Protective effects of baicalin on experimental myocardial infarction in rats

Abstract Objective: This study aimed to investigate the protective effects of baicalin on myocardial infarction in rats and explore the related mechanisms. Methods: Fifty Sprague Dawley rats were randomly divided into the control, model, and low-, medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then, the myocardial infarction model was established. The hemodynamic of rats was tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein expressions were determined. Results: Compared with the model group, in the high-dose baicalin group the ST segment height and LVEDP were significantly decreased (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and TXA2 levels were significantly decreased (P<0.05), the PGI2 level was significantly increased (P<0.05), the myocardial SOD level was significantly increased (P<0.05), and the myocardial MDA level was significantly decreased (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the Bax protein level was significantly decreased (P<0.05). Conclusion: Baicalin has protective effects on myocardial infarction in rats. The possible mechanisms may be related to its resistance to oxidative stress, and up-regulation of Bcl-2 protein expression and down-regulation of Bax protein expression in myocardial tissue.

The effects of inhaled NO on plasma vasoactive factor and CTnI level in rabbits with acute massive pulmonary embolism

Abstract Purpose: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. Methods: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). Results: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. Conclusion: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.

Role of endothelial cell dysfunction in essential hypertension.

BACKGROUND: Hypertension is associated with functional and morphological alterations of the endothelium, which disturbs delicate balance of endothelium-derived factors resulting in endothelial dysfunction. The endothelial dysfunction could then facilitate the maintenance of elevated peripheral resistance, which would favor the occurrence of atherosclerosis. AIMS AND OBJECTIVES: The aim of the present study was to determine the circulating levels of vasodilators [nitric oxide (NO) and prostacyclin (PGI2)] and vasoconstrictors [endothelin I (ET-I) and thromboxane (TX)A2)], which reflect endothelial cell dysfunction. METHOD: Nitric oxide as nitrites and nitrates (NOx) were measured spectrophotometrically; ET-I, TXA2 (as TXB2) and PGI2 (as 6 keto PGFIalpha) were measured using enzyme immunoassay methods in 54 male subjects having predominantly untreated, mild hypertension and compared with age-matched 75 healthy controls. RESULTS: Significantly higher levels of ET-I (p<0.001) and TXB2 (p<0.001) were found in essential hypertension subjects (EHT) as compared to controls. No significant difference was observed in NOx and 6 keto PGFIalpha between the two groups. There was significant increase (p = 0.005) in the ratio of TXB2/6 keto PGFIalpha in EHT subjects as compared to controls. CONCLUSIONS: Elevated levels of vasoconstrictors in untreated essential hypertension subjects as compared to controls confirmed the presence of endothelial dysfunction, even in mild cases of hypertension. Early detection of endothelial dysfunction may be a useful measure to guide therapy before the damaging effects of hypertension manifests.

Value of doppler waveform velocities, the biophysical profile scoring, maternal thromboxane and prostacyclin levels as indicators of severity of preeclampsia and perinatal outcome

This study included forty cases who were divided into two groups: Group I included twenty cases [control group] and group II included twenty cases [preeclamptic group]. For all cases, the maternal plasma levels of thromboxane B2, 6 keto-prostaglandin F1 alpha, Doppler study of both uterine and umbilical arteries, modified biophysical scoring value, Apgar score and neonatal birth weight were all done to know the relative importance of these investigations in determining both the severity of preeclampsia and the perinatal outcome. Both thromboxane B2 and umbilical artery Doppler A/B ratio were increased significantly only in cases with severe preeclampsia. So, both could be used as indicators of severity of preeclampsia. They could reflect also the fetal condition. Uterine artery Doppler A/B ratio was increased significantly in both mild and severe cases of preeclampsia. So, it has a limited value in reflecting the fetal condition or severity of preeclampsia. The biophysical profiles scoring showed significant reduction in preeclamptic cases having an umbilical artery Doppler A/B ratio more than 3 if compared with those with ratios less than 3. This indicated that biophysical profile is a valuable tool for evaluation of the fetal condition in utero with easy detection of fetal hypoxia. This could be added to the other advantages as being simple, noninvasive, rapid and inexpensive test. The umbilical artery Doppler study could be used as confirmatory, not a substituting, test to the biophysical profile for evaluation of the fetal condition

A study of platelet aggregation, thromboxane A2 and prostacyclin in central aortic and coronary sinus blood in ischemic heart disease.

Aortic and coronary sinus platelet aggregation, thromboxane A2 (TXA2) and prostacyclin (PG12) levels were studied in fourteen patients of stable angina (SA), six of vasopastic angina (VA) and six control subjects (C). Patients of SA were studied at rest and during incremental atrial pacing and patients with VA were studied at rest and during various stages of vasospasm. Platelet aggregation was studied with different working concentrations of ADP, epinephrine and collagen. TX A2 and PGI2 concentrations were estimated by measuring levels of their stable metabolites viz. thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) respectively. Platelet aggregation was increased in SA and VA patients (p < 0.01) and further increase was seen during vasospasm (p < 0.001). However, it failed to increase on incremental atrial pacing. Similarly, TXB2 and PGF1 alpha levels were raised in SA and VA patients. While TXB2 further increased during vasospasm but not during atrial pacing. PGF1 infinity failed to rise with either. Thus platelets are in an activated state in SA and VA. This activated state is a cause and not an effect in SA and VA. An imbalance in the levels of TXA2 and PG12 could account for the vasospasm.

Lipid peroxidation and plasma thromboxane A2 / prostacyclin RAT10 in type 2 diabetics

This study was carried out with the aim to investigate the relationship between plasma level of lipid peroxides and the degree of diabetic control in type 2 diabetics, and if such relation have any correlation to thromboxane A2/prostacyclin, which reflecting the platelet coagulability status, and if all these changes can be related to the accelerated atherosclerosis in type 2 diabetics. In conclusion, it was suggested that the changes in the oxidative status and the accelerated atherosclerosis in type 2 diabetes are related to the increase in plasma lipid peroxides and the hyperaggregability status in uncontrolled diabetics. Furthermore, the correlation with the degree of metabolic imbalance suggested a possible role for lipid peroxidation in the occurrence of glucose-induced macromolecular changes. They also support the clinical recommendation of tight diabetes control in retarding the macroangiopathic complications and support the consideration of natural antioxidants [like vitamin C and E] as additive therapeutic tools in the global management of the diabetic state in type 2 [NIDDM] patients, and that the usage of sulfonylurea that improves oxidative status and platelet aggregation is a better choice in managing those patients

Clinical study on antithrombotic effects of ticlopidine in ischemic stroke.

The investigators conducted a clinical study on antithrombotic effectiveness in ischemic stroke at Siriraj Hospital Medical School, Mahidol University from May 1987 to May 1989. Twenty-nine patients, 16 males and 13 females were enrolled in the study. The ages of the patients ranged from 30-87 years with a mean age of 63 +/- 11 years. Ticlopidine (250 mg) could significantly inhibit platelet aggregation induced by ADP and collagen within 24 hours of drug administration. After 1 week to 6 months, only aggregation by ADP was still inhibited significantly without significant effects on fibrinolytic activity and prostacyclin. Hematocrit was significantly decreased at the 1st and 2nd month of treatment. Serious side effects were skin rash and severe headache while the other common ones were dizziness, and diarrhea but these effects disappeared without discontinuing the drug. Most patients who suffered from nausea, diarrhea and headache, had temporary elevated SGPT. It may be concluded that only half of the recommended dose of ticlopidine has inhibitory effects on both phases of ADP-induced aggregation without interfering with fibrinolytic activity and can maintain prostacyclin. However, it also possesses either serious or common side-effects. This drug, therefore, should be used with the awareness of the clinician.

Plasma prostacyclin (PGI2) in dengue hemorrhagic fever.

Dengue hemorrhagic fever (DHF) is an epidemic viral disease. The exact mechanism attributable to platelet and vascular dysfunctions is still obscure. Plasma 6-keto-PGF1a (6KPGF1), the stable metabolite of PGI2 was determined in 60 DHF patients and in 11 non-DHF (NDHF) patients with fever of over 38.5 degrees C to compare with that of 33 normal children (NC) in the same age group (2-15 years). Among 60 DHF patients, 32 had blood obtained during impending shock, whereas blood samples of the remainder were taken during normotension. Their plasma 6 KPGF1 values (mean +/- SE) were 201.06 +/- 12.42 and 132.87 +/- 13.08 pg/ml respectively. All patients had serology positive for acute dengue viral infection. The plasma 6 KPGF1 (mean +/- SE) of 33 NC and 11 - NDHF subjects were 149.82 +/- 4.93 and 108.69 +/- 14.53 respectively. The plasma 6KPGF1 levels of 32 DHF patients with impending shock were significantly higher than those of 28 normotensive DHF patients (p less than 0.005), 33 NC (p less than 0.005) and 11 - NDHF patients (p less than 0.005). However the levels in 28 normotensive DHF patients are not statistically different from the values of 33 NC and 11 - NDHF patients. It is concluded that there is a tendency of excessive PGI2 production in DHF patients during hypotensive crisis.

Síntesis de éteres cíclicos prostanoides con actividad hematológica o inmunológica / Synthesis of prostandid cyclic ethers with hematological or inmunological activity

En este trabajo se presenta la síntesis de algunos éteres cíclicos prostanoides, análogos de la prostaciclina obtenidos partiendo del intermediario PGA2 (extraído del coral blando Plexura homomalla, recolectado en la costa note de Venezuela); conjuntamente con algunas pruebas farmacológicas preminares en el área de inmunología o hematología