the mitochondrion against gradients from 15- to 100-fold greater than the value predicted for passive electroneutral exchange. It is concluded that the observed gradients are too large to be sustained by passive Ca2+/2Na+ exchange. The observed gradients are compatible with an electrogenic Ca2+/3Na+ exchange. Alternatively another source of energy is available to support these gradients.

Biological Transport↗

Myocardial functions of children with acute poststreptococcal glomerulonephritis.

Left ventricular function was investigated by two-dimensional and M-mode echocardiography in 35 patients with acute poststreptococcal glomerulonephritis and in 25 healthy controls. Six of these patients were found to have myocardial dysfunction during the acute congestive phase and convalescent phases of APSGN. One of these 6 patients, later, died. No correlations were determined between myocardial dysfunction and hypertension, cardiac failure, pericardial and pleural effusion. As a result, left ventricular function may be impaired in acute congestive phase of APSGN and this may affect the course and prognosis of the disease.

Child↗

Surgical treatment in tetralogy of Fallot diagnosed by echocardiography.

The purpose of this paper is to present the authors' 3-yr experience of echocardiographic examination of patients with the clinical diagnosis of tetralogy of Fallot, and their evaluation for surgical treatment without prior cardiac catheterization. Among the patients with the clinical diagnosis of tetralogy of Fallot 227 had a definite diagnosis made by M-mode, two-dimensional, Doppler and contrast echocardiography. For the diagnosis of tetralogy of Fallot, ventricular septal defect, pulmonary stenosis, and overriding of the aorta were considered to be fundamental. Ventricular septal defect could be seen easily in the subaortic region by two-dimensional echocardiography. However, in some patients whose ventricular septal defect was not seen clearly, peripheral vein contrast echocardiography was performed. The diameters of pulmonary artery, and main branches at a few millimeters distal to their origin were measured. These parameters were correlated with the aortic diameter for evaluation as to whether they were able to accept the total cardiac output. In patients whose left ventricular end-diastolic dimension was small, shunt operation was preferred. In 115 patients the pediatric cardiologist performing the echocardiography thought that cardiac catheterization was necessary. In these cases the reliability of echocardiography in detecting important cardiac abnormalities was evaluated. Detection of ventricular septal defect, presence of pulmonary valve, detection of stenosis on the pulmonary bifurcation and/or main branches revealed a high sensitivity. Two-hundred-and-one patients diagnosed by echocardiography underwent total correction. In all cases except one the preoperative diagnosis was confirmed by surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The relationship between mitral valve prolapse and acute rheumatic fever in pediatric patients.

Mitral valve prolapse (MVP) is a clinical syndrome of which mitral regurgitation and congestive heart failure are the late sequelae. It can be usually diagnosed by echocardiography. In this study, we reevaluated the patients with acute rheumatic fever (ARF) who were followed-up regularly for aspects of MVP. Physical examination, echocardiography and Doppler study were performed for all the patients. One hundred twenty-seven cases of polyarthritis (54.7%), and 105 cases of valvular involvement (45.3%) were diagnosed. Echocardiography demonstrated MVP in 46.8% with isolated mitral insufficiency, in 38.2% with combined valvular defect and in 12.6% with only polyarthritis. One hundred healthy children comprised the control group. Statistical analyses revealed a significant difference in favor of valvular involvement between the groups.

Child↗