Simultaneous intrastriatal and intranigral dopaminergic grafts in the parkinsonian rat model: role of the intranigral graft

The current transplantation strategy in experimental and clinical Parkinson's disease (PD) has been to place nigral dopaminergic grafts not in their ontogenic site (substantia nigra) but in their target area (striatum). Although intrastriatal dopaminergic grafts are capable of reinnervating the striatum, they fail to reinnervate the nigra, which may be an important factor limiting the efficacy of fetal tissue transplantation in parkinsonian patients. We have previously shown that simultaneous intrastriatal and intranigral dopaminergic grafts (double grafts) may provide a more complete restoration of the nigrostriatal circuitry (Mendez et al. [1996] J Neurosci 16:7216-7227; Mendez and Hong [1997] Brain Res 778:194-205). In the present study, we investigated the contribution of the intranigral graft to functional recovery in double-grafted hemiparkinsonian rats. Twenty Wistar rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway were divided into two groups and received either double grafts (n = 10) or intrastriatal grafts alone (n = 10). Following transplantation, both intrastriatally and double-grafted animals had a significant decrease in rotational behavior. However, only animals with double grafts exhibited a significant increase in contralateral adjusting step performance. The intranigral graft was subsequently lesioned by a second 6-OHDA injection. Following the second lesion, animals with double grafts exhibited a significant reversal of rotational behavior and a 51% reduction in contralateral adjusting step performance. The reversal in functional recovery correlated with a significant loss of intranigral grafted neurons. These results suggest that the intranigral graft has an important role in the functional recovery of double-grafted animals. Restoration of dopaminergic innervation to both the nigra and the striatum may be crucial for optimizing graft efficacy and may be a superior strategy in neural transplantation for PD.     

Enhancement of survival of stored dopaminergic cells and promotion of graft survival by exposure of human fetal nigral tissue to glial cell line--derived neurotrophic factor in patients with Parkinson's disease. Report of two cases and technical considerations

The authors have studied the ability of glial cell line-derived neurotrophic factor (GDNF) to promote survival of human fetal dopaminergic tissue after a storage period of 6 days and subsequent implantation into the human putamen. The results indicate that GDNF promotes survival of stored dopaminergic cells. Cells stored without GDNF had a 30.1% decrease in survival time compared with those exposed to GDNF. Two patients with Parkinson's disease received bilateral putaminal implants of fetal dopaminergic cells exposed to GDNF for 6 days and showed enhancement of graft survival as assessed by positron emission tomography scanning. A mean increase of 107% in putaminal fluorodopa uptake from baseline values was observed 12 months postgrafting.     

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

Hearing Function and Nutritional Status in Aviation Pilots from Spain Exposed to High Acoustic Damage

Noise-induced hearing loss is the most frequent and preventable occupational disease. Aviation pilots are a vulnerable population, as they spend many hours exposed to noise pollution in their working environment. Different studies suggest that certain dietary compounds may play a key role in the etiology and prevention of this pathology. We aimed to study the relationship linking auditory function, dietary intake, and some serum biomarkers in pilots, exposed to noise in the work environment. A total of 235 pilots, who undergo a periodic medical examination at the Centro de Instrucción de Medicina Aeroespacial (Madrid, SPAIN), were evaluated. Auditory function was assessed by tonal audiometry. Energy and nutrient intakes were estimated by 24 h recall (DIAL^TM program). Serum homocysteine (Hcy) was determined in a Cobas 6000^TM multi-analyzer while folate, vitamin B₁₂, and D were analyzed in a Cobas e411^TM. The prevalence of hearing loss (HL) was 64.3%. HL was significantly related to age (r = 0.588, p ≤ 0.001) and flight hours (r = 0.283, p ≤ 0.001). A multiple linear regression model was used to assess the relationship among HL, flight hours, serum folate, and Hcy serum levels. HL was significantly (p < 0.050) associated with flight hours (β = 0.246), serum folate (β = −0.143), and serum Hcy (β = 0.227). Nutritional interventions would be of great interest to monitor and slow down the HL progression in populations exposed to noise pollution in their workplace.     

前胡丙素与硝苯啶对大鼠工作心脏缺血再灌注损伤的保护作用

大鼠ip前胡丙素(Pra-C 15 mg/kg,bid×3d)和硝苯啶(Nif 60μg/kg,bid×3d),使离体缺血再灌注工作心脏的收缩(AP,LVSP,+dP/dt_max)舒张(-dP/dt_max LVEDP和T值)性能在35min时得到改善,尤以舒张性能改善明显,并能促进CO,CF,SV及HR恢复,改善心脏工作效率,减少CK释放和心肌线粒体钙含量,表明Pra-C和Nif对心肌缺血都有保护作用,Pra-C的效应与Nif相近。     

Association of Lifetime Exposure to Glyphosate and Aminomethylphosphonic Acid (AMPA) with Liver Inflammation and Metabolic Syndrome at Young Adulthood: Findings from the CHAMACOS Study

Background: The prevalence of liver disorders and metabolic syndrome has increased among youth. Glyphosate, the most widely used herbicide worldwide, could contribute to the development of these conditions.Objective: We aimed to assess whether lifetime exposure to glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), is associated with elevated liver transaminases and metabolic syndrome among young adults.Methods: We conducted a prospective cohort study (n=480 mother–child dyads) and a nested case–control study (n=60 cases with elevated liver transaminases and 91 controls) using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). We measured glyphosate and AMPA concentrations in urine samples collected during pregnancy and at child ages 5, 14, and 18 y from cases and controls. We calculated glyphosate residue concentrations: [glyphosate +(1.5×AMPA)]. We estimated the amount of agricultural-use glyphosate applied within a 1-km radius of every residence from pregnancy to age 5 y for the full cohort using California Pesticide Use Reporting data. We assessed liver transaminases and metabolic syndrome at 18 y of age.Results: Urinary AMPA at age 5 y was associated with elevated transaminases [relative risk (RR) per 2-fold increase=1.27, 95% confidence interval (CI): 1.06, 1.53] and metabolic syndrome (RR=2.07, 95% CI: 1.38, 3.11). Urinary AMPA and glyphosate residues at age 14 y were associated with metabolic syndrome [RR=1.80 (95% CI: 1.10, 2.93) and RR=1.88 (95% CI: 1.03, 3.42), respectively]. Overall, a 2-fold increase in urinary AMPA during childhood was associated with a 14% and a 55% increased risk of elevated liver transaminases and metabolic syndrome, respectively. Living near agricultural glyphosate applications during early childhood (birth to 5 y of age) was also associated with metabolic syndrome at age 18 y in the case–control group (RR=1.53, 95% CI: 1.16, 2.02).Discussion: Childhood exposure to glyphosate and AMPA may increase risk of liver and cardiometabolic disorders in early adulthood, which could lead to more serious diseases later in life. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP11721","term_id":"372011122","term_text":"EHP11721"}}EHP11721     

Community‐based health literacy focused intervention for cervical cancer control among Black women living with human immunodeficiency virus: A randomized pilot trial

BackgroundHealth literacy plays an essential role in how individuals process health information to make decisions about health behaviours including cancer screening. Research is scarce to address health literacy as a strategy to improve cancer screening participation among women living with human immunodeficiency virus (HIV), particularly Black women who, despite the heavy burden of cervical cancer, report consistently low screening rates.AimTo assess the feasibility, acceptability and preliminary efficacy of a health literacy‐focused intervention called CHECC‐uP—Community‐based, HEalth literacy focused intervention for Cervical Cancer control—among women living with HIV.MethodsWe conducted a community‐based, single‐blinded randomized pilot trial. A total of 123 eligible women were enrolled and randomized to one of two conditions, control (i.e., cervical cancer brochure) or intervention (cervical cancer brochure plus 30–60 min health literacy‐focused education followed by monthly phone counselling and navigation assistance for 6 months). Study assessments were done at baseline, 3 and 6 months. The final analysis sample included 58 women who completed all data points and whose Papanicolaou (Pap) test status was confirmed by medical records.ResultsAll intervention participants who completed the programme would recommend the CHECC‐uP to other women living with HIV. However, adherence in the experimental conditions was low (49.6% attrition rate including 20 women who dropped out before the intervention began) due, in large part, to phone disconnection. Those who had received the intervention had a significantly higher Pap test rate compared to women in the control group at 6 months (50% vs. 21.9%, p = .025). Participation in the intervention programme was associated with improved health literacy and other psychosocial outcomes at 3 months but the trend was attenuated at 6 months.ConclusionsThe CHECC‐uP was highly acceptable and led to improved Pap testing rates among Black women living with HIV. Future research should consider addressing social determinants of health such as phone connectivity as part of designing a retention plan targeting low‐income Black women living with HIV.ImplicationsThe findings should be incorporated into a future intervention framework to fulfil the unmet needs of Black women living with HIV to facilitate their decision‐making about Pap test screening.Patient or Public ContributionNineteen community members including women living with HIV along with HIV advocates and care providers participated in four focus groups to develop cervical cancer screening decision‐relevant information and the health literacy intervention. Additionally, a community advisory board was involved to provide guidance in the general design and conduct of the study.     

A comparison of the effects of epinephrine and vagal stimulation upon the refractory periods of the A-V node and the bundle of His

Summary In dog hearts perfused from donor animals, recording and stimulating electrodes were located in the right atrium and in the proximal portion of the bundle of His. The minimal interval between two His responses propagated from the atrium (A-H F.R.P.) was determined, and the recovery of excitability of the bundle was directly measured at the same basic driving frequency.In the absence of autonomic influences the minimal interval between two His responses propagated from the atrium was longer than the total refractory period (absolute plus relative) of the bundle.The possibility that a decrease of the action potential of the lower elements of the node was responsible for long delays or block in the activation of the bundle was tested and found unlikely.During vagal stimulation the recovery of excitability of the bundle and its diastolic threshold were not modified, but the A-H F.R.P. was increased.During epinephrine administration it was possible on occasion to show that the A-H F.R.P. was equal to the H F.R.P. estimated by stimulating the bundle directly with strong electrical shocks.These results suggest that in the absence of autonomic influence and during vagal stimulation the weakest link for propagation is located within the A-V node rather than at the junction of node and bundle. During strong adrenergic influences, the functional refractory period of the bundle may be a limiting factor in the propagation of impulses from atrium to the bundle of His.With 9 Figures in the TextDedicated to Professor Otto Krayer on the occasion of his 65th birthday.Supported in part by grants from the American Heart Association and the New York State Heart Assembly (Oneida County Heart Committee).     

Energy density,diet quality,and central body fat in a nationwide survey of young Spaniards

ObjectivesTo determine the impact of energy density on diet quality and anthropometric proxy measures for central body fat in young Spaniards.MethodsData were obtained from a representative national sample of 2513 young Spaniards aged 10 to 24 y. Dietary assessment was performed with a 24-h recall. Adherence to the Mediterranean diet was measured by the KIDMED index. Reduced rank regression analysis was used to identify energy-density dietary patterns. Waist circumferences and height were measured.ResultsPastries and sausages showed the strongest loading for the dietary energy density factor score (DED-FS), with fruits and vegetables at the opposite end of the scale. Multiple linear regression analysis showed a positive association (P < 0.01) of dietary energy density (DED) and the DED-FS with waist circumferences regressed on height and age (WC_height+age) and waist-to-height ratio (WHtR). The adjusted odds ratio for elevated WC_height+age and WHtR increased across quartile distribution of DED (P < 0.001) and DED-FS (P < 0.05). Diet quality characterized by the KIDMED index was negatively associated (P < 0.001) with DED and the DED-FS.ConclusionsHigher DED is a risk for increased central fat distribution and is associated with low adherence to the Mediterranean diet.