Transvenous left bundle branch pacing during cardiac surgery: A case report.

Left bundle branch pacing (LBBP) was a promising physiological pacing method, which could prevent or treat heart failure. We reported a young woman with severe valvular disease and heart failure receiving LBBP under direct vision and without x-ray assistance during cardiac surgery. To the best of our knowledge, this was the first case report of this type of pace maker implantation.

His-Purkinje system pacing reduced tricuspid regurgitation in patients with persistent atrial fibrillation after left-sided valve surgery.

Background & objective: Tricuspid regurgitation after left-sided valve surgery was a common and difficult problem. Atrial fibrillation was considered to be an important etiology of tricuspid regurgitation. His-Purkinje system pacing (HPSP) was a physiological pacing method, which could prevent and treat heart failure and might reduce tricuspid regurgitation. Our study aimed to investigate the effect of HPSP on tricuspid regurgitation in patients with persistent atrial fibrillation after left-sided valve surgery. Methods: This study was a retrospective study. The 3-year patient review focused on those who underwent permanent cardiac pacemaker implantation of HPSP after mitral valve and/or aortic valve replacement from Jan 1st, 2019 to Jan 1st, 2022. HPSP included His bundle pacing (HBP) or left bundle branch pacing (LBBP). Clinical data collected included electrocardiogram, pacing parameters, ultrasonic cardiogram parameters and chest x-ray at implantation and 3-month follow up. Univariate and multivariate linear regression analysis of tricuspid regurgitation velocity were performed. Results: A total of 44 patients was retrospectively reviewed. Eight patients who had undergone implantation of HPSP after left-sided heart valve replacement were enrolled in the study. All patients had persistent atrial fibrillation. Three of them received HBP and five underwent LBBP. At 3-month follow-up, the tricuspid regurgitation grade was significantly lower than that before implantation (P = 0.007). The tricuspid regurgitation velocity significantly decreased (317 ± 74 cm/s vs. 261 ± 52 cm/s, P = 0.022) and tricuspid valve pressure gradient (PG) reduced (42 ± 21 mmHg vs. 28 ± 10 mmHg, P = 0.040). The cardiothoracic ratio of patients was significantly lower than that before implantation (0.61 ± 0.08 vs. 0.64 ± 0.09, P = 0.017). The NYHA classification of patients also improved (P = 0.013). In multivariate liner regression analysis, the pacing ratio (ß = 0.736, P = 0.037) was an independent determinant of tricuspid regurgitation velocity variation. Conclusion: HPSP might reduce tricuspid regurgitation and improve cardiac function in patients with persistent atrial fibrillation after left-sided valve surgery.

Effect of angiotensin receptor-neprilysin inhibitor on atrial electrical instability in atrial fibrillation.

Background and objective: Around 33.5 million patients suffered from atrial fibrillation (AF), causing complications and increasing mortality and disability rate. Upstream treatment for AF is getting more popular in clinical practice in recent years. The angiotensin receptor-neprilysin inhibitor (ARNI) is one of the potential treatment options. Our study aimed to investigate the effect of ARNI on atrial electrical instability and structural remodeling in AF. Methods: Our research consisted of two parts - a retrospective real-world clinical study and an animal experiment on calmness to verify the retrospective founding. In the retrospective study, we reviewed all patients (n = 110) who had undergone the first AF ablation from 1 August 2018 to 1 March 2022. Patients with ARNI (n = 36) or angiotensin II receptor antagonist (ARB) (n = 35) treatment were enrolled. Their clinical data, ultrasound cardiogram (UCG) and Holter parameters were collected before radiofrequency catheter ablation (RFCA) as baseline and at 24-week follow-up. Univariate and multivariate logistic regression analysis were performed. In the animal experiment, we established an AF model (n = 18) on canines by rapid atrial pacing. After the successful procedure of pacing, all the 15 alive beagles were equally and randomly assigned to three groups (n = 5 each): Control group, ARB group, and ARNI group. UCG was performed before the pacing as baseline. Physiological biopsy, UCG, and electrophysiological study (EPS) were performed at 8-week. Results: Clinical data showed that the atrial arrhythmia rate at 24-week was significantly lower in ARNI group compared to ARB group (P < 0.01), and ARNI was independently associated with a lower atrial arrhythmia rate (P < 0.05) at 24-week in multivariate regression logistic analysis. In the animal experiment, ARNI group had a higher atrial electrical stability score and a shorter AF duration in the EPS compared to Control and ARB group (P < 0.05). In the left atrium voltage mapping, ARNI group showed less low voltage and disordered zone compared to Control and ARB group. Compared to Control group, right atrium diameter (RAD), left ventricle end-diastolic volume index (LVEDVI), E/A, and E/E' were lower in ARNI group (P < 0.05) at the 8-weeks follow-up, while left atrium ejection fraction (LAEF) and left ventricle ejection fraction (LVEF) were higher (P < 0.01). Compared to ARB group, LVEF was higher in ARNI group at the 8-week follow-up (P < 0.05). ARB and ARNI group had a lower ratio of fibrotic lesions in the left atrium tissues compared to Control group (P < 0.01), but no difference was found between the ARB and the ARNI group. Conclusion: ARNI could reduce atrial electrical instability in AF in comparison with ARB in both retrospective study and animal experiment.

The relationship between carotid intima-media thickness and carotid plaque: a cohort study in China.

Both carotid intima-media thickness (cIMT) and carotid plaque (CP) quantified by B-mode ultrasound have been proposed as surrogate imaging biomarkers of subclinical atherosclerosis, while the relationship between cIMT and CP, whether cIMT evaluation in a given patient might allow for predicting the development of a carotid plaque, is still discussed controversially. We investigated the cross-sectional relationship between cIMT and CP, and the predictive value of cIMT for incident CP formation in 1078 subjects with mean age of 52 ± 5 years in a community based atherosclerosis cohort in Beijing. Participants underwent ultrasonography of bilateral carotid arteries and received vascular risk factor assessment at baseline and after a mean of 2.35 years follow-up. The prevalence of plaque was increased by 3.75-fold for upper quartile cIMT compare with the lower quartile even after adjustments for traditional risk factors at baseline. Among the 746 plaque-free subjects at baseline, 230 (31.0%) developed new CP. After adjusted for demographics and vascular risk factors, neither baseline cIMT nor the cIMT change from baseline to follow-up predicted incident CP. In conclusion, although cIMT associates with CP cross-sectionally, increased cIMT dose not independently predict future plaque development. Our data suggest that paying attention to the traditional risk factors might prevent subjects from developing carotid plaques regardless from IMT changes.

Decreased GFR and its joint association with type 2 diabetes and hypertension with prevalence and severity of carotid plaque in a community population in China.

BACKGROUND: Type 2 diabetes (T2DM), hypertension and kidney dysfunction are known risk factors for cardiovascular disease, but their combined effect on carotid plaque remains uncertain. This study aims to assess the associations between T2DM, hypertension, kidney dysfunction and carotid plaque, and further explore the combined effect of three diseases. PATIENTS AND METHODS: We conducted a cross-sectional analysis among 3,815 community-dwelling adults in a Chinese atherosclerosis cohort. Estimated glomerular filtration rate (eGFR), hypertension and T2DM were evaluated as risk factors for carotid plaque. The presence, number and total area of carotid plaques were also assessed. Using logistic model, mutinomial logistic model and generalized linear regression model, the relationship between risk factors and carotid plaque was examined. RESULTS: T2DM, hypertension, decreased GFR, and, inversely, eGFR, were independently associated with the presence, number and total area of carotid plaque. Stratified analysis by T2DM and hypertension showed T2DM attenuated the association between eGFR change and carotid plaque. There was a cumulative relationship between three risk factors and carotid plaque burden. The OR for the number of plaques was 1.0 (reference), 1.55 to 2.03, 1.94 to 3.14, and 3.69 (all P<0.05), respectively, for individuals with none, one, two, and three risk factors. Likewise, combining three risk factors was associated with greater increase in total plaque area (ß, 20.63; 95% CI, 14.04-27.22). CONCLUSION: The coexistence of decreased GFR, diabetes and hypertension is associated with increased risk of carotid plaque, and these comorbidities may contribute additively to the development of plaque.

Higher blood pressure increases arterial stiffness modified by blood glucose levels in a Chinese community-based study.

Background: Increased arterial stiffness measured by brachial-ankle pulse wave velocity is associated with cardiovascular disease. However, the rates at which brachial-ankle pulse wave velocity and blood glucose accelerate within individuals who differ in blood pressure levels are largely unknown. Methods: This study was based on the baseline data of a Chinese community-based atherosclerosis cohort which included 7402 individuals. Using generalized linear regression models, the relationship between blood glucose levels and brachial-ankle pulse wave velocity, and the relationship between blood pressure levels and brachial-ankle pulse wave velocity were examined. Results: A marked interaction between hypertensive state and diabetic state was seen for brachial-ankle pulse wave velocity (P for interaction <0.001). The adjusted coefficient for subjects stratified by hypertensive groups and diabetic states showed that the highest brachial-ankle pulse wave velocity risk subjects were those who had both diabetes and hypertension (B=403.24; 95% CI: 372.43-434.05; P<0.001). Conclusions: The participants with increased arterial stiffness demonstrate a high prevalence of higher blood pressure. When high blood glucose levels co-occur with high blood pressure levels, there is a remarkable increase in arterial stiffness.

Different Techniques of Minimally Invasive Craniopuncture for the Treatment of Hypertensive Intracerebral Hemorrhage.

OBJECTIVE: Efficacy of minimally invasive craniopuncture with the YL-1 puncture needle (hard-channel) and soft drainage tube (soft-channel) in treating hypertensive intracerebral hemorrhage (HICH). MATERIALS AND METHODS: A total of 150 patients with HICH were randomly assigned into 3 groups: conservative group (n = 50), hard-channel group (n = 50), and soft-channel group (n = 50). Computed tomography, National Institutes of Health Stroke Scale (NIHSS) and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA) in serum and in drainage fluid were examined on days 2, 4, and 6 after operation. RESULTS: Compared with the conservative group, the serum levels of IL-6, TNF-α, and MDA were decreased and SOD was increased (P < 0.05); volumes of hematoma and perihematomal edema as well as NIHSS were reduced (P < 0.05) in minimally invasive groups on days 7, 14, and 28 after operation. Compared with the hard-channel group, the serum levels of IL-6, TNF-α, MDA, and SOD showed the same trend as above in the soft-channel group. In the soft-channel group, MDA was reduced and SOD was increased in brain drainage fluid on days 2, 4, and 6 (P < 0.05); volumes of hematoma and perihematomal edema on days 14 and 28 were found to be reduced compared with the hard-channel group (P < 0.05). There was no significant difference of volumes of hematoma and perihematomal edema on day 7 between minimally invasive groups. NIHSS of the soft-channel group appeared to be significantly reduced on days 7, 14, and 28 after operation (P < 0.05). CONCLUSIONS: Soft-channel minimally invasive craniopuncture is an ideal technique for treating HICH, with advantages of alleviating cerebral edema, reducing oxidative stress, and inhibiting inflammatory response.

Noninvasive central systolic blood pressure, not peripheral systolic blood pressure, independently predicts the progression of carotid intima-media thickness in a Chinese community-based population.

This study aimed to investigate the predictive values of central systolic blood pressure (cSBP) and peripheral systolic blood pressure (pSBP) for the progression of carotid intima-media thickness (cIMT). A total of 953 Chinese participants from an atherosclerosis cohort with complete information, including baseline cSBP, questionnaire information, biochemical examination, baseline, and follow-up carotid ultrasonography quantitative data, were included in this study. A multilinear regression model, adjusted for possible covariates, was used to investigate the predictive values of cSBP and pSBP for rate of cIMT change. The average age of all participants was (52.11 ± 4.74 years). The baseline levels of cSBP, pSBP, max cIMT, and mean cIMT were (132.55 ± 18.18)mmHg, (130.76 ± 15.40)mmHg, (813.52 ± 118.49)µm and (681.11 ± 99.90)µm, respectively Those with hypertension, diabetes and dyslipidemia accounted for 40.71% (388), 18.05% (172), and 70.41% (671), respectively. After 2.3 years of follow-up, the average rates of max and mean cIMT change were 8.70 (-0.49-19.43)% and 2.59 (-4.72-10.81)%, respectively. Per standard deviation increase of cSBP, but not pSBP, was associated with increases of max (for cSBP, ß 1.07, 95%CI 0.18-1.96, p = 0.018; for pSBP, ß 0.48, 95%CI -0.45-1.41, p = 0.315) and mean (for cSBP, ß 0.84%, 95%CI 0.10-1.58, p = 0.027; for pSBP, ß 0.59%, 95%CI -0.18-1.37, p = 0.135) cIMT change rate after adjusting for possible covariates. In conclusion, cSBP, but not pSBP, is independently associated with cIMT progression in our community-based Chinese population. cSBP should be considered for the purpose of CVD primary prevention.

Randomized controlled study on the curative effects of twist-drill craniotomy and burr-hole craniotomy in the treatment of chronic subdural hematoma.

The present randomized controlled study investigated the differences in the curative effects of twist-drill craniotomy (TDC) and burr-hole craniotomy (BHC) in the treatment of chronic subdural hematoma (CSDH). A total of 40 patients diagnosed with CSDH via head computed tomography (CT) who required surgical decompression from January 2016 to January 2017 were enrolled in the present study, and were randomly divided into a TDC group (n=20) and a BHC group (n=20). The modified Rankin scale (mRS) scores of patients were recorded prior to the operation, and at 48 h and 3 months after the operation. The differences in the mRS score (VmRS) among the groups were calculated using the Mann-Whitney U test. The 40 patients enrolled comprised 33 males and 7 females, and there were no significant differences in the general clinical characteristics between the two groups. In the BHC group, 3 patients had a pre-operative mRS score of 5 points, among which 2 cases died at 32 and 45 days after discharge. In the TDC group, 4 patients had a pre-operative mRS score of 5 points, among which 1 case died of epilepsy and pulmonary infection at 1 month after the operation. No difference in the mortality rate was present between the two groups. During the 3-month follow-up, head CT indicated that the intracranial hematoma in a total of 4 patients, including 3 cases in the TDC group and 1 case in the BHC group, completely disappeared. In the BHC group, 3 cases required a repeated incision and drainage after the first operation, while no secondary operation was required in any of the cases of the TDC group. The average length of stay at the hospital (LOS) after TDC was 9.00±2.91 days, which was significantly shorter than that after BHC (14.75±5.95 days). In the total sample of 40 patients, a longer LOS was associated with a higher risk of secondary operation due to recurrence after discharge. The variation value of the mRS score at 3 months after the operation and its ratio vs. the pre-operative score in the TDC group were significantly different from those in the BHC group, suggesting that the improvement of neurological function after TDC was significantly greater than that after BHC. Although 18 patients (90%) in the TDC group were cured, there was no significant difference from the cure rate in the BHC group [15 patients (75%)]. In conclusion, no significant differences were identified in the cure rate and the mortality rate of patients with CSDH after the two types of surgical treatment. However, the mRS score in the TDC group at 3 months after the operation exhibited a significantly greater improvement compared with that in the BHC group, and the overall LOS in the TDC group was significantly shorter than that in BHC group. Therefore, TDC is superior to BHC in the treatment of CSDH (trial registration no. ChiCTR-INR-16008368).

Brachial-Ankle Pulse Wave Velocity is Associated with the Risk of New Carotid Plaque Formation: Data from a Chinese Community-based Cohort.

Artery stiffness is an independent marker for atherosclerotic cardiovascular diseases. However, whether the brachial-ankle pulse wave velocity (ba-PWV) is related to new carotid plaque formation is unresolved. This study aimed to investigate the association between baseline ba-PWV and new carotid plaque formation in a Chinese community-based population without carotid plaques at baseline. This study population consisted of a total of 738 participants from an atherosclerosis cohort in Beijing, China. After a mean 2.3-year follow-up, the incidence of carotid plaques were 21.2% and 36.5% in the groups with ba-PWV < 1,400 cm/s and ≥1,400 cm/s, respectively. Compared with baseline ba-PWV < 1,400 cm/s group, ba-PWV ≥ 1,400 cm/s group was significantly associated with the incidence of new carotid plaque formation (odds ratio [OR] = 2.14, 95% CI: 1.50-3.03, P < 0.01), even after adjusting for common risk factors (OR = 1.52, 95% CI: 1.02-2.25, P = 0.04). Furthermore, there was a strong relationship between baseline ba-PWV and carotid plaque formation in subjects with ba-PWV < 1,400 cm/s, but no such relationship was found in subjects with baseline ba-PWV ≥ 1,400 cm/s. In conclusion, this study suggests that baseline ba-PWV is independently associated with the risk of carotid plaque formation in a Chinese community-based population.

Association between short sleep duration and carotid atherosclerosis modified by age in a Chinese community population.

BACKGROUND AND AIM: Short sleep duration is a risk factor of cardiovascular disorder; however, the association between short sleep duration and carotid atherosclerosis has not been completely characterised. The aim of this study is to investigate the association between short sleep duration and carotid atherosclerosis. METHODS: We used the cross-sectional data collected between May 2014 and July 2014, which were based on a cardiovascular disease cohort study including 3798 participants aged 40 years and older who are residents of Beijing, China. We used logistic regression models to examine the associations between sleep duration and carotid atherosclerosis. RESULTS: After the adjustment of covariates, short sleep duration (less than 5 hours per night) was found to be associated with carotid atherosclerosis, and it also elevated the risk of, in both terms, the increment of prevalence (OR=1.31, P<0.05) and the quantity of carotid plaques (OR=1.28, P<0.05). When age was also taken into consideration, the largest association, in both terms of prevalence (OR=3.46, P<0.01) and the number of carotid plaques (OR=4.23, P<0.01), was found in subjects over the age of 60 with short sleep duration. CONCLUSION: In conclusion, sleep duration less than 5 hours per night is associated with a higher risk of carotid atherosclerosis compared with subjects who sleeps for 5 or over 5 hours per night, and the association may be modified by age.

Cerebral vasomotor reactivity predicts the development of acute stroke in patients with internal carotid artery stenosis.

OBJECTIVE: To investigate the relationship between cerebral vasomotor reactivity (VMR) and acute stroke in patients with internal carotid artery stenosis. METHODS: 54 patients with internal carotid artery stenosis were enrolled. VMR was calculated by transcranial Doppler monitoring of the velocity of blood flow. 3-Dimensional dynamic contrast enhanced magnetic resonance angiography was used to detect stenosis, and diffusion weighted imaging was used to detect infarction. RESULTS: VMR value was significantly lower in patients with carotid artery stenosis than in control group (T=3.112, P=0.002), and significantly lower in patients with aortic atherosclerotic stroke than in non-infarct group (T=10.930, P=0.000). However, VMR value was significantly higher in patients with new-onset small-artery occlusion stroke than in non-infarction group (T=-2.538, P=0.013). Scatter plots showed that aortic atherosclerotic stroke occurred mainly in patients with severe internal carotid artery stenosis, and VMR value in cerebral artery significantly decreased. CONCLUSION: Decreased VMR value is an important prognostic factor for the occurrence of aortic atherosclerotic stroke, and can be used as a reference for preoperative hemodynamic evaluation in patients with internal carotid artery stenosis.

Effects of low oxygen dead space ventilation and breath-holding test in evaluating cerebrovascular reactivity: A comparative observation.

OBJECTIVE: This study aims to explore the application prospect of low oxygen dead space ventilation (LODSV) in evaluating vasomotor reactivity (VMR) by comparison between LODSV and breath-holding test (BHT). METHODS: Outpatient or inpatient patients who underwent transcranial Doppler sonography (TCD) were enrolled into this study. These patients successively underwent BHT and LODSV. The cooperation degree, tolerance conditions and adverse reactions in patients were recorded, and VMR was calculated, compared and analyzed. RESULTS: Patients had poor cooperation during BHT. Except for compensatory tachypnea after BHT, patients basically had no adverse reaction. The main manifestations of patients undergoing LODSV were deepened breathing and accelerated frequency in the end of the ventilation, and increased heart rate and a slight decline in pulse oxygen that rapidly recovered after ventilation. The increase rate of blood flow velocity in patients undergoing LODSV was significantly higher than in BHT (P<0.001), and its calculated VMR value was approximately 15% higher than BHT (P<0.001). BHT revealed a monophasic curve that slightly descends and rapidly increases, and LODSV revealed a curve that descends for a short time and slowly increases with a platform. CONCLUSION: LODSV can effectively eliminate the affect of poor cooperation in patients, and avoid intolerance caused by hypoxia. Hence, VMR value is more accurate than that determined by BHT; and this can reflect the maximum reaction ability of the blood vessels. Therefore, this method has higher clinical application value.

Impact of serum uric acid, albumin and their interaction on Parkinson's disease.

The study aimed to investigate the correlation between Parkinson's disease (PD) and serum levels of uric acid (UA), albumin and their interaction. A cross-sectional study was conducted to evaluate the relationship of serum UA, albumin with PD. A total of 96 PD patients and 108 healthy controls were recruited at Huai'an First People's Hospital, Nanjing Medical University. Baseline data included age, gender, body mass index (BMI), disease duration, Hoehn and Yahr scale (H&Y) stage, serum UA and albumin levels. The levels of serum UA and albumin were significantly lower in PD patients than those in controls (P = 0.001; P = 0.000). Serum albumin levels were strikingly different in H&Y group (P = 0.004). Multivariable logistic regression showed that the levels of serum UA (P = 0.001, adjusted OR 0.993, 95% CI 0.988-0.997) and albumin (P = 0.000, adjusted OR 0.513, 95% CI 0.425-0.620) were independent risk factors in PD. The receiver operating characteristic (ROC) curve analyses showed that the area under curve (AUC) for serum UA and albumin was 0.669 (95% CI 0.594-0.744) and 0.883 (95% CI 0.835-0.931), respectively. The combination of serum albumin and UA improved the AUC to 0.898 (95% CI 0.854-0.942). Serum UA and albumin levels significantly decreased in PD patients and were independent risk factors for PD. More studies are needed to confirm our findings.

Appropriate management of asymptomatic carotid stenosis.

With modern intensive medical therapy, the annual risk of ipsilateral stroke in patients with asymptomatic carotid stenosis (ACS) is now down to ∼0.5%. Despite this, there is a widespread practice of routine intervention in ACS with carotid endarterectomy (CEA) and stenting (CAS). This is being justified on the basis of much higher risks with medical therapy in trials conducted decades ago, compared with lower risks of intervention in recent trials with no medical arm. Such extrapolations are invalid. Although recent trials have shown that after subtracting periprocedural risks the outcomes with CEA and CAS are now comparable to medical therapy, the periprocedural risks still far outweigh the risks with medical therapy. In the asymptomatic carotid trial (ACT) 1 trial, the 30-day risk of stroke or death was 2.9% with CAS and 1.7% with CEA. In the CREST trial, the 30-day risk of stroke or death among asymptomatic patients was 2.5% for stenting and 1.4% for endarterectomy. Thus, intensive medical therapy is much safer than either CAS or CEA. The only patients with ACS who should receive intervention are those who can be identified as being at high risk. The best validated method is transcranial Doppler embolus detection. Other approaches in development for identifying vulnerable plaques include intraplaque haemorrhage on MRI, ulceration and plaque lucency on ultrasound, and plaque inflammation on positron emission tomography/CT. Intensive medical therapy for ACS includes smoking cessation, a Mediterranean diet, effective blood pressure control, antiplatelet therapy, intensive lipid-lowering therapy and treatment with B vitamins (with methylcobalamin instead of cyanocobalamin), particularly in patients with metabolic B12 deficiency. A new strategy called 'treating arteries instead of risk factors', based on measurement of carotid plaque volume, is promising but requires validation in randomised trials.

Evidence that orphanin FQ mediates progesterone negative feedback in the ewe.

Orphanin FQ (OFQ), a member of the opioid family, is found in many areas of the hypothalamus and, when given centrally OFQ inhibits episodic LH secretion in rodents and sheep. Because GnRH neurons are devoid of the appropriate receptors to mediate steroid negative feedback directly, neurons that release OFQ may be involved. Using immunocytochemistry, we first determined that most OFQ neurons in the arcuate nucleus (ARC) and other hypothalamic regions of luteal phase ewes contained both estrogen receptor α and progesterone (P) receptor. Given a similar high degree of steroid receptor colocalization in other ARC subpopulations, we examined whether OFQ neurons of the ARC contained those other neuropeptides and neurotransmitters. OFQ did not colocalize with kisspeptin, tyrosine hydroxylase, or agouti-related peptide, but all ARC OFQ neurons coexpressed proopiomelanocortin. To test for a role for endogenous OFQ, we examined the effects of an OFQ receptor antagonist, [Nphe1,Arg14,Lys15]Nociceptin-NH2 (UFP-101) (30 nmol intracerebroventricular/h), on LH secretion in steroid-treated ewes in the breeding season and ovary-intact ewes in anestrus. Ovariectomized ewes with luteal phase concentrations of P and estradiol showed a significant increase in LH pulse frequency during infusion of UFP-101 (4.5 ± 0.5 pulses/6 h) compared with saline infusion (2.6 ± 0.4 pulses/6 h), whereas ewes implanted with only estradiol did not. Ovary-intact anestrous ewes displayed no significant differences in LH pulse amplitude or frequency during infusion of UFP-101. Therefore, we conclude that OFQ mediates, at least in part, the negative feedback action of P on GnRH/LH pulse frequency in sheep.

[Effects of ginseng total saponin on traumatic brain edema of rats].

OBJECTIVE: To observe the effects of ginseng total saponin (GTS) on the water content in the brain tissue, the activity of superoxide dismutase (SOD), the content of malondialdehyde (MDA), the expression levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta), and the neurological function in rats with traumatic brain injury (TBI), and to explore the roles of GTS in treating traumatic brain edema rats and its possible mechanisms. METHODS: The TBI rat model was established using modified Feeney's method. Rats were randomly divided into 3 groups, i.e., the sham-operation group, the TBI group, and the GTS-treated group. All rats were sacrificed after their neurological behavior was scored at day 1, 3, 5, and 7 of TBI. The brain tissue was taken out to measure the brain water content with wet-dry weight method. The activity of SOD in the brain tissue and the content of MDA were determined using biochemistry method. The expression levels of TNF-alpha and IL-1beta in the brain tissue were detected using ELISA. RESULTS: Compared with the TBI group at the same time point, the brain water content and the content of MDA decreased, the activity of SOD increased, the expression levels of TNF-alpha and IL-1beta obviously decreased, and the neurological functions were obviously improved in the GTS-treated group (P<0.05). CONCLUSIONS: GTS could obviously alleviate the degree of traumatic brain edema after TBI, and attenuate the deleted neurological behavioral symptoms. The underlying mechanisms might be achieved through reducing the production of MDA, decreasing the expression levels of TNF-alpha and IL-1beta, elevating the activity of SOD, inhibiting free radical reaction, and alleviating inflammatory reactions.

Triflusal reduces cerebral ischemia induced inflammation in a combined mouse model of Alzheimer's disease and stroke.

Clinical data has shown that stroke exacerbates dementia in Alzheimer's disease (AD) patients. Previous work, combining rat models of AD and stroke have shown that neuroinflammation may be the common mediator between AD and stroke toxicity. This study examined the effects of triflusal (2-acetoxy-4-trifluoromethylbenzoic acid) in APP(23) transgenic mice receiving strokes. Six month-old APP(23) mice over-expressing mutant human amyloid precursor protein (APP) were used to model AD in this study. Unilateral injections of a potent vasoconstrictor, endothelin-1, into the striatum were used to mimic small lacunar infarcts. Immunohistochemical analysis was performed to examine AD-like pathology and inflammatory correlates of stroke and AD. APP(23) mice showed increases in AD-like pathology and inflammatory markers of AD in the cortex and hippocampus. Endothelin-induced ischemia triggered an inflammatory response along with increases in AD pathological markers in the region of the infarct. Triflusal reduced inflammation surrounding the endothelin-induced infarct only. At the dose used, anti-inflammatory treatment may be beneficial in reducing the AD and inflammatory correlates of stroke in a combined AD-stroke mouse model.

The kisspeptin/neurokinin B/dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep.

Recent work in sheep has identified a neuronal subpopulation in the arcuate nucleus that coexpresses kisspeptin, neurokinin B, and dynorphin (referred to here as KNDy cells) and that mediate the negative feedback influence of progesterone on GnRH secretion. We hypothesized that sex differences in progesterone negative feedback are due to sexual dimorphism of KNDy cells and compared neuropeptide and progesterone receptor immunoreactivity in this subpopulation between male and female sheep. In addition, because sex differences in progesterone negative feedback and neurokinin B are due to the influence of testosterone (T) during fetal life, we determined whether prenatal T exposure would mimic sex differences in KNDy cells. Adult rams had nearly half the number of kisspeptin, neurokinin B, dynorphin, and progesterone receptor-positive cells in the arcuate nucleus as did females, but the percentage of KNDy cells colocalizing progesterone receptors remained high in both sexes. Prenatal T treatment also reduced the number of dynorphin, neurokinin B, and progesterone receptor-positive cells in the female arcuate nucleus; however, the number of kisspeptin cells remained high and at levels comparable to control females. Thus, sex differences in kisspeptin in the arcuate nucleus, unlike that of dynorphin and neurokinin B, are not due solely to exposure to prenatal T, suggesting the existence of different critical periods for multiple peptides coexpressed within the same neuron. In addition, the imbalance between inhibitory (dynorphin) and stimulatory (kisspeptin) neuropeptides in this subpopulation provides a potential explanation for the decreased ability of progesterone to inhibit GnRH neurons in prenatal T-treated ewes.

Progressive increase in infarct size, neuroinflammation, and cognitive deficits in the presence of high levels of amyloid.

BACKGROUND AND PURPOSE: In the elderly, cerebral ischemia (CI) occurs in the presence of high levels of amyloid. Neuroinflammation plays a critical role in the pathophysiology of Alzheimer's disease and CI. This study examined infarct size, neuroinflammation, and cognitive deficits over time in rat models of Alzheimer's disease and CI. METHODS: beta-amyloid toxicity was modeled using bilateral intracerebroventricular injections of beta-amyloid 25 to 35 peptides. CI was modeled using unilateral injections of the potent vasoconstrictor, endothelin-1, into the striatum. RESULTS: Infarct volumes were higher in the presence of amyloid and compared with the CI model alone. In the CI model alone, the infarct volume was significantly smaller 28 days after surgery compared with 7 days after surgery. However, when Alzheimer's disease and CI models were combined, the infarct volume was significantly larger 28 days after surgery compared with 7 days after surgery. The neuroinflammation in the region of the infarct was also significantly increased. The Barnes circular platform test showed time-dependent increases in memory and learning deficits in the beta-amyloid-treated rats that were even greater when beta-amyloid treatment was combined with CI. CONCLUSIONS: CI in the presence of high levels of amyloid results in progressive increases in infarct size, neuroinflammation, and cognitive deficits.