Genetic predisposition to essential hypertension in a Mongolian population——Detecting the C825T polymorphism of the G-protein beta 3 subunit gene

BACKGROUND： The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful for prevention to develop researches on the genetics of various diseases including hypertension in Mongolian population. OBJECTIVE： To analyze the association between C825T polymorphisms of G-protein beta 3 subunit gene （GNB3）, the important candidate gene of various disease of cardiovascular system, and Mongolian patients with essential hypertension. DESIGN： A comparative observation. SETTINGS： Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society. PARTICIPANTS： Totally 267 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia. The patients were screened based on the diagnostic standard of hypertension set by WHO in 1999, and the enrolled subjects were divided into two groups according to the level of blood pressure： ① Normal blood pressure group （n =124）： 64 males and 60 females, systolic blood pressure （SBP） 〈 140 mm Hg （1 mm Hg=0.133 kPa）, diastolic blood pressure （DBP） 〈 90 mm Hg;②Essential hypertension group （n =143）： 71 males and 72 females, including 60 patients with simple high SBP （SBP ranged 145 to 195 mm Hg, whereas DBP 〈 90 mm Hg）. METHODS： Peripheral venous blood （5 mL） was drawn from all the subjects, the genome DNA was extracted, and the polymorphisms of the GNB3 C825T genotype were detected with the Sequenom system. Polyrnerase chain reaction （PCR） experiment and SNP detection were performed in Beijing Huada gene laboratory. Then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio （OR） and 95% confidence interval （CI） were calculated. MAIN OUTCOME MEASURES： The distributions of GNB3 C825T genotypes and alleles were observed. RESULTS： All the 267 Mongolian subjects were involved in the analysis of results.① GNB3 C825T genotypes： In Mongolian population, the frequencies of CC, CT and TT genotypes at GNB3 C825T site in the essential hypertension group （48%, 41%, 11%） were not obvious different from those in the normal blood pressure group （43%, 47%, 10%, x^2 =0.162, P =0.688; OR：1.176, 95%CI： 0.533- 2.592）, whereas there were also no obvious differences between the simple high SBP group （57%, 35%, 8%） and the normal blood pressure group （x^2 =0.733, P =0.392; OR：1.957, 95%CI： 0.623- 6.143）. ②GNB3 C825T alleles： In Mongolian population, The frequencies of C and T alleles in the essential hypertension group （69%, 31%） were not obviously different from those in the normal blood pressure group （67%, 33%, x^2 =0.094, P = 0.759; OR：0.945, 95%CI：0.657 - 1.358）, whereas there were also no obvious differences between the simple high SBP group （74%, 26%） and the normal blood pressure group （ x^2 =2.133, P =0.144; OR：0.697, 95%CI： 0.428- 1.133）. CONCLUSION： GNB3 C825T site may be not a genetic marker of essential hypertension and simple high SBP in Mongolian population.     

Spontaneous and renal hypertensive rats: responsiveness of isolated right and left atria to noradrenaline,isoprenaline and methoxamine

The adrenergic responsiveness of right and left atria isolated from spontaneously hypertensive rats (SHR) and renal hypertensive rats (RHR) was studied. Right atria isolated from SHR showed subsensitivity to the chronotropic effect of noradrenaline (21.3-fold at the EC₅₀ level, P < 0.05) and isoprenaline (12.0-fold, P < 0.05). However, atria isolated from RHR did not exhibit any significant alteration (P > 0.05) in sensitivity to the chronotropic effect of noradrenaline or isoprenaline. Chronotropic responsiveness to theophyline was not altered in right atria isolated from SHR or RHR. α₁-Mediated inotropic responses to noradrenaline and methoxamine were blunted in left atria isolated from SHR. Left atria isolated from RHR showed supersensitivity to the inotropic effect of noradrenaline (5.4-fold at the EC₅₀ level, P < 0.05) and subsensitivity to the inotropic effect of methoxamine (6.0-fold, P < 0.05). It is concluded that the present results could, at least partially, explain the reduced cardiac output observed during established hypertension in SHR and the increased cardiac output observed in the initial phase of renal hypertension in RHR.     

Diurnal Blood Pressure and Heart Rate Variability in Hypertensive Patients with Cerebral Small Vessel Disease: A Case-Control Study

BackgroundWhether autonomic dysfunction contributes to cerebral small vessel disease (CSVD) remains unclear. This study aimed to explore the relationship between CSVD and blood pressure variability (BPV) and heart rate variability (HRV).MethodsThis case-control study recruited 50 patients with CSVD and 50 non-CSVD hypertensive age- and gender-matched controls. All participants completed a 24-h ambulatory electrocardiogram recording and ambulatory BP monitoring (ABPM). Differences in HRV and BPV between the two groups were examined. BPV indices assessed by ABPM included mean systolic BP (SBP), mean diastolic BP (DBP), coefficient of variation and weighted standard deviation of SBP and DBP.ResultsCSVD patients had significant higher 24-h mean systolic BP (SBP), 24-h mean diastolic BP (DBP), daytime mean SBP, nocturnal mean SBP, and nocturnal mean DBP (P < .05 for all). CSVD patients had a significant lower nocturnal SBP fall rate compared with controls (median: 1.0 versus 6.2, respectively; P < .001) and were more likely to be non-dippers and reverse dippers. There were no differences in HRV variables between the two groups. Five logistic models were built to explore the correlations between BPV indices and CSVD. BPV indices were separately entered into the logistic regression models, together with hyperlipidemia, ischemic stroke history, current use of anti-hypertensive agents, and serum blood urea nitrogen. In models 1?3, 24-h mean SBP and nocturnal mean SBP and DBP were significantly correlated with CSVD (r² = 0.308?0.340). In model 4, the nocturnal SBP fall rate was negatively correlated with CSVD (odds ratio [OR] = 0.871, 95% confidence interval [CI] = 0.804?0.943; P = .001), with r² = 0.415 fitting the model. In model 5, the pattern of SBP dipping was significantly associated with CSVD, with non-dipper (OR = 8.389, 95%CI = 1.489?47.254; P = .016) and reverse dipper (OR = 27.008, 95%CI = 3.709?196.660; P = .001) having the highest risks of CSVD (r² = 0.413).ConclusionsLower nocturnal SBP fall rate is associated with CSVD. Non-dipper and reverse dipper hypertensive patients have a higher risk of CSVD.     

Effect of BMI on Central Arterial Reflected Wave Augmentation Index,Toe-Brachial Index,Brachial-Ankle Pulse Wave Velocity and Ankle-Brachial Index in Chinese Elderly Hypertensive Patients with Hemorrhagic Stroke

BackgroundHypertensive cerebral hemorrhage seriously endangers the health of the elderly. However, the relationship between obesity and arterial elasticity in hypertensive cerebral hemorrhage remains to be clarified. The purpose of our study is to explore the associations between body mass index (BMI) and central arterial reflected wave augmentation index (cAIx), toe-brachial index (TBI), brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI) in the elderly hypertensive patients with hemorrhagic stroke.Materials and MethodsA total of 502 elderly hypertensive patients with hemorrhagic stroke and 100 healthy controls were collected. According to the BMI, patients were divided into normal BMI, overweight, obesity, and obese groups. The multivariate logistic regression model was used to establish a risk model for elderly hypertensive hemorrhagic stroke.ResultsCompared with the normal BMI group, systolic blood pressure (SBP), diastolic blood pressure (DBP), cAIx, and baPWV in the abnormal BMI group were significantly increased (P < 0.05), while TBI and ABI were significantly decreased (P < 0.05). Logistic regression showed that BMI (OR = 1.031, 95%CI: 1.009–1.262), cAIx (OR = 1.214, 95%CI: 1.105–1.964), TBI (OR = 0.913, 95%CI: 0.885–0.967), baPWV (OR = 1.344, 95%CI: 1.142–2.147), and ABI (OR = 0.896, 95%CI: 0.811–0.989) are important factors for the occurrence of hemorrhagic stroke in the elderly hypertensive patients. ROC curve analysis showed that the AUC of cAIx, TBI, baPWV, ABI, and BMI were 0.914, 0.797, 0.934, 0.833, and 0.608, respectively. The final prediction model of hemorrhagic stroke elderly hypertensive patients was Y_(P)= 65.424 + 0.307(cAIx) - 13.831(TBI) + 0.012(baPWV) - 0.110(ABI) + 0.339(BMI).ConclusionsObesity is associated with decreased arterial elasticity. Therefore, reasonable weight management of the elderly may be of great significance for reducing the risk of hemorrhagic stroke in patients with hypertension.     

The Association Between ACE2 Gene Polymorphism and the Stroke Recurrence in Chinese Population

Objectives

The angiotensin-converting enzyme 2 (ACE2) is closely associated with cardiovascular disease and cerebrovascular disease. Most studies on ACE2 gene polymorphism focused on its relations with cardiovascular disease, but there was a lack of research on its relations with stroke. Our study aimed to explore the association between 4 single-nucleotidepolymorphisms (SNPs) of ACE2 gene polymorphism and stroke recurrence.

Neurovascular compression and decompression of the intracranial vagus for blood pressure

BACKGROUND: Previous researches demonstrated that neurovascular decompression could cure hypertension; however, whether it could effectively control refractory hypertension after hypertensive cerebral hemorrhage should be further studied. OBJECTIVE: To observe the effect of neruovascular compression on intracranial vagus for blood pressure of dogs and investigate the effect of neurovascular decompression on blood pressure of patients with hypertensive cerebral hemorrhage. DESIGN: Randomized controlled animal study, clinical effects and retrospective analysis. SETTING: Department of Neurosurgery, Changzheng Hospital Affiliated to the Second Military Medical University of Chinese PLA. MATERIALS: The experiment was carried out in the Department of Neurosurgery, Changzheng Hospital Affiliated to the Second Military Medical University of Chinese PLA from May to October 2006. A total of 15 healthy adult dogs of both genders were randomly divided into experimental group (n =10) and control group (n =5). Clinical observation: A total of 41 patients with hypertensive cerebral hemorrhage were selected from the Department of Neurosurgery, General Hospital of Nanjing Military Area Command of Chinese PLA and the Department of Neurosurgery, Changzheng Hospital Affiliated to the Second Military Medical University of Chinese PLA from October 1999 to October 2006. Among them, one patient had brain stem hemorrhage. There were 27 males and 14 females aged from 41 to 66 years. Inclusion criteria: All patients were diagnosed with CT examination once or several times. Volume of hematoma ranged from 50 to 120 mL and had obviously operative indication. All patients provided consents. In addition, another 281 patients with hypertensive cerebral hemorrhage who received traditionally internal and surgical therapies in our departments of neurosurgery, neurology and emergency room were selected in the control group. METHODS: ① Animal experiments: 20 cm autochthonous great saphenous vein was taken from dogs in the experimental group and coincided with tip of facial artery to form arterial loop so as to oppress left vagus and lateral bulb abdomen. In addition, 20 cm autochthonous great saphenous vein was taken from dogs in the control group and coincided with tip of facial artery to establish arterial loop so as to oppress left cerebellum to observe changes of blood pressure before and at 1, 2, 3 and 4 weeks after operation. ② Clinical observation: Among 41 patients with hypertensive cerebral hemorrhage including one with brain stem hemorrhage, they received microvascular decompression of vagus immediately after getting rid of intracerebral hematoma and stopping bleeding to observe its effect of depressurization. All patients and their relatives provided consents. ③ A total of 281 patients with hypertensive cerebral hemorrhage who discharged after the treatment of traditionally internal and surgical therapies were studied retrospectively to observe changes of blood pressure after routine treatment and compare the results with neurovascular decompression. MAIN OUTCOME MEASURES: ① Changes of blood pressure of experimental dogs; ② effect of vascular decompression of vagus for blood pressure of patients with hypertensive cerebral hemorrhage after clearing intracerebral hematoma; ③ different effects of neurovascular decompression and routinely internal and surgical therapies on hypertension. RESULTS: ① Results of animal experiments: Nine dogs in the experimental group survived. At 1, 2, 3 and 4 weeks after operation, blood pressure of dogs in the experimental group was (139.77±4.06), (149.11±4.90), (148.10±4.16), (147.76±4.15) mm Hg (1 mm Hg=0.133 kPa), which was higher than that of dogs in the control group [(117.20±2.74), (116.65±3.74), (116.26±1.8), (115.81±3.76) mm Hg, P < 0.01]. ② Results of clinical observation: Among 41 patients, 8 (20%) cases died during the operation. In addition, among other 33 (80%) survival patients, 11 (33%) cases had normal blood pressure; blood pressure of 14 (43%) cases was improved or closed to normal value; blood pressure of 8 (24%) cases was not changed obviously as compared with that before operation. ③ The results demonstrated that, by using traditionally internal and surgical therapies, among 281 patients with hypertensive cerebral hemorrhage, blood pressure of about 15% cases was recovered or closed to normal value. Those mentioned above did not have history of hypertension before hemorrhage. However, patients who had history of hypertension before hemorrhage received the traditionally internal or surgical therapies, and the blood pressure was not improved to the normal value after the treatment. CONCLUSION: ① Neurovascular compression in left intracranial vagus can cause obvious increase of blood pressure of dogs, and the increasing volume was 30 mm Hg. ② Vascular decompression of vagus has a great effect on refractory hypertension, and the improvement of blood pressure is superior to traditionally internal and surgical therapies in clinic.     

Twenty-four-hour blood pressure profile,orthostatic hypotension,and cardiac dysautonomia in elderly type 2 diabetic hypertensive patients

Purpose

The aim of this study was to evaluate the relationship between orthostatic hypotension (OH), defined as a decrease in systolic blood pressure (SBP) ≥20 mmHg and/or a decrease in diastolic blood pressure (DBP) ≥10 mmHg, and 24-h ambulatory BP profile in elderly hypertensive type 2 diabetic patients.

Methods

After a 2-week antihypertensive wash-out period, 200 hypertensive well-controlled diabetic outpatients, aged 65–75 years, underwent a clinical examination, including BP measurements, ECG, 24-h ABP monitoring (ABPM), an orthostatic test, and three tests for cardiovascular autonomic function assessment [deep breathing, heart rate (HR) variability, resting HR].

Results

According to their nighttime BP profile, patients were divided into three groups: dippers (n = 86) (BP fall during nighttime ≥10 %), non-dippers (n = 80) (BP fall during nighttime 0–10 %), and reverse dippers (n = 34) (nighttime BP > daytime BP). Orthostatic test produced a significantly greater orthostatic SBP fall in dippers and even more in reverse dippers. In these latter, a significant fall was observed also in DBP. Prevalence of OH was 9.3 % in dippers, 30 % in non-dippers, and 79.4 % in reverse dippers.

Conclusions

In elderly hypertensive type 2 diabetics, a blunted nocturnal BP fall is associated with OH and autonomic dysfunction. These data suggest that ABPM should be performed in the assessment of hypertensive diabetic patients in whom the cardiovascular dysautonomia is suspected or the signs of it are present (such as OH).

     

肾血管性高血压大鼠自发脑卒中

通过研究双肾双夹型肾血管性高血压大鼠自发脑卒中的病理形态,发现高血压所致的脑内细小动脉纤维素样坏死、透明变性和微动脉瘤形成等是出血性脑卒中和脑梗塞的共同病理基础。探讨了高血压动脉硬化性脑卒中的发病机制,并为混合性脑卒中提供了实验依据。     

Blood pressure evolution in young patients with acute ischemic stroke: a new model for understanding the natural course of spontaneous hypertension?

Background: Approximately 80% of patients suffering an acute ischemic stroke develop transient hypertension. The physiopathological mechanism remains unclear. Due to the lack of vascular risk factors, young adults could be a useful model for understanding blood pressure (BP) evolution in this setting.

Methods: Patients between 18 and 55 years old admitted with an acute ischemic stroke were included. BP was evaluated during the following 48 h. Hypertension was defined as: systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg. Patients were divided into two groups: RF group included those who had a previous vascular risk factor and/or other medical condition known to affect the autonomic function; noRF group included patients without any of the previously stated conditions.

Results: Thirty-nine patients were included: mean age: 44.26 years old, 21 were males (53.8%). Mean SBP and DBP at admission were 139.77 ± 5.35 mmHg (range: 90–243) and 84.44 ± 3.02 mmHg (range: 60–128), respectively; 43.58% patients were hypertensive at admission. SBP decreased significantly during the first 48 h (p = 0.044) for the entire population. RF group has higher SBP (p = 0.009) and DBP (p = 0.011) at admission than the noRF group.

Conclusion: Most patients were normotensive at admission and BP fell spontaneously despite BP at admission. Young patients without medical conditions that could alter the autonomic system function could be a useful model for understanding acute hypertension in ischemic stroke.     

Personality and reporting of symptoms in normo- and hypertensive 50 year old males.

From a screening examination of the 50 yr old, male population in Göteborg, Sweden, a 3 per cent subsample was randomly selected as a reference group (n = 80). All subjects without antihypertensive treatment and with SBP > 175 or DBP > 115 mm Hg on two separate occasions made up the untreated hypertension group (n = 35). Subjects on antihypertensive treatment at screening were included in the treated hypertension group (n = 22). The reference group and the hypertension groups were subjected to the same investigations including a personality inventory (CMPS) and a questionnaire measuring the tendency to report symptoms. The results were: Untreated, newly discovered hypertensives had a greater need for autonomy than the treated hypertensives, who in turn had a greater need to be taken care of. Untreated hypertensives, foremost those with organ damage, tended to report fewer symptoms than the treated hypertensives. These differences in personality and in the tendency to report symptoms may partly explain, why approximately half the male hypertensive population had not come under treatment. The results indicate that screening activity might be necessary in order to find those hypertensive subjects. The psychological set-up of this group should be considered in the future development of hypertension control programs.     

Protective effect of Angelica sinensis on cerebral neurons from rat embryos under hypoxia

BackgroundThe enhanced expression of c-Fos protein in nerve cells after hypoxia is the marker for converting extracellular hypoxia information to intracellular changes at hypoxia, and it is suspected that the increase of c-Fos protein can lead to the synthesis and excretion of related neurotrophic factor and nerve growth factor. However, it is still unclear what functional changes of nerve cells are induced by the increase of c-Fos protein at hypoxia, and whether it is good for the survival of damaged neurons.ObjectiveTo observe the expression of c-Fos in the cerebral neurons from embryos of rats with hypoxia in uterus, and investigate the pathway for the protective effect of Angelica sinensis injection on the cerebral neurons from rat embryos under hypoxia.DesignA completely randomized controlled study.SettingDepartment of Histology and Embryology, Luzhou Medical College.MaterialsTwelve female Wistar rats in oestrum and 1 male adult Wistar rat with body mass of 220 to 250 g were selected. Rabbit-anti-rat neuro-specific enolase (NSE) and rabbit-anti-rat c-Fos were purchased from Wuhan Boster Biological Technology Co., Ltd.; Double-staining kit was bought from Beijing Zhongshan Golden Bridge Biotechnology Co., Ltd. Angelica sinensis injection was produced by the Department of Pharmacy, the Second Affiliated Hospital of Hubei Medical University.MethodsThe experiments were completed in the experimental animal center and the Department of Histology and Embryology of Luzhou Medical College from December 2004 to December 2005.

Twelve adult female Wistar rats in oestrum and 1 male Wistar rat were housed in one rearing cage. The appearance of vaginal embolus at 8:00 in the next morning was recorded as 0 day of pregnancy and the rats were recorded for 15 days, and they were divided randomly into three groups, control group (n =4), hypoxia group (n =4) and Angelica group (n =4). The pregnant rats in the hypoxia group were firstly injected with saline (8 mL/kg), then put into 2 L wide-mouthed bottle containing 100 g sodalime, and then the lid of the bottle was closed tightly to induce hypotonic hypoxia for 1 hour followed by 1-hour re-oxygenation. The pregnant rats were killed under anesthesia, and then fetuses were taken out by rapid cesarean. Part of the brain tissues were exposed and then fixed in formaldehyde (40 g/L). The pregnant rats in the Angelica group were treated the same as those in the hypoxia group except that saline was replaced by 250 g/L Angelica sinensis injection which was injected via caudal vein (8 mL/kg). The rats in the control group were injected with saline (8 mL/kg) slowly via caudal vein, but not put into the wide-mouthed bottle for hypoxia, and then the brain tissues were removed and fixed as those in the hypoxia group after 1 hour.

Twenty embryos from rats were chosen randomly in each group and then routinely embedded in paraffin. Paraffin sections of 4 μm thick were prepared through the anterior fontanelle of head of the fetal rats. The sections were immunohistologically stained with c-Fos/NSE.

The one-way analysis of variance (ANOVA) was used to compare the differences of measurement data among the groups, and the q test was applied in the two-two comparison.Main outcome measuresThe numbers of c-Fos and c-Fos/NSE positive neurons in cerebrum from rat embryos were observed.Results

Numbers of NSE positive neurons in cerebrum of rat embryos in the control group, hypoxia group and Angelica group were (84.3±9.0), (90.2±12.5) and (86.7±9.7) cells/high power field (P > 0.05).

The number of c-Fos/NSE positive neurons was more in the hypoxia group than in the control group and Angelica group [(38.4±5.28), (11.35±2.67), (20.65±4.07) cells/high power field, q =29.17, 19.14, P < 0.05].ConclusionHypoxia can stimulate the expression of c-Fos in cerebral neurons from rat embryos. Angelica sinensis injection could reducing the damage of hypoxia to neurons and play a neuroprotective role by decreasing the expression of c-Fos protein in hypoxic neurons.     

ACE inhibition reduces infarction in normotensive but not hypertensive rats: correlation with cortical ACE activity

Angiotensin-converting enzyme (ACE) inhibition can reduce stroke risk by up to 43% in humans and reduce the associated disability, and hence understanding the mechanism of improvement is important. In animals and humans, these effects may be independent of the blood pressure-lowering effects of ACE inhibition. Normotensive (Wistar–Kyoto (WKY)) and hypertensive (spontaneously hypertensive rat (SHR)) animals were treated with the ACE inhibitors ramipril or lisinopril for 7 or 42 days before 2 hours of transient middle cerebral artery occlusion (MCAo). Blood pressure, serum ACE, and blood glucose levels were measured and stroke infarct volume was recorded 24 hours after stroke. Despite greater reductions in blood pressure, infarct size was not improved by ACE inhibition in hypertensive animals. Short-term ACE inhibition produced only a modest reduction in blood pressure, but WKY rats showed marked reductions in infarct volume. Long-term ACE inhibition had additional reductions in blood pressure; however, infarct volumes in WKY rats did not improve further but worsened. WKY rats differed from SHR in having marked cortical ACE activity that was highly sensitive to ACE inhibition. The beneficial effects of ACE inhibition on infarct volume in normotensive rats do not correlate with changes in blood pressure. However, WKY rats have ACE inhibitor-sensitive cortical ACE activity that is lacking in the SHR.     

Sympathetic neural and cardiovascular responses during static handgrip exercise in women with a history of hypertensive pregnancy

Purpose

Women with a history of hypertensive pregnancy are at greater risk for future cardiovascular events; however, the mechanisms for this increased risk are unknown. Evidence suggests that an exercise stimulus unmasks latent hypertensive tendencies, identifying individuals at the greatest risk for developing cardiovascular disease. The current study examined the hypothesis that women with a hypertensive pregnancy history exhibit an augmented exercise pressor response.

Methods

Normotensive women with a history of healthy pregnancy (CON; n = 9) and hypertensive pregnancy (HP+; n = 12) were studied during the mid-luteal phase of the menstrual cycle. Heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), and muscle sympathetic nerve activity (MSNA) were measured during a cold pressor test (CPT), and, following a sufficient period of recovery, during static handgrip to fatigue (SHG) and post-exercise circulatory arrest (PECA).

Results

The BP, HR, and MSNA responses to the CPT were similar between groups. The SBP response to SHG and PECA was similar between groups, but DBP and HR were significantly greater in HP+ women (both p < 0.05). MSNA burst frequency, but not burst incidence or total activity, tended to be elevated in HP+ women during the stressor (peak Δ from baseline 31 ± 13 vs. 23 ± 13 bursts/min; p for group = 0.06).

Conclusion

Despite no clinical signs of cardiovascular disease or hypertension, women with a history of hypertensive pregnancy display an enhanced cardiovascular reactivity to an exercise stimulus compared to women with a healthy pregnancy history. This response may be indicative of impaired cardiovascular control that precedes the clinical manifestation of hypertension or cardiovascular events.

     

Brain metabolism following bilateral carotid occlusion in 2 different models of experimental hypertensive rats

Brain metabolites and arterial acid-base measurements were made one hr after bilateral carotid artery occlusion in 2 different models of hypertensive rats. Animals used included renovascular hypertensive rats (RHR) with an altered renin-angiotensin system and desoxycorticosterone hypertensive rats (DHR) with low plasma renin activity (PRA). The mean value for supratentorial lactate of 7.41 mM/kg in RHR was significantly higher than in DHR (3.90 MM/kg) or in control normotensive rats (3.10 - 2.56 mM/kg). Concomitantly, the lactate/pyruvate ratio tended to increase and ATP to decrease in RHR only. In these same rats (RHR) infratentorial lactate was also increased. The results suggest that bilateral carotid occlusion leads to anaerobic metabolism of the brain in RHR but not in DHR, suggesting that the renin-angiotensin system may play some role in the susceptibility to cerebral ischemia following carotid occlusion in the hypertensive rats.     

Stroke symptoms impact on mental and physical health: A Lebanese population based study

Background/ObjectiveStroke symptoms in the absence of diagnosed stroke are common worldwide and associated with stroke risk factors and great impact on the physical and mental health functioning. The aim of this study was to assess, at the national level, the association of stroke symptoms with mental and physical health.MethodsQuality of life was assessed using physical and mental component summary scores (PCS and MCS) of the Short Form 12v2 Health Survey in the Lebanese population. We assessed the differences in the mean PCS and MCS scores among asymptomatic individuals with no stroke/transient ischemic attack (TIA) history (n = 1167), symptomatic individuals with no stroke/TIA history (n = 125) and those with stroke/TIA history (n = 46). Psychometric properties of the Lebanese version of the SF- 12v2 were evaluated using principal component analysis.ResultsSymptomatic individuals had an average PCS scores of 2.31 (95%CI: 0.75–3.88) points lower and those with stroke/TIA history had 3.26 (95%CI: 1.01–5.51) points lower when compared with asymptomatic individuals with no stroke/TIA history. Similarly, MCS scores for symptomatic individuals were 2.58 (95%CI: 1.02–4.13) points lower and those with stroke/TIA history had 3.28 (95%CI: 1.06–5.50) points lower than asymptomatic individuals.ConclusionPhysical and mental health functioning declined among symptomatic individuals and those with stroke/TIA history. Thus, frequent monitoring for the early detection of stroke symptoms may be recommended.     

Fluoxetine for poststroke depression ——A randomized placebo controlled clinical trial

BACKGROUND: Studies have demonstrated that poststroke depression(PSD) may be related with the disequilibrium between noradrenaline and 5-hydroxytryptamine (5-HT) caused by cerebral injury. The injured regions involve noradrenergic and 5-hydroxytryptaminergic neurons as well as conduction pathway. The levels of noradrenaline and 5-HT would be decreased. OBJECTIVE: To observe the effect of fluoxetine on preventing against PSD and recovery of neurologic function, and analyze the relationship of fluoxetine and the 5-HT level. DESIGN: A randomized controlled clinical trial. SETTING: Department of Neurology, First Hospital Affiliated to Soochow University. PARTICIPANTS: Ninety consecutive patients, 47 female and 43 male, were recruited who admitted to hospital for recent stroke in the Department of Neurology, First Affiliated Hospital of Soochow University between September 2003 and February 2005. Subjects were aged (64±7 ) years, ranging from 47 to 79 years old. They all met the diagnosis criteria of various cerebrovascular diseases formulated in the 4th National Cerebrovascular Disease Conference and confirmed as stroke by skull CT or MRI; The time from onset to tentative administration was less than 7 days; The patients had clear consciousness, without obvious language disorder. They were randomized into treatment group (n =48) and placebo group (n =42). METHODS: ①All the patients were given routine treatment according to treatment guideline of cerebrovascular disease after admission. Patients in the treatment group and placebo group received 20 mg/d fluoxetine and placebo (component: vitamin C) for 8 weeks, respectively. ② Neurologic deficit was assessed according to 24-item Hamilton Rating Scale for Depression (HAMD) and Activity of Daily Living Scale (ADL) before and at 2,4 and 8 weeks after test, separately; Meanwhile, the levels of platelet 5-HT and plasma 5-HT were determined. Grading criteria of HAMD intergral depression: non-depression < 8 points; mild depression 8–20 points; moderate depression 21–35 points; severe depression > 35 points. ADL was assessed with Barthel index score (full mark 100 points). Higher points indicated better incidence and smaller dependence. Neurologic deficit score was made according to scoring criteria of neurologic deficit formulated in 1995 4th National Cerebrovascular Disease Conference: a score of 0–15 indicated a mild focal neurologic deficit, a score of 16–30 a moderate focal neurologic deficit, and a score of 31–45 a severe focal deficit. MAIN OUTCOME MEASURES: Scores of HAMD, ADL and neurologic deficit, and levels of plasma and platelet 5-HT of patients from 2 groups before, 2,4 and 8 weeks after test. RESULRS: Seventy-three of 90 randomized patients participated in the final analysis. In the treatment group, 11 patients dropped out due to insufficient clinical response (n =4), somatic side effects (n =2), intervening medical illness (n =1), hypomania (n =3), and other reasons (n =2). In the placebo group, 6 patients existed due to insufficient clinical response (n =2), somatic side effects (n =1) and other reasons (n =3). ① Before treatment, there were no significant differences in scores of HAMD, DAL and neurologic deficit in patients between two groups (P > 0.05). After 8 weeks of treatment, the scores of HAMD, DAL and neurologic deficit in the treatment group were significantly different from those in the placebo group (12.6±5.3 vs. 16.3 ±3.7; 8.6±6.4 vs. 11.2±6.4; 60.4±12.5 vs. 52.3±13.5, P < 0.01). ② After 8 weeks of treatment, platelet 5-HT level of patients in the treatment group was significantly lower than that in the placebo group [(325.3± 110.5) mg/L vs. (653.6±138.4) mg/L, P < 0.05], while there were no significant differences in plasma 5-HT between two groups (P > 0.05). CONCLUSION: Early fluoxetine treatment obviously retards PSD. The increase of platelet 5-HT level promotes the recovery of neurologic function.     

Alteration of P2X3 expression in dorsal root ganglia after sciatic nerve ligation

BACKGROUND: The expressions of P2X3 receptor in dorsal root ganglia (DRG) after different peripheral nerve injuries are diverse. It indicates the different roles of P2X3 in different models-caused neuropathologic pains. OBJECTIVE: To observe the expressions of P2X3 in corresponding DRG after sciatic nerve ligation in rats. DESIGN: Controlled observation experiment. SETTING: Department of Morphology, Hunan Traditional Chinese Medical College; Department of Human Anatomy and Neurobiology, Xiangya Medical College, Central South University. MATERIALS: Thirty-five healthy adult SD rats of clean grade an d either gender, weighing （200±20）g, were involved. According to the random digits table, the involved rats were randomized into 3 groups: normal group (n =5), sham-operated group (n =5) and experimental group (n =25). The experimental group were subdivided into 3,7,14,21,28 days groups according to different surviving time after operation, 5 rats at each time point. Polyclonal rabbit anti-P2X3 antibody (ABCAM company); biotinylated goat anti-rabbit IgG (Zhongshanjingqiao Biotechnical Co., Ltd., Beijing); Motic fluorescence microscope (Motic, Germany). METHODS: The experiments were carried out in the Department of Human Anatomy and Neurobiology, Xiangya Medical College, Central South University from June to December 2006. ① Rats of experimental group were created into models by ligation of right sciatic nerve according to the method of Seltzer et al. Left sciatic nerve was used as self-control. As for rats in the sham-operated group, ligation of sciatic nerve was omitted, but other procedures were the same as those in the experimental group. Rats of normal group were untouched. ② Rats of the normal group and sham-operated group survived for 14 days separately, and those of experimental group survived for corresponding time. After being deeply anesthetized by intraperitoneal injection of over-dose sodium pentobarbital, the rats of experimental group were transcardially perfused. L4–6 corresponding DRG connected to sciatic nerve were taken for preparing transverse sections serially. ③P2X3 expression in L4–6 DRG was detected by immunohistochemistry, immunofluorescence and image analysis techniques. MAIN OUTCOME MEASURES: P2X3 expression in L4–6 DRG of rats in each group. RESULTS: Thirty-five SD rats were involved in the final analysis. ① P2X3 expression in DRG: In normal DRG of rats, there were abundant P2X3 immuno-positive small- and medium-sized primary sensory neurons, especially the small ones, which mostly received the input from C fibers. There were only a few large neurons expressing P2X3. The immuno-positive products mostly were located in the cytoplasm and processes. The expression of P2X3 had a slight but significant decrease in ipsilateral L4–6 DRG 3 days after sciatic nerve ligation, and a decreasing tendency was observed with the elongation of time. At 28 days, the expression had not returned to base line, and still maintained at a low level. ② P2X3 immuno-positive gray scale in DRG: P2X3 immuno-positive gray scale in ipsilateral side L4–6 DRG was 117.74±2.38,129.12±4.86,133.56±3.79,148.75±6.90 and 150.49±5.15, respectively at 3,7,14, 21 and 28 days after sciatic nerve ligation, which was significantly higher than that in the normal group and sham-operated group （105.11±3.52,104.22±5.41,F =78.861,P < 0.05）, also significantly higher than that in the contralateral side （105.53±5.85,108.54±3.70,104.07±4.16,106.55±2.02,106.29±5.19,t =3.48–13.95,P < 0.05）; There were no significant differences when comparing sham-operated group or contralateral side at each time point with normal group (P > 0.05) CONCLUSION: P2X3 is significantly down regulated in L4–6 DRG after sciatic nerve ligation. It may exert certain effects in neuropathic pain.     

Is there a bad time for intravenous thrombolysis? The experience of Polish stroke centers

Background and purposeThe outcome in acute stroke strongly depends on patient-related issues, as well as on the availability of human and diagnostic resources. Our aim was to evaluate safety and effectiveness of intravenous alteplase for stroke according to the time of admission to the hospital.Materials and methodsWe analyzed the data of all acute stroke patients treated with alteplase between October 2003 and December 2010, contributed to the Safe Implementation of Thrombolysis for Stroke registry from 27 Polish stroke centers. According to the time of admission we distinguished between: (1) non-working days (Friday 14:30–Monday 08:00 plus national holidays); (2) out-of-office hours (non-working days plus 14:30–08:00 during working days); and (3) night hours (time from 23:00 to 06:00). Patients admitted during regular working hours (Monday 08:00–Friday 14:30, excluding national holidays) were used as the reference.ResultsOf 1330 patients, 448 (32.5%) were admitted on non-working days, 868 (65.3%) at out-of-office hours, and 105 (7.9%) during night hours. In multivariate logistic regression, none of the evaluated periods showed association with symptomatic intracranial hemorrhage, 7-day mortality, and neurological improvement ≥4 points in the National Institutes of Health Stroke Scale score at day 7. Patients admitted during night hours had lower odds (OR 0.53, 95% CI: 0.29–0.95, p = 0.032) for achieving favorable outcome (modified Rankin Scale score 0–2).ConclusionsThere is no bad time for thrombolysis. Stroke centers should feel confident about the treatment outside regular working hours, irrespective of equipment and staff availability. However, it may be reasonable to pay additional attention during nighttime.     

Effect of erhuangfang on cerebral and spinal demyelination and regeneration as well as expression of glial fibrillary acidic protein in rats with experimental allergic encephalomyelitis

BACKGROUND: It demonstrates that erhuangfang can improve clinical symptoms of multiple sclerosis and relieve side effects of hormone. However, whether erhuangfang can improve experimental allergic encephalomyelitis (EAE) or not needs a further study. OBJECTIVE: To observe the effect of erhuangfang on neuro-pathology and astrocyte in EAE rats and compare with the effect of hormone. DESIGN: Randomized controlled animal study. SETTINGS: Department of Traditional Chinese Medicine, Beijing Tiantan Hospital, Capital Medical University; College of Traditional Chinese Medicine, Capital Medical University. MATERIALS: The experiment was carried out in the Laboratory Center of Capital Medical University from August to October 2005. Ten adult guinea pigs (SPF grade, weighing 400–450 g) and 70 adult Lewis rats (SPF grade, weighing 200–220 g) were selected in this study. Erhuangfang consisted of jiudahuang, shengdi, shuizhi, dabeimu, etc. METHODS: ① Experimental intervention: Rats were randomly divided into normal group (n=10), model group (n=20), western medicine group (n=20) and Chinese herb group (n=20). Mixed emulsion, which was consisted of Freund's adjuvant and spinal cord homogenate of guinea pigs, was subcutaneously injected into palms of the two hindfeet of rats in the latter three groups to establish EAE models. Foot pads were injected with saline and then rats were perfused with saline in the normal group. In the model group, models were established as the same as those mentioned above, and rats were also perfused with saline. Rats in the western medicine group were perfused with saline and then 5 mg/kg prednisone acetate suspension. Rats in the Chinese herb group were perfused with erhuangfang decoction (15 g raw materials per kilogram) at 5 days before model establishment. The dosage in the four groups was 3 mL/day per rat. ② Experimental evaluation: At 28 days after model establishment, rats were randomly selected for cerebral (mainly surrounding cerebral ventricle) and spinal cord (cervical enlargement and lumbar enlargement) collections, and then haematine-eosin (HE) staining and SLG myelin staining were used to observe demyelination and regeneration; meanwhile, immunohistochemical staining was used to observe the expression of glial fibriliary acidic protein (GFAP). MAIN OUTCOME MEASURES: Cerebral and spinal demyelination and regeneration as well as expression of GFAP in EAE rats. RESULTS: All 70 Lewis rats were involved in the final analysis. ① Demyelination and regeneration: Infiltration of inflammatory cells surrounding cerebrum and small venous vessels of spinal cord white matter, demyelination surrounding vessels and plentiful foam cells at myelinolysis sites were observed in the model group. Symptoms were relieved in the western medicine group and the Chinese herb group as compared with those in the model group. While, numbers of inflammatory infiltrated cells and vascular cuffs were decreased in focal region as compared with those in the model group; in addition, areas of softening focus and demyelination were decreased. ② Expression of GFAP: Volumes and numbers of positive cells of GFAP in white matter region were respectively bigger and higher than those of normal cells in the model group. Plentiful positive cells of GFAP were disorderly aggregated in hippocampus and surrounding small vessel cuffs. While, expression of GFAP was mildly increased surrounding focus in the Chinese herb group; however, GFAP did not express surrounding focus in the western medicine group. In addition, expressions of GFAP were not increased in non-focal region in both Chinese herb group and western medicine group. CONCLUSION: Both erhuangfang and hormone can relieve inflammatory reaction of central nervous system and demyelination of EAE rats. On one hand, erhuangfang can regulate reaction of astrocyte in two ways, relieve reaction and proliferation of astrocyte in non-focal region and maintain the protective effect of astrocyte on brain tissue in focal region; on the other hand, hormone can overall inhibit reaction of astrocyte.     

Abnormal admission kidney function predicts higher mortality in stroke patients

Objectives:To to investigate the impact of abnormal kidney function on stroke outcome.Methods:This was a retrospective cohort of stroke patients admitted to King Abdulaziz University Hospital in Kingdom of Saudi Arabia between 2010 and 2014. Serum creatinine and urine protein were collected at admis-sion. We defined proteinuria as urine protein dipstick ≥+1. Estimated glomerular filtration (eGFR) rate was calculated by Modification of Diet in Renal Disease Study equation in mL/min/1.73m². Abnormal kidney disease was defined as Creatinine>126 mg/dl or eGFR<60. Clinical characteristics and outcomes including one-year mortality and 30-day readmission were compared between patients with versus (vs.) without abnormal kidney function and/or proteinuria.Results:Out of 548 patients, 507 had creatinine measurement at admission and 193 patients had ab-normal kidney function. These patients tended to be older (median age 67 years vs. 60.5 for those with normal kidney function), men (66.7% vs. 54.3%), and hypertensive (96% vs. 88%). Diabetes prevalence did not differ between the 2 groups. Proteinuria was not associ-ated with future mortality. Abnormal kidney function was a significant predictor of post-stroke one-year mortality (adjusted OR=2.5, 95% CI=1.4 to 4.6; p-value=0.003).Conclusion:Abnormal kidney function doubled the risk of one-year mortality post stroke in our cohort. High-risk groups, including older hypertensive men, could be targeted for aggressive moni-toring and early treatment of risk factors.

Stroke is a leading cause of mortality and morbidity worldwide.1 There are many modifiable and non-modifiable stroke risk factors including hypertension, diabetes, hyperlipidemia, and ethnicity.2 Many of these risk factors are shared between stroke and other diseases like coronary artery disease, chronic kidney disease, and peripheral artery disease.3 Chronic kidney disease (CKD) affects 10-15% of the general population.4 However, it is not regarded as one of the traditional stroke risk factors. Yet, both stroke and CKD have similar risk factors and the interaction between the 2 conditions could impact the outcome of the other. The presence of abnormal kidney function could have implications for stroke prognosis. The presence of atherosclerosis together with the activated reninangiotensin system will eventually lead to vascular manifestations including stroke.5 In addition, several CKD-associated mechanisms may contribute to platelet dysfunction, coagulation disorders, endothelial dysfunction, inflammation and increased risk of atrial fibrillation:6 one of the most common stroke mechanisms. Moreover, the limited use of oral anticoagulants and other antithrombotic treatments in CKD patients will lead to poor stroke outcome in these patients with an in-creased mortality risk at 1- and 10-years.7Given the reported high prevalence of vascular risk factors in Saudi population, the prevalence of CKD in stroke patients is expected to be high. However, the degree of this association and whether it would still carry poor outcome compared to the published literature is not known. This study aims to investigate the association and impact of abnormal baseline kidney function on the outcome of stroke in these patients.