Induction of apoptosis and inhibition of growth of human hepatoma HepG2 cells by heparin

BACKGROUND/AIMS: Apoptotic and anti-proliferative effects of heparin on a number of cancers have been described. There have been no studies analyzing the effect of heparin on human hepatoma cells. The aim of this study was to investigate the effect of heparin on human hepatoma cell line, HepG2. METHODOLOGY: HepG2 cell line was cultured with different concentrations of heparin. Colony count, viability assay, percentage of the apoptosis and proliferative index were assessed at the end of the 7th day. Trypan blue was used to assess viability. Apoptosis and proliferative indexes were assessed by flow-cytometry. RESULTS: Hepatoma cells were arrested at the G0/G1 phase with heparin incubation and proliferative indexes decreased significantly in 20, 40 and 80 U/mL of heparin concentrations in comparison with the control (36 +/- 1%, 30 +/- 5% and 29 +/- 8% vs. 44 +/- 1%, p < 0.01). Flow cytometry revealed a statistically significant increase in apoptosis in groups incubated with 40 and 80 U/mL of heparin in comparison with the control (39 +/- 26% and 58 +/- 18% vs. 0.83 +/- 1.3%, p < 0.01). Colony counts per well and viable cells per microL decreased significantly in 80 U/mL of heparin. CONCLUSIONS: Heparin leads to a significant anti-proliferative and an apoptotic effect on human hepatoma cells in vitro.     

In vivo effect of losartan on platelet aggregation in patients with hypertension

The angiotensin II receptor, losartan, has been found to inhibit platelet aggregability to some extent in in vitro experiments. There have been conflicting results about the in vivo effects of losartan. We sought to clarify the in vivo effect of losartan on platelet aggregation. Forty patients with grade I essential hypertension were treated with losartan for 3 weeks. Platelet aggregation tests with adenosine diphosphate (ADP) and ristocetin were analyzed and compared before and at the end of the study. Losartan effectively decreased systolic (SBP) and diastolic (DBP) blood pressure. Mean SBP before and after treatment was 159.6 ± 12.8 and 149.2 ± 17.3mmHg, respectively. Mean DBP decreased from 93.7 ± 8.2 to 87.7 ± 10.3mmHg after treatment. The results of the platelet aggregation tests with ADP and ristocetin were not significantly different when both rate and amplitude of maximal aggregation were included. Peak platelet aggregation with ADP regarding the lowest light transmission in the aggregometer was 59.8% ± 24.3% before and 58.3% ± 18.1% after the treatment. The same variables with ristocetin were 66.8% ± 21.6% and 60.8% ± 23.3%, respectively. In vivo effects of losartan on platelet aggregation with ADP and ristocetin were insignificant.     

Is the Change of Late Potential Over Time Related to Enzyme Levels?Ichemic Burden in Acute Myocardial Infarction

Background: The ventricular late potential (VLP) detected using the technique of signal average electrocardiography (SAECG) interacts with several factors, primarily time. Method: In this study, we examined the interaction, over time, of VLP with the initial ischemic burden and enzyme levels in acute myocardial infarction. Patients diagnosed as having acute myocardial infarction were included in the study. On the first day, the patients underwent enzyme analysis and electrocardiography (ECG) follow‐up every 6 hours. A 24‐hour ambulatory ECG was performed on the seventh day in order to determine the ischemic burden. SAECG findings (TQRS, RMS, LAS were obtained on the seventh day, in the first and third months. The study was continued with the patients who did not require angioplasty as decided with angiographic evaluation in the first month. Results: The study included 30 patients with acute myocardial infarction (mean age 51 ± 12, 28 males and 2 females). The initial mean CK‐MB levels and the mean ischemic burden were 98 ± 31 U/L and 44 ± 96 minutes. The TQRS (ms), LAS (ms), and RMS (μV) values (mean ± SD) obtained at day 7, month 1, and month 3 are 97 ± 12, 96 ± 9, 103 ± 11, P = 0.01; 31 ± 10, 31 ± 11, 32 ± 10, P = 0.46; 43 ± 28, 41 ± 26, 33 ± 25, P = 0.01, respectively. We observed that the TQRS and RMS values changed significantly with time, but these levels of significance disappeared when adjusted for the initial ischemic burden and CK‐MB levels (P = 0.06; P = 0.53). The VLP frequency was 33% at day 7 and 23% at month 3. Unlike the CK‐MB level, the initial ischemic burden was significantly different between the patients with and without VLP at month 3 (150.85 ± 149.28, 12.34 ± 26.48, P = 0.001). When tested together with age and gender, it was found that the high initial ischemic burden increased the possibility of VLP (OR: 24, Cl: 2.09–279.52, P = 0.01) at month 3. Conclusion: SAECG findings in patients with myocardial infarction changed with time; however, this change occurred depending on the initial ischemic burden and CK‐MB levels. Of these, only the initial ischemic burden, especially in high levels, was a determinant for the presence of VLP in the late period of myocardial infarction. A.N.E. 2002;7(3):242–246     

Effects of octreotide and propranolol on colonic mucosa in rats with portal hypertensive colopathy

BACKGROUND/AIMS: The aim of the study is to clarify the effects of octreotide and propranolol, agents used in the treatment of portal hypertension, on mucosal changes in portal hypertensive colopathy. METHODOLOGY: Portal hypertension was induced in all rats by partial portal vein ligation, and after the operation all rats were caged for a 10-week period. Then, animals were divided into three groups and for two weeks medical treatment were administered to the individual groups as follows: Control group, saline 0.5 mL/day, intraperitoneally. Octreotide group, octreotide 100 micrograms/kg/12 hours, subcutaneously. Propranolol group, propranolol 20 mg/kg/day, intraperitoneally. In order to assess the portal hypertensive colopathy, criteria such as mean diameters of dilated vessels in colonic mucosa, and the existence of mucosal edema, capillary ectasia, hyperemia and hemorrhage, inflammation were used. RESULTS: When parameters were compared for the control versus propranolol groups, mucosal edema and hyperemia and hemorrhage criteria were found to be significant for the propranolol group; control versus octreotide groups, mucosal edema, capillary ectasia, and hyperemia and hemorrhage criteria were found to be significant for the octreotide group; octreotide versus propranolol groups, capillary ectasia and mucosal edema criteria were found to be significant for the octreotide group. CONCLUSIONS: The mucosal changes in portal hypertensive colopathy could be corrected by drugs modifying portal blood flow, octreotide may find a place in the treatment of portal hypertensive colopathy.     

Transcatheter closure of congenital coronary arterial fistulas in adults

OBJECTIVES: We have described our experience with transcatheter occlusion of congenital coronary arterial fistulas in adults. METHODS: Six symptomatic patients, mean aged 41+/-12 years (four men, two women) underwent transcatheter occlusion of fistulas. All had chest pain or dyspnea on exertion. Four of the patients had single fistula. Two of the patients had multiple fistulas. The fistulas originated from the left anterior descending coronary artery in four patients, and from the circumflex artery in two. They all drained into the pulmonary trunk. Graft stenting was used in two patients who had multiple fistulas, and coils in four who had a single fistula. The coils were implanted through a microcatheter, which was passed through a JL 4 8F guiding catheter. RESULTS: Coils were used to completely occlude fistulas. Two 3.0x20 mm coronary graft stents were deployed in the coronary arteries to occlude the fistulas. The procedures were uncomplicated. At follow up, all patients underwent coronary angiography, and one of the patients with coil embolization and one of the patients with graft stenting had small residual flow. Patient's chest pain or dyspneas have resolved after the procedure. CONCLUSION: Transcatheter closure in adults of congenital coronary fistulas with graft stents and coils are safe and effective, and can be regarded as an acceptable alternative to surgery.     

HLA-DR B1 and DQ B1 polymorphisms in patients with coronary artery ectasia

OBJECTIVES: The purpose of our study was to evaluate the significance of polymorphisms in HLA class II genes in coronary artery ectasia (CAE) patients. METHODS AND RESULTS: Twenty-six patients with CAE without associated cardiac defects were enrolled in the study. CAE was defined as luminal dilation of 1.5- to 2.0-fold of normal limits. Ninety-five healthy subjects who were donors for different organ transplantations, were chosen as control group. Physical examination, electrocardiography and chest X-ray were completely normal in these cases. Both the patients and the control group were screened and compared for their HLA class II genotypes. HLA-DR B1*13, DR16, DQ2 and DQ5 genotypes were significantly more frequent in the patient group.When the known risk factors of coronary heart disease were compared in the patients carrying these genotypes with the non-carrying group, no significant differences were encountered. CONCLUSIONS: HLA-DR B1*13, DR16, DQ2 and DQ5 may be associated with the pathogenesis and increase the risk of CAE.     

Hepatic apoptosis and proliferation in male and female rats fed alcohol: role of cytokines

Background: The female liver is more sensitive to the toxic effect of chronic alcohol intake than the male liver. The aim of the study was to compare the influence of gender and sex hormonal status on apoptosis and cell proliferation following chronic ethanol intake.
Methods: Male and female rats were pair fed for 8 weeks a liquid diet containing 36% of their total daily calories as ethanol (ETOH group) or sucrose (control group). Liver samples were analyzed for apoptosis and hepatocyte proliferation by immunohistochemistry. The hepatic production of factors able to influence cell death and proliferation, such as tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) were determined.
Results: In both male and female rats, ethanol intake promoted apoptosis in the liver. This effect of ethanol was more evident in female than male rat livers. Hepatic TNFα levels, which promote apoptosis, are significantly more elevated in female than in male livers. Hepatic IL-6 production, which promotes hepatocyte proliferation, was induced by ethanol only in males, but not female animals.
Conclusion: This observed difference in cytokine responses may contribute to the enhanced sensitivity of female liver to EtOH-induced injury.     

Povidone iodine in the treatment of adenoviral conjunctivitis in infants

Context: Adenoviral conjunctivitis.

Objective: To examine the effects of conjunctival irrigation with povidone iodine in infants with adenoviral conjunctivitis.

Material and methods: An outbreak of adenovirus conjunctivitis occurred between September and December 2012 at the neonatal intensive care unit of our hospital. Forty-three infants with adenoviral conjunctivitis were examined in this study. Thirty-five eyes of 35 infants who had detailed ophthalmological examination and clinical scoring were included. The conjunctiva of 15 infants (Group 1) were irrigated with povidone iodine 2.5% solution and then treated with preservative-free artificial tears and preservative-free antibiotic drops. Twenty infants (Group 2) were treated only with the same drops with the same posology, without conjunctival irrigation with povidone iodine. Patients were examined two times a week until the complete recovery. Lid edema, conjunctival chemosis, fragility of conjunctival vasculature, pseudomembrane formation, and corneal involvement were scored clinically.

Results: Twenty patients (57%) were female and 15 patients (43%) were male and mean age was 3.1 months (ranged from 1 to 4 months). No relation was found between gender and clinical scores. Statistically significant lower clinical scores were obtained from Group 1. The median recovery time was earlier in Group 1 (7?d) than Group 2 (12?d) (p?=?0.001).

Conclusion: Conjunctival irrigation with 2.5% povidone iodine is effective in the treatment of adenoviral conjunctivitis in infants.     

Usefulness of coronary angiography for assessing left ventricular systolic function

OBJECTIVE: In previous echocardiographic studies, a correlation between ejection fraction of the left ventricle and change in the movement of the mitral annular ring was found. In the light of these studies, we planned to investigate the relationship between systolic shortening (SS) and percent of systolic shortening (PSS), calculated from the long axis frame in coronary angiography and left ventricular systolic function. METHODS AND RESULTS: One hundred and thirty-eight patients (40 men and 98 women; mean age 58 +/- 10 years) who had been referred for coronary angiography and left ventriculography were included in the study. Ejection fraction (EF) was calculated from left ventriculography obtained from 30 degrees right anterior oblique projection. Distance from the lower border of the ostium of the left coronary artery to the most apical border of the left anterior descending (LAD) artery was measured at end-systole (ES) and end-diastole (ED) using coronary angiography obtained from the same projection. SS as ED-ES and PSS as SS/ED were calculated. Correlation of SS and PSS with EF was calculated (EF = 13.7 + 4.8 x SS, r = 0.91, p < 0.001 and EF = 14.2 + 6.5 x PSS, r = 0.90, p < 0.01). SS < 7 mm (criterion A) and PSS < 6% (criterion B) suggested that left ventricle EF was less than 50%, with a sensitivity, specificity and diagnostic accuracy of 83%, 100%, 95%; 95%, 86% and 88%, respectively. CONCLUSION: SS and PSS highly significantly correlate with left ventricular EF. Therefore, left ventriculography could be omitted in selected patients undergoing coronary angiography if it is not necessary to define the anatomic structure of the left ventricle.     

Leptin response to oral glucose tolerance test in obese and nonobese premenopausal women

The objective of this study was to investigate the serum leptin response to oral glucose stimulation in a group of obese and nonobese normotensive, normolipidemic, and glucose-tolerant premenopausal women. Twenty-one obese (BMI: 37.7 +/- 6.3 kg/m2) and 14 nonbese (BMI: 21.5 +/- 1.0 kg/m2) age-matched, healthy premenopausal women were included in the study. Serum glucose, insulin, and leptin levels were measured at 30 min intervals during the 120 min of an oral glucose tolerance test (OGTT). Mean serum glucose, insulin, and leptin levels were significantly higher in the obese group compared to nonobese subjects during OGTT. Except for a 120 min decrement noted in obese women, no changes occurred in serum leptin levels during oral glucose stimulation in both groups. As a conclusion, absence of a significant elevation in serum leptin levels during OGTT in our obese subjects compared to nonobese subjects may be related to their normal metabolic variables despite being abdominally obese and insulin resistant.