Changes of aqueous vascular endothelial growth factor and interleukin‐6 after intravitreal triamcinolone for branch retinal vein occlusion

Background: To investigate sequential changes of aqueous vascular endothelial growth factor (VEGF) and interleukin (IL)‐6 in macular oedema secondary to branch retinal vein occlusion after single intravitreal injection of triamcinolone acetonide (IVTA). Methods: We recruited 10 healthy controls and 30 patients at Chonnam National University Hospital, Gwangju, Korea. Aqueous and plasma levels of VEGF and IL‐6 were measured by enzyme‐linked immunosorbent assay at the time of IVTA and 3 months later. Non‐response to IVTA was defined as showing persistent macular oedema based on a reduction of central macular thickness by less than 20% from baseline measurements by optical coherence tomography and vision improvement by less than 0.3 logMAR. Fluorescein angiography was performed 6 months after IVTA. We compared aqueous levels of VEGF and IL‐6 between responders and non‐responders. Results: The aqueous levels of VEGF and IL‐6 were significantly higher in 12 non‐responders than in 18 responders at baseline measurements (511 ± 245 pg/mL vs. 230 ± 108 pg/mL, P < 0.001; 38 ± 31 pg/mL vs. 16 ± 13 pg/mL, P < 0.001, respectively). Aqueous levels of VEGF were still higher in non‐responders (312 ± 64 pg/mL) 3 months after IVTA, and aqueous levels of VEGF in responders returned to normal (86 ± 21 pg/mL, P < 0.001). Aqueous levels of IL‐6 normalized in all patients 3 months after IVTA. Fluorescein angiography revealed that non‐responders showed higher frequencies of macular ischaemia and ischaemic branch retinal vein occlusion. Conclusions: IL‐6‐independent VEGF secretion may contribute to persistent macular oedema associated with ischaemic BRVO after IVTA.     

Kinetic Changes of COX-2 Expression during Reperfusion Period after Ischemic Preconditioning Play a Role in Protection Against Ischemic Damage in Rat Brain

A brief ischemic insult induces significant protection against subsequent massive ischemic events. The molecular mechanisms known as preconditioning (PC)-induced ischemic tolerance are not completely understood. We investigated whether kinetic changes of cyclooxygenase (COX)-2 during reperfusion time-periods after PC were related to ischemic tolerance. Rats were given PC by occlusion of middle cerebral artery (MCAO) for 10 min and sacrificed after the indicated time-periods of reperfusion (1, 2, 4, 8, 12, 18 or 24 h). In PC-treated rats, focal ischemia was induced by occlusion of MCA for 24 h and brain infarct volume was then studied to determine whether different reperfusion time influenced the damage. We report that the most significant protection against focal ischemia was obtained in rats with 8 h reperfusion after PC. Administration of indomethacin (10 mg/kg, oral) or rofecoxib (5 mg/kg, oral) 48 h prior to PC counteracted the effect of PC. Immunohistochemical analysis showed that COX-2 and HO-1 protein were induced in PC-treated rat brain, which was significantly inhibited by rofecoxib. Taken together, we concluded that the kinetic changes of COX-2 expression during the reperfusion period after PC might be partly responsible for ischemic tolerance.     

Genotoxicity testing of aqueous extracts of Mahwangyounpae-tang, a polyherbal formula

Mahwangyounpae-tang (MT), consisting of 22 types of herbal extracts has been used for thousands of years in Korean traditional medicine for the oral treatment of respiratory diseases including asthma. As part of a safety evaluation of MT extracts for use in asthma, the potential genotoxicity of an aqueous MT extract was evaluated using the standard battery of tests (bacterial reverse mutation assay; chromosomal aberrations assay; mouse micronucleus assay) recommended by Korea Food and Drug Administration (KFDA). The MT extract was determined not to be genotoxic under the conditions of the reverse mutation assay, chromosomal aberrations assay and mouse micronucleus assay. Use of MT is presently expected to be safe, as anticipated intake is small compared to the doses administered in the genotoxicity assays and may, after further toxicity research, prove to be a useful anti-asthma agent.     

Soybean isoflavone extract improves glucose tolerance and raises the survival rate in streptozotocin-induced diabetic rats

The present study evaluated the effect of various dosages of soybean isoflavone extract on body weight changes, glucose tolerance and liver function in streptozotocin-induced diabetic rats. One group of normal rats (normal control) was fed an AIN-76-based experimental diet and four groups of diabetic rats were fed the same diet supplemented with four different levels of soybean isoflavone extract for seven weeks. The daily dosages of pure isoflavone for four diabetic groups were set to be 0 mg (diabetic control), 0.5 mg (ISO-I), 3.0 mg (ISO-II) and 30.0 mg (ISO-III) per kilogram of body weight, respectively. The daily consumption of isoflavone at the level of 3.0mg per kilogram of body weight resulted in the suppression of body weight loss and increased the survival rate of diabetic animals one and half times compared to that of the diabetic control group. Blood glucose levels in a fasting state and after the oral administration of glucose were significantly lower in the ISO-II group during the oral glucose tolerance test. The ISO-II group showed a tendency to elongate the gastrointestinal transit time. The activity of serum aminotransferases, indicator of liver function, was not negatively affected by any intake level of isoflavone. The present study demonstrated that the soybean isoflavone extract may be beneficial to diabetic animals by improving their glucose tolerance and suppressing weight loss without incurring hepatotoxicity at the daily dosage of 3.0 mg per kg of body weight.     

Decreased entropy of symbolic heart rate dynamics during daily activity as a predictor of positive head-up tilt test in patients with alleged neurocardiogenic syncope

Entropy measures of RR interval variability during daily activity over a 24h period were compared in 30 patients with a positive head-up tilt (HUT) test and 30 patients with a negative HUT test who had a history of alleged neurocardiogenic syncope. Two different entropies, approximate entropy (ApEn) and entropy of symbolic dynamics (SymEn), were employed. In patients showing a positive HUT test, the entropies were significantly decreased when compared with the patients with a negative HUT test. In addition, SymEn in the patients with a negative HUT test was significantly lower than in the normal controls. Discriminant analysis using SymEn could correctly identify 89.3% (520/582) of the 1 h RR interval data of the patients with a positive HUT test regardless of the time of day. Baseline entropies of heart rate dynamics during daily activity were found to be significantly lower in patients with alleged neurocardiogenic syncope and a positive HUT test than in those with the same history but with a negative HUT test. The decreased entropy of symbolic heart rate dynamics may be of predictive value of a positive HUT test in patients with alleged neurocardiogenic syncope.     

Changes in nerve growth factor levels in dorsal root ganglia and spinal nerves in a rat neuropathic pain model

The purpose of this study was to measure the changes in levels of nerve growth factor (NGF) in dorsal root ganglia (DRG) and spinal nerves with the aim of investigating the role of NGF in a rat neuropathic pain model. Nerve injuries were made by tight ligation of the left L5 and L6 spinal nerves using 6-0 silk thread in male Sprague-Dawley rats. Before surgery and 1, 3, 5, 7, and 14 days after surgery, tissue samples collected included the L3-6 DRGs bilaterally, segments of the ipsilateral L5-6 spinal nerves proximal and distal to ligation sites, and corresponding sites of the contralateral L3-6 and the ipsilateral L3-4 spinal nerves. NGF levels in the DRGs of the injured spinal nerves (the left L5 and L6) did not change significantly from control values. The spinal nerve segments distal to ligation sites had higher levels of NGF than the control values. Unlesioned sites did not show any significant changes in NGF levels. The increase of NGF in distal segments of injured spinal nerves may be due to an accumulation of retrogradely transported NGF. The maintenance of NGF levels in the DRGs that had lost peripheral connections may reflect local synthesis after nerve injury.     

Vasopressin in the treatment of milrinone-induced hypotension in severe heart failure

The use of phosphodiesterase inhibitors such as milrinone in the treatment of severe heart failure is frequently restricted because they cause vasodilation and hypotension. In patients with decompensated heart failure with hypotension after treatment with milrinone, low doses of vasopressin restored blood pressure without inhibiting the inotropic effect of milrinone.     

Antimicrobial therapy in preterm premature rupture of membranes: results of a prospective, double-blind, placebo-controlled trial of erythromycin

This study was conducted to evaluate the effectiveness of oral erythromycin treatment in safely prolonging pregnancy among women experiencing preterm premature rupture of membranes. Sixty-five women were randomly assigned to receive double-blind treatment with either erythromycin base or an identical-appearing placebo three times daily for 7 days. Only women between 23 and 34 completed weeks' gestation who did not have an indication for delivery were enrolled in the study. Pretreatment microbiologic tests were obtained and women were followed expectantly. Fifty-five women and their newborns completed the protocol and were fully evaluated. Overall, time from rupture of membranes to onset of labor and to delivery was longer, although not significantly, for erythromycin-treated women. Similarly, there was a trend for reduced neonatal intensive care (level II, p = 0.07). When gestational age at enrollment was controlled, erythromycin treatment of women between 28 to 32 weeks' gestation was associated with a prolonged interval from enrollment to delivery [erythromycin: 292 hours (5 to 679); placebo: 54 (12 to 323); p less than 0.044]. Fifty percent of erythromycin-treated women between 28 to 32 weeks' gestation continued their pregnancies at least 13 days after premature rupture of membranes, whereas 50% of placebo-treated women were delivered of infants within 4 days (p = 0.02). Erythromycin treatment among women less than 28 and between 33 to 34 weeks' gestation was not associated with prolonged latency or other changes. There were no differences between erythromycin- and placebo-treated women in the occurrence of clinically recognized chorioamnionitis, postpartum endometritis, or neonatal infectious morbidity. In this double-blind, placebo-controlled trial, erythromycin treatment was well tolerated, safe, and associated with prolongation of pregnancy and reduced intensive neonatal care requirements for selected mother-newborn pairs with preterm premature rupture of membranes.     

Vaginal birth after cesarean delivery in the twin gestation

The pregnancy outcomes of 56 women with a twin gestation and a prior cesarean birth were analyzed to determine whether a trial of labor was a reasonable consideration. Of these patients, 31 (55%) underwent an elective repeat cesarean delivery and 25 (45%) attempted vaginal delivery. Of those who attempted vaginal delivery, 18 (72%) were vaginally delivered of both infants. The dehiscence rate among women with twin pregnancies who attempted a trial of labor was 4% compared with 2% in women with singleton pregnancies. There were no significant differences in maternal or neonatal morbidity or mortality rates in trial of labor versus no trial of labor groups. We conclude in this limited population that a trial of labor in a twin gestation after a previous cesarean delivery appears to be a reasonable consideration. The usual safeguards for attempted vaginal delivery in the twin gestation should be followed.