Emergent loading dose of antiplatelets for stenting after IV rt-PA in acute ischemic stroke: a feasibility study.

BACKGROUND: A loading dose of antiplatelets reduces in-stent thrombosis after stent implantation. However, whether it is safe in patients undergoing acute stenting after intravenous recombinant tissue plasminogen activator (rt-PA) is unclear. METHODS: A case series of acute ischemic stroke patients treated with intravenous rt-PA followed by emergent stenting were prospectively included in Jinling Hospital Stroke Unit. An emergent loading dose of antiplatelets (aspirin 300 mg and clopidogrel 300 mg) were administered to all patients through a nasogastric tube immediately before stenting. Clinical and angiographic outcomes were evaluated in these patients. RESULTS: A total of 12 patients were included. The median of NIHSS score on admission was 15 points (interquartile range 11-19). The median of time from stroke symptom onset to start IV rt-PA and stent placement was 172 min (interquartile range 123.75-189) and 311.5 min (interquartile range 285.5-349.5), respectively. All patients reached complete or partial recanalization (TICI ≥2a). One patient occurred hemorrhagic transformation at 24 h following the emergent loading dose of antiplatelets. A favorable outcome as defined by mRS ≤2 at 90 days was obtained in 58.3% (7/12) of all patients. CONCLUSION: Our finding preliminary suggested that an emergent loading dose of antiplatelets may be safe and feasible for acute stenting after IV rt-PA.

Severity assessment of intracranial large artery stenosis by pressure gradient measurements: A feasibility study.

BACKGROUND: Fractional flow reserve (FFR)-guided revascularization strategy is popular in coronary intervention. However, the feasibility of assessing stenotic severity in intracranial large arteries using pressure gradient measurements still remains unclear. METHODS: Between March 2013 and May 2014, 12 consecutive patients with intracranial large artery stenosis (including intracranial internal carotid artery, middle cerebral M1 segment, intracranial vertebral artery, and basilar artery) were enrolled in this study. The trans-stenotic pressure gradient was measured before and/or after percutaneous transluminal angioplasty and stenting (PTAS), and was then compared with percent diameter stenosis. A Pd /Pa cut-off of ≤0.70 was used to guide stenting of hemodynamically significant stenoses. The device-related and procedure-related serious adverse events and recurrent cerebral ischemic events were recorded. RESULTS: The target vessel could be reached in all cases. No technical complications occurred due to the specific study protocol. Excellent pressure signals were obtained in all patients. For seven patients who performed PTAS, the mean pre-procedural pressure gradient decreased from 59.0 ± 17.2 to 13.3 ± 13.6 mm Hg after the procedure (P < 0.01). Only one patient who refused stenting experienced a TIA event in the ipsilateral MCA territory. No recurrent ischemic event was observed in other patients. CONCLUSION: Mean trans-stenotic pressure gradients can be safely and easily measured with a 0.014-inch fluid-filled guide wire in intracranial large arteries. © 2016 Wiley Periodicals, Inc.

[Prognostic effect of posterior cerebral artery laterality on middle cerebral artery occlusion].

OBJECTIVE: To explore the prognostic value of posterior cerebral artery (PCA) laterality in patients with symptomatic middle cerebral artery (MCA) occlusion on standard medical therapy. METHODS: Forty consecutive patients with first onset isolated atherosclerotic occlusion in M1 segment of MCA received medication from June 2009 to March 2013. All patients underwent magnetic resonance angiography (MRA) for assessment of PCA laterality. Clinical data and modified Rankin Scale (mRS) at 3 months were compared between PCA positive and negative patients. Retrospective analysis was performed on their clinical and imaging data. RESULTS: Among them, 20 patients (50%) showed PCA laterality on MRA and 32 patients (80%) completed a 3-month follow-up. No significant difference existed between PCA laterality positive and negative groups in a favorable outcome of mRS = 0-1 at 3 months (P = 0.433). CONCLUSION: The presence of PCA laterality showed no prognostic effect on patients with symptomatic MCA occlusion on standard medical therapy.

[Intranasal dosing of nerve growth factor protects brain from poisoning of organophosphorus compounds in rats].

OBJECTIVE: To explore the protective effects of intranasal (IN) dosing of nerve growth factor (NGF) on brain injury induced by organophosphorus compounds (OP) in rats. METHODS: The OP-treated Sprague-Dawley rats received an intraperitoneal injection of atropine sulphate and pralidoxime at 1 min after intoxication. Then NGF or saline was dosed via the olfactory pathway. All rats were sacrificed 24 hours after OP exposure. Damaged nerve cells were estimated on corpus striatum strained with hematoxylin-eosin (H&E) method. And the activity of acetylcholinesterase (AchE) and the concentrations of malondialdehyde (MDA) and reduced glutathione hormone (GSH) in corpus striatum were measured by colorimetric method. RESULTS: As assessed by H&E staining, a large number of degenerated and necrotic nerve cells were observed in corpus striatum in rats from in IN saline group. But in IN NGF group, the number of degenerated neurons was smaller than in IN NS group. Following OP exposure, the activity of AchE decreased in corpus striatum in both IN saline and IN NGF groups (0.46 ± 0.11 vs 0.35 ± 0.09 U/mg prot). No significant differences existed between two groups. But the concentrations of MDA in corpus striatum of IN NGF group rats reduced markedly by 25.14% (4.02 ± 0.85 vs 5.37 ± 1.33 nmol/mg prot) and the level of GSH increased sharply by 15.73% (52.82 ± 2.80 vs 45.64 ± 4.88 mg/g prot) as compared with IN saline group (P < 0.05). CONCLUSION: Intranasal dosing of NGF may improve neuropathology and protect rats against OP-induced oxidative damage in corpus striatum.

[Predictors of Wingspan in-stent restenosis for the treatment of symptomatic intracranial arterial stenosis].

OBJECTIVE: To analyze the predictors of Wingspan in-stent restenosis (ISR) for the treatment of symptomatic intracranial arterial stenosis. METHODS: Between January 2007 and November 2009, 42 patients with symptomatic intracranial arterial stenosis registered in Nanjing stroke registry program (NSRP) were treated with Wingspan stent system. Clinical and follow-up results were retrospectively analyzed. They were divided into the non-restenosis and restenosis groups according to their follow-up imaging data. ISR was defined as > 50% stenosis within 5 mm or adjacent to stent or an absolute luminal loss > 20%. The analysis of stepwise multivariate Cox regression was performed to evaluate the independent predictive factors. RESULTS: ISR was found in 15 patients (15/42, 35.7%) with 16 lesions (16/43, 37.2%) at a median follow-up period of 7 months (range: 4 - 23). Diabetes (HR = 0.281; 95%CI = 0.088 - 0.898; P = 0.032) and stent diameter (HR = 0.213; 95%CI = 0.049 - 0.918; P = 0.038) were two independent predictors for ISR. CONCLUSION: Diabetes and stent diameter may be two independent predictors for ISR after a treatment of Wingspan system.

[Plasma homocysteine levels in ischemic stroke patients with obstructive sleep apnea].

OBJECTIVE: To investigate the association of plasma homocysteine and OSA (obstructive sleep apnea) syndrome in ischemic stroke (IS). METHODS: A total of 92 male IS patients were classified by apnea hypopnea index (AHI) into 2 groups: non-OSA group (AHI < 5/h) and OSA group (AHI > or = 5). All patients were tested for plasma homocysteine when polysomnography was finished at (14 +/- 2) d after the onset of IS. RESULTS: The mean level of homocysteine was significantly higher in the OSA group than that in the non-OSA group (17 +/- 5 vs 11 +/- 3 micromol/L, P < 0.01). Pearson correlation analysis revealed a positive correlation between the homocysteine level and the severity of AHI (r = 0.482, P < 0.01). Further multiple linear regression analysis showed that AHI and folate were independent predictors of homocysteine level (R2 = 0.553, P < 0.01, beta for AHI = 0.671, beta for folate = -0.256). CONCLUSION: The severity of OSA is significantly associated with an elevated level of homocysteine in IS patients. And this association is independent of other causative factors of an elevated level of homocysteine.

[Influencing factors for cerebral microbleeds in patients with acute ischemic stroke].

OBJECTIVE: To investigate the relationship between cerebral microbleeds (CMB), cardiovascular risk factors, and plasma fibrinogen in patients with acute ischemic stroke. METHODS: Sixty-eight patients with acute ischemic stroke from June 2008 to March 2009 were enroued prospectively. All patients received cranial magnetic resonance imaging at the first week, and T2(*)-weighted gradient echo MRI sequence was performed to detect CMB. Plasma fibrinogen, uric acid levels and other biochemical parameters were measured on the next day of admission. All data were selected from Nanjing Stroke Registry Program. RESULTS: Among a total 68 patients, 29 (43%) patients had 109 lesions of cerebral microbleeds on gradient-echo MRI. Age, hypertension, fibrinogen and uric acid were significantly associated with the presence of CMB (P = 0.004, 0.024, 0.020, 0.027 respectively). Through a logistic regression analysis, age, hypertension and plasma fibrinogen were significantly associated with the presence of cerebral microbleeds [(P = 0.02, OR = 1.10, 95%CI 1.02 to 1.19; P = 0.003, OR = 9.35, 95%CI 2.17 to 40.23; P = 0.019, OR = 1.01, 95%CI 1.00 to 1.02]. CONCLUSION: There is a high prevalence of CMB in patients with acute ischemic stroke. And it has a strong relationship with high plasma fibrinogen.

[Effect of lesion length on in-stent restenosis after intracranial stenting].

OBJECTIVE: To evaluate the effect of lesion length on in-stent restenosis (ISR) after intracranial stenting. METHODS: Between March 2004 and September 2009, 65 patients with symptomatic intracranial arterial stenosis were successfully implanted with single bare metal balloon-mounted stent. All received a conventional angiographic follow-up. The patients were divided into three groups according to lesion length: short lesions (< 5 mm), medium lesions (5-10 mm) and long lesions (> 10 mm). ISR was defined as > 50% stenosis within stent or absolute luminal loss > 20%. The influence of different lesion lengths on ISR was evaluated. Furthermore, the independent predictive factors for ISR were selected. RESULTS: There were short lesions (n = 28), medium lesions (n = 29) and long lesions (n = 8). The median interval of angiographic follow-up was 7 months with a range of 5-30 months. Of 65 patients, 19 (29.2%) had ISR. The ISR rates were 14.3%, 37.9% and 50% in short lesions, medium lesions and long lesions respectively (P = 0.045). Multivariate Cox regression analysis showed that lesion length (HR = 1.210; 95%CI = 1.011-1.446; P = 0.037) and diabetes (HR = 2.630; 95%CI = 1.032-6.705; P = 0.043) were associated with ISR. CONCLUSION: Lesion length and diabetes are two independent predictors for ISR after intracranial stenting.

Intranasal bFGF-induced progenitor cell proliferation and neuroprotection after transient focal cerebral ischemia.

Basic fibroblast growth factor (bFGF) is a neurotrophic and vasoactive factor, and has therapeutic potential for some central nervous system (CNS) disorders. In this study, we used the intranasal pathway to administer bFGF in adult rats, and evaluated its neuroprotective benefits and effects on endogenous neural stem cells. The bFGF levels after intranasal administration in normal rats were determined by western blot. Transient focal ischemia was achieved by occlusion of the right middle cerebral artery for 2 h. bFGF was given intranasally 2 h after reperfusion and daily thereafter on 3 successive days. Dividing progenitor cells were labeled with bromodeoxyuridine (BrdU) on day 3 of reperfusion. Rats were killed the next day after BrdU labeling. bFGF levels were significantly raised in the olfactory bulb (OB) and striatum following intranasal administration. Intranasal bFGF treatment improved neurological function and reduced infarct volume after cerebral ischemia/reperfusion, while no influence was observed on the blood pressure. And the BrdU incorporation was enhanced in the ipsilateral subventricular zone (SVZ) and striatum following intranasal administration of bFGF. These results demonstrated that bFGF can be directly delivered into brain following intranasal administration, and protects against cerebral ischemia/reperfusion. The protective effects may be attributed to the reduction of infarct volume and enhancement of endogenous progenitors in brain. Therefore, intranasal administration of bFGF may provide an alternative treatment for brain ischemia and some other CNS disorders.

Intranasally delivered bFGF enhances neurogenesis in adult rats following cerebral ischemia.

Basic fibroblast growth factor (bFGF) is a very important mitogenic factor with proved neurogenesis effects in the central nervous system. Intranasal administration can bypass blood-brain barrier and deliver drugs into the brain directly. We investigated whether intranasal administration of bFGF at later time points after ischemia could promote adult neurogenesis and improve neurologic functions. Rats received bFGF or saline intranasally once daily for 6 consecutive days, starting at 1 day after transient middle cerebral artery occlusion (MCAO). Bromodeoxyuridine (BrdU) was injected at 5 and 6 days after MCAO. Rats were killed at 7 or 28 days after MCAO. Neurogenesis was assessed by immunostaining for BrdU and cell type-specific markers. Neurological functions were evaluated by the modified Neurological Severity Scores. Compared with the control animals, intranasal administration of bFGF improved behavioral recovery without affecting infarct size, and enhanced proliferation of progenitor cells in the subventricular zone and the subgranular zone of the dentate gyrus (DG). Furthermore, the new proliferated cells could differentiate into neurons (BrdU+NeuN+ cells) in the striatum and DG at 28 days after MCAO. Intranasal administration of bFGF offers a non-invasive alternative for the treatment of stroke.

Intranasally delivered TGF-beta1 enters brain and regulates gene expressions of its receptors in rats.

This study is aimed to evaluate the brain distribution of transforming growth factor-beta1 (TGF-beta1) following intranasal administration and the subsequent biological effects of TGF-beta1. Adult rats were given recombinant human TGF-beta1 (rhTGF-beta1) or vehicle solution intranasally. TGF-beta1 concentrations were significantly raised in several brain regions and the trigeminal nerve following intranasal delivery. The elevation appeared within 30 min and was sustained for at least 6 h, reaching its greatest level at 60 min. A concentration gradient in the central nervous system (CNS) regions was produced during the first 2 h after intranasal administration, with the OB presenting a significantly higher concentration than any other CNS regions. The nasally administered TGF-beta1 subsequently regulated gene expressions of its two receptors (TGF-beta receptor types I and II) in vivo, but did not affect mRNA level of TGF-beta1 itself. Our results suggest that TGF-beta1 can be transported into the CNS via the olfactory and trigeminal pathways, and may consequently exert its biological effects by regulating gene expressions of its receptors. Intranasal administration of neurotrophic factors may offer a potential strategy for treating some CNS disorders.

Sensitive and Rapid Detection of Traditional Chinese Herbs by Loop-Mediated Isothermal Amplification Method and Real-Time Fluorescence Quantitative PCR

ABSTRACT Adulterant herbal materials are threats to import and export trade and consumer safety. In this study, we established a simple and rapid examination system for the detection of Phellodendron chinense Schneid. Two detection methods, real-time fluorescence quantitative PCR (real-time PCR) and loop-mediated isothermal amplification (LAMP), were developed for traditional Chinese medicine detection, and their specificity and sensitivity were compared. The DNA of P. chinense was extracted and its special periods amplified with designed primers. Real-time PCR and LAMP experiments were conducted to test the specificity of primers in contrast to other similar species. The template concentration was diluted from 101 ng/µL to 10-5 ng/µL in order to contrast sensitivity between real-time PCR and LAMP. Real-time PCR and Lamp method has shown specificity because P. chinense was positive as opposed to other negative similar species. The Lamp method could detect a limited DNA concentration of 10-4ng/µL in 60 minutes with same sensitivity to real-time PCR. The results indicate that real-time PCR and LAMP are sensitive, accurate and specific in detection of P. chinense. However, LAMP is more convenient and cast less time. What's more, expensive equipments are not necessary for LAMP detector. For a better detection, we suggest an establishment of a real-time PCR and LAMP method for TCM market supervision which depends on DNA barcode sequences and LAMP.