[Cerebral vascular complication of hyperhomocysteinemia. Controlling thromboembolic complications with folates]. / Accident vasculaire cérébral avec hyperhomocystéinémie. Arrêt des accidents thromboemboliques sous folates.

BACKGROUND: Young patients who experience cardiovascular events may have raised levels of homocysteine. There may be several causes for this hyperhomocysteinemia. CASE REPORT: Cerebrovascular disease occurred in a 40-year-old female smoker with hyperhomocysteinemia. This patient subsequently had several episodes of thromboembolism involving the brain and lower limb arteries. Prothrombin concentration was difficult to control with antivitamin K anticoagulants. Investigations to identify a genetic cause of hyperhomocysteinemia revealed that she was homozygous for the C677T mutation on the methylenetetrahydrofolate reductase gene. There was no G1691A mutation of the factor V gene, a risk factor for familial thrombosis. Supplementation with folic acid successfully halted episodes of thromboembolism (follow-up 2 years) and prothrombin levels stabilized under treatment. DISCUSSION: The C677T mutation, which is common in the general population (15.7%), cannot explain the effect of folate supplementation alone. Other mutations affecting homocysteine metabolism could have a potentializing effect on vascular events.

Influence of garlic compared to aspirin on induced photothrombosis in mouse pial microvessels, in vivo.

Effect of garlic on photochemically-induced platelet aggregation in pial microvessels of the mouse, in vivo, was compared to that of acetyl salicylic acid (ASA). Three trials were carried out, in which garlic at doses of 12.5, 25, 50 and 100 mg/kg and ASA doses of 25, 50 and 100 mg/kg were used. Each trial included treatment groups of male mice, approximately 30 g, and a control group. Animals were anesthetized (urethane, 1-2 mg/g, i.p.), the trachea was intubated and a craniotomy was performed. Induction of platelet aggregation was made by activation of circulating sodium fluorescein (0.1 ml of 5% solution/25 g, i.v.) with an intense mercury light. Garlic, ASA and vehicle solutions were injected, i.p., 60 min prior to the photochemical insult. The time for the first platelet aggregate to appear in pial arterioles was significantly delayed (P < 0.001) only by the 100 mg/kg garlic dose and by all ASA doses. The effect of this garlic dose on first aggregate was comparable to that of the 25 and 50 mg/kg ASA doses. Only the ASA doses delayed (P < 0.05) the appearance of first aggregate in venules. Arteriolar and venular diameter changes were not different among groups of all trials. Data of this study documented that garlic was capable of delaying platelet aggregation in mouse pial arterioles, in vivo.

[A novel photochemical model of the middle cerebral artery for thrombosis research and evaluation of anti-thrombotic agents].

We have established a novel thrombosis model of the middle cerebral artery (MCA). The thrombotic occlusion of the MCA was induced by the photochemical reaction between Rose Bengal and green light, which causes endothelial injury followed by platelet adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the site of the photochemical reaction. With this model, we have investigated the effects of anti-thrombotic agents, thrombolytic agents and neuroprotective agents. In our model, ADP, thromboxane A2 (TXA2) and thrombin play a key role in thrombus formation of the MCA. Tissue-type plasminogen activator (tPA) could cause an opening of the thrombotic MCA occlusion and reduced the size of the cerebral infarction. Furthermore, a TXA2 antagonist enhanced the thrombolytic efficacy of tPA. MS-153 ((R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline), a glutamate release inhibitor and YM90K [6-(1 H-imidazol-1-yl)-7-nitro-2,3(1H, 4H)-qunoxalinedione monohydrochloride, an alpha-amino-3hydroxy-5methyl-4-isoxazole (AMPA) antagonist reduced the cerebral infarction 24 hr after the MCA occlusion. This model is very useful for investigating the mechanisms of anti-thrombotic and neuroprotective agents and evaluating the effects of these agents.

AMPA receptor antagonist, YM90K, reduces infarct volume in thrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats.

We examined the effects of a potent and selective antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of glutamate receptor, YM90K, on brain infarction using a newly developed stroke model of thrombotic distal middle cerebral artery occlusion. Male spontaneously hypertensive rats (5-7 months old) were subjected to photochemically-induced distal middle cerebral artery occlusion as previously described [Stroke 26 (1996) 333-336]. Intravenous infusion of YM90K (n = 8) (5 mg/kg per h for 1 h) or the same amount of vehicle (n = 8) (alkaline saline) was started 5 min after distal middle cerebral artery occlusion. Penumbral cerebral blood flow was determined with laser-Doppler flowmetry. Three days after the ischemic insult, brains were stained with 2,3,5-triphenyltetrazolium chloride and infarct volumes were determined. One hour infusion of YM90K significantly reduced infarct volume by 34% (93 +/- 23 mm3 in control group vs. 61 +/- 25 mm3 in YM90K-treated group, P = 0.017). There were no significant differences in the degrees of cerebral blood flow reduction after distal middle cerebral artery occlusion between the YM90K treated and control groups. YM90K reduces infarct volume in experimental ischemia produced by photothrombotic distal middle cerebral artery occlusion in rats. The present results demonstrated beneficial effects of AMPA receptor blockade on acute ischemic stroke.

Cerebral venous thrombosis and activated protein C resistance.

BACKGROUND: Activated protein C resistance (APC-R) due to factor V Leiden has recently been established as an important risk factor for cerebral venous thrombosis (CVT). The clinical significance of abnormal or borderline functional APC-R in the absence of factor V Leiden is uncertain. Our observations suggest that APC-R due to mechanisms other than factor V Leiden may also contribute to the development of CVT. CASE DESCRIPTIONS: We describe three women who had superior sagittal and lateral sinus thrombosis while taking oral contraceptives and had a number of additional risk factors for CVT. Each had APC-R for different reasons. CONCLUSIONS: Inherited thrombophilia, including APC-R, should be looked for in all patients with CVT. Functional APC-R is a highly prevalent coagulopathy, but the reasons for this abnormality are diverse; abnormal and borderline functional APC-R results should be supplemented by DNA analysis for the presence of factor V Leiden.

Beneficial effect of CV-4151 (Isbogrel), a thromboxane A2 synthase inhibitor, in a rat middle cerebral artery thrombosis model.

Effects of thromboxane A2 (TXA2) synthase inhibitors (CV-4151 and ozagrel) on cerebral thrombosis and cerebral damage were examined in a rat middle cerebral artery (MCA) thrombosis model and their potencies were compared with the conventional antithrombotic agents, aspirin and ticlopidine. CV-4151 significantly inhibited photochemically induced MCA thrombosis by oral (1 and 10 mg/kg) and intravenous (1 mg/kg) administration. Ozagrel (10 mg/kg, p.o.) also inhibited it. The potency of CV-4151 was about 10 times stronger than that of ozagrel, being comparable with the inhibition of blood TXA2 generation. Aspirin (100 mg/kg, p.o.) and ticlopidine (300 mg/kg, p.o.) showed an inhibitory tendency on MCA thrombosis. Twenty-four h after photochemical stimulation, cerebral edema and cerebral infarction were observed, and the lactate content in the brain increased. CV-4151 and ozagrel prevented this edema, and the antiedema effects of the drugs were correlated with the antithrombotic effect on thrombotic MCA occlusion. CV-4151 (10 mg/kg, p.o.), furthermore, significantly reduced the infarct size and inhibited the increase in lactate content. These results indicate that TXA2 synthase inhibitors inhibit cerebral damage by inhibition of MCA occlusion with thrombosis, probably resulting from the inhibition of TXA2 generation, and their effects are superior to those of aspirin and ticlopidine. TXA2 might play an important role in cerebral damage in the MCA thrombosis model. CV-4151 might be a useful drug for the treatment of cerebral thrombosis and for the prevention of cerebral infarction.

[Effects of leech and ground beetle powder on hemorheology and blood lipid of ischemic stroke].

In order to improve blood supply for the brain, restore the functions of the cerebral cells and the limbs, and increas the curative rate, the leech (Hirudo nipponica and ground beetle Eupolyphage sinensis), powder (LGBP) to the patients according to the principle of promoting the blood circulation to remove the stasis was administered, and the clinical observation and experimental study was conducted. Its effects were compared with those of Western medicines. The results showed that after medication of LGBP, the blood flow of brain significantly increased, the hypoxia was improved, blood viscosity and blood lipid were lowered and thrombosis was inhibited in vitro or in vivo. No toxic side-effects caused by LGBP was found.

Therapeutic efficacy of tirilazad in experimental multiple cerebral emboli: a randomized, controlled trial.

OBJECTIVE: A significant proportion of patients who undergo cardiac surgery or carotid endarterectomy appear to develop subtle cognitive deficits, with the occurrence of multiple cerebral microemboli documented by Doppler ultrasound during these procedures. We used an experimental multiple cerebral embolism model to test whether treatment with tirilazad (U74006F), a putative inhibitor of lipid peroxidation, would improve functional outcome after multiple brain emboli. DESIGN: Randomized, controlled trial. SETTING: Animal care facility procedure room. SUBJECTS: A total of 44 New Zealand White rabbits weighing 2 to 3.0 kg. INTERVENTIONS: Variable quantities of 125I-labeled 50-microns microspheres were injected via a carotid catheter to produce multifocal brain ischemia. Rabbits randomly received either: tirilazad (3 mg/kg i.v.) 5 mins before embolization (pretreatment), or 30 mins after embolization (posttreatment) followed by 1.5 mg/kg every 5 hrs x 3 doses. A third group received vehicle only (control) 5 mins before, followed by three doses every 5 hrs. MEASUREMENTS AND MAIN RESULTS: The animals were rated by a blinded observer at 18 hrs after ischemia and scored as either grossly abnormal/dead or normal. The animals were killed and the amount of microspheres in the brain that were required to produce abnormal function at 18 hrs was calculated for each group. To determine if tirilazad also modified leukocyte function during ischemia, neutrophil adhesion to laminin was determined at baseline and 18 hrs after ischemia using a myeloperoxidase assay. In this study, pretreatment, but not posttreatment with tirilazad produced a significant reduction in neurologic deficits. Tirilazad also attenuated postischemic increases in neutrophil adhesion. CONCLUSIONS: Tirilazad pretreatment reduces neurologic deficits from multiple cerebral emboli. This significant protective effect suggests that pretreatment with tirilazad may play a role in clinical situations where the risk of cerebral emboli is high, with changes in leukocyte adherence as a potential mechanism.

[Clinical effect and experimental study of xijian tongshuan pill].

Xijian Tongshuan pill (XJTS), consisted of Siegesbeckia orientalis, Moschus moschiferus, Hirudo nipponica, Prunus Persicae, Carthamus tinctoruis, Ligusticum wallichi, Panax notoginseng, Angelica Sinensis, Borneolum, etc, were used in treating 70 patients with cerebral thrombosis. The marked effective rate was 82.9%, total effective rate was 96.7%. In control group A, Dextranum and Venoruton were used, in control group B cyclandelate capsule were used. The marked effective rate was 61.7% and 61.1% respectively, the total effective rate was 81.7% and 83.3%. The differences were significant (P < 0.01). The improvement of blood rheology and CT of brain were also significant (P < 0.01). The experiment proved that XJTS pill could inhibit and delay the thrombosis of rabbit, inhibit the platelet aggregation. Acute and subacute toxicity tests proved that XJTS pill was safe and effective.

[Clinical and experimental research of buyang huanwu tang granule in treatment of ischemic apoplexy].

38 cases of ischemic apoplexy were randomly divided into three groups. Among them 26 cases were treated with type I and type III of Buyang Huanwu Tang Granule (BYHWTG) for 10 weeks, respectively. The other 12 cases served as a control group. The results showed that clinical cure and markedly effective rate were 42.3%, the total effective rate was 88.5% in BYHWTG group. The effective rate of BYHWTG type I for the treatment of ischemic apoplexy was 100% and it was superior to type III (84.6). BYHWTG could significantly improve hemorheologic indexes in the patients of ischemic apoplexy. The activity of RBC sodium pump was markedly raised from 0.210 +/- 0.003 to 0.250 +/- 0.008 1/h (P < 0.001) in BYHWTG type I. The results of this study suggested that BYHWTG had evident efficacy in the treatment of ischemic apoplexy.

Evaluation of the combination of a tissue-type plasminogen activator, SUN9216, and a thromboxane A2 receptor antagonist, vapiprost, in a rat middle cerebral artery thrombosis model.

BACKGROUND AND PURPOSE: We aimed to evaluate a modified tissue-type plasminogen activator, SUN9216, and the combination of SUN9216 and a thromboxane A2 receptor antagonist, vapiprost, in a rat middle cerebral artery thrombosis model. METHODS: Under anesthesia, the left middle cerebral artery was observed under an operation microscope without cutting the dura mater via a subtemporal craniotomy. Photoillumination (wave length, 540 nm) was applied to the middle cerebral artery, and then rose bengal (20 mg/kg) was administered intravenously. The reopening of the middle cerebral artery by SUN9216, injected 30 minutes after middle cerebral artery occlusion, was observed under an operation microscope for a 60-minute observation period. Twenty-four hours after the operation, sections of the cerebrum were stained with triphenyltetrazolium chloride, and the area of cerebral infarction was analyzed by a computer. RESULTS: The combination of SUN9216 and vapiprost caused reopening of the middle cerebral artery in 58.8% of the rats, which was a greater percentage than that achieved with SUN9216 alone (31.6%). In contrast, saline did not cause reopening of the middle cerebral artery during the 60-minute observation period. The area of cerebral infarction in rats reperfused with SUN9216 was significantly reduced compared with that in the control group. The infarction area in rats treated with the combination of SUN9216 and vapiprost was reduced compared with that in rats treated with SUN9216 alone; this was the case whether or not the occlusion was reperfused. There was a significant correlation between the time of reopening of the middle cerebral artery and area of cerebral infarction. CONCLUSIONS: A single injection of SUN9216 was effective in recanalizing the vessel and reducing the area of cerebral infarction.

Effect of Y-20811, a thromboxane synthetase inhibitor, on photochemically induced cerebral embolism in rabbits.

The effect of Y-20811, a selective thromboxane A2 synthetase inhibitor, was investigated on cerebral embolism using a new model of embolic cerebral infarction in rabbits. Most of cerebral infarctions were observed in the hemisphere, ipsilateral to the irradiated carotid artery. Cerebral infarction, ranging from 0.2 to 1.0 mm in size, appeared only on the surface of the cortex. The platelet emboli were identified in the carotid artery and cortex arteriole by light microscopy. In our study, 83% of the control group had cerebral infarction. Y-20811 significantly suppressed the infarction number and the incidence at doses of 1 mg/kg and 10 mg/kg (p.o.), respectively. Aspirin significantly inhibited the infarction number at a dose of 10 mg/kg, but its inhibitory effect decreased at 30 mg/kg. Ticlopidine showed no effect even at a dose of 300 mg/kg. These results indicate that Y-20811 may be useful in preventing embolic cerebral infarction and transient ischemic attacks.

[Clinical and experimental study on cerebral thrombosis treated with antithrombotic xinmaining].

Antithrombotic xinmaining were composed with Moschus, Calculus Bovis, Borneol, Radix Ligusticum, Flos Sophorae Immaturus, Radix Salviae Miltiorrhizae, Leech, etc. This preparation was suitable for treating channels and collaterals type of cerebral thrombosis. The dosage was 2-4 capsules (0.5 g/capsule) oral administration twice per day, 3-4 weeks as a therapeutic course. The authors studied 158 cases of these patients compared with 117 cases of control group with dextran and Vinorutone. The clinical result showed that the obvious effective rate in the therapeutic group was 62.1% and the total effective rate 96.3%; the values in the control group were 38.5% and 86.3% respectively (P less than 0.01). The laboratory results showed that the blood viscosity, serum viscosity, hematocrit (vol %), RBC electrophoresis rate (micron/sec/v/cm) and platelet aggregation rate (%) before antithrombotic xinmaining administration were 5.82 +/- 0.82, 1.82 +/- 0.02, 52.81 +/- 6.70, 0.82 +/- 0.19 and 28.33 +/- 12.02 respectively; and those after the treatment were 4.72 +/- 0.65, 1.70 +/- 0.02, 48.76 +/- 0.40, 0.97 +/- 0.17 and 23.05 +/- 10.01 (mean +/- S), P less than 0.01. The toxicological study proved that the preparation was safe, no significant side-effect and good for cerebral thrombosis medication.

[Comparative study of cerebral infarction treated with acupuncture at 6 acupoints of yang meridian and calan].

UNLABELLED: This article reports the curative effects of acupuncture on 6 acupoints of Yang meridian in treating 32 cases of cerebral infarction in comparison with another 31 cases treated with calan tablets 55 out of 63 patients have been diagnosed as cerebral infarction by computer tomography. Diagnosis of 8 cases relied on history, symptoms, signs together with cerebrospinal fluid examination. Patients were divided randomly into two treatment groups: acupuncture group and calan tablet group. Therapeutic method: (1) For acupuncture group, main acupoints consisted of Jianyu (L.I. 15), Quchi (I. I. 11), Hegu (L. I.4) in the upper extremity and Huantiao (G. B. 30), Yanglingquan (G. B. 34), Guangming (G. B. 37) in the lower extremity. According to the syndrome differentiation, Taichong (Liv. 3), Fengchi (G. B. 20), Tianshu (St. 25), Fenglong (St. 40), Zusanli (St. 36), Sanyinjiao (Sp. 6), Taixi (K. 3) were added. The lifting and thrusting was manipulated. The needles were retained for 30 minutes after the patient felt local sourness, distension and heaviness. Acupuncture was carried out every day for 6 weeks. (2) For calan tablet group, calan tablet 5 mg was administered 3 times a day for the same treatment session as the former group. RESULT: The total effective rates were 93. 75% and 83.87% respectively. The therapeutic effect in the acupuncture group was much better than that in the calan tablet group (P less than 0.05). The majority of hemorheological indices of patients in two groups were obviously higher than those of the normal in the same age group.(ABSTRACT TRUNCATED AT 250 WORDS)