Effects of DDT on Amyloid Precursor Protein Levels and Amyloid Beta Pathology: Mechanistic Links to Alzheimer’s Disease Risk

Background: The interaction of aging-related, genetic, and environmental factors is thought to contribute to the etiology of late-onset, sporadic Alzheimer’s disease (AD). We previously reported that serum levels of p,p′-dichlorodiphenyldichloroethylene (DDE), a long-lasting metabolite of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT), were significantly elevated in patients with AD and associated with the risk of AD diagnosis. However, the mechanism by which DDT may contribute to AD pathogenesis is unknown.Objectives: This study sought to assess effects of DDT exposure on the amyloid pathway in multiple in vitro and in vivo models.Methods: Cultured cells (SH-SY5Y and primary neurons), transgenic flies overexpressing amyloid beta (Aβ), and C57BL/6J and 3xTG-AD mice were treated with DDT to assess impacts on the amyloid pathway. Real time quantitative polymerase chain reaction, multiplex assay, western immunoblotting and immunohistochemical methods were used to assess the effects of DDT on amyloid precursor protein (APP) and other contributors to amyloid processing and deposition.Results: Exposure to DDT revealed significantly higher APP mRNA and protein levels in immortalized and primary neurons, as well as in wild-type and AD-models. This was accompanied by higher levels of secreted Aβ in SH-SY5Y cells, an effect abolished by the sodium channel antagonist tetrodotoxin. Transgenic flies and 3xTG-AD mice had more Aβ pathology following DDT exposure. Furthermore, loss of the synaptic markers synaptophysin and PSD95 were observed in the cortex of the brains of 3xTG-AD mice.Discussion: Sporadic Alzheimer’s disease risk involves contributions from genetic and environmental factors. Here, we used multiple model systems, including primary neurons, transgenic flies, and mice to demonstrate the effects of DDT on APP and its pathological product Aβ. These data, combined with our previous epidemiological findings, provide a mechanistic framework by which DDT exposure may contribute to increased risk of AD by impacting the amyloid pathway. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10576","term_id":"372009961","term_text":"EHP10576"}}EHP10576     

Mapping the global literature output on nocturia: A bibliometric and visualized analysis

Purpose:This study aims to facilitate researchers’ and clinicians’ understanding of research frontiers and trends in nocturia. It explores the scientific research outcomes and key bibliometric indices and plots global research on nocturia.Methods:A bibliometric retrospective study was designed, and an online search was conducted in the Web of Science Core Collection database using the potential search keywords related to nocturia in the title field with some specific filtration. HistCite™ and VOSviewer software for windows were used to analyze the data obtained for authors, journals, countries, institutions, keywords, and visualization mapping.Results:The initial search retrieved 1479 hits. A total of 1445 publications were included in the final analysis. Of these, 43.53% were published as articles. The most studied area in nocturia is urology nephrology. The most productive year was 2019 (n = 121, citations = 335), and the most prolific author, both in terms of publications (n = 97) and citations (1658) was Weiss JP. The most cited journal in nocturia research was the Journal of Urology (n = 293, citations = 3050). The most widely used keyword in nocturia publications was nocturia (n = 1249). Visualization mapping shows that the USA was the most influential and highly cited country in nocturia research.Conclusion:This study showed that there has been an increasing research trend in nocturia over the past few years. The current findings provide important empirical evidence for researchers, clinicians, and physicians to understand research frontiers and trends, achievements, collaborative networks, and hotspot research topics in the research field of nocturia.     

Phase I trial of fludarabine and paclitaxel in non-Hodgkin's lymphoma

Fludarabine is an active agent in low-grade non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Paclitaxel is also active in patients with refractory lymphoma, and preclinical data suggest an additive effect with fludarabine in vitro. We performed a phase I trial of fludarabine (25 mg/m² d 1–3) plus a 3-h infusion of paclitaxel (125, 150, or 175 mg/m²) on d 3 every 28 d in 13 patients with non-Hodgkin’s lymphoma. The paclitaxel dose was escalated in cohorts of 3–4 patients using standard phase I design schema. Dose-limiting toxicity was defined as febrile neutropenia, platelet nadir less than 50,000/μL, or grade 3–4 nonhematologic toxicity. Thirteen patients were accrued to the study, 8 of these 13 patients (62%) had received prior chemotherapy. At the 125-, 150-, and 175-mg/m² dose levels of paclitaxel, dose-limiting toxicity occurred in 1/4, 0/4, and 0/4 patients, respectively. The single patient with dose-limiting toxicity had febrile neutropenia. Partial response occurred in two of eight patients with low-grade lymphoma and none of five patients with other types of lymphoma. A paclitaxel dose of 175 mg/m² given as a 3-h infusion on d 3 in conjunction with fludarabine (25 mg/m² d 1–3 every 4 wk) is a well-tolerated regimen for non-Hodgkin’s lymphoma. Further study will be required in order to determine whether the fludarabine-paclitaxel is more active than fludarabine alone in patients with low-grade lymphoma and chronic lymphocytic leukemia.     

An account of the botanical anthelmintics used in traditional veterinary practices in Sahiwal district of Punjab, Pakistan

AIM OF THE STUDY: The present study was aimed at documentation of botanical anthelmintics used in the traditional veterinary practices in Sahiwal district of Punjab, Pakistan. MATERIALS AND METHODS: In rapid rural appraisal, 331 traditional veterinary healers (TVH) were identified as key respondents in the study area followed by participatory rural appraisal for data collection using a well-structured questionnaire. Information was collected through interviews, focused group discussions and field visits over a period of 2 years. RESULTS: A total of 49 traditional recipes, with 41 plant species representing 39 genera and 27 families, were recorded for the treatment of helminthosis in animals. Most frequently used plants (>/=5 times) were Brassica campestris L. and Mallotus philippinensis (Lam.) Muell.-Arg. and most frequently used families (>/=5 times) were Brassicaceae, Euphorbiaceae and Solanaceae. Most frequently used part of the plant was leaves (n=10) followed in order by seeds (n=9), whole fruit (n=5), aerial parts and whole plant (n=4), fruit (n=3), bulb (n=2) and bark, rhizome, stem, stem plus root and twigs (n=1). Five recipes out of 49 (10.2%) contained more than one plant species and rest 44 (89.8%) contained single plant species. CONCLUSIONS: Twenty out of 41 plants (48.78%) are reported for the first time for their traditional use as anthelmintics in Pakistan. Further studies on pharmacokinetics using scientific procedures may prove these plants as promising candidates for their future use as anthelmintics.     

The nature of intrauterine adhesions following reproductive hysteroscopic surgery as determined by early and late follow-up hysteroscopy: clinical implications

Objective To evaluate the rate and characteristics of postoperative intrauterine adhesions (IUA) that might be formed following hysteroscopic reproductive surgery from both a gross and a histologic perspective as determined by early and late follow-up diagnostic hysteroscopy. Methods Retrospective analysis of 61 women wishing a pregnancy and suffering from a significant intrauterine pathology affecting their reproductive outcome were reviewed. All patients were treated hysteroscopically. Subsequently, they were randomly assigned to perform a follow-up diagnostic hysteroscopy at a variable intervals from their initial surgery. Multiple hysteroscopic-guided biopsies from IUA, when present, were obtained in several cases. Twenty patients were in the early group and had follow-up hysteroscopy performed 2–4 weeks after the initial operation. The late diagnostic group consisted of 41 patients with follow-up hysteroscopy at about 12 months (8–16 months). The two groups were similar to composition. Postoperatively, none of the early diagnostic group underwent hysterosalpingography (HSG) whereas all of the late group performed HSG 4 months following the initial surgery, which showed at least one-third of the cavity free of adhesions. When adhesions were present, no effort was made to lyse them. Results At follow-up hysteroscopy, 25% of both groups had no significant adhesions. Grade I adhesions (thin, filmy) occurred in 60% of the early hysteroscopy patients and in only 12% of the late group (P < 0.05). Grade II adhesions were present in 10% of the early group and in up to 41% in the late group (P < 0.05), whereas Grade III adhesions were present in only 5% of the early hysteroscopy group, but in 22% of the late one (P < 0.05). Correlation between hysteroscopic and histologic findings were good in most of cases in both groups. Follow-up to determine the subsequent reproductive outcome revealed similar conception rates in both groups. Conclusion The IUA that might be formed immediately following hysteroscopic reproductive surgery are histologically different from those appearing a longer time after the original operation. Routine early follow-up hysteroscopy can influence the prognosis resulting from the original surgery.     

Kiwi Omnicup versus Malmstrom metal cup in vacuum assisted delivery: a randomized comparative trial

AIM: To compare the success, clinical outcomes, and maternal and neonatal complications between the Kiwi Omnicup and the Malmstrom metal cup in vacuum assisted delivery. METHODS: This was a prospective randomized comparative trial. Women who required vacuum assisted vaginal delivery were randomized into the Kiwi Omnicup (KO) group and the Malmstrom metal cup (MM) group. The vacuum assisted deliveries were conducted according to hospital protocol. Details of the procedure and delivery outcomes including success and complications were analyzed. RESULTS: One hundred and sixty-four women were recruited - 85 were assigned to vacuum assisted delivery using the KO and 79 the MM. One hundred percent delivery success was achieved with no significant differences between the two instruments in terms of maternal morbidity (P = 0.66). Six women in the MM group sustained post delivery complications in comparison to five in the KO group. Three babies were diagnosed with birth asphyxia in each group. More babies in the MM group were admitted to the Neonatal Intensive Care Unit (NICU) (10 babies versus 5 babies) and suffered complications (14 versus 12 babies), compared to the KO group, although the difference was not statistically significant. There were no intrapartum or neonatal deaths and of those admitted to the NICU, all were discharged within a week without any serious consequences. CONCLUSION: Kiwi Omnicup is an effective alternative to the currently available Malmstrom metal cup for vacuum assisted delivery with no increase in maternal or neonatal morbidity or mortality.     

Diluted magnetic semiconductor properties in TM doped ZnO nanoparticles

The hydrothermal method was used to create dilute magnetic semiconductor nanoparticles of Zn_1−xCo_xO (x = 0, 0.01, 0.05, 0.09). The effect of cobalt doping on the microstructure, morphological and optical properties of Zn_1−xCo_xO was also studied and the Co doping to host ZnO was confirmed from XRD and EDX analysis. The structural analysis showed that doping of cobalt into ZnO decreased the crystallinity, but the preferred orientation didn''t change. SEM analysis revealed that the cobalt dopant did not have a strong influence on the shape of the synthesized nanoparticles. No defect-related absorption peaks were observed in the UV-Vis spectra. The crystallinity of the doped samples was improved by high growth temperature and long growth time. Ferromagnetic behavior above room temperature was detected in co-doped ZnO nanoparticles. The ferromagnetic behavior increased with increasing Co (up to x = 0.05) doping. The ferromagnetic behavior declined when the Co content was further increased. Related research shows that doped ZnO nanoparticles have better dielectric, electrical conductivity, and magnetic properties than pure ZnO. This high ferromagnetism is usually a response reported for dilute magnetic semiconductors. These semiconductor nanoparticles were further used to designed spintronic based applications.

The enlarged central part M–H loop shows for the Co = 0.09 doped ZnO sample, the ferromagnetic (FM) behavior increased, i.e., a M_r of 0.2412 emu g⁻¹ with a H_c of 85 Oe.     

槟榔子中抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分（英文）

目的：研究槟榔子（Areca catechu）粗提取物中所含的抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分及其作用机制。方法：使用70%甲醇水溶液对槟榔子进行粗提取。使用生物发光血小板凝集仪在富血小板血浆中测定槟榔子粗提取物的抗血小板聚集作用,使用分光光度计在试管内测定槟榔子粗提取物对乙酰胆碱酯酶活性的抑制作用。检测槟榔子中的多种化合物以测定槟榔子中抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分。结果：槟榔子粗提取物能够抑制花生四烯酸、二磷酸腺苷、血小板活化因子、肾上腺素及钙离子载体引起的血小板聚集,尤其对二磷酸腺苷及钙离子载体引起的血小板聚集的抑制最为明显;槟榔子粗提取物能够显著抑制乙酰胆碱酯酶的活性。在所检测的槟榔子所含化合物中,只有儿茶素对肾上腺素引起的血小板聚集有显著的抑制作用,而这种抑制作用显著弱于槟榔子粗提取物,提示槟榔子中的其他成分参与了这种抑制作用;鞣酸、没食子酸、薯蓣皂苷元和异去甲槟榔次碱能够抑制乙酰胆碱酯酶的活性,其中鞣酸的抑制作用强于槟榔子粗提取物。结论：槟榔子中含有抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分,而发挥这些功效的确切成分有待进一步的研究证实。