Comparative Study of Antimalarial and Other Drugs on G6PD Deficient Red Cells.

DTIC Science & Technology

33063 (1600 mg x day for 6 days) and WR 30090 (690 mg x day for 3- 6 days) demonstrated that these drugs were not hemolytic for G6PD deficient red cells...The studies concerning the effects of DFD on G6PD deficient red cells of the A- and B- variants were completed during the course of this contract...DFD is especially hemolytic even at low single dosages for G6PD deficient red cells of the B- type. The investigations on the new antimalarials WR

Vinpocetine attenuates MPTP-induced motor deficit and biochemical abnormalities in Wistar rats.

PubMed

Sharma, S; Deshmukh, R

2015-02-12

Up-regulation in phosphodiesterase 1 (PDE1) expression and decreased levels of cyclic nucleotides (cAMP and cGMP) have been reported in patients and experimental animal models of Parkinson's disease (PD). Phosphodiesterase (PDE) inhibitors have been reported to be beneficial in cognitive and motor deficit states. The present study is designed to investigate the effect of vinpocetine, a PDE1 inhibitor in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental PD-like symptoms in rats. To produce stable motor deficit, MPTP was repeatedly administered intranigrally (bilaterally) at an interval of 1 week (days 1, 7 and 14). Following development of stable motor deficit, which was observed after the third infusion of MPTP (day 14) in rats, the animals were treated with vinpocetine (5-, 10- and 20-mg/kg, i.p.) from days 15 to 28. Movement abnormalities were assessed by a battery of behavioral tests. Moreover, levels of malondialdehyde, nitrite and reduced glutathione were measured in striatal brain homogenate to confirm the role of oxidative and nitrosative stress in PD. Repeated intranigral administration of MPTP produced stable motor deficits, reduced the cyclic nucleotides and dopamine levels and caused elevation in oxidative-nitrosative stress markers. Chronic administration of vinpocetine (for 14 days) significantly and dose dependently attenuated movement disabilities and oxidative-nitrosative stress in MPTP-treated rats. Moreover, vinpocetine treatment enhances cyclic nucleotide levels and restores the dopamine level in MPTP-treated rats. The observed results of the present study are indicative of the therapeutic potential of vinpocetine in PD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

The impact of transfer from hemodialysis on peritoneal dialysis technique survival.

PubMed

Nessim, Sharon J; Bargman, Joanne M; Jassal, S Vanita; Oliver, Matthew J; Na, Yingbo; Perl, Jeffrey

2015-01-01

A significant proportion of peritoneal dialysis (PD) patients receive an initial period of hemodialysis (HD) before transitioning to PD ("PD-switch"). We sought to better understand the risks of PD technique failure (TF) and mortality for those patients compared with patients starting with PD as their first dialysis modality ("PD-first"). Using Canadian Organ Replacement Register data, we compared the risk of PD TF between PD-first and PD-switch patients within the first year after HD initiation. In a secondary analysis, the PD-switch patients were stratified into three groups based on timing of the switch from initial HD to PD as follows: 0 - 90 days, 91 - 180 days, and 181 - 365 days. Each group was compared with PD-first patients for risk of PD TF and death. Between 2001 and 2010, 9404 patients initiated PD as their first renal replacement therapy, and 3757 switched from HD to PD. After multivariable adjustment, the risk of PD TF was higher among PD-switch patients than among PD-first patients [adjusted hazard ratio (AHR): 1.37; 95% confidence interval (CI): 1.26 to 1.49], particularly within the first year after the switch from HD to PD (AHR: 1.51; 95% CI: 1.36 to 1.68). There was no association between time on HD within the first year and subsequent risk of PD TF. For all the stratified PD-switch groups, death rates were higher than those for PD-first patients. Compared with patients who start renal replacement therapy with PD, those who transfer from HD to PD within the first year on dialysis experience higher rates of PD TF and death, with the highest risk being observed in the initial year after the switch to PD. Copyright © 2015 International Society for Peritoneal Dialysis.

Timed Release of Cerebrolysin Using Drug-Loaded Titanate Nanospheres Reduces Brain Pathology and Improves Behavioral Functions in Parkinson's Disease.

PubMed

Ozkizilcik, Asya; Sharma, Aruna; Muresanu, Dafin F; Lafuente, José V; Tian, Z Ryan; Patnaik, Ranjana; Mössler, Herbert; Sharma, Hari S

2018-01-01

Previous studies from our laboratory show that intraperitoneal injections of 1-metyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP, 20 mg/kg) daily within 2-h intervals for 5 days in mice induce Parkinson's disease (PD)-like symptoms on the 8th day. A significant decrease in dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) along with a marked decrease in the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta (SNpc) and striatum (STr) confirms the validity of this model for studying PD. Since cerebrolysin (CBL) is a well-balanced composition of several neurotrophic factors and active peptide fragments, in the present investigation we examined the timed release of CBL using titanate nanospheres (TiNS) in treating PD in our mouse model. Our observations show that TiNS-CBL (in a dose of 3 ml/kg, i.v.) given after 2 days of MPTP administration for 5 days resulted in a marked increase in TH-positive cells in the SNpc and STr as compared to normal CBL. Also, TiNS-CBL resulted in significantly higher levels of DA, DOPAC, and HVA in SNpc and STr on the 8th day as compared to normal CBL therapy. TiNS-CBL also thwarted increased α-synuclein levels in the brain and in the cerebrospinal fluid (CSF) as well as neuronal nitric oxide synthase (nNOS) in the in PD brain as compared to untreated group. Behavioral function was also significantly improved in MPTP-treated animals that received TiNS-CBL. These observations are the first to demonstrate that timed release of TiNS-CBL has far more superior neuroprotective effects in PD than normal CBL.

Peritoneal dialysis technique success during the initial 90 days of therapy.

PubMed

Guest, Steven; Hayes, Andrew C; Story, Kenneth; Davis, Ira D

2012-01-01

Comparisons of technique success by peritoneal dialysis (PD) modality have typically excluded the initial 90 days of therapy. We analyzed a database of 51,469 new PD starts from 2004 to 2008 in the United States. The analysis concentrated on the initial 90 days of therapy to determine technique success and the impact of the continuous ambulatory PD (CAPD) and automated PD (APD) modalities. Overall, 13.3% of patients stopped PD within 90 days. Of patients starting directly on APD, 14.3% stopped PD within 90 days. Of patients starting on CAPD, 12.6% stopped PD within 90 days, and 63.4% changed to APD within 90 days. Only 3.3% of the latter patients failed to reach 90 days of therapy. By comparison, technique failure occurred in 28.8% of those initiating with and remaining on CAPD. We conclude that initial training to perform CAPD, with timely transfer to APD within the first 3 months, was associated with the greatest technique success at 90 days. The reasons for that success are unclear, and further research should be directed to determining factors responsible. It is possible that patients trained initially to CAPD but converted to APD have a greater understanding of the total therapy, which improves confidence. Those converted to APD may be more appreciative of the lifestyle benefits of APD, which translates into improved compliance; alternatively, technical factors associated with APD may be responsible. Those technical factors may include improved catheter function in the recumbent position during APD or the reduced infection risk associated with just 2 connect/disconnect procedures in APD compared with 8 in CAPD.

Levetiracetam attenuates rotenone-induced toxicity: A rat model of Parkinson's disease.

PubMed

Erbaş, Oytun; Yılmaz, Mustafa; Taşkıran, Dilek

2016-03-01

Levetiracetam (LEV), a second-generation anti-epileptic drug, is used for treatment of both focal and generalized epilepsy. Growing body of evidence suggests that LEV may have neuroprotective effects. The present study was undertaken to investigate the neuroprotective effects of LEV on rotenone-induced Parkinson's disease (PD) in rats. Twenty-four adult Sprague-Dawley rats were infused with rotenone (3 μg/μl in DMSO) or vehicle (1 μl DMSO) into the left substantia nigra pars compacta (SNc) under stereotaxic surgery. PD model was assessed by rotational test ten days after drug infusion. The valid PD rats were randomly distributed into two groups; Group 1 (n=8) and Group 2 (n=8) were administered saline (1 ml/kg/day, i.p.) and LEV (600 mg/kg/day, i.p.) through 21 days, respectively. The effects of LEV treatment were evaluated by behavioral (rotation score), biochemical (brain homovalinic acid level and oxidant/antioxidant status) and immunohistochemical (tyrosine hydroxylase) parameters. Apomorphine-induced rotations in PD rats were significantly suppressed by LEV treatment. While unilateral rotenone lesion induced a dramatic loss of dopaminergic neurons both in the striatum and SNc, LEV treatment significantly attenuated the degenerative changes in dopaminergic neurons. Furthermore, LEV significantly decreased lipid peroxide levels, a marker of lipid peroxidation, and induced glutathione levels, catalase and superoxide dismutase activity in PD rats compared with saline group. We conclude that LEV may have beneficial effects on dopaminergic neurons against rotenone-induced injury. The underlying mechanism may be associated with the attenuation of oxidative stress. Copyright © 2016 Elsevier B.V. All rights reserved.

MIV-150-containing intravaginal rings protect macaque vaginal explants against SHIV-RT infection.

PubMed

Ouattara, Louise A; Barnable, Patrick; Mawson, Paul; Seidor, Samantha; Zydowsky, Thomas M; Kizima, Larisa; Rodriguez, Aixa; Fernández-Romero, José A; Cooney, Michael L; Roberts, Kevin D; Gettie, Agegnehu; Blanchard, James; Robbiani, Melissa; Teleshova, Natalia

2014-05-01

Recent studies demonstrated that intravaginal rings (IVRs) containing 100 mg of the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 significantly protect macaques against a chimeric simian-human immunodeficiency virus that expresses the HIV-1 HxB2 reverse transcriptase (SHIV-RT) when present before and after vaginal challenge. The objectives of this study were to (i) evaluate the pharmacodynamics (PD) of MIV-150 in vaginal fluids (VF) and in ectocervical and vaginal tissues following 100-mg MIV-150 IVR exposure and to (ii) gain more insight whether pharmacokinetics (PK) of MIV-150 can predict PD. MIV-150 in VF collected at 1 day and 14 days post-MIV-150 IVR insertion inhibited ex vivo SHIV-RT infection in vaginal biopsy specimens from untreated animals (not carrying IVRs) in a dose-dependent manner. Previous PK studies demonstrated a significant increase of ectocervical and vaginal tissue MIV-150 concentrations 14 days versus 1 day post-IVR insertion, with the highest increase in vaginal tissue. Therefore, we tested PD of MIV-150 in tissues 14 days post-MIV-150 IVR insertion. Ex vivo SHIV-RT infection of vaginal, but not ectocervical, tissues collected 14 days post-MIV-150 IVR insertion was significantly inhibited compared to infection at the baseline (prior to MIV-150 IVR exposure). No changes in vaginal and ectocervical tissue infection were observed after placebo IVR exposure. Overall, these data underscore the use of the ex vivo macaque explant challenge models to evaluate tissue and VF PK/PD of candidate microbicides before in vivo animal efficacy studies. The data support further development of MIV-150-containing IVRs.

Repeated aripiprazole treatment causes dopamine D2 receptor up-regulation and dopamine supersensitivity in young rats

PubMed Central

Varela, Fausto A.; Der-Ghazarian, Taleen; Lee, Ryan J.; Charntikov, Sergios; Crawford, Cynthia A.; McDougall, Sanders A.

2017-01-01

Aripiprazole is a second-generation antipsychotic that is increasingly being prescribed to children and adolescents. Despite this trend, little preclinical research has been done on the neural and behavioral actions of aripiprazole during early development. In the present study, young male and female Sprague-Dawley rats were pretreated with vehicle, haloperidol (1 mg/kg), or aripiprazole (10 mg/kg) once daily on postnatal days (PD) 10–20. After one, four, or eight days (i.e., on PD 21, PD 24, or PD 28), amphetamine-induced locomotor activity and stereotypy, as well as dorsal striatal D2 receptor levels, were measured in separate groups of rats. Pretreating young rats with aripiprazole or haloperidol increased D2 binding sites in the dorsal striatum. Consistent with these results, dopamine supersensitivity was apparent when aripiprazole- and haloperidol-pretreated rats were given a test day injection of amphetamine (2 or 4 mg/kg). Increased D2 receptor levels and altered behavioral responding persisted for at least eight days after conclusion of the pretreatment regimen. Contrary to what has been reported in adults, repeated aripiprazole treatment caused D2 receptor up-regulation and persistent alterations of amphetamine-induced behavior in young rats. These findings are consistent with human clinical studies showing that children and adolescents are more prone than adults to aripiprazole-induced side-effects, including extrapyramidal symptoms. PMID:24045880

Neonatal Hyperbilirubinemia in infants with G6PD c.563C > TVariant

PubMed Central

2012-01-01

Background There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4–14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T. Methods This was a case–control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing. Results G6PD variants c.563C > T and c.131 C > G were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean ± 1SD; 0.3 ± 0.2 U/gHb vs. 14.0 ± 4.5 U/gHb, p < 0.001) experienced higher peak levels of total serum bilirubin (mean ± 1SD; 16.8 ± 5.4 mg/dl vs. 13.8 ± 4.6 mg/dl, p = 0.008) which peaked earlier after birth (mean ± 1SD 2.9 ± 1.6 vs. 4.3 ± 2.3 days, p = 0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups. Conclusions We concluded that infants with G6PD c.563C > T variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, G6PD c.563C > T carrying infants had significantly low G6PD activity. PMID:22906047

Implementation of enhanced recovery programme after pancreatoduodenectomy: a single-centre UK pilot study.

PubMed

Abu Hilal, Mohammed; Di Fabio, Francesco; Badran, Abdallah; Alsaati, Hani; Clarke, Hannah; Fecher, Imogen; Armstrong, Thomas H; Johnson, Colin D; Pearce, Neil W

2013-01-01

Data on enhanced recovery programmes after pancreatoduodenectomy (ERP-PD) is limited. The aim of this pilot study was to evaluate the feasibility, safety and clinical outcomes of ERP-PD when implemented at a high-volume UK university referral centre. This was an observational single-surgeon case-control study (before-and-after pathway). A total of 20 consecutive patients were prospectively enrolled for the ERP-PD and compared with 24 consecutive patients previously treated during an equal time frame. Patients in the ERP-PD group had a significant shorter time to remove naso-gastric tube (median of 5 vs. 7 days, p = 0.0001), start liquid diet (median of 2 vs. 5 days, p < 0.0001), start solid food (median of 4 vs. 9 days, p < 0.0001), pass stools (median of 6 vs. 7 days, p = 0.002), and had shorter length of stay (median of 8.5 days vs. 13 days, p = 0.015) compared to the pre-pathway group. Postoperative complications were overall less frequent but not significantly different in the ERP-PD group (p = 0.077). No difference in mortality and readmission rates was found. Our findings support the feasibility and safety of ERP-PD. Improved patients' outcomes, significant bed day savings and increase National Health Service productivity are anticipated with implementation of ERP-PD on a larger scale. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Investigating plasmodesmata genetics with virus-induced gene silencing and an agrobacterium-mediated GFP movement assay.

PubMed

Brunkard, Jacob O; Burch-Smith, Tessa M; Runkel, Anne M; Zambryski, Patricia

2015-01-01

Plasmodesmata (PD) are channels that connect the cytoplasm of adjacent plant cells, permitting intercellular transport and communication. PD function and formation are essential to plant growth and development, but we still know very little about the genetic pathways regulating PD transport. Here, we present a method for assaying changes in the rate of PD transport following genetic manipulation. Gene expression in leaves is modified by virus-induced gene silencing. Seven to ten days after infection with Tobacco rattle virus carrying a silencing trigger, the gene(s) of interest is silenced in newly arising leaves. In these new leaves, individual cells are then transformed with Agrobacterium to express GFP, and the rate of GFP diffusion via PD is measured. By measuring GFP diffusion both within the epidermis and between the epidermis and mesophyll, the assay can be used to study the effects of silencing a gene(s) on PD transport in general, or transport through secondary PD specifically. Plant biologists working in several fields will find this assay useful, since PD transport impacts plant physiology, development, and defense.

Prevalence of glucose-6-phosphate dehydrogenase deficiency in jaundiced Egyptian neonates.

PubMed

M Abo El Fotoh, Wafaa Moustafa; Rizk, Mohammed Soliman

2016-12-01

The enzyme, Glucose-6-phosphate dehydrogenase (G6PD), deficiency leads to impaired production of reduced glutathione and predisposes the red cells to be damaged by oxidative metabolites, causing hemolysis. Deficient neonates may manifest clinically as hyperbilirubinemia or even kernicterus. This study was carried out to detect erythrocyte G6PD deficiency in neonatal hyperbilirubinemia. To determine the frequency and effect of G6PD deficiency, this study was conducted on 202 neonates with indirect hyperbilirubinemia. All term and preterm babies up to 13 day of age admitted with clinically evident jaundice were taken for the study. G6PD activity is measured by the UV-Kinetic Method using cellular enzyme determination reagents by spectrophotometry according to manufacturer's instructions. A total of 202 babies were enrolled in this study. Male babies outnumbered the female (71.3% versus 28.7%). Mean age of the study newborns was 3.75 ± 2.5 days. Eighteen neonates (8.9%) had G6PD deficiency, all are males. One case had combined G6PD deficiency and RH incompatibility. Mean serum total bilirubin was 17.2 ± 4.4 in G6PD deficient cases. There was significant positive correlation between the time of appearance of jaundice in days and G6PD levels in G6PD deficient cases. Neonatal hyperbilirubinemia is associated with various clinical comorbidities. G6PD deficiency is found to one important cause of neonatal jaundice developing on day 2 onwards.

Immune evasion via PD-1/PD-L1 on NK cells and monocyte/macrophages is more prominent in Hodgkin lymphoma than DLBCL

PubMed Central

Vari, Frank; Arpon, David; Keane, Colm; Hertzberg, Mark S.; Talaulikar, Dipti; Jain, Sanjiv; Cui, Qingyan; Han, Erica; Tobin, Josh; Bird, Robert; Cross, Donna; Hernandez, Annette; Gould, Clare; Birch, Simone

2018-01-01

Much focus has been on the interaction of programmed cell death ligand 1 (PD-L1) on malignant B cells with programmed cell death 1 (PD-1) on effector T cells in inhibiting antilymphoma immunity. We sought to establish the contribution of natural killer (NK) cells and inhibitory CD163+ monocytes/macrophages in Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). Levels of PD-1 on NK cells were elevated in cHL relative to DLBCL. Notably, CD3−CD56hiCD16-ve NK cells had substantially higher PD-1 expression relative to CD3−CD56dimCD16+ cells and were expanded in blood and tissue, more marked in patients with cHL than patients with DLBCL. There was also a raised population of PD-L1-expressing CD163+ monocytes that was more marked in patients with cHL compared with patients with DLBCL. The phenotype of NK cells and monocytes reverted back to normal once therapy (ABVD [doxorubicin 25 mg/m2, bleomycin 10 000 IU/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2, all given days 1 and 15, repeated every 28 days] or R-CHOP [rituximab 375 mg/m2, cyclophosphamide 750 mg/m2 IV, doxorubicin 50 mg/m2 IV, vincristine 1.4 mg/m2 (2 mg maximum) IV, prednisone 100 mg/day by mouth days 1-5, pegfilgrastim 6 mg subcutaneously day 4, on a 14-day cycle]) had commenced. Tumor-associated macrophages (TAMs) expressed high levels of PD-L1/PD-L2 within diseased lymph nodes. Consistent with this, CD163/PD-L1/PD-L2 gene expression was also elevated in cHL relative to DLBCL tissues. An in vitro functional model of TAM-like monocytes suppressed activation of PD-1hi NK cells, which was reversed by PD-1 blockade. In line with these findings, depletion of circulating monocytes from the blood of pretherapy patients with cHL and patients with DLBCL enhanced CD3−CD56hiCD16-ve NK-cell activation. We describe a hitherto unrecognized immune evasion strategy mediated via skewing toward an exhausted PD-1-enriched CD3−CD56hiCD16-ve NK-cell phenotype. In addition to direct inhibition of NK cells by the malignant B cell, suppression of NK cells can occur indirectly by PD-L1/PD-L2-expressing TAMs. The mechanism is more prominent in cHL than DLBCL, which may contribute to the clinical sensitivity of cHL to PD-1 blockade. PMID:29449276

Transdermal Patch of Rotigotine Attenuates Freezing of Gait in Patients with Parkinson's Disease: An Open-Label Comparative Study of Three Non-Ergot Dopamine Receptor Agonists.

PubMed

Ikeda, Ken; Hirayama, Takehisa; Takazawa, Takanori; Kawabe, Kiyokazu; Iwasaki, Yasuo

Objective Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic neurons. Rotigotine is a non-ergot dopamine receptor agonist (DA). Its transdermal patch maintains the effective concentrations for 24 hours. Freezing of gait (FOG) is a common and devastating symptom in PD patients. Little is known about therapeutic effects of rotigotine on FOG in PD patients. Herein we compared how three non-ergot DAs of rotigotine, pramipexole LA and ropinirole CR influence FOG, besides classical motor deficits in PD patients. Methods Rotigotine (maintenance doses of 9-27 mg/day) was administered in 51 patients, 36 patients received pramipexole LA (1.5-4.5 mg/day) and 35 patients received ropinirole CR (8-16 mg/day). The Unified PD Rating Scale (UPDRS) parts I-IV, FOG questionnaire (16 items) and wearing off time were examined from baseline to 7 months after DA administration. UPDRS parts I-IV were evaluated during on time and FOG was recorded during off time if patients experienced wearing off. Results A total of 111 patients completed the study. UPDRS parts II-III scores and wearing off time were significantly reduced after each DA treatment compared to baseline. FOG was found in 54 patients (49%). Most patients developed FOG during off time only. FOG scores were significantly decreased at 2 months after rotigotine treatment whereas pramipexole LA and ropinirole treatment did not alter FOG scores. Conclusion The present study indicates that transdermal patch of rotigotine attenuated the FOG off time. The similar binding affinities to dopamine receptors between rotigotine and dopamine, and 24 hours steady hemodynamics could contribute to the therapeutic mechanism of rotigotine on FOG in PD patients with wearing off.

Transdermal Patch of Rotigotine Attenuates Freezing of Gait in Patients with Parkinson's Disease: An Open-Label Comparative Study of Three Non-Ergot Dopamine Receptor Agonists

PubMed Central

Ikeda, Ken; Hirayama, Takehisa; Takazawa, Takanori; Kawabe, Kiyokazu; Iwasaki, Yasuo

2016-01-01

Objective Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic neurons. Rotigotine is a non-ergot dopamine receptor agonist (DA). Its transdermal patch maintains the effective concentrations for 24 hours. Freezing of gait (FOG) is a common and devastating symptom in PD patients. Little is known about therapeutic effects of rotigotine on FOG in PD patients. Herein we compared how three non-ergot DAs of rotigotine, pramipexole LA and ropinirole CR influence FOG, besides classical motor deficits in PD patients. Methods Rotigotine (maintenance doses of 9-27 mg/day) was administered in 51 patients, 36 patients received pramipexole LA (1.5-4.5 mg/day) and 35 patients received ropinirole CR (8-16 mg/day). The Unified PD Rating Scale (UPDRS) parts I-IV, FOG questionnaire (16 items) and wearing off time were examined from baseline to 7 months after DA administration. UPDRS parts I-IV were evaluated during on time and FOG was recorded during off time if patients experienced wearing off. Results A total of 111 patients completed the study. UPDRS parts II-III scores and wearing off time were significantly reduced after each DA treatment compared to baseline. FOG was found in 54 patients (49%). Most patients developed FOG during off time only. FOG scores were significantly decreased at 2 months after rotigotine treatment whereas pramipexole LA and ropinirole treatment did not alter FOG scores. Conclusion The present study indicates that transdermal patch of rotigotine attenuated the FOG off time. The similar binding affinities to dopamine receptors between rotigotine and dopamine, and 24 hours steady hemodynamics could contribute to the therapeutic mechanism of rotigotine on FOG in PD patients with wearing off. PMID:27725534

Dialysate bacterial endotoxin as a prognostic indicator of peritoneal dialysis related peritonitis.

PubMed

Szeto, Cheuk-Chun; Lai, Ka-Bik; Chow, Kai-Ming; Kwan, Bonnie Ching-Ha; Law, Man-Ching; Pang, Wing-Fai; Ma, Terry King-Wing; Leung, Chi-Bon; Li, Philip Kam-Tao

2016-12-01

Peritonitis is the major complication of peritoneal dialysis (PD). The aim of our present study is to explore the prognostic value of endotoxin level in PD effluent for the prediction of treatment failure in PD-related peritonitis. We studied 325 peritonitis episodes in 223 patients. PD effluent (PDE) was collected every 5 days for endotoxin level and leukocyte count. Patients were followed for relapsing or recurrent peritonitis. We found 20 episodes (6.2%) had primary treatment failure; 41 (12.6%) developed relapsing, 19 (5.8%) had recurrent, and 22 (6.8%) had repeat episodes. Endotoxin was detectable in the PDE of 19 episodes (24.4%) caused by Gram negative organisms, 4 episodes (6.8%) of mixed bacterial growth, and none of the culture negative episodes or those by Gram positive organisms. For episodes caused by Gram negative bacteria, a detectable endotoxin level in PDE on day 5 had a sensitivity and specificity of 66.7% and 83.3%, respectively, for predicting primary treatment failure. In contrast, PDE leukocyte count > 1000 per mm3 on day 5 had a sensitivity and specificity of 88.9% and 89.1%, respectively; the addition of PDE endotoxin assay did not improve the sensitivity or specificity. We conclude that detectable endotoxin in PDE 5 days after antibiotic therapy might predict primary treatment failure in peritonitis episodes caused by Gram negative organisms. However, the sensitivity and specificity of PDE endotoxin assay was inferior to PDE leukocyte count. © 2016 Asian Pacific Society of Nephrology.

Eyeblink conditioning in the developing rabbit

PubMed Central

Brown, Kevin L.; Woodruff-Pak, Diana S.

2011-01-01

Eyeblink classical conditioning in pre-weanling rabbits was examined in the present study. Using a custom lightweight headpiece and restrainer, New Zealand white littermates were trained once daily in 400 ms delay eyeblink classical conditioning from postnatal days (PD) 17–21 or PD 24–28. These ages were chosen because eyeblink conditioning emerges gradually over PD 17–24 in rats (Stanton, Freeman, & Skelton, 1992), another altricial species with neurodevelopmental features similar to those of rabbits. Consistent with well-established findings in rats, rabbits trained from PD 24–28 showed greater conditioning relative to littermates trained from PD 17–21. Both age groups displayed poor retention of eyeblink conditioning at retraining one month after acquisition. These findings are the first to demonstrate eyeblink conditioning in the developing rabbit. With further characterization of optimal conditioning parameters, this preparation may have applications to neurodevelopmental disease models as well as research exploring the ontogeny of memory. PMID:21953433

Effects of virtual reality training on mobility in individuals with Parkinson's disease.

PubMed

Melo, G; Kleiner, A F R; Lopes, J; Zen, G Z D; Marson, N; Santos, T; Dumont, A; Galli, M; Oliveira, C

2018-06-19

The aim of the present study was to evaluate the effects of gait training with virtual reality (VR) on mobility in patients with Parkinson's disease (PD). Thirty-seven individuals with PD were allocated to three groups (control = 12, VR = 12 and treadmill = 13) submitted to 12 twenty-minute training sessions. Evaluations involved the Timed Up and Go (TUG) test before the intervention, after one session, after all 12 sessions and 30 days after the end of the intervention. The groups submitted to VR and treadmill training took less time to execute the TUG test than the control group. Individuals with PD submitted to VR and treadmill gait training presented mobility improvements in comparison to traditional physiotherapeutic training. Copyright © 2018. Published by Elsevier B.V.

KSC-02pd1653

NASA Image and Video Library

2002-10-23

KENNEDY SPACE CENTER, FLA. -- KSC employees look over a race car on display during Spaceport Super Safety & Health Day. Dozens of presentations and exhibits across the Center focused attention on safety at work and home.

Describing Ovarian Cycles, Pregnancy Characteristics, and the Use of Contraception in Female White-faced Marmosets, Callithrix geoffroyi

PubMed Central

MUSTOE, AARYN C.; JENSEN, HEATHER A.; FRENCH, JEFFREY A.

2012-01-01

Endocrine data and characteristics of nonconceptive ovarian cycling and pregnancy are limited within the genus Callithrix to the common marmoset (C. jacchus) and Wied's black tufted-ear marmoset (C. kuhlii). This paper presents patterns of urinary pregnandiol-3-glucuronide (PdG) excretion, as determined by enzyme immunoassay, throughout the course of ovarian cycling and pregnancy in white-faced marmosets (C. geoffroyi). Furthermore, characteristics of reproductive parameters including litter size, duration of gestation, maternal age, and information about ovarian cycling following administration of contraceptives are also described. A steep increase in PdG, an indication of ovulation, characterizes normative ovarian cycles, with peak-to-peak intervals between cycles being 27.82 ± 1.49 days in length. PdG excretion (μg/mg Cr) across pregnancy peaked during the 1st and 2nd trimesters (1st = 20.71 ± 2.98, 2nd = 21.16 ± 2.60) and declined gradually to near preconception levels over the 3rd trimester until parturition (3rd = 5.74 ± 1.60). Gestation lasted 148.55 ± 1.89 days. Most pregnancies (82.8%) resulted in an immediate postpartum ovulation (PPO) of 17.45 ± 2.22 days with 58.3% of PPOs resulting in conception. No differences in PdG excretion during the 1st trimester between full pregnancies and miscarriages were found, and pregnancy characteristics such as litter size, duration of gestation, and maternal age were not associated with PdG concentrations. Administration of cloprostenol resulted in shorter cycle durations, but ovulation was detectable with similar concentrations of peak PdG to a normal non-conceptive cycle. Conversely, medroxyprogesterone acetate (DMPA) injections resulted in little to no PdG excretion across the ovarian cycle, with both methods of contraception providing effective prevention of conception. Overall, these results show that strong similarities in reproductive parameters persist within the genus Callithrix and to a lesser extent across the Callitrichidae family. PMID:22865351

Validation of a Behavioral Approach for Measuring Saccades in Parkinson's Disease.

PubMed

Turner, Travis H; Renfroe, Jenna B; Duppstadt-Delambo, Amy; Hinson, Vanessa K

2017-01-01

Speed and control of saccades are related to disease progression and cognitive functioning in Parkinson's disease (PD). Traditional eye-tracking complexities encumber application for individual evaluations and clinical trials. The authors examined psychometric properties of standalone tasks for reflexive prosaccade latency, volitional saccade initiation, and saccade inhibition (antisaccade) in a heterogeneous sample of 65 PD patients. Demographics had minimal impact on task performance. Thirty-day test-retest reliability estimates for behavioral tasks were acceptable and similar to traditional eye tracking. Behavioral tasks demonstrated concurrent validity with traditional eye-tracking measures; discriminant validity was less clear. Saccade initiation and inhibition discriminated PD patients with cognitive impairment. The present findings support further development and use of the behavioral tasks for assessing latency and control of saccades in PD.

Tracking Parkinson's: Study Design and Baseline Patient Data.

PubMed

Malek, Naveed; Swallow, Diane M A; Grosset, Katherine A; Lawton, Michael A; Marrinan, Sarah L; Lehn, Alexander C; Bresner, Catherine; Bajaj, Nin; Barker, Roger A; Ben-Shlomo, Yoav; Burn, David J; Foltynie, Thomas; Hardy, John; Morris, Huw R; Williams, Nigel M; Wood, Nicholas; Grosset, Donald G

2015-01-01

There is wide variation in the phenotypic expression of Parkinson's disease (PD), which is driven by both genetic and epidemiological influences. To define and explain variation in the clinical phenotype of PD, in relation to genotypic variation. Tracking Parkinson's is a multicentre prospective longitudinal epidemiologic and biomarker study of PD. Patients attending specialist clinics in the United Kingdom with recent onset (<3.5 years) and young onset (diagnosed <50 years of age) PD were enrolled. Motor, non-motor and quality of life assessments were performed using validated scales. Cases are followed up 6 monthly up to 4.5 years for recent onset PD, and up to 1 year for young onset PD. We present here baseline clinical data from this large and demographically representative cohort. 2247 PD cases were recruited (1987 recent onset, 260 young onset). Recent onset cases had a mean (standard deviation, SD) age of 67.6 years (9.3) at study entry, 65.7% males, with disease duration 1.3 years (0.9), MDS-UPDRS 3 scores 22.9 (12.3), LEDD 295 mg/day (211) and PDQ-8 score 5.9 (4.8). Young onset cases were 53.5 years old (7.8) at study entry, 66.9% male, with disease duration 10.2 years (6.7), MDS-UPDRS 3 scores 27.4 (15.3), LEDD 926 mg/day (567) and PDQ-8 score 11.6 (6.1). We have established a large clinical PD cohort, consisting of young onset and recent onset cases, which is designed to evaluate variation in clinical expression, in relation to genetic influences, and which offers a platform for future imaging and biomarker research.

Analysis of PD-1 expression in the monocyte subsets from non-septic and septic preterm neonates

PubMed Central

Lenart, Marzena; Rutkowska-Zapała, Magdalena; Stec, Małgorzata; Durlak, Wojciech; Grudzień, Andrzej; Krzeczkowska, Agnieszka; Mól, Nina; Pilch, Marta; Siedlar, Maciej; Kwinta, Przemko

2017-01-01

Programmed death-1 (PD-1) receptor system represents a part of recently reported immunoregulatory pathway. PD-1 is an immune checkpoint molecule, which plays an important role in downregulating the immune system proinflammatory activity. Until recently, PD-1 expression was not established on immune cells of the preterm infants. The study objectives were to confirm expression of the PD-1 receptors on the monocytes isolated from very low birth weight newborns (VLBW), and to analyze their expression during the first week of life and late-onset sepsis. Peripheral blood mononuclear cells were isolated from 76 VLBW patients without early-onset sepsis on their 5th day of life (DOL). PD-1 expression was determined on the monocyte subsets (classical, intermediate, non-classical) by flow cytometry. In case of late-onset sepsis (LOS), the same analysis was performed. Our results demonstrated that on the 5th DOL, PD-1 receptors were present in all the monocyte subsets. Children, whose mothers had received antenatal steroids, presented higher absolute numbers of non-classical monocytes with PD-1 expression. Infants born extremely preterm who later developed LOS, initially showed a lower percentage of PD-1 receptor-positive intermediate monocytes in comparison to neonates born very preterm. During LOS, we observed a rise in the percentage of classical monocytes with PD-1 expression. In case of septic shock or fatal outcome, there was a higher percentage and absolute count of intermediate monocytes with PD-1 expression in comparison to children without these complications. In conclusion, monocytes from VLBW children express PD-1 receptors. Antenatal steroid administration seems to induce PD-1 receptor expression in the non-classical monocytes. PD-1 might play a role in immunosuppressive phase of sepsis in the prematurely born children with septic shock and fatal outcome. PMID:29049359

Design innovations and baseline findings in a long-term Parkinson's trial: the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease Long-Term Study-1.

PubMed

Elm, Jordan J

2012-10-01

Based on the preclinical data and the results of a phase II futility study, creatine was selected for an efficacy trial in Parkinson's disease (PD). We present the design rationale and a description of the study cohort at baseline. A randomized, multicenter, double-blind, parallel-group, placebo-controlled phase III study of creatine (10 g daily) in participants with early, treated PD, the Long-term Study-1 (LS-1), is being conducted by the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease network. The study utilizes a global statistical test (GST) encompassing five clinical rating scales to provide a multidimensional assessment of disease progression. A total of 1,741 PD participants from 45 sites in the United States and Canada were randomized 1:1 to either 10 g of creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10 g/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5-year follow-up visit against the background of dopaminergic therapy and best PD care. Copyright © 2012 Movement Disorder Society.

High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency.

PubMed

Fanello, Caterina I; Karema, Corine; Avellino, Pamela; Bancone, Germana; Uwimana, Aline; Lee, Sue J; d'Alessandro, Umberto; Modiano, David

2008-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited human enzyme defect. This deficiency provides some protection from clinical malaria, but it can also cause haemolysis after administration of drugs with oxidant properties. The safety of chlorproguanil-dapsone+artesunate (CD+A) and amodiaquine+sulphadoxine-pyrimethamine (AQ+SP) for the treatment of uncomplicated P. falciparum malaria was evaluated according to G6PD deficiency in a secondary analysis of an open-label, randomized clinical trial. 702 children, treated with CD+A or AQ+SP and followed for 28 days after treatment were genotyped for G6PD A- deficiency. In the first 4 days following CD+A treatment, mean haematocrit declined on average 1.94% (95% CI 1.54 to 2.33) and 1.05% per day (95% CI 0.95 to 1.15) respectively in patients with G6PD deficiency and normal patients; a mean reduction of 1.3% per day was observed among patients who received AQ+SP regardless of G6PD status (95% CI 1.25 to 1.45). Patients with G6PD deficiency recipients of CD+A had significantly lower haematocrit than the other groups until day 7 (p = 0.04). In total, 10 patients had severe post-treatment haemolysis requiring blood transfusion. Patients with G6PD deficiency showed a higher risk of severe anaemia following treatment with CD+A (RR = 10.2; 95% CI 1.8 to 59.3) or AQ+SP (RR = 5.6; 95% CI 1.0 to 32.7). CD+A showed a poor safety profile in individuals with G6PD deficiency most likely as a result of dapsone induced haemolysis. Screening for G6PD deficiency before drug administration of potentially pro-oxidants drugs, like dapsone-containing combinations, although seldom available, is necessary.

The risk stratification and prognostic evaluation of soluble programmed death-1 on patients with sepsis in emergency department.

PubMed

Zhao, Yongzhen; Jia, Yumei; Li, Chunsheng; Fang, Yingying; Shao, Rui

2018-01-01

To evaluate the efficacy of soluble programmed death-1 (sPD-1) for risk stratification and prediction of 28-day mortality in patients with sepsis, we compared serum sPD-1 with procalcitonin (PCT), C-reactive protein (CRP), and the Mortality in Emergency Department Sepsis (MEDS) score. A total of 60 healthy volunteers and 595 emergency department (ED) patients were recruited for this prospective cohort study. According to the severity of their condition on ED arrival, the patients were allocated to the systemic inflammatory response syndrome group (130 cases), sepsis group (276 cases), severe sepsis group (121 cases), and septic shock group (68 cases). In addition, all patients with sepsis were also divided into the survivor group (349 cases) and nonsurvivor group (116 cases) according to the 28-day outcomes. When the severity of sepsis increased, the levels of sPD-1 gradually increased. The levels of sPD-1, PCT, CRP and the MEDS score were also higher in the nonsurvivor group compared to the survivor group. Logistic regression suggested that sPD-1, PCT, and the MEDS score were independent risk factors for 28-day mortality of patients with sepsis. Area under the curve (AUC) of sPD-1, PCT and the MEDS score for 28-day mortality was 0.725, 0.693, and 0.767, respectively, and the AUC was improved when all 3 factors were combined (0.843). Serum sPD-1 is positively correlated with the severity of sepsis, and it is valuable for risk stratification of patients and prediction of 28-day mortality. Combining sPD-1 with PCT and the MEDS score improves the prognostic evaluation. Copyright © 2017 Elsevier Inc. All rights reserved.

Association of postdischarge complications with reoperation and mortality in general surgery.

PubMed

Kazaure, Hadiza S; Roman, Sanziana A; Sosa, Julie A

2012-11-01

To describe procedure-specific types, rates, and risk factors for postdischarge (PD) complications occurring within 30 days after 21 groups of inpatient general surgery procedures. Retrospective cohort study. American College of Surgeons National Surgical Quality Improvement Program 2005 through 2010 Participant Use Data Files. A total of 551,510 adult patients who underwent one of 21 groups of general surgery procedures in the inpatient setting. Postdischarge complications, reoperation, and mortality. Of 551,510 patients (mean age, 54.6 years), 16.7% experienced a complication; 41.5% occurred PD. Of the PD complications, 75.0% occurred within 14 days PD. Proctectomy (14.5%), enteric fistula repair (12.6%), and pancreatic procedures (11.4%) had the highest PD complication rates. Breast, bariatric, and ventral hernia repair procedures had the highest proportions of complications that occurred PD (78.7%, 69.4%, and 62.0%, respectively). For all procedures, surgical site complications, infections, and thromboembolic events were the most common. Occurrence of an inpatient complication increased the likelihood of a PD complication (12.5% vs 6.2% without an inpatient complication; P < .001). Compared with patients without a PD complication, those with a PD complication had higher rates of reoperation (4.6% vs 17.9%, respectively; P < .001) and death (2.0% vs 6.9%, respectively; P < .001) within 30 days after surgery; those whose PD complication was preceded by an inpatient complication had the highest rates of reoperation (33.7%) and death (24.7%) (all P < .001). After adjustment, PD complications were associated with procedure type, American Society of Anesthesiologists class higher than 3, and steroid use. The PD complication rates vary by procedure, are commonly surgical site related, and are associated with mortality. Fastidious, procedure-specific patient triage at discharge as well as expedited patient follow-up could improve PD outcomes.

G6PD Deficiency and Antimalarial Efficacy for Uncomplicated Malaria in Bangladesh: A Prospective Observational Study.

PubMed

Ley, Benedikt; Alam, Mohammad Shafiul; Thriemer, Kamala; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Auburn, Sarah; Poirot, Eugenie; Price, Ric N; Khan, Wasif Ali

2016-01-01

The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy. Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0-2) plus single dose primaquine (0.75mg/kg on day2) for P. falciparum infections, or with chloroquine (days 0-2) plus 14 days primaquine (3.5mg/kg total over 14 days) for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374). Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections). Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2-27.3) hours for P. falciparum, 20.0 (IQR: 9.5-22.7) hours for P. vivax and 16.6 (IQR: 10.0-46.0) hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174) had severe G6PD deficiency (<10% activity), five participants (5/174) had mild G6PD deficiency (10-60% activity). The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0%) and -7.4% (95%CI: -4.5 to -10.4%) respectively. The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal individuals was attributable to acute malaria rather than primaquine administration. ClinicalTrials.gov NCT02389374.

Safety of primaquine given to people with G6PD deficiency: systematic review of prospective studies.

PubMed

Uthman, Olalekan A; Graves, Patricia M; Saunders, Rachel; Gelband, Hellen; Richardson, Marty; Garner, Paul

2017-08-22

Haemolysis risk with single dose or short course primaquine was evaluated in glucose-6-phosphate dehydrogenase (G6PD) deficient people. Major electronic databases (to August 2016) were searched for single or short course 8-aminoquinolines (8-AQ) in (1) randomized comparisons against placebo in G6PD deficient people; and (2) observational comparisons in G6PD deficient compared to replete people. Two authors independently assessed eligibility, risk-of-bias, and extracted data. Five randomized controlled trials and four controlled observational cohorts were included. In G6PD deficient individuals, high-dose (0.75 mg/kg) PQ resulted in lower average haemoglobin levels at 7 days (mean difference [MD] -1.45 g/dl, 95% CI -2.17 to -0.74, 2 trials) and larger percentage fall from baseline to day 7 (MD -10.31%, 95% CI -17.69 to -2.92, 3 trials) compared to placebo. In G6PD deficient compared to replete people, average haemoglobin was lower at 7 days (MD -1.19 g/dl, 95% CI -1.94 to -0.44, 2 trials) and haemoglobin change from baseline to day 7 was greater (MD -9.10%, 95% CI -12.55 to -5.65, 5 trials). One small trial evaluated mid-range PQ dose (0.4-0.5 mg/kg) in G6PD deficient people, with no difference detected in average haemoglobin at day 7 compared to placebo. In one cohort comparing G6PD deficient and replete people there was a greater fall with G6PD deficiency (MD -4.99%, 95% CI -9.96 to -0.02). For low-dose PQ (0.1-0.25 mg/kg) in G6PD deficient people, haemoglobin change from baseline was similar to the placebo group (MD 1.72%, 95% CI -1.89 to 5.34, 2 trials). Comparing low dose PQ in G6PD deficient with replete people, the average haemoglobin was lower in the G6PD deficient group at 7 days (-0.57 g (95% CI -0.97 to -0.17, 1 trial)); although change from baseline was similar (MD -1.45%, 95% CI -5.69 to 2.78, 3 trials). Falls in average haemoglobin are less marked with the 0.1 to 0.25 mg/kg PQ than with the 0.75 mg/kg dose, and severe haemolytic events are not common. However, data were limited and the evidence GRADE was low or very low certainty.

Suppression of muscle protein turnover and amino acid degradation by dietary protein deficiency

NASA Technical Reports Server (NTRS)

Tawa, N. E. Jr; Goldberg, A. L.

1992-01-01

To define the adaptations that conserve amino acids and muscle protein when dietary protein intake is inadequate, rats (60-70 g final wt) were fed a normal or protein-deficient (PD) diet (18 or 1% lactalbumin), and their muscles were studied in vitro. After 7 days on the PD diet, both protein degradation and synthesis fell 30-40% in skeletal muscles and atria. This fall in proteolysis did not result from reduced amino acid supply to the muscle and preceded any clear decrease in plasma amino acids. Oxidation of branched-chain amino acids, glutamine and alanine synthesis, and uptake of alpha-aminoisobutyrate also fell by 30-50% in muscles and adipose tissue of PD rats. After 1 day on the PD diet, muscle protein synthesis and amino acid uptake decreased by 25-40%, and after 3 days proteolysis and leucine oxidation fell 30-45%. Upon refeeding with the normal diet, protein synthesis also rose more rapidly (+30% by 1 day) than proteolysis, which increased significantly after 3 days (+60%). These different time courses suggest distinct endocrine signals for these responses. The high rate of protein synthesis and low rate of proteolysis during the first 3 days of refeeding a normal diet to PD rats contributes to the rapid weight gain ("catch-up growth") of such animals.

Comparison of GT3X accelerometer and YAMAX pedometer steps/day in a free-living sample of overweight and obese adults.

PubMed

Barriera, Tiago V; Tudor-Locke, Catrine; Champagne, Catherine M; Broyles, Stephanie T; Johnson, William D; Katzmarzyk, Peter T

2013-02-01

The purpose of this study was to compare steps/day detected by the YAMAX SW-200 pedometer versus the Actigraph GT3X accelerometer in free-living adults. Daily YAMAX and GT3X steps were collected from a sample of 23 overweight and obese participants (78% female; age = 52.6 ± 8.4 yr.; BMI = 31.0 ± 3.7 m·kg-2). Because a pedometer is more likely to be used in a community-based intervention program, it was used as the standard for comparison. Percent difference (PD) and absolute percent difference (APD) were calculated to examine between-instrument agreement. In addition, days were categorized based on PD: a) under-counting (> -10 PD), b) acceptable counting (-10 to 10 PD), and c) over-counting (> 10 PD). The YAMAX and GT3X detected 8,025 ± 3,967 and 7131 ± 3066 steps/day, respectively, and the outputs were highly correlated (r = .87). Average PD was -3.1% ± 30.7% and average APD was 23.9% ± 19.4%. Relative to the YAMAX, 53% of the days detected by the GT3X were classified as under-counting, 25% acceptable counting, and 23% over-counting. Although the output of these 2 instruments is highly correlated, caution is advised when directly comparing or using their output interchangeably.

Dialysis Modality and Readmission Following Hospital Discharge: A Population-Based Cohort Study.

PubMed

Perl, Jeffrey; McArthur, Eric; Bell, Chaim; Garg, Amit X; Bargman, Joanne M; Chan, Christopher T; Harel, Shai; Li, Lihua; Jain, Arsh K; Nash, Danielle M; Harel, Ziv

2017-07-01

Readmissions following hospital discharge among maintenance dialysis patients are common, potentially modifiable, and costly. Compared with patients receiving in-center hemodialysis (HD), patients receiving peritoneal dialysis (PD) have fewer routine dialysis clinic encounters and as a result may be more susceptible to a hospital readmission following discharge. Population-based retrospective-cohort observational study. Patients treated with maintenance dialysis who were discharged following an acute-care hospitalization during January 1, 2003, to December 31, 2013, across 164 acute-care hospitals in Ontario, Canada. For those with multiple hospitalizations, we randomly selected a single hospitalization as the index hospitalization. Dialysis modality PD or in-center HD. Propensity scores were used to match each patient on PD therapy to 2 patients on in-center HD therapy to ensure that baseline indicators of health were similar between the 2 groups. All-cause 30-day readmission following the index hospital discharge. 28,026 dialysis patients were included in the study. 4,013 PD patients were matched to 8,026 in-center HD patients. Among the matched cohort, 30-day readmission rates were 7.1 (95% CI, 6.6-7.6) per 1,000 person-days for patients on PD therapy and 6.0 (95% CI, 5.7-6.3) per 1,000 person-days for patients on in-center HD therapy. The risk for a 30-day readmission among patients on PD therapy was higher compared with those on in-center HD therapy (adjusted HR, 1.19; 95% CI, 1.08-1.31). The primary results were consistent across several key prespecified subgroups. Lack of information for the frequency of nephrology physician encounters following discharge from the hospital in both the PD and in-center HD cohorts. Limited validation of International Classification of Diseases, Tenth Revision codes. The risk for 30-day readmission is higher for patients on home-based PD compared to in-center HD therapy. Interventions to improve transitions in care between the inpatient and outpatient settings are needed, particularly for patients on PD therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of frequency, risk factors, and time course of postoperative delirium in octogenarians after transcatheter aortic valve implantation versus surgical aortic valve replacement.

PubMed

Eide, Leslie S P; Ranhoff, Anette H; Fridlund, Bengt; Haaverstad, Rune; Hufthammer, Karl Ove; Kuiper, Karel K J; Nordrehaug, Jan Erik; Norekvål, Tone M

2015-03-15

Postoperative delirium (PD) after transcatheter aortic valve implantation (TAVI) remains to be explored. We sought to (1) determine the incidence of PD in octogenarians who underwent TAVI or surgical aortic valve replacement (SAVR), (2) identify its risk factors, and (3) describe possible differences in the onset and course of PD between treatment groups. A prospective cohort study of consecutive patients aged ≥80 years with severe aortic stenosis who underwent elective TAVI or SAVR (N = 143) was conducted. The incidence of PD was assessed for 5 days using the Confusion Assessment Method (CAM). Risk factors for PD were studied with logistic regression. Patients treated with TAVI were older (p ≤0.001), had lower cognitive scores (p = 0.007), and more co-morbidities (p = 0.003). Despite this, significantly fewer (p = 0.013) patients treated with TAVI (44%) experienced PD compared to patients treated with SAVR (66%). Undergoing SAVR (p = 0.02) and having lower cognitive function (p = 0.03) emerged as risk factors for PD, whereas gender, activities of daily living, frailty, atrial fibrillation, and postoperative use of opioids and anxiolytics did not. Patients treated with TAVI and without PD during the first 2 postoperative days were unlikely to experience PD on subsequent days. The onset of PD after SAVR could occur at any time during the postoperative evaluation. In conclusion, SAVR in octogenarian patients with aortic stenosis might be considered as a predisposing factor for PD. Our data also suggest that the onset of PD was more unpredictable after SAVR. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali.

PubMed

Kone, Abdoulaye K; Sagara, Issaka; Thera, Mahamadou A; Dicko, Alassane; Guindo, Aldiouma; Diakite, Seidina; Kurantsin-Mills, Joseph; Djimde, Abdoulaye; Walcourt, Asikiya; Doumbo, Ogabara

2010-11-21

Artemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group. Blood samples from children and adults participants (1 to 70 years old) with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem®) or artesunate plus mefloquine (Artequin™). A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A-) allele of the gene mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene. The DNA amplified from 315 samples using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%). The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median parasitaemia and other baseline characteristics (mean haemoglobin, sex and age groups) between G6PD deficiency (hemizygous, heterozygous, and homozygous) and G6PD-normal participants were comparable (p > 0.05). After treatment, parasite clearance did not change significantly whether the participants were G6PD deficient or G6PD normal on day 1 (OR = 1.3; CI = 0.70-2.47; p > 0.05) and on day 2 (OR = 0.859; CI = 0.097-7.61; p > 0.05). The presence of G6PD deficiency does not appear to significantly influence the clearance of P. falciparum in the treatment of uncomplicated malaria using ACT.

Monitoring of ovarian activity by measurement of urinary excretion rates using the Ovarian Monitor, Part IV: the relationship of the pregnanediol glucuronide threshold to basal body temperature and cervical mucus as markers for the beginning of the post-ovulatory infertile period.

PubMed

Blackwell, Leonard F; Vigil, Pilar; Alliende, María Elena; Brown, Simon; Festin, Mario; Cooke, Delwyn G

2016-02-01

Do the basal body temperature (BBT) shift and the cervical mucus markers for the beginning of the post-ovulatory infertile phase (POIP) of a menstrual cycle agree with the corresponding urinary pregnanediol glucuronide (PdG) threshold value? Perfect agreement between the cervical mucus markers and BBT shift and the hormonal definition of the start of post-ovulatory infertility occurred for only 7-17% of the cycles. The PdG threshold of 7.0 µmol/24 h is an objective and accurate marker for the beginning of the POIP. The rise in serum progesterone also produces the BBT shift and changes in cervical mucus which determine the mucus peak. Serum progesterone and urinary PdG are closely correlated when variations in urine volume are taken into account. Individual menstrual cycle profiles of urinary PdG excretion rates for 91 fertile cycles from normally cycling women were analysed to identify the day of the beginning of the POIP. These days were compared with those determined by the day of the BBT shift +2 days, the day of the mucus peak +4 days and the later of these two indicators. The study lasted 3 years. A total of 62 women with normal menstrual cycles were recruited from three centres: Palmerston North, New Zealand; Sydney, Australia and Santiago, Chile. The cycles were displayed individually in a proprietary database program which recorded the PdG excretion rates, the BBT shift day and the cervical mucus peak day. A group of 15 women from a separate Chilean study had PdG urinary data measured as well as their day of ovulation determined by ultrasound. The BBT and cervical mucus markers differed significantly in their identification of the beginning of the POIP when compared with the PdG excretion rate of 7.0 µmol/24 h. The observation that the BBT shift day and the mucus peak day could be identified even though the PdG excretion rates were still at baseline levels in some cycles could lead to an unexpected pregnancy for women using these natural family planning (NFP) indicators. The study consisted only of fertile cycles from women with regular cycles of 20-40 days duration. All the women were intending to avoid a pregnancy during the study, thus the limits of the fertile window were not tested. The NFP signals occurring earlier than the PdG threshold day could lead to an unexpected pregnancy. The signals occurring on the same day or later than the PdG threshold would not lead to unexpected pregnancies, but would require extra abstinence that could lead to non-compliance with the NFP method. A possible improvement in reliability of NFP methods is suggested. This study (project #90905) was funded by the NDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. currently works for a diagnostic development company, Science Haven Ltd. The other authors have nothing to declare. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat

PubMed Central

Bruder, Eric D.; Taylor, Jennifer K.; Kamer, Kimberli J.; Raff, Hershel

2008-01-01

Acute episodes of severe hypoxia are among the most common stressors in neonates. An understanding of the development of the physiological response to acute hypoxia will help improve clinical interventions. The present study measured ACTH and corticosterone responses to acute, severe hypoxia (8% inspired O2 for 4 h) in neonatal rats at postnatal days (PD) 2, 5, and 8. Expression of specific hypothalamic, anterior pituitary, and adrenocortical mRNAs was assessed by real-time PCR, and expression of specific proteins in isolated adrenal mitochondria from adrenal zona fascisulata/reticularis was assessed by immunoblot analyses. Oxygen saturation, heart rate, and body temperature were also measured. Exposure to 8% O2 for as little as 1 h elicited an increase in plasma corticosterone in all age groups studied, with PD2 pups showing the greatest response (∼3 times greater than PD8 pups). Interestingly, the ACTH response to hypoxia was absent in PD2 pups, while plasma ACTH nearly tripled in PD8 pups. Analysis of adrenal mRNA expression revealed a hypoxia-induced increase in Ldlr mRNA at PD2, while both Ldlr and Star mRNA were increased at PD8. Acute hypoxia decreased arterial O2 saturation (SPo2) to ∼80% and also decreased body temperature by 5–6°C. The hypoxic thermal response may contribute to the ACTH and corticosterone response to decreases in oxygen. The present data describe a developmentally regulated, differential corticosterone response to acute hypoxia, shifting from ACTH independence in early life (PD2) to ACTH dependence less than 1 wk later (PD8). PMID:18703410

Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial.

PubMed

Goetz, Christopher G; Damier, Philippe; Hicking, Christine; Laska, Eugene; Müller, Thomas; Olanow, C Warren; Rascol, Olivier; Russ, Hermann

2007-01-15

The objective of this study is to conduct a dose-finding study of sarizotan in Parkinson's disease (PD) patients with dyskinesia to identify a safe dose and to identify a sensitive dyskinesia rating measure. Sarizotan is a novel compound with full 5-HT(1A) agonist properties and additional high affinity for D(3) and D(4) receptors. An open label study documented improvements in PD patients with levodopa-induced dyskinesia. There is no precedent for study designs or outcome measures in pivotal trials of antidyskinesia therapies. The approach used here was a multicenter, randomized, placebo-controlled, double-blind, parallel study. Included were PD patients optimized to levodopa and dopaminergic drugs with moderately disabling dyskinesias present greater than or equal to 25% of the waking day. Interventions included sarizotan 2, 4, or 10 mg/day or matching placebo, given in two doses. There were two outcome measures: the primary measure was change from baseline in diary-based on time without dyskinesia; the secondary measures were change from baseline in scores on the Abnormal Involuntary Movement Scale (AIMS), the composite score of Unified Parkinson's Disease Rating Scale (UPDRS) Items 32+33 (dyskinesia duration and disability) and total UPDRS. A total of 398 subjects were randomized, with 381 included in the intention-to-treat population. No significant changes occurred on sarizotan compared to placebo on any diary-based measure of dyskinesia or the AIMS score. The composite score of UPDRS Items 32+33 was significantly improved with 2 mg/day sarizotan, with a trend at 10 mg/day. Adverse events were not significantly different in sarizotan- and placebo-treated patients, but off time significantly increased with sarizotan 10 mg/day. Sarizotan 2 mg/day is a safe agent in PD patients with dyskinesia. To test its role in abating dyskinesia, future studies should focus on this dose and will use the composite score of UPDRS Items 32+33 as the primary outcome. (c) 2006 Movement Disorder Society.

Ceftriaxone prevents the neurodegeneration and decreased neurogenesis seen in a Parkinson's disease rat model: An immunohistochemical and MRI study.

PubMed

Weng, Jun-Cheng; Tikhonova, Maria A; Chen, Jian-Horng; Shen, Mei-Shiuan; Meng, Wan-Yun; Chang, Yen-Ting; Chen, Ke-Hsin; Liang, Keng-Chen; Hung, Ching-Sui; Amstislavskaya, Tamara G; Ho, Ying-Jui

2016-05-15

Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique for detecting neuronal activity in the brain of a living animal. Ceftriaxone (CEF) has been shown to have neuroprotective effects in neurodegenerative diseases. The present study was aimed at clarifying whether, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) rat model, the known CEF-induced neuronal protection was accompanied by neurogenesis and decreased loss of neuronal activity. After MPTP lesioning (day 0), the rats were treated with CEF (100mg/kg/day, i.p.) or saline for 15 days. They were then injected with MnCl2 (40mg/kg, i.p.) on day 13 and underwent a brain MRI scan on day 14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased neuronal activity and density in the nigrostriatal dopaminergic (DAergic) system and the hippocampal CA1, CA3, and dentate gyrus (DG) areas and reduced neurogenesis in the DG, but in hyperactivity in the subthalamic nucleus (STN). These neuronal changes were prevented by CEF treatment. Positive correlations between MEMRI R1 values and neuronal density in the hippocampus were evidenced. Neuronal densities in the hippocampus and SNc were positively correlated. In addition, the R1 value of the STN showed a positive correlation with its neuronal activity but showed a negative correlation with the density of DAergic neurons in the SNc. Therefore, MEMRI R1 value may serve as a good indicator for PD severity and the effect of treatment. To our knowledge, this is the first study showing that CEF prevents loss of neuronal activity and neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD. Copyright © 2016 Elsevier B.V. All rights reserved.

Ceftriaxone reverses deficits of behavior and neurogenesis in an MPTP-induced rat model of Parkinson's disease dementia.

PubMed

Hsieh, Ming-Hong; Meng, Wan-Yun; Liao, Wen-Chieh; Weng, Jun-Cheng; Li, Hsin-Hua; Su, Hong-Lin; Lin, Chih-Li; Hung, Ching-Sui; Ho, Ying-Jui

2017-06-01

Hyperactivity of the glutamatergic system is involved in excitotoxicity and neurodegeneration in Parkinson's disease (PD) so that glutamatergic modulation maybe a potential therapeutic target for PD. Ceftriaxone (CEF) has been reported to increase glutamate uptake by increasing glutamate transporter expression and has been demonstrated neuroprotective effects in animal study. The aim of this study was to determine the effects of CEF on behavior and neurogenesis in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. MPTP was stereotaxically injected into the substantia nigra pars compacta (SNc) of male Wistar rats. Starting on the same day after MPTP lesioning (day 0), the rats were injected daily with either CEF or saline for 14days and underwent a T-maze test on days 8-10 and an object recognition test on days 12-14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased motor function, working memory, and object recognition and reduced neurogenesis in the substantial nigra and dentate gyrus of the hippocampus. These behavioral and neuronal changes were prevented by CEF treatment. To our knowledge, this is the first study showing that CEF prevents loss of neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD. Copyright © 2017 Elsevier Inc. All rights reserved.

Exit Site Infection due to Mycobacterium chelonae in an Elderly Patient on Peritoneal Dialysis.

PubMed

Hibi, Arata; Kasugai, Takahisa; Kamiya, Keisuke; Ito, Chiharu; Kominato, Satoru; Miura, Toshiyuki; Koyama, Katsushi

2018-01-01

Nontuberculous mycobacteria (NTM) are rarely isolated from peritoneal dialysis (PD)-associated catheter infections. However, NTM infection is usually difficult to treat and leads to catheter loss. Prompt diagnosis is essential for appropriate treatment. A 70-year-old Japanese man who had been on PD for 2 years and with a medical history of 2 episodes of exit site infections (ESIs) due to methicillin-resistant Staphylococcus aureus was admitted to the hospital due to suspected ESI recurrence. However, Gram staining of the pus revealed no gram-positive cocci. Instead, weakly stained gram-positive rods were observed after 7 days of incubation, which were also positive for acid-fast staining. Rapidly growing NTM Mycobacterium chelonae was isolated on day 14. Despite administering a combination antibiotic therapy, ESI could not be controlled, and catheter removal surgery was performed on day 21. Although PD was discontinued temporarily, the patient did not require hemodialysis, without any uremic symptoms. The catheter was reinserted on day 48, and PD was reinitiated on day 61. The patient was discharged on day 65. Antibiotic therapy was continued for 3 months after discharge, with no indications of recurrent infections observed. It is important to consider the risk of NTM infections in patients on PD. Acid-fast staining could be a key test for prompt diagnosis and provision of an appropriate treatment.

KSC-03PD-2176

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Former astronaut Story Musgrave signs autographs for employees children after his presentation during a welcome ceremony in the IMAX Theatre, KSC Visitor Complex. Employees were invited to share their work experience with their children for Take Our Children to Work Day.

An exploration of factors associated with post-traumatic stress in ER nurses.

PubMed

Lavoie, Stéphane; Talbot, Lise R; Mathieu, Luc; Dallaire, Clémence; Dubois, Marie-France; Courcy, François

2016-03-01

Emergency room (ER) nurses are frequently exposed to traumatic events (TE) at work. These events can lead to symptoms of post-traumatic stress disorder (PTSD). The goal of the present study was to describe the factors associated with PTSD symptoms. A cross-sectional descriptive correlational design was used. The sample consisted of 35 nurses from an ER in Québec (Canada). Data were collected through self-administered questionnaires. TEs presenting a grief component (e.g. intentional injury to a child and patient suicide) are positively associated with peritraumatic distress (PD) in the days after the event. PD is positively associated with PTSD symptoms. Two personality traits (neuroticism and extraversion) should also be considered. Neuroticism is positively associated with PD whereas extraversion is negatively associated with PD and PTSD symptoms. The results are consistent with the literature, but some of these results are new to nurses. They suggest that in this population, TEs in the ER represent 'red flags'. Their occurrence should mobilise support structures. PD and its personality traits are also key factors to consider. To provide adequate support for nurses, ER managers should be on the alert for these conditions. Interventions should be adapted to these findings. © 2015 John Wiley & Sons Ltd.

Early Parkinson's disease patients on rasagiline present with better odor discrimination.

PubMed

Haehner, Antje; Habersack, Angela; Wienecke, Miriam; Storch, Alexander; Reichmann, Heinz; Hummel, Thomas

2015-11-01

The effects of rasagiline on olfaction in animal studies are convincing. However, apart from various anecdotal patient reports, they could not be reproduced in prospective studies in humans. Cross-sectional data of large patient groups are still missing. The aim of this study was therefore to determine the olfactory function in a broad heterogeneous Parkinson's disease (PD) population with and without rasagiline intake. In this single-center, cross-sectional study 224 PD patients with and without rasagiline (1 mg/day) participated. Seventy-four of them received rasagiline as mono, or adjunct therapy. One-hundred fifty patients were untreated or received PD medication other than rasagiline. Comprehensive olfactory testing was performed for phenyl-ethyl alcohol odor thresholds, odor discrimination, and odor identification. Olfactory function did not differ between the two treatment groups with disease duration up to 29 years. Rasagiline-treated patients with disease duration of less than 8 years, however, presented with significant better odor discrimination abilities compared to PD patients without rasagiline treatment. This effect was no longer evident in patients with longer disease duration and proofed to be independent of age, sex, and medication. Our results may suggest that rasagiline treatment has a positive effect on the processing of olfactory information in early PD.

Use of low frequency repetitive transcranial magnetic stimulation to reduce context-dependent learning in people with Parkinson's disease.

PubMed

Lee, Ya-Yun; Fisher, Beth E

2017-05-22

Compared with age-matched non-disabled adults, people with Parkinson's disease (PD) demonstrated greater context-dependent learning, a phenomenon in which an individual shows inferior motor performance when the testing environmental context is different from the original practice context. Additionally, enhanced context- dependency has been shown to be associated with an increased activation of the dorsolateral prefrontal cortex (DLPFC). This study aimed to determine whether context-dependent learning in people with PD could be reduced by decreasing DLPFC activation with low frequency repetitive transcranial magnetic stimulation (rTMS). Quasi-experimental pre-post test controlled study. University laboratory. Twenty-seven participants (18 individuals with PD and 9 age-matched non- disabled adults) were recruited into the PD, PD_rTMS (PD participants who received low frequency rTMS), and Control groups. All participants practiced a finger sequence task containing 3 sequences embedded within specific contexts (colored circles and spatial location on a computer screen) on the first day. On day 2, the participants were tested under the SWITCH and SAME conditions. In the SWITCH condition, the sequence-context association changed from that of practice; in the SAME condition, the sequence-context association remained the same as practice. The PD_rTMS group received 1 Hz rTMS applied over the left DLPFC on the second day before the testing conditions. Switch cost, the performance difference between the SWITCH and SAME conditions, was calculated to indicate context-dependency. All participants improved throughout practice on the first day. Analysis of the switch cost revealed a significant group main effect (p = 0.050). Post-hoc analysis revealed that the PD_rTMS group had significantly smaller switch cost than the PD group (p = 0.031) but not the Control group. Low frequency rTMS applied over DLPFC reduced context-dependency in people with PD. The findings provide a preliminary evidence of using low frequency rTMS as an adjuvant intervention approach to facilitate individuals with PD to generalize a learned motor task from one environmental context to another.

[Evaluating the relation of premenstrual syndrome and primary dysmenorrhea in women diagnosed with fibromyalgia].

PubMed

Terzi, Rabia; Terzi, Hasan; Kale, Ahmet

2015-01-01

In this study, we aimed to investigate the presence of premenstrual syndrome (PMS), primary dysmenorrhea (PD) and depression among women with fibromyalgia (FM) and healthy females and to determine possible factors related with PMS and PD in FM. The present study was conducted on 98 female patients diagnosed with FM and 102 age and sex-matched healthy controls. All patients were evaluated for premenstrual syndrome (PMS) and primary dysmenorrhea (PD). Premenstrual syndrome was assessed among the patients for the presence of one or more affective or somatic symptoms within the five days preceding menses. The diagnosis of primary dysmenorrhea was defined as having abdominal pain or lower back pain lasting at least two days during a menstrual period. Dysmenorrhea was assessed via visual analog scale. Dysmenorrhea was rated via Multidimensional Scoring System. The Hamilton depression scale was applied to all patients. Primary dysmenorrhea was established in 41% of FM patients and 28% of the control group. A statistically significant difference was found in PD between the two groups (p=0.03). PMS was established in 42% of the FM patients and 25% of the control group. A statistically significant difference was found in PMS between the two groups (p=0.03). There is an increased frequency of premenstrual syndrome and dysmenorrhea in FM patients. The patients with high symptom severity scores and high depression scores among the FM patients are at risk of PMS and PD. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Correlating the magic numbers of inorganic nanomolecular assemblies with a {Pd84} molecular-ring Rosetta Stone

PubMed Central

Xu, Feng; Miras, Haralampos N.; Scullion, Rachel A.; Long, De-Liang; Thiel, Johannes; Cronin, Leroy

2012-01-01

Molecular self-assembly has often been suggested as the ultimate route for the bottom-up construction of building blocks atom-by-atom for functional nanotechnology, yet structural design or prediction of nanomolecular assemblies is still far from reach. Whereas nature uses complex machinery such as the ribosome, chemists use painstakingly engineered step-by-step approaches to build complex molecules but the size and complexity of such molecules, not to mention the accessible yields, can be limited. Herein we present the discovery of a palladium oxometalate {Pd84}-ring cluster 3.3 nm in diameter; [Pd84O42(OAc)28(PO4)42]70- ({Pd84} ≡ {Pd12}7) that is formed in water just by mixing two reagents at room temperature, giving crystals of the compound in just a few days. The structure of the {Pd84}-ring has sevenfold symmetry, comprises 196 building blocks, and we also show, using mass spectrometry, that a large library of other related nanostructures is present in solution. Finally, by analysis of the symmetry and the building block library that construct the {Pd84} we show that the correlation of the symmetry, subunit number, and overall cluster nuclearity can be used as a “Rosetta Stone” to rationalize the “magic numbers” defining a number of other systems. This is because the discovery of {Pd84} allows the relationship between seemingly unrelated families of molecular inorganic nanosystems to be decoded from the overall cluster magic-number nuclearity, to the symmetry and building blocks that define such structures allowing the prediction of other members of these nanocluster families. PMID:22753516

Haemolysis in G6PD Heterozygous Females Treated with Primaquine for Plasmodium vivax Malaria: A Nested Cohort in a Trial of Radical Curative Regimens.

PubMed

Chu, Cindy S; Bancone, Germana; Moore, Kerryn A; Win, Htun Htun; Thitipanawan, Niramon; Po, Christina; Chowwiwat, Nongnud; Raksapraidee, Rattanaporn; Wilairisak, Pornpimon; Phyo, Aung Pyae; Keereecharoen, Lily; Proux, Stéphane; Charunwatthana, Prakaykaew; Nosten, François; White, Nicholas J

2017-02-01

Radical cure of Plasmodium vivax malaria with 8-aminoquinolines (primaquine or tafenoquine) is complicated by haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD heterozygous females, because of individual variation in the pattern of X-chromosome inactivation (Lyonisation) in erythroid cells, may have low G6PD activity in the majority of their erythrocytes, yet are usually reported as G6PD "normal" by current phenotypic screening tests. Their haemolytic risk when treated with 8-aminoquinolines has not been well characterized. In a cohort study nested within a randomised clinical trial that compared different treatment regimens for P. vivax malaria, patients with a normal standard NADPH fluorescent spot test result (≳30%-40% of normal G6PD activity) were randomised to receive 3 d of chloroquine or dihydroartemisinin-piperaquine in combination with primaquine, either the standard high dose of 0.5 mg base/kg/day for 14 d or a higher dose of 1 mg base/kg/d for 7 d. Patterns of haemolysis were compared between G6PD wild-type and G6PD heterozygous female participants. Between 21 February 2012 and 04 July 2014, 241 female participants were enrolled, of whom 34 were heterozygous for the G6PD Mahidol variant. Haemolysis was substantially greater and a larger proportion of participants reached the threshold of clinically significant haemolysis (fractional haematocrit reduction >25%) in G6PD heterozygotes taking the higher (7 d) primaquine dose (9/17 [53%]) compared with G6PD heterozygotes taking the standard high (14 d) dose (2/16 [13%]; p = 0.022). In heterozygotes, the mean fractional haematocrit reductions were correspondingly greater with the higher primaquine dose (7-d regimen): -20.4% (95% CI -26.0% to -14.8%) (nadir on day 5) compared with the standard high (14 d) dose: -13.1% (95% CI -17.6% to -8.6%) (nadir day 6). Two heterozygotes taking the higher (7 d) primaquine dose required blood transfusion. In wild-type participants, mean haematocrit reductions were clinically insignificant and similar with both doses: -5.8 (95% CI -7.2% to -4.4%) (nadir day 3) compared with -5.5% (95% CI -7.4% to -3.7%) (nadir day 4), respectively. Limitations to this nested cohort study are that the primary objective of the trial was designed to measure efficacy and not haemolysis in relation to G6PD genotype and that the heterozygote groups were small. Higher daily doses of primaquine have the potential to cause clinically significant haemolysis in G6PD heterozygous females who are reported as phenotypically normal with current point of care tests. ClinicalTrials.gov NCT01640574.

Can dialysis patients be accurately identified using healthcare claims data?

PubMed

Taneja, Charu; Berger, Ariel; Inglese, Gary W; Lamerato, Lois; Sloand, James A; Wolff, Greg G; Sheehan, Michael; Oster, Gerry

2014-01-01

While health insurance claims data are often used to estimate the costs of renal replacement therapy in patients with end-stage renal disease (ESRD), the accuracy of methods used to identify patients receiving dialysis - especially peritoneal dialysis (PD) and hemodialysis (HD) - in these data is unknown. The study population consisted of all persons aged 18 - 63 years in a large US integrated health plan with ESRD and dialysis-related billing codes (i.e., diagnosis, procedures) on healthcare encounters between January 1, 2005, and December 31, 2008. Using billing codes for all healthcare encounters within 30 days of each patient's first dialysis-related claim ("index encounter"), we attempted to designate each study subject as either a "PD patient" or "HD patient." Using alternative windows of ± 30 days, ± 90 days, and ± 180 days around the index encounter, we reviewed patients' medical records to determine the dialysis modality actually received. We calculated the positive predictive value (PPV) for each dialysis-related billing code, using information in patients' medical records as the "gold standard." We identified a total of 233 patients with evidence of ESRD and receipt of dialysis in healthcare claims data. Based on examination of billing codes, 43 and 173 study subjects were designated PD patients and HD patients, respectively (14 patients had evidence of PD and HD, and modality could not be ascertained for 31 patients). The PPV of codes used to identify PD patients was low based on a ± 30-day medical record review window (34.9%), and increased with use of ± 90-day and ± 180-day windows (both 67.4%). The PPV for codes used to identify HD patients was uniformly high - 86.7% based on ± 30-day review, 90.8% based on ± 90-day review, and 93.1% based on ± 180-day review. While HD patients could be accurately identified using billing codes in healthcare claims data, case identification was much more problematic for patients receiving PD. Copyright © 2014 International Society for Peritoneal Dialysis.

Risk and Prognosis of Bacteremia and Fungemia Among Peritoneal Dialysis Patients: A Population-Based Cohort Study.

PubMed

Dalgaard, Lars Skov; Nørgaard, Mette; Povlsen, Johan Vestergaard; Jespersen, Bente; Jensen-Fangel, Søren; Ellermann-Eriksen, Svend; Østergaard, Lars; Schønheyder, Henrik Carl; Søgaard, Ole Schmeltz

♦ BACKGROUND: The incidence of bacteremia and fungemia (BAF) is largely unknown in end-stage renal disease (ESRD) patients initiating peritoneal dialysis (PD). ♦ OBJECTIVE: The main objective was to estimate and compare incidence rates of first episodes of BAF in incident PD patients and a comparison cohort. A secondary objective was to compare causative agents and 30-day post-BAF mortality between PD patients and the comparison cohort. ♦ METHODS: Design: Observational cohort study. Central and North Denmark regions. patients who initiated PD during 1995 - 2010. For each patient we sampled up to 10 controls from the general population matched on age, sex, and municipality. ♦ MAIN OUTCOME: Data on positive blood cultures were retrieved from electronic microbiology databases covering the 2 regions. We calculated incidence rates (IRs) of first-time BAF for PD patients and population controls. Incidence-rate ratios (IRRs) were calculated to compare these rates. Thirty-day mortality was estimated by Kaplan-Meier analysis. ♦ RESULTS: Among 1,024 PD patients and 10,215 population controls, we identified 75 and 282 episodes of BAF, respectively. Incidence rates of BAF were 4.7 (95% confidence interval [CI], 3.8 - 5.9) per 100 person-years of follow-up (PYFU) in PD patients and 0.5 (95% CI, 0.4 - 0.5) per 100 PYFU in population controls (IRR = 10.4; 95% CI, 8.1 - 13.5). In PD patients, the most frequent microorganisms were Escherichia coli (18.7%) and Staphylococcus aureus (13.3%). Escherichia coli (27.3%) also ranked first among population controls. Thirty-day mortality following BAF was 20.8% (95% CI, 12.6 - 31.0) and 20.7% (95% CI, 16.3 - 25.9) among PD patients and population controls, respectively. ♦ CONCLUSIONS: Peritoneal dialysis patients are at markedly higher risk of BAF than population controls. Causative agents and the 30-day post-BAF mortality were similar in the 2 cohorts. Copyright © 2016 International Society for Peritoneal Dialysis.

Ameliorative Effect of Quercetin on Neurochemical and Behavioral Deficits in Rotenone Rat Model of Parkinson's Disease: Modulating Autophagy (Quercetin on Experimental Parkinson's Disease).

PubMed

El-Horany, Hemat E; El-Latif, Rania N Abd; ElBatsh, Maha M; Emam, Marwa N

2016-07-01

Autophagy is necessary for neuronal homeostasis and its dysfunction has been implicated in Parkinson's disease (PD) as it can exacerbate endoplasmic reticulum (ER) stress and ER stress-induced apoptosis. Quercetin is a flavonoid known for its neuroprotective and antioxidant effects. The present study investigated the protective, autophagy-modulating effects of quercetin in the rotenone rat model of PD. Rotenone was intraperitoneally injected at dose of 2 ml/kg/day for 4 weeks. Simultaneous intraperitoneal injection of quercetin was given at a dose of 50 mg/kg/day also for 4 weeks. Neurobehavioral changes were studied. Oxidative/antioxidant status, C/EBP homologous protein (CHOP), Beclin-1, and dopamine levels were assessed. DNA fragmentation and histopathological changes were evaluated. This research work revealed that quercetin significantly attenuated rotenone-induced behavioral impairment, augmented autophagy, ameliorated ER stress- induced apoptosis with attenuated oxidative stress. From the current study, quercetin can act as an autophagy enhancer in PD rat model and modulates the microenvironment that leads to neuronal death. © 2016 Wiley Periodicals, Inc.

Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease.

PubMed

Qi, Hui; Li, Shixue

2014-04-01

A dose-response meta-analysis was carried out between Parkinson's disease (PD) risk, and coffee, tea and caffeine consumption. A comprehensive search was carried out to identify eligible studies. The fixed or random effect model was used based on heterogeneity test. The dose-response relationship was assessed by restricted cubic spline. A total of 13 articles involving 901 764 participants for coffee, eight articles involving 344 895 participants for tea and seven articles involving 492 724 participants for caffeine were included. A non-linear relationship was found between coffee consumption and PD risk overall, and the strength of protection reached the maximum at approximately 3 cups/day (smoking-adjusted relative risk: 0.72, 95% confidence interval 0.65-0.81). A linear relationship was found between tea and caffeine consumption, and PD risk overall, and the smoking-adjusted risk of PD decreased by 26% and 17% for every two cups/day and 200 mg/day increments, respectively. The association of coffee and tea consumption with PD risk was stronger for men than that for women, and the association of caffeine consumption with PD risk was stronger for ever users of hormones than that for never users of hormones among postmenopausal women. The aforementioned associations were weaker for USA relative to Europe or Asia. A linear dose-relationship for decreased PD risk with tea and caffeine consumption was found, whereas the strength of protection reached a maximum at approximately 3 cups/day for coffee consumption overall. Further studies are required to confirm the findings. © 2013 Japan Geriatrics Society.

(+/-)3,4-Methylenedioxymethamphetamine (MDMA) dose-dependently impairs spatial learning in the morris water maze after exposure of rats to different five-day intervals from birth to postnatal day twenty.

PubMed

Vorhees, Charles V; Schaefer, Tori L; Skelton, Matthew R; Grace, Curtis E; Herring, Nicole R; Williams, Michael T

2009-01-01

During postnatal days (PD) 11-20, (+/-)3,4-methylenedioxymethamphetamine (MDMA) treatment impairs egocentric and allocentric learning, and reduces spontaneous locomotor activity; however, it does not have these effects during PD 1-10. How the learning impairments relate to the stress hyporesponsive period (SHRP) is unknown. To test this association, the preweaning period was subdivided into 5-day periods from PD 1-20. Separate pups within each litter were injected subcutaneously with 0, 10, 15, 20, or 25 mg/kg MDMA x4/day on PD 1-5, 6-10, 11-15, or 16-20, and tested as adults. The 3 highest MDMA dose groups showed reduced locomotor activity during the first 10 min (of 60 min), especially in the PD 1-5 and 6-10 dosing regimens. MDMA groups in all dosing regimens showed impaired allocentric learning in the Morris water maze (on acquisition and reversal, all MDMA groups were affected; on the small platform phase, the 2 high-dose groups were affected). No effects of MDMA were found on anxiety (elevated zero maze), novel object recognition, or egocentric learning (although a nonsignificant trend was observed). The Morris maze results did not support the idea that the SHRP is critical to the effects of MDMA on allocentric learning. However, since no effects on egocentric learning were found, but were apparent after PD 11-20 treatment, the results show that these 2 forms of learning have different exposure-duration sensitivities. 2009 S. Karger AG, Basel.

Combined PD-1 blockade and GITR triggering induce a potent antitumor immunity in murine cancer models and synergizes with chemotherapeutic drugs

PubMed Central

2014-01-01

Background The coinhibitory receptor Programmed Death-1 (PD-1) inhibits effector functions of activated T cells and prevents autoimmunity, however, cancer hijack this pathway to escape from immune attack. The costimulatory receptor glucocorticoid-induced TNFR related protein (GITR) is up-regulated on activated T cells and increases their proliferation, activation and cytokine production. We hypothesize that concomitant PD-1 blockade and GITR triggering would synergistically improve the effector functions of tumor-infiltrating T cells and increase the antitumor immunity. In present study, we evaluated the antitumor effects and mechanisms of combined PD-1 blockade and GITR triggering in a clinically highly relevant murine ID8 ovarian cancer model. Methods Mice with 7 days-established peritoneal ID8 ovarian cancer were treated intraperitoneally (i.p.) with either control, anti-PD-1, anti-GITR or anti-PD-1/GITR monoclonal antibody (mAb) and their survival was evaluated; the phenotype and function of tumor-associated immune cells in peritoneal cavity of treated mice was analyzed by flow cytometry, and systemic antigen-specific immune response was evaluated by ELISA and cytotoxicity assay. Results Combined anti-PD-1/GITR mAb treatment remarkably inhibited peritoneal ID8 tumor growth with 20% of mice tumor free 90 days after tumor challenge while treatment with either anti-PD-1 or anti-GITR mAb alone exhibited little antitumor effect. The durable antitumor effect was associated with a memory immune response and conferred by CD4+ cells and CD8+ T cells. The treatment of anti-PD-1/GITR mAb increased the frequencies of interferon-γ-producing effector T cells and decreased immunosuppressive regulatory T cells and myeloid-derived suppressor cells, shifting an immunosuppressive tumor milieu to an immunostimulatory state in peritoneal cavity. In addition, combined treatment of anti-PD-1/GITR mAb mounted an antigen-specific immune response as evidenced by antigen-specific IFN-γ production and cytolytic activity of spleen cells from treated mice. More importantly, combined treatment of anti-PD-1/GITR mAb and chemotherapeutic drugs (cisplatin or paclitaxel) further increased the antitumor efficacy with 80% of mice obtaining tumor-free long-term survival in murine ID8 ovarian cancer and 4 T1 breast cancer models. Conclusions Combined anti-PD-1/GITR mAb treatment induces a potent antitumor immunity, which can be further promoted by chemotherapeutic drugs. A combined strategy of anti-PD-1/GITR mAb plus cisplatin or paclitaxel should be considered translation into clinic. PMID:24502656

Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali

PubMed Central

2010-01-01

Background Artemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group. Methods Blood samples from children and adults participants (1 to 70 years old) with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem®) or artesunate plus mefloquine (Artequin™). A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A-) allele of the gene mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene. Results The DNA amplified from 315 samples using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%). The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median parasitaemia and other baseline characteristics (mean haemoglobin, sex and age groups) between G6PD deficiency (hemizygous, heterozygous, and homozygous) and G6PD-normal participants were comparable (p > 0.05). After treatment, parasite clearance did not change significantly whether the participants were G6PD deficient or G6PD normal on day 1 (OR = 1.3; CI = 0.70-2.47; p > 0.05) and on day 2 (OR = 0.859; CI = 0.097-7.61; p > 0.05). Conclusions The presence of G6PD deficiency does not appear to significantly influence the clearance of P. falciparum in the treatment of uncomplicated malaria using ACT. PMID:21092137

Short- and Long-Term Outcomes of Deep Brain Stimulation in Patients 70 Years and Older with Parkinson Disease.

PubMed

Mathkour, Mansour; Garces, Juanita; Scullen, Tyler; Hanna, Joshua; Valle-Giler, Edison; Kahn, Lora; Arrington, Teresa; Houghton, David; Lea, Georgia; Biro, Erin; Bui, Cuong J; Sulaiman, Olawale A R; Smith, Roger D

2017-01-01

Parkinson disease (PD) is a common neurodegenerative disease in elderly patients that may be treated with deep brain stimulation (DBS). DBS is an accepted surgical treatment in PD patients <70 years that demonstrates marked improvement in disease symptomology. Patients ≥70 years historically have been excluded from DBS therapy. Our objective is to evaluate the short- and long-term outcomes in patients with PD ≥70 years who underwent DBS at our center. In our single-center study, we retrospectively assessed a prospective registry of patients with PD treated with DBS who were ≥70 years old at the time of their procedure. Univariate analyses and 1-sample paired t test were used to evaluate data. Motor scores were evaluated with the Unified Parkinson's Disease Rating Scale III, and the effects on medication requirements were evaluated with levodopa equivalence daily doses (LEDD). Thirty-seven patients were followed for an average of 42.2 months post-DBS. The average ages at diagnosis and at the time of DBS surgery were 63.05 years and 72.45 years, respectively. Significant reductions in the average Unified Parkinson's Disease Rating Scale III score were observed (preoperative 31.8; postoperative 15.6; P < 0.0001). Significant reductions in the average LEDD (preoperative 891.94 mg; postoperative 559.6 mg; P = 0.0008) and medication doses per day (preoperative 11.54; postoperative 7.97; P = 0.0112) also were present. DBS is effective in treating elderly patients with PD. Patients experienced improvement in motor function, LEDD, and medication doses per day after DBS. Our results suggest that DBS is an effective treatment modality in elderly patients with PD. Copyright © 2016 Elsevier Inc. All rights reserved.

Protection of MPTP-induced neuroinflammation and neurodegeneration by Pycnogenol

PubMed Central

Khan, Mohammad Moshahid; Kempuraj, Duraisamy; Thangavel, Ramasamy; Zaheer, Asgar

2013-01-01

Oxidative stress and inflammation play a crucial role in Parkinson’s disease (PD) pathogenesis and may represent a target for treatment. Current PD drugs provide only symptomatic relief and have limitations in terms of adverse effects and inability to prevent neurodegeneration. Flavonoids have been suggested to exert human health benefits by its anti-oxidant and anti-inflammatory properties. Therefore, in the present study, using 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydro pyridine (MPTP)-induced mouse model of Parkinsonism, we investigated the neuroprotective potential of bioflavonoid compound Pycnogenol® (PYC), an extract of Pinus maritime bark. MPTP injected mice developed significantly severe oxidative stress and impaired motor coordination at day 1 and day 7 postinjection. This was associated with significantly increased inflammatory responses of astrocyte and microglia as assessed by ionized calcium binding adaptor molecule 1 (Iba 1) and glial fibrillary acidic protein (GFAP) immunohistochemistry, and nuclear transcription factor-κB (NF-kB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in the striata by Western blot. Additionally, there was significant upregulation of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) expression in the striata of MPTP injected mice compared to saline controls. The MPTP-induced neuroinflammation, neurodegeneration and behavioral impairments were markedly repudiated by treatment with PYC. These results suggest that PYC protects dopaminergic neurons from MPTP toxicity in the mouse model of PD. Thus, the present finding of PYC-induced adaptation to oxidative stress and inflammation could suggest a novel avenue for clinical intervention in neurodegenerative diseases including PD. PMID:23391521

Obtaining Reliable Estimates of Ambulatory Physical Activity in People with Parkinson's Disease.

PubMed

Paul, Serene S; Ellis, Terry D; Dibble, Leland E; Earhart, Gammon M; Ford, Matthew P; Foreman, K Bo; Cavanaugh, James T

2016-05-05

We determined the number of days required, and whether to include weekdays and/or weekends, to obtain reliable measures of ambulatory physical activity in people with Parkinson's disease (PD). Ninety-two persons with PD wore a step activity monitor for seven days. The number of days required to obtain a reliable estimate of daily activity was determined from the mean intraclass correlation (ICC2,1) for all possible combinations of 1-6 consecutive days of monitoring. Two days of monitoring were sufficient to obtain reliable daily activity estimates (ICC2,1 > 0.9). Amount (p = 0.03) but not intensity (p = 0.13) of ambulatory activity was greater on weekdays than weekends. Activity prescription based on amount rather than intensity may be more appropriate for people with PD.

EXPOSURE TO DEXAMETHASONE DURING LATE GESTATION CAUSES FEMALE-SPECIFIC DECREASES IN CORE BODY TEMPERATURE AND PREPRO-THYROTROPIN-RELEASING HORMONE EXPRESSION IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS IN RATS

PubMed Central

Carbone, David L.; Zuloaga, Damian G.; Lacagnina, Anthony F.; McGivern, Robert F.; Handa, Robert J.

2012-01-01

Synthetic glucocorticoids (GC) have been used to promote lung development in preterm infants, thereby decreasing respiratory distress syndrome and mortality, yet, concern has arisen from reports that such treatment predisposes individuals to disease in adulthood. Given the variety of preclinical studies that show metabolic and behavioral abnormalities in adulthood following fetal exposure to synthetic GC, we examined the effect of in utero exposure to the synthetic GC, dexamethasone (DEX), on hypothalamic expression of thyrotropin-releasing hormone (TRH) a central neuropeptide involved in mediating behavior and metabolic balance. Pregnant Sprague-Dawley rats were administered 0.4 mg/kg DEX on gestational days 18–21. As adults (postnatal day (PD) 60), the offspring were fitted with temperature sensing transmitters allowing real-time monitoring of core body temperature (CBT) across the 24 hr light dark period. This revealed a significant decrease in CBT throughout the day in prenatal DEX-treated females on estrus and diestrus, but not in male offspring. The reduction in CBT by prenatal DEX exposure was accompanied by a significant decrease in the expression of Trh transcript in the paraventricular nucleus of the hypothalamus (PVN) of female rats at PD 60 and this effect was also present on PD7. There was also a female-specific reduction in the number of preproTRH -immunoreactive (ir) neurons in the PVN, with ppTRH-ir nerve fibers decreases that were present in both male and female offspring. No changes in thyroid hormone (triiodothyronine, T3; thyroxine, T4) were observed in adult offspring, but during development, both males and females (PD14) had lower T3 and T4 levels. These data indicate abnormal expression of TRH results from fetal DEX exposure during late gestation, possibly explaining the decreased CBT observed in the female offspring. PMID:22884559

Dietary protein deficiency reduces lysosomal and nonlysosomal ATP-dependent proteolysis in muscle

NASA Technical Reports Server (NTRS)

Tawa, N. E. Jr; Kettelhut, I. C.; Goldberg, A. L.

1992-01-01

When rats are fed a protein deficient (PD) diet for 7 days, rates of proteolysis in skeletal muscle decrease by 40-50% (N. E. Tawa, Jr., and A. L. Goldberg. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E317-325, 1992). To identify the underlying biochemical adaptations, we measured different proteolytic processes in incubated muscles. The capacity for intralysosomal proteolysis, as shown by sensitivity to methylamine or lysosomal protease inhibitors, fell 55-75% in muscles from PD rats. Furthermore, extracts of muscles of PD rats showed 30-70% lower activity of many lysosomal proteases, including cathepsins B, H, and C, and carboxypeptidases A and C, as well as other lysosomal hydrolases. The fall in cathepsin B and proteolysis was evident by 3 days on the PD diet, and both returned to control levels 3 days after refeeding of the normal diet. In muscles maintained under optimal conditions, 80-90% of protein breakdown occurs by nonlysosomal pathways. In muscles of PD rats, this ATP-dependent process was also 40-60% slower. Even though overall proteolysis decreased in muscles of PD rats, their capacity for Ca(2+)-dependent proteolysis increased (by 66%), as did the activity of the calpains (+150-250%). Thus the lysosomal and the ATP-dependent processes decrease coordinately and contribute to the fall in muscle proteolysis in PD animals.

The Association Between Glucose Exposure and the Risk of Peritonitis in Peritoneal Dialysis Patients.

PubMed

van Diepen, Anouk T N; van Esch, Sadie; Struijk, Dirk G; Krediet, Raymond T

♦ Little or no clinical evidence is available on the association between glucose exposure and peritoneal host defense in peritoneal dialysis (PD) patients. The objective of the present study was to quantify the exposure to glucose during the first year on PD and investigate the association with subsequent peritonitis. ♦ We analyzed prospectively collected demographic and peritonitis data from incident adult PD patients between 1990 and 2010. For the present study, we conducted a review of both in- and outpatient medical records of all patients to obtain their day-to-day dialysis schemes during the first year on PD. From these data, the average exposure to glucose was quantified. The exposure was stratified into low- and high-glucose groups based on the median, analyzed per standard deviation and in quartiles. Cox proportional hazard models were used to calculate crude and adjusted hazard ratios (HRs) and 95% confidence intervals for the association between glucose exposure and peritonitis. Adjustments were made for age, sex, primary kidney disease, diabetes mellitus, Davies comorbidity score and the treatment period. ♦ In total, 230 patients were included in the study of whom 151 (66%) experienced a first peritonitis episode. The median follow-up time was 2.6 years (interquartile range [IQR]: 1.9 - 3.8) in the low-glucose group and 3.1 (IQR: 2.1 - 4.2) in the high-glucose group. After adjustment for confounding factors, no association between high glucose exposure and the risk of peritonitis was found (HR: 0.81; 0.55 - 1.17). No association was present when glucose exposure was analyzed per standard deviation (SD) (HR: 0.98; 0.79 - 1.21) or patient quartiles were applied. No association was identified between glucose exposure and severe peritonitis, Staphylococcus aureus peritonitis, or a peritonitis episode that lasted more than 14 days. ♦ Exposure to glucose is not associated with an increased risk of peritonitis. The equilibrium between glycemic harm to peritoneal host defense and detrimental effects of glucose on invading microorganisms may determine the susceptibility to peritoneal infection. Copyright © 2016 International Society for Peritoneal Dialysis.

Immunophenotyping of Monocytes During Human Sepsis Shows Impairment in Antigen Presentation: A Shift Toward Nonclassical Differentiation and Upregulation of FcγRi-Receptor.

PubMed

Ferreira da Mota, Nadijane Valeria; Brunialti, Milena Karina Colo; Santos, Sidneia Sousa; Machado, Flavia Ribeiro; Assunçao, Murillo; de Azevedo, Luciano Cesar Pontes; Salomao, Reinaldo

2017-12-05

Monocytes and macrophages are pivotal in the host response to sepsis, recognizing the infecting microorganism and triggering an inflammatory response. These functions are, at least in part, modulated by the expression of cell surface receptors. We aimed to characterize the monocyte phenotype from septic patients during an ongoing sepsis process and its association with clinical outcomes. Sixty-one septic patients and 31 healthy volunteers (HVs) were enrolled in the study. Samples were obtained from patients at baseline (D0, N = 61), and after 7 (D7, N = 36) and 14 days of therapy (D14, N = 22). Monocytes from septic patients presented decreased expression of CD86, HLA-DR, CD200R, CCR2, CXCR2, and CD163 compared with HV monocytes. In contrast, the PD-1, PD-L1, CD206, CD64, and CD16 expression levels were upregulated in patients. HLA-DR, CD64, PD-1, and PD-L1 expression levels were higher in survivors than in nonsurvivors. Increased CD86, HLA-DR, and CXCR2 expression levels were observed in follow-up samples; in contrast, CD64 and CD16 GMFI decreased over time. In conclusion, monocytes from septic patients show antigen presentation impairment as characterized by decreased HLA-DR and costimulatory CD86 expression and increased PD-1 and PD-L1 expression. On the contrary, increased monocyte inflammatory and phagocytic activities may be inferred by the increased CD16 and CD64 expression. We found conflicting results regarding differentiation toward the M2 phenotype, with increased CD206 expression and decreased CD163 expression on monocytes from septic patients, whereas the subset of nonclassical monocytes was demonstrated by increased CD16.

Health service costs and clinical gains of psychotherapy for personality disorders: a randomized controlled trial of day-hospital-based step-down treatment versus outpatient treatment at a specialist practice

PubMed Central

2013-01-01

Background Day-hospital-based treatment programmes have been recommended for poorly functioning patients with personality disorders (PD). However, more research is needed to confirm the cost-effectiveness of such extensive programmes over other, presumably simpler, treatment formats. Methods This study compared health service costs and psychosocial functioning for PD patients randomly allocated to either a day-hospital-based treatment programme combining individual and group psychotherapy in a step-down format, or outpatient individual psychotherapy at a specialist practice. It included 107 PD patients, 46% of whom had borderline PD, and 40% of whom had avoidant PD. Costs included the two treatment conditions and additional primary and secondary in- and outpatient services. Psychosocial functioning was assessed using measures of global (observer-rated GAF) and occupational (self-report) functioning. Repeated assessments over three years were analysed using mixed models. Results The costs of step-down treatment were higher than those of outpatient treatment, but these high costs were compensated by considerably lower costs of other health services. However, costs and clinical gains depended on the type of PD. For borderline PD patients, cost-effectiveness did not differ by treatment condition. Health service costs declined during the trial, and functioning improved to mild impairment levels (GAF > 60). For avoidant PD patients, considerable adjuvant health services expanded the outpatient format. Clinical improvements were nevertheless superior to the step-down condition. Conclusion Our results indicate that decisions on treatment format should differentiate between PD types. For borderline PD patients, the costs and gains of step-down and outpatient treatment conditions did not differ. For avoidant PD patients, the outpatient format was a better alternative, leaning, however, on costly additional health services in the early phase of treatment. Trial registration Clinical Trials NCT00378248 PMID:24268099

Cross-modal transfer of the conditioned eyeblink response during interstimulus interval discrimination training in young rats

PubMed Central

Brown, Kevin L.; Stanton, Mark E.

2008-01-01

Eyeblink classical conditioning (EBC) was observed across a broad developmental period with tasks utilizing two interstimulus intervals (ISIs). In ISI discrimination, two distinct conditioned stimuli (CSs; light and tone) are reinforced with a periocular shock unconditioned stimulus (US) at two different CS-US intervals. Temporal uncertainty is identical in design with the exception that the same CS is presented at both intervals. Developmental changes in conditioning have been reported in each task beyond ages when single-ISI learning is well developed. The present study sought to replicate and extend these previous findings by testing each task at four separate ages. Consistent with previous findings, younger rats (postnatal day – PD - 23 and 30) trained in ISI discrimination showed evidence of enhanced cross-modal influence of the short CS-US pairing upon long CS conditioning relative to older subjects. ISI discrimination training at PD43-47 yielded outcomes similar to those in adults (PD65-71). Cross-modal transfer effects in this task therefore appear to diminish between PD30 and PD43-47. Comparisons of ISI discrimination with temporal uncertainty indicated that cross-modal transfer in ISI discrimination at the youngest ages did not represent complete generalization across CSs. ISI discrimination undergoes a more protracted developmental emergence than single-cue EBC and may be a more sensitive indicator of developmental disorders involving cerebellar dysfunction. PMID:18726989

The impact of the peritoneal glucose load index on hydration status and inflammation in peritoneal dialysis patients.

PubMed

Hassan, Kamal; Hassan, Fadi; Edgem, Rabia; Moshe, Smadar; Hassan, Shadi

2015-02-01

To evaluate the impact of the peritoneal glucose load (PGL) on hydration status and inflammation in peritoneal dialysis (PD) patients. This cross-sectional study evaluated stable PD patients using a novel PGL index (PGLI), which was calculated as the net glucose content (g) in the PD solutions administered in the daily PD prescription divided by the dry body weight (kg) assessed by whole-body bioimpedance spectroscopy. The relationship between PGLI and glycosylated haemoglobin (HbA1c), fluid overload (FO), and inflammatory markers was investigated. A total of 43 stable PD patients participated in the study. Significant positive correlations were found between PGLI and HbA1c, FO, plasma high sensitivity C-reactive protein (hsCRP), and plasma interleukin-6 (IL-6) levels. HbA1c, FO, plasma hsCRP and plasma IL-6 levels were significantly higher in patients with PGLI >3 g/kg/day compared with those with PGLI ≤3 g/kg/day. PGLI values >3 g/kg/day may be associated with poor glycaemic control, over hydration and augmented inflammation. PGLI might be a useful tool for the quantitative assessment of the PGL and could be applied when managing PD patients. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

UK Renal Registry 18th Annual Report: Chapter 11 2014 Multisite Dialysis Access Audit in England, Northern Ireland and Wales and 2013 PD One Year Follow-up: National and Centre-specific Analyses.

PubMed

Rao, Anirudh; Evans, Rebecca; Wilkie, Martin; Fluck, Richard; Kumwenda, Mick

2016-01-01

Data are presented from the third combined vascular and peritoneal dialysis access audit. In 2014, 53 centres in England, Wales and Northern Ireland (out of 62) returned data on first access from 4,339 incident haemodialysis (HD) patients and 1,090 incident peritoneal dialysis (PD) patients. Of the 5,429 incident patients, 20.1% started dialysis on PD, 27.8% started with an arteriovenous fistula (AVF), 1.0% with an arteriovenous graft (AVG), 27.1% on a tunnelled line (TL) and 24.0% on a non-tunnelled line (NTL). Older patients (565 years) were more likely to start haemodialysis using AVF compared to their younger counterparts (36.2% vs. 32.8%). Thirteen of the nineteen centres (68%) using the physician led percutaneous insertion technique had over 20% of their incident patients starting on PD when compared to only seven out of fourteen centres (50%) which used single technique (open surgical or laparoscopic) for their PD catheter insertion. Wide variations were apparent between centres for use of AVF as the first haemodialysis access ranging from 10–54%. Eight of the 49 centres were achieving close to the 65% target for AV fistula in their incident patients. Length of time known to nephrology services and likelihood of commencing dialysis using either an AVF or a PD catheter are strongly associated. Patients who were known to a nephrologist for over one year were more likely to start dialysis with AVF, as compared to those who were referred between 90–365 days (39.2% vs. 24.6%). Similarly, patients who were known to a nephrologist between 90 days and one year were more likely to start on PD when compared to patients who were referred <90 days prior to dialysis start (26.9% vs. 9.1%). By comparison, amongst the late presenters, only 3.5% had first access documented as an AVF and 87.3% started dialysis on either a tunnelled line or a non-tunnelled line. Initial surgical assessment was a key determinant of the likelihood of AVF formation. Of the incident patients known to renal services for longer than three months and in those assessed by a surgeon at least three months prior to starting dialysis, 71.4% started dialysis with an AVF whereas of those who were not seen by a surgeon only 10.8% did. Thirty one of the 38 centres were 2 or 3 standard deviations below the 85% target for prevalent haemodialysis patients with an AV fistula. For centres returning data on one-year peritoneal dialysis outcomes, the majority of centres (28/32) maintained 550% of patients on PD at one year, having censored for transplantation. This report demonstrates wide variations in practice between centres across several domains in the provision of dialysis access and further work will be required to understand the underlying reasons.

Passive Response to Stress in Adolescent Female and Adult Male Mice after Intermittent Nicotine Exposure in Adolescence

PubMed Central

Thanos, Panayotis; Delis, Foteini; Rosko, Lauren; Volkow, Nora D

2013-01-01

Smoking is frequently co-morbid with depression. Although it is recognized that depression increases the risk for smoking, it is unclear if early smoking exposure may increase the risk for depression. To test this possibility we assessed the effects of adolescent nicotine exposure on the Forced Swim Test (FST), which is used as a measure of passive coping, and depressive-like behavior in rodents, and on the open field test (OFT), which is used as a measure of locomotion and exploratory behavior. Male and female mice received daily saline or nicotine (0.3 or 0.6 mg/kg) injections from postnatal day (PD) 30 to PD 44. FST and OFT were performed either 1 or 30 days after the last injection (PD 45 and PD 74, respectively). In females, treatment with 0.3 mg/kg nicotine lead to increased FST immobility (64%) and decreased OFT locomotor activity (12%) one day following the last nicotine injection (PD 45); while no effects were observed in adulthood (PD 74). In contrast, on PD45, nicotine treatment did not change the male FST immobility but lead to lower OFT locomotor activity (0.6 mg/kg, 10%). In adulthood (PD 74), both nicotine doses lead to higher FST immobility (87%) in males while 0.6 mg/kg nicotine to lower OFT locomotor activity (13%). The results (i) identify females as more vulnerable to the immediate withdrawal that follows nicotine discontinuation in adolescence and (ii) suggest that adolescent nicotine exposure may enhance the risk for passive response towards unavoidable stress in adult males. PMID:24619539

AT2R (Angiotensin II Type 2 Receptor)-Mediated Regulation of NCC (Na-Cl Cotransporter) and Renal K Excretion Depends on the K Channel, Kir4.1.

PubMed

Wu, Peng; Gao, Zhong-Xiuzi; Duan, Xin-Peng; Su, Xiao-Tong; Wang, Ming-Xiao; Lin, Dao-Hong; Gu, Ruimin; Wang, Wen-Hui

2018-04-01

AT2R (AngII [angiotensin II] type 2 receptor) is expressed in the distal nephrons. The aim of the present study is to examine whether AT2R regulates NCC (Na-Cl cotransporter) and Kir4.1 of the distal convoluted tubule. AngII inhibited the basolateral 40 pS K channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule treated with losartan but not with PD123319. AT2R agonist also inhibits the K channel, indicating that AT2R was involved in tonic regulation of Kir4.1. The infusion of PD123319 stimulated the expression of tNCC (total NCC) and pNCC (phosphorylated NCC; Thr 53 ) by a time-dependent way with the peak at 4 days. PD123319 treatment (4 days) stimulated the basolateral 40 pS K channel activity, augmented the basolateral K conductance, and increased the negativity of distal convoluted tubule membrane. The stimulation of Kir4.1 was essential for PD123319-induced increase in NCC because inhibiting AT2R increased the expression of tNCC and pNCC only in wild-type but not in the kidney-specific Kir4.1 knockout mice. Renal clearance study showed that thiazide-induced natriuretic effect was larger in PD123319-treated mice for 4 days than untreated mice. However, this effect was absent in kidney-specific Kir4.1 knockout mice which were also Na wasting under basal conditions. Finally, application of AT2R antagonist decreased the renal ability of K excretion and caused hyperkalemia in wild-type but not in kidney-specific Kir4.1 knockout mice. We conclude that AT2R-dependent regulation of NCC requires Kir4.1 in the distal convoluted tubule and that AT2R plays a role in stimulating K excretion by inhibiting Kir4.1 and NCC. © 2018 American Heart Association, Inc.

Effects of L-arginine pre-treatment in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s diseases in Balb/c mice

PubMed Central

Hami, Javad; Hosseini, Mehran; Shahi, Sekineh; Lotfi, Nassim; Talebi, Abolfazl; Afshar, Mohammad

2015-01-01

Background: Parkinson’s disease (PD) is a common neurodegenerative disease resulting from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Increasing evidence demonstrated that mice treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in motor functions associated with disruption of DA neurons in SNc conceivably analogous to those observed in PD. L-arginine has been proposed as a novel neuroprotective agent that plays protective roles in several models of neuronal cellular damage. This study aimed to evaluate the effects of L-arginine on the numerical density of dark neurons (DNs) in the SNc of Balb/c mice subjected to MPTP administration. Methods: In the present study, we demonstrated that repeated treatment with L-arginine (300 mg/kg, i.p.) during 7 consecutive days attenuated the production of DNs in SNc of adult male Balb/c mice infused with a single intranasal administration of MPTP (1 mg/nostril). Results: Pre-treatment with L-arginine significantly decreased the numerical density of DNs in SNc of mice 21 days after intranasal MPTP administration. Conclusion: This investigation provides new insights in experimental models of PD, indicating that L-arginine represents a potential neuroprotective agent for the prevention of DA neuron degeneration in SNc observed in PD patients. PMID:26885338

A novel therapeutic approach to 6-OHDA-induced Parkinson's disease in rats via supplementation of PTD-conjugated tyrosine hydroxylase.

PubMed

Wu, Shao Ping; Fu, Ai Ling; Wang, Yu Xia; Yu, Lei Ping; Jia, Pei Yuan; Li, Qian; Jin, Guo Zhang; Sun, Man Ji

2006-07-21

The present study aimed to evaluate whether the protein transduction domain (PTD)-conjugated human tyrosine hydroxylase (TH) fusion protein was effective on the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) model rats. An expression vector pET-PTD-TH harbouring the PTD-TH gene was constructed and transformed to the Escherichia coli BL21 cells for expression. The expressed recombinant PTD-TH with a molecular weight of 61 kD was successfully transduced (1 microM) into the dopaminergic SH-sy5y human neuroblastoma cells in vitro and visualized by immunohistochemical assay. An in vivo experiment in rats showed that the iv administered PTD-TH protein (8 mg/kg) permeated across the blood-brain barrier, penetrated into the striatum and midbrain, and peaked at 5-8 h after the injection. The behavioral effects of PTD-TH on the apomorphine-induced rotations in the PD model rats 8 weeks after the 6-OHDA lesion showed that a single bolus of PTD-TH (8 mg/kg) iv injection caused a decrement of 60% of the contralateral turns on day 1 and 40% on days 5-17. The results imply that iv delivery of PTD-TH is therapeutically effective on the 6-OHDA-induced PD in rats, the PTD-mediated human TH treatment opening a promising therapeutic direction in treatment of PD.

Narrative Organization Deficit in Lewy Body Disorders Is Related to Alzheimer Pathology

PubMed Central

Grossman, Murray; Irwin, David J.; Jester, Charles; Halpin, Amy; Ash, Sharon; Rascovsky, Katya; Weintraub, Daniel; McMillan, Corey T.

2017-01-01

Background: Day-to-day interactions depend on conversational narrative, and we examine here the neurobiological basis for difficulty organizing narrative discourse in patients with Lewy body disorders (LBD). Method: Narrative organization was examined in 56 non-aphasic LBD patients, including a non-demented cohort (n = 30) with Parkinson's disease (PD) or PD-Mild Cognitive Impairment PD-MCI,) and a cohort with mild dementia (n = 26) including PD-dementia (PDD) and dementia with Lewy bodies (DLB), with similar age and education but differing in MMSE (p < 0.001). We used a previously reported procedure that probes patients' judgments of the organization of brief, familiar narratives (e.g., going fishing, wrapping a present). A subgroup of 24 patients had MRI assessment of regional gray matter (GM) atrophy and cerebrospinal fluid (CSF) levels of biomarkers for Alzheimer's disease (AD) pathology, including beta amyloid (Aβ), total-tau (t-tau), and phosphorylated-tau (p-tau). Results: Mildly demented LBD patients had a significant deficit judging narratives compared to non-demented patients, but this deficit was not correlated with MMSE. Regression analyses instead related narrative organization to regions of frontal GM atrophy, and CSF levels of Aβ and t-tau associated with presumed AD pathology in these frontal regions. Conclusion: These findings are consistent with the hypothesis that CSF markers of AD pathology associated with frontal regions play a role in difficulty organizing narratives in LBD. PMID:28228714

Short-term effects of scaling and root planing with or without adjunctive use of an essential-oil-based mouthwash in the treatment of periodontal inflammation in smokers.

PubMed

Alshehri, Mohammad; Alshail, Faisal; Alqahtani, Sami H; Aloriny, Tawfeeg Saleh; Alsharif, Abdulhakim; Kujan, Omar

2015-09-01

The aim of the present short-term follow-up study was to assess the effects of scaling and root planing (SRP) with or without adjunctive use of an essential-oil-based mouthwash in the treatment of periodontal inflammation in smokers. In total, 120 individuals were divided into 2 groups. In Group-1, 60 smokers with periodontal inflammation received SRP alone; and in Group-2, 60 smokers with periodontal inflammation received adjunct essential-oil mouthwash therapy. Periodontal parameters (plaque index [PI], bleeding-on-probing [BOP], and probing pocket depth [PD] ≥ 4 mm) were assessed at baseline and after 90 days of treatment. There was no significant difference in periodontal parameters (PI, BOP, and PD ≥ 4 mm) among participants in Group-1 and -2. Participants in both groups showed significant reductions in PI (P < 0.01), BOP (P < 0.01), and PD ≥ 4 mm (P < 0.01) at follow-up compared to baseline. At 90 days of follow-up, PI (P < 0.05), BOP (P < 0.05), and PD ≥ 4 mm (P < 0.05) were significantly higher in Group-1 compared to Group-2. SRP with adjunct essential-oil mouthwash therapy is more effective in the treatment of periodontal inflammation in smokers as compared to when SRP is performed alone.

Narrative Organization Deficit in Lewy Body Disorders Is Related to Alzheimer Pathology.

PubMed

Grossman, Murray; Irwin, David J; Jester, Charles; Halpin, Amy; Ash, Sharon; Rascovsky, Katya; Weintraub, Daniel; McMillan, Corey T

2017-01-01

Background: Day-to-day interactions depend on conversational narrative, and we examine here the neurobiological basis for difficulty organizing narrative discourse in patients with Lewy body disorders (LBD). Method: Narrative organization was examined in 56 non-aphasic LBD patients, including a non-demented cohort ( n = 30) with Parkinson's disease (PD) or PD-Mild Cognitive Impairment PD-MCI,) and a cohort with mild dementia ( n = 26) including PD-dementia (PDD) and dementia with Lewy bodies (DLB), with similar age and education but differing in MMSE ( p < 0.001). We used a previously reported procedure that probes patients' judgments of the organization of brief, familiar narratives (e.g., going fishing, wrapping a present). A subgroup of 24 patients had MRI assessment of regional gray matter (GM) atrophy and cerebrospinal fluid (CSF) levels of biomarkers for Alzheimer's disease (AD) pathology, including beta amyloid (Aβ), total-tau ( t -tau), and phosphorylated-tau ( p -tau). Results: Mildly demented LBD patients had a significant deficit judging narratives compared to non-demented patients, but this deficit was not correlated with MMSE. Regression analyses instead related narrative organization to regions of frontal GM atrophy, and CSF levels of Aβ and t -tau associated with presumed AD pathology in these frontal regions. Conclusion: These findings are consistent with the hypothesis that CSF markers of AD pathology associated with frontal regions play a role in difficulty organizing narratives in LBD.

Professional Development of Faculty: How Do We Know It Is Effective?

NASA Astrophysics Data System (ADS)

Derting, T. L.; Ebert-May, D.; Hodder, J.

2011-12-01

Professional development (PD) of faculty has been an integral component of curriculum reform efforts in STEM. Traditionally, PD occurs through workshops that last from hours to several days. Regardless of the particular model of PD used during a workshop, its effectiveness is usually assessed through self-report surveys of faculty satisfaction, perceived learning, and reports of applications in faculty classrooms. My presentation focuses on ways of assessing the effectiveness of models of PD, with an emphasis on the need for objective measures of change in faculty teaching. The data that I present raise two significant questions about faculty PD. Are traditional approaches to faculty PD effective in changing classroom teaching practices and improving student learning? What evidence is needed to determine the effectiveness of different models of PD? Self-report data have been useful in identifying variables that can influence the extent to which faculty implement new teaching strategies. These variables include faculty beliefs about student learning, self-efficacy, level of dissatisfaction with student learning, departmental rewards for teaching and learning, time limitations, and peer interactions. Self-report data do not, however, provide a complete or necessarily accurate assessment of the impacts of PD on classroom practices and student learning. Objective assessment of teaching and learning is also necessary, yet seldom conducted. Two approaches to such assessment will be presented, one based on student performance and the other based on observations of faculty teaching. In multiple sections of a student-centered, inquiry-based course, learning gains were higher for students taught by faculty who were trained in student-centered teaching compared with faculty with no such training. In two national projects that focused on faculty PD, self-report data indicated that faculty increased their use of student-centered teaching following PD. Objective assessment measures, however, showed that most faculty actually used teacher-centered methods with only minor use of student-centered teaching practices. Moreover, variables that have been associated with change in teaching practices, or the lack thereof, contributed little to explaining observed classroom teaching practice after PD. For example, faculty with less teaching experience engaged in more student-centered teaching compared with faculty with more years of teaching experience. Also, departmental and peer support for faculty use of non-lecture approaches to teaching had no significant relationship with the classroom practices used by faculty. These and other data suggest that assumptions about the effectiveness of traditional models of PDs need to be validated using objective, as well as subjective measures. The data also indicate a need for new models of PD for STEM faculty.

Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (G6PD Mahidol Variant) versus G6PD-Normal Volunteers.

PubMed

Rueangweerayut, Ronnatrai; Bancone, Germana; Harrell, Emma J; Beelen, Andrew P; Kongpatanakul, Supornchai; Möhrle, Jörg J; Rousell, Vicki; Mohamed, Khadeeja; Qureshi, Ammar; Narayan, Sushma; Yubon, Nushara; Miller, Ann; Nosten, François H; Luzzatto, Lucio; Duparc, Stephan; Kleim, Jörg-Peter; Green, Justin A

2017-09-01

Tafenoquine is an 8-aminoquinoline under investigation for the prevention of relapse in Plasmodium vivax malaria. This open-label, dose-escalation study assessed quantitatively the hemolytic risk with tafenoquine in female healthy volunteers heterozygous for the Mahidol 487A glucose-6-phosphate dehydrogenase (G6PD)-deficient variant versus G6PD-normal females, and with reference to primaquine. Six G6PD-heterozygous subjects (G6PD enzyme activity 40-60% of normal) and six G6PD-normal subjects per treatment group received single-dose tafenoquine (100, 200, or 300 mg) or primaquine (15 mg × 14 days). All participants had pretreatment hemoglobin levels ≥ 12.0 g/dL. Tafenoquine dose escalation stopped when hemoglobin decreased by ≥ 2.5 g/dL (or hematocrit decline ≥ 7.5%) versus pretreatment values in ≥ 3/6 subjects. A dose-response was evident in G6PD-heterozygous subjects ( N = 15) receiving tafenoquine for the maximum decrease in hemoglobin versus pretreatment values. Hemoglobin declines were similar for tafenoquine 300 mg (-2.65 to -2.95 g/dL [ N = 3]) and primaquine (-1.25 to -3.0 g/dL [ N = 5]). Two further cohorts of G6PD-heterozygous subjects with G6PD enzyme levels 61-80% ( N = 2) and > 80% ( N = 5) of the site median normal received tafenoquine 200 mg; hemolysis was less pronounced at higher G6PD enzyme activities. Tafenoquine hemolytic potential was dose dependent, and hemolysis was greater in G6PD-heterozygous females with lower G6PD enzyme activity levels. Single-dose tafenoquine 300 mg did not appear to increase the severity of hemolysis versus primaquine 15 mg × 14 days.

[Clinical investigation on administration method of gatifloxacin based on PK/PD theory].

PubMed

Mikamo, Hiroshige; Tanaka, Kaori; Watanabe, Kunitomo; Tamaya, Teruhiko; Izumi, Koji

2006-10-01

There have not been sufficient clinical studies based on pharmacokinetics/pharmacodynamics (PK/PD) theory, on which many clinical doctors have recently focused. To consider the optimized administration method based on PK/PD theory for gatifloxacin (GFLX), which was one of the oral fluoroquinolone antibacterial, we influenzae investigated clinical efficacies and adverse events for pelvic inflammatory disease (PID) in giving GFLX daily 400 mg divided twice a day or four times a day. The number of leukocyte and the value of CRP were significantly reduced by chemotherapy in twice a day group, compared with four times a day group. We were able to measure the blood level in 4 cases. The AUC/MIC values for presumption causative bacteria (causative bacteria in both cases: Escherichia coli) in cured patients were 142.28 and 280.16, however, in therapy-failed patients, the AUC/MIC value to presumption causative bacterium were 4.10 (causative bacteria: Prevotella bivia) and 4.35 (causative bacteria: Pseudomonas aeruginosa). These results suggested the importance of the therapeutic method based on PK/PD theory.

Programmed cell death 1 (PD-1) regulates the effector function of CD8 T cells via PD-L1 expressed on target keratinocytes.

PubMed

Okiyama, Naoko; Katz, Stephen I

2014-09-01

Programmed cell death 1 (PD-1) is an inhibitory molecule expressed by activated T cells. Its ligands (PD-L1 and -L2; PD-Ls) are expressed not only by a variety of leukocytes but also by stromal cells. To assess the role of PD-1 in CD8 T cell-mediated diseases, we used PD-1-knockout (KO) OVA-specific T cell-receptor transgenic (Tg) CD8 T cells (OT-I cells) in a murine model of mucocutaneous graft-versus-host disease (GVHD). We found that mice expressing OVA on epidermal keratinocytes (K14-mOVA mice) developed markedly enhanced GVHD-like disease after transfer of PD-1-KO OT-I cells as compared to those mice transferred with wild-type OT-I cells. In addition, K14-mOVA × OT-I double Tg (DTg) mice do not develop GVHD-like disease after adoptive transfer of OT-I cells, while transfer of PD-1-KO OT-I cells caused GVHD-like disease in a Fas/Fas-L independent manner. These results suggest that PD-1/PD-Ls-interactions have stronger inhibitory effects on pathogenic CD8 T cells than does Fas/Fas-L-interactions. Keratinocytes from K14-mOVA mice with GVHD-like skin lesions express PD-L1, while those from mice without the disease do not. These findings reflect the fact that primary keratinocytes express PD-L1 when stimulated by interferon-γ in vitro. When co-cultured with K14-mOVA keratinocytes for 2 days, PD-1-KO OT-I cells exhibited enhanced proliferation and activation compared to wild-type OT-I cells. In addition, knockdown of 50% PD-L1 expression on the keratinocytes with transfection of PD-L1-siRNA enhanced OT-I cell proliferation. In aggregate, our data strongly suggest that PD-L1, expressed on activated target keratinocytes presenting autoantigens, regulates autoaggressive CD8 T cells, and inhibits the development of mucocutaneous autoimmune diseases. Published by Elsevier Ltd.

Metabolic Linkage and Correlations to Storage Capacity in Erythrocytes from Glucose 6-Phosphate Dehydrogenase-Deficient Donors.

PubMed

Reisz, Julie A; Tzounakas, Vassilis L; Nemkov, Travis; Voulgaridou, Artemis I; Papassideri, Issidora S; Kriebardis, Anastasios G; D'Alessandro, Angelo; Antonelou, Marianna H

2017-01-01

In glucose 6-phosphate dehydrogenase (G6PD) deficiency, decreased NADPH regeneration in the pentose phosphate pathway and subnormal levels of reduced glutathione result in insufficient antioxidant defense, increased susceptibility of red blood cells (RBCs) to oxidative stress, and acute hemolysis following exposure to pro-oxidant drugs and infections. Despite the fact that redox disequilibrium is a prominent feature of RBC storage lesion, it has been reported that the G6PD-deficient RBCs store well, at least in respect to energy metabolism, but their overall metabolic phenotypes and molecular linkages to the storability profile are scarcely investigated. We performed UHPLC-MS metabolomics analyses of weekly sampled RBC concentrates from G6PD sufficient and deficient donors, stored in citrate phosphate dextrose/saline adenine glucose mannitol from day 0 to storage day 42, followed by statistical and bioinformatics integration of the data. Other than previously reported alterations in glycolysis, metabolomics analyses revealed bioactive lipids, free fatty acids, bile acids, amino acids, and purines as top variables discriminating RBC concentrates for G6PD-deficient donors. Two-way ANOVA showed significant changes in the storage-dependent variation in fumarate, one-carbon, and sulfur metabolism, glutathione homeostasis, and antioxidant defense (including urate) components in G6PD-deficient vs. sufficient donors. The levels of free fatty acids and their oxidized derivatives, as well as those of membrane-associated plasticizers were significantly lower in G6PD-deficient units in comparison to controls. By using the strongest correlations between in vivo and ex vivo metabolic and physiological parameters, consecutively present throughout the storage period, several interactomes were produced that revealed an interesting interplay between redox, energy, and hemolysis variables, which may be further associated with donor-specific differences in the post-transfusion performance of G6PD-deficient RBCs. The metabolic phenotypes of G6PD-deficient donors recapitulate the basic storage lesion profile that leads to loss of metabolic linkage and rewiring. Donor-related issues affect the storability of RBCs even in the narrow context of this donor subgroup in a way likely relevant to transfusion medicine.

Urgent-Start Peritoneal Dialysis and Hemodialysis in ESRD Patients: Complications and Outcomes.

PubMed

Jin, Haijiao; Fang, Wei; Zhu, Mingli; Yu, Zanzhe; Fang, Yan; Yan, Hao; Zhang, Minfang; Wang, Qin; Che, Xiajing; Xie, Yuanyuan; Huang, Jiaying; Hu, Chunhua; Zhang, Haifen; Mou, Shan; Ni, Zhaohui

2016-01-01

Several studies have suggested that urgent-start peritoneal dialysis (PD) is a feasible alternative to hemodialysis (HD) in patients with end-stage renal disease (ESRD), but the impact of the dialysis modality on outcome, especially on short-term complications, in urgent-start dialysis has not been directly evaluated. The aim of the current study was to compare the complications and outcomes of PD and HD in urgent-start dialysis ESRD patients. In this retrospective study, ESRD patients who initiated dialysis urgently without a pre-established functional vascular access or PD catheter at a single center from January 2013 to December 2014 were included. Patients were grouped according to their dialysis modality (PD and HD). Each patient was followed for at least 30 days after catheter insertion (until January 2016). Dialysis-related complications and patient survival were compared between the two groups. Our study enrolled 178 patients (56.2% male), of whom 96 and 82 patients were in the PD and HD groups, respectively. Compared with HD patients, PD patients had more cardiovascular disease, less heart failure, higher levels of serum potassium, hemoglobin, serum albumin, serum pre-albumin, and lower levels of brain natriuretic peptide. There were no significant differences in gender, age, use of steroids, early referral to a nephrologist, prevalence of primary renal diseases, prevalence of co-morbidities, and other laboratory characteristics between the groups. The incidence of dialysis-related complications during the first 30 days was significantly higher in HD than PD patients. HD patients had a significantly higher probability of bacteremia compared to PD patients. HD was an independent predictor of short-term (30-day) dialysis-related complications. There was no significant difference between PD and HD patients with respect to patient survival rate. In an experienced center, PD is a safe and feasible dialysis alternative to HD for ESRD patients with an urgent need for dialysis.

Protective effect of tangeritin in transgenic Drosophila model of Parkinson's disease.

PubMed

Fatima, Ambreen; Khanam, Saba; Rahul, Rahul; Jyoti, Smita; Naz, Falaq; Ali, Fahad; Siddique, Yasir Hasan

2017-01-01

Parkinson's disease (PD) is a neurodegenerative disorder caused due to the loss of dopaminergic neurons in substantia nigra region of midbrain. The disease is characterized by the accumulation of alpha-synuclein into depositions known as lewy bodies. Till date there is no cure for PD but the limited number of medications may provide temporary relief from the PD symptoms. Flavonoids are a group of polyphenols found in plants. The health benefits of flavonoids have been universally accepted. Tangeritin is a pentamethoxy flavone found in the peels of Mandarin oranges ( Citrus reticulata ). The present study was conducted to study the effect of tangeritin on the symptoms of PD exhibited by the PD model transgenic flies ( Drosophila melanogaster) . Tangeritin at a final concentration of 5, 10 and 20 microM was added to the diet and the flies were allowed to feed on it for 24 days. At the same time other set of PD flies were allowed to feed on a diet having 10-3 M of L-Dopa. The effect of tangeritin was studied on the activity pattern, climbing ability, dopamine content, oxidative stress markers (lipid peroxidation, reduced glutathione, glutathione-S-transferase, protein carbonyl content and monoamine oxidase activity) and on the histopathology of the brain of PD model flies. The study showed that the exposure of PD flies to different doses of tangeritin showed a marked delay in the loss of climbing ability and increase in the dopamine content. Tangeritin also showed a reduction in various oxidative stress markers. Hence it is concluded that tangeritin showed a marked reduction in the PD symptoms and thus could be of great importance for further research in treating PD.

Profiling the dynamic expression of checkpoint molecules on cytokine-induced killer cells from non-small-cell lung cancer patients.

PubMed

Zhang, Lin; Wang, Jian; Wei, Feng; Wang, Kaiyuan; Sun, Qian; Yang, Fan; Jin, Hao; Zheng, Yu; Zhao, Hua; Wang, Limei; Yu, Wenwen; Zhang, Xiying; An, Yang; Yang, Lili; Zhang, Xinwei; Ren, Xiubao

2016-07-12

Immune checkpoints associate with dysfunctional T cells, which have a reduced ability to clear pathogens or cancer cells. T-cell checkpoint blockade may improve patient survival. However, checkpoint molecules on cytokine-induced killer (CIK) cell, a non-specific adoptive immunotherapy, remain unknown. In present study, we detected the dynamic expression of eight major checkpoint molecules (CTLA-4, PD-1, PD-L1, TIM- 3, CEACAM-1, LAG-3, TIGIT and BTLA) on CIK cells from NSCLC patients. The majority of these molecules, except BTLA, were sharply elevated during the early stage of CIK cell culture. Thereafter, PD-1 and TIGIT expressions decreased gradually towards the initial level (day 0). Moreover, CTLA-4 faded away during the later stage of CIK culture. LAG-3 expression decreased but was still significantly higher than the initial level. Of note, PD-L1 remained stably upregulated during CIK culture compared with PD-1, indicating that PD-L1 might act as an inhibitory molecule on CIK cells instead of PD-1. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation. BTLA displayed a distinct pattern, and its expression gradually decreased throughout the CIK culture. These observations suggested that CIK cells might be partly exhausted before clinical transfusion, characterized by the high expression of PD-L1, LAG-3, TIM- 3, and CEACAM-1 and the low expression of TIGIT, BTLA, PD-1, and CTLA-4 compared with initial culture. Our results imply that implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients.

Reduced Activated T Lymphocytes (CD4+CD25+) and Plasma Levels of Cytokines in Parkinson's Disease.

PubMed

Rocha, Natalia Pessoa; Assis, Frankcinéia; Scalzo, Paula Luciana; Vieira, Érica Leandro Marciano; Barbosa, Izabela Guimarães; de Souza, Mariana Soares; Christo, Paulo Pereira; Reis, Helton José; Teixeira, Antonio Lucio

2018-02-01

Parkinson's disease (PD) is the second most common neurodegenerative disease. The cause of neurodegeneration in PD is not completely understood, and evidence has shown that inflammatory/immune changes may be involved in PD pathophysiology. Herein, we aimed to determine the profile of the peripheral immune system in patients with PD in comparison with controls. Forty patients with PD and 25 age- and gender-matched controls were enrolled in this study. From these, 23 PD patients and 21 controls were included in the immunophenotyping analyses. Peripheral blood was drawn on the same day of the clinical assessment and submitted to plasma separation for enzyme-linked immunosorbent assay or cytometric bead array. Immunophenotyping analyses of the peripheral blood were performed by flow cytometry. We found that patients with PD presented peripheral immune changes evidenced by decreased percentage of T lymphocytes (CD3+ cells), especially activated T lymphocytes (CD4+CD25+ cells), when compared with controls. In line with these results, we also found decreased plasma levels of the cytokines IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A in the PD group. In vitro experiments demonstrated that the production of cytokines by peripheral blood mononuclear cells harvested from healthy young donors was reduced after exposure to the anti-parkinsonian drugs levodopa and pramipexole. Our data corroborate the hypothesis that immunological mechanisms are involved in PD. It is not clear whether the differences that we have found are due to adaptive mechanisms or to changes associated with PD, including pharmacological treatment, or even directly related to the disease pathophysiology. Future studies are needed in this regard.

The possible mechanism of Parkinson's disease progressive damage and the preventive effect of GM1 in the rat model induced by 6-hydroxydopamine.

PubMed

Xu, Renshi; Zhou, Yiyi; Fang, Xin; Lu, Yi; Li, Jiao; Zhang, Jie; Deng, Xia; Li, Shujuan

2014-12-10

The progressive pathogenesis and prevention of Parkinson's disease (PD) remains unknown at present. Therefore, the present study aimed to investigate the possible progressive pathogenesis and prevention of PD. Our study investigated the content of glutamate, mitochondria calcium, calmodulin, malonaldehyde and trace elements in striatum, cerebral cortex and hippocampus tissues; and the expression of bcl-2, bax and neuronal nitric oxide synthase (nNOS) in substantia nigra and striatum; and the change of apomorphine induced rotation behavior; and the treatmental effect of monosialotetrahexosylganglioside (GM1) intraperitoneal administration for 14 days in a PD rat model induced by 6-hydroxydopamine. The results revealed that the content of glutamate significantly decreased, and that of mitochondria calcium, calmodulin, malonaldehyde and ferrum significantly increased in striatum, cerebral cortex and hippocampus tissues; the content of magnesium significantly decreased, and that of cuprum and zinc significantly increased in cerebral cortex; the expression of bcl-2 significantly decreased, and that of bax and nNOS significantly increased in substantia nigra and striatum in PD rat. GM1 can partially improve the apomorphine induced rotation behavior and changes of glutamate, mitochondria calcium, calmodulin content in striatum of PD rat. Data suggested that dysfunction of excitatory amino acids neurotransmitter, calcium homeostasis disorder, abnormal metabolism of oxygen free radicals, abnormal trace elements distribution and/or deposition and excessive apoptosis participated in the progressive process of PD, and that GM1 could partially prevent the progressive damage. Copyright © 2014 Elsevier B.V. All rights reserved.

Parkinson's disease psychosis: symptoms, management, and economic burden.

PubMed

Hermanowicz, Neal; Edwards, Kari

2015-08-01

Parkinson’s disease psychosis (PDP) is a costly,debilitating condition that generally develops several years after diagnosis of Parkinson’s disease (PD).PD is the second-most common neurodegenerative disease, and it imposes a significant burden on the healthcare system. Non-motor symptoms commonly manifest in PD, contributing to the severity of a patient’s disability. The neuropsychiatric symptoms that are common in PD can be a significant source of distress to patients and caregivers. Recent studies have shown that more than 50% of patients with PD will develop psychosis at some time over the course of the disease. The responsibility for caring for a person with PDP frequently falls on family members. Caregiver distress is frequently predicted when patients with PD have symptoms of psychosis.Hallucinations and delusions are independent predictors of nursing home placement for patients with PDP. The authors sought to examine total healthcare expenditures among patients with PDP compared with patients with PD without psychosis.All costs were higher for patients with PDP than for those with PD without psychosis and all-Medicare cohorts, with the highest cost differentials found in long-term care costs ($31,178 for PDP vs $14,461 forPD without psychosis), skilled nursing facility costs($6601 for PDP vs $2067 for PD without psychosis),and inpatient costs ($10,125 for PDP vs $6024 for PD without psychosis). Patients with PDP spent an average of 179 days in long-term care, compared with 83 days for patients with PD without psychosis. As expected, long-term care utilization and expenditures were significantly higher for patients with PDP than for patients with PD without psychosis. Reducing long-term care utilization by patients with PDP may significantly lower the overall economic burden associated with PDP.

Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose.

PubMed

McDougall, Sanders A; Moran, Andrea E; Baum, Timothy J; Apodaca, Matthew G; Real, Vanessa

2017-09-01

Ketamine is used by preadolescent and adolescent humans for licit and illicit purposes. The goal of the present study was to determine the effects of acute and repeated ketamine treatment on the unconditioned behaviors and conditioned locomotor activity of preadolescent and adolescent rats. To assess unconditioned behaviors, female and male rats were injected with ketamine (5-40 mg/kg), and distance traveled was measured on postnatal day (PD) 21-25 or PD 41-45. To assess conditioned activity, male and female rats were injected with saline or ketamine in either a novel test chamber or the home cage on PD 21-24 or PD 41-44. One day later, rats were injected with saline and conditioned activity was assessed. Ketamine produced a dose-dependent increase in the locomotor activity of preadolescent and adolescent rats. Preadolescent rats did not exhibit sex differences, but ketamine-induced locomotor activity was substantially stronger in adolescent females than males. Repeated ketamine treatment neither caused a day-dependent increase in locomotor activity nor produced conditioned activity in preadolescent or adolescent rats. The activity-enhancing effects of ketamine are consistent with the actions of an indirect dopamine agonist, while the inability of ketamine to induce conditioned activity is unlike what is observed after repeated cocaine or amphetamine treatment. This dichotomy could be due to ketamine's ability to both enhance DA neurotransmission and antagonize N-methyl-D-aspartate (NMDA) receptors. Additional research will be necessary to parse out the relative contributions of DA and NMDA system functioning when assessing the behavioral effects of ketamine during early ontogeny.

Glucose-6-phosphate dehydrogenase enzyme stability in filter paper dried blood spots.

PubMed

Flores, Sharon R; Hall, Elizabeth M; De Jesús, Víctor R

2017-10-01

Prior to initial distribution of Glucose-6-phosphate dehydrogenase (G6PD) proficiency testing (PT) materials, we evaluated G6PD enzyme stability in dried blood spots (DBS) under various temperature and humidity environments to develop storage and usage guidelines for our new materials. We prepared fresh G6PD-normal DBS materials and conducted stability evaluations of daily use and short and long-term storage under various temperature and humidity environments. G6PD DBS PT materials retained 92% of initial activity after 30days of use at 4°C. Materials stored at -20°C and 4°C with desiccant for 30days retained 95% and 90% of initial activity, respectively. When stored for one year at -20°C or six months at 4°C specimens retained >90% of initial activity. Specimens stored at 37°C with desiccant lost 10% activity in three days. At the end of 30days, specimens stored under 'Extreme'-humidity >50% without desiccant- conditions at 37°C assayed below the NSQAP cut off for G6PD. Humidity exacerbated loss of enzyme activity with increasing temperature and time duration. Data suggest that G6PD PT materials can be stored at 4°C and used for up to one month and can be stored at -20°C for one year and yield >90% enzyme activity. Exposure to warm temperatures, especially with elevated humidity, should be avoided. Desiccant should always be used to mitigate humidity effects. Published by Elsevier Inc.

Evidence for Hippocampus-Dependent Contextual Learning at Postnatal Day 17 in the Rat

ERIC Educational Resources Information Center

Foster, Jennifer A.; Burman, Michael A.

2010-01-01

Long-term memory for fear of an environment (contextual fear conditioning) emerges later in development (postnatal day; PD 23) than long-term memory for fear of discrete stimuli (PD 17). As contextual, but not explicit cue, fear conditioning relies on the hippocampus; this has been interpreted as evidence that the hippocampus is not fully…

School-Based Learning for Individual Diversity in Education: The SLIDE Project

ERIC Educational Resources Information Center

Harrington, Ingrid

2013-01-01

Whole-School Professional Development (PD) days held regularly in schools are designed to promote and up-skill school staff on relevant areas of educational policy and practice. An aim of PD days is to empower participants with new knowledges and skills, and to confirm that current practices and interpretations of education policy and procedure…

School-Based Learning for Individual Diversity in Education: The SLIDE Project

ERIC Educational Resources Information Center

Harrington, Ingrid

2013-01-01

Whole-School Professional Development (PD) days held regularly in schools are designed to promote and up-skill teaching and administrative staff on relevant areas of educational policy and practice. An aim of PD days is to empower participants with new knowledges and skills, and to confirm that current practices and interpretations of education…

AB073. Classic infantile-onset Pompe disease: phenotypes and outcomes of 5 Vietnamese patients receiving enzyme replacement therapy

PubMed Central

Nguyen, Khanh Ngoc; Do, Mai Thi Thanh; Can, Ngoc Thi Bich; Hwu, Wuh-Liang; Vu, Dung Chi

2017-01-01

Background Pompe disease (PD) or glycogen storage disease type II is a lysosomal storage disorder, caused by mutations of GAA gene which results in deficiency of acid alpha-glucosidase (GAA) enzyme that involves in metabolism of glycogen in the lysosomes. Its incidence is 1/14,000–1/100,000. PD is divided into three types: classic infantile onset, non-classic infantile onset, and late onset. Early enzyme replacement therapy (ERT) before developing respiratory distress may lead to good outcome. Since 2013, we have identified 16 cases with classic infantile-onset and 5 cases were treated with ERT. Herein, we describe phenotypes and outcomes of five infantile-onset PD patients who received ERT. Methods GAA enzyme assay was done at National Taiwan University Hospital. Results Ages of diagnosis were 12, 38 and 70 days, 5 and 9 months of age. Clinical presentations included macroglossia (5/5), hypertrophic cardiomyopathy (5/5), failure to thrive (5/5), facial weakness and hypotonia (3 patients diagnosed after 70 days of age), respiratory failure (1 patient diagnosed at 9 months of age). All patients had mildly elevated plasma CK (270–380 UI/L) and transaminase (60–260 UI/l). Ages at starting ERT were 28 and 58 days, 3, 6 and 10 months. The time intervals from diagnosis to starting ERT were between 14 days and 1 month. The durations of ERT were 4–22 months. The outcomes were good. All patients had improvement of cardiac functions shown on echocardiography, respiratory status, and motor development. The patient who first received ERT at 10 months of age was reportedly dead at home due to food obstruction at 18 months of age. Current ages of the survivors were 5–24 months. Conclusions Patients with classic infantile-onset PD will have good outcomes if ERT is started early. Newborn screening for this disease is necessary to yield an early diagnosis.

The postpartum llama: fertility after parturition.

PubMed

Bravo, P W; Fowler, M E; Lasley, B L

1994-12-01

Fertility was evaluated at various times during the postpartum period in the llama. Fifty-six parous female llamas chosen at random were bred at 10, 20, and 30 days postpartum with six intact males. Half of the females copulated only once and the other half twice within an interval of 24 h. Ovarian activity was monitored by ultrasonography and analysis of urinary estrone sulfate and pregnanediol glucuronide (PdG). At the time of copulation, all females had developed ovulatory-size follicles. Ovulation was confirmed by the presence of a CL at 8 days after breeding and PdG concentrations > 1 ng/mg creatinine (Cr). Conception was defined as PdG concentrations > 1 ng/mg Cr at 15 days after breeding and the presence of a CL. Pregnancy was defined as the presence of a CL, PdG concentrations > 1 ng/mg Cr and an embryonic vesicle 20 days postbreeding. There were no significant differences in the proportion of females ovulating after breeding at different times postpartum; however, conception and pregnancy were significantly greater in females bred at Day 20 or 30. Ovarian follicle size was significantly larger at 30 days (9.1 mm) than at 10 and 20 days (7.9 and 8.8 mm, respectively) of breeding, with no difference in concentrations of estrone sulfate. The proportion of females conceiving as a result of breeding at 10 days postpartum (6 out of 10) was significantly less than for females bred at 20 (13 out of 15) or 30 days (16 out of 18).(ABSTRACT TRUNCATED AT 250 WORDS)

Postpartum thyroid dysfunction and postpartum depression: are they two linked disorders?

PubMed

Lucas, A; Pizarro, E; Granada, M L; Salinas, I; Sanmartí, A

2001-12-01

Postpartum has been considered as a period of risk for developing postpartum depression (PD) by some but not all authors, and this PD has been linked with postpartum thyroid dysfunction (PPTD). The major aim of this study was to evaluate the relation between the presence of PPTD and PD. Six hundred and forty-one healthy Caucasian women recruited between their 36th week of pregnancy and fourth day postpartum underwent clinical and laboratory evaluation and were checked again at 1 (n = 605), 3 (n = 552), 6 (n = 574), 9 (n = 431), and 12 (n = 444) months postpartum. At baseline and at each clinical evaluation, Beck Depression Inventory (BDI) was administered to screen PD. The definitive diagnoses of PD was performed by a psychiatrist according to the DSM-III-R criteria. At each visit, we determined serum free T4 and TSH concentrations. Thyroperoxidase and thyroglobulin antibodies were determined only in patients with abnormal hormone concentrations. Postpartum thyroiditis (PPT) was considered to be present in women with overt or subclinical transient hyperthyroidism between 1 and 3 months postpartum and/or overt or subclinical hypothyroidism between 3 and 6 months postpartum. Fifty-six women developed postpartum thyroid dysfunction (PPTD), corresponding to an incidence rate of 11%: 45 with PPT [incidence rate 7.8%; confidence interval (CI) 5.6-10%], eight with Graves' disease (incidence rate 1.5%; CI 0.5-2.5%) and three with nonpalpable toxic thyroid adenoma (incidence rate 0.5%; CI 0-1.5%). Five hundred and eighty of the evaluated women (incidence rate 90.5%; CI 95% 88.2-92.8) presented BDI scores below 21 and therefore the PD diagnoses was excluded. In 50 cases (incidence rate 7.8%; Cl 95% 5.7-9.8), we detected a BDI score over 21 in some evaluations, but the PD diagnosis was not confirmed. Another 11 (incidence rate 1.7%; CI 95% 0.7-2.7) were diagnosed as having PD and required psychiatric treatment. None of the PPTD was diagnosed as having PD. The BDI scores frequency over 21 was similar between healthy women and those with PPTD. Patients with a previous history of depression developed PD more often (P < 0.0001). One hundred and ninety women breast fed their babies for more than 2 months, without observing a higher PD rate or BDI scores over 21 (P = 0.5). We found a general PD incidence rate of 1.7% in our group of patients. This figure is not higher in women with hormone abnormalities caused by PPTD. Women with a past history of depression present a higher risk of PD while those who breast fed did not have an increased risk.

A Syllabus for Teaching Peritoneal Dialysis to Patients and Caregivers.

PubMed

Figueiredo, Ana E; Bernardini, Judith; Bowes, Elaine; Hiramatsu, Miki; Price, Valerie; Su, Chunyan; Walker, Rachael; Brunier, Gillian

Being aware of controversies and lack of evidence in peritoneal dialysis (PD) training, the Nursing Liaison Committee of the International Society for Peritoneal Dialysis (ISPD) has undertaken a review of PD training programs around the world in order to develop a syllabus for PD training. This syllabus has been developed to help PD nurses train patients and caregivers based on a consensus of training program reviews, utilizing current theories and principles of adult education. It is designed as a 5-day program of about 3 hours per day, but both duration and content may be adjusted based on the learner. After completion of our proposed PD training syllabus, the PD nurse will have provided education to a patient and/or caregiver such that the patient/caregiver has the required knowledge, skills and abilities to perform PD at home safely and effectively. The course may also be modified to move some topics to additional training times in the early weeks after the initial sessions. Extra time may be needed to introduce other concepts, such as the renal diet or healthy lifestyle, or to arrange meetings with other healthcare professionals. The syllabus includes a checklist for PD patient assessment and another for PD training. Further research will be needed to evaluate the effect of training using this syllabus, based on patient and nurse satisfaction as well as on infection rates and longevity of PD as a treatment. Copyright © 2016 International Society for Peritoneal Dialysis.

Sex Differences in Early Postnatal Microglial Colonization of the Developing Rat Hippocampus Following a Single-Day Alcohol Exposure.

PubMed

Ruggiero, M J; Boschen, K E; Roth, T L; Klintsova, A Y

2018-06-01

Microglia are involved in various homeostatic processes in the brain, including phagocytosis, apoptosis, and synaptic pruning. Sex differences in microglia colonization of the developing brain have been reported, but have not been established following alcohol insult. Developmental alcohol exposure represents a neuroimmune challenge that may contribute to cognitive dysfunction prevalent in humans with Fetal Alcohol Spectrum Disorders (FASD) and in rodent models of FASD. Most studies have investigated neuroimmune activation following adult alcohol exposure or following multiple exposures. The current study uses a single day binge alcohol exposure model (postnatal day [PD] 4) to examine sex differences in the neuroimmune response in the developing rat hippocampus on PD5 and 8. The neuroimmune response was evaluated through measurement of microglial number and cytokine gene expression at both time points. Male pups had higher microglial number compared to females in many hippocampal subregions on PD5, but this difference disappeared by PD8, unless exposed to alcohol. Expression of pro-inflammatory marker CD11b was higher on PD5 in alcohol-exposed (AE) females compared to AE males. After alcohol exposure, C-C motif chemokine ligand 4 (CCL4) was significantly increased in female AE pups on PD5 and PD8. Tumor necrosis factor-α (TNF-α) levels were also upregulated by AE in males on PD8. The results demonstrate a clear difference between the male and female neuroimmune response to an AE challenge, which also occurs in a time-dependent manner. These findings are significant as they add to our knowledge of specific sex-dependent effects of alcohol exposure on microglia within the developing brain.

Removal of gadolinium by peritoneal dialysis.

PubMed

Murashima, M; Drott, H R; Carlow, D; Shaw, L M; Milone, M; Bachman, M; Tsai, D E; Yang, S-L; Bloom, R D

2008-05-01

An association between gadolinium-containing contrast and the development of nephrogenic systemic fibrosis (NSF) has been increasingly recognized. For patients receiving hemodialysis (HD) who are exposed to gadolinium, the Federal Drug Administration (FDA) recommends HD to remove this contrast agent in order to minimize the risk of NSF. This study examines if gadolinium can be removed by frequent exchanges by peritoneal dialysis (PD). Following administration of 0.1 mmol/kg of gadodiamide to a patient with end-stage renal disease, the serum clearance of this contrast agent by automated PD was examined. 10 and 15 exchanges of PD using an automated cycler were respectively performed during the first and second 24-hour periods after gadolinium exposure. Serum gadolinium levels were measured 1 hour after the gadolinium administration, then at 24 and 48 hours after PD was initiated. 90% of the gadolinium was removed from the circulation in 2 days with a regimen of 10-15 exchanges per day of PD. For patients on chronic maintenance PD who receive gadolinium, our case suggests that a temporary intensive automated PD regimen, aimed at maximizing clearance of this contrast agent immediately after exposure, could be an effective alternative when institution of HD is problematic.

KSC-03PD-2817

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Before the start of the kickoff presentation for Spaceport Super Safety and Health Day, Center Director Jim Kennedy (left) chats with guest speaker Capt. Charles Plumb (USNR retired) and United Space Alliance Vice President and Deputy Program Manager, Florida Operations, Bill Pickavance. Spaceport Super Safety and Health Day is an annual event at KSC and Cape Canaveral Air Force Station dedicated to reinforcing safe and healthful behaviors in the workforce. Safety Awards were also given to individuals and groups.

Reduced glutathione and glutathione disulfide in the blood of glucose-6-phosphate dehydrogenase-deficient newborns.

PubMed

Gong, Zhen-Hua; Tian, Guo-Li; Huang, Qi-Wei; Wang, Yan-Min; Xu, Hong-Ping

2017-07-20

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency. The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard. G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 μmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 μmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P < 0.001 for DBS samples plus sodium citrate that were examined the first day after preparation, there were no significant differences in the mean GSH concentration and GSH/GSSG ratio between the G6PD deficiency-positive and negative groups when examined three days after sample preparation. The concentration of GSH and the ratio of GSH/GSSG in blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.

Affect Regulation and Purging: An Ecological Momentary Assessment Study in Purging Disorder

PubMed Central

Haedt-Matt, Alissa A.; Keel, Pamela K.

2015-01-01

Research suggests that affect may play an important role in the propensity to purge among women with Purging Disorder (PD). However, prior work has been constrained to cross-sectional or laboratory designs which impact temporal interpretations and ecological validity. This study examined the role of negative affect (NA) and positive affect (PA) in triggering and maintaining purging in PD using ecological momentary assessment. Women with PD (N=24) made multiple daily ratings of affect and behavior for two weeks. Multilevel models examined associations between affect and purging at different levels of analysis, including a novel analytic approach to address the specificity of changes in affect relative to purging behavior by comparing trajectories of change on purge versus non-purge days. For trajectories of affect over time, NA increased before purging and decreased following purging on purge days; however, only the decrease in NA following purging was significantly different from the trajectory of NA on non-purge days. Conversely, PA failed to increase before purging on purge days compared to a matched time-point on non-purge days. These findings suggest unique roles of PA in triggering and NA in maintaining purging in PD and support models in which purging functions to regulate affect. For comparisons of ratings before and after purging, NA increased and PA decreased after purging, highlighting how different analytic strategies produce different findings requiring integration into affect regulation models. These data provide insight into why women with PD purge after consuming normal amounts of food, a crucial first step for developing effective interventions. PMID:25688426

Gene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie's disease.

PubMed

Davila, Hugo H; Magee, Thomas R; Vernet, Dolores; Rajfer, Jacob; Gonzalez-Cadavid, Nestor F

2004-11-01

The goal of the present study was to investigate the antifibrotic role of inducible nitric oxide synthase (iNOS) in Peyronie's disease (PD) by determining whether a plasmid expressing iNOS (piNOS) injected into a PD-like plaque can induce regression of the plaque. A PD-like plaque was induced with fibrin in the penile tunica albuginea of mice and then injected with a luciferase-expressing plasmid (pLuc), either alone or with piNOS, following luciferase expression in vivo by bioluminescence imaging. Rats were treated with either piNOS, an empty control plasmid (pC), or saline. Other groups were treated with pC or piNOS, in the absence of fibrin. Tissue sections were stained for collagen, transforming growth factor (TGF) beta1, and plasminogen-activator inhibitor (PAI-1) as profibrotic factors; copper-zinc superoxide dismutase (CuZn SOD) as scavenger of reactive oxygen species (ROS); and nitrotyrosine to detect nitric oxide reaction with ROS. Quantitative image analysis was applied. Both iNOS and xanthine oxido-reductase (XOR; oxidative stress) were estimated by Western blot analysis. Luciferase reporter expression was restricted to the penis, peaked at 3 days after injection, but continued for at least 3 wk. In rats receiving piNOS, iNOS expression also peaked at 3 days, but expression decreased at the end of treatment, when a considerable reduction of plaque size occurred. Protein nitrotyrosine, XOR, and CuZn SOD increased, and TGFbeta1 and PAI-1 decreased. The piNOS gene transfer regressed the PD plaque and expression of profibrotic factors, supporting the view that endogenous iNOS induction in PD is defense mechanism by the tissue against fibrosis.

Impaired Sense of Smell in a Drosophila Parkinson’s Model

PubMed Central

Poddighe, Simone; Bhat, Krishna Moorthi; Setzu, Maria Dolores; Solla, Paolo; Angioy, Anna Maria; Marotta, Roberto; Ruffilli, Roberta; Marrosu, Francesco; Liscia, Anna

2013-01-01

Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by the clinical triad: tremor, akinesia and rigidity. Several studies have suggested that PD patients show disturbances in olfaction at the earliest onset of the disease. The fruit fly Drosophila melanogaster is becoming a powerful model organism to study neurodegenerative diseases. We sought to use this system to explore olfactory dysfunction, if any, in PINK1 mutants, which is a model for PD. PINK1 mutants display many important diagnostic symptoms of the disease such as akinetic motor behavior. In the present study, we describe for the first time, to the best of our knowledge, neurophysiological and neuroanatomical results concerning the olfactory function in PINK1 mutant flies. Electroantennograms were recorded in response to synthetic and natural volatiles (essential oils) from groups of PINK1 mutant adults at three different time points in their life cycle: one from 3–5 day-old flies, from 15–20 and from 27–30 days. The results obtained were compared with the same age-groups of wild type flies. We found that mutant adults showed a decrease in the olfactory response to 1-hexanol, α-pinene and essential oil volatiles. This olfactory response in mutant adults decreased even more as the flies aged. Immunohistological analysis of the antennal lobes in these mutants revealed structural abnormalities, especially in the expression of Bruchpilot protein, a marker for synaptic active zones. The combination of electrophysiological and morphological results suggests that the altered synaptic organization may be due to a neurodegenerative process. Our results indicate that this model can be used as a tool for understanding PD pathogensis and pathophysiology. These results help to explore the potential of using olfaction as a means of monitoring PD progression and developing new treatments. PMID:24009736

Pain in Parkinson´s Disease: A Cross-Sectional Study of Its Prevalence, Types, and Relationship to Depression and Quality of Life

PubMed Central

Singliarova, Helena; Harsany, Jan; Hanakova, Marta; Martinkova, Jana; Benetin, Jan

2015-01-01

Pain is an important and distressing symptom in Parkinson’s disease (PD). Our aim was to determine the prevalence of pain, its various types and characteristics, as well as its impact on depression and quality of life (QoL) in patients with PD. How pain differs in early- and advanced-stage PD and male and female PD patients was of special interest. One hundred PD patients on dopaminergic medications had a neurological examination and participated in a structured interview on pain characteristics and completed standardized questionnaires. A total of 76% of the patients had pain. The following types of pain were present: musculoskeletal pain accounted for 41% of the total pain, dystonic pain for 17%, central neuropathic pain for 22%, radicular pain for 27%, and other pains (non-radicular low back pain, arthritic, and visceral pain) made up 24%. One type of pain affected 29% of all the subjects, two types 35%, three types 10%, and four types of pain were reported by 2%. All types of pain were more prevalent in advanced-stage PD subjects than in early-stage PD subjects, except for arthritic pain (subclassified under”other pain”). The frequency and intensity of actual, average, and worst experienced pain were significantly more severe in advanced-stage subjects. PD subjects with general pain and in advanced stages were more depressed and had poorer QoL. Depression correlated with worst pain in the last 24 hours and with pain periodicity (the worst depression score in patients with constant pain). QoL correlated with average pain in the last 7 days. Pain is a frequent problem in PD patients, and it worsens during the course of the disease. PMID:26309254

ER Stress Induced by Tunicamycin Triggers α-Synuclein Oligomerization, Dopaminergic Neurons Death and Locomotor Impairment: a New Model of Parkinson's Disease.

PubMed

Cóppola-Segovia, Valentín; Cavarsan, Clarissa; Maia, Flavia G; Ferraz, Anete C; Nakao, Lia S; Lima, Marcelo Ms; Zanata, Silvio M

2017-10-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons of the substantia nigra pars compacta (SNpc), leading to the major clinical abnormalities that characterize this disease. Although PD's etiology is unknown, α-synuclein aggregation plays a pivotal role in PD pathogenesis, which could be associated to some pathological processes such as oxidative stress, endoplasmic reticulum (ER) stress, impaired protein degradation, and mitochondrial dysfunction. Increasing experimental evidence indicates that ER stress is involved in PD, however most of the described results employed cultured cell lines and genetically modified animal models. In this study, we developed a new ER stress rat model employing the well-known ER stressor tunicamycin (Tm). To evaluate if ER stress was able to induce PD features, we performed an intranigral injection of Tm (0.1 μg/cerebral hemisphere) and animals (male Wistar rats) were analyzed 7 days post injection. The classical 6-OHDA neurotoxin model (1 μg/cerebral hemisphere) was used as an established positive control for PD. We show that Tm injection induced locomotor impairment, dopaminergic neurons death, and activation of astroglia. In addition, we observed an extensive α-synuclein oligomerization in SNpc of Tm-injected animals when compared with DMSO-injected controls. Finally, both Tm and 6-OHDA treated animals presented increased levels of ER stress markers. Taken together, these findings show for the first time that the ER stressor Tm recapitulates some of the phenotypic characteristics observed in rodent models of PD, reinforcing the concept that ER stress could be an important contributor to the pathophysiology of PD. Therefore, we propose the intranigral Tm injection as a new ER stress-based model for the study of PD in vivo.

Pain in Parkinson's Disease: A Cross-Sectional Study of Its Prevalence, Types, and Relationship to Depression and Quality of Life.

PubMed

Valkovic, Peter; Minar, Michal; Singliarova, Helena; Harsany, Jan; Hanakova, Marta; Martinkova, Jana; Benetin, Jan

2015-01-01

Pain is an important and distressing symptom in Parkinson's disease (PD). Our aim was to determine the prevalence of pain, its various types and characteristics, as well as its impact on depression and quality of life (QoL) in patients with PD. How pain differs in early- and advanced-stage PD and male and female PD patients was of special interest. One hundred PD patients on dopaminergic medications had a neurological examination and participated in a structured interview on pain characteristics and completed standardized questionnaires. A total of 76% of the patients had pain. The following types of pain were present: musculoskeletal pain accounted for 41% of the total pain, dystonic pain for 17%, central neuropathic pain for 22%, radicular pain for 27%, and other pains (non-radicular low back pain, arthritic, and visceral pain) made up 24%. One type of pain affected 29% of all the subjects, two types 35%, three types 10%, and four types of pain were reported by 2%. All types of pain were more prevalent in advanced-stage PD subjects than in early-stage PD subjects, except for arthritic pain (subclassified under"other pain"). The frequency and intensity of actual, average, and worst experienced pain were significantly more severe in advanced-stage subjects. PD subjects with general pain and in advanced stages were more depressed and had poorer QoL. Depression correlated with worst pain in the last 24 hours and with pain periodicity (the worst depression score in patients with constant pain). QoL correlated with average pain in the last 7 days. Pain is a frequent problem in PD patients, and it worsens during the course of the disease.

Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (G6PD Mahidol Variant) versus G6PD-Normal Volunteers

PubMed Central

Rueangweerayut, Ronnatrai; Bancone, Germana; Harrell, Emma J.; Beelen, Andrew P.; Kongpatanakul, Supornchai; Möhrle, Jörg J.; Rousell, Vicki; Mohamed, Khadeeja; Qureshi, Ammar; Narayan, Sushma; Yubon, Nushara; Miller, Ann; Nosten, François H.; Luzzatto, Lucio; Duparc, Stephan; Kleim, Jörg-Peter; Green, Justin A.

2017-01-01

Abstract. Tafenoquine is an 8-aminoquinoline under investigation for the prevention of relapse in Plasmodium vivax malaria. This open-label, dose-escalation study assessed quantitatively the hemolytic risk with tafenoquine in female healthy volunteers heterozygous for the Mahidol487A glucose-6-phosphate dehydrogenase (G6PD)-deficient variant versus G6PD-normal females, and with reference to primaquine. Six G6PD-heterozygous subjects (G6PD enzyme activity 40–60% of normal) and six G6PD-normal subjects per treatment group received single-dose tafenoquine (100, 200, or 300 mg) or primaquine (15 mg × 14 days). All participants had pretreatment hemoglobin levels ≥ 12.0 g/dL. Tafenoquine dose escalation stopped when hemoglobin decreased by ≥ 2.5 g/dL (or hematocrit decline ≥ 7.5%) versus pretreatment values in ≥ 3/6 subjects. A dose–response was evident in G6PD-heterozygous subjects (N = 15) receiving tafenoquine for the maximum decrease in hemoglobin versus pretreatment values. Hemoglobin declines were similar for tafenoquine 300 mg (−2.65 to −2.95 g/dL [N = 3]) and primaquine (−1.25 to −3.0 g/dL [N = 5]). Two further cohorts of G6PD-heterozygous subjects with G6PD enzyme levels 61–80% (N = 2) and > 80% (N = 5) of the site median normal received tafenoquine 200 mg; hemolysis was less pronounced at higher G6PD enzyme activities. Tafenoquine hemolytic potential was dose dependent, and hemolysis was greater in G6PD-heterozygous females with lower G6PD enzyme activity levels. Single-dose tafenoquine 300 mg did not appear to increase the severity of hemolysis versus primaquine 15 mg × 14 days. PMID:28749773

Supplemental choline during the periweaning period protects against trace conditioning impairments attributable to post-training ethanol exposure in adolescent rats.

PubMed

Hunt, Pamela S

2012-08-01

Supplemental choline during early stages of development can result in long-lasting improvements to memory function. In addition, pre- or postnatal choline has been shown to be protective against some of the adverse effects of early alcohol exposure. The present experiment examined whether supplemental choline given to rats would protect against the effects of posttraining alcohol administration on trace fear conditioning. Posttraining alcohol exposure in adolescent rats results in poor performance in this hippocampus-dependent task, although delay conditioning is unaffected. Here, rats were given an s.c. injection of either saline or choline chloride daily on postnatal days (PD) 15-26. On PD 30 subjects were trained in a trace fear conditioning procedure. For the next 3 days animals were administered 2.5 g/kg ethanol or water control, and conditional stimulus (CS)-elicited freezing was measured on PD 34. Results indicated that posttraining alcohol disrupted the expression of trace conditioning and that supplemental choline on PD 15-26 was protective against this effect. That is, choline-treated animals subsequently given posttraining ethanol performed as well as animals not given ethanol. These results indicate that supplemental choline given during the periweaning period protects against ethanol-induced impairments in a hippocampus-dependent learning task. Findings contribute to the growing literature showing improvements in learning and memory in subjects given extra dietary choline during critical periods of brain development.

SUPPLEMENTAL CHOLINE DURING THE PERIWEANING PERIOD PROTECTS AGAINST TRACE CONDITIONING IMPAIRMENTS DUE TO POST-TRAINING ETHANOL EXPOSURE IN ADOLESCENT RATS

PubMed Central

Hunt, Pamela S.

2012-01-01

Supplemental choline during early stages of development can result in long-lasting improvements to memory function. In addition, pre- or postnatal choline has been shown to be protective against some of the adverse effects of early alcohol exposure. The present experiment examined whether supplemental choline given to rats would protect against the effects of post-training alcohol administration on trace fear conditioning. Post-training alcohol exposure in adolescent rats results in poor performance in this hippocampus-dependent task, although delay conditioning is unaffected. Here, rats were given an s.c. injection of either saline or choline chloride daily on postnatal days (PD) 15-26. On PD 30 subjects were trained in a trace fear conditioning procedure. For the next three days animals were administered 2.5 g/kg ethanol or water control, and CS-elicited freezing was measured on PD 34. Results indicated that post-training alcohol disrupted the expression of trace conditioning and that supplemental choline on PD 15-26 was protective against this effect. That is, choline-treated animals subsequently given post-training ethanol performed as well as animals not given ethanol. These results indicate that supplemental choline given during the periweaning period protects against ethanol-induced impairments in a hippocampus-dependent learning task. Findings contribute to the growing literature showing improvements in learning and memory in subjects given extra dietary choline during critical periods of brain development. PMID:22687150

Delayed gastric emptying following pancreatoduodenectomy with alimentary reconstruction according to Roux-en-Y or Billroth-II.

PubMed

Glowka, Tim R; Webler, Markus; Matthaei, Hanno; Schäfer, Nico; Schmitz, Volker; Kalff, Jörg C; Standop, Jens; Manekeller, Steffen

2017-03-20

Delayed gastric emptying (DGE) remains the most frequent complication following pancreatoduodenectomy (PD) with published incidences as high as 61%. The present study investigates the impact of bowel reconstruction techniques on DGE following classic PD (Whipple-Kausch procedure) with pancreatogastrostomy (PG). We included 168 consecutive patients who underwent PD with PG with either Billroth II type (BII, n = 78) or Roux-en-Y type reconstruction (ReY, n = 90) between 2004 and 2015. Excluded were patients with conventional single loop reconstruction after pylorus preserving procedures. DGE was classified according to the 2007 International Study Group of Pancreatic Surgery definition. Patients were analyzed regarding severity of DGE, morbidity and mortality, length of hospital stay and demographic factors. No difference was observed between BII and ReY regarding frequency of DGE. Overall rate for clinically relevant DGE was 30% (ReY) and 26% (BII). BII and ReY did not differ in terms of demographics, morbidity or mortality. DGE significantly prolongs ICU (four vs. two days) and hospital stay (20.5 vs. 14.5 days). Risk factors for DGE development are advanced age, retrocolic reconstruction, postoperative hemorrhage and major complications. The occurrence of DGE can not be influenced by the type of alimentary reconstruction (ReY vs. BII) following classic PD with PG. Old age and major complications could be identified as important risk factors in multivariate analysis. German Clinical Trials Register (DRKS) DRKS00011860 . Registered 14 March 2017.

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana – A Cohort Study

PubMed Central

Owusu, Ruth; Asante, Kwaku Poku; Mahama, Emmanuel; Awini, Elizabeth; Anyorigiya, Thomas; Dosoo, David; Amu, Alberta; Jakpa, Gabriel; Ofei, Emmanuel; Segbaya, Sylvester; Oduro, Abraham Rexford; Gyapong, Margaret; Hodgson, Abraham; Bart-Plange, Constance; Owusu-Agyei, Seth

2015-01-01

Background Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. Methods and Findings Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. Conclusions There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is required to confirm consistency of findings. PMID:26327623

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana - A Cohort Study.

PubMed

Owusu, Ruth; Asante, Kwaku Poku; Mahama, Emmanuel; Awini, Elizabeth; Anyorigiya, Thomas; Dosoo, David; Amu, Alberta; Jakpa, Gabriel; Ofei, Emmanuel; Segbaya, Sylvester; Oduro, Abraham Rexford; Gyapong, Margaret; Hodgson, Abraham; Bart-Plange, Constance; Owusu-Agyei, Seth

2015-01-01

Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is required to confirm consistency of findings.

What can we do with sodium retention in peritoneal dialysis patients?

PubMed

Lichodziejewska-Niemierko, M

2008-01-01

Salt intake in XXI century in an average person exceeds 10-15 grams per day. The key organ responsible for sodium regulation is kidney and renal failure patients present with positive sodium balance. In peritoneal dialysis (PD) patients rising hypertension is often connected with volume overload and sodium retention. The reasons for inadequate sodium removal in PD patients are: too small gradient between standard 134 mmol/l sodium PD solutions, sodium seiving effect and lack of residual renal function. APD patients are at higher risk of sodium overload in comparison to CAPD ones. As it has been shown that a degree of sodium removal correlates with survival, sodium management appears to be crucial in these patients. The concept of low sodium solutions has been developed over the years with single-dwell ultra-low solutions and recently with low sodium balance solution given as a continuous treatment in CAPD patients. Preliminary results show that low sodium solutions may be a safe and viable option of treatment of PD patients with sodium and fluid overload.

Environmental tests of metallization systems for terrestrial photovoltaic cells

NASA Technical Reports Server (NTRS)

Alexander, P., Jr.

1985-01-01

Seven different solar cell metallization systems were subjected to temperature cycling tests and humidity tests. Temperature cycling excursions were -50 deg C to 150 deg C per cycle. Humidity conditions were 70 deg C at 98% relative humidity. The seven metallization systems were: Ti/Ag, Ti/Pd/Ag, Ti/Pd/Cu, Ni/Cu, Pd/Ni/Solder, Cr/Pd/Ag, and thick film Ag. All metallization systems showed a slight to moderate decrease in cell efficiencies after subjection to 1000 temperature cycles. Six of the seven metallization systems also evidenced slight increases in cell efficiencies after moderate numbers of cycles, generally less than 100 cycles. The copper based systems showed the largest decrease in cell efficiencies after temperature cycling. All metallization systems showed moderate to large decreases in cell efficiencies after 123 days of humidity exposure. The copper based systems again showed the largest decrease in cell efficiencies after humidity exposure. Graphs of the environmental exposures versus cell efficiencies are presented for each metallization system, as well as environmental exposures versus fill factors or series resistance.

The PD-1: PD-L1 pathway promotes development of brain-resident memory T cells following acute viral encephalitis.

PubMed

Prasad, Sujata; Hu, Shuxian; Sheng, Wen S; Chauhan, Priyanka; Singh, Amar; Lokensgard, James R

2017-04-13

Previous work from our laboratory has demonstrated that during acute viral brain infection, glial cells modulate antiviral T cell effector responses through the PD-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation. Here, we evaluated the PD-1: PD-L1 pathway in development of brain-resident memory T cells (bT RM ) following murine cytomegalovirus (MCMV) infection. Flow cytometric analysis of immune cells was performed at 7, 14, and 30 days post-infection (dpi) to assess the shift of brain-infiltrating CD8 + T cell populations from short-lived effector cells (SLEC) to memory precursor effector cells (MPEC), as well as generation of bT RMs . In wild-type (WT) animals, we observed a switch in the phenotype of brain-infiltrating CD8 + T cell populations from KLRG1 + CD127 - (SLEC) to KLRG1 - CD127 + (MPEC) during transition from acute through chronic phases of infection. At 14 and 30 dpi, the majority of CD8 + T cells expressed CD127, a marker of memory cells. In contrast, fewer CD8 + T cells expressed CD127 within brains of infected, PD-L1 knockout (KO) animals. Notably, in WT mice, a large population of CD8 + T cells was phenotyped as CD103 + CD69 + , markers of bT RM , and differences were observed in the numbers of these cells when compared to PD-L1 KOs. Immunohistochemical studies revealed that brain-resident CD103 + bT RM cells were localized to the parenchyma. Higher frequencies of CXCR3 were also observed among WT animals in contrast to PD-L1 KOs. Taken together, our results indicate that bT RMs are present within the CNS following viral infection and the PD-1: PD-L1 pathway plays a role in the generation of this brain-resident population.

Silibinin suppresses astroglial activation in a mouse model of acute Parkinson's disease by modulating the ERK and JNK signaling pathways.

PubMed

Lee, Yujeong; Chun, Hye Jeong; Lee, Kyung Moon; Jung, Young-Suk; Lee, Jaewon

2015-11-19

Parkinson's disease (PD) is the second-most common neurodegenerative disease after Alzheimer's disease, and is characterized by dopaminergic neuronal loss in midbrain. The MPTP-induced PD model has been well characterized by motor deficits and selective dopaminergic neuronal death accompanied by glial activation. Silibinin is a constituent of silymarin, an extract of milk thistle seeds, and has been proposed to have hepatoprotective, anti-cancer, anti-oxidative, and neuroprotective effects. In the present study, the authors studied the neuroprotective effects of silibinin in an acute MPTP model of PD. Silibinin was administered for 2 weeks, and then MPTP was administered to mice over 1 day (acute MPTP induced PD). Silibinin pretreatment effectively ameliorated motor dysfunction, dopaminergic neuronal loss, and glial activations caused by MPTP. In addition, an in vitro study demonstrated that silibinin suppressed astroglial activation and ERK and JNK phosphorylation in primary astrocytes in response to MPP(+) treatment. These findings show silibinin protected dopaminergic neurons in an acute MPTP-induced mouse model of PD, and suggest its neuroprotective effects might be mediated by the suppression of astrocyte activation via the inhibition of ERK and JNK phosphorylation. In conclusion, the study indicates silibinin should be viewed as a potential treatment for PD and other neurodegenerative diseases associated with neuroinflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

APF and dentifrice effect on root dentin demineralization and biofilm.

PubMed

Vale, G C; Tabchoury, C P M; Del Bel Cury, A A; Tenuta, L M A; ten Cate, J M; Cury, J A

2011-01-01

Because dentin is more caries-susceptible than enamel, its demineralization may be more influenced by additional fluoride (F). We hypothesized that a combination of professional F, applied as acidulated phosphate F (APF), and use of 1100-ppm-F dentifrice would provide additional protection for dentin compared with 1100-ppm-F alone. Twelve adult volunteers wore palatal appliances containing root dentin slabs, which were subjected, during 4 experimental phases of 7 days each, to biofilm accumulation and sucrose exposure 8x/day. The volunteers were randomly assigned to the following treatments: placebo dentifrice (PD), 1100-ppm-F dentifrice (FD), APF + PD, and APF+FD. APF gel (1.23% F) was applied to the slabs once at the beginning of the experimental phase, and the dentifrices were used 3x/day. APF and FD increased F concentration in biofilm fluid and reduced root dentin demineralization, presenting an additive effect. Analysis of the data suggests that the combination of APF gel application and daily regular use of 1100-ppm-F dentifrice may provide additional protection against root caries compared with the dentifrice alone.

Safety of Single-Dose Primaquine in G6PD-Deficient and G6PD-Normal Males in Mali Without Malaria: An Open-Label, Phase 1, Dose-Adjustment Trial.

PubMed

Chen, Ingrid; Diawara, Halimatou; Mahamar, Almahamoudou; Sanogo, Koualy; Keita, Sekouba; Kone, Daouda; Diarra, Kalifa; Djimde, Moussa; Keita, Mohamed; Brown, Joelle; Roh, Michelle E; Hwang, Jimee; Pett, Helmi; Murphy, Maxwell; Niemi, Mikko; Greenhouse, Bryan; Bousema, Teun; Gosling, Roly; Dicko, Alassane

2018-03-28

The World Health Organization recommendation on the use of a single low dose of primaquine (SLD-PQ) to reduce Plasmodium falciparum malaria transmission requires more safety data. We conducted an open-label, nonrandomized, dose-adjustment trial of the safety of 3 single doses of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in Mali, followed by an assessment of safety in G6PD-deficient boys aged 11-17 years and those aged 5-10 years, including G6PD-normal control groups. The primary outcome was the greatest within-person percentage drop in hemoglobin concentration within 10 days after treatment. Fifty-one participants were included in analysis. G6PD-deficient adult males received 0.40, 0.45, or 0.50 mg/kg of SLD-PQ. G6PD-deficient boys received 0.40 mg/kg of SLD-PQ. There was no evidence of symptomatic hemolysis, and adverse events considered related to study drug (n = 4) were mild. The mean largest within-person percentage change in hemoglobin level between days 0 and 10 was -9.7% (95% confidence interval [CI], -13.5% to -5.90%) in G6PD-deficient adults receiving 0.50 mg/kg of SLD-PQ, -11.5% (95% CI, -16.1% to -6.96%) in G6PD-deficient boys aged 11-17 years, and -9.61% (95% CI, -7.59% to -13.9%) in G6PD-deficient boys aged 5-10 years. The lowest hemoglobin concentration at any point during the study was 92 g/L. SLD-PQ doses between 0.40 and 0.50 mg/kg were well tolerated in G6PD-deficient males in Mali. NCT02535767.

Stability of Antibiotics for Intraperitoneal Administration in Extraneal 7.5% Icodextrin Peritoneal Dialysis Bags (STAB Study).

PubMed

Ranganathan, Dwarakanathan; Naicker, Saiyuri; Wallis, Steven C; Lipman, Jeffrey; Ratanjee, Sharad K; Roberts, Jason A

2016-01-01

♦ Patients with peritoneal dialysis (PD)-associated peritonitis may be advised to store PD-bags with pre-mixed antibiotics at home, although there is a paucity of antibiotic stability studies in the commonly used icodextrin solutions. The purpose of this study was to assess the stability of various antibiotics in PD-bags when stored at different temperatures over a 14-day period. ♦ 7.5% icodextrin PD-bags were dosed with gentamicin 20 mg/L (n = 9), vancomycin 1,000 mg/L (n = 9), cefazolin 500 mg/L (n = 9) and ceftazidime 500 mg/L (n = 9) as for intermittent dosing. Combinations of gentamicin/vancomycin (n = 9), cefazolin/ceftazidime (n = 9), and cefazolin/gentamicin (n = 9) were also tested. Nine drug-free bags were used as controls. Bags were stored in triplicate at 37°C, room-temperature (25°C), and refrigeration (4°C). Antibiotic concentrations were quantified at various time intervals using validated chromatography. Storage duration was considered unstable if the concentration of the antibiotic dropped ≤ 90% of the initial value. ♦ Gentamicin was stable for 14 days at all temperatures. Vancomycin was stable for 4 days at 37°C and for 14 days at both 25°C and 4°C. The gentamicin and vancomycin combination was stable for 4 days at 37°C and for 14 days at 25°C and 4°C. Cefazolin alone was stable for 24 hours at 37°C, 7 days at 25°C, and 14 days at 4°C. Ceftazidime alone was stable for only 6 hours at 37°C, 2 days at 25°C, and 14 days at 4°C. The cefazolin and ceftazidime combination was stable for 24 hours at 37°C, 2 days at 25°C, and 14 days at 4°C. The cefazolin and gentamicin combination was stable for 1 day at 37°C, 4 days at 25°C, and 14 days at 4°C. ♦ Antibiotics premixed in icodextrin PD-bags have varying stabilities with stability generally least at 37°C and best at 4(o)C, permitting storage for 14 days when refrigerated and prewarming to body temperature prior to administration. Further research confirming the sterility of these antibiotic-containing bags is recommended. Copyright © 2016 International Society for Peritoneal Dialysis.

The retina as an early biomarker of neurodegeneration in a rotenone-induced model of Parkinson's disease: evidence for a neuroprotective effect of rosiglitazone in the eye and brain.

PubMed

Normando, Eduardo Maria; Davis, Benjamin Michael; De Groef, Lies; Nizari, Shereen; Turner, Lisa A; Ravindran, Nivedita; Pahlitzsch, Milena; Brenton, Jonathan; Malaguarnera, Giulia; Guo, Li; Somavarapu, Satyanarayana; Cordeiro, Maria Francesca

2016-08-18

Parkinson's Disease (PD) is the second most common neurodegenerative disease worldwide, affecting 1 % of the population over 65 years of age. Dopaminergic cell death in the substantia nigra and accumulation of Lewy bodies are the defining neuropathological hallmarks of the disease. Neuronal death and dysfunction have been reported in other central nervous system regions, including the retina. Symptoms of PD typically manifest only when more than 70 % of dopaminergic cells are lost, and the definitive diagnosis of PD can only be made histologically at post-mortem, with few biomarkers available.In this study, a rotenone-induced rodent model of PD was employed to investigate retinal manifestations in PD and their usefulness in assessing the efficacy of a novel therapeutic intervention with a liposomal formulation of the PPAR-γ (Peroxisome proliferator-activated receptor gamma) agonist rosiglitazone.Retinal assessment was performed using longitudinal in vivo imaging with DARC (detection of apoptosing retinal cells) and OCT (optical coherence tomography) technologies and revealed increased RGCs (Retinal Ganglion Cells) apoptosis and a transient swelling of the retinal layers at day 20 of the rotenone insult. Follow-up of this model demonstrated characteristic histological neurodegenerative changes in the substantia nigra and striatum by day 60, suggesting that retinal changes precede the "traditional" pathological manifestations of PD. The therapeutic effect of systemic administration of different formulations of rosiglitazone was then evaluated, both in the retina and the brain. Of all treatment regimen tested, sustained release administration of liposome-encapsulated rosiglitazone proved to be the most potent therapeutic strategy, as evidenced by its significant neuroprotective effect on retinal neurons at day 20, and on nigrostriatal neurons at day 60, provided convincing evidence for its potential as a treatment for PD.Our results demonstrate significant retinal changes occurring in this model of PD. We show that rosiglitazone can efficiently protect retinal neurons from the rotenone insult, and that systemic administration of liposome-encapsulated rosiglitazone has an enhanced neuroprotective effect on the retina and CNS (Central Nervous System). To our knowledge, this is the first in vivo evidence of RGCs loss and early retinal thickness alterations in a PD model. Together, these findings suggest that retinal changes may be a good surrogate biomarker for PD, which may be used to assess new treatments both experimentally and clinically.

Retinal Angiogenesis Is Mediated by an Interaction between the Angiotensin Type 2 Receptor, VEGF, and Angiopoietin

PubMed Central

Sarlos, Stella; Rizkalla, Bishoy; Moravski, Christina J.; Cao, Zemin; Cooper, Mark E.; Wilkinson-Berka, Jennifer L.

2003-01-01

There is evidence that angiotensin II, vascular endothelial growth factor (VEGF), angiopoietins, and their cognate receptors participate in retinal angiogenesis. We investigated whether angiotensin type 2-receptor blockade (AT2-RB) reduces retinal angiogenesis and alters the expression of VEGF/VEGF-R2 and angiopoietin-Tie2. Retinopathy of prematurity (ROP) was induced in Sprague Dawley (SD) rats by exposure to 80% oxygen from postnatal (P) days 0 to 11, followed by 7 days in room air. ROP shams were in room air from P0–18. A group of ROP rats received the AT2-RB, PD123319, by mini-osmotic pump (5 mg/kg/day) from P11–18 (angiogenesis period). Evaluation of the retinal status of the AT2 receptor indicated that this receptor, as assessed by real-time PCR, immunohistochemistry, and in vitro autoradiography, was present in the retina, was more abundant than the AT1 receptor in the neonatal retina, and was increased in the ROP model. AT2-RB reduced retinal angiogenesis. VEGF and VEGF-R2 mRNA were increased in ROP and localized to blood vessels, ganglion cells, and the inner nuclear layer, and were decreased by PD123319. Angiopoietin2 and Tie2, but not angiopoietin1 mRNA were increased with ROP, and angiopoietin2 was reduced with PD123319. This study has identified a potential retinoprotective role for AT2-RB possibly mediated via interactions with VEGF- and angiopoietin-dependent pathways. PMID:12937129

KSC-04PD-2209

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. Lockheed Martin representatives explain some of the activities they are working on for safe Return to Flight of the Space Shuttle. The exhibit was one of many presented to KSC employees during Spaceport Super Safety and Health Day. Vendors exhibits were set up in the parking areas outside the Vehicle Assembly Building and the O&C Building. The day-long event also featured presentations by guest speakers Dr. Pamela Peeke, Navy Com. Stephen E. Iwanowicz, NASAs Dr. Kristine Calderon and Olympic-great Bruce Jenner. Super Safety and Health Day was initiated at KSC in 1998 to increase awareness of the importance of safety and health among the government and contractor workforce. The theme for this years event was Safety and Health: A Winning Combination.

[Promotion effects of vitamin B12 on the degradation of 2, 4, 4'-trichlorobiphenyl by Nostoc PD-2].

PubMed

Liu, Jia-Yu; Xiao, Wen-Feng; Lu, Li-Ping; Zhang, Hang-Jun

2014-08-01

Polychlorinated biphenyls are typical persistent chlorinated organic compounds in the environment. Bioremediation of PCB-contaminated environment has become one of the hot issues. In this study, vitamin B12 (VB12) and chlorine-free culture medium were applied to study the effects of VB12 on the degradation of 2,4,4'-trichlorobiphenyl (PCB28) by Nostoc PD-2 and the gene expression during the PCB-degradation process. Results showed that addition of different concentrations of vitamin B12 could improve the PCB-biodegradation rates by Nostoc PD-2. Compared with the control group, the 7-day degradation rate in 10 microg x L(-1), 100 microg x L(-1), and 1 000 microg x L(-1) VB12-treated groups increased by 11.0%, 19.7%, and 21.9% , respectively. The degradation half-time decreased from 5.53 days (treated with 10 microg x L(-1) VB12) to 3.08 days (treated with 100 microg x L(-1) VB12). The expression of cytochrome b6f complex iron-sulfur protein gene and dioxygenase gene showed significant correlation with PCB28-degradation by Nostoc PD-2. While the expression of iron-sulfur protein gene showed more significant correlation with PCB28-degradation. Results in this study indicated that adding VB12 could promote PCB28-degradation by Nostoc PD-2. Moreover, VB12 addition improved the PCB-degradation activity of Nostoc PD-2 at the gene level. The above conclusions could provide a new choice for developing efficient bioremediation technology for PCB-contaminated environment and a new insight into the PCB-biodegradation mechanism by Nostoc PD-2.

Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma.

PubMed

Dickson, Mark A; Tap, William D; Keohan, Mary Louise; D'Angelo, Sandra P; Gounder, Mrinal M; Antonescu, Cristina R; Landa, Jonathan; Qin, Li-Xuan; Rathbone, Dustin D; Condy, Mercedes M; Ustoyev, Yelena; Crago, Aimee M; Singer, Samuel; Schwartz, Gary K

2013-06-01

CDK4 is amplified in > 90% of well-differentiated (WDLS) and dedifferentiated liposarcomas (DDLS). The selective cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitor PD0332991 inhibits growth and induces senescence in cell lines and xenografts. In a phase I trial of PD0332991, several patients with WDLS or DDLS experienced prolonged stable disease. We performed an open-label phase II study to determine the safety and efficacy of PD0332991 in patients with advanced WDLS/DDLS. Patients age ≥ 18 years experiencing disease progression while receiving systemic therapy before enrollment received PD0332991 200 mg orally once per day for 14 consecutive days in 21-day cycles. All were required to have CDK4 amplification by fluorescence in situ hybridization and retinoblastoma protein (RB) expression by immunohistochemistry (≥ 1+). The primary end point was progression-free survival (PFS) at 12 weeks, with 12-week PFS of ≥ 40% considered promising and ≤ 20% not promising. If ≥ nine of 28 patients were progression free at 12 weeks, PD0332991 would be considered active. We screened 48 patients (44 of 48 had CDK4 amplification; 41 of 44 were RB positive). Of those, 30 were enrolled, and 29 were evaluable for the primary end point. Grade 3 to 4 events included anemia (17%), thrombocytopenia (30%), neutropenia (50%), and febrile neutropenia (3%). At 12 weeks, PFS was 66% (90% CI, 51% to 100%), significantly exceeding the primary end point. The median PFS was 18 weeks. There was one partial response. Treatment with the CDK4 inhibitor PD0332991 was associated with a favorable progression-free rate in patients with CDK4-amplified and RB-expressing WDLS/DDLS who had progressive disease despite systemic therapy.

Assessing Agreement Between Salivary Alpha Amylase Levels Collected by Passive Drool and Eluted Filter Paper in Adolescents With Cancer

PubMed Central

Ameringer, Suzanne; Munro, Cindy; Elswick, R.K.

2014-01-01

Purpose/Objectives To assess the validity of filter paper (FP) against the gold standard of passive drool (PD) for collecting salivary alpha amylase as a surrogate biomarker of psychological stress in adolescents with cancer. Design Part of a longitudinal, descriptive study of symptoms in adolescents with cancer during chemotherapy. Setting A pediatric hematology/oncology treatment center. Sample 33 saliva sample pairs from nine adolescents with cancer, aged 13–18 years. Methods Salivary alpha amylase was collected by PD and FP at four time points during a cycle of chemotherapy: days 1 (time 1) and 2 (time 2) of chemotherapy, day 7–10 (time 3), and day 1 of the next cycle (time 4). A random effects regression was used to assess the correlation between PD and FP values, and a Bland Altman analysis was conducted to assess agreement between the values. Main Research Variables Salivary alpha amylase. Findings The estimated correlation between PD and FP values was r = 0.91, p < 0.001. Regression results were also used to rescale FP values to the levels of the PD values because the FP values were on a different scale than the PD values. The Bland Altman analysis revealed that the agreement between the rescaled FP values and PD values was not satisfactory. Conclusions Eluted FP may not be a valid method for collecting salivary alpha amylase in adolescents with cancer. Implications for Nursing Psychological stress in adolescents with cancer may be linked to negative outcomes, such as greater symptom severity and post-traumatic stress disorder. Nurses need valid, efficient, biobehavioral measures to assess psychological stress in the clinical setting. PMID:22750901

Aprepitant, granisetron, and dexamethasone versus palonosetron and dexamethasone for prophylaxis of cisplatin-induced nausea and vomiting in patients with upper gastrointestinal cancer: a randomized crossover phase II trial (KDOG 1002).

PubMed

Ishido, Kenji; Higuchi, Katsuhiko; Azuma, Mizutomo; Sasaki, Tohru; Tanabe, Satoshi; Katada, Chikatoshi; Yano, Takafumi; Wada, Takuya; Koizumi, Wasaburo

2016-10-01

We conducted a randomized trial to compare the safety and effectiveness of aprepitant, granisetron, and dexamethasone (AGD) with those of palonosetron and dexamethasone (PD) in patients who received highly emetogenic chemotherapy (HEC). Patients with esophageal or gastric cancer who were scheduled to receive HEC including at least 60 mg/m of cisplatin as the first-line treatment were randomly assigned to receive AGD (oral aprepitant 125 mg on day 1 and 80 mg on days 2-3; intravenous granisetron 3 mg on day 1; intravenous dexamethasone 6.6 mg on day 1 and oral dexamethasone 4 mg on days 2-3) or PD (intravenous palonosetron 0.75 mg on day 1; intravenous dexamethasone 13.2 mg on day 1 and oral dexamethasone 8 mg on days 2-3). The primary endpoint was a complete response during the overall study period (0-120 h after the start of chemotherapy) in the first cycle. Eighty-five patients were enrolled, and 84 were eligible. The complete response rate did not differ between the treatment groups, but the proportion of patients with no vomiting was significantly higher in the AGD group than in the PD group (81.4 vs. 58.5%; P=0.031). The results of a quality-of-life survey indicated that the proportion of patients with no or minimal impact on daily life in the vomiting domain was significantly higher in the AGD group (79.1 vs. 53.7%; P=0.020). The primary endpoint of complete response was not achieved, but AGD seems to be more effective than PD for the prevention of HEC-induced vomiting.

Daily diary study of personality disorder traits: Momentary affect and cognitive appraisals in response to stressful events.

PubMed

Jarnecke, Amber M; Miller, Michelle L; South, Susan C

2017-01-01

Difficulties in emotional expression and emotion regulation are core features of many personality disorders (PDs); yet, we know relatively little about how individuals with PDs affectively respond to stressful situations. The present study seeks to fill this gap in the literature by examining how PD traits are associated with emotional responses to subjective daily stressors, while accounting for cognition and type of stressor experienced (interpersonal vs. noninterpersonal). PD features were measured with the Schedule for Nonadaptive and Adaptive Personality-2 (SNAP-2) diagnostic scores. Participants (N = 77) completed a 1-week experience sampling procedure that measured affect and cognition related to a current stressor 5 times per day. Hierarchical linear modeling (HLM) was used to examine whether and how baseline PD features, momentary cognitions, and type of stressor predicted level of affect. Results demonstrated that paranoid, borderline, and avoidant PD traits predicted negative affect beyond what could be accounted for by cognitions and type of stressor. No PD traits predicted positive affect after accounting for the effects of cognitive appraisals and type of stressor. Findings have implications for validating the role of affect in PDs and understanding how individuals with PDs react in the presence of daily hassles. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Espresso Coffee for the Treatment of Somnolence in Parkinson’s Disease: Results of n-of-1 Trials

PubMed Central

Ferreira, Joaquim J.; Mestre, Tiago; Guedes, Leonor Correia; Coelho, Miguel; Rosa, Mário M.; Santos, Ana T.; Barra, Márcio; Sampaio, Cristina; Rascol, Olivier

2016-01-01

There is limited information available concerning the treatment of daytime somnolence associated with Parkinson’s disease (PD); the most frequently applied therapeutic strategies include decreasing the dose of dopamine agonists or adding potential wake-promoting agents. There is recent data from a placebo-controlled trial concluding on a non-significant trend in favor of caffeine. We aimed to evaluate the efficacy of espresso-coffee in the treatment of daytime somnolence in PD. To evaluate the efficacy of espresso-coffee in the treatment of daytime somnolence in PD, we have conducted multiple single-patient (n-of-1) clinical trials comparing regular espresso coffee to decaffeinated coffee in PD patients presenting moderate to severe daytime somnolence defined as an Epworth Sleepiness Scale score >9. Each single-patient (n-of-1) trial included a sequence of three crossovers (two treatment periods separated by two days of washout). Four patients were included in the studies and three completed the three pairs of treatment periods. In two of the four patients, espresso coffee was considered beneficial. This study concludes that multiple single patient trials are feasible in PD and suggests that espresso-coffee may have a beneficial effect on daytime somnolence in some patients. These results cannot be generalized beyond the patients included in these trials. PMID:27014181

Activation of microglia induces symptoms of Parkinson’s disease in wild-type, but not in IL-1 knockout mice

PubMed Central

2013-01-01

Background Parkinson’s disease (PD) is an age-related progressive neurodegenerative disorder caused by selective loss of dopaminergic neurons from the substantia nigra (SN) to the striatum. The initial factor that triggers neurodegeneration is unknown; however, inflammation has been demonstrated to be significantly involved in the progression of PD. The present study was designed to investigate the role of the pro-inflammatory cytokine interleukin-1 (IL-1) in the activation of microglia and the decline of motor function using IL-1 knockout (KO) mice. Methods Lipopolysaccharide (LPS) was stereotaxically injected into the SN of mice brains as a single dose or a daily dose for 5 days (5 mg/2 ml/injection, bilaterally). Animal behavior was assessed with the rotarod test at 2 hr and 8, 15 and 22 days after the final LPS injection. Results LPS treatment induced the activation of microglia, as demonstrated by production of IL-1β and tumor necrosis factor (TNF) α as well as a change in microglial morphology. The number of cells immunoreactive for 4-hydroxynonenal (4HNE) and nitrotyrosine (NT), which are markers for oxidative insults, increased in the SN, and impairment of motor function was observed after the subacute LPS treatment. Cell death and aggregation of α-synuclein were observed 21 and 30 days after the final LPS injection, respectively. Behavioral deficits were observed in wild-type and TNFα KO mice, but IL-1 KO mice behaved normally. Tyrosine hydroxylase (TH) gene expression was attenuated by LPS treatment in wild-type and TNFα KO mice but not in IL-1 KO mice. Conclusions The subacute injection of LPS into the SN induces PD-like pathogenesis and symptoms in mice that mimic the progressive changes of PD including the aggregation of α-synuclein. LPS-induced dysfunction of motor performance was accompanied by the reduced gene expression of TH. These findings suggest that activation of microglia by LPS causes functional changes such as dopaminergic neuron attenuation in an IL-1-dependent manner, resulting in PD-like behavioral impairment. PMID:24289537

GABA(A) receptor modulation during adolescence alters adult ethanol intake and preference in rats.

PubMed

Hulin, Mary W; Amato, Russell J; Winsauer, Peter J

2012-02-01

To address the hypothesis that GABA(A) receptor modulation during adolescence may alter the abuse liability of ethanol during adulthood, the effects of adolescent administration of both a positive and negative GABA(A) receptor modulator on adult alcohol intake and preference were assessed. Three groups of adolescent male rats received 12 injections of lorazepam (3.2 mg/kg), dehydroepiandrosterone (DHEA, 56 mg/kg), or vehicle on alternate days starting on postnatal day (PD) 35. After this time, the doses were increased to 5.6 and 100 mg/kg, respectively, for 3 more injections on alternate days. Subjects had access to 25 to 30 g of food daily, during the period of the first 6 injections, and 18 to 20 g thereafter. Food intake of each group was measured 60 minutes after food presentation, which occurred immediately after drug administration on injection days or at the same time of day on noninjection days. When subjects reached adulthood (PD 88), ethanol preference was determined on 2 separate occasions, an initial 3-day period and a 12-day period, in which increasing concentrations of ethanol were presented. During each preference test, intake of water, saccharin, and an ethanol/saccharin solution was measured after each 23-hour access period. During adolescence, lorazepam increased 60-minute food intake, and this effect was enhanced under the more restrictive feeding schedule. DHEA had the opposite effect on injection days, decreasing food intake compared with noninjection days. In adulthood, the lorazepam-treated group preferred the 2 lowest concentrations of ethanol/saccharin more than saccharin alone compared with vehicle-treated subjects, which showed no preference for any concentration of ethanol/saccharin over saccharin. DHEA-treated subjects showed no preference among the 3 solutions. These data demonstrate that GABA(A) receptor modulation during adolescence can alter intake and preference for ethanol in adulthood and highlights the importance of drug history as an important variable in the liability for alcohol abuse. Copyright © 2011 by the Research Society on Alcoholism.

Hospital readmission after a pancreaticoduodenectomy: an emerging quality metric?

PubMed Central

Kastenberg, Zachary J; Morton, John M; Visser, Brendan C; Norton, Jeffrey A; Poultsides, George A

2013-01-01

Background Hospital readmission has attracted attention from policymakers as a measure of quality and a target for cost reduction. The aim of the study was to evaluate the frequency and patterns of rehospitalization after a pancreaticoduodenectomy (PD). Methods The records of all patients undergoing a PD at an academic medical centre for malignant or benign diagnoses between January 2006 and September 2011 were retrospectively reviewed. The incidence, aetiology and predictors of subsequent readmission(s) were analysed. Results Of 257 consecutive patients who underwent a PD, 50 (19.7%) were readmitted within 30 days from discharge. Both the presence of any post-operative complication (P = 0.049) and discharge to a nursing/rehabilitation facility or to home with health care services (P = 0.018) were associated with readmission. The most common reasons for readmission were diet intolerance (36.0%), pancreatic fistula/abscess (26.0%) and superficial wound infection (8.0%). Nine (18.0%) readmissions had lengths of stay of 2 days or less and in four of those (8.0%) diagnostic evaluation was eventually negative. Conclusion Approximately one-fifth of patients require hospital readmission within 30 days of discharge after a PD. A small fraction of these readmissions are short (2 days or less) and may be preventable or manageable in the outpatient setting. PMID:23297725

Fluid Status in Peritoneal Dialysis Patients: The European Body Composition Monitoring (EuroBCM) Study Cohort

PubMed Central

Van Biesen, Wim; Williams, John D.; Covic, Adrian C.; Fan, Stanley; Claes, Kathleen; Lichodziejewska-Niemierko, Monika; Verger, Christian; Steiger, Jurg; Schoder, Volker; Wabel, Peter; Gauly, Adelheid; Himmele, Rainer

2011-01-01

Background Euvolemia is an important adequacy parameter in peritoneal dialysis (PD) patients. However, accurate tools to evaluate volume status in clinical practice and data on volume status in PD patients as compared to healthy population, and the associated factors, have not been available so far. Methods We used a bio-impedance spectroscopy device, the Body Composition Monitor (BCM) to assess volume status in a cross-sectional cohort of prevalent PD patients in different European countries. The results were compared to an age and gender matched healthy population. Results Only 40% out of 639 patients from 28 centres in 6 countries were normovolemic. Severe fluid overload was present in 25.2%. There was a wide scatter in the relation between blood pressure and volume status. In a multivariate analysis in the subgroup of patients from countries with unrestricted availability of all PD modalities and fluid types, older age, male gender, lower serum albumin, lower BMI, diabetes, higher systolic blood pressure, and use of at least one exchange per day with the highest hypertonic glucose were associated with higher relative tissue hydration. Neither urinary output nor ultrafiltration, PD fluid type or PD modality were retained in the model (total R2 of the model = 0.57). Conclusions The EuroBCM study demonstrates some interesting issues regarding volume status in PD. As in HD patients, hypervolemia is a frequent condition in PD patients and blood pressure can be a misleading clinical tool to evaluate volume status. To monitor fluid balance, not only fluid output but also dietary input should be considered. Close monitoring of volume status, a correct dialysis prescription adapted to the needs of the patient and dietary measures seem to be warranted to avoid hypervolemia. PMID:21390320

The Role of Programmed Cell Death Ligand-1 (PD-L1/CD274) in the Development of Graft versus Host Disease

PubMed Central

Al-Chaqmaqchi, Heevy; Sadeghi, Behnam; Abedi-Valugerdi, Manuchehr; Al-Hashmi, Sulaiman; Fares, Mona; Kuiper, Raoul; Lundahl, Joachim

2013-01-01

Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease. PMID:23593203

Neurochemical effects of a 20 kHz magnetic field on the central nervous system in prenatally exposed mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dimberg, Y.

1995-09-01

C57/B1 mice were exposed during pregnancy (gestation days 0--19) to a 20 kHz magnetic field (MF). The asymmetric sawtooth-waveform magnetic field in the exposed racks had a flux density of 15 {micro}T (peak to peak). After 19 days, the exposure was terminated, and the mice were housed individually under normal laboratory conditions. On postnatal day (PD) 1, PD21, and PD308, various neurochemical markers in the brains of the offspring were investigated and the brains weighed. No significant difference was found in the whole brain weight at PD1 or PD21 between exposed offspring and control animals. However, on PD308, a significantmore » decrease in weight of the whole brain was detected in exposed animals. No significant differences were found in the weight of cortex, hippocampus, septum, or cerebellum on nay of the sampling occasions, nor were any significant differences detected in protein-, DNA-level, nerve growth factor (NGF), acetylcholine esterase- (AChE), or 2{prime},3{prime}-cyclic nucleotide 3{prime}-phosphodiesterase- (CNP; marker for oligodendrocytes) activities on PD21 in cerebellum. Cortex showed a more complex pattern of response to MF: MF treatment resulted in a decrease in DNA level and increases in the activities of CNP, AChE, and NGF protein. On PD308, the amount of DNA was significantly reduced in MF-treated cerebellum and CNP activity was still enhanced in MF-treated cortex compared to controls. Most of the effect of MF treatment during the embryonic period were similar to those induced by ionizing radiation but much weaker. However, the duration of the exposure required to elucidate the response of different markers to MF seems to be greater and effects appear later during development compared to responses to ionizing radiation.« less

Success of Urgent-Start Peritoneal Dialysis in a Large Canadian Renal Program

PubMed Central

Alkatheeri, Ali M.A.; Blake, Peter G.; Gray, Daryl; Jain, Arsh K.

2016-01-01

♦ Background: Many patients start renal replacement therapy urgently on in-center hemodialysis via a central venous catheter, which is considered suboptimal. An alternative approach to manage these patients is to start them on peritoneal dialysis (PD). In this report, we describe the first reported Canadian experience with an urgent-start PD program. Additionally we reviewed the literature in this area. ♦ Methods: In this prospective observational study, we report on our experience in a single academic center. This program started in July 2010. We included patients who initiated PD urgently, that is within 2 weeks of catheter insertion. We followed all incident PD patients until October 2013 for mechanical and infectious complications. Peritoneal dialysis catheters were inserted either percutaneously or laparoscopically and dialysis was initiated in either an inpatient or outpatient setting. ♦ Results: Thirty patients were started on urgent PD during our study period. Follow-up ranged from 28 to 1,050 days. Twenty insertions (66.7 %) were done percutaneously and 10 (33.3%) were laparoscopic. Dialysis was initiated within 2 weeks (range: 0 – 13 days, median = 6 days). Twenty-four patients (80%) started PD in an outpatient setting and 6 patients (20%) required immediate inpatient PD start. Three patients (10%) developed a minor peri-catheter leak during the first week of training that was managed conservatively. There were no episodes of peritonitis or exit-site/tunnel infection during the first 4 weeks post-insertion. Four patients (13.3 %) from the percutaneous insertion group and 2 patients (6.7%) from laparoscopic insertions developed catheter dysfunction due to migration, which was managed by repositioning, without need for catheter replacement or modality switch. ♦ Conclusions: Our results are consistent with other studies in this area and demonstrate that urgent-start PD is an acceptable and safe alternative to hemodialysis in patients who need to start dialysis urgently without established dialysis access. PMID:26374834

Success of Urgent-Start Peritoneal Dialysis in a Large Canadian Renal Program.

PubMed

Alkatheeri, Ali M A; Blake, Peter G; Gray, Daryl; Jain, Arsh K

2016-01-01

♦ Many patients start renal replacement therapy urgently on in-center hemodialysis via a central venous catheter, which is considered suboptimal. An alternative approach to manage these patients is to start them on peritoneal dialysis (PD). In this report, we describe the first reported Canadian experience with an urgent-start PD program. Additionally we reviewed the literature in this area. ♦ In this prospective observational study, we report on our experience in a single academic center. This program started in July 2010. We included patients who initiated PD urgently, that is within 2 weeks of catheter insertion. We followed all incident PD patients until October 2013 for mechanical and infectious complications. Peritoneal dialysis catheters were inserted either percutaneously or laparoscopically and dialysis was initiated in either an inpatient or outpatient setting. ♦ Thirty patients were started on urgent PD during our study period. Follow-up ranged from 28 to 1,050 days. Twenty insertions (66.7%) were done percutaneously and 10 (33.3%) were laparoscopic. Dialysis was initiated within 2 weeks (range: 0-13 days, median = 6 days). Twenty-four patients (80%) started PD in an outpatient setting and 6 patients (20%) required immediate inpatient PD start. Three patients (10%) developed a minor peri-catheter leak during the first week of training that was managed conservatively. There were no episodes of peritonitis or exit-site/tunnel infection during the first 4 weeks post-insertion. Four patients (13.3%) from the percutaneous insertion group and 2 patients (6.7%) from laparoscopic insertions developed catheter dysfunction due to migration, which was managed by repositioning, without need for catheter replacement or modality switch. ♦ Our results are consistent with other studies in this area and demonstrate that urgent-start PD is an acceptable and safe alternative to hemodialysis in patients who need to start dialysis urgently without established dialysis access. Copyright © 2016 International Society for Peritoneal Dialysis.

Age and experience dependent changes in Egr-1 expression during the ontogeny of the context preexposure facilitation effect (CPFE).

PubMed

Robinson-Drummer, P A; Chakraborty, T; Heroux, N A; Rosen, J B; Stanton, M E

2018-04-01

The context preexposure facilitation effect (CPFE) is a variant of contextual fear conditioning in which acquisition of the contextual representation and association of the retrieved contextual memory with an immediate foot-shock are separated by 24 h. During the CPFE, learning- related expression patterns of the early growth response-1 gene (Egr-1) vary based on training phase and brain sub-region in adult and adolescent rats (Asok, Schreiber, Jablonski, Rosen, & Stanton, 2013; Schreiber, Asok, Jablonski, Rosen, & Stanton, 2014; Chakraborty, Asok, Stanton, & Rosen, 2016). The current experiments extended our previous findings by examining Egr-1 expression in infant (PD17) and juvenile (PD24) rats during the CPFE using preexposure protocols involving single-exposure (SE) or multiple-exposure (ME) to context. Following a 5 min preexposure to the training context (i.e. the SE protocol), Egr-1 expression in the medial prefrontal cortex (mPFC), dorsal hippocampus (dHPC) and lateral nucleus of the amygdala (LA) was differentially increased in PD24 rats relative to PD17 rats. In contrast, increased Egr-1 expression following an immediate foot-shock (2s, 1.5 mA) did not differ between PD17 and PD24 rats, and was not learning-related. Interestingly, increasing the number of exposures to the training chamber on the preexposure day (i.e. ME protocol) altered training-day expression such that a learning-related increase in expression was observed in the mPFC in PD24 but not PD17 rats. Together, these results illustrate a clear maturation of Egr-1 expression that is both age- and experience-dependent. In addition, the data suggest that regional activity and plasticity within the mPFC on the preexposure but not the training day may contribute to the ontogenetic profile of the effect. Further studies are necessary to elucidate the causal role of sub-region-specific neuroplasticity in the ontogeny of the CPFE. Copyright © 2018 Elsevier Inc. All rights reserved.

Survival and engraftment of dopaminergic neurons manufactured by a Good Manufacturing Practice-compatible process.

PubMed

Peng, Jun; Liu, Qiuyue; Rao, Mahendra S; Zeng, Xianmin

2014-09-01

We have previously reported a Good Manufacturing Practice (GMP)-compatible process for generating authentic dopaminergic neurons in defined media from human pluripotent stem cells and determined the time point at which dopaminergic precursors/neurons (day 14 after neuronal stem cell [NSC] stage) can be frozen, shipped and thawed without compromising their viability and ability to mature in vitro. One important issue we wished to address is whether dopaminergic precursors/neurons manufactured by our GMP-compatible process can be cryopreserved and engrafted in animal Parkinson disease (PD) models. In this study, we evaluated the efficacy of freshly prepared and cryopreserved dopaminergic neurons in the 6-hydroxydopamine-lesioned rat PD model. We showed functional recovery up to 6 months post-transplantation in rats transplanted with our cells, whether freshly prepared or cryopreserved. In contrast, no motor improvement was observed in two control groups receiving either medium or cells at a slightly earlier stage (day 10 after NSC stage). Histologic analysis at the end point of the study (6 months post-transplantation) showed robust long-term survival of donor-derived tyrosine hydroxylase (TH)(+) dopaminergic neurons in rats transplanted with day 14 dopaminergic neurons. Moreover, TH(+) fibers emanated from the graft core into the surrounding host striatum. Consistent with the behavioral analysis, no or few TH(+) neurons were detected in animals receiving day 10 cells, although human cells were present in the graft. Importantly, no tumors were detected in any grafted rats, but long-term tumorigenic studies will need to determine the safety of our products. Dopaminergic neurons manufactured by a GMP-compatible process from human ESC survived and engrafted efficiently in the 6-OHDA PD rat model. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Peritoneal Dialysis Catheter Removal Post-Transplant - A Rare Case of Delayed Bowel Perforation.

PubMed

Maxted, Andrew P; Davies, Brian; Colliver, Daniel; Williams, Alun; Lunn, Andrew

2017-01-01

Peritoneal dialysis (PD) is a well-established form of renal replacement therapy and the practice of leaving catheters in situ post-transplantation widely accepted. We present a rare complication: a child presenting with anal protrusion of the PD catheter.The patient is an 11-year-old boy with a background of renal dysplasia and congenital cutis laxa. Twenty-three weeks after dialysis was commenced, the patient underwent a renal transplant. Thirteen weeks post-transplant, the patient felt an unusual sensation after defecation. The curled end of the catheter was seen protruding from the anus. He was admitted, and investigations showed stable graft function, with abdominal X ray showing no free air.Intraoperative findings showed a small perforation of the sigmoid colon sealed off by adherence of several small intestinal loops. This was repaired laparoscopically after removal of the distal part of the catheter per rectum. No peritoneal contamination was seen. He was treated with 5 days of intravenous antibiotics and gradual introduction of enteral feeds. His graft function remained stable throughout.Timing of catheter removal varies, from the time of transplantation to over 3 months post-transplantation. Bowel perforation due to PD catheter insertion is rare and tends to occur at the time of insertion. Anal protrusion of a PD catheter in childhood is extremely rare and unrecorded in a pediatric patient with a connective tissue disorder. Our case highlights that serious complications can occur in the period between transplantation and elective PD catheter removal and that, in the immunocompromised patient, signs can be subtle. Copyright © 2017 International Society for Peritoneal Dialysis.

Toxicity of zearalenone on the intestines of pregnant sows and their offspring and alleviation with modified halloysite nanotubes.

PubMed

Liu, Min; Zhu, Dandan; Guo, Tao; Zhang, Yuanyuan; Shi, Baoming; Shan, Anshan; Chen, Zhihui

2018-01-01

The objective of this study was to examine the effects of maternal exposure to zearalenone (ZEN) on the intestines of pregnant sows and offspring on postnatal days (PD) 1, 21 and 188. Eighteen pregnant sows (six per treatment) were fed a control diet (ZEN, 0.03 mg kg -1 ), ZEN diet (ZEN, 2.77 mg kg -1 ) and ZEN + 1% modified halloysite nanotube (MHNT) diet (ZEN, 2.76 mg kg -1 ) respectively from gestation days (GD) 35 to 70. At the end of the experiment, three sows of each group on GD70 and the offspring on PD1, PD21 and PD188 were killed to analyze the changes of intestines. The results showed that ZEN caused oxidative stress, an inflammatory response, changes in the structure of jejunum and alterations of the bacterial numbers in cecal digesta in pregnant sows and PD1 and PD21 piglets. On PD188, bacterial numbers were also altered. MHNTs supplementation reduced the amount of ZEN in the intestine and reversed to a large extent the effects induced by ZEN on the intestines of pregnant sows and offspring. The results obtained from this study indicated that MHNTs treatment was beneficial for the adsorption of ZEN in the intestine of sows. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Changes in muscle activation patterns and subjective low back pain ratings during prolonged standing in response to an exercise intervention.

PubMed

Nelson-Wong, Erika; Callaghan, Jack P

2010-12-01

Low back pain (LBP) development has been associated with occupational standing. Increased hip and trunk muscle co-activation is considered to be predisposing for LBP development during standing in previously asymptomatic individuals. The purpose of this work was to investigate muscle activation and LBP responses to a prescribed exercise program. Pain-developing (PD) individuals were expected to have decreased LBP and muscle co-activation following exercise intervention. Electromyography (EMG) data were recorded from trunk and hip muscle groups during 2-h of standing. An increase of >10mm on visual analog scale (VAS) during standing was threshold for PD categorization. Participants were assigned to progressive exercise program with weekly supervision or control (usual activity) for 4 weeks then re-tested. Forty percent were categorized as PD on day 1, VAS=24.2 (±4.0)mm. PD exercisers (PDEX) had lower VAS scores (8.93±3.66 mm) than PD control (PDCON) (16.5±6.3 mm) on day 2 (p=0.007). Male PDEX had decreased gluteus medius co-activation levels (p<0.05) on day 2. The exercise program proved beneficial in reducing LBP during standing. There were changes in muscle activation patterns previously associated with LBP. Predisposing factors for LBP during standing were shown to change positively with appropriate exercise intervention. Copyright © 2010 Elsevier Ltd. All rights reserved.

Nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: association of pancreatic exocrine deficiency and infection.

PubMed

Murata, Yasuhiro; Mizuno, Shugo; Kato, Hiroyuki; Kishiwada, Masashi; Ohsawa, Ichiro; Hamada, Takashi; Usui, Masanobu; Sakurai, Hiroyuki; Tabata, Masami; Nishimura, Keisuke; Fukutome, Kazuo; Isaji, Shuji

2011-08-01

Previous clinical study has demonstrated that 30-40% of patients undergoing pancreaticoduodenectomy (PD) developed hepatic steatosis. However, nonalcoholic steatohepatitis (NASH) is a little-known complication after PD. Recently we encountered two patients with PD who later developed NASH diagnosed by liver biopsy. Case 1 was a 79-year-old woman who underwent PD for intraductal papillary mucinous neoplasm (IPMN). She had postoperative severe diarrhea due to pseudomembranous enterocolitis. Severe liver dysfunction was observed on the 31st postoperative day. Abdominal computed tomography (CT) on the 32nd day showed remarkably decreased hepatic CT value of 6 HU. Immediate liver biopsy revealed NASH (Brunt criteria: grade 2, stage 2). Case 2 was a 71-year-old woman who underwent PD for IPMN. Liver biopsy on 70th postoperative day, which was performed for assessment of moderate liver dysfunction and decreased hepatic CT value of 44 HU, demonstrated simple steatosis. In the 21st postoperative month, she developed severe urinary tract infection together with marked liver dysfunction. Immediate liver biopsy revealed NASH (Brunt criteria: grade 1, stage 1). For each patient, treatment of infection and high-dose pancreatic enzyme supplements improved liver dysfunction and liver steatosis. Clinical features of our cases seem to support the current leading hypothesis of the pathogenesis of NASH, i.e., the two-hit theory.

Glucose-Dependent Insulinotropic Polypeptide Mitigates 6-OHDA-Induced Behavioral Impairments in Parkinsonian Rats

PubMed Central

Yu, Yu-Wen; Hsueh, Shih-Chang; Lai, Jing-Huei; Chen, Yen-Hua; Kang, Shuo-Jhen; Hsieh, Tsung-Hsun; Hoffer, Barry J.; Li, Yazhou; Greig, Nigel H.; Chiang, Yung-Hsiao

2018-01-01

In the present study, the effectiveness of glucose-dependent insulinotropic polypeptide (GIP) was evaluated by behavioral tests in 6-hydroxydopamine (6-OHDA) hemi-parkinsonian (PD) rats. Pharmacokinetic measurements of GIP were carried out at the same dose studied behaviorally, as well as at a lower dose used previously. GIP was delivered by subcutaneous administration (s.c.) using implanted ALZET micro-osmotic pumps. After two days of pre-treatment, male Sprague Dawley rats received a single unilateral injection of 6-OHDA into the medial forebrain bundle (MFB). The neuroprotective effects of GIP were evaluated by apomorphine-induced contralateral rotations, as well as by locomotor and anxiety-like behaviors in open-field tests. Concentrations of human active and total GIP were measured in plasma during a five-day treatment period by ELISA and were found to be within a clinically translatable range. GIP pretreatment reduced behavioral abnormalities induced by the unilateral nigrostriatal dopamine (DA) lesion produced by 6-OHDA, and thus may be a novel target for PD therapeutic development. PMID:29641447

Safety and Efficacy of Adding a Single Low Dose of Primaquine to the Treatment of Adult Patients With Plasmodium falciparum Malaria in Senegal, to Reduce Gametocyte Carriage: A Randomized Controlled Trial.

PubMed

Tine, Roger C; Sylla, Khadime; Faye, Babacar T; Poirot, Eugenie; Fall, Fatou B; Sow, Doudou; Wang, Duolao; Ndiaye, Magatte; Ndiaye, Jean Louis; Faye, Babacar; Greenwood, Brian; Gaye, Oumar; Milligan, Paul

2017-08-15

More information is needed about the safety of low-dose primaquine in populations where G6PD deficiency is common. Adults with Plasmodium falciparum malaria were randomized to receive 1 of 3 artemisinin combination therapies (ACTs) with or without primaquine (0.25 mg/kg). Glucose-6-phosphate dehydrogenase (G6PD) status was determined using a rapid test. Patients were followed for 28 days to record hemoglobin concentration, adverse events, and gametocyte carriage. The primary end point was the change in Hb at day 7. In sum, 274 patients were randomized, 139 received an ACT alone, and 135 received an ACT + primaquine. The mean reduction in Hb at day 7 was similar in each group, a difference in the ACT + PQ versus the ACT alone group of -0.04 g/dL (95% confidence interval [CI] -0.23, 0.31), but the effect of primaquine differed according to G6PD status. In G6PD-deficient patients the drop in Hb was 0.63 g/dL (95% CI 0.03, 1.24) greater in those who received primaquine than in those who received an ACT alone. In G6PD-normal patients, the reduction in Hb was 0.22 g/dL (95% CI -0.08, 0.52) less in those who received primaquine (interaction P = .01). One G6PD normal patient who received primaquine developed moderately severe anaemia (Hb < 8 g/dL). Dark urine was more frequent in patients who received primaquine. Primaquine was associated with a 73% (95% CI 24-90) reduction in gametocyte carriage (P = .013). Primaquine substantially reduced gametocyte carriage. However, the fall in Hb concentration at day 7 was greater in G6PD-deficient patients who received primaquine than in those who did not and one patient who received primaquine developed moderately severe anemia. PACTR201411000937373 (www.pactr.org). © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2.

PubMed

Zhai, Mei-Li; Chen, Yi; Liu, Chong; Wang, Jian-Bo; Yu, Yong-Hao

2018-05-23

Opioid use has been limited in the treatment of chronic pain due to their side effects, including analgesic tolerance. Previous studies demonstrated that glucocorticoid receptors (GRs) may be involved in the development of chronic morphine tolerance; however, the mechanism remains unknown. It was hypothesized that the expression of spinal phosphorylated mitogen‑activated protein kinase [MAPK; phosphorylated extracellular signal‑regulated kinase (ERK)] is regulated through the spinal GRs, following chronic treatment with morphine. In the first experiment, the experimental rats were randomly divided into four groups: Control, morphine, morphine+GR antagonist mifepristone (RU38486) and morphine+GR agonist dexamethasone (Dex). Each group was treated with continuous intrathecal (IT) injection of the drugs for 6 days. The expression of GRs and MAPK 3/1 (p‑ERK 1/2) in the spinal dorsal horn was detected by western blot analysis and immunofluorescence staining. In the second experiment, the MAPK inhibitor PD98059 was added and the rats were randomly divided into four groups: Control, morphine, PD98059+morphine and PD98059+morphine+Dex. The continuous IT injection lasted for 7 days in each group. For all experiments, the tail flick test was conducted 30 min following administration every day to assess the thermal hyperalgesia of the rats. The experimental results demonstrated that there was a co‑existence of GRs and p‑ERK 1/2 in the spinal cord dorsal horn by double immunofluorescence staining. The GR antagonist RU38486 attenuated the morphine analgesia tolerance by inhibiting the expression of GR and increasing the expression of p‑ERK. The MAPK inhibitor PD98059 increased the effect of morphine tolerance and prolonged the duration of morphine tolerance. The present results suggest that spinal GRs may serve an important role in the development of morphine tolerance through the ERK signaling pathway.

The Impact of Preoperative Enteral Nutrition Enriched with Eicosapentaenoic Acid on Postoperative Hypercytokinemia after Pancreatoduodenectomy: The Results of a Double-Blinded Randomized Controlled Trial.

PubMed

Ashida, Ryo; Okamura, Yukiyasu; Wakabayashi-Nakao, Kanako; Mizuno, Takashi; Aoki, Shuichi; Uesaka, Katsuhiko

2018-06-08

To investigate whether preoperative enteral diets -enriched in eicosapentaenoic acid (EPA) supplements could reduce the incidence of hypercytokinemia after pancreatoduodenectomy (PD) in a double-blinded randomized -controlled trial. Patients with resectable periampullary cancer were randomized into either the control group or the treatment group. Patients in the treatment group received oral supplementation (600 kcal/day) containing EPA for 7 days before surgery. Patients in the control group received isocaloric isonitrogenous standard nutrition (600 kcal/day) without EPA for 7 days before surgery. The primary endpoint was postoperative serum concentrations of interleukin-6 (IL-6). The secondary endpoints were the postoperative nutritional status and the incidence of postoperative infectious complications. Twenty-four patients were enrolled in the present study. After exclusion, 20 patients (control group, n = 9; treatment group, n = 11) were analyzed. There were no significant differences in the curves for the serum concentration of IL-6 (p = 0.68) or the incidence of infectious complications between the 2 groups (control group: 78%, treatment group: 55%, p = 0.37). The results of a double-blinded randomized controlled trial indicated that preoperative immunonutrition had no marked impact on the rates of postoperative hypercytokinemia or infectious complications after PD. © 2018 S. Karger AG, Basel.

[A functional statistical analysis of the action potentials in the brain multineuronal activity of waking cats].

PubMed

Merzhanova, G Kh; Porada, I

1990-01-01

In the present work a method is substantiated of the correction of singled out impulses series by identification of parameters of neurones discharges (PD) during a long period of recording (up to 120 days) of the neuronal activity by means of chronically implanted nichrome semimicroelectrode in different brain part of alert cats.

A pancreaticoduodenectomy risk model derived from 8575 cases from a national single-race population (Japanese) using a web-based data entry system: the 30-day and in-hospital mortality rates for pancreaticoduodenectomy.

PubMed

Kimura, Wataru; Miyata, Hiroaki; Gotoh, Mitsukazu; Hirai, Ichiro; Kenjo, Akira; Kitagawa, Yuko; Shimada, Mitsuo; Baba, Hideo; Tomita, Naohiro; Nakagoe, Tohru; Sugihara, Kenichi; Mori, Masaki

2014-04-01

To create a mortality risk model after pancreaticoduodenectomy (PD) using a Web-based national database system. PD is a major gastroenterological surgery with relatively high mortality. Many studies have reported factors to analyze short-term outcomes. After initiation of National Clinical Database, approximately 1.2 million surgical cases from more than 3500 Japanese hospitals were collected through a Web-based data entry system. After data cleanup, 8575 PD patients (mean age, 68.2 years) recorded in 2011 from 1167 hospitals were analyzed using variables and definitions almost identical to those of American College of Surgeons-National Surgical Quality Improvement Program. The 30-day postoperative and in-hospital mortality rates were 1.2% and 2.8% (103 and 239 patients), respectively. Thirteen significant risk factors for in-hospital mortality were identified: age, respiratory distress, activities of daily living within 30 days before surgery, angina, weight loss of more than 10%, American Society of Anesthesiologists class of greater than 3, Brinkman index of more than 400, body mass index of more than 25 kg/m, white blood cell count of more than 11,000 cells per microliter, platelet count of less than 120,000 per microliter, prothrombin time/international normalized ratio of more than 1.1, activated partial thromboplastin time of more than 40 seconds, and serum creatinine levels of more than 3.0 mg/dL. Five variables, including male sex, emergency surgery, chronic obstructive pulmonary disease, bleeding disorders, and serum urea nitrogen levels of less than 8.0 mg/dL, were independent variables in the 30-day mortality group. The overall PD complication rate was 40.0%. Grade B and C pancreatic fistulas in the International Study Group on Pancreatic Fistula occurred in 13.2% cases. The 30-day and in-hospital mortality rates for pancreatic cancer were significantly lower than those for nonpancreatic cancer. We conducted the reported risk stratification study for PD using a nationwide surgical database. PD outcomes in the national population were satisfactory, and the risk model could help improve surgical practice quality.

KSC-04PD-2206

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. Employees at KSC walk through a tent filled with vendors exhibits during Spaceport Super Safety and Health Day. Vendors exhibits were set up in the parking areas outside the Vehicle Assembly Building and the O&C Building. The day-long event also featured presentations by guest speakers Dr. Pamela Peeke, Navy Com. Stephen E. Iwanowicz, NASAs Dr. Kristine Calderon and Olympic-great Bruce Jenner. Super Safety and Health Day was initiated at KSC in 1998 to increase awareness of the importance of safety and health among the government and contractor workforce. The theme for this years event was Safety and Health: A Winning Combination.

KSC-04PD-2208

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. Employees at KSC take time to look at safety equipment on display during Spaceport Super Safety and Health Day. Vendors exhibits were set up in the parking areas outside the Vehicle Assembly Building and the O&C Building. The day-long event also featured presentations by guest speakers Dr. Pamela Peeke, Navy Com. Stephen E. Iwanowicz, NASAs Dr. Kristine Calderon and Olympic-great Bruce Jenner. Super Safety and Health Day was initiated at KSC in 1998 to increase awareness of the importance of safety and health among the government and contractor workforce. The theme for this years event was Safety and Health: A Winning Combination.

KSC-04PD-2207

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. Inside a tent, employees at KSC look over an exhibit of safety equipment during Spaceport Super Safety and Health Day. Vendors exhibits were set up in the parking areas outside the Vehicle Assembly Building and the O&C Building. The day-long event also featured presentations by guest speakers Dr. Pamela Peeke, Navy Com. Stephen E. Iwanowicz, NASAs Dr. Kristine Calderon and Olympic-great Bruce Jenner. Super Safety and Health Day was initiated at KSC in 1998 to increase awareness of the importance of safety and health among the government and contractor workforce. The theme for this years event was Safety and Health: A Winning Combination.

KSC-04PD-2205

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. Inside a tent, employees at KSC look over an exhibit of special equipment during Spaceport Super Safety and Health Day. Vendors exhibits were set up in the parking areas outside the Vehicle Assembly Building and the O&C Building. The day-long event also featured presentations by guest speakers Dr. Pamela Peeke, Navy Com. Stephen E. Iwanowicz, NASAs Dr. Kristine Calderon and Olympic-great Bruce Jenner. Super Safety and Health Day was initiated at KSC in 1998 to increase awareness of the importance of safety and health among the government and contractor workforce. The theme for this years event was Safety and Health: A Winning Combination.

A case report of a 4-year-old child with glucose-6-phosphate dehydrogenase deficiency: An evidence based approach to nutritional management.

PubMed

Pinto, Alex; MacDonald, Anita; Cleto, Esmeralda; Almeida, Manuela Ferreira; Ramos, Paula Cristina; Rocha, Júlio César

2017-01-01

Pinto A, MacDonald A, Cleto E, Almeida MF, Ramos PC, Rocha JC. A case report of a 4-year-old child with glucose-6-phosphate dehydrogenase deficiency: An evidence based approach to nutritional management. Turk J Pediatr 2017; 59: 189-192. The objective was to describe the nutritional management of a 4-year-old child with glucose-6-phosphate dehydrogenase (G6PD) deficiency. A 4-year-old male child, African descent, born from non-consanguineous parents presented with a clinical history of frequent respiratory infections, usually treated with antibiotics. At 30 months of age, G6PD diagnosis was made after eating one portion (40 - 60 g) of fava beans, resulting in severe hemolytic anemia hospitalization for 5 days. Diagnosis was confirmed by G6PD activity measurement. Nutritional counseling was given to avoid dietary oxidative stressors particularly the exclusion of fava beans and accidental ingestion of other similar beans. Dietary intake of high vitamin C containing foods was discouraged and adequate hydration advised. Nutritional management is crucial in preventing acute stress events in patients with G6PD deficiency.

The Role of Monitoring Gentamicin Levels in Patients with Gram-Negative Peritoneal Dialysis-Associated Peritonitis

PubMed Central

Tang, Wen; Cho, Yeoungjee; Hawley, Carmel M.; Badve, Sunil V.; Johnson, David W.

2014-01-01

♦ Background: There is limited available evidence regarding the role of monitoring serum gentamicin concentrations in peritoneal dialysis (PD) patients receiving this antimicrobial agent in gram-negative PD-associated peritonitis. ♦ Methods: Using data collected in all patients receiving PD at a single center who experienced a gram-negative peritonitis episode between 1 January 2005 and 31 December 2011, we investigated the relationship between measured serum gentamicin levels on day 2 following initial empiric antibiotic therapy and subsequent clinical outcomes of confirmed gram-negative peritonitis. ♦ Results: Serum gentamicin levels were performed on day 2 in 51 (77%) of 66 first gram-negative peritonitis episodes. Average serum gentamicin levels on day 2 were 1.83 ± 0.84 mg/L with levels exceeding 2 mg/L in 22 (43%) cases. The overall cure rate was 64%. No cases of ototoxicity were observed. Day-2 gentamicin levels were not significantly different between patients who did and did not have a complication or cure. Using multivariable logistic regression analysis, failure to cure peritonitis was not associated with either day-2 gentamicin level (adjusted odds ratio (OR) 0.96, 95% confidence interval (CI) 0.25 - 3.73) or continuation of gentamicin therapy beyond day 2 (OR 0.28, 0.02 - 3.56). The only exception was polymicrobial peritonitis, where day-2 gentamicin levels were significantly higher in episodes that were cured (2.06 ± 0.41 vs 1.29 ± 0.71, p = 0.01). In 17 (26%) patients receiving extended gentamicin therapy, day-5 gentamicin levels were not significantly related to peritonitis cure. ♦ Conclusion: Day-2 gentamicin levels did not predict gentamicin-related harm or efficacy during short-course gentamicin therapy for gram-negative PD-related peritonitis, except in cases of polymicrobial peritonitis, where higher levels were associated with cure. PMID:24385334

Development of sensory innervation in rat tibia: co-localization of CGRP and substance P with growth-associated protein 43 (GAP-43)

PubMed Central

Gajda, Mariusz; Litwin, Jan A; Cichocki, Tadeusz; Timmermans, Jean-Pierre; Adriaensen, Dirk

2005-01-01

The development of sensory innervation in long bones was investigated in rat tibia in fetuses on gestational days (GD) 16–21 and in neonates and juvenile individuals on postnatal days (PD) 1–28. A double immunostaining method was applied to study the co-localization of the neuronal growth marker growth-associated protein 43 (GAP-43) and the pan-neuronal marker protein gene product 9.5 (PGP 9.5) as well as that of two sensory fibre-associated neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP). The earliest, not yet chemically coded, nerve fibres were observed on GD17 in the perichondrium of the proximal epiphysis. Further development of the innervation was characterized by the successive appearance of nerve fibres in the perichondrium/periosteum of the shaft (GD19), the bone marrow cavity and intercondylar eminence (GD21), the metaphyses (PD1), the cartilage canals penetrating into the epiphyses (PD7), and finally in the secondary ossification centres (PD10) and epiphyseal bone marrow (PD14). Maturation of the fibres, manifested by their immunoreactivity for CGRP and SP, was visible on GD21 in the epiphyseal perichondrium, the periosteum of the shaft and the bone marrow, on PD1 in the intercondylar eminence and the metaphyses, on PD7 in the cartilage canals, on PD10 in the secondary ossification centres and on PD14 in the epiphyseal bone marrow. The temporal and topographic pattern of nerve fibre appearance corresponds with the development of regions characterized by active mineralization and bone remodelling, suggesting a possible involvement of the sensory innervation in these processes. PMID:16050900

Non-genetic factors associated with the risk of Parkinson’s disease in Iranian patients

PubMed Central

Hosseinitabatabaei, Narges; Babakhani, Babak; Hosseini-Tabatabaei, Azadeh; Vahabi, Zahra; Soltanzadeh, Akbar

2013-01-01

Summary The aim of this study was to investigate some of non-genetic factors associated with Parkinson’s disease (PD) in a sample of Iranian patients. This case-control study included 75 patients with idiopathic PD and 75 control patients. The patients in the control group were found to have drunk more glasses of tea per day than the case group before the onset of their problem (p=0.019). Every extra glass of tea per day decreased the risk of PD by 0.8 times (OR=0.8, 95%CI=0.73–0.97, p=0.02). Each cup of coffee per week decreased the chance of developing PD by 0.5 times (OR=0.5, 95%CI=0.28–0.9, p=0.021). A previous history of evening work increased PD risk by 4.6 times (OR=4.6, 95%CI=1.29–16.86, p=0.019) while major stressful events increased it by 13.5 times (OR=13.5, 95%CI=4.7–38.1, p=0.0001). In conclusion, coffee and tea consumption may exert a protective effect against PD, while evening work and stress may be risk factors for the development of the disease. PMID:24125560

Quantitative bone scan lesion area as an early surrogate outcome measure indicative of overall survival in metastatic prostate cancer.

PubMed

Brown, Matthew S; Kim, Grace Hyun J; Chu, Gregory H; Ramakrishna, Bharath; Allen-Auerbach, Martin; Fischer, Cheryce P; Levine, Benjamin; Gupta, Pawan K; Schiepers, Christiaan W; Goldin, Jonathan G

2018-01-01

A clinical validation of the bone scan lesion area (BSLA) as a quantitative imaging biomarker was performed in metastatic castration-resistant prostate cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71 placebo) from a clinical trial involving a different drug from the initial biomarker development. BSLA computation involved automated image normalization, lesion segmentation, and summation of the total area of segmented lesions on bone scan AP and PA views as a measure of tumor burden. As a predictive biomarker, treated subjects with baseline BSLA [Formula: see text] had longer survival than those with higher BSLA ([Formula: see text] and [Formula: see text]). As a surrogate outcome biomarker, subjects were categorized as progressive disease (PD) if the BSLA increased by a prespecified 30% or more from baseline to week 12 and non-PD otherwise. Overall survival rates between PD and non-PD groups were statistically different ([Formula: see text] and [Formula: see text]). Subjects without PD at week 12 had longer survival than subjects with PD: median 398 days versus 280 days. BSLA has now been demonstrated to be an early surrogate outcome for overall survival in different prostate cancer drug treatments.

Biocompatibility of peritoneal dialysis fluids: long-term exposure of nonuremic rats.

PubMed

Musi, Barbara; Braide, Magnus; Carlsson, Ola; Wieslander, Anders; Albrektsson, Ann; Ketteler, Markus; Westenfeld, Ralf; Floege, Jürgen; Rippe, Bengt

2004-01-01

Long-term peritoneal dialysis (PD) leads to structural and functional changes in the peritoneum. The aim of the present study was to investigate the long-term effects of PD fluid components, glucose and glucose degradation products (GDP), and lactate-buffered solution on morphology and transport characteristics in a nonuremic rat model. Rats were subjected to two daily intraperitoneal injections (20 mL/day) during 12 weeks of one of the following: commercial PD fluid (Gambrosol, 4%; Gambro AB, Lund, Sweden), commercial PD fluid with low GDP levels (Gambrosol trio, 4%; Gambro AB), sterile-filtered PD fluid (4%) without GDP, or a glucose-free lactate-buffered PD fluid. Punctured and untreated controls were used. Following exposure, the rats underwent a single 4-hour PD dwell (30 mL, 4% glucose) to determine peritoneal function. Additionally, submesothelial tissue thickness, percentage of high mesothelial cells (perpendicular diameter > 2 microm), vascular density, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF) beta1 mRNA expression were determined. Submesothelial collagen concentration was estimated by van Gieson staining. Submesothelial tissue thickness and vascular density, mediated by VEGF and TGFbeta production, in the diaphragmatic peritoneum increased significantly in rats exposed to any PD fluid. Gambrosol induced a marked increased fibrosis of the hepatic peritoneum. A significant increase in high mesothelial cells was observed in the Gambrosol group only. Net ultrafiltration was reduced in the Gambrosol and in the glucose-free groups compared to untreated controls. Small solute transport was unchanged, but all groups exposed to fluids showed significantly increased lymph flow. Our results show that long-term exposure to different components of PD fluids leads to mesothelial cell damage, submesothelial fibrosis, and neoangiogenesis. Mesothelial cell damage could be connected to the presence of GDP; the other changes were similar for all fluids. Peritoneal transport characteristics did not change in any consistent way and the neoangiogenesis observed was not paralleled by increased solute transport.

Rearrangement of the dendritic morphology in limbic regions and altered exploratory behavior in a rat model of autism spectrum disorder.

PubMed

Bringas, M E; Carvajal-Flores, F N; López-Ramírez, T A; Atzori, M; Flores, G

2013-06-25

Valproic acid (VPA) is a blocker of histone deacetylase widely used to treat epilepsy, bipolar disorders, and migraine; its administration during pregnancy increases the risk of autism spectrum disorder (ASD) in the child. Thus, prenatal VPA exposure has emerged as a rodent model of ASD. In the present study, we aimed to investigate the effect of prenatal administration of VPA (500mg/kg) at E12.5 on the exploratory behavior and locomotor activity in a novel environment, as well as on neuronal morphological rearrangement in the prefrontal cortex (PFC), in the hippocampus, in the nucleus accumbens (NAcc), and in the basolateral amygdala (BLA) at three different ages: immediately after weaning (postnatal day 21 [PD21]), prepubertal (PD35) and postpubertal (PD70) ages. Hyper-locomotion was observed in a novel environment in VPA animals at PD21 and PD70. Interestingly, exploratory behavior assessed by the hole board test at PD70 showed a reduced frequency but an increase in the duration of head-dippings in VPA-animals compared to vehicle-treated animals. In addition, the latency to the first head-dip was longer in prenatal VPA-treated animals at PD70. Quantitative morphological analysis of dendritic spine density revealed a reduced number of spines at PD70 in the PFC, dorsal hippocampus and BLA, with an increase in the dendritic spine density in NAcc and ventral hippocampus, in prenatal VPA-treated rats. In addition, at PD70 increases in neuronal arborization were observed in the NAcc, layer 3 of the PFC, and BLA, with retracted neuronal arborization in the ventral and dorsal hippocampus. Our results extend the list of altered behaviors (exploratory behavior) detected in this model of ASD, and indicate that the VPA behavioral phenotype is accompanied by previously undescribed morphological rearrangement in limbic regions. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Similar numbers of neurons are generated in the male and female rat preoptic area in utero.

PubMed

Orikasa, Chitose; Kondo, Yasuhiko; Usui, Sumiko; Sakuma, Yasuo

2010-09-01

The birth date of neurons comprising the sexually dimorphic nucleus of the rat preoptic area (SDN-POA) was determined by bromodeoxyuridine (BrdU) injections at a prescribed time during the embryonic period. Calbindin immunostaining was used as a marker to identity the SDN-POA. The animals were bred from dams injected with BrdU on days 14, 16 or 18 of pregnancy (fertilization defined as day 1). On day 15 after birth (PD), all offspring were euthanized and brain sections were prepared for histology. Neurogenesis in the SDN-POA began around embryonic day (ED) 14 and culminated on ED 18, whereas the preoptic neurons surrounding the SDN-POA generated earlier than did those of the SDN-POA. Although the SDN-POA was significantly larger in males than in females at PD15, the total numbers of neurons comprising the SDN-POA were not significantly different between sexes. Similar aggregates of somatostatin mRNA-positive cells in the central portion of the SDN-POA were observed in both sexes at PD8. On PD15, the aggregates became scattered in males, whereas the aggregates in females remained congested. These data suggest that sexual dimorphism in the SDN-POA results from male-specific postnatal radial spreading of cells rather than cell proliferation during embryonic neurogenesis. 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Comparison of treatment outcomes of endoscope-guided pneumatic dilation and laparoscopic Heller myotomy.

PubMed

Wang, Hsin-Ming; Tai, Wei-Chen; Chuah, Seng-Kee; Lu, Hung-I; Lu, Lung-Sheng; Liang, Chih-Ming; Kuo, Chung-Huang; Chiu, Yi-Chun; Wu, Keng-Liang; Changchien, Chi-Sin

2015-12-01

The debate on which is the better choice between laparoscopic Heller myotomy (LHM) and endoscopic pneumatic dilation (PD) for esophageal achalasia has been ongoing for decades. This study aims to compare the results of endoscope-guided PD and LHM in 42 patients with achalasia between May 1996 and August 2011. Twenty-one patients who had received PD and 21 who had received LHM were enrolled. The cumulative remission rate was analyzed using the Kaplan-Meier method with the assessment of symptom scores between grades before and after PD or LHM done at 6 weeks, 6 months, 1 year, and then every year thereafter. Possible confounding factors related to the remissions were analyzed by Cox's proportional hazard model. For PD, the cumulative remission rates were 81.0% (1 year), 76.2% (2), 66.7% (3), 61.9% (4), and 47.6% (5). For LHM, the cumulative remission rates were 90.5% every year from the 1(st) to the 5(th). The LHM patients had significantly better remission rates than the PD patients (p = 0.033, by log-rank test). The LHM group had a longer hospital stay than the PD group [median (interquartile range): 8 (6.5-10) days vs. 3 (2-3) days, p < 0.001) and had more reflux complications (52.4% vs. 19.0%, p = 0.024). No perforation occurred in either group. In conclusion, the 5-year cumulative effectiveness of LHM is better than that of PD despite the association of LHM with more reflux events (52.4%). Copyright © 2015. Published by Elsevier Taiwan.

Antibiotic Use in Small Community Hospitals.

PubMed

Stenehjem, Edward; Hersh, Adam L; Sheng, Xiaoming; Jones, Peter; Buckel, Whitney R; Lloyd, James F; Howe, Stephen; Evans, R Scott; Greene, Tom; Pavia, Andrew T

2016-11-15

 Antibiotic use and misuse is driving drug resistance. Much of US healthcare takes place in small community hospitals (SCHs); 70% of all US hospitals have <200 beds. Antibiotic use in SCHs is poorly described. We evaluated antibiotic use using data from the National Healthcare and Safety Network antimicrobial use option from the Centers for Disease Control and Prevention.  We used Intermountain Healthcare's monthly antibiotic use reports for 19 hospitals from 2011 to 2013. Hospital care units were categorized as intensive care, medical/surgical, pediatric, or miscellaneous. Antibiotics were categorized based on spectrum of coverage. Antibiotic use rates, expressed as days of therapy per 1000 patient-days (DOT/1000PD), were calculated for each SCH and compared with rates in large community hospitals (LCHs). Negative-binomial regression was used to relate antibiotic use to predictor variables.  Total antibiotic use rates varied widely across the 15 SCHs (median, 436 DOT/1000PD; range, 134-671 DOT/1000PD) and were similar to rates in 4 LCHs (509 DOT/1000PD; 406-597 DOT/1000PD). The proportion of patient-days spent in the respective unit types varied substantially within SCHs and had a large impact on facility-level rates. Broad-spectrum antibiotics accounted for 26% of use in SCHs (range, 8%-36%), similar to the proportion in LCHs (32%; range, 26%-37%). Case mix index, proportion of patient-days in specific unit types, and season were significant predictors of antibiotic use.  There is substantial variation in patterns of antibiotic use among SCHs. Overall usage in SCHs is similar to usage in LCHs. Small hospitals need to become a focus of stewardship efforts. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Quantifying daily physical activity and determinants in sedentary patients with Parkinson's disease.

PubMed

Dontje, M L; de Greef, M H G; Speelman, A D; van Nimwegen, M; Krijnen, W P; Stolk, R P; Kamsma, Y P T; Bloem, B R; Munneke, M; van der Schans, C P

2013-10-01

Although physical activity is beneficial for Parkinson's disease (PD) patients, many do not meet the recommended levels. The range of physical activity among sedentary PD patients is unknown, as are factors that determine this variability. Hence, we aimed to (1) assess daily physical activity in self-identified sedentary PD patients; (2) compare this with criteria of a daily physical activity guideline; and (3) identify determinants of daily physical activity. Daily physical activity of 586 self-identified sedentary PD patients was measured with a tri-axial accelerometer for seven consecutive days. Physical fitness and demographic, disease-specific, and psychological characteristics were assessed. Daily physical activity was compared with the 30-min activity guideline. A linear mixed-effects model was estimated to identify determinants of daily physical activity. Accelerometer data of 467 patients who fulfilled all criteria revealed that >98% of their day was spent on sedentary to light-intensity activities. Eighty-two percent of the participants were 'physically inactive' (0 days/week of 30-min activity); 17% were 'semi-active' (1-4 days/week of 30-min activity). Age, gender, physical fitness, and scores on the Unified Parkinson's Disease Rating Scale explained 69% of the variability in daily physical activity. Performance-based measurements confirmed that most self-identified sedentary PD patients are 'physically inactive'. However, the variance in daily physical activity across subjects was considerable. Higher age, being female, and lower physical capacity were the most important determinants of reduced daily physical activity. Future therapeutic interventions should aim to improve daily physical activity in these high-risk patients, focusing specifically on modifiable risk factors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Methods for the field evaluation of quantitative G6PD diagnostics: a review.

PubMed

Ley, Benedikt; Bancone, Germana; von Seidlein, Lorenz; Thriemer, Kamala; Richards, Jack S; Domingo, Gonzalo J; Price, Ric N

2017-09-11

Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk of severe haemolysis following the administration of 8-aminoquinoline compounds. Primaquine is the only widely available 8-aminoquinoline for the radical cure of Plasmodium vivax. Tafenoquine is under development with the potential to simplify treatment regimens, but point-of-care (PoC) tests will be needed to provide quantitative measurement of G6PD activity prior to its administration. There is currently a lack of appropriate G6PD PoC tests, but a number of new tests are in development and are likely to enter the market in the coming years. As these are implemented, they will need to be validated in field studies. This article outlines the technical details for the field evaluation of novel quantitative G6PD diagnostics such as sample handling, reference testing and statistical analysis. Field evaluation is based on the comparison of paired samples, including one sample tested by the new assay at point of care and one sample tested by the gold-standard reference method, UV spectrophotometry in an established laboratory. Samples can be collected as capillary or venous blood; the existing literature suggests that potential differences in capillary or venous blood are unlikely to affect results substantially. The collection and storage of samples is critical to ensure preservation of enzyme activity, it is recommended that samples are stored at 4 °C and testing occurs within 4 days of collection. Test results can be visually presented as scatter plot, Bland-Altman plot, and a histogram of the G6PD activity distribution of the study population. Calculating the adjusted male median allows categorizing results according to G6PD activity to calculate standard performance indicators and to perform receiver operating characteristic (ROC) analysis.

Assessing depression and factors possibly associated with depression during the course of Parkinson’s disease

PubMed Central

Farabaugh, Amy H.; Locascio, Joseph J.; Yap, Liang; Fava, Maurizio; Bitran, Stella; Sousa, Jessica L.; Growdon, John H.

2011-01-01

BACKGROUND Although research suggests depression is common among individuals with Parkinson’s disease (PD), it is unclear how to best assess depression in PD (dPD). We wanted to examine the prevalence of dPD using different definitions of depression, as well as examine factors associated with dPD. METHODS One hundred fifty-eight individuals (68% male; age 66.8 ± 9.6 SD) with a primary diagnosis of PD were assessed for depression using the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS) in an outpatient setting at the Movement Disorders Clinic at Massachusetts General Hospital. We defined depression using 4 thresholds based on the HANDS and whether or not an individual was ever on an antidepressant regimen. We also examined potential predictors of the presence of dPD. RESULTS The prevalence of depression among study participants ranged from 11% to 57%, depending on which of the 4 definitions of depression was applied. Younger age and longer duration of PD predicted a relatively higher prevalence of depression. Having a history of depression prior to onset of PD also was predictive of dPD. CONCLUSIONS Depression appears to be relatively common among individuals with PD, and history of depression, younger age, and longer PD duration may be factors associated with dPD. PMID:21808748

Mesenchymal stem cells increase skin graft survival time and up-regulate PD-L1 expression in splenocytes of mice.

PubMed

Moravej, Ali; Geramizadeh, Bita; Azarpira, Negar; Zarnani, Amir-Hassan; Yaghobi, Ramin; Kalani, Mehdi; Khosravi, Maryam; Kouhpayeh, Amin; Karimi, Mohammad-Hossein

2017-02-01

Recently, mesenchymal stem cells (MSCs) have gained considerable interests as hopeful therapeutic cells in transplantation due to their immunoregulatory functions. But exact mechanisms underlying MSCs immunoregulatory function is not fully understood. Herein, in addition to investigate the ability of MSCs to prolong graft survival time, the effects of them on the expression of PD-L1 and IDO immunomodulatory molecules in splenocytes of skin graft recipient mice was clarified. To achieve this goal, full-thickness skins were transplanted from C57BL/6 to BALB/c mice. MSCs were isolated from bone marrow of BALB/c mice and injected to the recipient mice. Skin graft survival was monitored daily to determine graft rejection time. On days 2, 5 and 10 post skin transplantation, serum cytokine levels and expression of PD-L1 and IDO mRNA and protein in the splenocytes of recipient mice were evaluated. The results showed that administration of MSCs prolonged skin graft survival time from 11 to 14 days. On days 2 and 5 post transplantation, splenocytes PD-L1 expression and IL-10 serum level in MSCs treated mice were higher than those in the controls, while IL-2 and IFN-γ levels were lower. Rejection in MSCs treated mice was accompanied by an increase in IL-2 and IFN-γ, and decrease in PD-L1 expression and IL-10 level. No difference in the expression of IDO between MSCs treated mice and controls was observed. In conclusion, we found that one of the mechanisms underlying MSCs immunomodulatory function could be up-regulating PD-L1 expression. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease.

PubMed

Farrand, Ariana Q; Helke, Kristi L; Gregory, Rebecca A; Gooz, Monika; Hinson, Vanessa K; Boger, Heather A

Parkinson's disease (PD) is a progressive, neurodegenerative disorder with no disease-modifying therapies, and symptomatic treatments are often limited by debilitating side effects. In PD, locus coeruleus noradrenergic (LC-NE) neurons degenerate prior to substantia nigra dopaminergic (SN-DA) neurons. Vagus nerve stimulation (VNS) activates LC neurons, and decreases pro-inflammatory markers, allowing improvement of LC targets, making it a potential PD therapeutic. To assess therapeutic potential of VNS in a PD model. To mimic the progression of PD degeneration, rats received a systemic injection of noradrenergic neurotoxin DSP-4, followed one week later by bilateral intrastriatal injection of dopaminergic neurotoxin 6-hydroxydopamine. At this time, a subset of rats also had vagus cuffs implanted. After eleven days, rats received a precise VNS regimen twice a day for ten days, and locomotion was measured during each afternoon session. Immediately following final stimulation, rats were euthanized, and left dorsal striatum, bilateral SN and LC were sectioned for immunohistochemical detection of monoaminergic neurons (tyrosine hydroxylase, TH), α-synuclein, astrocytes (GFAP) and microglia (Iba-1). VNS significantly increased locomotion of lesioned rats. VNS also resulted in increased expression of TH in striatum, SN, and LC; decreased SN α-synuclein expression; and decreased expression of glial markers in the SN and LC of lesioned rats. Additionally, saline-treated rats after VNS, had higher LC TH and lower SN Iba-1. Our findings of increased locomotion, beneficial effects on LC-NE and SN-DA neurons, decreased α-synuclein density in SN TH-positive neurons, and neuroinflammation suggest VNS has potential as a novel PD therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term efficacy and safety of safinamide as add-on therapy in early Parkinson's disease.

PubMed

Schapira, A H V; Stocchi, F; Borgohain, R; Onofrj, M; Bhatt, M; Lorenzana, P; Lucini, V; Giuliani, R; Anand, R

2013-02-01

Safinamide is an α-aminoamide with both dopaminergic and non-dopaminergic mechanisms of action in Phase III clinical development as a once-daily add-on to dopamine agonist (DA) therapy for early Parkinson's disease (PD). Study 017 was a 12-month, randomized, double-blind, placebo-controlled pre-planned extension study to the previously reported Study 015. Patients received safinamide 100 or 200 mg/day or placebo added to a single DA in early PD. The primary efficacy endpoint was the time from baseline (Study 015 randomization) to 'intervention', defined as increase in DA dose; addition of another DA, levodopa or other PD treatment; or discontinuation due to lack of efficacy. Safinamide groups were pooled for the primary efficacy endpoint analysis; post hoc analyses were performed on each separate dose group. Of the 269 patients randomized in Study 015, 227 (84%) enrolled in Study 017 and 187/227 (82%) patients completed the extension study. Median time to intervention was 559 and 466 days in the pooled safinamide and placebo groups, respectively (log-rank test; P = 0.3342). In post hoc analyses, patients receiving safinamide 100 mg/day experienced a significantly lower rate of intervention compared with placebo (25% vs. 51%, respectively) and a delay in median time to intervention of 9 days (P < 0.05; 240- to 540-day analysis). The pooled data from the safinamide groups failed to reach statistical significance for the primary endpoint of median time from baseline to additional drug intervention. Post hoc analyses indicate that safinamide 100 mg/day may be effective as add-on treatment to DA in PD. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Antibacterial and remineralizing orthodontic adhesive containing quaternary ammonium resin monomer and amorphous calcium phosphate nanoparticles.

PubMed

Liu, Yan; Zhang, Ling; Niu, Li-Na; Yu, Tao; Xu, Hockin H K; Weir, Michael D; Oates, Thomas W; Tay, Franklin R; Chen, Ji-Hua

2018-05-01

To evaluate the bonding performance, antibacterial activity, and remineralization effect on enamel of the orthodontic adhesive containing MAE-DB and NACP. Eighty non-carious human premolars were divided into 3 groups: Transbond XT (TB), PEHB + 5% MAE-DB (PD), and PEHB + 40% NACP + 5% MAE-DB (PND). Premolars were bonded with orthodontic brackets, the first subgroup (n = 10) and the second subgroup (n = 10) were subjected to shear bond strength testing after immersed in water for 1 day and in demineralization solution for 28 days respectively and then tested surface roughness, while the third subgroup (n = 6) was used for microhardness evaluation after aged in demineralization solution for 28 days. For each adhesive, fifty disk samples were prepared for antibacterial study. Specimens measuring 12 mm × 2 mm × 2 mm were fabricated for ion release test. Bond strengths were in the order TB = PND > PND = PD for "1-day in water", and in the order TB = PND > PD for "28-days in pH 4 solution". No significant difference in the ARI scores for the three adhesive. Numerous bacteria adhered to TB surface, while PD and PND had minimal bacterial growth and activity. PND showed high levels of Ca and P ions release and enamel hardness. The surface roughness of enamel in PND was much lower than TB and PD and showed no significant difference with the sound, control enamel. PND adhesive with 5% MAE-DB and 40% NACP exhibits antibacterial and remineralizing capabilities, and did not adversely affect bond strength compared to commercial adhesive. Novel adhesive containing quaternary ammonium monomer and nano-amorphous calcium phosphate represents a promising candidate in combating enamel white spot lesions and even dental caries. Copyright © 2018 Elsevier Ltd. All rights reserved.

Associations of coffee consumption and caffeine intake with mammographic breast density.

PubMed

Yaghjyan, Lusine; Colditz, Graham; Rosner, Bernard; Gasparova, Aleksandra; Tamimi, Rulla M

2018-05-01

Previous studies suggest that coffee and caffeine intake may be associated with reduced breast cancer risk. We investigated the association of coffee and caffeine intake with mammographic breast density by woman's menopausal status and, in postmenopausal women, by hormone therapy (HT). This study included 4130 cancer-free women within the Nurses' Health Study and Nurses' Health Study II cohorts. Percent breast density (PD) was measured from digitized film mammograms using a computer-assisted thresholding technique and square root-transformed for the analysis. Average cumulative coffee/caffeine consumption was calculated using data from all food frequency questionnaires preceding the mammogram date. Information regarding breast cancer risk factors was obtained from questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations of regular, decaffeinated, and total coffee, and energy-adjusted caffeine intake with percent density. In multivariable analyses, decaffeinated coffee was positively associated with PD in premenopausal women (2+ cups/day: β = 0.23, p trend = 0.03). In postmenopausal women, decaffeinated and total coffee were inversely associated with PD (decaffeinated 2+ cups/day: β = - 0.24, p trend = 0.04; total 4+ cups/day: β = - 0.16, p trend = 0.02). Interaction of decaffeinated coffee with menopausal status was significant (p-interaction < 0.001). Among current HT users, regular coffee and caffeine were inversely associated with PD (regular coffee 4+ cups/day: β = - 0.29, p trend = 0.01; caffeine 4th vs. 1st quartile: β = - 0.32, p trend = 0.01). Among past users, decaffeinated coffee was inversely associated with PD (2+ cups/day β = - 0.70, p trend = 0.02). Associations of decaffeinated coffee with percent density differ by woman's menopausal status. Associations of regular coffee and caffeine with percent density may differ by HT status.

Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors.

PubMed

De Martin, Eleonora; Michot, Jean-Marie; Papouin, Barbara; Champiat, Stéphane; Mateus, Christine; Lambotte, Olivier; Roche, Bruno; Antonini, Teresa Maria; Coilly, Audrey; Laghouati, Salim; Robert, Caroline; Marabelle, Aurélien; Guettier, Catherine; Samuel, Didier

2018-06-01

Immunotherapy for metastatic cancer can be complicated by the onset of hepatic immune-related adverse events (IRAEs). This study compared hepatic IRAEs associated with anti-programmed cell death protein 1 (PD-1)/PD ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) monoclonal antibodies (mAbs). Among 536 patients treated with anti-PD-1/PD-L1 or CTLA-4 immunotherapies, 19 (3.5%) were referred to the liver unit for grade ≥3 hepatitis. Of these patients, nine had received anti-PD-1/PD-L1 and seven had received anti-CTLA-4 mAbs, in monotherapy or in combination with anti-PD-1. Liver investigations were undertaken in these 16 patients, including viral assays, autoimmune tests and liver biopsy, histological review, and immunostaining of liver specimens. In the 16 patients included in this study, median age was 63 (range 33-84) years, and nine (56%) were female. Time between therapy initiation and hepatitis was five (range, 1-49) weeks and median number of immunotherapy injections was two (range, 1-36). No patients developed hepatic failure. Histology related to anti-CTLA-4 mAbs demonstrated granulomatous hepatitis including fibrin ring granulomas and central vein endotheliitis. Histology related to anti-PD-1/PD-L1 mAbs was characterised by lobular hepatitis. The management of hepatic IRAEs was tailored according to the severity of both the biology and histology of liver injury: six patients improved spontaneously; seven received oral corticosteroids at 0.5-1 mg/kg/day; two were maintained on 0.2 mg/kg/day corticosteroids; and one patient required pulses and 2.5 mg/kg/day of corticosteroids, and the addition of a second immunosuppressive drug. In three patients, immunotherapy was reintroduced without recurrence of liver dysfunction. Acute hepatitis resulting from immunotherapy for metastatic cancer is rare (3.5%) and, in most cases, not severe. Histological assessment can distinguish between anti-PD-1/PD-L1 and anti-CTLA-4 mAb toxicity. The severity of liver injury is helpful for tailoring patient management, which does not require systematic corticosteroid administration. Immunotherapy for metastatic cancer can be complicated by immune-related adverse events in the liver. In patients receiving immunotherapy for metastatic cancer who develop immune-mediated hepatitis, liver biopsy is helpful for the diagnosis and evaluation of the severity of liver injury. This study demonstrates the need for patient-oriented management, which could eventually avoid unnecessary systemic corticosteroid treatment. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Laparoscopic hand-assisted pancreaticoduodenectomy: initial UK experience.

PubMed

Ammori, B J

2004-04-01

By and large, the limited world experience with laparoscopic pancreaticoduodenectomy (PD) has been unfavorable, but the laparoscopic hand-assisted approach to PD has recently shown promising results. We report the first successful UK experience with laparoscopic hand-assisted PD (LHAPD). A 62-year-old man who presented with painless obstructive jaundice was found at endoscopy, to have an ampullary tumor. Preoperative biopsy specimens confirmed the diagnosis of an adenocarcinoma, and CT showed no evidence of either vascular involvement or metastatic disease. A staging laparoscopy showed no intraabdominal metastases, and an LHAPD was performed using a Gelport. The intraoperative course was uneventful. Two units of blood were transfused intraoperatively, but no postoperative blood transfusion was required. The operative time was 11 h (plus a 30-min break). The patients postoperative recovery was uneventful except for superficial pressure sores over the buttocks and elbows. The patient resumed oral fluid and dietary intake on the 1st and 3rd postoperative days, respectively, and was discharged from hospital on the 9th postoperative day. Histology demonstrated an ampullary adenocarcinoma with clear resection margins and involvement of two of the 13 lymph nodes examined. At 2-month follow-up, the patient remains well and is receiving adjuvant chemotherapy. LHAPD achieves good oncological clearance and can be performed safely in selected patients. The early promising results with this approach will undoubtedly encourage wider adoption of this procedure and are likely to widen the selection criteria.

KSC-03PD-2829

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Capt. Charles Plumb (USNR retired) begins his dramatic presentation of his six years as a prisoner of war in Vietnam. The block of light on the stage represented the size of the cell he was confined in. Plumb was keynote speaker for the kickoff of Spaceport Super Safety and Health Day at KSC, an annual event dedicated to reinforcing safe and healthful behaviors in the workforce.

Puberty, ovarian cycle, pregnancy, and postpartum ovulation in captive Sichuan golden monkeys (Rhinopithecus roxellana) based on changes in urinary and fecal gonadal steroid metabolites.

PubMed

Muren; Kusuda, Satoshi; Doi, Osamu; Naito, Hitomi; Hashikawa, Hisashi

2017-01-01

The purpose of this study was to evaluate the reproductive status and clarify the reproductive physiology of captive Sichuan golden monkeys. The concentrations of urinary estradiol-3-glucuronide (E 2 G) and pregnanediol-glucuronide (PdG) or fecal estradiol-17β (E 2 ) and PdG in two females, and fecal testosterone concentrations in a male, were measured continuously using enzyme immunoassays. On the basis of these hormone profiles, the follicular phase, luteal phase, and ovarian cycle were calculated to be 14.7 ± 4.8, 10.4 ± 2.8, and 25.1 ± 3.3 days, respectively. The first ovulation (puberty) in a female monkey was observed at 5.1 years old, and the first pregnancy was diagnosed at 6.4 years old. For the first 2 months of pregnancy (204 days), fecal E 2 and PdG maintained constant high values and then increased until parturition. These profiles were similar to urinary E 2 G and PdG changes. During the last trimester of a twin pregnancy, fecal PdG was up to approximately three times higher compared with a single pregnancy. Therefore, fecal PdG levels in late pregnancy may be effective for the detection of a twin pregnancy. The first postpartum ovulation occurred 66 (fetal death and artificial rearing), 143 (fetal death), and 189 (natural suckling) days after parturition. The anovulation period of the natural suckling case was longer than the others. Conception and postpartum ovulation were detected between September and January. Fecal testosterone levels of the male were correlated with the fecal E 2 level of the nonpregnancy period in exhibited together female. Our results reported that urinary (E 2 G and PdG) and fecal (E 2 and PdG) hormone measurement is effective for monitoring the reproductive status, thereby expanding knowledge of the reproductive endocrinology of this endangered species. Copyright © 2016 Elsevier Inc. All rights reserved.

Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese.

PubMed

Tan, E-K; Tan, C; Fook-Chong, S M C; Lum, S Y; Chai, A; Chung, H; Shen, H; Zhao, Y; Teoh, M L; Yih, Y; Pavanni, R; Chandran, V R; Wong, M C

2003-12-15

Few studies have examined the relationship of coffee and tea in Parkinson's disease (PD). The potential protective effect of coffee intake and risk of PD has not been studied in a Chinese population. There is a high prevalence of caffeine takers among Chinese in our population. We undertook a case control study to examine the relationship between coffee and tea drinking, cigarette smoking, and other enviromental factors and risk of PD among ethnic Chinese in our population. 300 PD and 500 population controls were initially screened. Two hundred case control pairs matched for age, gender, and race were finally included in the analysis. Univariate analysis revealed significant association of PD with coffee drinking (p<0.0005), tea drinking (p=0.019), alcohol drinking (p=0.001), cigarette smoking (p<0.0005), and exposure to heavy metals (p=0.006). Conditional logistic regression analysis demonstrated that amount of coffee drunk (OR 0.787, 95%CI 0.664-0.932, p=0.006), amount of tea drunk (OR 0.724, 95%CI 0.559-0.937, p=0.014), number of cigarettes smoked (OR 0.384, 95%CI 0.204-0.722, p=0.003), history of heavy metal and toxin exposure (OR 11.837, 95%CI 1.075-130.366, p=0.044), and heart disease (OR 5.518, 95%CI 1.377-22.116, p=0.016) to be significant factors associated with PD. One unit of coffee and tea (3 cups/day for 10 years) would lead to a 22% and 28% risk reduction of PD. One unit of cigarette smoke (3 packs/day for 10 years) reduced the risk of PD by 62%. We demonstrated a dose-dependent protective effect of PD in coffee and tea drinkers and smokers in an ethnic Chinese population. A history of exposure to heavy metals increased the risk of PD, supporting the multifactorial etiologies of the disease.

Self-administration of methamphetamine alters gut biomarkers of toxicity

PubMed Central

Flack, Amanda; Persons, Amanda L.; Kousik, Sharanya M.; Napier, T. Celeste; Moszczynska, Anna

2018-01-01

Methamphetamine (METH) is a highly abused psychostimulant that is associated with an increased risk for developing Parkinson’s disease (PD). This enhanced vulnerability likely relates to the toxic effects of METH that overlap with PD pathology, for example, aberrant functioning of α-synuclein and parkin. In PD, peripheral factors are thought to contribute to central nervous system (CNS) degeneration. For example, α-synuclein levels in the enteric nervous system (ENS) are elevated, and this precedes the onset of motor symptoms. It remains unclear whether neurons of the ENS, particularly catecholaminergic neurons, exhibit signs of METH-induced toxicity as seen in the CNS. The aim of this study was to determine whether self-administered METH altered the levels of α-synuclein, parkin, tyrosine hydroxylase (TH), and dopamine-β-hydroxylase (DβH) in the myenteric plexus of the distal colon ENS. Young adult male Sprague-Dawley rats self-administered METH for 3 h per day for 14 days and controls were saline-yoked. Distal colon tissue was collected at 1, 14, or 56 days after the last operant session. Levels of α-synuclein were increased, while levels of parkin, TH, and DβH were decreased in the myenteric plexus in the METH-exposed rats at 1 day following the last operant session and returned to the control levels after 14 or 56 days of forced abstinence. The changes were not confined to neurofilament-positive neurons. These results suggest that colon biomarkers may provide early indications of METH-induced neurotoxicity, particularly in young chronic METH users who may be more susceptible to progression to PD later in life. PMID:28661099

[Use of marker genes located on X-chromosomes to analyze lens development in Arctic fox/fox hybrids].

PubMed

Serov, O L; Zakiian, S M; Kulichkov, V A

1982-01-01

Glucose-6-phosphate dehydrogenase (G6PD) isozymes were studied in the lens and some tissues of Arctic fox x fox female hybrids at different developmental stages. During the embryonic and early postnatal (till the 2nd day of life) development the lens is characterized by a high degree of individual variation of the ratio between parental G6PD forms. The number of stem cells for the lens was determined to be equal to six by means of binomial method of description of this variation. Taking into account the similarity of G6PD spectra in the right and left lenses, a suggestion was put forward that both the lenses develop from the common pool of stem cells. After the 4th day of postnatal life a hemizygote-like phenotype of maternal type was observed in the lenses of all hybrid females. It is suggested that the formation of pseudohemizygote phenotype is due to the posttranslation chemical modification of G6PD isozymes.

Approach to management of penile fracture in men with underlying Peyronie's disease.

PubMed

Minor, Thomas X; Brant, William O; Rahman, Nadeem U; Lue, Tom F

2006-10-01

To report on a series of patients with Peyronie's disease (PD) who experienced a penile fracture, examining the history, presentation, and management. Additionally, we describe an unreported surgical technique implementing combined fracture repair and tunica plication. PD is an acquired inflammatory condition of the penis that can cause fibrotic, nonexpansile thickening of the tunica albuginea, resulting in a focal bend or narrowing on erection. From October 1999 to July 2003, 4 patients with nonsurgically treated PD had a penile fracture during sexual activity. The mean patient age was 43 years (range 29 to 52), with an average of 5.5 days (range 3 to 8) transpiring from the time of penile trauma to surgery in the men presenting early. Penile ultrasonography was used to locate the site of tunica laceration. Either circumcising or ventral midline incisions were selected to treat these patients. During penile exploration, the tunica defect in the corpus cavernosum was identified and closed with 2-0 Maxon suture. Subsequent artificial erection displayed penile curvature in 3 patients, and plication was then performed to straighten the tunica angulation using 2-0 TiCron suture. The fourth patient had a minimal bend with slight waisting, not requiring plication. No perioperative complications occurred. These 4 patients regained their preoperative level of erectile rigidity with lasting nonpainful correction of their deformity. Patients with PD who have a penile fracture are candidates for combined fracture repair and tunica plication at the same setting.

Glucose-6-phosphate dehydrogenase variants associated with favism in Thai children.

PubMed

Laosombat, Vichai; Sattayasevana, Benjamas; Chotsampancharoen, Teerachit; Wongchanchailert, Malai

2006-02-01

In a study conducted at Songklanagarind Hospital in the south of Thailand, the subjects were 225 patients (210 boys and 15 girls) with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Favism was found in 3.6% of the G6PD-deficient children. Approximately one half of the G6PD-deficient patients with favism were younger than 2 years. Sudden onset of anemia was found within 1 to 3 days after ingestion of dried fava beans. The classic features of favism, which are pallor, hemoglobinuria, and jaundice, were detected in all cases. To characterize the known G6PD mutations in Thai children, molecular analysis was performed for 8 G6PD-deficient children with favism by a combination of polymerase chain reaction-restriction fragment length polymorphism analysis and amplification refractory mutation system analysis. The G6PD variants in these children were G6PD Kaiping 1388,G-->A; G6PD Mahidol 487,G-->A; G6PD Viangchan 871,G-->A; and uncharacterized mutation with silent mutation 1311,C-->T.

PD-1 regulates T cell proliferation in a tissue and subset specific manner during normal mouse pregnancy

PubMed Central

Shepard, Michelle T.; Bonney, Elizabeth A.

2014-01-01

The regulation of T cell homeostasis during pregnancy has important implications for maternal tolerance and immunity. Evidence suggests that Programmed Death-1 (PD-1) participates in regulation of T cell homeostasis and peripheral tolerance. To examine the contribution of PD-1 signaling on T cell homeostasis during normal mouse pregnancy, we examined T cell number or proportion, PD-1 expression, proliferation, and apoptosis by flow cytometry, BrdU incorporation, and TUNEL assay in pregnant mice given anti-PD-1 blocking antibody or control on days 10, 12, and 14 of gestation. We observed tissue, treatment, and T cell-specific differences in PD-1 expression. Both pregnancy and PD-1 blockade increased T cell proliferation in the spleen while this effect was limited to CD4 T cells in the uterine- draining nodes. In the uterus, PD-1 blockade markedly altered the composition of the T cell pool. These studies support the idea that pregnancy is a state of dynamic T cell homeostasis and suggest that this state is partially supported by PD-1 signaling. PMID:23782245

Perinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats.

PubMed

Thomas, Jennifer D; Garrison, Megan; O'Neill, Teresa M

2004-01-01

Children exposed to alcohol prenatally suffer from a variety of behavioral alterations, including hyperactivity and learning deficits. Given that women continue to drink alcohol during pregnancy, it is critical that effective interventions and treatments be identified. Previously, we reported that early postnatal choline supplementation can reduce the severity of learning deficits in rats exposed to alcohol prenatally. The present study examined whether choline supplementation can reduce the severity of behavioral alterations associated with alcohol exposure during the third trimester equivalent brain growth spurt. Male neonatal rats were assigned to one of three treatment groups. One group was exposed to alcohol (6.6 g/kg/day) from postnatal days (PD) 4-9 via an artificial rearing procedure. Artificially reared and normally reared control groups were included. One half of subjects from each treatment received daily subcutaneous injections of a choline chloride solution from PD 4-30, whereas the other half received saline vehicle injections. On PD 31-34, after choline treatment was complete, activity level was monitored and, on PD 40-42, subjects were tested on a serial spatial discrimination reversal learning task. Subjects exposed to alcohol were significantly hyperactive compared to controls. The severity of ethanol-induced hyperactivity was attenuated with choline treatment. In addition, subjects exposed to ethanol during the neonatal period committed a significantly greater number of perseverative-type errors on the reversal learning task compared to controls. Exposure to choline significantly reduced the number of ethanol-related errors. Importantly, these behavioral changes were not due to the acute effects of choline, but were related to long-lasting organizational effects of early choline supplementation. These data suggest that early dietary interventions may reduce the severity of fetal alcohol effects.

Multi-Target Protective Effects of Gintonin in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Mediated Model of Parkinson's Disease via Lysophosphatidic Acid Receptors.

PubMed

Choi, Jong Hee; Jang, Minhee; Oh, Seikwan; Nah, Seung-Yeol; Cho, Ik-Hyun

2018-01-01

Gintonin is a ginseng-derived lysophosphatidic acid receptor (LPAR) ligand. Although previous in vitro and in vivo studies demonstrated the therapeutic role of gintonin against Alzheimer's disease, the neuroprotective effects of gintonin in Parkinson's disease (PD) are still unknown. We investigated whether gintonin (50 and 100 mg/kg/day, p.o., daily for 12 days) had neuroprotective activities against neurotoxicity in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Pre-administration of 100 mg/kg gintonin displayed significantly ameliorating effects in neurological disorders (motor and welfare) as measuring using pole, rotarod, and nest building tests, and in the survival rate. These effects were associated to the reduction of the loss of tyrosine hydroxylase-positive neurons, microglial activation, activation of inflammatory mediators (interleukin-6, tumor necrosis factor, and cyclooxygenase-2), and alteration of blood-brain barrier (BBB) integrity in the substantia nigra pars compacta and/or striatum following MPTP injection. The benefits of gintonin treatment against MPTP also included the activation of the nuclear factor erythroid 2-related factor 2 pathways and the inhibition of phosphorylation of the mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways. Interestingly, these neuroprotective effects of gintonin were blocked by LPAR1/3 antagonist, Ki16425. Overall, the present study shows that gintonin attenuates MPTP-induced neurotoxicity via multiple targets. Gintonin combats neuronal death, and acts as an anti-inflammatory and an anti-oxidant agent. It maintains BBB integrity. LPA receptors play a key role in gintonin-mediated anti-PD mechanisms. Finally, gintonin is a key agent for prevention and/or treatment of PD.

7-Fluoro-1,3-diphenylisoquinoline reverses motor and non-motor symptoms induced by MPTP in mice: Role of striatal neuroinflammation.

PubMed

Sampaio, Tuane Bazanella; Marcondes Sari, Marcel Henrique; Pesarico, Ana Paula; Mantovani, Anderson Carboni; Zeni, Gilson; Nogueira, Cristina Wayne

2018-01-15

Parkinson's disease (PD) is a dopaminergic neurodegenerative disorder, which presents motor and non-motor symptoms. 7-Fluoro-1,3-diphenylisoquinoline (FDPI) is an isoquinoline compound with antioxidant and antidepressant properties. This study investigated whether FDPI reverses motor and non-motor symptoms in an acute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). It was also assessed the anti-inflammatory mechanisms in FDPI pharmacological action. C57Bl/6 male adult mice received four MPTP (20mg/kg, intraperitoneal) or saline (vehicle) injections to induce an acute PD model. FDPI (10mg/kg, intragastric) was daily administered to mice from the 2nd to 9th day after the induction and mice performed the behavioral tests on the 8th and 9th days. Striatum samples were collected for biochemical and molecular analyses. The results of the rotarod and challenging beam tests demonstrated that the administration of FDPI attenuated the impairments in balance and coordination of mice induced by MPTP. The FDPI reversed the short-term memory deficit and depressive-like behavior induced by MPTP in mice. FDPI attenuated the reduction in the striatal tyrosine hydroxylase levels, and it reversed the increase in the cyclooxygenase-2 levels and myeloperoxidase activity caused by MPTP in mice. Therefore, FDPI reversed motor and non-motor symptoms induced by an acute PD model and its restorative effects seem to be mediated by an anti-inflammatory action associated with a modulation of the striatal cyclooxygenase-2 levels and myeloperoxidase activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Similar decrease in spontaneous morphine abstinence by methadone and RB 101, an inhibitor of enkephalin catabolism.

PubMed

Ruiz, F; Fournié-Zaluski, M C; Roques, B P; Maldonado, R

1996-09-01

1. The dual inhibitor of enkephalin degrading enzymes, RB 101, is able to block endogenous enkephalin metabolism completely, leading to potent antinociceptive responses potentiated by blockade of CCKB receptors. In this study we have investigated the effects induced by RB 101 given alone, or with the CCKB antagonist, PD-134,308, on a model of spontaneous morphine withdrawal and substitutive maintenance in rats. 2. Animals were chronically treated with morphine for 7 days followed, 36 h after the interruption of drug administration, by a maintenance treatment for 5 days with methadone (2 mg kg-1, i.p.), clonidine (0.025 mg kg-1, i.p.), RB 101 (40 mg kg-1, i.p.), PD-134,308 (3 mg kg-1, i.p.) or a combination of RB 101 plus PD-134,308. Several behavioural observations were made during this period in order to evaluate the acute effects as well as the consequence of chronic maintenance induced on spontaneous withdrawal by the different treatments. 3. Methadone was the most effective compound in decreasing the spontaneous withdrawal syndrome after acute administration. Both, methadone and RB 101 had similar effectiveness in reducing opiate abstinence during the period of substitutive treatment. PD-134,308 did not show any effect when administered alone and did not modify the effect of RB 101. 4. Naloxone (1 mg kg-1, s.c.) failed to precipitate any sign of withdrawal when injected at the end of the chronic maintenance treatment suggesting that, under the present conditions, methadone and RB 101 did not induce significant physical opiate-dependence. 5. The mildness of the side effects induced by chronic RB 101, suggests that systemically active inhibitors of enkephalin catabolism could represent a promising treatment in the maintenance of opiate addicts.

Similar decrease in spontaneous morphine abstinence by methadone and RB 101, an inhibitor of enkephalin catabolism.

PubMed Central

Ruiz, F.; Fournié-Zaluski, M. C.; Roques, B. P.; Maldonado, R.

1996-01-01

1. The dual inhibitor of enkephalin degrading enzymes, RB 101, is able to block endogenous enkephalin metabolism completely, leading to potent antinociceptive responses potentiated by blockade of CCKB receptors. In this study we have investigated the effects induced by RB 101 given alone, or with the CCKB antagonist, PD-134,308, on a model of spontaneous morphine withdrawal and substitutive maintenance in rats. 2. Animals were chronically treated with morphine for 7 days followed, 36 h after the interruption of drug administration, by a maintenance treatment for 5 days with methadone (2 mg kg-1, i.p.), clonidine (0.025 mg kg-1, i.p.), RB 101 (40 mg kg-1, i.p.), PD-134,308 (3 mg kg-1, i.p.) or a combination of RB 101 plus PD-134,308. Several behavioural observations were made during this period in order to evaluate the acute effects as well as the consequence of chronic maintenance induced on spontaneous withdrawal by the different treatments. 3. Methadone was the most effective compound in decreasing the spontaneous withdrawal syndrome after acute administration. Both, methadone and RB 101 had similar effectiveness in reducing opiate abstinence during the period of substitutive treatment. PD-134,308 did not show any effect when administered alone and did not modify the effect of RB 101. 4. Naloxone (1 mg kg-1, s.c.) failed to precipitate any sign of withdrawal when injected at the end of the chronic maintenance treatment suggesting that, under the present conditions, methadone and RB 101 did not induce significant physical opiate-dependence. 5. The mildness of the side effects induced by chronic RB 101, suggests that systemically active inhibitors of enkephalin catabolism could represent a promising treatment in the maintenance of opiate addicts. Images Figure 4 PMID:8872371

Gypenosides attenuate the development of L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

PubMed

Shin, Keon Sung; Zhao, Ting Ting; Park, Keun Hong; Park, Hyun Jin; Hwang, Bang Yeon; Lee, Chong Kil; Lee, Myung Koo

2015-04-21

Gypenosides (GPS) and ethanol extract of Gynostemma pentaphyllum (GP-EX) show anxiolytic effects on affective disorders in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD). Long-term administration of L-3,4-dihydroxyphenylalanine (L-DOPA) leads to the development of severe motor side effects such as L-DOPA-induced-dyskinesia (LID) in PD. The present study investigated the effects of GPS and GP-EX on LID in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. Daily administration of L-DOPA (25 mg/kg) in the 6-OHDA-lesioned rat model of PD for 22 days induced expression of LID, which was determined by the body and locomotive AIMs scores and contralateral rotational behaviors. However, co-treatments of GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg) with L-DOPA significantly attenuated the development of LID without compromising the anti-parkinsonian effects of L-DOPA. In addition, the increases in ∆FosB expression and ERK1/2 phosphorylation in 6-OHDA-lesioned rats induced by L-DOPA administration were significantly reduced by co-treatment with GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg). These results suggest that GPS (25 and 50 mg/kg) and GP-EX (50 mg/kg) effectively attenuate the development of LID by modulating the biomarker activities of ∆FosB expression and ERK1/2 phosphorylation in the 6-OHDA-lesioned rat model of PD. GPS and GP-EX will be useful adjuvant therapeutics for LID in PD.

Evaluation of taurine as an osmotic agent for peritoneal dialysis solution.

PubMed

Nishimura, Hideki; Ikehara, Osamu; Naito, Takashi; Higuchi, Chieko; Sanaka, Tsutomu

2009-01-01

The development of a glucose-free peritoneal dialysis (PD) solution is important because glucose has been associated with functional and morphological damage to the peritoneal membrane. The ultrafiltration (UF) and biocompatibility of new PD solutions containing taurine (PD-taurine) instead of glucose as an osmolite were tested in a rat PD model. To determine the solution's UF ability, different concentrations of taurine in PD solutions were compared to glucose-based PD solutions (PD-glucose) by giving single intraperitoneal injections for 2, 4, and 6 hours. To examine the biocompatibility of PD-taurine, the rats were divided into 3 groups: a 3.86% PD-glucose group, a 3.5% PD-taurine group and a not dialyzed group. The rats were given 10-mL injections of PD fluids intraperitoneally 3 times daily for 7 days. A peritoneal equilibration test (PET) was performed using a 1.9% xylitol solution at the time the rats were sacrificed. Mesothelial cell monolayers were obtained from the animals and studied based on a population analysis. The net UF of PD-taurine increased in a dose-dependent manner; the 3.5% PD-taurine solution was equivalent to the 3.86% PD-glucose solution after 4 hours. The PET showed that the drainage volume and the D(4)/D(0) ratio for xylitol after 4 hours with PD-taurine solution were significantly greater than with the PD-glucose solution (p < 0.001 and p < 0.001 respectively). Mesothelial and fibroblast-like cell proliferation was significantly less with PD-taurine than with PD-glucose (p < 0.01). These results indicate that PD-taurine resulted in net UF equivalent to that of PD-glucose and was more biocompatible than PD-glucose with respect to the peritoneal membrane.

Survival analysis: comparing peritoneal dialysis and hemodialysis in Taiwan.

PubMed

Huang, Chiu-Ching; Cheng, Kuang-Fu; Wu, Hong-Dar Isaac

2008-06-01

Comparisons of survival in patients on peritoneal dialysis (PD) and on hemodialysis (HD) have been conducted in many Western countries, but publications on this subject in Asian populations are scarce. The present study estimated the survival and the relative mortality hazard for HD and PD patients in Taiwan. Incident end-stage renal disease patients reported to the Taiwan Renal Registry during 1995 - 2002 were included in the study. Patients had to be 20 years of age or older and had to have survived for the first 90 days on dialysis. A total of 45,820 incident HD and 2,809 incident PD patients formed the study population. Patients on PD were treated mainly with traditional glucose-based solutions. Using an intent-to-treat analysis, the Cox proportional hazards (CPH) model was applied to identify the factors that predict survival by treatment modality. Subgroup analyses were conducted by stratifying patients according to sex, comorbidity, age, and diabetes status. Kaplan-Meier estimates were used to explore the survival of HD and PD patients. Adjustments were implemented using the CPH model. The overall 1-year, 2-year, 3-year, 5-year and 10-year survival rates for PD patients were 89.8%, 77.6%, 67.6%, 55.5%, and 35% respectively. The equivalent survival rates for HD patients were 87.5%, 76.6%, 68.1%, 54.3%, and 33.8%. The differences were not statistically significant (p = 0.125). The CPH analysis stratified by diabetes status and age revealed that PD patients 55 years of age or younger and nondiabetic had a lower mortality ratio (MR) of 0.94. But the MR increased to 1.31 for nondiabetic patients older than 55. The MR for PD versus HD further increased to 1.72 for diabetic patients 55 years of age or younger, and to 1.99 for diabetic patients older than 55. After adjusting for both demographic and clinical case-mix differences, PD and HD patients were observed to have similar long-term survival. Subgroup analyses revealed that, among diabetic patients and patients older than 55, those on HD experienced better survival than did those on PD.

Teacher Perceptions of Their Curricular and Pedagogical Shifts: Outcomes of a Project-Based Model of Teacher Professional Development in the Next Generation Science Standards

PubMed Central

Shernoff, David J.; Sinha, Suparna; Bressler, Denise M.; Schultz, Dawna

2017-01-01

In this study, we conducted a model of teacher professional development (PD) on the alignment of middle and high school curricula and instruction to the Next Generation Science Standards (NGSSs), and evaluated the impact of the PD on teacher participants’ development. The PD model included a 4-day summer academy emphasizing project-based learning (PBL) in the designing of NGSS-aligned curricula and instruction, as well as monthly follow-up Professional Learning Community meetings throughout the year providing numerous opportunities for teachers to develop and implement lesson plans, share results of lesson writing and implementation (successes and challenges), provide mutual feedback, and refine curricula and assessments. Following the summer academy, six female teachers were interviewed about their current conceptualizations of NGSS, the extent of curricular shifts made that are required by NGSS, their self-perceptions regarding their level of accomplishment in curriculum writing, and the benefits of the PD in reaching their goals related to NGSS. Interviews were supplemented with an analysis of lesson plans written while participating in the PD program. The interviewed teachers suggested that they had made important conceptual and pedagogical shifts required by NGSS as they participated in the PD, and also noted a variety of challenges as they made this shift. While all teachers were relative novices at NGSS curriculum writing before the PD, most of the teachers interviewed felt that they had achieved the status of an “accomplished novice” following the summer academy. An analysis of their written lessons suggested a great range in the extent to which teachers effectively applied their understanding of NGSS to write lessons aligned to NGSS. Interviewed teachers believed that the PD model was helpful to their development as science teachers, and all reported that there were no aspects of the PD that were not helpful. Even though most teachers obtained a basic understanding and conceptualization of NGSS and PBL, their application of this understanding in their curriculum writing varied. The present study may help to inform future efforts to support teachers to align curricula and instruction to NGSS through teacher PD. PMID:28670294

Teacher Perceptions of Their Curricular and Pedagogical Shifts: Outcomes of a Project-Based Model of Teacher Professional Development in the Next Generation Science Standards.

PubMed

Shernoff, David J; Sinha, Suparna; Bressler, Denise M; Schultz, Dawna

2017-01-01

In this study, we conducted a model of teacher professional development (PD) on the alignment of middle and high school curricula and instruction to the Next Generation Science Standards (NGSSs), and evaluated the impact of the PD on teacher participants' development. The PD model included a 4-day summer academy emphasizing project-based learning (PBL) in the designing of NGSS-aligned curricula and instruction, as well as monthly follow-up Professional Learning Community meetings throughout the year providing numerous opportunities for teachers to develop and implement lesson plans, share results of lesson writing and implementation (successes and challenges), provide mutual feedback, and refine curricula and assessments. Following the summer academy, six female teachers were interviewed about their current conceptualizations of NGSS, the extent of curricular shifts made that are required by NGSS, their self-perceptions regarding their level of accomplishment in curriculum writing, and the benefits of the PD in reaching their goals related to NGSS. Interviews were supplemented with an analysis of lesson plans written while participating in the PD program. The interviewed teachers suggested that they had made important conceptual and pedagogical shifts required by NGSS as they participated in the PD, and also noted a variety of challenges as they made this shift. While all teachers were relative novices at NGSS curriculum writing before the PD, most of the teachers interviewed felt that they had achieved the status of an "accomplished novice" following the summer academy. An analysis of their written lessons suggested a great range in the extent to which teachers effectively applied their understanding of NGSS to write lessons aligned to NGSS. Interviewed teachers believed that the PD model was helpful to their development as science teachers, and all reported that there were no aspects of the PD that were not helpful. Even though most teachers obtained a basic understanding and conceptualization of NGSS and PBL, their application of this understanding in their curriculum writing varied. The present study may help to inform future efforts to support teachers to align curricula and instruction to NGSS through teacher PD.

Expression of Hsp70 reveals significant differences between fin regeneration and inflammation in Paramisgurnus dabryanus.

PubMed

Li, Li; Wang, Linlin; He, Jingya; Chang, Zhongjie

2017-05-01

Hsp70 is the most strongly induced in response to various cellular stresses and a good candidate for investigating its role in tissue injury. We firstly cloned full-length cDNA of hsp70 from Paramisgurnus dabryanus (PdHsp70) by RACE method (GenBank: KP402408.1). Then regeneration and inflammation of fin were established by amputation and scratch respectively. Quantitative RT-PCR detected the PdHsp70 began to increase rapidly its expression at 1 days post amputation (dpa) and reached the peak at 2 dpa during fin regeneration. Its expression was also up-regulated at 2 days post scratch (dps) of inflammation but still significant weaker in comparison with it in regenerated fin at 2 dpa. Next, immunohistochemistry analysis of PdHsp70 showed that PdHsp70 located mainly in the deeper epidermis of regenerated fin and was stronger than its expression in the scratched inflammatory fin which was involved in whole epidermal. SDS-PAGE and Western blotting confirmed that the PdHsp70 protein expressed efficiently in Escherichia coli BL21. These findings have implied that PdHsp70 are implicated in different regulation of regeneration and inflammation in response to injury stimulation. During the regeneration, it is involved in the formation of wound epidermis by mediating cellular protection whereas it can modulate inflammatory by activating the innate immune response. Copyright © 2017. Published by Elsevier Ltd.

Involvement of postnatal apoptosis on sex difference in number of cells generated during late fetal period in the sexually dimorphic nucleus of the preoptic area in rats.

PubMed

Kato, Yukinori; Nakashima, Shizuka; Maekawa, Fumihiko; Tsukahara, Shinji

2012-05-16

Postnatal apoptosis is involved in formation of the sex difference in neuron number of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in rats. In this study, we examined the origin of neurons that die with apoptosis on the postnatal period to exhibit the sex difference in neuron number of the SDN-POA. First, we measured the number of cells that were labeled with 5-bromo-2'-deoxyuridine (BrdU) on embryonic day (ED) 17, ED18, and ED19 in the SDN-POA of rats on postnatal day (PD) 4 and PD8. The SDN-POA had many more cells labeled with BrdU on ED17 and ED18 than those on ED19. Significantly fewer cells labeled with BrdU on ED18 in the female SDN-POA from PD4 to PD8 resulted in a significant sex difference in the number at PD8. Next, combination analyses of BrdU-labeling and immunohistochemistry for single-stranded DNA (ssDNA), an apoptotic marker, were succeeded to investigate whether SDN-POA neurons generated during ED17-18 were removed by apoptosis. Many more ssDNA-immunoreactive cells that had been labeled with BrdU during ED17-18 were found in the SDN-POA of PD8 females, but few in the SDN-POA of PD8 males and PD4 females and males. These results suggest that the sex difference in the number of SDN-POA neurons generated during the late fetal period was caused by postnatal apoptosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Screening for personality disorder in incarcerated adolescent boys: preliminary validation of an adolescent version of the standardised assessment of personality - abbreviated scale (SAPAS-AV).

PubMed

Kongerslev, Mickey; Moran, Paul; Bo, Sune; Simonsen, Erik

2012-07-30

Personality disorder (PD) is associated with significant functional impairment and an elevated risk of violent and suicidal behaviour. The prevalence of PD in populations of young offenders is likely to be high. However, because the assessment of PD is time-consuming, it is not routinely assessed in this population. A brief screen for the identification of young people who might warrant further detailed assessment of PD could be particularly valuable for clinicians and researchers working in juvenile justice settings. We adapted a rapid screen for the identification of PD in adults (Standardised Assessment of Personality - Abbreviated Scale; SAPAS) for use with adolescents and then carried out a study of the reliability and validity of the adapted instrument in a sample of 80 adolescent boys in secure institutions. Participants were administered the screen and shortly after an established diagnostic interview for DSM-IV PDs. Nine days later the screen was readministered. A score of 3 or more on the screening interview correctly identified the presence of DSM-IV PD in 86% of participants, yielding a sensitivity and specificity of 0.87 and 0.86 respectively. Internal consistency was modest but comparable to the original instrument. 9-days test-retest reliability for the total score was excellent. Convergent validity correlations with the total number of PD criteria were large. This study provides preliminary evidence of the validity, reliability, and usefulness of the screen in secure institutions for adolescent male offenders. It can be used in juvenile offender institutions with limited resources, as a brief, acceptable, staff-administered routine screen to identify individuals in need of further assessment of PD or by researchers conducting epidemiological surveys.

Association between keeping home records of catheter exit-site and incidence of peritoneal dialysis-related infections.

PubMed

Iida, Hidekazu; Kurita, Noriaki; Fujimoto, Shino; Kamijo, Yuka; Ishibashi, Yoshitaka; Fukuma, Shingo; Fukuhara, Shunichi

2018-04-01

To prevent peritoneal dialysis (PD)-related infection, components of self-catheter care have been emphasized. However, studies on the effectiveness of home recording for the prevention of PD-related infections are limited. This study aimed to examine the association between keeping home records of catheter exit site and incidence of PD-related infections. Home record books were submitted by patients undergoing PD. The proportion of days on which exit-site home recording was carried out for 120 days (0-100%) was obtained. The patients were divided into the frequent home recording group (≥ 40.5%; median value) and the infrequent home recording group (< 40.5%). The associations between the recording group and the incidence rate ratios (IRRs) of PD-related infections were estimated via negative binomial regression models. A total of 67 patients participated in this study (mean age, 66.7 years). The incidence rates for exit-site infection, tunnel infection, and peritonitis were 0.42, 0.22, and 0.06 times/patient-year, respectively. The IRRs of the frequent versus infrequent home recording groups for PD-related infection were 1.58 (95% confidence interval [CI], 0.72-3.46) in the univariate analysis and 1.49 (95% CI, 0.65-3.42) in the multivariate analysis. The IRRs of the frequent versus infrequent home recording groups for composite of surgery to create a new exit site and removal of PD catheter were 0.55 (95% CI, 0.78-3.88) and 0.35 (95% CI, 0.06-1.99), respectively. This study could not prove that keeping home records of patients' catheter exit site is associated with a lower incidence of PD-related infections.

Screening for personality disorder in incarcerated adolescent boys: preliminary validation of an adolescent version of the standardised assessment of personality – abbreviated scale (SAPAS-AV)

PubMed Central

2012-01-01

Background Personality disorder (PD) is associated with significant functional impairment and an elevated risk of violent and suicidal behaviour. The prevalence of PD in populations of young offenders is likely to be high. However, because the assessment of PD is time-consuming, it is not routinely assessed in this population. A brief screen for the identification of young people who might warrant further detailed assessment of PD could be particularly valuable for clinicians and researchers working in juvenile justice settings. Method We adapted a rapid screen for the identification of PD in adults (Standardised Assessment of Personality – Abbreviated Scale; SAPAS) for use with adolescents and then carried out a study of the reliability and validity of the adapted instrument in a sample of 80 adolescent boys in secure institutions. Participants were administered the screen and shortly after an established diagnostic interview for DSM-IV PDs. Nine days later the screen was readministered. Results A score of 3 or more on the screening interview correctly identified the presence of DSM-IV PD in 86% of participants, yielding a sensitivity and specificity of 0.87 and 0.86 respectively. Internal consistency was modest but comparable to the original instrument. 9-days test-retest reliability for the total score was excellent. Convergent validity correlations with the total number of PD criteria were large. Conclusion This study provides preliminary evidence of the validity, reliability, and usefulness of the screen in secure institutions for adolescent male offenders. It can be used in juvenile offender institutions with limited resources, as a brief, acceptable, staff-administered routine screen to identify individuals in need of further assessment of PD or by researchers conducting epidemiological surveys. PMID:22846474

CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity.

PubMed

Straub, Melanie; Drecoll, Enken; Pfarr, Nicole; Weichert, Wilko; Langer, Rupert; Hapfelmeier, Alexander; Götz, Carolin; Wolff, Klaus-Dietrich; Kolk, Andreas; Specht, Katja

2016-03-15

Immunomodulatory therapies, targeting the immune checkpoint receptor-ligand complex PD-1/PD-L1 have shown promising results in early phase clinical trials in solid malignancies, including carcinomas of the head and neck. In this context, PD-L1 protein expression has been proposed as a potentially valuable predictive marker. In the present study, expression of PD-L1 and PD-1 was evaluated by immunohistochemistry in 80 patients with predominantly HPV-negative oral squamous cell carcinomas and associated nodal metastasis. In addition, CD274/PD-L1 gene copy number status was assessed by fluorescence in situ hybridization analysis. PD-L1 expression was detected in 36/80 (45%) cases and concordance of PD-L1 expression in primary tumor and corresponding nodal metastasis was present in only 20/28 (72%) cases. PD-1 expression was found in tumor-infiltrating lymphocytes (TILs) but not in tumor cells. CD274/PD-L1 gene amplification was detected in 19% of cases, with high level PD-L1 amplification present in 12/80 (15%), and low level amplification in 3/80 (4%). Interestingly, CD274/PD-L1 gene amplification was associated with positive PD-L1 immunostaining in only 73% of cases. PD-L1 copy number status was concordant in primary tumor and associated metastases. Clinically, PD-L1 tumor immunopositivity was associated with a higher risk for nodal metastasis at diagnosis, overall tumor related death und recurrence. Based on our findings we propose to include PD-L1 copy number status in addition to protein status in screening programs for future clinical trials with immunotherapeutic strategies targeting the PD-1/PD-L1 axis.

CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity

PubMed Central

Straub, Melanie; Drecoll, Enken; Pfarr, Nicole; Weichert, Wilko; Langer, Rupert; Hapfelmeier, Alexander; Götz, Carolin; Wolff, Klaus-Dietrich; Kolk, Andreas; Specht, Katja

2016-01-01

Immunomodulatory therapies, targeting the immune checkpoint receptor-ligand complex PD-1/PD-L1 have shown promising results in early phase clinical trials in solid malignancies, including carcinomas of the head and neck. In this context, PD-L1 protein expression has been proposed as a potentially valuable predictive marker. In the present study, expression of PD-L1 and PD-1 was evaluated by immunohistochemistry in 80 patients with predominantly HPV-negative oral squamous cell carcinomas and associated nodal metastasis. In addition, CD274/PD-L1 gene copy number status was assessed by fluorescence in situ hybridization analysis. PD-L1 expression was detected in 36/80 (45%) cases and concordance of PD-L1 expression in primary tumor and corresponding nodal metastasis was present in only 20/28 (72%) cases. PD-1 expression was found in tumor-infiltrating lymphocytes (TILs) but not in tumor cells. CD274/PD-L1 gene amplification was detected in 19% of cases, with high level PD-L1 amplification present in 12/80 (15%), and low level amplification in 3/80 (4%). Interestingly, CD274/PD-L1 gene amplification was associated with positive PD-L1 immunostaining in only 73% of cases. PD-L1 copy number status was concordant in primary tumor and associated metastases. Clinically, PD-L1 tumor immunopositivity was associated with a higher risk for nodal metastasis at diagnosis, overall tumor related death und recurrence. Based on our findings we propose to include PD-L1 copy number status in addition to protein status in screening programs for future clinical trials with immunotherapeutic strategies targeting the PD-1/PD-L1 axis. PMID:26918453

KSC-04PD-2216

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. This panel comprising former and current Safety and Mission Assurance (S&MA) management talk about identifying and comparing safety challenges of the past, present and future during Spaceport Super Safety and Health Day (SS&H) at KSC. Larry Crawford, left, is director of S&MA. SS&H Day included guest speakers Dr. Pamela Peeke, Navy Com. Stephen E. Iwanowicz, NASAs Dr. Kristine Calderon and Olympic-great Bruce Jenner. In addition, many vendors exhibits were on display for employees. Super Safety and Health Day was initiated at KSC in 1998 to increase awareness of the importance of safety and health among the government and contractor workforce. The theme for this years event was Safety and Health: A Winning Combination.

Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial.

PubMed

Chagas, Marcos Hortes N; Zuardi, Antonio W; Tumas, Vitor; Pena-Pereira, Márcio Alexandre; Sobreira, Emmanuelle T; Bergamaschi, Mateus M; dos Santos, Antonio Carlos; Teixeira, Antonio Lucio; Hallak, Jaime E C; Crippa, José Alexandre S

2014-11-01

Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS). We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H(1)-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05). Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn. © The Author(s) 2014.

The economics of recovery after pancreatic surgery: detailed cost minimization analysis of an enhanced recovery program.

PubMed

Kagedan, Daniel J; Devitt, Katharine S; Tremblay St-Germain, Amélie; Ramjaun, Aliya; Cleary, Sean P; Wei, Alice C

2017-11-01

Clinical pathways (CPW) are considered safe and effective at decreasing postoperative length of stay (LoS), but the effect on economic costs is uncertain. This study sought to elucidate the effect of a CPW on direct hospitalization costs for patients undergoing pancreaticoduodenectomy (PD). A CPW for PD patients at a single Canadian institution was implemented. Outcomes included LoS, 30-day readmissions, and direct costs of hospital care. A retrospective cost minimization analysis compared patients undergoing PD prior to and following CPW implementation, using a bootstrapped t test and deviation-based cost modeling. 121 patients undergoing PD after CPW implementation were compared to 74 controls. Index LoS was decreased following CPW implementation (9 vs. 11 days, p = 0.005), as was total LoS (10 vs. 11 days, p = 0.003). The mean total cost of postoperative hospitalization per patient decreased in the CPW group ($15,678.45 CAD vs. $25,732.85 CAD, p = 0.024), as was the mean 30-day cost including readmissions ($16,627.15 CAD vs. $29,872.72 CAD, p = 0.016). Areas of significant cost savings included laboratory tests and imaging investigations. CPWs may generate cost savings by reducing unnecessary investigations, and improve quality of care through process standardization and decreasing practice variation. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

KSC-03PD-2820

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Employees fill the Training Auditorium for the kickoff presentation for Spaceport Super Safety and Health Day. Along with Center Director Jim Kennedy, guest speakers were Brig. Gen. J. Gregory Pavlovich, 45th Space Wing, Maj. Gen. Kevin Chilton, and Capt. Charles Plumb (USNR retired), who spoke about his experiences in the Navy and as a prisoner of war in Vietnam. Spaceport Super Safety and Health Day is an annual event at KSC and Cape Canaveral Air Force Station dedicated to reinforcing safe and healthful behaviors in the workforce. Safety Awards were also given to individuals and groups.

KSC-03PD-2821

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Brig. Gen. J. Gregory Pavlovich, 45th Space Wing, speaks to the employees and guests gathered in the KSC Training Auditorium for Spaceport Super Safety and Health Day. The kickoff presentation also included speakers Maj. Gen. Kevin Chilton and Capt. Charles Plumb (USNR retired), who spoke about his experiences in the Navy and as a prisoner of war in Vietnam. Spaceport Super Safety and Health Day is an annual event at KSC and Cape Canaveral Air Force Station dedicated to reinforcing safe and healthful behaviors in the workforce. Safety Awards were also given to individuals and groups.

KSC-03PD-2822

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. Maj. Gen. Kevin Chilton speaks to the employees and guests gathered in the KSC Training Auditorium for Spaceport Super Safety and Health Day. The kickoff presentation also included speakers Brig. Gen. J. Gregory Pavlovich, 45th Space Wing, and Capt. Charles Plumb (USNR retired), who spoke about his experiences in the Navy and as a prisoner of war in Vietnam. Spaceport Super Safety and Health Day is an annual event at KSC and Cape Canaveral Air Force Station dedicated to reinforcing safe and healthful behaviors in the workforce. Safety Awards were also given to individuals and groups.

Impact of Pre-Dialysis Care on Clinical Outcomes in Peritoneal Dialysis Patients.

PubMed

Spigolon, Dandara N; de Moraes, Thyago P; Figueiredo, Ana E; Modesto, Ana Paula; Barretti, Pasqual; Bastos, Marcus Gomes; Barreto, Daniela V; Pecoits-Filho, Roberto

2016-01-01

Structured pre-dialysis care is associated with an increase in peritoneal dialysis (PD) utilization, but not with peritonitis risk, technical and patient survival. This study aimed at analyzing the impact of pre-dialysis care on these outcomes. All incident patients starting PD between 2004 and 2011 in a Brazilian prospective cohort were included in this analysis. Patients were divided into 2 groups: early pre-dialysis care (90 days of follow-up by a nephrology team); and late pre-dialysis care (absent or less than 90 days follow-up). The socio-demographic, clinical and biochemical characteristics between the 2 groups were compared. Risk factors for the time to the first peritonitis episode, technique failure and mortality based on Cox proportional hazards models. Four thousand one hundred seven patients were included. Patients with early pre-dialysis care presented differences in gender (female - 47.0 vs. 51.1%, p = 0.01); race (white - 63.8 vs. 71.7%, p < 0.01); education (<4 years - 61.9 vs. 71.0%, p < 0.01), respectively, compared to late care. Patients with early pre-dialysis care presented a higher prevalence of comorbidities, lower levels of creatinine, phosphorus, and glucose with a significantly better control of hemoglobin and potassium serum levels. There was no impact of pre-dialysis care on peritonitis rates (hazard ratio (HR) 0.88; 95% CI 0.77-1.01) and technique survival (HR 1.12; 95% CI 0.92-1.36). Patient survival (HR 1.20; 95% CI 1.03-1.41) was better in the early pre-dialysis care group. Earlier pre-dialysis care was associated with improved patient survival, but did not influence time to the first peritonitis nor technique survival in this national PD cohort. © 2016 S. Karger AG, Basel.

Risks of Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficient Infants Exposed to Chlorproguanil-Dapsone, Mefloquine and Sulfadoxine-Pyrimethamine as Part of Intermittent Presumptive Treatment of Malaria in Infants.

PubMed

Poirot, Eugenie; Vittinghoff, Eric; Ishengoma, Deus; Alifrangis, Michael; Carneiro, Ilona; Hashim, Ramadhan; Baraka, Vito; Mosha, Jacklin; Gesase, Samwel; Chandramohan, Daniel; Gosling, Roland

2015-01-01

Chlorproguanil-dapsone (CD) has been linked to hemolysis in symptomatic glucose-6-phosphate dehydrogenase deficient (G6PDd) children. Few studies have explored the effects of G6PD status on hemolysis in children treated with Intermittent Preventive Treatment in infants (IPTi) antimalarial regimens. We sought to examine the joint effects of G6PD status and IPTi antimalarial treatment on incidence of hemolysis in asymptomatic children treated with CD, sulfadoxine-pyrimethamine (SP), and mefloquine (MQ). A secondary analysis of data from a double-blind, placebo-controlled trial of IPTi was conducted. Hemoglobin (Hb) measurements were made at IPTi doses, regular follow-up and emergency visits. G6PD genotype was determined at 9 months looking for SNPs for the A- genotype at coding position 202. Multivariable linear and logistic regression models were used to examine hemolysis among children with valid G6PD genotyping results. Hemolysis was defined as the absolute change in Hb or as any post-dose Hb <8 g/dL. These outcomes were assessed using either a single follow-up Hb on day 7 after an IPTi dose or Hb obtained 1 to 14 or 28 days after each IPTi dose. Relative to placebo, CD reduced Hb by approximately 0.5 g/dL at day 7 and within 14 days of an IPTi dose, and by 0.2 g/dL within 28 days. Adjusted declines in the CD group were larger than in the MQ and SP groups. At day 7, homo-/hemizygous genotype was associated with higher odds of Hb <8 g/dL (adjusted odds ratio = 6.7, 95% CI 1.7 to 27.0) and greater absolute reductions in Hb (-0.6 g/dL, 95% CI -1.1 to 0.003). There was no evidence to suggest increased reductions in Hb among homo-/hemizygous children treated with CD compared to placebo, SP or MQ. While treatment with CD demonstrated greater reductions in Hb at 7 and 14 days after an IPTi dose compared to both SP and MQ, there was no evidence that G6PD deficiency exacerbated the adverse effects of CD, despite evidence for higher hemolysis risk among G6PDd infants.

[Resveratrol derived from rhizoma et radix polygoni cuspidati and its liposomal form protect nigral cells of Parkinsonian rats].

PubMed

Wang, Yanchun; Xu, Hanlin; Fu, Qin; Ma, Rong; Xiang, Jizhou

2011-04-01

Oxidative stress is a hallmark in the pathogenesis of Parkinson disease (PD), which involves the selective loss of nigral dopaminergic neurons in PD. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is well known for its powerful antioxidant property and a wide range of other biological effects. In this study, we investigated the protective effect of resveratrol derived from Rhizoma Et Radix Polygoni Cuspidati and its liposomal form on the nigral cells of PD rats induced by unilateral microinjection of 6-hydroxy dopamine in the striatum. The results showed that after 14 days gavage of resveratrol and resveratrol liposome respectively (20 mg x kg(-1) WB per day), the abnormal rotational behavior of PD rats were deceased evidently, the numbers of total nigral cells, total nigral neurons and TH immuno-positive neurons were more than that of PD rats without given resveratrol or resveratrol liposome, simultaneously, the number of apoptotic nigral cells were decreased obviously. The results also showed that resveratrol and resveratrol liposome could decrease the total ROS activity, increase the total antioxidant capability of the nigral tissues. All the data indicated that resveratrol liposome performed stronger effects than resveratrol except for behavioral improvement. Our study confirmed that resveratrol derived from Rhizoma Et Radix Polygoni Cuspidati and its liposomal form could inhibit the loss of dopaminergic neurons of PD rats, the underlying mechanism may be attributed to their radical scavenging effect and antioxidant property. Due to presumably increased bioavailability, resveratrol liposome possesses the stronger therapeutic effect and may become a better clinical agent for the treatment of PD than free resveratrol.

Zolpidem improves neuropsychiatric symptoms and motor dysfunction in a patient with Parkinson's disease after deep brain stimulation.

PubMed

Huang, Hung-Yu; Hsu, Yi-Ting; Wu, Yu-Chin; Chiou, Shang-Ming; Kao, Chia-Hung; Tsai, Mu-Chieh; Tsai, Chon-Haw

2012-06-01

To illustrate the beneficial effect of zolpidem on the neuropsychiatric and motor symptoms in a patient with Parkinson disease (PD) after bilateral subthalamic nucleus deep brain stimulation. The 61-year-old housewife was diagnosed to have PD for 12 years with initial presentation of clumsiness and rest tremor of right limbs. She was referred to our hospital in March 2009 due to shortening of drug beneficial period since 3 years ago and on-phase dyskinesia in recent 2 years. Bilateral STN DBS was conducted on 18 June, 2009. Fluctuating spells of mental confusion were developed on the next day after surgery. Electric stimuli via DBS electrodes were delivered with parameters of 2 volts, 60 μs, 130 Hz on bilateral STN 32 days after DBS. The incoherent behaviors and motor fluctuation remained to occur. The beneficial effect of zolpidem on her neuropsychiatric and motor symptoms was detected incidentally in early July 2009. She could chat normally with her caregiver and walk with assistance after taking zolpidem. The beneficial period may last for 2 hours. Zolpidem was then given in dosage of 10 mg three times per day. The neuropsychiatric inventory was scored 56 during zolpidem 'off' and 30 during zolpidem 'on'. To understand the intriguing feature, we conducted FDG-PET during 'off' and 'on' zolpidem conditions. The results revealed that the metabolism was decreased in the right frontal, parietal cortex and caudate nucleus during zolpidem 'off'. These cool spots can be partially restored by zolpidem. Zolpidem ameliorated the neuropsychiatric and parkinsonian motor symptom in the PD patient. Since GABAA benzodiazepine receptors are widely distributed throughout the central nervous system, zolpidem probably acts via modulating structures lying within the cortico-subcortical loop or by direct effect on these cortical regions.

Urinary steroid hormone analysis of ovarian cycles and pregnancy in mandrills (Mandrillus sphinx) indicate that menses, copulatory behavior, sexual swellings and reproductive condition are associated with changing estrone conjugates (E(1)C) and pregnanediol-3-glucuronide (PdG).

PubMed

Phillips, Rebecca Sellin; Wheaton, Catharine J

2008-07-01

The objective of this study was to determine if sexual swellings in mandrills (Mandrillus sphinx) are a reflection of reproductive endocrine state. Urine samples were assayed using an enzyme immunoassay measuring pregnanediol-3-glucuronide (PdG) and estrone conjugates (E(1)C). Hormone patterns of ovarian cycles, pregnancy and lactation were characterized and compared with sexual swellings and copulations relative to menses and peak E(1)C. Cycle lengths averaging 28.7 days and pregnancy length of 181 days determined by hormonal and sexual swelling measures were similar to those reported in other Old World primate species. First day of copulation was observed during rising E(1)C concentrations and preceded observations of peak swelling by 1-2 days. Observations of peak sexual swellings occurred at or on the day after peak E(1)C and decreased following the ovulatory increase in PdG. Observations of menses and sexual swellings are a useful method to track mandrill ovarian cycles and can assist zoos in determining the reproductive state of females in their collections. Zoo Biol 27:320-330, 2008. (c) 2008 Wiley-Liss, Inc.

Effects of Dexamethasone and Placebo on Symptom Clusters in Advanced Cancer Patients: A Preliminary Report.

PubMed

Yennurajalingam, Sriram; Williams, Janet L; Chisholm, Gary; Bruera, Eduardo

2016-03-01

Advanced cancer patients frequently experience debilitating symptoms that occur in clusters, but few pharmacological studies have targeted symptom clusters. Our objective was to examine the effects of dexamethasone on symptom clusters in patients with advanced cancer. We reviewed the data from a previous randomized clinical trial to determine the effects of dexamethasone on cancer symptoms. Symptom clusters were identified according to baseline symptoms by using principal component analysis. Correlations and change in the severity of symptom clusters were analyzed after study treatment. A total of 114 participants were included in this study. Three clusters were identified: fatigue/anorexia-cachexia/depression (FAD), sleep/anxiety/drowsiness (SAD), and pain/dyspnea (PD). Changes in severity of FAD and PD significantly correlated over time (at baseline, day 8, and day 15). The FAD cluster was associated with significant improvement in severity at day 8 and day 15, whereas no significant change was observed with the SAD cluster or PD cluster after dexamethasone treatment. The results of this preliminary study suggest significant correlation over time and improvement in the FAD cluster at day 8 and day 15 after treatment with dexamethasone. These findings suggest that fatigue, anorexia-cachexia, and depression may share a common pathophysiologic basis. Further studies are needed to investigate this cluster and target anti-inflammatory therapies. ©AlphaMed Press.

Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease.

PubMed

Bolitho, Samuel J; Naismith, Sharon L; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R; Lewis, Simon J G

2013-01-01

Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms.

Objective Measurement of Daytime Napping, Cognitive Dysfunction and Subjective Sleepiness in Parkinson’s Disease

PubMed Central

Bolitho, Samuel J.; Naismith, Sharon L.; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R.; Lewis, Simon J. G.

2013-01-01

Introduction Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson’s disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Methods Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Results Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. Conclusion This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms. PMID:24278399

Modified Peritoneal Dialysis Catheter Insertion: Comparison with a Conventional Method.

PubMed

Lee, Yong Kyu; Yang, Pil-Sung; Park, Kyoung Sook; Choi, Kyu Hun; Kim, Beom Seok

2015-07-01

The conventional trocar and cannula method in peritoneal dialysis (PD) catheter insertion has its limitation in clinical setting. The aim of this study was to compare a modified method for percutaneous PD catheter insertion with the conventional method, and demonstrate advantages of the modified method. Patients at a single center who had percutaneous PD catheters inserted by nephrologists from January 2006 until September 2012, using either a modified method (group M) or the conventional trocar and cannula method (group C), were retrospectively analyzed, in terms of baseline characteristics, complications experienced up to 3 months after the procedure, and the suitability of the procedure for patients. Group M included 82 subjects, while group C included 66 cases. The overall early complication rate in group M (1.2%) was significantly lower than that in group C (19.7%) (p<0.001). The catheter revision rate during timeframe for early complications was significantly lower in group M (0%) than in group C (6.1%) (p=0.024). When comparing Procedure time (1 h 3 min±16 min vs. 1 h 36 min±19 min, p<0.01), immediate post-procedural pain (2.43±1.80 vs. 3.14±2.07, p<0.05), and post-procedure days until ambulation (3.95±1.13 days vs. 6.17±1.34 days, p<0.01), group M was significantly lower than group C. There was no significant difference in total hospitalization period (14.71±7.05 days vs. 13.86±3.7 days). Our modified PD catheter insertion method shows its advantages in early complication rate, early complications revision rate, and the patients' conveniences.

Modified Peritoneal Dialysis Catheter Insertion: Comparison with a Conventional Method

PubMed Central

Lee, Yong Kyu; Yang, Pil-Sung; Park, Kyoung Sook; Choi, Kyu Hun

2015-01-01

Purpose The conventional trocar and cannula method in peritoneal dialysis (PD) catheter insertion has its limitation in clinical setting. The aim of this study was to compare a modified method for percutaneous PD catheter insertion with the conventional method, and demonstrate advantages of the modified method. Materials and Methods Patients at a single center who had percutaneous PD catheters inserted by nephrologists from January 2006 until September 2012, using either a modified method (group M) or the conventional trocar and cannula method (group C), were retrospectively analyzed, in terms of baseline characteristics, complications experienced up to 3 months after the procedure, and the suitability of the procedure for patients. Results Group M included 82 subjects, while group C included 66 cases. The overall early complication rate in group M (1.2%) was significantly lower than that in group C (19.7%) (p<0.001). The catheter revision rate during timeframe for early complications was significantly lower in group M (0%) than in group C (6.1%) (p=0.024). When comparing Procedure time (1 h 3 min±16 min vs. 1 h 36 min±19 min, p<0.01), immediate post-procedural pain (2.43±1.80 vs. 3.14±2.07, p<0.05), and post-procedure days until ambulation (3.95±1.13 days vs. 6.17±1.34 days, p<0.01), group M was significantly lower than group C. There was no significant difference in total hospitalization period (14.71±7.05 days vs. 13.86±3.7 days). Conclusion Our modified PD catheter insertion method shows its advantages in early complication rate, early complications revision rate, and the patients' conveniences. PMID:26069120

A Waist-Worn Inertial Measurement Unit for Long-Term Monitoring of Parkinson’s Disease Patients

PubMed Central

Rodríguez-Martín, Daniel; Pérez-López, Carlos; Samà, Albert; Català, Andreu; Moreno Arostegui, Joan Manuel; Cabestany, Joan; Mestre, Berta; Alcaine, Sheila; Prats, Anna; de la Cruz Crespo, María; Bayés, Àngels

2017-01-01

Inertial measurement units (IMUs) are devices used, among other fields, in health applications, since they are light, small and effective. More concretely, IMUs have been demonstrated to be useful in the monitoring of motor symptoms of Parkinson’s disease (PD). In this sense, most of previous works have attempted to assess PD symptoms in controlled environments or short tests. This paper presents the design of an IMU, called 9 × 3, that aims to assess PD symptoms, enabling the possibility to perform a map of patients’ symptoms at their homes during long periods. The device is able to acquire and store raw inertial data for artificial intelligence algorithmic training purposes. Furthermore, the presented IMU enables the real-time execution of the developed and embedded learning models. Results show the great flexibility of the 9 × 3, storing inertial information and algorithm outputs, sending messages to external devices and being able to detect freezing of gait and bradykinetic gait. Results obtained in 12 patients exhibit a sensitivity and specificity over 80%. Additionally, the system enables working 23 days (at waking hours) with a 1200 mAh battery and a sampling rate of 50 Hz, opening up the possibility to be used for other applications like wellbeing and sports. PMID:28398265

Glutamate Neonatal Excitotoxicity Modifies VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 Protein Expression Profiles During Postnatal Development of the Cerebral Cortex and Hippocampus of Male Rats.

PubMed

Castañeda-Cabral, Jose Luis; Beas-Zarate, Carlos; Gudiño-Cabrera, Graciela; Ureña-Guerrero, Monica E

2017-09-01

Vascular endothelial growth factor (VEGF) exerts both neuroprotective and proinflammatory effects in the brain, depending on the VEGF (A-E) and VEGF receptor (VEGFR1-3) types involved. Neonatal monosodium glutamate (MSG) treatment triggers an excitotoxic degenerative process associated with several neuropathological conditions, and VEGF messenger RNA (mRNA) expression is increased at postnatal day (PD) 14 in rat hippocampus (Hp) following the treatment. The aim of this work was to establish the changes in immunoreactivity to VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 proteins induced by neonatal MSG treatment (4 g/kg, subcutaneous, at PD1, 3, 5 and 7) in the cerebral motor cortex (CMC) and Hp. Samples collected from PD2 to PD60 from control and MSG-treated male Wistar rats were assessed by western blotting for each protein. Considering that immunoreactivity measured by western blotting is related to the protein expression level, we found that each protein in each cerebral region has a specific expression profile throughout the studied ages, and all profiles were differentially modified by MSG. Specifically, neonatal MSG treatment significantly increased the immunoreactivity to the following: (1) VEGF-A at PD8-PD10 in the CMC and at PD6-PD8 in the Hp; (2) VEGF-B at PD2, PD6 and PD10 in the CMC and at PD8-PD9 in the Hp; and (3) VEGFR-2 at PD6-PD8 in the CMC and at PD21-PD60 in the Hp. Also, MSG significantly reduced the immunoreactivity to the following: (1) VEGF-B at PD8-PD9 and PD45-PD60 in the CMC; and (2) VEGFR-1 at PD4-PD6 and PD14-PD21 in the CMC and at PD4, PD9-PD10 and PD60 in the Hp. Our results indicate that VEGF-mediated signalling is involved in the excitotoxic process triggered by neonatal MSG treatment and should be further characterized.

Herb-drug interaction of Nisha Amalaki and Curcuminoids with metformin in normal and diabetic condition: A disease system approach.

PubMed

Shengule, Sushant; Kumbhare, Kalyani; Patil, Dada; Mishra, Sanjay; Apte, Kishori; Patwardhan, Bhushan

2018-05-01

Nisha Amalaki (NA), formulation with Curcuma longa Linn (Turmeric, Haridra, Nisha in Sanskrit; Family: Zingiberaceae) and Phyllanthus emblica Linn (Indian gooseberry, Amlaki in Sanskrit; Family: Phyllanthaceae) which is described for various diseases including diabetes in ayurvedic texts and Nighantus. The aim of the present study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) interactions of chemically standardized NA and Curcuminoids (CE) with metformin (MET) in normal and diabetic animals. Oral administration of NA (200 mg/kg) and CE (30 mg/kg) was carried out for seven days followed by co-administration of MET till fifteen days. MET plasma PK parameters including C max , AUC 0-∞ , t 1/2 , CL and V d were measured on the eighth day. PD parameters including plasma glucose AUC followed by oral glucose tolerance test, high-density lipoproteins (HDL), total cholesterol (TC) and triglycerides (TG) were measured on the fifteenth day. In normal animals, co-administration of NA + MET and CE + MET resulted in significant increase (p < 0.05) in C max , AUC 0-∞ , t 1/2, and reduction of CL and V d . We report that co-administration of NA + MET and CE + MET significantly (p < 0.01, p < 0.001) reduced plasma glucose level, HDL level while a notable reduction in TG and TC level was observed. Interestingly, in diabetic condition, co-administration of NA + MET and CE + MET indicated a significant decrease (p < 0.05) in C max , AUC 0-∞ , t 1/2 and enhanced CL and V d. Hence, to conclude, co-administration of NA + MET and CE + MET resulted in beneficial PK and PD interactions leading to antihyperglycemic and antihyperlipidemic effects in both conditions. However, PK interaction was drastically different in diabetic and normal conditions. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Utility of feeding jejunostomy tubes in pancreaticoduodenectomy.

PubMed

Waliye, Hussein E; Wright, G Paul; McCarthy, Caitlin; Johnson, Jared; Scales, Alex; Wolf, Andrea; Chung, Mathew

2017-03-01

Routine placement of jejunostomy tubes (JT) during pancreaticoduodenectomy (PD) is controversial. A retrospective chart review of patients undergoing PD from 1/1/08 through 12/31/14 was performed. The patients were divided into groups by placement of JT. Outcome measures were 90-day morbidity, 90-day mortality, length of stay, rate of delayed gastric emptying (DGE), and JT-specific complications. 256 patients were included. There were no significant differences in 90-day morbidity (39.9% vs. 37.9%, p = 0.747), 90-day mortality (3.9% vs. 1.0%, p = 0.247) or TPN use (24.8 vs. 25.2%, p = 0.941) between those with and without JT, respectively. Patients with a JT had a higher rate of DGE (p < 0.001), longer hospital stay (14.3 vs. 11.6, p < 0.001), and longer time to solid intake (9.4 vs. 7.3, p < 0.001). Eleven patients (7.2%) with JT had tube-related morbidity. Routine placement of JT at the time of PD should be abandoned with efforts focused on preoperative nutrition optimization and early oral diet trials. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells

PubMed Central

Odorizzi, Pamela M.; Pauken, Kristen E.; Paley, Michael A.; Sharpe, Arlene

2015-01-01

Programmed Death-1 (PD-1) has received considerable attention as a key regulator of CD8+ T cell exhaustion during chronic infection and cancer because blockade of this pathway partially reverses T cell dysfunction. Although the PD-1 pathway is critical in regulating established “exhausted” CD8+ T cells (TEX cells), it is unclear whether PD-1 directly causes T cell exhaustion. We show that PD-1 is not required for the induction of exhaustion in mice with chronic lymphocytic choriomeningitis virus (LCMV) infection. In fact, some aspects of exhaustion are more severe with genetic deletion of PD-1 from the onset of infection. Increased proliferation between days 8 and 14 postinfection is associated with subsequent decreased CD8+ T cell survival and disruption of a critical proliferative hierarchy necessary to maintain exhausted populations long term. Ultimately, the absence of PD-1 leads to the accumulation of more cytotoxic, but terminally differentiated, CD8+ TEX cells. These results demonstrate that CD8+ T cell exhaustion can occur in the absence of PD-1. They also highlight a novel role for PD-1 in preserving TEX cell populations from overstimulation, excessive proliferation, and terminal differentiation. PMID:26034050

Evaluation of the Immunologic Impact of RAF Inhibitors to Guide Optimal Combination of RAF Inhibitors and Immunotherapy for the Treatment of Advanced Melanoma

DTIC Science & Technology

2016-03-01

TILS (Vehicle) Fr eq o f P ar en t CD4+ T cells CD4+CD25+Foxp3+ CD8+ CD8+PD1+ CD8+GrzB...PDL1+ CD 4+ T ce lls CD 4+ CD 25 +F ox p3 + CD 8+ CD 8+ PD 1+ CD 8+ Gr zB + CD 8+ Ki6 7+ 0 10 20 30 40 Day 5 - TILS (BRAFi) Fr eq o f P ar en t...ce lls CD 4+ CD 25 +F ox p3 + CD 8+ CD 8+ PD 1+ CD 8+ Gr zB + CD 8+ Ki6 7+ 0 10 20 30 40 Day 2 - TILS (Vehicle) Fr eq o f P ar en t CD4+ T cells

Minilaparotomy salvage of malfunctioning catheters in peritoneal dialysis.

PubMed

Li, Jian-Ri; Cheng, Chi-Hung; Chiu, Kun-Yuan; Cheng, Chen-Li; Yang, Chi-Rei; Ho, Hao-Chung; Ko, Jiunn-Liang; Ou, Yen-Chuan

2013-01-01

Catheter malfunction is a common and significant complication during peritoneal dialysis (PD). We developed a minilaparotomy procedure to rescue malfunctioning catheters and to prevent recurrence of malfunction. From 2006 to 2011, 11 patients receiving PD had a malfunctioning catheter. In all patients, a 2-cm incision, 5 cm caudally to the previous peritoneal entry site was used to correct the malfunctioning catheter, with concomitant fixation of the catheter to the peritoneum. Catheter tip migration occurred in 7 patients, omental wrapping in 3, and blood clot obstruction in 1. The mean onset time to catheter malfunction was 197.5 days (range: 4 - 1270 days), and the mean operating time was 41 minutes (range: 35 - 56 minutes). There was no recurrence of catheter malfunction and no surgery-related peritonitis. Our minilaparotomy procedure is safe and feasible for the salvage of malfunctioning PD catheters.

Better preservation of residual renal function in peritoneal dialysis patients treated with a low-protein diet supplemented with keto acids: a prospective, randomized trial.

PubMed

Jiang, Na; Qian, Jiaqi; Sun, Weilan; Lin, Aiwu; Cao, Liou; Wang, Qin; Ni, Zhaohui; Wan, Yanping; Linholm, Bengt; Axelsson, Jonas; Yao, Qiang

2009-08-01

While a low-protein diet may preserve residual renal function (RRF) in chronic kidney disease (CKD) patients before the start of dialysis, a high-protein intake is usually recommended in dialysis patients to prevent protein-energy wasting. Keto acids, which were often recommended to pre-dialysis CKD patients treated with a low-protein diet, had also been reported to be associated with both RRF and nutrition maintenance. We conducted a randomized trial to test whether a low-protein diet with or without keto acids would be safe and associated with a preserved RRF during peritoneal dialysis (PD). To assess the safety of low protein, we first conducted a nitrogen balance study in 34 incident PD patients randomized to receive in-centre diets containing 1.2, 0.9 or 0.6 g of protein/kg ideal body weight (IBW)/day for 10 days. Second, 60 stable PD patients [RRF 4.04 +/- 2.30 ml/ min/1.73 m(2), urine output 1226 +/- 449 ml/day, aged 53.6 +/- 12.8 years, PD duration 8.8 (1.5-17.8) months] were randomized to receive either a low- (LP: 0.6-0.8 g/kg IBW/day), keto acid-supplemented low- (sLP: 0.6-0.8 g/kg IBW/day with 0.12 g/kg IBW/day of keto acids) or high-protein (HP: 1.0-1.2 g/kg IBW/day) diet. The groups were followed for 1 year and RRF as well as nutritional status was evaluated serially. A neutral or positive nitrogen balance was achieved in all three groups. RRF remained stable in group sLP (3.84 +/- 2.17 to 3.39 +/- 3.23 ml/min/1.73 m(2), P = ns) while it decreased in group LP (4.02 +/- 2.49 to 2.29 +/- 1.72 ml/min/1.73 m(2), P < 0.05) and HP (4.25 +/- 2.34 to 2.55 +/- 2.29 ml/min/1.73 m(2), P < 0.05). There was no change from baseline on nutritional status in any of the groups during follow-up. A diet containing 0.6-0.8 g of protein/kg IBW/day is safe and, when combined with keto acids, is associated with an improved preservation of RRF in relatively new PD patients without significant malnutrition or inflammation.

Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice.

PubMed

Lopez, Marcelo F; Doremus-Fitzwater, Tamara L; Becker, Howard C

2011-06-01

Experience with stress situations during early development can have long-lasting effects on stress- and anxiety-related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2), and chronic variable stress (CVS) alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate housed (one mouse/cage) or group housed (four mice/cage) according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to CVS or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a two-bottle choice (ethanol 15% vol/vol vs. water) for a 2-h limited access procedure. Early social isolation resulted in greater ethanol intake compared with the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared with the corresponding group-housed mice (Experiment 2). For mice that did not experience CVS, early social isolation resulted in greater ethanol intake compared with group-housed mice (Experiment 3). CVS subsequently resulted in a significant increase in ethanol intake in group-housed mice, but CVS failed to further increase ethanol intake in mice that experienced chronic social isolation early in life (Experiment 3). Overall, female mice consumed more ethanol than males, whether isolated (early or late) or group housed. These results indicate that early but not late social isolation can subsequently influence ethanol consumption in C57BL/6J mice. Thus, the developmental timing of chronic social isolation appears to be an important factor in defining later effects on ethanol self-administration behavior. In addition, experience with CVS early in life results in elevated ethanol intake later in adulthood. Taken together, these results emphasize the important role of early stress experiences that modulate later voluntary ethanol intake during adulthood. Copyright © 2011 Elsevier Inc. All rights reserved.

Daytime REM Sleep in Parkinson’s Disease

PubMed Central

Bliwise, Donald L.; Trotti, Lynn Marie; Juncos, Jorge J.; Factor, Stewart A.; Freeman, Alan; Rye, David B.

2012-01-01

Background Previous studies have demonstrated both clinical and neurochemical similarities between Parkinson’s disease (PD) and narcolepsy. The intrusion of REM sleep into the daytime remains a cardinal feature of narcolepsy, but the importance of these intrusions in PD remains unclear. In this study we examined REM sleep during daytime Maintenance of Wakefulness Testing (MWT) in PD patients. Methods Patients spent 2 consecutive nights and days in the sleep laboratory. During the daytime, we employed a modified MWT procedure in which each daytime nap opportunity (4 per day) was extended to 40 minutes, regardless of whether the patient was able to sleep or how much the patient slept. We examined each nap opportunity for the presence of REM sleep and time to fall asleep. Results Eleven of 63 PD patients studied showed 2 or more REM episodes and 10 showed 1 REM episode on their daytime MWTs. Nocturnal sleep characteristics and sleep disorders were unrelated to the presence of daytime REM sleep, however, patients with daytime REM were significantly sleepier during the daytime than those patients without REM. Demographic and clinical variables, including Unified Parkinson’s Disease Rating Scale motor scores and levodopa dose equivalents, were unrelated to the presence of REM sleep. Conclusions A sizeable proportion of PD patients demonstrated REM sleep and daytime sleep tendency during daytime nap testing. These data confirm similarities in REM intrusions between narcolepsy and PD, perhaps suggesting parallel neurodegenerative conditions of hypocretin deficiency. PMID:22939103

Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease.

PubMed

Kadoguchi, Naoto; Okabe, Shinji; Yamamura, Yukio; Shono, Misaki; Fukano, Tatsuya; Tanabe, Akie; Yokoyama, Hironori; Kasahara, Jiro

2014-06-25

Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson's disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD. Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively. Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment.

Peritoneal dialysis: Experience of the department of pediatrics of the hospital Charles Nicolle of Tunis.

PubMed

Jellouli, Manel; Ferjani, Meriem; Oueslati, Amal; Abidi, Kamel; Naija, Ouns; Hammi, Yousra; Ben Abdallah, Taieb; Gargah, Tahar

2016-05-01

Introduction Peritoneal dialysis (PD) is still the most common modality used in treatment for children with End Stage Renal Disease (ESRD). The objective of this study was to identify the epidemiological, clinical, and microbiological factors affecting the outcome of PD. Methods In this study, we retrospectively reviewed the records of 85 patients who were treated with DP for the last ten years (from January 2004 to December 2013) in the Department of Pediatrics in Charles Nicolle hospital, Tunis. Results The mean duration of PD was 18.1±12 months (3.5-75 months). The average age of PD onset was 9.3±5.7 years (29 days-23 years). The sex ratio was 1.5. In a significant number of cases with ESRD, the primary cause is Congenital Anomalies of the Kidneys and Urinary Tract (CAKUT). Seventy-four of our patients (87%) had been treated with Automated PD. The average time between catheter placement and PD commencement was 3.9±4.6 days. Catheter change was 1.62 (1-5). Sixty-one patients (71.8%) had experienced at least one episode of peritonitis. The most frequently isolated organisms was the Gram-positive bacteria (61%). Survival rates without peritonitis at 12th, 24th and 36th months were 40%, 32% and 18%, respectively. Transition to permanent hemodialysis was required in 66% of patients. Conclusion Considering the important incidence of peritonitis in our patients, it is imperative to establish a targeted primary prevention.

The impact of PD-L1 on survival and value of the immune check point inhibitors in non-small-cell lung cancer; proposal, policies and perspective.

PubMed

Guirgis, Helmy M

2018-02-20

The impact of programmed death receptor-ligand1 (PD-L1) on costs and value of the immune check point inhibitors (ICPI) has received minimal attention. 1- Design a sliding scale to grade survival in 2nd-line non-small-cell lung cancer (NSCLC). 2- Compare costs and value of Nivolumab (Nivo), Atezolizumab (Atezo) and Pembrolizumab (Pembro) vs. Docetaxel (Doc). Previously reported median overall survival (OS) and prices posted by parent company were utilized. The OS gains over controls in days were graded (gr) from A+ to D. Docetaxel costs were calculated for 6-12 cycles and the ICPI for 1 year. Adverse events treatment costs (AEsTC) were reported separately. The cost/life-year gain (C/LYG) was computed as drug yearly-cost/OS gain over control in days × 360 days. The relative value of the ICPI were expressed as $100,000/C/LYG. Costs of Doc 6 cycles were $23,868, OS/gr 87/C, AEs gr ¾ > 20%, AEsTC $1978 and 6- 12 cycle C/LYG $98,764 -$197,528. Nivo, Atezo and Pembro gr ¾ were < 20% at average costs of $1480. In non-squamous NSCLC, Nivo demonstrated OS/g 84/C and C/LYG $558,326 as compared with 264/A and $177,645 in PD-L1 > 10%. Atezolizumab OS/g were 87/B and C/LYG $551,407 improving in enriched PD-L1 to 162/A and $332,020 respectively. Pembrolizumab in PD-L1 > 1.0% demonstrated OS/g 57/C and C/LYG $659,059 improving in > 50% PD-L1 to 201/A and $186,897. PD-L1 enrichment increased RV of Nivo from 0.18 to 0.56, Atezo from 0.16 to 0.66 and Pembro from 0.15 to 0.53. Simplified methodology to grade OS and weigh value of anticancer drugs was proposed. In 2nd-line non-squamous NSCLC, value of Doc, Nivo, Atezo and Pembro regardless of PDL-1 expression were limited and modest. Enrichment of PD-L1 resulted in unprecedented OS, improved grades and enhanced value at seemingly justifiable costs.

Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria.

PubMed

Van Malderen, Carine; Van Geertruyden, Jean-Pierre; Machevo, Sonia; González, Raquel; Bassat, Quique; Talisuna, Ambrose; Yeka, Adoke; Nabasumba, Carolyn; Piola, Patrice; Daniel, Atwine; Turyakira, Eleanor; Forret, Pascale; Van Overmeir, Chantal; van Loen, Harry; Robert, Annie; D' Alessandro, Umberto

2012-07-10

Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children<5 years of age with uncomplicated malaria. This case-control study was performed in the context of a larger multicentre randomized clinical trial comparing safety and efficacy of four different ACT in children with uncomplicated malaria. Children, who after treatment experienced a haemoglobin drop≥2 g/dl (cases) within the first four days (days 0, 1, 2, and 3), were compared with those without an Hb drop (controls). Cases and controls were matched for study site, sex, age and baseline haemoglobin measurements. Data were analysed using a conditional logistic regression model. G6PD deficiency prevalence, homo- or hemizygous, was 8.5% (10/117) in cases and 6.8% (16/234) in controls (p=0.56). The risk of a Hb drop≥2 g/dl was not associated with either G6PD deficiency (adjusted odds ratio (AOR): 0.81; p=0.76) or CDA treatment (AOR: 1.28; p=0.37) alone. However, patients having both risk factors tended to have higher odds (AOR: 11.13; p=0.25) of experiencing a Hb drop≥2 g/dl within the first four days after treatment, however this finding was not statistically significant, mainly because G6PD deficient patients treated with CDA were very few. In non-G6PD deficient individuals, the proportion of cases was similar between treatment groups while in G6PD-deficient individuals, haemolytic anaemia occurred more frequently in children treated with CDA (56%) than in those treated with other ACT (29%), though the difference was not significant (p=0.49). The use of CDA for treating uncomplicated malaria may increase the risk of haemolytic anaemia in G6PD-deficient children.

Enhanced or Reduced Fetal Growth Induced by Embryo Transfer into Smaller or Larger Breeds Alters Post-Natal Growth and Metabolism in Pre-Weaning Horses

PubMed Central

Peugnet, Pauline; Wimel, Laurence; Duchamp, Guy; Sandersen, Charlotte; Camous, Sylvaine; Guillaume, Daniel; Dahirel, Michèle; Dubois, Cédric; Jouneau, Luc; Reigner, Fabrice; Berthelot, Valérie; Chaffaux, Stéphane; Tarrade, Anne; Serteyn, Didier; Chavatte-Palmer, Pascale

2014-01-01

In equids, placentation is diffuse and nutrient supply to the fetus is determined by uterine size. This correlates with maternal size and affects intra-uterine development and subsequent post-natal growth, as well as insulin sensitivity in the newborn. Long-term effects remain to be described. In this study, fetal growth was enhanced or restricted through ET using pony (P), saddlebred (S) and draft (D) horses. Control P-P (n = 21) and S-S (n = 28) pregnancies were obtained by AI. Enhanced and restricted pregnancies were obtained by transferring P or S embryos into D mares (P-D, n = 6 and S-D, n = 8) or S embryos into P mares (S-P, n = 6), respectively. Control and experimental foals were raised by their dams and recipient mothers, respectively. Weight gain, growth hormones and glucose homeostasis were investigated in the foals from birth to weaning. Fetal growth was enhanced in P-D and these foals remained consistently heavier, with reduced T3 concentrations until weaning compared to P-P. P-D had lower fasting glucose from days 30 to 200 and higher insulin secretion than P-P after IVGTT on day 3. Euglycemic clamps in the immediate post-weaning period revealed no difference in insulin sensitivity between P-D and P-P. Fetal growth was restricted in S-P and these foals remained consistently lighter until weaning compared to S-D, with elevated T3 concentrations in the newborn compared to S-S. S-P exhibited higher fasting glycemia than S-S and S-D from days 30 to 200. They had higher maximum increment in plasma glucose than S-D after IVGTT on day 3 and clamps on day 200 demonstrated higher insulin sensitivity compared to S-D. Neither the restricted nor the enhanced fetal environment affected IGF-1 concentrations. Thus, enhanced and restricted fetal and post-natal environments had combined effects that persisted until weaning. They induced different adaptive responses in post-natal glucose metabolism: an early insulin-resistance was induced in enhanced P-D, while S-P developed increased insulin sensitivity. PMID:25006665

Acute dialysis-associated peritonitis in children with D+ hemolytic uremic syndrome.

PubMed

Adragna, Marta; Balestracci, Alejandro; García Chervo, Laura; Steinbrun, Silvina; Delgado, Norma; Briones, Liliana

2012-04-01

Acute peritoneal dialysis (PD) is the preferred therapy for renal replacement in children with post-diarrheal hemolytic uremic syndrome (D+ HUS), but peritonitis remains a frequent complication of this procedure. We reviewed data from 149 patients with D+ HUS who had undergone acute PD with the aim of determining the prevalence and risk factors for the development of peritonitis. A total of 36 patients (24.2%) presented peritonitis. The median onset of peritonitis manifestations was 6 (range 2-18) days after the initiation of dialysis treatment, and Gram-positive microorganisms were the predominant bacterial type isolated (15/36 patients). The patients were divided into two groups: with or without peritonitis, respectively. Univariate analysis revealed that a longer duration of the oligoanuric period, more days of dialysis, catheter replacement, stay in the intensive care unit, and hypoalbuminemia were significantly associated to the development of peritonitis. The multivariate analysis, controlled by duration of PD, identified the following independent risk factors for peritonitis: catheter replacement [p = 0.037, odds ratio (OR) 1.33, 95% confidence interval (CI) 1.02-1.73], stay in intensive care unit (p = 0.0001, OR 2.62, 95% CI 1.65-4.19), and hypoalbuminemia (p = 0.0076, OR 1.45, 95% CI 1.10-1.91). Based on these findings, we conclude that the optimization of the aseptic technique during catheter manipulation and early nutritional support are targets for the prevention of peritonitis, especially in critically ill patients.

The phosphodiesterase inhibitor, ibudilast, attenuates neuroinflammation in the MPTP model of Parkinson’s disease

PubMed Central

Joniec-Maciejak, Ilona; Cudna, Agnieszka; Mirowska-Guzel, Dagmara; Kurkowska-Jastrzębska, Iwona

2017-01-01

Background/Aims Since the degeneration of the nigrostriatal dopaminergic pathway in Parkinson’s disease (PD) is associated with the inflammation process and decreased levels of cyclic nucleotides, inhibition of up-regulated cyclic nucleotide phosphodiesterases (PDEs) appears to be a promising therapeutic strategy. We used ibudilast (IBD), a non-selective PDE3,4,10,11 inhibitor, due to the abundant PDE 4 and 10 expression in the striatum. The present study for the first time examined the efficacy of IBD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Methods IBD [0, 20, 30, 40, or 50 mg/kg] was injected b.i.d. subcutaneously for nine days to three-month-old male C57Bl/10Tar mice, beginning two days prior to MPTP (60 mg/kg) intoxication. High-pressure liquid chromatography, Western blot analysis, and real time RT-PCR methods were applied. Results Our study demonstrated that chronic administration of IBD attenuated astroglial reactivity and increased glial cell-derived neurotrophic factor (GDNF) production in the striatum. Moreover, IBD reduced TNF-α, IL-6, and IL-1β expression. Conclusion IBD had a well-defined effect on astroglial activation in the mouse model of PD; however, there was no protective effect in the acute phase of injury. Diminished inflammation and an increased level of GDNF may provide a better outcome in the later stages of neurodegeneration. PMID:28753652

Comparison of linear–stochastic and nonlinear–deterministic algorithms in the analysis of 15-minute clinical ECGs to predict risk of arrhythmic death

PubMed Central

Skinner, James E; Meyer, Michael; Nester, Brian A; Geary, Una; Taggart, Pamela; Mangione, Antoinette; Ramalanjaona, George; Terregino, Carol; Dalsey, William C

2009-01-01

Objective: Comparative algorithmic evaluation of heartbeat series in low-to-high risk cardiac patients for the prospective prediction of risk of arrhythmic death (AD). Background: Heartbeat variation reflects cardiac autonomic function and risk of AD. Indices based on linear stochastic models are independent risk factors for AD in post-myocardial infarction (post-MI) cohorts. Indices based on nonlinear deterministic models have superior predictability in retrospective data. Methods: Patients were enrolled (N = 397) in three emergency departments upon presenting with chest pain and were determined to be at low-to-high risk of acute MI (>7%). Brief ECGs were recorded (15 min) and R-R intervals assessed by three nonlinear algorithms (PD2i, DFA, and ApEn) and four conventional linear-stochastic measures (SDNN, MNN, 1/f-Slope, LF/HF). Out-of-hospital AD was determined by modified Hinkle–Thaler criteria. Results: All-cause mortality at one-year follow-up was 10.3%, with 7.7% adjudicated to be AD. The sensitivity and relative risk for predicting AD was highest at all time-points for the nonlinear PD2i algorithm (p ≤0.001). The sensitivity at 30 days was 100%, specificity 58%, and relative risk >100 (p ≤0.001); sensitivity at 360 days was 95%, specificity 58%, and relative risk >11.4 (p ≤0.001). Conclusions: Heartbeat analysis by the time-dependent nonlinear PD2i algorithm is comparatively the superior test. PMID:19707283

Medication burden in CKD-5D: impact of dialysis modality and setting.

PubMed

Parker, Kathrine; Nikam, Milind; Jayanti, Anuradha; Mitra, Sandip

2014-12-01

Medication adherence is thought to be around 50% in the general and dialysis population. Reducing the pill burden (PB) reduces regime complexity and can improve adherence. Increased adherence should lead to improvement in treatment outcomes and patient quality of life. There is currently little published data on PB in CKD-5D across dialysis modalities. This is a retrospective, single renal network study. All in-centre HD (MHD), peritoneal dialysis (PD) and home HD (HHD) patients were identified in the Greater Manchester East sector renal network. Information collected included age, sex, comorbidities, daily PB, dialysis vintage and adequacy. Data were retrieved from a customized renal database, clinic and discharge letters with cross validation from the general practitioner when needed. Two hundred and thirty-six prevalent dialysis patients were studied. HHD patients had a significantly lower PB (11 ± 7 pills/day) compared with PD and MHD (16 ± 7 pills/day). The HHD patients required fewer BP medications to meet the recommended target. HD setting was the only significant factor for reducing PB. For home therapies (HHD versus PD), weekly Kt/v and serum phosphate were significant factors influencing PB. When comparing all modalities, OR of PB ≥ 15/day for MHD versus HHD was 3.9 and PD versus HHD was 4.9. The influence of HHD is dominant above factors such as comorbidities or clinical variables in reducing PB for MHD. Higher clearances achieved by HHD could explain differences in PB with PD. This is the first comparative study of PB across all dialysis modalities and factors that influence it. The PB advantage in HHD may result in greater adherence and might contribute to the outcome benefit often seen with this modality. Higher clearances achieved by HHD could explain differences in PB with PD but the precise reasons for lower PB remain speculative and deserve further research in larger settings.

Personal digital assistant-based self-monitoring adherence rates in 2 dialysis dietary intervention pilot studies: BalanceWise-HD and BalanceWise-PD.

PubMed

Stark, Susan; Snetselaar, Linda; Piraino, Beth; Stone, Roslyn A; Kim, Sunghee; Hall, Beth; Burke, Lora E; Sevick, Mary Ann

2011-11-01

The dialysis dietary regimen is complicated, and computer-based dietary self-monitoring may be useful for helping dialysis patients manage their dietary regimen. In this report, we describe dietary self-monitoring rates among study participants randomized to the intervention arms of 2 pilot studies. Both studies tested similar interventions involving dietary counseling paired with personal digital assistant-based self-monitoring. One study was performed in hemodialysis (HD) and one in peritoneal dialysis (PD) patients. HD intervention participants entered an average of 244.9 meals (median = 288; interquartile range [IQR]: 186 to 342) over the 16-week intervention, 2.2 meals per day (median = 2.6; IQR: 1.7 to 3.1), and 73% of expected meals (median = 86; IQR: 55 to 102), assuming intake of 3 meals per day. At least some meals were entered in 87% of the observed weeks (median = 100%; IQR: 81 to 100). PD intervention participants entered an average of 212.1 meals (median = 203; IQR: 110 to 312) over the 16-week intervention, 1.9 meals per day (median = 1.8; IQR: 1 to 2.8), and 63% of expected meals (median = 60; IQR: 33 to 93), assuming 3 meals per day. At least some meals were entered in 80% of the observed weeks (median = 94; IQR: 50 to 100). These HD and PD patients demonstrated excellent rates of self-monitoring. Additional research with a larger sample is required to confirm these findings. Copyright © 2011 National Kidney Foundation, Inc. All rights reserved.

Comparison of surgical outcomes between open and robot-assisted minimally invasive pancreaticoduodenectomy.

PubMed

Kim, Hyeong Seok; Han, Youngmin; Kang, Jae Seung; Kim, Hongbeom; Kim, Jae Ri; Koon, Wooil; Kim, Sun-Whe; Jang, Jin-Young

2018-02-01

Robot surgery is a new method that maintains advantages and overcomes disadvantages of conventional methods, even in pancreatic surgery. This study aimed to evaluate safety and benefits of robot-assisted minimally invasive pancreaticoduodenectomy (robot PD). This study included 237 patients who underwent PD between 2015 and 2017. Demographics and surgical outcomes were evaluated. Fifty-one patients underwent robot PD and 186 underwent open PD. Robot PD group had younger age (60.7 vs. 65.4 years, P = 0.006) and lower body mass index (22.7 vs. 24.0, P = 0.007). Robot PD group had lower proportion of patients with firm or hard pancreatic texture (15.7% vs. 38.2%, P = 0.004) and smaller pancreatic duct size (2.3 vs. 3.3 mm, P = 0.002). Two groups had similar operation time (robot vs. open: 335.6 vs. 330.1 min) and complications (15.7% vs. 21.0%), including postoperative pancreatic fistula rate (6.0% vs. 12.0%). Robot PD group had lower postoperative pain score (3.7 vs. 4.1 points, P = 0.008), and shorter postoperative stay (10.6 vs. 15.3 days, P = 0.001). Robot PD is comparable to open PD in early outcomes. Robot PD is safe and feasible and enables early recovery; indication for robot PD is expected to expand in the near future. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Effects of prenatal binge-like ethanol exposure and maternal stress on postnatal morphological development of hippocampal neurons in rats.

PubMed

Jakubowska-Dogru, Ewa; Elibol, Birsen; Dursun, Ilknur; Yürüker, Sinan

2017-10-01

Alcohol is one of the most commonly used drugs of abuse negatively affecting human health and it is known as a potent teratogen responsible for fetal alcohol syndrome (FAS), which is characterized by cognitive deficits especially pronounced in juveniles but ameliorating in adults. Searching for the potential morphological correlates of these effects, in this study, we compared the course of developmental changes in the morphology of principal hippocampal neurons in fetal-alcohol (A group), intubated control (IC group), and intact control male rats (C group) over a protracted period of the first two postnatal months. Ethanol was administered to the pregnant Wistar dams intragastrically, throughout gestation days (GD) 7-20, at a total dose of 6g/kg/day resulting in the mean blood alcohol concentration (BAC) of 246.6±40.9mg/dl. Ten morphometric parameters of Golgi-stained hippocampal neurons (pyramidal and granule) from CA1, CA3, and DG areas were examined at critical postnatal days (PD): at birth (PD1), at the end of the brain growth spurt period (PD10), in juveniles (PD30), and in young adults (PD60). During postnatal development, the temporal pattern of morphometric changes was shown to be region-dependent with most significant alterations observed between PD1-30 in the CA region and between PD10-30 in the DG region. It was also parameter-dependent with the soma size (except for CA3 pyramids), number of primary dendrites, dendrite diameter, dendritic tortuosity and the branch angle demonstrating little changes, while the total dendritic field area, dendritic length, number of dendritic bifurcations, and spine density being highly increased in all hippocampal regions during the first postnatal month. Moderate ethanol intoxication and the maternal intubation stress during gestation, showed similar, transient effects on the neuron development manifested as a smaller soma size in granule cells, reduced dendritic parameters and lower spine density in pyramidal neurons at PD1. Full recovery from these effects took place within the first 10 postnatal days. This study showed regional and temporal differences in the development of different morphometric features of principal hippocampal neurons in intact subjects over a protracted 2-months postnatal period. It also demonstrated an overlap in the effects of a moderate fetal ethanol intoxication and a mild maternal stress produced by the intragastric intubation, a commonly used method of ethanol administration to the pregnant dams. Fast recovery from the adverse effects on the soma size, dendritic arborization and spines density observed at birth indicates towards the fetal ethanol/stress induced developmental retardation. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Effects of neonatal paternal deprivation or early deprivation on anxiety and social behaviors of the adults in mandarin voles.

PubMed

Jia, Rui; Tai, Fadao; An, Shucheng; Zhang, Xia; Broders, Hugh

2009-11-01

This study examined whether neonatal paternal deprivation (PD: father was removed and pups were raised just by mother) or early deprivation (ED: pups were raised by both parents except separated from not only the dam but also the peers for three hours a day from PND 0 to 13) has long-term effects on anxiety and social behaviors of adult mandarin voles. Newborn mandarin voles of F2 generation were randomly assigned to one of three groups: bi-parental care (PC: pups were raised by both parents), PD and ED. The parental care behaviors of F1 generation were observed at the age of 0, 13 and 21 days (PND 0, 13, 21) of F2 generation of PC and PD groups. Moreover, each mandarin vole of F2 generation received an open field test and a social interaction test on PND 70 and PND 75, respectively. No significant differences of parental behavior were observed between mothers and fathers from PC families, showing typical parental behavior of socially monogamous rodents. In addition, no significant differences of maternal behaviors were found between mothers from PC and PD families, indicating no maternal compensation towards pups for the absence of the paternal care. In the open field test, mandarin voles from both PD and ED families displayed higher levels of anxiety and lower locomotor activity, relative to offspring of PC family. In the social interaction test, both PD and ED mandarin voles also showed lower levels of social behavior and higher levels of anxiety. Thus, both PD and ED significantly increase anxiety and reduce social behavior of adult mandarin voles, suggesting that variation in parental investment may lead to variation in anxiety and social behaviors in rodents with different mating systems.

In utero betamethasone affects 3β-hydroxysteroid dehydrogenase and inhibin-α immunoexpression during testis development.

PubMed

Pedrana, G; Viotti, H; Lombide, P; Sanguinetti, G; Pino, C; Cavestany, D; Sloboda, D M; Martin, G B

2016-08-01

Prenatal glucocorticoids, commonly used in women at risk of preterm delivery, can predispose the newborn to disease in later life. Since male reproductive function is likely to reflect testis development during fetal life, we studied the effects of prenatal glucocorticoids on two key intra-testicular factors that play roles in cellular proliferation and differentiation, 3β-hydroxysteroid dehydrogenase (3β-HSD) and inhibin-α. Pregnant sheep (n=42) were treated with betamethasone (0.5 mg/kg) or saline (control) at 104, 111 and 118 days of gestation (DG). Testicular tissue was sampled from fetuses at 121 and 132DG, and from lambs at 45 and 90 postnatal days (PD). Within the betamethasone treated group, 3β-HSD immunostaining area was greater at 121DG than at 90PD (P=0.04), but the intensity of immunostaining was higher at 90PD than at 121DG (P=0.04), 132DG (P=0.04) and 45PD (P=0.03). Control animals showed no changes in 3β-HSD area or intensity of immunostaining. No significant differences were observed between treated and control animals in immunostaining area, but immunostaining was more intense in the treated group than in the control group at 90PD (P=0.03). For inhibin-α, the proportion of immunostaining area declined in treated offspring from 121DG to 45PD, in contrast to control values, but recovered fully by 90PD, concomitantly with the onset of spermatogenesis. In conclusion, prenatal betamethasone increased the postnatal testicular expression of inhibin-α but reduced the expression of 3β-HSD. These effects could compromise androgen-mediated testicular development and therefore adult capacity for spermatogenesis.

[Role of primaquine in malaria control and elimination in French-speaking Africa].

PubMed

Briolant, S; Pradines, B; Basco, L K

2017-08-01

Primaquine, an 8-aminoquinoline, is a relatively unknown and underutilized drug in French-speaking African countries. It acts against the liver stage parasites of all human malaria species, asexual blood stages of Plasmodium vivax and, to a lesser degree, Plasmodium falciparum; P. falciparum mature gametocytes, and P. vivax and Plasmodium ovale hypnozoites. Gastrointestinal disturbances are its most common side effects. The clinical utility of primaquine is limited due to its hematological side effects in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency and other contraindications (pregnant woman, breastfeeding woman, infants less than 6 months old). In the light of the recent recommendations of the World Health Organization (WHO), we propose to examine how primaquine can be used in French-speaking Africa to improve malaria control and move towards malaria elimination. Two indications supported by the WHO are of relevance in Africa. First, artemisinin-based combination therapies and primaquine given as a single low dose (0.25 mg base/kg) are effective to kill asexual and sexual parasites of P. falciparum, are well-tolerated, and have very little risk even in mild to moderate G6PD-deficient patients. This strategy may be helpful to contain transmission in an area in Africa where P. falciparum malaria incidence has decreased considerably. There is an ethical concern in administering primaquine as a gametocytocide as it does not confer any direct benefit to the treated patient. However, the single low-dose primaquine is most likely associated with very low risk for adverse hematological effects, and WHO recommends its use even without prior G6PD testing. In our opinion, clinical studies including G6PD test should be conducted to assess the safety of low-dose primaquine in African patients. Second, primaquine is effective and necessary for radical treatment of P. vivax and P. ovale, but the standard 14-day treatment (0.25-0.5 mg base/kg/day) is not recommended in patients with G6PD deficiency. Prior G6PD testing is required before prescribing primaquine for radical treatment. The use of primaquine for radical treatment in patients without contraindications does not raise any major ethical problem since the probability of relapse in patients who do not receive anti-hypnozoite treatment can be relatively high and each relapse can cause or aggravate anemia, especially in children. In our opinion, patients with mild or moderate G6PD deficiency should not be treated with primaquine at present. Further clinical studies are necessary to define the role of this drug for radical treatment in G6PD-deficient African patients. Without primaquine, the eventual elimination of P. vivax and P. ovale malaria appears to be very difficult. Updated epidemiological data on G6PD, Duffy antigen, and the current distribution of and burden due to P. vivax and P. ovale are required for a rational use of primaquine in the African continent. Moreover, clinical studies on primaquine are required in Africa.

Affinity adsorption of glucose degradation products improves the biocompatibility of conventional peritoneal dialysis fluid.

PubMed

Ishikawa, Naoyoshi; Miyata, Toshio; Ueda, Yasuhiko; Inagi, Reiko; Izuhara, Yuko; Yuzawa, Hiroko; Onogi, Hiroshi; Nishina, Makoto; Nangaku, Masaomi; Van Ypersele De Strihou, Charles; Kurokawa, Kiyoshi

2003-01-01

Reactive carbonyl compounds (RCOs) present in peritoneal dialysis (PD) fluid have been incriminated in the progressive deterioration of the peritoneal membrane in long-term PD patients. They are initially present in fresh conventional heat-sterilized glucose PD fluid and are supplemented during dwell time by the diffusion of blood RCOs within the peritoneal cavity. In the present study, RCO entrapping agents were immobilized on affinity beads to adsorb RCOs both in fresh PD fluid and in PD effluent. The RCO trapping potential of various compounds was assessed in vitro first by dissolving them in the tested fluid and subsequently after coupling with either epoxy- or amino-beads. The tested fluids include fresh heat-sterilized glucose and non-glucose PD fluids, and PD effluent. Their RCOs contents, that is, glyoxal (GO), methylglyoxal (MGO), 3-deoxyglucosone (3-DG), formaldehyde, 5-hydroxymethylfuraldehyde, acetaldehyde, and 2-furaldehyde were monitored by reverse-phase high-pressure liquid chromatography. The biocompatibility of PD fluid was assessed by a cytotoxic assay with either human epidermoid cell line A431 cells or with primary cultured human peritoneal mesothelial cells. Among the tested RCO entrapping agents, hydrazine coupled to epoxy-beads proved the most efficient. It lowered the concentrations of three dicarbonyl compounds (GO, MGO, and 3-DG) and those of aldehydes present in fresh heat-sterilized glucose PD fluid toward the low levels observed in filter-sterilized glucose PD fluid. It did not change the glucose and electrolytes concentration of the PD fluid but raised its pH from 5.2 to 5.9. Hydrazine-coupled epoxy-bead also lowered the PD effluent content of total RCOs, measured by the 2,4-dinitrophenylhydrazone (DNPH) method. The cytotoxicity of heat-sterilized PD fluid incubated with hydrazine-coupled epoxy-beads was decreased to the level observed in filter-sterilized PD fluid as the result of the raised pH and the lowered RCOs levels. Hydrazine-coupled epoxy-beads reduce the levels of a variety of dicarbonyls and aldehydes present in heat-sterilized glucose PD fluid to those in filter-sterilized PD fluid, without altering glucose, lactate, and electrolytes contents but with a rise in pH. Incubated with PD effluents, it is equally effective in reducing the levels of serum-derived RCOs. RCO entrapping agents immobilized on affinity beads improve in vitro the biocompatibility of conventional heat-sterilized glucose PD fluid. Their clinical applicability requires further studies.

Peritoneal drainage does not stabilize extremely low birth weight infants with perforated bowel: data from the NET Trial.

PubMed

Rees, Clare M; Eaton, Simon; Khoo, A Kate; Kiely, Edward M; Pierro, Agostino

2010-02-01

Proponents of peritoneal drainage (PD) hypothesize that it allows stabilization before laparotomy. We examined this hypothesis by comparing clinical status before and after either PD or primary laparotomy (LAP). In an ethically approved, international, prospective randomized controlled trial (2002-2006), extremely low birth weight (<1000 g) infants with pneumoperitoneum received primary PD (n = 35) or LAP (n = 34). Physiologic data were collected prospectively and organ failure scores calculated and compared between preprocedure and day 1 after procedure. Data, expressed as mean +/- SD or median (range), were analyzed using appropriate statistical tests. There was no postprocedure improvement in either PD or LAP group comparing heart rate (PD, P = 1.0; LAP, P = .6), blood pressure (PD, P = .6; LAP, P = .8), inotrope requirement (PD, P = .2; LAP, P = .3), or Arterial partial pressure of oxygen/fraction of inspired oxygen ratio (PD, P = .1; LAP, P = .5). Infants managed with PD had a worsening cardiovascular status (P = .05). There were no differences in total organ failure score in either group (PD, P = .5; LAP, P = 1). Only 4 infants survived with PD alone with no difference between preprocedure and postprocedure organ failure score (P = .4). Peritoneal drainage does not immediately improve clinical status in extremely low birth weight infants with bowel perforation. The use of PD as a stabilizing or temporizing measure is not supported by these results. Copyright 2010 Elsevier Inc. All rights reserved.

Activation of mitochondrial calpain and release of apoptosis-inducing factor from mitochondria in RCS rat retinal degeneration.

PubMed

Mizukoshi, Sayuri; Nakazawa, Mitsuru; Sato, Kota; Ozaki, Taku; Metoki, Tomomi; Ishiguro, Sei-ichi

2010-09-01

The present study was performed to investigate changes of cytosolic and mitochondrial calpain activities, and effects of intravitreously injected calpain inhibitor on photoreceptor apoptosis in Royal College of Surgeon's (RCS) rats. Time courses of activities for both cytosolic and mitochondrial calpains and amount of calpastatin in RCS rat retina were analyzed by subcellular fractionation, calpain assay and western blotting. Calpain assay was colorimetrically performed using Suc-LLVY-Glo as substrate. Effects of intravitreously injected calpain inhibitor (ALLN and PD150606) on RCS rat retinal degeneration were analyzed by TUNEL staining. Effects of mitochondrial calpain activity on activation and translocation of apoptosis-inducing factor (AIF) were analyzed by western blotting. Mitochondrial calpain started to be significantly activated at postnatal (p) 28 days in RCS rat retina, whereas cytosolic micro-calpain was activated at p 35 days, although specific activity of mitochondrial calpain was 13% compared to cytosolic micro-calpain. Intravitreously injected ALLN and PD150606 effectively inhibited photoreceptor apoptosis only when injected at p 25 days, but did not inhibit photoreceptor apoptosis when injected at p 32 days. Parts of AIF were truncated/activated by mitochondrial calpains and translocated to the nucleus. These results suggest that 1), calpain presents not only in the cytosolic fraction but also in the mitochondrial fraction in RCS rat retina; 2), mitochondrial calpain is activated earlier than cytosolic calpain during retinal degeneration in RCS rats; 3), photoreceptor apoptosis may be regulated by not only calpain systems but also other mechanisms; 4), mitochondrial calpain may activate AIF to induce apoptosis; and 5), calpain inhibitors may be partially effective to inhibit photoreceptor apoptosis in RCS rats. The present study provides new insights into the molecular basis for photoreceptor apoptosis in RCS rats and the future possibility of new pharmaceutical treatments for retinitis pigmentosa. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Phylodiversity to inform conservation policy: An Australian example.

PubMed

Laity, Tania; Laffan, Shawn W; González-Orozco, Carlos E; Faith, Daniel P; Rosauer, Dan F; Byrne, Margaret; Miller, Joseph T; Crayn, Darren; Costion, Craig; Moritz, Craig C; Newport, Karl

2015-11-15

Phylodiversity measures summarise the phylogenetic diversity patterns of groups of organisms. By using branches of the tree of life, rather than its tips (e.g., species), phylodiversity measures provide important additional information about biodiversity that can improve conservation policy and outcomes. As a biodiverse nation with a strong legislative and policy framework, Australia provides an opportunity to use phylogenetic information to inform conservation decision-making. We explored the application of phylodiversity measures across Australia with a focus on two highly biodiverse regions, the south west of Western Australia (SWWA) and the South East Queensland bioregion (SEQ). We analysed seven diverse groups of organisms spanning five separate phyla on the evolutionary tree of life, the plant genera Acacia and Daviesia, mammals, hylid frogs, myobatrachid frogs, passerine birds, and camaenid land snails. We measured species richness, weighted species endemism (WE) and two phylodiversity measures, phylogenetic diversity (PD) and phylogenetic endemism (PE), as well as their respective complementarity scores (a measure of gains and losses) at 20 km resolution. Higher PD was identified within SEQ for all fauna groups, whereas more PD was found in SWWA for both plant groups. PD and PD complementarity were strongly correlated with species richness and species complementarity for most groups but less so for plants. PD and PE were found to complement traditional species-based measures for all groups studied: PD and PE follow similar spatial patterns to richness and WE, but highlighted different areas that would not be identified by conventional species-based biodiversity analyses alone. The application of phylodiversity measures, particularly the novel weighted complementary measures considered here, in conservation can enhance protection of the evolutionary history that contributes to present day biodiversity values of areas. Phylogenetic measures in conservation can include important elements of biodiversity in conservation planning, such as evolutionary potential and feature diversity that will improve decision-making and lead to better biodiversity conservation outcomes. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Investigation of the neuroprotective effects of bee-venom acupuncture in a mouse model of Parkinson's disease by using immunohistochemistry and In-vivo 1H magnetic resonance spectroscopy at 9.4 T

NASA Astrophysics Data System (ADS)

Yoon, Moon-Hyun; Lee, Do-Wan; Kim, Hyun-Jin; Chung, Jin-Yeung; Doo, Ah-Reum; Park, Hi-Joon; Kim, Seung-Nam; Choe, Bo-Young

2013-01-01

Neuroprotective therapeutics slows down the degeneration process in animal models of Parkinson's disease (PD). The neuronal survival in PD animal models is often measured by using immunohistochemistry. However, dynamic changes in the pathology of the brain cannot be explored with this technique. Application of in-vivo 1H magnetic resonance spectroscopy (1H MRS) can cover this shortcoming, as these techniques are non-invasive and can be repeated over time in the same animal. Thus, the sensitivity of both techniques to measure changes in the PD pathology was explored in an experiment studying the neuroprotective effects of the vigilance enhancer bee-venom (BV) in a mouse model of PD. The mice were pre-treated with 0.02-ml BV administered to the acupuncture point GB34 (Yangneungcheon) once every 3 days for 2 weeks. Three groups were classified as control, MPTP-intoxicated PD model and BV-treated mice. Outer volume suppression combined with the ultra-short echo-time STEAM (TE = 2.2 ms, TM = 20 ms, TR = 5000 ms) was used for localized in-vivo 1H MRS. Based on the 1H MRS spectral analysis, substantial changes of the neurochemical profiles were evaluated in the three investigated groups. In particular, the glutamate complex (Glx)/creatine (Cr) ratio (7.72 ± 1.25) in the PD group was significantly increased compared to that in the control group (3.93 ± 2.21, P = 0.001). Compared to the baseline values, the Glx/Cr ratio of the BV-treated group was significantly decreased 2 weeks after MPTP intoxication (one-way ANOVA, p < 0.05). In conclusion, the present study demonstrated that neurochemical alterations occurred in the three groups and that the neuroprotective effects of the BV acupuncture in a mouse model of PD could be quantified by using immunohistochemistry and 1H MRS.

Demethoxycurcumin, a Natural Derivative of Curcumin Abrogates Rotenone-induced Dopamine Depletion and Motor Deficits by Its Antioxidative and Anti-inflammatory Properties in Parkinsonian Rats

PubMed Central

Ramkumar, Muthu; Rajasankar, Srinivasagam; Gobi, Veerapan Venkatesh; Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin; Essa, Musthafa Mohamed; Chidambaram, Ranganathan; Chidambaram, Saravana Babu; Guillemin, Giles J.

2018-01-01

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder (NDD) associated with the loss of dopaminergic neurons in the substantia nigra and subsequently has an effect on motor function and coordination. The pathology of PD is multifactorial, in which neuroinflammation and oxidative damage are the two of the main protagonists. Objectives: The present study aims to assess the potential antioxidant and anti-inflammatory effects of demethoxycurcumin (DMC), a natural derivative of curcumin, against rotenone-induced PD in rats. Materials and Methods: Rats were randomized and divided into six groups: control, rotenone (0.5 mg/kg/day, intraperitoneal in sunflower oil) treated for 7 days, rotenone and DMC (5, 10, and 20 mg/kg b.w) cotreated, and DMC (20 mg/kg b.w) alone treated groups. Results: Based on the dopamine concentration and biochemical estimations, the effective dose of DMC was selected and the chronic study was performed. At the end of the experimental period, behavioral studies and protein expression patterns of inflammatory markers were analyzed. Rotenone treatment led to motor dysfunctions, neurochemical deficits, and oxidative stress and enhanced expressions of inflammatory markers, whereas oral administration of DMC attenuated all the above. Conclusion: Even though further research is needed to prove its efficacy in clinical trial, the results of our study showed that DMC may offer a promising and new therapeutic lead for the treatment of NDDs including PD. SUMMARY Curcumin and their derivatives have been shown to be potent neuroprotective effectDemethoxycurcumin (DMC) amolerated the rotenone induced behavioural alterationsDMC abrogated the rotenone induced dopamine deficitsDMC attenuated the rotenone induced oxidative stressDMC diminished the rotenone mediated inflammation. Abbreviations used: COX-2: Cyclooxygenase-2; DA: Dopamine; DMC: Demethoxycurcumin; DMRT: Duncan's multiple range test; GSH: Reduced glutathione; GPx: Glutathione peroxidase; IL-1 β: Interleukin-1 β; IL-6: Interleukin-6; iNOS: Inducible nitric oxide synthase; PD: Parkinson's disease; SN: Substantia nigra; SOD: Superoxide dismutase; TBARS: Thiobarbituric acid reactive substances; TNF-α: Tumor necrosis factor-α. PMID:29576695

Short-term clinical and microbiologic effects of pocket debridement with an Er:YAG laser during periodontal maintenance.

PubMed

Tomasi, Cristiano; Schander, Kerstin; Dahlén, Gunnar; Wennström, Jan L

2006-01-01

The erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser is considered a useful tool for subgingival debridement because the laser treatment creates minimal damage to the root surface and has potential antimicrobial effects. The aim of this randomized controlled clinical trial was to evaluate clinical and microbiologic effects of pocket debridement using an Er:YAG laser in patients during periodontal maintenance. Twenty patients at a recall visit for maintenance were consecutively recruited if presenting at least four teeth with residual probing depth (PD) > or = 5 mm. Two pockets in each of two jaw quadrants were randomly assigned to subgingival debridement using 1) an Er:YAG laser (test) or 2) an ultrasonic scaler (control). The laser beam was set at 160 mJ with a pulse frequency of 10 Hz. Clinical variables were recorded at baseline, 1 month, and 4 months after treatment. Primary clinical outcome variables were changes in PD and clinical attachment level (CAL). Microbiologic analysis of subgingival samples was performed at baseline, 2 days, and 30 days after treatment using a checkerboard DNA-DNA hybridization technique against 12 periodontal disease-associated species. The mean initial PD was 6.0 mm (SD: 1.2) in the test group and 5.8 mm (SD: 0.9) in the control group. At 1 month post-treatment, the PD reduction was significantly greater for test than control sites (0.9 versus 0.5 mm; P <0.05). The CAL gain also was significantly greater (0.5 versus 0.06 mm; P <0.01). At the 4-month examination, no significant differences were detected in PD reduction (1.1 versus 1.0 mm) or CAL gain (0.6 versus 0.4 mm). Both treatments resulted in reduction of the subgingival microflora. No significant differences in microbiologic composition were identified between the treatment groups at various time intervals. Degree of treatment discomfort scored significantly lower for the test than the control treatment modality. The results of the trial failed to demonstrate any apparent advantage of using an Er:YAG laser for subgingival debridement, except less treatment discomfort perceived by the patients.

Dopamine and Consolidation of Episodic Memory: Timing Is Everything

PubMed Central

Grogan, John; Bogacz, Rafal; Tsivos, Demitra; Whone, Alan; Coulthard, Elizabeth

2016-01-01

Memory consolidation underpins adaptive behavior and dopaminergic networks may be critical for prolonged, selective information storage. To understand the time course of the dopaminergic contribution to memory consolidation in humans, here we investigate the effect of dopaminergic medication on recall and recognition in the short and longer term in Parkinson disease (PD). Fifteen people with PD were each tested on or off dopaminergic medication during learning/early consolidation (Day 1) and/or late consolidation (Day 2). Fifteen age-matched healthy participants were tested only once. On Day 1 participants learned new information, and early episodic memory was tested after 30 min. Then on Day 2, recall and recognition were retested after a 24-hr delay. Participants on medication on Day 1 recalled less information at 30 min and 24 hr. In contrast, patients on medication on Day 2 (8–24 hr after learning) recalled more information at 24 hr than those off medication. Although recognition sensitivity was unaffected by medication, response bias was dependent on dopaminergic state: Medication during learning induced a more liberal bias 24 hr later, whereas patients off medication during learning were more conservative responders 24 hr later. We use computational modeling to propose possible mechanisms for this change in response bias. In summary, dopaminergic medication in PD patients during learning impairs early consolidation of episodic memory and makes delayed responses more liberal, but enhances late memory consolidation presumably through a dopamine-dependent consolidation pathway that may be active during sleep. PMID:26102227

Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania.

PubMed

Mwaiswelo, Richard; Ngasala, Billy E; Jovel, Irina; Gosling, Roland; Premji, Zul; Poirot, Eugenie; Mmbando, Bruno P; Björkman, Anders; Mårtensson, Andreas

2016-06-10

This study assessed the safety of the new World Health Organization (WHO) recommendation of adding a single low-dose of primaquine (PQ) to standard artemisinin-based combination therapy (ACT), regardless of individual glucose-6-phosphate dehydrogenase (G6PD) status, for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Men and non-pregnant, non-lactating women aged ≥1 year with uncomplicated P. falciparum malaria were enrolled and randomized to either standard artemether-lumefantrine (AL) regimen alone or with a 0.25 mg/kg single-dose of PQ. PQ was administered concomitantly with the first AL dose. All drug doses were supervised. Safety was evaluated between days 0 and 28. G6PD status was assessed using rapid test (CareStart™) and molecular genotyping. The primary endpoint was mean percentage relative reduction in haemoglobin (Hb) concentration (g/dL) between days 0 and 7 by genotypic G6PD status and treatment arm. Overall, 220 patients, 110 per treatment arm, were enrolled, of whom 33/217 (15.2 %) were phenotypically G6PD deficient, whereas 15/110 (13.6 %) were genotypically hemizygous males, 5/110 (4.5 %) homozygous females and 22/110 (20 %) heterozygous females. Compared to genotypically G6PD wild-type/normal [6.8, 95 % confidence interval (CI) 4.67-8.96], only heterozygous patients in AL arm had significant reduction in day-7 mean relative Hb concentration (14.3, 95 % CI 7.02-21.55, p=0.045), however, none fulfilled the pre-defined haemolytic threshold value of ≥25 % Hb reduction. After adjustment for baseline parasitaemia, Hb, age and sex the mean relative Hb reduction was not statistically significant in both heterozygous and hemizygous/homozygous patients in both arms. A majority of the adverse events (AEs) were mild and unrelated to the study drugs. However, six (4.4 %) episodes, three per treatment arm, of acute haemolytic anaemia occurred between days 0 and 7. Three occurred in phenotypically G6PD deficient patients, two in AL and one in AL + PQ arm, but none in genotypically hemizygous/homozygous patients. All patients with acute haemolytic anaemia recovered without medical intervention. The findings support that the WHO recommendation of adding a single low-dose of PQ to standard AL regimen is safe for the treatment of acute uncomplicated P. falciparum malaria regardless of G6PD status in Tanzania. Trial registration number NCT02090036.

Gait consistency over a 7-day interval in people with Parkinson's disease.

PubMed

Urquhart, D M; Morris, M E; Iansek, R

1999-06-01

To evaluate the consistency of temporal and spatial parameters of the walking pattern in subjects with idiopathic Parkinson's disease (PD) over a 7-day interval during the "on" phase of the levodopa medication cycle. Walking patterns were measured on a 12-meter walkway at the Kingston Gait Laboratory, Cheltenham, using a computerized stride analyzer. Sixteen subjects (7 women, 9 men) with PD recruited from the Movement Disorders Clinic at Kingston Centre. Speed of walking, stride length, cadence, and the percentage of the walking cycle spent in the double limb support phase of gait were measured, together with the level of disability as indexed by the modified Webster scale. Product-moment correlation coefficients and intraclass correlation coefficients (ICC 2,1) for repeat measures over a 7-day interval were high for speed (r = .90; ICC = .93), cadence (r = .90; ICC = .86), and stride length (r = 1.00; ICC = .97) and moderate for double limb support duration after removal of outliers (r = .75; ICC = .73); 95% confidence intervals for the change scores were within clinically acceptable limits for all variables. The mean modified Webster score was 11.4 on the first day and 10.1 7 days later. The gait pattern and level of disability in subjects with PD without severe motor fluctuations remained stable over a 1-week period when optimal medication prevailed.

Safety and efficacy of rasagiline in addition to levodopa for the treatment of idiopathic Parkinson's disease: a meta-analysis of randomised controlled trials.

PubMed

Cai, Jiang-Ping; Chen, Wan-Jin; Lin, Yu; Cai, Bin; Wang, Ning

2015-01-01

To assess the safety and efficacy of rasagiline for the treatment of Parkinson's disease (PD) among individuals currently receiving levodopa. A systematic literature search was conducted to identify randomised controlled trials (RCT) comparing rasagiline with placebo/no treatment in individuals with PD currently receiving levodopa. Outcome measures included improvement in motor functions; symptomatic improvement; improvement in quality of life; adverse effects. Random-effect meta-analytical techniques were conducted for the outcome measure and subgroup analyses. Three RCTs were included (n = 1002). The results showed significantly greater improvements in daily 'on' time without dyskinesia in levodopa-treated participants with idiopathic PD receiving 1 mg/day rasagiline compared to placebo (n = 712, 2 RCTs, MD 0.80, CI 0.45 to 1.15; p < 0.00001), and significantly greater improvements in Unified Parkinson's Disease Rating Scale motor performance scores during 'on' time in participants receiving 0.5-1 mg/day rasagiline (0.5 mg/day: n = 282, MD -2.91, CI -4.59 to -1.23; p = 0.0007; 1 mg/day: n = 712, 2 RCTs, MD -2.91, CI -4.02 to -1.80; p < 0.00001). There were no significant differences in adverse effects. 0.5 to 1 mg/day rasagiline in addition to levodopa is a safe and well-tolerated combination therapy for individuals with Parkinson's disease.

High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients.

PubMed

Mizuno, Masashi; Suzuki, Yasuhiro; Higashide, Keiko; Sei, Yumi; Iguchi, Daiki; Sakata, Fumiko; Horie, Masanobu; Maruyama, Shoichi; Matsuo, Seiichi; Morgan, B Paul; Ito, Yasuhiko

2017-01-01

We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis. We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF. When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms. Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis.

Comparative Study of Antimalarial and Other Drugs on G6PD Deficient Red Cells.

DTIC Science & Technology

the WR compounds previously studied. The suggested use of xylitol as a protective agent against hemolytic drugs (Wang et al) had raised considerable...expectation. Unfortunately, xylitol at the dosages of 20 and 30 g./day was unable, in our experimental set up (transfusion of 51 Cr tagged G6PD

The Effects of Professional Development on Universal Design for Instruction on Faculty Perception and Practice

ERIC Educational Resources Information Center

Park, Hye Jin; Roberts, Kelly; Delise, Danielle

2017-01-01

The authors conducted professional development (PD) for university personnel, focused on Universal Design for Instruction (UDI), over three days during a summer institute. The UDI-focused PD provided 20 hours of training across six content areas: (a) UDI, (b) accessible distance education and assistive technology, (c) student and faculty rights…

Evaluation of PD/PID controller for insulin control on blood glucose regulation in a Type-I diabetes

NASA Astrophysics Data System (ADS)

Mahmud, Farhanahani; Isse, Nadir Hussien; Daud, Nur Atikah Mohd; Morsin, Marlia

2017-01-01

This project introduces a simulation of Proportional-Derivative (PD) and Proportional-Integral-Derivative (PID) controller based on a virtual Type 1 Diabetes Mellitus (T1DM) patient: Hovorka diabetic model using MATLAB-Simulink software. The results of these simulations are based on three tuning responses for each controller which are fast, slow and oscillation responses. The main purpose of this simulation is to achieve an acceptable stability and fastness response towards the regulation of glucose concentration using PD and PID controller response with insulin infusion rate. Therefore, in order to analyze and compare the responses of both controller performances, one-day simulations of the insulin-glucose dynamic have been conducted using a typical day meal plan that contains five meals of different bolus size. It is found that the PID closed-loop control with a short rise time is required to retrieve a satisfactory glucose regulation.

Ghrelin and lipid levels in panic disorder before and after treatment and their relationship with agoraphobia.

PubMed

Gul, Isil Gogcegoz; Cumurcu, Birgul Elbozan; Karlidag, Rifat; Turkoz, Yusuf

2015-09-01

We aimed to evaluate serum ghrelin (GHR) levels and lipid profile in panic disorder (PD), with and without agoraphobia, and to compare these parameters before and after treatment. The GHR and lipid profiles were measured in blood samples taken from 31 PD patients with agoraphobia, 22 PD patients without agoraphobia, and 53 control group subjects. 23 of the 53 patients who were prescribed 20 to 40 mg/day paroxetine had continued treatment. The 23 patients who had continued treatment were measured again at the end of twelve weeks. The GHR and triglyceride (TRG), total cholesterol (Total-C), low-density lipoproteins (LDL-C), and very low-density lipoproteins (VLDL-C) levels were higher in the PD with agoraphobia group than the PD without agoraphobia and control groups. The 23 patients that had continued their treatment were re-evaluated, and the serum GHR, Total-C levels, and BMI after treatment were significantly decreased, compared to the values before treatment. There may be a pathophysiological relationship between the GHR and lipid profiles that interact with each other in PD. In fact, this relationship was more marked in PD with agoraphobia than in PD without agoraphobia.

Effect of a Health Care System Respiratory Fluoroquinolone Restriction Program To Alter Utilization and Impact Rates of Clostridium difficile Infection.

PubMed

Shea, Katherine M; Hobbs, Athena L V; Jaso, Theresa C; Bissett, Jack D; Cruz, Christopher M; Douglass, Elizabeth T; Garey, Kevin W

2017-06-01

Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States despite their association with adverse consequences, including Clostridium difficile infection (CDI). We sought to evaluate the impact of a health care system antimicrobial stewardship-initiated respiratory fluoroquinolone restriction program on utilization, appropriateness of quinolone-based therapy based on institutional guidelines, and CDI rates. After implementation, respiratory fluoroquinolone utilization decreased from a monthly mean and standard deviation (SD) of 41.0 (SD = 4.4) days of therapy (DOT) per 1,000 patient days (PD) preintervention to 21.5 (SD = 6.4) DOT/1,000 PD and 4.8 (SD = 3.6) DOT/1,000 PD posteducation and postrestriction, respectively. Using segmented regression analysis, both education (14.5 DOT/1,000 PD per month decrease; P = 0.023) and restriction (24.5 DOT/1,000 PD per month decrease; P < 0.0001) were associated with decreased utilization. In addition, the CDI rates decreased significantly ( P = 0.044) from preintervention using education (3.43 cases/10,000 PD) and restriction (2.2 cases/10,000 PD). Mean monthly CDI cases/10,000 PD decreased from 4.0 (SD = 2.1) preintervention to 2.2 (SD = 1.35) postrestriction. A significant increase in appropriate respiratory fluoroquinolone use occurred postrestriction versus preintervention in patients administered at least one dose (74/130 [57%] versus 74/232 [32%]; P < 0.001), as well as in those receiving two or more doses (47/65 [72%] versus 67/191 [35%]; P < 0.001). A significant reduction in the annual acquisition cost of moxifloxacin, the formulary respiratory fluoroquinolone, was observed postrestriction compared to preintervention within the health care system ($123,882 versus $12,273; P = 0.002). Implementation of a stewardship-initiated respiratory fluoroquinolone restriction program can increase appropriate use while reducing overall utilization, acquisition cost, and CDI rates within a health care system. Copyright © 2017 American Society for Microbiology.

Predictors of road crossing safety in pedestrians with Parkinson's disease.

PubMed

Lin, Chin-Hsien; Ou, Yang-Kun; Wu, Ruey-Meei; Liu, Yung-Ching

2013-03-01

Road-crossing safety is an important issue in an aging society. Information regarding the risk of crossing the street to pedestrians with Parkinson's disease (PD) is limited. To assess the risk and predictors of unsafe crossing behaviors in patients with PD, we compared 31 pedestrians with mild-to-moderate PD to 50 age/gender/education-matched controls using a battery of cognitive, visual, and motor tests. With a simulated simple street-crossing situation, we determined the remaining time and safety margin for each participant in different traffic situations, including variable motor vehicle speed, time gap, and time of the day. Odds ratios (ORs) were estimated by logistic regression models. We found that pedestrians with PD were more vulnerable to traffic accidents than controls (OR 1.61 [1.28-2.02], P=0.01). The risk of crossing road correlated in a dose-dependent manner with the severity of PD, based on both Hoehn and Yahr (H&Y) stages and unified Parkinson's disease rating scale (UPDRS) motor scores (OR 1.13 for each increasing point of UPDSR, P<0.01). Among PD patients, scores of clock drawing test (OR 0.8 [0.74-0.88], P<0.01) and visual form discrimination (OR 1.14 [1.07-1.22], P<0.01) predicted worsening of safety errors, rather than executive function. Environmental factors, such as fast approaching motor vehicle speed (OR 4.50 [2.92-6.95], P<0.01), short time gap (OR 45.98 [27.04-78.18], P<0.01), and time of day (OR 4.45 [3.11-6.36], P<0.01) also affected road-crossing safety. Future large sample studies are needed to confirm our findings. Training programs or portable stimulator devices that compensate for the visual-spatial disabilities of PD patients are required to improve road safety for PD patients. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Behavioral deficits induced by third-trimester equivalent alcohol exposure in male C57BL/6J mice are not associated with reduced adult hippocampal neurogenesis but are still rescued with voluntary exercise.

PubMed

Hamilton, G F; Bucko, P J; Miller, D S; DeAngelis, R S; Krebs, C P; Rhodes, J S

2016-11-01

Prenatal alcohol exposure can produce permanent alterations in brain structure and profound behavioral deficits. Mouse models can help discover mechanisms and identify potentially useful interventions. This study examined long-term influences of either a single or repeated alcohol exposure during the third-trimester equivalent on survival of new neurons in the hippocampus, behavioral performance on the Passive avoidance and Rotarod tasks, and the potential role of exercise as a therapeutic intervention. C57BL/6J male mice received either saline or 5g/kg ethanol split into two s.c. injections, two hours apart, on postnatal day (PD)7 (Experiment 1) or on PD5, 7 and 9 (Experiment 2). All mice were weaned on PD21 and received either a running wheel or remained sedentary from PD35-PD80/81. From PD36-45, mice received i.p. injections of 50mg/kg bromodeoxyuridine (BrdU) to label dividing cells. Behavioral testing occurred between PD72-79. Number of surviving BrdU+ cells and immature neurons (doublecortin; DCX+) was measured at PD80-81. Alcohol did not affect number of BrdU+ or DCX+ cells in either experiment. Running significantly increased number of BrdU+ and DCX+ cells in both treatment groups. Alcohol-induced deficits on Rotarod performance and acquisition of the Passive avoidance task (Day 1) were evident only in Experiment 2 and running rescued these deficits. These data suggest neonatal alcohol exposure does not result in long-term impairments in adult hippocampal neurogenesis in the mouse model. Three doses of ethanol were necessary to induce behavioral deficits. Finally, the mechanisms by which exercise ameliorated the neonatal alcohol induced behavioral deficits remain unknown. Copyright © 2016 Elsevier B.V. All rights reserved.

FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1-Selected Patients with Non-Small-Cell Lung Cancer.

PubMed

Spigel, David R; Chaft, Jamie E; Gettinger, Scott; Chao, Bo H; Dirix, Luc; Schmid, Peter; Chow, Laura Q M; Hicks, Rodney J; Leon, Larry; Fredrickson, Jill; Kowanetz, Marcin; Sandler, Alan; Funke, Roel; Rizvi, Naiyer A

2018-05-15

The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases). Patients received 1200 mg atezolizumab, Day 1 (21-day cycles). Primary endpoint: investigator-assessed modified Response Evaluation Criteria in Solid Tumors (mRECIST), objective response rate (ORR; RECIST v1.1). Secondary endpoints: overall survival, progression-free survival, duration of response, safety. Patients (n=138) were enrolled (137 evaluable for response: Cohort 1, n=31; Cohort 2, n=93; Cohort 3, n=13). Investigator-assessed ORR was 32%, 21%, and 23% for Cohorts 1, 2, and 3, respectively. Treatment-related adverse events (TRAEs) were reported in 81%, 67%, and 69% of patients, respectively, including grade 3-4 TRAEs in 16%, 19%, and 15%. Moreover, 88.6% (n=86/97) paired baseline tumor samples had <5% change in TC/IC PD-L1 expression over time. Atezolizumab monotherapy showed clinical activity in patients with NSCLC, including those with brain metastases; safety was consistent with previous trials. Atezolizumab has completed phase III monotherapy studies in second-line; front-line trials are ongoing, confirming these favorable results. Copyright © 2018. Published by Elsevier Inc.

PPARα, PPARγ and SREBP-1 pathways mediated waterborne iron (Fe)-induced reduction in hepatic lipid deposition of javelin goby Synechogobius hasta.

PubMed

Chen, Guang-Hui; Luo, Zhi; Chen, Feng; Shi, Xi; Song, Yu-Feng; You, Wen-Jing; Liu, Xu

2017-07-01

The 42-day experiment was conducted to investigate the effects and mechanism of waterborne Fe exposure influencing hepatic lipid deposition in Synechogobius hasta. For that purpose, S. hasta were exposed to four Fe concentrations (0 (control), 0.36, 0.72 and 1.07μM Fe) for 42days. On days 21 and 42, morphological parameters, hepatic lipid deposition and Fe contents, and activities and mRNA levels of enzymes and genes related to lipid metabolism, including lipogenic enzymes (6PGD, G6PD, ME, ICDH, FAS and ACC) and lipolytic enzymes (CPTI, HSL), were analyzed. With the increase of Fe concentration, hepatic Fe content tended to increase but HSI and lipid content tended to decrease. On day 21, Fe exposure down-regulated the lipogenic activities of 6PGD, G6PD, ICDH and FAS as well as the mRNA levels of G6PD, ACCa, FAS, SREBP-1 and PPARγ, but up-regulated CPT I, HSLa and PPARα mRNA levels. On day 42, Fe exposure down-regulated the lipogenic activities of 6PGD, G6PD, ICDH and FAS as well as the mRNA levels of 6PGD, ACCa, FAS and SREBP-1, but up-regulated CPT I, HSLa, PPARα and PPARγ mRNA levels. Using primary S. hasta hepatocytes, specific pathway inhibitors (GW6471 for PPARα and fatostatin for SREBP-1) and activator (troglitazone for PPARγ) were used to explore the signaling pathways of Fe reducing lipid deposition. The GW6471 attenuated the Fe-induced down-regulation of mRNA levels of 6PGD, G6PD, ME, FAS and ACCa, and attenuated the Fe-induced up-regulation of mRNA levels of CPT I, HSLa and PPARα. Compared with single Fe-incubated group, the mRNA levels of G6PD, ME, FAS, ACCa, ACCb and PPARγ were up-regulated while the CPT I mRNA levels were down-regulated after troglitazone pre-treatment; fatostatin pre-treatment down-regulated the mRNA levels of 6PGD, ME, FAS, ACCa, ACCb and SREBP-1, and increased the CPT I and HSLa mRNA levels. Based on these results above, our study indicated that Fe exposure reduced hepatic lipid deposition by down-regulating lipogenesis and up-regulating lipolysis, and PPARα, PPARγ and SREBP-1 pathways mediated the Fe-induced reduction of hepatic lipid deposition in S. hasta. Copyright © 2017 Elsevier Inc. All rights reserved.

Structure and Interactions of the Human Programmed Cell Death 1 Receptor*

PubMed Central

Cheng, Xiaoxiao; Veverka, Vaclav; Radhakrishnan, Anand; Waters, Lorna C.; Muskett, Frederick W.; Morgan, Sara H.; Huo, Jiandong; Yu, Chao; Evans, Edward J.; Leslie, Alasdair J.; Griffiths, Meryn; Stubberfield, Colin; Griffin, Robert; Henry, Alistair J.; Jansson, Andreas; Ladbury, John E.; Ikemizu, Shinji; Carr, Mark D.; Davis, Simon J.

2013-01-01

PD-1, a receptor expressed by T cells, B cells, and monocytes, is a potent regulator of immune responses and a promising therapeutic target. The structure and interactions of human PD-1 are, however, incompletely characterized. We present the solution nuclear magnetic resonance (NMR)-based structure of the human PD-1 extracellular region and detailed analyses of its interactions with its ligands, PD-L1 and PD-L2. PD-1 has typical immunoglobulin superfamily topology but differs at the edge of the GFCC′ sheet, which is flexible and completely lacks a C″ strand. Changes in PD-1 backbone NMR signals induced by ligand binding suggest that, whereas binding is centered on the GFCC′ sheet, PD-1 is engaged by its two ligands differently and in ways incompletely explained by crystal structures of mouse PD-1·ligand complexes. The affinities of these interactions and that of PD-L1 with the costimulatory protein B7-1, measured using surface plasmon resonance, are significantly weaker than expected. The 3–4-fold greater affinity of PD-L2 versus PD-L1 for human PD-1 is principally due to the 3-fold smaller dissociation rate for PD-L2 binding. Isothermal titration calorimetry revealed that the PD-1/PD-L1 interaction is entropically driven, whereas PD-1/PD-L2 binding has a large enthalpic component. Mathematical simulations based on the biophysical data and quantitative expression data suggest an unexpectedly limited contribution of PD-L2 to PD-1 ligation during interactions of activated T cells with antigen-presenting cells. These findings provide a rigorous structural and biophysical framework for interpreting the important functions of PD-1 and reveal that potent inhibitory signaling can be initiated by weakly interacting receptors. PMID:23417675

Efficacy of Local and Systemic Antimicrobials in the Non-Surgical Treatment of Smokers With Chronic Periodontitis: A Systematic Review.

PubMed

Chambrone, Leandro; Vargas, Miguel; Arboleda, Silie; Serna, Maritza; Guerrero, Marcela; de Sousa, Jose; Lafaurie, Gloria Inés

2016-11-01

The aim of this systematic review is to evaluate whether use of local or systemic antimicrobials would improve clinical results of non-surgical periodontal therapy for smokers with chronic periodontitis (CP). Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, and The Cochrane Central Register of Controlled Trials were searched up to and including March 2016. Randomized clinical trials of duration of at least 6 months were included if they reported on treatment of smokers (≥10 cigarettes per day for minimum 12 months) with CP with non-surgical periodontal therapy either alone or associated with local or systemic antimicrobials. Random-effects meta-analyses were undertaken to evaluate mean differences in probing depth (PD) and clinical attachment level (CAL). Of 108 potentially eligible articles, seven were included. Most individual studies (75%) testing locally delivered antibiotics reported that smokers benefited from this treatment approach. Pooled estimates found additional PD reduction of 0.81 mm (P = 0.01) and CAL gain of 0.91 mm (P = 0.01) at sites with baseline PD ≥5 mm. Conversely, meta-analysis on systemic use of antimicrobials failed to detect significant differences in mean changes from baseline, and only one trial supported their use. In smokers with CP, adjunctive use of local antimicrobials improved efficacy of non-surgical periodontal therapy in reducing PD and improving CAL at sites presenting PD ≥5 mm before treatment. Current evidence does not demonstrate similar gains when scaling and root planing plus systemic antimicrobial/antibiotics were associated with therapy.

Minimally invasive fluoroscopic percutaneous peritoneal dialysis catheter salvage.

PubMed

Narayan, Rajeev; Fried, Terrance; Chica, Gerardo; Schaefer, Mathew; Mullins, Daniel

2014-06-01

Peritoneal dialysis catheter (PDC) dysfunction can often be treated fluoroscopically by manipulation with wire, balloon or stiff stylet, saving surgical intervention for refractory cases. We describe an enhanced percutaneous approach to PDC salvage that can lead to a more definitive intervention and salvage for cases refractory to fluoroscopic manipulation. In five cases of PD catheter malfunction, the deep cuff was dissected free after a 0.035 hydrophilic wire was passed into the peritoneum through the PDC. Only the intraperitoneal portion of the PDC was explanted. The PDC was cleared of obstruction and omentum. The intraperitoneal portion of the PDC was reimplanted over wire via a peel-away sheath and the deep cuff sutured. Omental entrapment was present in three of five patients and fibrin occlusion in four of the five cases. All catheters were repaired successfully by the described technique. Post procedure, 3-5 days of lower volume, recumbent PD exchanges were performed prior to full-dose PD. No perioperative complications or leaks were noted. All PDCs were patent at 6 months. One patient required laparoscopy for recurrent omental wrapping 3 months post intervention. PDC salvage in this manner is a cost-effective alternative to laparoscopic repair of PDCs failing catheter manipulation. The infection barrier afforded by the original superficial cuff and subcutaneous tunnel is maintained. PD can be resumed immediately. Only refractory cases need laparoscopy. This procedure allows for a more definitive correction of catheter migration and obstruction, avoids placement of a new PDC or temporary hemodialysis, is cost-effective and expands percutaneous options for dysfunctional PD catheters.

Clinical effectiveness of diode laser therapy as an adjunct to non-surgical periodontal treatment: a randomized clinical study.

PubMed

Dukić, Walter; Bago, Ivona; Aurer, Andrej; Roguljić, Marija

2013-08-01

The aim of this randomized clinical study is to evaluate the effect of a 980-nm diode laser as an adjunct to scaling and root planing (SRP) treatment. Thirty-five patients with chronic periodontitis were selected for the split-mouth clinical study. SRP was performed using a sonic device and hand instruments. Quadrants were equally divided between the right and left sides. Teeth were treated with SRP in two control quadrants (control groups [CG]), and the diode laser was used adjunctively with SRP in contralateral quadrants (laser groups [LG]). Diode laser therapy was applied to periodontal pockets on days 1, 3, and 7 after SRP. Baseline data, including approximal plaque index (API), bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL), were recorded before the treatment and 6 and 18 weeks after treatment. Changes in PD and CAL were analyzed separately for initially moderate (4 to 6 mm) and deep (7 to 10 mm) pockets. The results were similar for both groups in terms of API, BOP, PD in deep pockets, and CAL. The laser group showed only significant PD gain in moderate pockets during the baseline to 18-week (P <0.05) and 6- to 18- week (P <0.05) periods, whereas no difference was found between LG and CG in the remaining clinical parameters (P >0.05). The present study indicates that, compared to SRP alone, multiple adjunctive applications of a 980-nm diode laser with SRP showed PD improvements only in moderate periodontal pockets (4 to 6 mm).

Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells

PubMed Central

Wang, Chen; Yi, Tai; Qin, Lingfeng; Maldonado, Roberto A.; von Andrian, Ulrich H.; Kulkarni, Sanjay; Tellides, George; Pober, Jordan S.

2013-01-01

Human graft endothelial cells (ECs) can act as antigen-presenting cells to initiate allograft rejection by host memory T cells. Rapamycin, an mTOR inhibitor used clinically to suppress T cell responses, also acts on DCs, rendering them tolerogenic. Here, we report the effects of rapamycin on EC alloimmunogenicity. Compared with mock-treated cells, rapamycin-pretreated human ECs (rapa-ECs) stimulated less proliferation and cytokine secretion from allogeneic CD4+ memory cells, an effect mimicked by shRNA knockdown of mTOR or raptor in ECs. The effects of rapamycin persisted for several days and were linked to upregulation of the inhibitory molecules PD-L1 and PD-L2 on rapa-ECs. Additionally, rapa-ECs produced lower levels of the inflammatory cytokine IL-6. CD4+ memory cells activated by allogeneic rapa-ECs became hyporesponsive to restimulation in an alloantigen-specific manner and contained higher percentages of suppressive CD4+CD25hiCD127loFoxP3+ cells that did not produce effector cytokines. In a human-mouse chimeric model of allograft rejection, rapamycin pretreatment of human arterial allografts increased graft EC expression of PD-L1 and PD-L2 and reduced subsequent infiltration of allogeneic effector T cells into the artery intima and intimal expansion. Preoperative conditioning of allograft ECs with rapamycin could potentially reduce immune-mediated rejection. PMID:23478407

Illustrative cases for monitoring by quantitative analysis of BRAF/NRAS ctDNA mutations in liquid biopsies of metastatic melanoma patients who gained clinical benefits from anti-PD1 antibody therapy.

PubMed

Seremet, Teofila; Planken, Simon; Schreuer, Max; Jansen, Yanina; Delaunoy, Mélanie; El Housni, Hakim; Lienard, Danielle; Del Marmol, Véronique; Heimann, Pierre; Neyns, Bart

2018-02-01

Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of metastatic melanoma patients. Predictive or monitoring biomarkers for response to this therapy could improve the clinical management of these patients. To date, no established biomarkers are available for monitoring the response to immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as BRAF and NRAS mutations for melanoma patients have been proposed for monitoring of immunotherapy response. We present seven illustrative cases for the use of ctDNA BRAF and NRAS mutations' monitoring in plasma. The cases described exemplify four distinct clinical benefit patterns: rapid and durable complete response (CR), early progression, followed by CR, CR followed by early progression after interrupting treatment and long-term disease stabilization. These representative cases suggest that comprehensive BRAF/NRAS ctDNA monitoring during anti-PD1 therapy is informative and can be of added value for the monitoring of melanoma patients gaining clinical benefit on anti-PD1 treatment. An important advantage of our approach is that using the cartridge system on the Idylla platform for mutation analysis, the results become available the same day 2 h after plasma collection. Therefore, in the future, the ctDNA level can be an element in the clinical management of the patients.

Efficacy and safety of adjunctive rasagiline in Japanese Parkinson's disease patients with wearing-off phenomena: A phase 2/3, randomized, double-blind, placebo-controlled, multicenter study.

PubMed

Hattori, Nobutaka; Takeda, Atsushi; Takeda, Shinichi; Nishimura, Akira; Kato, Masafumi; Mochizuki, Hideki; Nagai, Masahiro; Takahashi, Ryosuke

2018-04-27

Rasagiline, a selective, irreversible monoamine oxidase-B inhibitor, is in development in Japan as adjunctive therapy to levodopa. This Phase 2/3 trial evaluated the efficacy and safety of adjunctive rasagiline in Japanese patients with Parkinson's disease (PD) and wearing-off phenomena. Patients aged 30-79 years with diagnosed PD and stable levodopa use were randomized 1:1:1 to rasagiline (0.5/1 mg/day) or placebo for 26 weeks. The primary endpoint was change from baseline in mean daily OFF-time during the treatment period. In total, 141, 134, and 129 patients were randomized to placebo, rasagiline 0.5 mg, or rasagiline 1 mg, respectively. Baseline characteristics were well balanced. Least squares (LS) mean differences vs. placebo for change from baseline in mean daily OFF-time were -0.84 h (rasagiline 1 mg/day) and -0.60 h (rasagiline 0.5 mg/day); both differences were statistically significant. LS mean differences vs. placebo for change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and Part III total scores (in ON-state) and Parkinson's Disease Questionnaire-39 Summary Index Score were: -1.27, -1.74, and -2.51 (0.5 mg/day) and -1.27, -2.14, and -3.84 (1 mg/day); all statistically significant. Treatment-emergent adverse events (TEAEs) occurred in 50.4/69.9/73.6% of the placebo, 0.5 mg/day, and 1 mg/day groups, respectively (most common TEAEs were nasopharyngitis [9.2/18.0/14.7%] and dyskinesia [7.1/8.3/16.3%]). As an adjunct to levodopa, rasagiline reduced OFF-time and improved PD symptoms/signs (MDS-UPDRS scores) and quality of life in Japanese patients with PD and wearing-off phenomena. No important safety concerns were raised. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Oral treatment with SRP299 (killed Mycobacterium vaccae) inhibits experimental periodontal disease in Wistar rats.

PubMed

Breivik, Torbjørn; Rook, Graham A W

2003-11-01

Mycobacterium vaccae injected subcutaneously was previously shown to prevent and treat ligature-induced periodontal disease (PD) in Wistar rats (Breivik & Rook 2000, 2002). Since mycobacteria are readily taken up via Peyer's patches in the intestine, we have now tested the ability of oral SRP299 (killed M. vaccae) to prevent ligature-enhanced PD in Wistar rats, and to modulate the accompanying cytokine and corticosterone responses. A single oral dose of SRP299 (1 mg) was given 14 days before the application of ligatures. PD was assessed when the ligatures had been in place for 56 days. Oral SRP299 reduced bone loss (p = 0.036, X-ray; p = 0.061, histometry) and fibre loss, both on the ligatured (p = 0.0047) and control (p = 0.005) sides, and also reduced the level of TNF-alpha (p = 0.0137) and corticosterone (p = 0.048) induced by intraperitoneal endotoxin lipopolysaccharide (LPS). SRP299 administered by the oral route diminishes ligature-induced bone and fibre loss in this model. This effect may be attributable to the known ability of SRP299 to evoke regulatory T cells, although the mechanism could not be investigated in this study. Treated rats also had less excitable hypothalamo-pituitary-adrenal (HPA) axes. HPA axis overactivity is a known risk factor in human PD. Trials of SRP299 in human PD are now justified.

Are individuals with Parkinson's disease capable of speech-motor learning? - A preliminary evaluation.

PubMed

Kaipa, Ramesh; Jones, Richard D; Robb, Michael P

2016-07-01

The benefits of different practice conditions in limb-based rehabilitation of motor disorders are well documented. Conversely, the role of practice structure in the treatment of motor-based speech disorders has only been minimally investigated. Considering this limitation, the current study aimed to investigate the effectiveness of selected practice conditions in spatial and temporal learning of novel speech utterances in individuals with Parkinson's disease (PD). Participants included 16 individuals with PD who were randomly and equally assigned to constant, variable, random, and blocked practice conditions. Participants in all four groups practiced a speech phrase for two consecutive days, and reproduced the speech phrase on the third day without further practice or feedback. There were no significant differences (p > 0.05) between participants across the four practice conditions with respect to either spatial or temporal learning of the speech phrase. Overall, PD participants demonstrated diminished spatial and temporal learning in comparison to healthy controls. Tests of strength of association between participants' demographic/clinical characteristics and speech-motor learning outcomes did not reveal any significant correlations. The findings from the current study suggest that repeated practice facilitates speech-motor learning in individuals with PD irrespective of the type of practice. Clinicians need to be cautious in applying practice conditions to treat speech deficits associated with PD based on the findings of non-speech-motor learning tasks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Handwriting training in Parkinson’s disease: A trade-off between size, speed and fluency

PubMed Central

Broeder, Sanne; Pereira, Marcelo P.; Swinnen, Stephan P.; Vandenberghe, Wim; Nieuwboer, Alice; Heremans, Elke

2017-01-01

Background In previous work, we found that intensive amplitude training successfully improved micrographia in Parkinson’s disease (PD). Handwriting abnormalities in PD also express themselves in stroke duration and writing fluency. It is currently unknown whether training changes these dysgraphic features. Objective To determine the differential effects of amplitude training on various hallmarks of handwriting abnormalities in PD. Methods We randomized 38 right-handed subjects in early to mid-stage of PD into an experimental group (n = 18), receiving training focused at improving writing size during 30 minutes/day, five days/week for six weeks, and a placebo group (n = 20), receiving stretch and relaxation exercises at equal intensity. Writing skills were assessed using a touch-sensitive tablet pre- and post-training, and after a six-week retention period. Tests encompassed a transfer task, evaluating trained and untrained sequences, and an automatization task, comparing single- and dual-task handwriting. Outcome parameters were stroke duration (s), writing velocity (cm/s) and normalized jerk (i.e. fluency). Results In contrast to the reported positive effects of training on writing size, the current results showed increases in stroke duration and normalized jerk after amplitude training, which were absent in the placebo group. These increases remained after the six-week retention period. In contrast, velocity remained unchanged throughout the study. Conclusion While intensive amplitude training is beneficial to improve writing size in PD, it comes at a cost as fluency and stroke duration deteriorated after training. The findings imply that PD patients can redistribute movement priorities after training within a compromised motor system. PMID:29272301

Handwriting training in Parkinson's disease: A trade-off between size, speed and fluency.

PubMed

Nackaerts, Evelien; Broeder, Sanne; Pereira, Marcelo P; Swinnen, Stephan P; Vandenberghe, Wim; Nieuwboer, Alice; Heremans, Elke

2017-01-01

In previous work, we found that intensive amplitude training successfully improved micrographia in Parkinson's disease (PD). Handwriting abnormalities in PD also express themselves in stroke duration and writing fluency. It is currently unknown whether training changes these dysgraphic features. To determine the differential effects of amplitude training on various hallmarks of handwriting abnormalities in PD. We randomized 38 right-handed subjects in early to mid-stage of PD into an experimental group (n = 18), receiving training focused at improving writing size during 30 minutes/day, five days/week for six weeks, and a placebo group (n = 20), receiving stretch and relaxation exercises at equal intensity. Writing skills were assessed using a touch-sensitive tablet pre- and post-training, and after a six-week retention period. Tests encompassed a transfer task, evaluating trained and untrained sequences, and an automatization task, comparing single- and dual-task handwriting. Outcome parameters were stroke duration (s), writing velocity (cm/s) and normalized jerk (i.e. fluency). In contrast to the reported positive effects of training on writing size, the current results showed increases in stroke duration and normalized jerk after amplitude training, which were absent in the placebo group. These increases remained after the six-week retention period. In contrast, velocity remained unchanged throughout the study. While intensive amplitude training is beneficial to improve writing size in PD, it comes at a cost as fluency and stroke duration deteriorated after training. The findings imply that PD patients can redistribute movement priorities after training within a compromised motor system.

Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson’s disease

PubMed Central

2014-01-01

Background Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson’s disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD. Results Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively. Conclusion Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment. PMID:24965042

Characterization of arthralgia induced by PD-1 antibody treatment in patients with metastasized cutaneous malignancies.

PubMed

Buder-Bakhaya, Kristina; Benesova, Karolina; Schulz, Carsten; Anwar, Hoda; Dimitrakopoulou-Strauss, Antonia; Weber, Tim F; Enk, Alexander; Lorenz, Hanns-Martin; Hassel, Jessica C

2018-02-01

PD-1 antibodies (PD1ab) are increasingly used in metastatic melanoma and other malignancies. Arthralgia is an underestimated side effect of PD-1 antibody treatment with unknown cause. Our aim was to characterize PD1ab-induced arthralgia. We retrospectively included patients with metastatic cutaneous malignancies treated with pembrolizumab or nivolumab ± ipilimumab at the National Center for Tumor Diseases (Heidelberg) between 01/2013 and 09/2016. Arthralgia was characterized by laboratory diagnostics, imaging, and if indicated, rheumatologic consultation. 26 of 195 patients (13.3%) developed arthralgia. The median onset of symptoms was 100 days (7-780 days). Most frequently, arthralgia involved large joints (shoulders, knees) in a predominantly symmetrical pattern. Only two patients were seropositive for rheumatoid factor and/or anti-citrullinated protein antibodies. Ten patients developed the clinical picture of arthritis, with seven of them showing synovitis in MRI or PET/CT. Five patients showed inflammation in joints pre-damaged by osteoarthritis. In 11 patients arthralgia could not be specified. The majority of patients was satisfactorily treated with non-steroidal anti-inflammatory drugs (NSAIDs), 23.1% required additional low-dose corticosteroids and only 7.6% of our patients received further immunosuppressive treatment. Patients with arthralgia showed a better treatment response and improved PFS and OS. Arthralgia is frequent during PD1ab treatment. The clinical picture varies between synovitis of predominantly large joints, progressive osteoarthritis and arthralgia without evident joint damage. Vast majority of cases can be satisfactorily managed by NSAID and/or low-dose corticosteroids.

Hyperbaric oxygen treatment for Parkinson's disease with severe depression and anxiety: A case report.

PubMed

Xu, Jin-Jin; Yang, Si-Tong; Sha, Ying; Ge, Yuan-Yuan; Wang, Jian-Meng

2018-03-01

Patients with Parkinson's disease (PD) frequently suffer from psychiatric disorders, and treating these symptom whereas managing the motor symptoms associated with PD can be a therapeutic challenge. We report a case of PD patient with severe depression and anxiety that refused to be treated with dopaminagonists or SSRIs, the most common treatments for PD patients suffering from psychiatric symptoms. Parkinson's disease with severe depression and anxiety. This man was treated with hyperbaric oxygen treatment for 30 days. Clinical assessment scores for depression and anxiety, including Unified Parkinson's Disease Rating ScaleI (UPDRS I), UPDRS II, Hanmilton Depression Rating Scale, and Hamiliton Anxiety Rating Scale, were improved following the hyperbaric oxygen treatment. Hyperbaric oxygen treatment may be a potential therapeutic method for PD patient suffering from depression and anxiety. Further research is needed to validate this finding and explore a potential mechanism.

The role of rasagiline in the treatment of Parkinson's disease.

PubMed

Leegwater-Kim, Julie; Bortan, Elena

2010-05-25

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 1% to 2% of people older than 60 years. Treatment of PD consists of symptomatic therapies while neuroprotective strategies have remained elusive. Rasagiline is a novel, potent, and irreversible monoamine oxidase type B (MAO-B) inhibitor which has been approved for treatment of PD. Rasagiline inhibits MAO-B more potently than selegiline and has the advantage of once-daily dosing. In several large, randomized, placebo-controlled trials, rasagiline has demonstrated efficacy as monotherapy in early PD and as adjunctive therapy in advanced PD. In addition, rasagiline has been shown to have neuroprotective effects in in vitro and in vivo studies. The recently completed delayed-start ADAGIO (Attenuation of Disease Progression with Azilect Given Once-daily) trial suggests a potential disease-modifying effect for rasagiline 1 mg/day, though the clinical import of this finding has yet to be established.

The role of rasagiline in the treatment of Parkinson’s disease

PubMed Central

Leegwater-Kim, Julie; Bortan, Elena

2010-01-01

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 1% to 2% of people older than 60 years. Treatment of PD consists of symptomatic therapies while neuroprotective strategies have remained elusive. Rasagiline is a novel, potent, and irreversible monoamine oxidase type B (MAO-B) inhibitor which has been approved for treatment of PD. Rasagiline inhibits MAO-B more potently than selegiline and has the advantage of once-daily dosing. In several large, randomized, placebo-controlled trials, rasagiline has demonstrated efficacy as monotherapy in early PD and as adjunctive therapy in advanced PD. In addition, rasagiline has been shown to have neuroprotective effects in in vitro and in vivo studies. The recently completed delayed-start ADAGIO (Attenuation of Disease Progression with Azilect Given Once-daily) trial suggests a potential disease-modifying effect for rasagiline 1 mg/day, though the clinical import of this finding has yet to be established. PMID:20517484

Osimertinib-induced interstitial lung disease in a patient with non-small cell lung cancer pretreated with nivolumab: A case report.

PubMed

Takakuwa, Osamu; Oguri, Tetsuya; Uemura, Takehiro; Sone, Kazuki; Fukuda, Satoshi; Okayama, Minami; Kanemitsu, Yoshihiro; Ohkubo, Hirotsugu; Takemura, Masaya; Ito, Yutaka; Maeno, Ken; Niimi, Akio

2017-09-01

Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for EGFR-T790M-positive non-small cell lung cancer. A high incidence of interstitial lung disease (ILD) during combination treatment with osimertinib and anti-programmed cell death-ligand 1 (PD-L1) inhibitor has been reported. The current study presents a case of ILD development during osimertinib treatment following nivolumab (an anti-PD-1 antibody) treatment. The 59-year-old female was diagnosed with stage IV lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene. Following nivolumab as a sixth-line treatment, an EGFR-T790M-encoding mutation in EGFR exon 20 was identified by re-biopsy. Osimertinib was therefore initiated as a seventh-line treatment. A partial response was subsequently noted; however, 63 days after initiation of the treatment the patient presented with dyspnea with decreased oxygenation in the absence of fever and sputum. A computed tomography scan revealed the emergence of ground-glass opacities with bronchiectasis in both lungs, and a diagnosis of ILD due to osimertinib was made. Following steroid pulse therapy with discontinuation of osimertinib, the patient's chest findings and respiratory condition improved. Therefore, it is considered that anti-PD-1 therapies may be associated with a risk of ILD during subsequent osimertinib treatment.

Feasibility of large-scale deployment of multiple wearable sensors in Parkinson's disease

PubMed Central

Hahn, Tim; Evers, Luc J. W.; de Vries, Nienke M.; Cohen, Eli; Afek, Michal; Bataille, Lauren; Daeschler, Margaret; Claes, Kasper; Boroojerdi, Babak; Terricabras, Dolors; Little, Max A.; Baldus, Heribert; Bloem, Bastiaan R.; Faber, Marjan J.

2017-01-01

Wearable devices can capture objective day-to-day data about Parkinson’s Disease (PD). This study aims to assess the feasibility of implementing wearable technology to collect data from multiple sensors during the daily lives of PD patients. The Parkinson@home study is an observational, two-cohort (North America, NAM; The Netherlands, NL) study. To recruit participants, different strategies were used between sites. Main enrolment criteria were self-reported diagnosis of PD, possession of a smartphone and age≥18 years. Participants used the Fox Wearable Companion app on a smartwatch and smartphone for a minimum of 6 weeks (NAM) or 13 weeks (NL). Sensor-derived measures estimated information about movement. Additionally, medication intake and symptoms were collected via self-reports in the app. A total of 953 participants were included (NL: 304, NAM: 649). Enrolment rate was 88% in the NL (n = 304) and 51% (n = 649) in NAM. Overall, 84% (n = 805) of participants contributed sensor data. Participants were compliant for 68% (16.3 hours/participant/day) of the study period in NL and for 62% (14.8 hours/participant/day) in NAM. Daily accelerometer data collection decreased 23% in the NL after 13 weeks, and 27% in NAM after 6 weeks. Data contribution was not affected by demographics, clinical characteristics or attitude towards technology, but was by the platform usability score in the NL (χ2 (2) = 32.014, p<0.001), and self-reported depression in NAM (χ2(2) = 6.397, p = .04). The Parkinson@home study shows that it is feasible to collect objective data using multiple wearable sensors in PD during daily life in a large cohort. PMID:29261709

Toward a Model of Professional Social Media Use for Teachers' Informal Professional Development: A Delphi Study

ERIC Educational Resources Information Center

Kaiser, Heather

2017-01-01

The effectiveness of teacher professional development (PD) has been scrutinized for decades. Although scholars generally agree that collaboration is a critical component of sustainable PD, among schools in the United States, time for collaboration embedded within the school day is lacking. In the most recent era of social media, school districts…

Orthoptic Treatment of Convergence Insufficiency in Parkinson's Disease: A Case Series.

PubMed

Kergoat, Hélène; Law, Caroline; Chriqui, Estefania; Kergoat, Marie-Jeanne; Leclerc, Bernard-Simon; Panisset, Michel; Postuma, Ronald; Irving, Elizabeth L

2017-01-01

Introduction: This study reports a case series of orthoptic treatment (OT) for convergence insufficiency (CI) in individuals with Parkinson's disease (PD). Method: We are reporting two cases of individuals with PD who completed OT for CI. Both had a confirmed diagnosis of CI, accompanied by CI-type symptomatology. They each underwent an OT program consisting of three office-based visits and 8 weeks of home-based exercises. Treatment outcome was based on the changes measured pre- versus post-OT on the near point of convergence, positive fusional vergences, and symptomatology score. Results: The two participants successfully completed therapy, gained ability to converge, had fewer symptoms, and were satisfied with the OT-induced changes they felt in their day-to-day lives. Conclusion: This case series show that OT for CI in PD is possible. Further research is required as these results demonstrate that OT has the potential to improve symptomatic CI in these patients. In the meantime, the positive results obtained in these two cases should encourage clinicians to consider OT (a therapy with no/minimal risk) for CI in patients with PD whose quality of life is affected by this binocular dysfunction.

Postoperative Nutritional Effects of Early Enteral Feeding Compared with Total Parental Nutrition in Pancreaticoduodectomy Patients: A Prosepective, Randomized Study

PubMed Central

Park, Joon Seong; Chung, Hye-Kyung; Hwang, Ho Kyoung; Kim, Jae Keun

2012-01-01

The benefits of early enteral feeding (EEN) have been demonstrated in gastrointestinal surgery. But, the impact of EEN has not been elucidated yet. We assessed the postoperative nutritional status of patients who had undergone pancreaticoduodenectomy (PD) according to the postoperative nutritional method and compared the clinical outcomes of two methods. A prospective randomized trial was undertaken following PD. Patients were randomly divided into two groups; the EEN group received the postoperative enteral feed and the control group received the postoperative total parenteral nutrition (TPN) management. Thirty-eight patients were included in our analyses. The first day of bowel movement and time to take a normal soft diet was significantly shorter in EEN group than in TPN group. Prealbumin and transferrin were significantly reduced on post-operative day (POD) 7 and were slowly recovered until POD 90 in the TPN group than in the EEN group. EEN group rapidly recovered weight after POD 21 whereas it was gradually decreased in TPN group until POD 90. EEN after PD is associated with preservation of weight compared with TPN and impact on recovery of digestive function after PD. PMID:22379336

Maternal Geophagy of Calabash Chalk on Foetal Cerebral Cortex Histomorphology.

PubMed

Ekanem, Theresa Bassey; Ekong, Moses Bassey; Eluwa, Mokutima Amarachi; Igiri, Anozeng Oyono; Osim, Eme Efiom

2015-01-01

Calabash chalk, a kaolin-base substance is a common geophagic material mostly consumed by pregnant women. This study investigated its effect on the histomorphology of the foetal cerebral cortex. Twelve gestating Wistar rats were divided equally into groups 1 and 2. On pregnancy day seven (PD7), group 2 animals were administered 200 mg/kg body weight of calabash chalk suspension, while group 1 animals served as the control and received 1 ml of distilled water, by oral gavages and for 14 days (PD7-PD20). On PD21, the dams were sacrificed, and the foetuses removed, examined for gross malformations, weighed and culled to two foetuses per mother. Their whole brains were excised, weighed and preserved using 10% buffered formalin, and routinely processed by haematoxylin and eosin, and Luxol fast blue methods. The foetuses showed no morphological change, but their mean body weights was higher (p=0.0001). Histomorphological sections of the cerebral cortex showed hypertrophy and hyperplasia of cells in all the cortical layers, with less demonstrated Nissl and higher (p=0.001) cellular population compared with the control group. Calabash chalk cause body weight increase and histomorphological changes in the cerebral cortex of foetuses.

Anticholinesterase Effect on Motor Kinematic Measures and Brain Activation in Parkinson’s Disease

PubMed Central

Mentis, Marc J.; Delalot, Dominique; Naqvi, Hassan; Gordon, Mark F.; Gudesblatt, Mark; Edwards, Christine; Donatelli, Luke; Dhawan, Vijay; Eidelberg, David

2015-01-01

Anticholinesterase (AChE) drugs are being prescribed off label for nonmotor symptoms in Parkinson’s disease (PD). Theoretically, these drugs can impair motor function. A small literature suggests AChE therapy has little effect on clinical motor evaluation; however, no study has made objective motor kinematic measures or evaluated brain function. We hypothesized that even if clinical examination was normal in PD patients on dopamine therapy, (1) sensitive kinematic measures would be abnormal during AChE therapy or (2) normal kinematic measures would be maintained by compensatory brain activation. We carried out a randomized, double-blind, placebo-controlled trial of 8 weeks donepezil (10 mg/day) in 17 PD subjects. Subjects carried out a computerized motor task during a positron emission tomography (PET) scan before starting the drug and again after 8 weeks of donepezil or placebo. Kinematic measures of motor function and PET scans were analyzed to compare the effects of donepezil and placebo. Neither placebo nor donepezil altered motor kinematic measures. Furthermore, movement integrity while on donepezil was maintained without compensatory brain activity. Donepezil 10 mg/day can be given for nonmotor symptoms in PD without adverse motor effects or compensatory brain activity. PMID:16228997

CBT for the treatment of depression in Parkinson's disease: a promising nonpharmacological approach.

PubMed

Dobkin, Roseanne DeFronzo; Menza, Matthew; Bienfait, Karina L

2008-01-01

Depression is very common in Parkinson's disease (PD) and linked with a faster progression of physical symptoms, greater cognitive decline and poorer quality of life. Nonpharmacological approaches, such as cognitive-behavioral therapy (CBT), for the treatment of depression in PD (dPD) have received little experimental attention despite strong demonstrated efficacy in other geriatric and medical populations. Depressed PD patients often differ from the depressed non-PD elderly in that they present with increased rates of both executive dysfunction and comorbid psychiatric diagnoses, may differ in their depressive symptom presentation and typically have caregivers who are highly involved in their treatment. Therefore, it is not possible to conclude that empirically validated treatments in the depressed aged will generalize to those with PD. In order to be most effective for PD patients, CBT should be tailored to their unique needs. Additional controlled research is needed to further explore the efficacy of CBT for dPD.

Predictors of Peritonitis and the Impact of Peritonitis on Clinical Outcomes of Continuous Ambulatory Peritoneal Dialysis Patients in Taiwan—10 Years’ Experience in a Single Center

PubMed Central

Hsieh, Yao-Peng; Chang, Chia-Chu; Wen, Yao-Ko; Chiu, Ping-Fang; Yang, Yu

2014-01-01

♦ Objective: Peritoneal dialysis (PD) has become more prevalent as a treatment modality for end-stage renal disease, and peritonitis remains one of its most devastating complications. The aim of the present investigation was to examine the frequency and predictors of peritonitis and the impact of peritonitis on clinical outcomes. ♦ Methods: Our retrospective observational cohort study enrolled 391 patients who had been treated with continuous ambulatory PD (CAPD) for at least 90 days. Relevant demographic, biochemical, and clinical data were collected for an analysis of CAPD-associated peritonitis, technique failure, drop-out from PD, and patient mortality. ♦ Results: The peritonitis rate was 0.196 episodes per patient-year. Older age (>65 years) was the only identified risk factor associated with peritonitis. A multivariate Cox regression model demonstrated that technique failure occurred more often in patients experiencing peritonitis than in those free of peritonitis (p < 0.001). Kaplan-Meier analysis revealed that the group experiencing peritonitis tended to survive longer than the group that was peritonitis-free (p = 0.11). After multivariate adjustment, the survival advantage reached significance (hazard ratio: 0.64; 95% confidence interval: 0.46 to 0.89; p = 0.006). Compared with the peritonitis-free group, the group experiencing peritonitis also had more drop-out from PD (p = 0.03). ♦ Conclusions: The peritonitis rate was relatively low in the present investigation. Elderly patients were at higher risk of peritonitis episodes. Peritonitis independently predicted technique failure, in agreement with other reports. However, contrary to previous studies, all-cause mortality was better in patients experiencing peritonitis than in those free of peritonitis. The underlying mechanisms of this presumptive “peritonitis paradox” remain to be clarified. PMID:24084840

Beneficial effect of etazolate on depression-like behavior and, learning, and memory impairment in a model of Parkinson's disease.

PubMed

Alzoubi, Karem H; Mokhemer, Enas; Abuirmeileh, Amjad N

2018-09-17

The aim of this study was to evaluate etazolate against depression-like behavior and, learning and memory impairment induced by 6- hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD). This aim was achieved through comparing 6-OHDA lesioned rats in the presence and absence of etazolate. The 6-OHDA was used to induce lesion as a model of PD. Etazolate was administered at a dose of 1 mg/kg/day for 14 days, starting 7 days after lesion induction. Apomorphine-induced rotation test was used to evaluate 6-OHDA-induced motor deficits, tail suspension test was used to assess depression-like symptoms, and the radial arms water maze (RAWM) was used to evaluate special learning and memory functions. Antioxidant biomarkers and BDNF protein levels were assessed in the hippocampus. Results revealed that etazolate administration significantly improved 6-OHDA-induced PD related symptoms including motor deficits, depression-like behavior and impairment of both short- and long- term memory. Moreover, etazolate significantly prevented 6-OHDA-induced reduction in oxidative stress biomarkers (GSH/GSSG ratio, GPx) and BDNF levels. In conclusion, motor dysfunction, depressive- like behavior, and learning and memory deficits in the 6-OHDA rat model of PD can be significantly prevented by etazolate. This prevention could be attributed to etazolate's ability to prevent reduction in antioxidative stress biomarkers and BDNF levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Mitochondrial Dysfunction and Oxidative Stress Promote Apoptotic Cell Death in the Striatum via Cytochrome c/Caspase-3 Signaling Cascade Following Chronic Rotenone Intoxication in Rats

PubMed Central

Lin, Tsu-Kung; Cheng, Ching-Hsiao; Chen, Shang-Der; Liou, Chia-Wei; Huang, Chi-Ren; Chuang, Yao-Chung

2012-01-01

Parkinson’s disease (PD) is a progressive neurological disorder marked by nigrostriatal dopaminergic degeneration. Evidence suggests that mitochondrial dysfunction may be linked to PD through a variety of different pathways, including free-radical generation and dysfunction of the mitochondrial Complex I activity. In Lewis rats, chronic systemic administration of a specific mitochondrial Complex I inhibitor, rotenone (3 mg/kg/day) produced parkinsonism-like symptoms. Increased oxidized proteins and peroxynitrite, and mitochondrial or cytosol translocation of Bim, Bax or cytochrome c in the striatum was observed after 2–4 weeks of rotenone infusion. After 28 days of systemic rotenone exposure, imunohistochemical staining for tyrosine hydroxylase indicated nigrostriatal dopaminergic neuronal cell degeneration. Characteristic histochemical (TUNEL or activated caspase-3 staining) or ultrastructural (electron microscopy) features of apoptotic cell death were present in the striatal neuronal cell after chronic rotenone intoxication. We conclude that chronic rotenone intoxication may enhance oxidative and nitrosative stress that induces mitochondrial dysfunction and ultrastructural damage, resulting in translocation of Bim and Bax from cytosol to mitochondria that contributes to apoptotic cell death in the striatum via cytochrome c/caspase-3 signaling cascade. PMID:22942730

Gingival response in orthodontic patients: Comparative study between self-ligating and conventional brackets.

PubMed

Folco, Alejandra A; Benítez-Rogé, Sandra C; Iglesias, Marina; Calabrese, Diana; Pelizardi, Cristina; Rosa, Alcira; Brusca, Marisa I; Hecht, Pedro; Mateu, María E

2014-01-01

Orthodontic brackets contribute to the accumulation of bacterial plaque on tooth surfaces because they hinder oral hygiene. In contrast to conventional brackets, self-ligating brackets do not require additional parts to support the arches, thus improving dental hygiene. The aim of this study was to compare the gingival response in orthodontic patients wearing self-ligating or conventional brackets. A sample of 22 patients aged 16 to 30 years was divided into two groups: Group A, treated with selfligating brackets (Damon system) and Group B, treated with conventional brackets (Roth technique). The following were assessed during the treatment: Plaque Index (PI), Gingival Index (GI) and Probing Depth (PD), and sub-gingival samples were taken from teeth 14/24 for microbiological observation. No statistically significant difference was found between Groups A and B; p>0.05 (sign-ranked) or between PI, GI and PD at the different times (Friedman's Analysis of Variance), even though the indices were found to increase at 14 days, particularly for self-ligating brackets. The quantity and quality of microorganisms present were compatible with health on days 0, 28 and 56. As from day 14 there is a predominance of microbiota compatible with gingivitis in both groups. In the samples studied, orthodontic treatment increases bacterial plaque and inflammatory gingival response, but gingival-periodontal health can be maintained with adequate basic therapy. Self-ligating and conventional brackets produced similar gingival response.

Chloroquine-Primaquine versus Chloroquine Alone to Treat Vivax Malaria in Afghanistan: An Open Randomized Superiority Trial.

PubMed

Awab, Ghulam Rahim; Imwong, Mallika; Bancone, Germana; Jeeyapant, Atthanee; Day, Nicholas P J; White, Nicholas J; Woodrow, Charles J

2017-12-01

Afghanistan's national guidelines recommend primaquine (PQ) for radical treatment of Plasmodium vivax malaria, but this is rarely implemented because of concerns over potential hemolysis in patients who have G6PD deficiency. Between August 2009 and February 2014, we conducted an open-label, randomized controlled trial of chloroquine (CQ) alone versus chloroquine plus primaquine (0.25 mg base/kg/day for 14 days) (CQ+PQ) in patients aged 6 months and older with microscopy confirmed P. vivax infection. In the CQ+PQ group, G6PD deficiency was excluded by fluorescent spot testing. The primary outcome was P. vivax recurrence assessed by survival analysis over one year follow-up. Of 593 patients enrolled, 570 attended at or after 14 days of follow-up. Plasmodium vivax recurrences occurred in 37 (13.1%) of 282 patients in the CQ+PQ arm versus 86 (29.9%) of 288 in the CQ arm (Cox proportional hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.25-0.54) (intention-to-treat analysis). Protection against recurrence was greater in the first 6 months of follow-up (HR 0.082; 95% CI 0.029-0.23) than later (HR 0.65, 95% CI 0.41-1.03). Five of seven patients requiring hospital admission were considered possible cases of PQ-related hemolysis, and PQ was stopped in a further six; however, in none of these cases did hemoglobin fall by ≥ 2 g/dL or to below 7 g/dL, and genotyping did not detect any cases of Mediterranean variant G6PD deficiency. PQ 0.25 mg/kg/day for 14 days prevents relapse of P. vivax in Afghanistan. Patient visits during the first week may improve adherence. Implementation will require deployment of point-of-care phenotypic tests for G6PD deficiency.

Chloroquine–Primaquine versus Chloroquine Alone to Treat Vivax Malaria in Afghanistan: An Open Randomized Superiority Trial

PubMed Central

Awab, Ghulam Rahim; Imwong, Mallika; Bancone, Germana; Jeeyapant, Atthanee; Day, Nicholas P. J.; White, Nicholas J.; Woodrow, Charles J.

2017-01-01

Abstract. Afghanistan’s national guidelines recommend primaquine (PQ) for radical treatment of Plasmodium vivax malaria, but this is rarely implemented because of concerns over potential hemolysis in patients who have G6PD deficiency. Between August 2009 and February 2014, we conducted an open-label, randomized controlled trial of chloroquine (CQ) alone versus chloroquine plus primaquine (0.25 mg base/kg/day for 14 days) (CQ+PQ) in patients aged 6 months and older with microscopy confirmed P. vivax infection. In the CQ+PQ group, G6PD deficiency was excluded by fluorescent spot testing. The primary outcome was P. vivax recurrence assessed by survival analysis over one year follow-up. Of 593 patients enrolled, 570 attended at or after 14 days of follow-up. Plasmodium vivax recurrences occurred in 37 (13.1%) of 282 patients in the CQ+PQ arm versus 86 (29.9%) of 288 in the CQ arm (Cox proportional hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.25–0.54) (intention-to-treat analysis). Protection against recurrence was greater in the first 6 months of follow-up (HR 0.082; 95% CI 0.029–0.23) than later (HR 0.65, 95% CI 0.41–1.03). Five of seven patients requiring hospital admission were considered possible cases of PQ-related hemolysis, and PQ was stopped in a further six; however, in none of these cases did hemoglobin fall by ≥ 2 g/dL or to below 7 g/dL, and genotyping did not detect any cases of Mediterranean variant G6PD deficiency. PQ 0.25 mg/kg/day for 14 days prevents relapse of P. vivax in Afghanistan. Patient visits during the first week may improve adherence. Implementation will require deployment of point-of-care phenotypic tests for G6PD deficiency. PMID:29141719

Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS).

PubMed

Monaghan, Sean F; Chung, Chun-Shiang; Chen, Yaping; Lomas-Neira, Joanne; Fairbrother, William G; Heffernan, Daithi S; Cioffi, William G; Ayala, Alfred

2016-11-11

Acute respiratory distress syndrome (ARDS) remains a common organ dysfunction in the critically ill patient. Mechanisms for its development have focused on immune mediated causes, aspects of our understanding are not complete, and we lack biomarkers. Blood and bronchial alveolar lavage fluid (BAL) from humans (n = 10-13) with ARDS and controls (n = 5-10) as well as a murine model of ARDS (n = 5-6) with controls (n = 6-7) were studied. ARDS was induced in mice by hemorrhagic shock (day 1) followed by poly-microbial sepsis (day 2). Samples were then collected on the third day after the animals were euthanized. Ex vivo experiments used splenocytes from animals with ARDS cultured with and without soluble programmed death receptor-1 (sPD-1). Levels of sPD-1 are increased in both the serum (11,429.3 pg/mL(SD 2133.3) vs. 8061.4(SD 4187.8), p = 0.036) and bronchial alveolar lavage (BAL) fluid (6,311.1 pg/mL(SD 3758.0) vs. 90.7 pg/mL(SD 202.8), p = 0.002) of humans with ARDS. Similar results are seen in the serum (9396.1 pg/mL(SD 1546.0) vs. 3464.5 pg/mL(SD 2511.8), p = 0.001) and BAL fluid (2891.7 pg/mL(SD 868.1) vs. 1385.9 pg/mL(SD 927.8), p = 0.012) of mice. sPD-1 levels in murine blood (AUC = 1(1-1), p = 0.006), murine BAL fluid (AUC = 0.905(0.717-1.093), p = 0.015), and human BAL (AUC = 1(1-1), p = 0.001) fluid predicted ARDS. To assess the importance of sPD-1 in ARDS, ex vivo experiments were undertaken. BAL fluid from mice with ARDS dampens the TNF-α production compared to cells cultured with BAL lacking sPD-1 (2.7 pg/mL(SD 3.8) vs. 52.38 pg/mL(SD 25.1), p = 0.002). This suggests sPD-1 is elevated in critical illness and may represent a potential biomarker for ARDS. In addition, sPD-1 has an anti-inflammatory mechanism in conditions of marked stress and aids in the resolution of severe inflammation. sPD-1 could be used to not only diagnose ARDS, but may be a potential therapy.

Enduring Effects of Paternal Deprivation in California Mice (Peromyscus californicus): Behavioral Dysfunction and Sex-Dependent Alterations in Hippocampal New Cell Survival

PubMed Central

Glasper, Erica R.; Hyer, Molly M.; Hunter, Terrence J.

2018-01-01

Early-life experiences with caregivers can significantly affect offspring development in human and non-human animals. While much of our knowledge of parent-offspring relationships stem from mother-offspring interactions, increasing evidence suggests interactions with the father are equally as important and can prevent social, behavioral, and neurological impairments that may appear early in life and have enduring consequences in adulthood. In the present study, we utilized the monogamous and biparental California mouse (Peromyscus californicus). California mouse fathers provide extensive offspring care and are essential for offspring survival. Non-sibling virgin male and female mice were randomly assigned to one of two experimental groups following the birth of their first litter: (1) biparental care: mate pairs remained with their offspring until weaning; or (2) paternal deprivation (PD): paternal males were permanently removed from their home cage on postnatal day (PND) 1. We assessed neonatal mortality rates, body weight, survival of adult born cells in the dentate gyrus of the hippocampus, and anxiety-like and passive stress-coping behaviors in male and female young adult offspring. While all biparentally-reared mice survived to weaning, PD resulted in a ~35% reduction in survival of offspring. Despite this reduction in survival to weaning, biparentally-reared and PD mice did not differ in body weight at weaning or into young adulthood. A sex-dependent effect of PD was observed on new cell survival in the dentate gyrus of the hippocampus, such that PD reduced cell survival in female, but not male, mice. While PD did not alter classic measures of anxiety-like behavior during the elevated plus maze task, exploratory behavior was reduced in PD mice. This observation was irrespective of sex. Additionally, PD increased some passive stress-coping behaviors (i.e., percent time spent immobile) during the forced swim task—an effect that was also not sex-dependent. Together, these findings demonstrate that, in a species where paternal care is not only important for offspring survival, PD can also contribute to altered structural and functional neuroplasticity of the hippocampus. The mechanisms contributing to the observed sex-dependent alterations in new cell survival in the dentate gyrus should be further investigated. PMID:29487509

Glucose-6-phosphate dehydrogenase deficiency prevalence and genetic variants in malaria endemic areas of Colombia.

PubMed

Valencia, Sócrates Herrera; Ocampo, Iván Darío; Arce-Plata, María Isabel; Recht, Judith; Arévalo-Herrera, Myriam

2016-05-26

Glucose 6-phosphate dehydrogenase (G6PD) is an enzyme involved in prevention of cellular oxidative damage, particularly protecting erythrocytes from haemolysis. An estimated 400 million people present variable degrees of inherited G6PD deficiency (G6PDd) which puts them at risk for developing haemolysis triggered by several risk factors including multiple drugs and certain foods. Primaquine (PQ) is a widely used anti-malarial drug that can trigger haemolysis in individuals with G6PDd. Intensification of malaria control programmes worldwide and particularly malaria elimination planning in some regions recommend a more extensive use of PQ and related drugs in populations with different G6PDd prevalence. This a preliminary study to assess the prevalence of G6PDd in representative malaria endemic areas of Colombia by measuring G6PD phonotype and genotypes. Volunteers (n = 426) from four malaria endemic areas in Colombia (Buenaventura, Tumaco, Tierralta and Quibdo) were enrolled. Blood samples were drawn to evaluate G6PD enzymatic activity by using a quantitative G6PD test and a subset of samples was analysed by PCR-RFLP to determine the frequency of the three most common G6PD genotypic variants: A-, A+ and Mediterranean. A total of 28 individuals (6.56 %) displayed either severe or intermediate G6PDd. The highest prevalence (3.51 %) was in Buenaventura, whereas G6PDd prevalence was lower (<1 %) in Tierralta and Quibdo. G6PD A alleles were the most frequent (15.23 %) particularly in Buenaventura and Tumaco. Overall, a high frequency of G6PD A- genotype, followed by A+ genotype was found in the analysed population. G6PDd based on enzymatic activity as well as G6PD A allelic variants were found in malaria-endemic populations on the Pacific coast of Colombia, where most of malaria cases are caused by Plasmodium vivax infections. These infections are treated for 14 days with PQ, however there are no official reports of PQ-induced haemolytic crises. Further assessment of G6PDd prevalence in malaria endemic areas in Colombia is crucial in view of possible mass drug administration for malaria elimination in these regions, as well as implementation of appropriate G6PDd diagnostic methods.

Perinatal choline supplementation does not mitigate motor coordination deficits associated with neonatal alcohol exposure in rats.

PubMed

Thomas, Jennifer D; O'Neill, Teresa M; Dominguez, Hector D

2004-01-01

Prenatal alcohol exposure can disrupt brain development, leading to a variety of behavioral alterations including learning deficits, hyperactivity, and motor dysfunction. We have been investigating the possibility that perinatal choline supplementation may effectively reduce the severity of alcohol's adverse effects on behavioral development. We previously reported that perinatal choline supplementation can ameliorate alcohol-induced learning deficits and hyperactivity in rats exposed to alcohol during development. The present study examined whether perinatal choline supplementation could also reduce the severity of motor deficits induced by alcohol exposure during the third trimester equivalent brain growth spurt. Male neonatal rats were assigned to one of three treatment groups. One group was exposed to alcohol (6.6 g/kg/day) from postnatal days (PD) 4 to 9 via an artificial rearing procedure. Artificially and normally reared control groups were included. One half of subjects from each treatment received daily subcutaneous injections of a choline chloride solution from PD 4 to 30, whereas the other half received saline vehicle injections. On PD 35-37, subjects were tested on a parallel bar motor task, which requires both balance and fine motor coordination. Ethanol-exposed subjects exhibited significant motor impairments compared to both control groups whose performance did not differ significantly from one another. Perinatal choline treatment did not affect motor performance in either ethanol or control subjects. These data indicate that the beneficial effects of perinatal choline supplementation in ethanol-treated subjects are task specific and suggest that choline is more effective in mitigating cognitive deficits compared to motor deficits associated with developmental alcohol exposure.

Efficacy of rasagiline in early Parkinson's disease: a meta-analysis of data from the TEMPO and ADAGIO studies.

PubMed

Hauser, Robert A; Abler, Victor; Eyal, Eli; Eliaz, Rom E

2016-10-01

To evaluate the efficacy of rasagiline versus placebo in a pooled population of patients with early Parkinson's disease (PD). TEMPO and ADAGIO were Phase III studies that evaluated the symptomatic efficacy of rasagiline versus placebo in patients with early PD. This meta-analysis included Unified Parkinson's Disease Rating Scale (UPDRS) observations from weeks 12, 24 and 36 in ADAGIO and from weeks 14 and 26 in TEMPO; TEMPO visits were recoded to weeks 12 and 24, respectively. The present analysis includes all patients who received rasagiline 1 mg/day, 2 mg/day or placebo, and had ≥1 post-baseline observations and a subgroup of patients whose baseline UPDRS Total scores were ≥27 (Upper Quartile population). Change from baseline in UPDRS scores were evaluated using mixed models repeated measures analyses. Of the 1578 patients randomized to the two studies, 1546 patients met criteria for inclusion in the meta-analysis. Effects on UPDRS Total, motor and activities of daily living scores were significantly better for both doses of rasagiline compared with placebo at all time periods. The Upper Quartile population included 402 patients with a UPDRS Total score ≥27 at baseline. These patients generally demonstrated a larger magnitude of treatment effect than was seen in the full population. This meta-analysis confirms the efficacy of rasagiline monotherapy over 36 weeks. Although TEMPO and ADAGIO are considered studies of "very early" PD, both contained a sizeable pool of patients with more severe disease. In addition, the meta-analysis showed a larger magnitude of effect in patients with more severe baseline disease.

The PD-1/B7-H1 pathway modulates the natural killer cells versus mouse glioma stem cells.

PubMed

Huang, Bo Yuan; Zhan, Yi Ping; Zong, Wen Jing; Yu, Chun Jiang; Li, Jun Fa; Qu, Yan Ming; Han, Song

2015-01-01

Glioblastoma multiforme (GBM) is the most malignant primary type of brain tumor in adults. There has been increased focus on the immunotherapies to treat GBM patients, the therapeutic value of natural killer (NK) cells is still unknown. Programmed death-1 (PD-1) is a major immunological checkpoint that can negatively regulate the T-cell-mediated immune response. We tested the combination of the inhibiting the PD-1/B7H1 pathway with a NK-cell mediated immune response in an orthotopic mouse model of GBM. Mouse glioma stem cells (GL261GSCs) and mouse NK cells were isolated and identified. A lactate dehydrogenase (LDH) assay was perfomed to detect the cytotoxicity of NK cells against GL261GSCs. GL261GSCs were intracranially implanted into mice, and the mice were stratified into 3 treatment groups: 1) control, 2) NK cells treatment, and 3) PD-1 inhibited NK cells treatment group. Overall survival was quantified, and animal magnetic resonance imaging (MRI) was performed to determine tumor growth. The brains were harvested after the mice were euthanized, and immunohistochemistry against CD45 and PCNA was performed. The mouse NK cells were identified as 90% CD3- NK1.1+CD335+ by flow cytometric analysis. In the LDH assay, the ratios of the damaged GL261GSCs, with the E:T ratios of 2.5:1, 5:1, and 10:1, were as follows: 1) non-inhibited group: 7.42%, 11.31%, and 15.1%, 2) B7H1 inhibited group: 14.75%, 18.25% and 29.1%, 3) PD-1 inhibited group: 15.53%, 19.21% and 29.93%, 4) double inhibited group: 33.24%, 42.86% and 54.91%. In the in vivo experiments, the mice in the PD-1 inhibited NK cells treatment group and IL-2-stimulated-NK cells treatment group displayed a slowest tumor growth (F = 308.5, P<0.01) and a slower tumor growth compared with control group (F = 118.9, P<0.01), respectively. The median survival of the mice in the three groups were as follows: 1) conrol group: 29 days, 2) NK cells treatment group: 35 days (P = 0.0012), 3) PD-1 inhibited NK cells treatment group: 44 days (P = 0.0024). Immunologic data of PCNA-positive cell ratios and CD45-positive cell ratios of the tumor specimens in the three groups were as follows: 1) control group: 65.72% (PCNA) and 0.92% (CD45), 2) NK treatment group: 27.66% (PCNA) and 13.46% (CD45), and 3) PD-1 inhibited NK cells treatment group: 13.66% (PCNA) and 23.66% (CD45) (P<0.001). The results demonstrated that blockade of PD-1/B7H1 pathway could promote mouse NK cells to kill the GL261GSCs, and the PD-1-inhibited NK cells could be a feasible immune therapeutic approach against GBM.

Consistency of visual assessments of mammographic breast density from vendor-specific "for presentation" images.

PubMed

Abdolell, Mohamed; Tsuruda, Kaitlyn; Lightfoot, Christopher B; Barkova, Eva; McQuaid, Melanie; Caines, Judy; Iles, Sian E

2016-01-01

Discussions of percent breast density (PD) and breast cancer risk implicitly assume that visual assessments of PD are comparable between vendors despite differences in technology and display algorithms. This study examines the extent to which visual assessments of PD differ between mammograms acquired from two vendors. Pairs of "for presentation" digital mammography images were obtained from two mammography units for 146 women who had a screening mammogram on one vendor unit followed by a diagnostic mammogram on a different vendor unit. Four radiologists independently visually assessed PD from single left mediolateral oblique view images from the two vendors. Analysis of variance, intra-class correlation coefficients (ICC), scatter plots, and Bland-Altman plots were used to evaluate PD assessments between vendors. The mean radiologist PD for each image was used as a consensus PD measure. Overall agreement of the PD assessments was excellent between the two vendors with an ICC of 0.95 (95% confidence interval: 0.93 to 0.97). Bland-Altman plots demonstrated narrow upper and lower limits of agreement between the vendors with only a small bias (2.3 percentage points). The results of this study support the assumption that visual assessment of PD is consistent across mammography vendors despite vendor-specific appearances of "for presentation" images.

[The prevalence of Parkinson's disease, associated dementia, and depression in Dresden].

PubMed

Riedel, O; Schneider, C; Klotsche, J; Reichmann, H; Storch, A; Wittchen, H-U

2013-02-01

Parkinson's disease (PD) is frequently compounded by dementia and depression. Yet local total estimates on the prevalence of PD with dementia/depression are still lacking. These are socioeconomically important, especially for the eastern federal states in Germany due to the demographic structures. We conducted a two-staged total estimation in the area of Dresden. First, all local office-based neurologists, hospitals and retirement homes were asked to list their patients/residents with PD on a single study day. Then a random sample of patients/home residents was neuropsycholoigcally examined, including the Mini-mental-state exam and the Montgomery-Asberg Depression rating scale. Dementia was diagnosed according to DSM-IV criteria. Overall, 886 PD cases (95 % CI: 809 - 926) were estimated, of which 252 (95 % CI: 226 - 279) suffered from dementia and 216 (95 % CI: 191 - 242) from depression. Dementia rates increased by age with 13.8 % (≤ 65 years) to 40.2 % (≥ 76 years). Depression rates ranged from 23.3 % to 28.0 %. Overall, 20.6 % of all ambulatory treated PD patients and 85.7 % of all home residents with PD had dementia. The prevalence of PD in Dresden dovetails with previous reported estimates. Dementia and depression are frequent complications in outpatients as well as home residents with PD. © Georg Thieme Verlag KG Stuttgart · New York.

Context-dependent extinction of an appetitive operant conditioned response in infant rats.

PubMed

Orellana Barrera, Estefanía; Arias, Carlos; González, Felisa; Abate, Paula

2017-04-01

The present study evaluated context-dependent learning under an operant conditioning procedure in infant rats. Preweanling rats were trained in context A during postnatal days (PDs) 16 and 17 to learn an appetitive operant conditioning task, employing milk chocolate as appetitive reinforcer. On PD18 the operant response was extinguished in context A, or in an alternative context B. The change from context A to B between acquisition and extinction did not affect the number of responses during extinction, but slightly modified the shape of the extinction curve. On PD19, a renewal test conducted in context A clearly showed ABA-renewal of the extinguished operant response. These results add to the body of evidence indicating that infants are able to acquire and retain contextual information, and support the notion that extinction during this ontogenetic period involves new learning. © 2017 Wiley Periodicals, Inc.

Polar-Drive--Implosion Physics on OMEGA and the NIF

NASA Astrophysics Data System (ADS)

Radha, P. B.

2012-10-01

Polar drive (PD) permits the execution of direct-drive--ignition experiments on facilities that are configured for x-ray drive such as the National Ignition Facility (NIF) and Laser M'egajoule. Experiments on the OMEGA laser are used to develop and validate models of PD implosions. Results from OMEGA PD shock-timing and warm implosions are presented. Experiments are simulated with the 2-D hydrodynamic code DRACO including full 3-D ray trace to model oblique beams. Excellent agreement is obtained in shock velocity and catch-up in PD geometry in warm, plastic shells. Predicted areal densities are measured in PD implosion experiments. Good agreement between simulation and experiments is obtained in the overall shape of the compressing shell when observed through x-ray backlighting. Simulated images of the hot core, including the effect of magnetic fields, are compared with experiments. Comparisons of simulated and observed scattered light and bang time in PD geometry are presented. Several techniques to increase implosion velocity are presented including beam profile variations and different ablator materials. Results from shimmed-target PD experiments will also be presented. Designs for future PD OMEGA experiments at ignition-relevant intensities will be presented. The implication of these results for NIF-scale plasmas is discussed. Experiments for the NIF in its current configuration, with indirect-drive phase plates, are proposed to study implosion energetics and shell asymmetries. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC52-08NA28302.

Treatment of complicated parapneumonic pleural effusion and pleural parapneumonic empyema.

PubMed

Rodríguez Suárez, Pedro; Freixinet Gilart, Jorge; Hernández Pérez, José María; Hussein Serhal, Mohamed; López Artalejo, Antonio

2012-07-01

We performed this observational prospective study to evaluate the results of the application of a diagnostic and therapeutic algorithm for complicated parapneumonic pleural effusion (CPPE) and pleural parapneumonic empyema (PPE). From 2001 to 2007, 210 patients with CPPE and PPE were confirmed through thoracocentesis and treated with pleural drainage tubes (PD), fibrinolytic treatment or surgical intervention (videothoracoscopy and posterolateral thoracotomy). Patients were divided into 3 groups: I (PD); II (PD and fibrinolytic treatment); IIIa (surgery after PD and fibrinolysis), and IIIb (direct surgery). The statistical study was done by variance analysis (ANOVA), χ2 and Fisher exact test. The presence of alcohol or drug consumption, smoking and chronic obstructive pulmonary disease (COPD) were strongly associated with a great necessity for surgical treatment. The IIIa group was associated with increased drainage time, length of stay and complications. No mortality was observed. The selective use of PD and intrapleural fibrinolysis makes surgery unnecessary in more than 75% of cases. The selective use of PD and fibrinolysis avoids surgery in more than 75% of cases. However, patients who require surgery have more complications, longer hospital stay, and more days on PD and they are more likely to require admittance to the Intensive Care Unit.

Factors associated with peritoneal dialysis catheter complications in children.

PubMed

Stewart, Camille L; Acker, Shannon N; Pyle, Laura L; Kulungowski, Ann; Cadnapaphornchai, Melissa; Bruny, Jennifer L; Karrer, Frederick

2016-01-01

Peritoneal dialysis (PD) is a common method of renal replacement therapy for children. However, placement of PD catheters has risk, and some are never used. We conducted a retrospective chart review of children with a PD catheter placed between 2000 and 2014. Logistic regression analyses were used to identify covariates associated with complications. We identified 175 children with PD catheters. 110 complications developed in 80 children (45.7%). Complications including unexpected return to the operating room and peritonitis increased as the length of time a catheter was in place increased. Children who weighed <12.4 kg had 3.2 times greater odds of developing a leak (95% CI 1.21-8.63, p=0.02). Twelve children never used their PD catheters, 9 with acute kidney injury (AKI) who recovered from their disease more quickly than expected. No covariate was associated with nonuse. Complications with PD catheters are common and increase the longer catheters are in place. Lower weight children are at greater risk of PD catheter leak. Decreased initial volumes of dialysate in smaller children may mitigate this risk. Nonuse may be reduced if dialysis is permitted the day of placement for children with AKI. Copyright © 2016 Elsevier Inc. All rights reserved.

An interaction between levodopa and enteral nutrition resulting in neuroleptic malignant-like syndrome and prolonged ICU stay.

PubMed

Bonnici, André; Ruiner, Carola-Ellen; St-Laurent, Lyne; Hornstein, David

2010-09-01

To describe a probable interaction between enteral feeds and levodopa leading to neuroleptic malignant-like syndrome (NMLS) in a polytrauma patient with Parkinson's disease (PD). A 63-year-old morbidly obese male polytrauma patient with PD and type 2 diabetes mellitus was admitted to our intensive care unit postoperatively. Enteral feeds were administered per nasogastric tube and provided 0.88 g /kg/day of protein based on ideal body weight (IBW). His PD medications (pramipexole, entacapone, and immediate-release levodopa/carbidopa 100 mg/25 mg, 1.5 tablets 4 times daily) were administered via nasogastric tube. To achieve better glycemic control, his enteral feeds were changed to a formula that provided 1.8 g/kg/day of protein based on IBW. In the following 24 hours, the patient's mental status deteriorated and he was reintubated. He developed a high fever (40.5 degrees C), leukocytosis, elevated serum creatine kinase (CK) (480-1801 units/L), and acute renal impairment. His enteral nutrition was changed to decrease protein intake to 1.0 g/kg/day based on IBW and he was given bromocriptine 5 mg 3 times daily via nasogastric tube. Within 24 hours, the patient's mental status improved, his temperature and CK decreased, and his renal function began to improve; the values returned to baseline levels on the 18th day of admission. Withdrawal or dose reduction of levodopa in patients with PD has been reported to precipitate NMLS, which is potentially fatal. Because dietary protein can decrease the absorp0tion of levodopa, a potential for an interaction between levodopa and enteral feedings exists, although published reports of such an interaction are limited. In this patient, the likelihood that a drug-nutrient interaction occurred between levodopa and enteral feedings is considered to be probable based on the Naranjo probability scale and the Horn Drug Interaction Probability Scale. Health-care professionals should be aware of the interaction between levodopa and protein content of enteral nutrition to avoid the occurrence of NMLS in patients with PD.

Population Pharmacokinetic and Pharmacodynamic Modeling of Lusutrombopag, a Newly Developed Oral Thrombopoietin Receptor Agonist, in Healthy Subjects.

PubMed

Katsube, Takayuki; Ishibashi, Toru; Kano, Takeshi; Wajima, Toshihiro

2016-11-01

The aim of this study was to develop a population pharmacokinetic (PK)/pharmacodynamic (PD) model for describing plasma lusutrombopag concentrations and platelet response following oral lusutrombopag dosing and for evaluating covariates in the PK/PD profiles. A population PK/PD model was developed using a total of 2539 plasma lusutrombopag concentration data and 1408 platelet count data from 78 healthy adult subjects following oral single and multiple (14-day once-daily) dosing. Covariates in PK and PK/PD models were explored for subject age, body weight, sex, and ethnicity. A three-compartment model with first-order rate and lag time for absorption was selected as a PK model. A three-transit and one-platelet compartment model with a sigmoid E max model for drug effect and feedback of platelet production was selected as the PD model. The PK and PK/PD models well described the plasma lusutrombopag concentrations and the platelet response, respectively. Body weight was a significant covariate in PK. The bioavailability of non-Japanese subjects (White and Black/African American subjects) was 13 % lower than that of Japanese subjects, while the simulated platelet response profiles using the PK/PD model were similar between Japanese and non-Japanese subjects. There were no significant covariates of the tested background data including age, sex, and ethnicity (Japanese or non-Japanese) for the PD sensitivity. A population PK/PD model was developed for lusutrombopag and shown to provide good prediction for the PK/PD profiles. The model could be used as a basic PK/PD model in the drug development of lusutrombopag.

In vivo blockade of the PD-1 pathway using soluble rPD-1-Fc enhances CD4+ and CD8+ T cell responses but has limited clinical benefit

PubMed Central

Amancha, Praveen K.; Hong, Jung Joo; Rogers, Kenneth; Ansari, Aftab A.; Villinger, Francois

2013-01-01

The PD-1/PD-Ligand pathway has been shown to limit cell mediated effector functions during chronic viral infections impeding clearance of pathogens. As a strategy to reverse this exhaustion and increase T cell poly-functionality, PD-1 ligands were blocked in vivo using a recombinant macaque PD1-Fc fusion protein (rPD-1-Fc) in SIVmac239 infected rhesus macaques during the early chronic phase of infection, either alone or in combination with ART. In vitro blockade showed improvement of antigen specific CD4+ and CD8+ T cells from monkeys chronically infected with SIV. Of note, a prolonged 5-day blockade in culture was beneficial for both gag specific CD4+ and CD8+ T cells based on proliferation and dual cytokine production. While the in vivo administration of a recombinant rhesus PD-1 Fc fusion protein (rPD-1-Fc) induced enhanced SIV specific CD4 and CD8 T cell proliferation both in the blood and gut, it failed to alter plasma viremia. However, rPD-1-Fc administration in the context of ART interruption induced a significant delay of viral load rebound. In addition, rPD-1-Fc administration in MamuA*001+ monkeys led to both an increase in the frequencies and Ki67 expression of GagCM9+ CD8+ T cells in the blood and rectal mucosa and poly-functionality of GagCM9+ CD8+ T cells in blood. In conclusion, however, our data suggest that PD-1/PD-Ligand blockade using soluble rPD-1-Fc instead of anti-PD1 Mab, while effective in rescuing the effector function of SIV-specific CD4+ and CD8+ T cells during the early chronic phase of infection, has limited clinical benefit. PMID:24227774

A Mini-Review for Cancer Immunotherapy: Molecular Understanding of PD-1/PD-L1 Pathway & Translational Blockade of Immune Checkpoints

PubMed Central

Li, Yongshu; Li, Fangfei; Jiang, Feng; Lv, Xiaoqing; Zhang, Rongjiang; Lu, Aiping; Zhang, Ge

2016-01-01

Interference of the binding of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) has become a new inspiring immunotherapy for resisting cancers. To date, the FDA has approved two PD-1 monoclonal antibody drugs against cancer as well as a monoclonal antibody for PD-L1. More PD-1 and PD-L1 monoclonal antibody drugs are on their way in clinical trials. In this review, we focused on the mechanism of the PD-1/PD-L1 signaling pathway and the monoclonal antibodies (mAbs) against PD-1 and PD-L1, which were approved by the FDA or are still in clinical trials. And also presented is the prospect of the PD-1/PD-L1 immune checkpoint blockade in the next generation of immunotherapy. PMID:27438833

Rotigotine transdermal patch in Chinese patients with advanced Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study.

PubMed

Zhang, Zhen-Xin; Liu, Chun-Feng; Tao, En-Xiang; Shao, Ming; Liu, Yi-Ming; Wang, Jian; Asgharnejad, Mahnaz; Xue, Hai-Bo; Surmann, Erwin; Bauer, Lars

2017-11-01

Rotigotine was demonstrated to be efficacious and well-tolerated in three placebo-controlled studies (CLEOPATRA-PD/PREFER/SP921) of patients with advanced-stage Parkinson's disease (PD), most of whom were Caucasian. This multicenter phase 3 study (SP1037; NCT01646255) was the first to investigate the efficacy and safety of rotigotine in Chinese patients with advanced-stage PD. Chinese patients with PD, inadequately controlled on levodopa (stable dose ≥200 mg/day), with ≥2.5 h/day "off" time, and Hoehn & Yahr stage 2-4, were randomized 1:1 to receive transdermal rotigotine or placebo, titrated over ≤7 weeks, maintained at optimal/maximum dose (4-16 mg/24 h) for 12 weeks. Primary efficacy variable: mean change in absolute "off" time (according to patient diaries) from baseline to end of maintenance. Safety variables included adverse events (AEs) and discontinuations due to AEs. 346 patients were randomized and 89.9% completed the study (87.8% placebo; 92.0% rotigotine). All were Chinese (58.7% male; mean ± SD age: 62.2 ± 8.9 years; mean ± SD time since PD diagnosis: 6.62 ± 3.70 years). Rotigotine significantly reduced "off" time vs placebo (LS mean [95% CI] treatment difference: -1.20 h/day [-1.83, -0.57]; p = 0.0002), and resulted in more responders (≥30% decrease in "off" time: 36.9% placebo; 48.8% rotigotine; p = 0.0269). AEs were reported for 86 (50.0%) placebo- and 103 (59.2%) rotigotine-treated patients; 15 discontinued due to AEs (placebo 7; rotigotine 8). The most common AEs (≥5%) were dizziness, nausea, pruritus, and dyskinesia. Rotigotine was efficacious in Chinese patients with advanced-stage PD as add-on therapy to levodopa, significantly reducing "off" time vs placebo; the treatment difference was similar to that observed in previous studies of mainly Caucasian patients. Rotigotine was generally well-tolerated and had a similar AE profile to those observed in previous studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies.

PubMed

Tan, Shuguang; Chen, Danqing; Liu, Kefang; He, Mengnan; Song, Hao; Shi, Yi; Liu, Jun; Zhang, Catherine W-H; Qi, Jianxun; Yan, Jinghua; Gao, Shan; Gao, George F

2016-12-01

Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.

Biodegradation of polychlorinated biphenyls (PCBs) by the novel identified cyanobacterium Anabaena PD-1

PubMed Central

Zhang, Hangjun; Jiang, Xiaojun; Lu, Liping; Xiao, Wenfeng

2015-01-01

Polychlorinated biphenyls (PCBs), a class of hazardous pollutants, are difficult to dissipate in the natural environment. In this study, a cyanobacterial strain Anabaena PD-1 showed good resistance against PCB congeners. Compared to a control group, chlorophyll a content decreased 3.7% and 11.7% when Anabaena PD-1 was exposed to 2 and 5 mg/L PCBs for 7 d. This cyanobacterial strain was capable of decomposing PCB congeners which was conclusively proved by determination of chloride ion concentrations in chlorine-free medium. After 7 d, the chloride ion concentrations in PCB-treated groups (1, 2, 5 mg/L) were 3.55, 3.05, and 2.25 mg/L, respectively. The genetic information of strain PD-1 was obtained through 16S rRNA sequencing analysis. The GenBank accession number of 16S rRNA of Anabaena PD-1 was KF201693.1. Phylogenetic tree analysis clearly indicated that Anabaena PD-1 belonged to the genus Anabaena. The degradation half-life of Aroclor 1254 by Anabaena PD-1 was 11.36 d; the total degradation rate for Aroclor 1254 was 84.4% after 25 d. Less chlorinated PCB congeners were more likely to be degraded by Anabaena PD-1 in comparison with highly chlorinated congeners. Meta- and para-chlorines in trichlorodiphenyls and tetrachlorobiphenyls were more susceptible to dechlorination than ortho-chlorines during the PCB-degradation process by Anabaena PD-1. Furthermore, Anabaena PD-1 can decompose dioxin-like PCBs. The percent biodegradation of 12 dioxin-like PCBs by strain PD-1 ranged from 37.4% to 68.4% after 25 days. Results above demonstrate that Anabaena PD-1 is a PCB-degrader with great potential for the in situ bioremediation of PCB-contaminated paddy soils. PMID:26177203

Long-term outcomes of an antimicrobial stewardship program implemented in a hospital with low baseline antibiotic use.

PubMed

Jenkins, Timothy C; Knepper, Bryan C; Shihadeh, Katherine; Haas, Michelle K; Sabel, Allison L; Steele, Andrew W; Wilson, Michael L; Price, Connie S; Burman, William J; Mehler, Philip S

2015-06-01

To evaluate the long-term outcomes of an antimicrobial stewardship program (ASP) implemented in a hospital with low baseline antibiotic use. Quasi-experimental, interrupted time-series study. Public safety net hospital with 525 beds. Implementation of a formal ASP in July 2008. We conducted a time-series analysis to evaluate the impact of the ASP over a 6.25-year period (July 1, 2008-September 30, 2014) while controlling for trends during a 3-year preintervention period (July 1, 2005-June 30, 2008). The primary outcome measures were total antibacterial and antipseudomonal use in days of therapy (DOT) per 1,000 patient-days (PD). Secondary outcomes included antimicrobial costs and resistance, hospital-onset Clostridium difficile infection, and other patient-centered measures. During the preintervention period, total antibacterial and antipseudomonal use were declining (-9.2 and -5.5 DOT/1,000 PD per quarter, respectively). During the stewardship period, both continued to decline, although at lower rates (-3.7 and -2.2 DOT/1,000 PD, respectively), resulting in a slope change of 5.5 DOT/1,000 PD per quarter for total antibacterial use (P=.10) and 3.3 DOT/1,000 PD per quarter for antipseudomonal use (P=.01). Antibiotic expenditures declined markedly during the stewardship period (-$295.42/1,000 PD per quarter, P=.002). There were variable changes in antimicrobial resistance and few apparent changes in C. difficile infection and other patient-centered outcomes. In a hospital with low baseline antibiotic use, implementation of an ASP was associated with sustained reductions in total antibacterial and antipseudomonal use and declining antibiotic expenditures. Common ASP outcome measures have limitations.

Study in Parkinson Disease of Exercise (SPARX): Translating high-intensity exercise from animals to humans

PubMed Central

Moore, Charity G.; Schenkman, Margaret; Kohrt, Wendy M.; Delitto, Anthony; Hall, Deborah A.; Corcos, Daniel

2013-01-01

A burgeoning literature suggests that exercise has a therapeutic benefit in persons with Parkinson disease (PD) and in animal models of PD, especially when animals exercise at high intensity. If exercise is to be prescribed as “first-line” or “add-on” therapy in patients with PD, we must demonstrate its efficacy and dose-response effects through testing phases similar to those used in the testing of pharmacologic agents. The SPARX Trial is a multicenter, randomized, controlled, single-blinded, Phase II study that we designed to test the feasibility of using high-intensity exercise to modify symptoms of PD and to simultaneously test the nonfutility of achieving a prespecified change in patients’ motor scores on the Unified Parkinson Disease Rating Scale (UPDRS). The trial began in May 2102 and is in the process of screening, enrolling, and randomly assigning 126 patients with early-stage PD to 1 of 3 groups: usual care (wait-listed controls), moderate-intensity exercise (4 days/week at 60%–65% maximal heart rate [HRmax]), or high-intensity exercise (4 days/week at 80%–85% HRmax). At 6-month follow-up, the trial is randomly reassigning usual care participants to a moderate-intensity or high-intensity exercise group for the remaining 6 months. The goals of the Phase II trial are to determine if participants can exercise at moderate and high intensities; to determine if either exercise yields benefits consistent with meaningful clinical change (nonfutility); and to document safety and attrition. The advantage of using a non-futility approach allows us to efficiently determine if moderate- or high-intensity exercise warrants further large-scale investigation in PD. PMID:23770108

Conservative management of esophageal perforations during pneumatic dilation for idiopathic esophageal achalasia.

PubMed

Vanuytsel, Tim; Lerut, Toni; Coosemans, Willy; Vanbeckevoort, Dirk; Blondeau, Kathleen; Boeckxstaens, Guy; Tack, Jan

2012-02-01

Esophageal perforation is the most serious adverse event of pneumatic dilation (PD) for achalasia; it is usually managed by surgical repair. We investigated risk factors for esophageal perforation after PD and evaluated safety and long-term outcome of nonsurgical management strategies. We analyzed medical records of patients with achalasia who were treated with PD from 1992-2010 at the University Hospital Gasthuisberg in Leuven, Belgium; all patients with esophageal perforation were contacted to determine long-term outcomes. Achalasia outcomes were assessed by using the Vantrappen criteria. Of 830 PD procedures performed on 372 patients with manometry-confirmed achalasia (57 ± 1 years, 51% male), 16 were complicated by transmural esophageal perforation (4.3% of patients, 1.9% of dilations). Age >65 years was the only significant risk factor for complications (odds ratio, 3.5; 95% confidence interval, 1.2-10.2). All patients were treated conservatively with broad-spectrum antibiotics and nothing by mouth. In 6 patients (38%) the clinical course was further complicated by a pleural effusion, which required a drain in 4 patients. One patient (6%) died of mediastinal hemorrhage within 12 hours after PD. Patients with complications were discharged after 19 ± 2.3 days, compared with 4 ± 0.2 days for those without complications (P < .0001). Long-term outcomes (mean follow-up, 84 ± 14 months) were determined for 12 patients (75%); 11 had excellent or good outcomes (69%), and 1 had a moderate outcome (6%). Age >65 years is a significant risk factor for esophageal perforation after PD. Nonsurgical management of transmural esophageal tears is feasible, with favorable short-term and long-term outcomes, but is not devoid of complications. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study.

PubMed

2005-02-01

Rasagiline (n-propargyl-1[R]-aminoindan) mesylate is a novel irreversible selective monoamine oxidase type B inhibitor, previously demonstrated to improve symptoms in early Parkinson disease (PD). To determine the safety, tolerability, and efficacy of rasagiline in levodopa-treated patients with PD and motor fluctuations. Multicenter, randomized, placebo-controlled, double-blind, parallel-group study. Parkinson disease patients (N = 472) with at least 21/2 hours of daily "off" (poor motor function) time, despite optimized treatment with other anti-PD medications. Rasagiline, 1.0 or 0.5 mg/d, or matching placebo. Change from baseline in total daily off time measured by patients' home diaries during 26 weeks of treatment, percentage of patients completing 26 weeks of treatment, and adverse event frequency. During the treatment period, the mean adjusted total daily off time decreased from baseline by 1.85 hours (29%) in patients treated with 1.0 mg/d of rasagiline, 1.41 hours (23%) with 0.5 mg/d rasagiline, and 0.91 hour (15%) with placebo. Compared with placebo, patients treated with 1.0 mg/d rasagiline had 0.94 hour less off time per day, and patients treated with 0.5 mg/d rasagiline had 0.49 hour less off time per day. Prespecified secondary end points also improved during rasagiline treatment, including scores on an investigator-rated clinical global impression scale and the Unified Parkinson's Disease Rating Scale (activities of daily living in the off state and motor performance in the "on" state). Rasagiline was well tolerated. Rasagiline improves motor fluctuations and PD symptoms in levodopa-treated PD patients. In light of recently reported benefits in patients with early illness, rasagiline is a promising new treatment for PD.

Neonatal alcohol exposure disrupts hippocampal neurogenesis and contextual fear conditioning in adult rats

PubMed Central

Hamilton, G.F.; Murawski, N.J.; St. Cyr, S.A.; Jablonski, S.A.; Schiffino, F.L.; Stanton, M.E.; Klintsova, A.Y.

2011-01-01

Developmental alcohol exposure can permanently alter brain structures and produce functional impairments in many aspects of behavior, including learning and memory. This study evaluates the effect of neonatal alcohol exposure on adult neurogenesis in the dentate gyrus of the hippocampus and the implications of such exposure for hippocampus-dependent contextual fear conditioning. Alcohol-exposed rats (AE) received 5.25 g/kg/day of alcohol on postnatal days (PD) 4-9 (third trimester in humans), in a binge-like manner. Two control groups were included: sham-intubated (SI) and suckle-control (SC). Animals were housed in social cages (3/cage) after weaning. On PD80, animals were injected with 200 mg/kg BrdU. Half of the animals were sacrificed two hours later. The remainder were sacrificed on PD114 to evaluate cell survival; separate AE, SI, and SC rats not injected with BrdU were tested for the context preexposure facilitation effect (CPFE; ∼PD117). There was no difference in the number of BrdU+ cells in AE, SI and SC groups on PD80. On PD114, cell survival was significantly decreased in AE rats, demonstrating that developmental alcohol exposure damages new cells' ability to incorporate into the network and survive. Behaviorally tested SC and SI groups preexposed to the training context 24h prior to receiving a 1.5mA 2s footshock froze significantly more during the context test than their counterparts preexposed to an alternate context. AE rats failed to show the CPFE. The current study shows the detrimental, long-lasting effects of developmental alcohol exposure on hippocampal adult neurogenesis and contextual fear conditioning. PMID:21816390

Long-Term Outcomes of an Antimicrobial Stewardship Program Implemented in a Hospital with Low Baseline Antibiotic Use

PubMed Central

Jenkins, Timothy C.; Knepper, Bryan C.; Shihadeh, Katherine; Haas, Michelle K.; Sabel, Allison L.; Steele, Andrew W.; Wilson, Michael L.; Price, Connie S.; Burman, William J.; Mehler, Philip S.

2016-01-01

Objective To evaluate the long-term outcomes of an antimicrobial stewardship program (ASP) implemented in a hospital with low baseline antibiotic use Design Quasi-experimental, interrupted-time series study Setting 525-bed public safety-net hospital Intervention Implementation of a formal ASP in July 2008 Methods We conducted a time-series analysis to evaluate the impact of the ASP over a 6.25-year period (July 1, 2008 – September 30, 2014) while controlling for trends during a 3-year preintervention period (July 1, 2005 – June 30, 2008). The primary outcome measures were total antibacterial and antipseudomonal use in days of therapy (DOT) per 1000 patient-days (PD). Secondary outcomes included antimicrobial costs and resistance, hospital-onset C. difficile infection, and other patient-centered measures. Results During the preintervention period, total antibacterial and antipseudomonal use were declining (−9.2 and −5.5 DOT/1000 PD per quarter, respectively). During the stewardship period, both continued to decline, although at lower rates (−3.7 and −2.2 DOT/1000 PD, respectively), resulting in a slope change of 5.5 DOT/1000 PD per quarter for total antibacterial use (P = .10) and 3.3 DOT/100 PD per quarter for antipseudomonal use (P = .01). Antibiotic expenditures declined markedly during the stewardship period (−$295.42/1000PD per quarter, p=.002). There were variable changes in antimicrobial resistance and few apparent changes in C. difficile infection and other patient-centered outcomes. Conclusion In a hospital with low baseline antibiotic use, implementation of an ASP was associated with sustained reductions in total antibacterial and antipseudomonal use and declining antibiotic expenditures; however, this study highlights limitations of commonly used stewardship outcome measures. PMID:25740560

Erectile function profiles in men with Peyronie's disease.

PubMed

Deveci, Serkan; Palese, Michael; Parker, Marilyn; Guhring, Patricia; Mulhall, John P

2006-05-01

In this study we investigated the erectile function status of men presenting with Peyronie's disease. Demographics of patients regarding age, duration of PD, nature of deformity and comorbidities were compared between the patients with PD, with and without erectile dysfunction. Patients with erectile dysfunction underwent dynamic infusion cavernosometry/cavernosography. The hemodynamic profile of patients presenting with combined PD and ED were analyzed and compared between those with onset of ED before and after diagnosis of PD. Of the 222 patients 78 had ED (35%) by self-report at presentation. The mean age of patients with PD and ED was 52 +/- 22 years old. Hypertension (71.5%), hyperlipidemia (60.4%) and smoking (49.2%) were the leading comorbidities in the entire group. Statistically significant differences were found between the groups with and without ED for hypertension (p = 0.02) and cigarette smoking (p = 0.009). Of 222 patients 45 (20%) had ED that predated PD onset (group 1) and 33 (15%) had ED that postdated the onset of PD (group 2). DICC showed normal hemodynamics in 14 of 78 patients (18%), arteriogenic insufficiency in 50 (64%) and corporoveno-occlusive dysfunction in 16 (20%). CVOD was evenly distributed between groups 1 and 2, whereas arteriogenic ED was significantly higher in group 1 (82%). Site specific leak was seen in 4 of 33 (12%), all group 2 patients. Patients in whom ED postdates the onset of PD are more likely to have normal erectile hemodynamics. Site specific leak is an uncommon contributor to PD and is seen only in the patients with PD in whom ED postdated PD onset. The leading vascular etiology of ED in PD is arteriogenic in older patients and those with greater associated comorbidities.

Comparison of pedometer and accelerometer derived steps in older individuals with Parkinson's disease or osteoporosis under free-living conditions.

PubMed

Wallén, Martin Benka; Dohrn, Ing-Mari; Ståhle, Agneta; Franzén, Erika; Hagströmer, Maria

2014-10-01

To compare self-reported pedometer steps with accelerometer steps under free-living conditions in individuals with Parkinson's disease (PD) or osteoporosis (OP). Seventy-three individuals with PD and 71 individuals with OP wore a pedometer (Yamax LS2000) and an accelerometer (ActiGraph GT1M/GT3X+) simultaneously for one week. Fifty-one individuals with PD (72.6 ± 5.3 years) and 61 with OP (75.6 ± 5.3 years) provided simultaneously recorded data for 3-7 consecutive days. Pedometer steps were significantly lower than accelerometer steps in the PD group (p = .002) but not in the OP group (p = .956). Bland-Altman plots demonstrated wide limits of agreement between the instruments in both PD (range = 6,911 steps) and OP (range = 6,794 steps). These results suggest that the ActiGraph GT1M/GT3X+ should be preferred over the Yamax LS2000 for the assessment of steps in both research and clinical evaluations, particularly in individuals with PD or altered gait.

Core-shell Au-Pd nanoparticles as cathode catalysts for microbial fuel cell applications

PubMed Central

Yang, Gaixiu; Chen, Dong; Lv, Pengmei; Kong, Xiaoying; Sun, Yongming; Wang, Zhongming; Yuan, Zhenhong; Liu, Hui; Yang, Jun

2016-01-01

Bimetallic nanoparticles with core-shell structures usually display enhanced catalytic properties due to the lattice strain created between the core and shell regions. In this study, we demonstrate the application of bimetallic Au-Pd nanoparticles with an Au core and a thin Pd shell as cathode catalysts in microbial fuel cells, which represent a promising technology for wastewater treatment, while directly generating electrical energy. In specific, in comparison with the hollow structured Pt nanoparticles, a benchmark for the electrocatalysis, the bimetallic core-shell Au-Pd nanoparticles are found to have superior activity and stability for oxygen reduction reaction in a neutral condition due to the strong electronic interaction and lattice strain effect between the Au core and the Pd shell domains. The maximum power density generated in a membraneless single-chamber microbial fuel cell running on wastewater with core-shell Au-Pd as cathode catalysts is ca. 16.0 W m−3 and remains stable over 150 days, clearly illustrating the potential of core-shell nanostructures in the applications of microbial fuel cells. PMID:27734945

Population pharmacokinetic-pharmacodynamic modeling of ketamine-induced pain relief of chronic pain.

PubMed

Dahan, Albert; Olofsen, Erik; Sigtermans, Marnix; Noppers, Ingeborg; Niesters, Marieke; Aarts, Leon; Bauer, Martin; Sarton, Elise

2011-03-01

Pharmacological treatment of chronic (neuropathic) pain is often disappointing. In order to enhance our insight in the complex interaction between analgesic drug and chronic pain relief, we performed a pharmacokinetic-pharmacodynamic (PK-PD) modeling study on the effect of S(+)-ketamine on pain scores in Complex Regional Pain Syndrome type 1 (CRPS-1) patients. Sixty CRPS-1 patients were randomly allocated to received a 100-h infusion of S(+)-ketamine or placebo. The drug infusion rate was slowly increased from 5 mg/h (per 70 kg) to 20 mg/h based upon the effect/side effect profile. Pain scores and drug blood samples were obtained during the treatment phase and pain scores were further obtained weekly for another 11 weeks. A population PK-PD model was developed to analyze the S(+)-ketamine-pain data. Plasma concentrations of S(+)-ketamine and its metabolite decreased rapidly upon the termination of S(+)-ketamine infusion. The chance for an analgesic effect from ketamine and placebo treatment was 67±10% and 23±9% (population value±SE), respectively. The pain data were well described by the PK-PD model with parameters C(50)=10.5±4.8 ng/ml (95% ci 4.37-21.2 ng/ml) and t½ for onset/offset=10.9±4.0 days (5.3-20.5 days). Long-term S(+)-ketamine treatment is effective in causing pain relief in CRPS-1 patients with analgesia outlasting the treatment period by 50 days. These data suggest that ketamine initiated a cascade of events, including desensitization of excitatory receptor systems in the central nervous system, which persisted but slowly abated when ketamine molecules were no longer present. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Plasma GH responses to GHRH, arginine, L-dopa, pyridostigmine, sequential administrations of GHRH and combined administration of PD and GHRH in Turner's syndrome.

PubMed

Hanew, K; Tanaka, A; Utsumi, A

1998-02-01

To investigate GH secretory capacities in patients with Turner's syndrome, GHRH, arginine, L-dopa and pyridostigmine (PD) were administered singly and GHRH was administered sequentially for 3 days. In addition, plasma GH and TSH responses to GHRH and TRH after pretreatment with PD were analyzed to investigate whether the hypothalamic cholinergic somatostatinergic system functioned normally. The maximal GH responses to GHRH, L-dopa and PD were significantly smaller in Turner's syndrome (no.=14) than in normal short children (NSC, no.=14). However, there was no difference in plasma GH responses to arginine between the two groups. In ten patients with Turner's syndrome, the plasma GH response to GHRH did not improve even after the sequential 3-day administrations. Although plasma GH and TSH responses to GHRH and TRH were significantly enhanced by the pretreatment of PD in NSC (no.=12), these responses were not enhanced in Turner's syndrome. Plasma GH response to GHRH in Turner's syndrome with normal body fat was still significantly lower than in NSC. It is therefore concluded that somatotroph sensitivity to GHRH is decreased in Turner's syndrome and that this may be due to the primary defects of the somatotrophs rather than to the increased body fat. In addition, the network of cholinergic-somatostatinergic systems seemed to be impaired in these patients, while the activity of hypothalamic somatostatin neurons was thought to be maintained.

EFFECTS OF THE ORGANOCHLORINE PESTICIDE METHOXYCHLOR ON DOPAMINE METABOLITES AND TRANSPORTERS IN THE MOUSE BRAIN

PubMed Central

Schuh, Rosemary A.; Richardson, Jason R.; Gupta, Rupesh K.; Flaws, Jodi A.; Fiskum, Gary

2009-01-01

Pesticide exposure has been suggested as an increased risk factor in developing Parkinson’s disease (PD). While the molecular mechanism underlying this association is not clear, several studies have demonstrated a role for mitochondrial dysfunction and oxidative damage in PD. Although data on specific pesticides associated with PD are often lacking, several lines of evidence point to the potential involvement of the organochlorine class of pesticides. Previously, we have found that the organochlorine pesticide methoxychlor (mxc) causes mitochondrial dysfunction and oxidative stress in isolated mitochondria. Here, we sought to determine whether mxc-induced mitochondrial dysfunction results in oxidative damage and dysfunction of the dopamine system. Adult female CD1 mice were dosed with either vehicle (sesame oil) or mxc (16, 32, or 64 mg/kg/day) for 20 consecutive days. Following treatment, we observed a dose-related increase in protein carbonyl levels in non-synaptic mitochondria, indicating oxidative modification of mitochondrial proteins which may lead to mitochondrial dysfunction. Mxc exposure also caused a dose-related decrease in striatal levels of dopamine (16–31%), which were accompanied by decreased levels of the dopamine transporter (DAT; 35–48%) and the vesicular monoamine transporter 2 (VMAT2; 21–44%). Because mitochondrial dysfunction, oxidative damage, and decreased levels of DAT and VMAT2 are found in PD patients, our data suggests that mxc should be investigated as a possible candidate involved in the association of pesticides with increased risk for PD, particularly in highly-exposed populations. PMID:19459224

Short-term air pollution exposure aggravates Parkinson’s disease in a population-based cohort

PubMed Central

Lee, Hyewon; Myung, Woojae; Kim, Doh Kwan; Kim, Satbyul Estella; Kim, Clara Tammy; Kim, Ho

2017-01-01

Increasing experimental evidence has suggested air pollution as new risk factor for neurological disease. Although long-term exposure is reportedly related to neurological disease, information on association with short-term exposure is scarce. We examined the association of short-term exposure to particles <2.5 μm (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO) with PD aggravation in Seoul from the National Health Insurance Service–National Sample Cohort, Korea during 2002–2013. PD aggravation cases were defined as emergency hospital admissions for primarily diagnosed PD and analyzed with a case-crossover analysis, designed for rare acute outcomes. Pollutants concentrations on case and control days were compared and effect modifications were explored. A unit increase in 8-day moving average of concentrations was significantly associated with PD aggravation. The association was consistent for PM2.5 (odds ratio [95% confidence interval]: 1.61 [1.14–2.29] per 10 μg/m3), NO2 (2.35 [1.39–3.97] per 10 ppb), SO2 (1.54 [1.11–2.14] per 1 ppb), and CO (1.46 [1.05–2.04] per 0.1 ppm). The associations were stronger in women, patients aged 65–74 years, and cold season, but not significant. In conclusion, short-term air pollution exposure increased risk of PD aggravation, and may cause neurological disease progression in humans. PMID:28300224

Tai Chi for Reducing Dual-task Gait Variability, a Potential Mediator of Fall Risk in Parkinson's Disease: A Pilot Randomized Controlled Trial.

PubMed

Vergara-Diaz, Gloria; Osypiuk, Kamila; Hausdorff, Jeffrey M; Bonato, Paolo; Gow, Brian J; Miranda, Jose Gv; Sudarsky, Lewis R; Tarsy, Daniel; Fox, Michael D; Gardiner, Paula; Thomas, Cathi A; Macklin, Eric A; Wayne, Peter M

2018-01-01

To assess the feasibility and inform design features of a fully powered randomized controlled trial (RCT) evaluating the effects of Tai Chi (TC) in Parkinson's disease (PD) and to select outcomes most responsive to TC assessed during off-medication states. Two-arm, wait-list controlled RCT. Tertiary care hospital. Thirty-two subjects aged 40-75 diagnosed with idiopathic PD within 10 years. Six-month TC intervention added to usual care (UC) versus UC alone. Primary outcomes were feasibility-related (recruitment rate, adherence, and compliance). Change in dual-task (DT) gait stride-time variability (STV) from baseline to 6 months was defined, a priori, as the clinical outcome measure of primary interest. Other outcomes included: PD motor symptom progression (Unified Parkinson's Disease Rating Scale [UPDRS]), PD-related quality of life (PDQ-39), executive function (Trail Making Test), balance confidence (Activity-Specific Balance Confidence Scale, ABC), and Timed Up and Go test (TUG). All clinical assessments were made in the off-state for PD medications. Thirty-two subjects were enrolled into 3 sequential cohorts over 417 days at an average rate of 0.08 subjects per day. Seventy-five percent (12/16) in the TC group vs 94% (15/16) in the UC group completed the primary 6-month follow-up assessment. Mean TC exposure hours overall: 52. No AEs occurred during or as a direct result of TC exercise. Statistically nonsignificant improvements were observed in the TC group at 6 months in DT gait STV (TC [20.1%] vs UC [-0.1%] group [effect size 0.49; P = .47]), ABC, TUG, and PDQ-39. UPDRS progression was modest and very similar in TC and UC groups. Conducting an RCT of TC for PD is feasible, though measures to improve recruitment and adherence rates are needed. DT gait STV is a sensitive and logical outcome for evaluating the combined cognitive-motor effects of TC in PD.

Lichenoid dermatitis in three patients with metastatic melanoma treated with anti-PD-1 therapy.

PubMed

Joseph, Richard W; Cappel, Mark; Goedjen, Brent; Gordon, Matthew; Kirsch, Brandon; Gilstrap, Cheryl; Bagaria, Sanjay; Jambusaria-Pahlajani, Anokhi

2015-01-01

Therapies that activate the immune system through blocking the binding of programmed death ligand 1 (PD-L1) present on tumors and PD-1 (programmed death 1) present on activated immune cells are revolutionizing the care for patients with cancer. These therapies work by inhibiting negative regulators of the immune system, thereby decreasing a tumor's ability to evade the immune system. The side effects of anti-PD-1/PD-L1 therapies are generally mild and as expected are related to autoimmune reactions. Two of the most common side effects of anti-PD-1/PD-L1 therapies are rash and pruritus occurring in approximately 20% of patients. Although the rash is generally recognized to be immune mediated, the exact mechanisms of the rash remain unclear. Herein, we report three cases of lichenoid dermatitis in three patients treated with MK-3475 (anti-PD-1) that were characterized with marked T-cell infiltrates with few PD-1-positive cells. The rashes in all three patients were relatively mild, allowing treatment to continue despite the rashes. ©2014 American Association for Cancer Research.

Green synthesis of Pd NPs from Pimpinella tirupatiensis plant extract and their application in photocatalytic activity dye degradation

NASA Astrophysics Data System (ADS)

Narasaiah, Palajonna; Mandal, Badal Kumar; Sarada, N. C.

2017-11-01

The present report the synthesis of palladium nanoparticles through the green method route offers few advantages over the common chemical and physical procedures, as it is an easy and fast, eco-friendly and does not involve any costly chemicals as well as hazardous chemicals. In this study, we reported synthesis of Pd NPs by using the Pimpinella tirupatiensis plant Extract (PTPE). The synthesized Pd NPs was characterization using different technique such as UV-Visible for the formation of Pd NPs. FT-IR spectroscopy was performed to detect the bio-active molecules liable for reduction and capping of biogenic Pd NPs. Crystallinity of Pd NPs conformed by powder - XRD. In the present study performed photo catalytic activity of synthesized Pd NPs using organic dye such as Congo red (CR). Hence, this study concludes the PTPE aqueous extract produced Pd NPs can be act as promising material for the degradation of organic pollutants.

Effects of gypenosides on anxiety disorders in MPTP-lesioned mouse model of Parkinson's disease.

PubMed

Shin, Keon Sung; Zhao, Ting Ting; Choi, Hyun Sook; Hwang, Bang Yeon; Lee, Chong Kil; Lee, Myung Koo

2014-06-03

Ethanol extract (GP-EX) of Gynostemma pentaphyllum (GP) ameliorates chronic stress-induced anxiety in mice. The present study investigated the effects of gypenoside-enriched components (GPS), GP-EX and water extract of GP (GP-WX) on MPTP lesion-induced affective disorders in C57BL/6 mice. GPS (50mg/kg) and GP-EX (50mg/kg) for 21 day-treatment period improved the symptom of anxiety disorders in the MPTP-lesioned mouse model of PD with or without L-DOPA treatment, which was examined by the elevated plus-maze and marble burying tests. In these states, treatments with GPS (50mg/kg) and GP-EX (50mg/kg) significantly increased the brain levels of dopamine and serotonin in the MPTP-lesioned mouse model of PD with or without l-DOPA treatment. In addition, treatments with GPS (50mg/kg) and GP-EX (50mg/kg) showed protective effects on dopaminergic neurons in MPTP-lesioned mouse model of PD with or without L-DOPA treatment. In contrast, GPS (30 mg/kg) and GP-WX (50mg/kg) showed anxiolytic effects in the same animal models, but it was not significant. These results suggest that GPS (50mg/kg) and GP-EX (50mg/kg) showed anxiolytic effects on affective disorders and protective effects on dopaminergic neurons by modulating the brain levels of dopamine and serotonin in the MPTP-lesioned mouse model of PD with or without l-DOPA treatment. Clinical trials of GPS and GP-EX need to be conducted further so as to develop adjuvant therapeutic agents for PD patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson's disease.

PubMed

Kim, Mia; Cho, Ki-Ho; Shin, Mal-Soon; Lee, Jae-Min; Cho, Han-Sam; Kim, Chang-Ju; Shin, Dong-Hoon; Yang, Hyeon Jeong

2014-04-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of nigral dopaminergic neurons and a reduction in striatal dopaminergic fibers, which result in tremors, rigidity, bradykinesia and gait disturbance. In addition to motor dysfunction, dementia is a widely recognized symptom of patients with PD. Berberine, an isoquinoline alkaloid isolated from Berberis vulgaris L., is known to exert anxiolytic, analgesic, anti-inflammatory, antipsychotic, antidepressant and anti-amnesic effects. In the present study, we investigated the effects of berberine on short-term memory in relation to dopamine depletion and hippocampal neurogenesis using a mouse model of PD, induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P) treatment. Mice in the berberine-treated groups were orally administered berberine once a day for a total of 5 weeks. Our results revealed that the injection of MPTP/P induced dopaminergic neuronal death in the substantia nigra and fiber loss in the striatum. This resulted in impaired motor balance and coordination, as assessed by the beam walking test. We further demonstrated that MPTP/P-induced apoptosis in the hippocampus deteriorated short-term memory, as shown by the step-down avoidance task. By contrast, neurogenesis in the hippocampal dentate gyrus, which is a compensatory adaptive response to excessive apoptosis, was increased upon PD induction. However, treatment with berberine enhanced motor balance and coordination by preventing dopaminergic neuronal damage. Treatment with berberine also improved short-term memory by inhibiting apoptosis in the hippocampus. Berberine demonstrated maximal potency at 50 mg/kg. Based on these data, treatment with berberine may serve as a potential therapeutic strategy for the alleviation of memory impairment and motor dysfunction in patients with PD.

Inhibition of neutral endopeptidase potentiates bronchoconstriction induced by neurokinin A in asthmatic patients.

PubMed

Crimi, N; Palermo, F; Oliveri, R; Polosa, R; Magrì, S; Mistretta, A

1994-02-01

The endogenous tachykinins exhibit a range of properties which may be relevant in the pathophysiology of asthma. Their effects on the airways seem to be modulated by a variety of lung peptidases, including neutral endopeptidase (NEP). In order to evaluate the potential role of endogenous NEP activity in modulating tachykinins-induced bronchoconstriction in man in vivo, six atopic asthmatic patients, with a mean FEV1 value of 3.38 +/- 0.76 l, and a histamine PD20 mean value of 0.024 mg, were studied. The influence of inhaled phosphoramidon (a potent NEP inhibitor) was examined against the NKA-induced bronchospasm in a double-blind, placebo-controlled randomized study. Changes in airway calibre were followed as FEV1 and agonists responsiveness expressed as PD20 and PD15 for histamine and NKA respectively. Patients received nebulized phosphoramidon sodium salt (10(-5) M) or a control solution 10 min prior to the bronchoprovocation test with NKA. No significant difference was noticed between any of the study days and after inhaled phosphoramidon on baseline FEV1 values (3.29 +/- 0.90 l) in comparison with the control solution (3.31 +/- 0.79 l). Inhaled NKA produced a dose-dependent fall in FEV1 values in all the subjects studied with a mean PD15 value of 20.91 x 10(-9) mol. Phosphoramidon administered by inhalation elicited a significant (P < 0.01 vs baseline and control solution) potentiation in the airway responsiveness to inhaled NKA, the NKA PD15 value decreasing to 9.45 x 10(-9) mol. The present study confirms that inhaled NKA induces a dose-related bronchoconstriction in asthmatic patients and demonstrates that inhaled phosphoramidon potentiates NKA-induced bronchoconstriction.

Urate predicts rate of clinical decline in Parkinson disease

PubMed Central

Ascherio, Alberto; LeWitt, Peter A.; Xu, Kui; Eberly, Shirley; Watts, Arthur; Matson, Wayne R.; Marras, Connie; Kieburtz, Karl; Rudolph, Alice; Bogdanov, Mikhail B.; Schwid, Steven R.; Tennis, Marsha; Tanner, Caroline M.; Beal, M. Flint; Lang, Anthony E.; Oakes, David; Fahn, Stanley; Shoulson, Ira; Schwarzschild, Michael A.

2009-01-01

Context The risk of Parkinson disease (PD) and its rate of progression may decline with increasing blood urate, a major antioxidant. Objective To determine whether serum and cerebrospinal fluid (CSF) concentrations of urate predict clinical progression in patients with PD. Design, Setting, and Participants 800 subjects with early PD enrolled in the DATATOP trial. Pre-treatment urate was measured in serum for 774 subjects and in CSF for 713. Main Outcome Measures Treatment-, age- and sex-adjusted hazard ratios (HRs) for clinical disability requiring levodopa therapy, the pre-specified primary endpoint. Results The HR of progressing to endpoint decreased with increasing serum urate (HR for 1 standard deviation increase = 0.82; 95% CI = 0.73 to 0.93). In analyses stratified by α-tocopherol treatment (2,000 IU/day), a decrease in the HR for the primary endpoint was seen only among subjects not treated with α-tocopherol (HR = 0.75; 95% CI = 0.62 to 0.89, versus those treated HR = 0.90; 95% CI = 0.75 to 1.08). Results were similar for the rate of change in the United Parkinson Disease Rating Scale (UPDRS). CSF urate was also inversely related to both the primary endpoint (HR for highest versus lowest quintile = 0.65; 95% CI: 0.54 to 0.96) and to the rate of change in UPDRS. As with serum urate, these associations were present only among subjects not treated with α-tocopherol. Conclusion Higher serum and CSF urate at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate and PD and the rationale for considering CNS urate elevation as a potential strategy to slow PD progression. PMID:19822770

Adolescent nicotine exposure disrupts context conditioning in adulthood in rats.

PubMed

Spaeth, Andrea M; Barnet, Robert C; Hunt, Pamela S; Burk, Joshua A

2010-10-01

Despite the prevalence of smoking among adolescents, few studies have assessed the effects of adolescent nicotine exposure on learning in adulthood. In particular, it remains unclear whether adolescent nicotine exposure has effects on hippocampus-dependent learning that persist into adulthood. The present experiment examined whether there were effects of adolescent nicotine exposure on context conditioning, a form of learning dependent on the integrity of the hippocampus, when tested during adulthood. Rats were exposed to nicotine during adolescence (postnatal days [PD] 28-42) via osmotic minipump (0, 3.0 or 6.0mg/kg/day). Context conditioning occurred in early adulthood (PD 65-70). Animals were exposed to an experimental context and were given 10 unsignaled footshocks or no shock. Additional groups were included to test the effects of adolescent nicotine on delay conditioning, a form of learning that is not dependent upon the hippocampus. Conditioning was assessed using a lick suppression paradigm. For animals in the context conditioning groups, adolescent nicotine resulted in significantly less suppression of drinking in the presence of context cues compared with vehicle-pretreated animals. For animals in the delay conditioning groups, there was a trend for adolescent nicotine (3.0mg/kg/day) to suppress drinking compared to vehicle-pretreated animals. There were no differences in extinction of contextual fear or cued fear between rats previously exposed to vehicle or nicotine. The data indicate that adolescent nicotine administration impairs context conditioning when animals are trained and tested as adults. The present data suggest that adolescent nicotine exposure may disrupt hippocampus-dependent learning when animals are tested during adulthood. (c) 2010 Elsevier Inc. All rights reserved.

Nonsurgical therapy of chronic periodontitis with adjunctive systemic azithromycin or amoxicillin/metronidazole.

PubMed

Jentsch, Holger F R; Buchmann, Andreas; Friedrich, Abel; Eick, Sigrun

2016-09-01

The objective of the present study is to compare the effect of systemic adjunctive use of azithromycin with amoxicillin/metronidazole to scaling and root planing (SRP) in a clinical study. Data from 60 individuals with chronic periodontitis were evaluated after full-mouth SRP. Antibiotics were given from the first day of SRP, in the test group (n = 29), azithromycin for 3 days and, in the control group (n = 31), amoxicillin/metronidazole for7 days. Probing depth (PD), attachment level (AL), and bleeding on probing (BOP) were recorded at baseline and after 3 and 12 months. Gingival crevicular fluid was analyzed for matrix metalloprotease (MMP)-8 and interleukin (IL)-1beta levels. Subgingival plaque was taken for assessment of the major bacteria associated with periodontitis. In both groups, PD, AL, and BOP were significantly reduced (p < 0.001). A few significant differences between the groups were found; AL and BOP were significantly better in the test than in the control group at the end of the study (p = 0.020 and 0.009). Periodontopathogens were reduced most in the test group. A noninferiority of the treatment with azithromycin in comparison with amoxicillin/metronidazole can be stated. The administration of azithromycin could be an alternative to the use of amoxicillin/metronidazole adjunctive to SRP in patients with moderate or severe chronic periodontitis; however, a randomized placebo-controlled multicenter study is needed. Application of azithromycin as a single antibiotic for 3 days might be considered as an additional adjunctive antibiotic to SRP in selected patients.

Semicomprehensive analysis of the postnatal age-related changes in the mRNA expression of sex steroidogenic enzymes and sex steroid receptors in the male rat hippocampus.

PubMed

Kimoto, Tetsuya; Ishii, Hirotaka; Higo, Shimpei; Hojo, Yasushi; Kawato, Suguru

2010-12-01

Although sex steroids play a crucial role in the postnatal brain development, the age-related changes in the hippocampal steroidogenesis remain largely unknown. We performed comprehensive investigations for the mRNA expressions of 26 sex steroidogenic enzymes/proteins and three sex steroid receptors in the male rat hippocampus, at the ages of postnatal day (PD) 1, PD4, PD7, PD10, PD14, 4 wk, and 12 wk (adult), by RT-PCR/Southern blotting analysis. The relative expression levels of these enzymes/receptors at PD1 were Srd5a1 > Star > Ar ∼ Hsd17b4 ∼ Hsd17b1 ∼ Hsd17b7 ∼ Esr1 ∼ Srd5a2 > Hsd17b3 > Esr2 > Cyp11a1 > Cyp17a1 > Cyp19a1 ∼ Hsd17b2 > 3β-hydroxysteroid dehydrogenase I. The mRNA levels of essential enzymes for progesterone/testosterone/estradiol metabolisms (Cyp17a1, Hsd17b7, and Cyp19a1) were approximately constant between PD1 and PD14 and then declined toward the adult levels. Cyp11a1 increased during PD4-PD14 and then considerably decreased toward the adult level (∼8% of PD1). Hsd17b1, Hsd17b2, and 3β-hydroxysteroid dehydrogenase I mRNA decreased approximately monotonously. Hsd17b3 increased to approximately 200% of PD1 during PD4-PD14 and was maintained at this high level. The 5α-reductase mRNA was maintained constant (Srd5a1) or decreased monotonically (Srd5a2) toward the adult level. The Esr1 level peaked at PD4 and decreased toward the adult level, whereas Ar greatly increased during PD1-PD14 and was maintained at this high level. The Star and Hsd17b4 levels were maintained constant from neonate to adult. These results suggest that the hippocampal sex steroidogenic properties are substantially altered during the postnatal development processes, which might contribute to brain sexual maturation.

Impact of a Health Management Program on Healthcare Outcomes among Patients on Augmentation Therapy for Alpha 1-Antitrypsin Deficiency: An Insurance Claims Analysis.

PubMed

Campos, Michael A; Runken, Michael C; Davis, Angela M; Johnson, Michael P; Stone, Glenda A; Buikema, Ami R

2018-04-01

Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder which reduces serum alpha 1-antitrypsin (AAT or alpha1-proteinase inhibitor, A1PI) and increases the risk of chronic obstructive pulmonary disease (COPD). Management strategies include intravenous A1PI augmentation, and, in some cases, a health management program (Prolastin Direct ® ; PD). This study compared clinical and economic outcomes between patients with and without PD program participation. This retrospective study included commercial and Medicare Advantage health insurance plan members with ≥ 1 claim with diagnosis codes for COPD and ≥ 1 medical or pharmacy claim including A1PI (on index date). Outcomes were compared between patients receiving only Prolastin ® or Prolastin ® -C (PD cohort) and patients who received a different brand without PD (Comparator cohort). Demographic and clinical characteristics were captured during 6 months pre-index. Post-index exacerbation episodes and healthcare utilization and costs were compared between cohorts. The study sample comprised 445 patients (n = 213 in PD cohort; n = 232 in Comparator cohort), with a mean age 55.5 years, 50.8% male, and 78.9% commercially insured. The average follow-up was 822 days (2.25 years), and the average time on A1PI was 747 days (2.04 years). Few differences were observed in demographic or clinical characteristics. Adjusting for differences in patient characteristics, the rate of severe exacerbation episodes was reduced by 36.1% in the PD cohort. Adjusted total annual all-cause costs were 11.4% lower, and adjusted mean respiratory-related costs were 10.6% lower in the PD cohort than the Comparator cohort. Annual savings in all-cause total costs in the PD cohort relative to the Comparator cohort was US$25,529 per patient, largely due to significantly fewer and shorter hospitalizations. These results suggest that comprehensive health management services may improve both clinical and economic outcomes among patients with COPD and AATD who receive augmentation therapy. Grifols Shared Services of North America, Inc.

Very early withdrawal from treatment in patients starting peritoneal dialysis

PubMed Central

Luo, Qimei; Xia, Xi; Lin, Zhenchuan; Lin, Jianxiong; Yang, Xiao; Huang, Fengxian; Yu, Xueqing

2018-01-01

Abstract Introduction: Very early withdrawal from treatment in patients undergoing peritoneal dialysis (PD) is an increasingly important, but poorly understood, issue. Here, we identified the reasons and risk factors for very early withdrawal from PD. Methods: Incident PD patients from The First Affiliated Hospital of Sun Yat-sen University above 18 years who started treatment between January 1 2006 and December 31 2011 were included. Cessation of PD therapy within the first 90 days after beginning dialysis was classified as very early withdrawal. Results: Totally 1444 patients were enrolled. Of these, 71 (4.9%) withdrew from PD therapy during the first 90 days. Primary reasons for very early withdrawal included death (34 patients, 47.9%), transplantation (21 patients, 29.6%) and transfer to hemodialysis (14 patients, 19.7%). The leading reasons for death were cardiovascular and infectious disease, accounting for 41.2% (14 patients) and 23.5% (8 patients) of total deaths, respectively. Dialysate leakage (six patients, 42.9%) and catheter dysfunction (five patients, 35.7%) were the main reasons for transfer to hemodialysis. In multivariate analysis, predictors for very early PD withdrawal were older age (per decade increasing; hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.03–1.45; p = .019), higher systolic blood pressure (per 10 mmHg increasing; HR, 1.35; 95% CI, 1.20–1.50; p < .001), lower hemoglobin (per 10 g/l increasing; HR, 0.67; 95% CI, 0.57–0.78; p < .001), lower high-density lipoprotein cholesterol (HR, 0.24; 95% CI, 0.10–0.54; p = .001) and lower residual urine volume (per 100 ml/d increasing; HR, 0.90; 95% CI, 0.84–0.95; p = .001). Conclusions: Death was the primary reason for very early withdrawal from PD. Risk factors for very early withdrawal from PD were older in age, had higher systolic blood pressure, lower hemoglobin, lower high-density lipoprotein cholesterol and lower residual urine volume. PMID:29297246

Identification of Targets for Prevention of Peritoneal Catheter Tunnel and Exit-Site Infections in Low Incidence Settings.

PubMed

Santos, Clara; Pérez-Fontán, Miguel; Rodríguez-Carmona, Ana; Calvo-Rodríguez, María; López-Muñiz, Andrés; López-Calviño, Beatriz; García-Falcón, Teresa

2016-01-01

♦ Peritoneal catheter tunnel and exit-site infection (TESI) complicates the clinical course of peritoneal dialysis (PD) patients. Adherence to recommendations for catheter insertion, exit-site care, and management of Staphylococcus aureus (SAu) carriage reduces, but does not abrogate the risk of these infections. ♦ To reappraise the risk profile for TESI in an experienced center with a long-term focus on management of SAu carriage and a low incidence of these infections. ♦ Following a retrospective, observational design, we investigated 665 patients incident on PD. The main study variable was survival to the first episode of TESI. We considered selected demographic, clinical, and technical variables, applying multivariate strategies of analysis. ♦ The overall incidence of TESI was 1 episode/68.5 patient-months. Staphylococcus aureus carriage disclosed at inception of PD (but not if observed sporadically during follow-up) (hazard ratio [HR] 1.53, p = 0.009), PD started shortly after catheter insertion (HR 0.98 per day, p = 0.011), PD after kidney transplant failure (HR 2.18, p = 0.017), lower hemoglobin levels (HR 0.88 per g/dL, p = 0.013) and fast peritoneal transport rates (HR 2.92, p = 0.03) portended an increased risk of TESI. Delaying PD ≥ 30 days after catheter insertion markedly improved the probability of TESI. Carriage of methicillin-resistant SAu since the start of PD was associated with a high incidence of TESI by these bacteria. On the contrary, resistance to mupirocin did not predict such a risk, probably due to the use of an alternative regime in affected patients. ♦ Adherence to current recommendations results in a low incidence of TESI in PD patients. Interventions on specific risk subsets have a potential to bring incidence close to negligible levels. Despite systematic screening and management, SAu carriage is still a predictor of TESI. Antibiotic susceptibility patterns may help to refine stratification of the risk of TESI by these bacteria. Early insertion of the peritoneal catheter should be considered whenever possible, to reduce the risk of later TESI. Copyright © 2016 International Society for Peritoneal Dialysis.

ROLE OF TUNGSTEN IN THE AQUEOUS PHASE HYDRODEOXYGENATION OF ETHYLENE GLYCOL ON TUNGSTATED ZIRCONIA SUPPORTED PALLADIUM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marin-Flores, Oscar G.; Karim, Ayman M.; Wang, Yong

2014-11-15

The focus of the present work was specifically on the elucidation of the role played by tungsten on the catalytic activity and selectivity of tungstated zirconia supported palladium (Pd-mWZ) for the aqueous phase hydrodeoxygenation (APHDO) of ethylene glycol (EG). Zirconia supported palladium (Pd-mZ) was used as reference. The catalysts were prepared via incipient wet impregnation and characterized using X-ray diffraction (XRD), temperature-programmed reduction (TPR), CO pulse chemisorption, CO-DRIFTS, ammonia temperature-programmed desorption (NH3-TPD) and pyridine adsorption. The presence of W results in larger Pd particles on supported Pd catalysts, i.e., 0.9 and 6.1 nm Pd particles are for Pd-mZ and Pd-mWZ,more » respectively. For comparison purposes, the activity of the catalytic materials used in this work was obtained using a well-defined set of operating conditions. The catalytic activity measurements show that the overall intrinsic activity of Pd particles on mWZ is 1.9 times higher than on mZ. APHDO process appears to be highly favored on Pd-mWZ whereas Pd-mZ exhibits a higher selectivity for reforming. This difference in terms of selectivity seems to be related to the high concentration of Brønsted acid sites and electron-deficient Pd species present on Pd-mWZ.« less

Differential expression of immune-regulatory genes associated with PD-L1 display in melanoma: implications for PD-1 pathway blockade

PubMed Central

Taube, Janis M.; Young, Geoffrey D.; McMiller, Tracee L.; Chen, Shuming; Salas, January T.; Pritchard, Theresa S.; Xu, Haiying; Meeker, Alan K.; Fan, Jinshui; Cheadle, Chris; Berger, Alan E.; Pardoll, Drew M.; Topalian, Suzanne L.

2015-01-01

Purpose Blocking the immunosuppressive PD-1/PD-L1 pathway has anti-tumor activity in multiple cancer types, and PD-L1 expression on tumor cells and infiltrating myeloid cells correlates with the likelihood of response. We previously found that IFNG (interferon-gamma) was over-expressed by TILs in PD-L1+ vs. PD-L1(−) melanomas, creating adaptive immune resistance by promoting PD-L1 display. The current study was undertaken to identify additional factors in the PD-L1+ melanoma microenvironment coordinately contributing to immunosuppression. Experimental design Archived, formalin-fixed paraffin-embedded melanoma specimens were assessed for PD-L1 protein expression at the tumor cell surface with immunohistochemistry (IHC). Whole genome expression analysis, quantitative (q)RT-PCR, immunohistochemistry, and functional in vitro validation studies were employed to assess factors differentially expressed in PD-L1+ versus PD-L1(−) melanomas. Results Functional annotation clustering based on whole genome expression profiling revealed pathways up-regulated in PD-L1+ melanomas, involving immune cell activation, inflammation, and antigen processing and presentation. Analysis by qRT-PCR demonstrated over-expression of functionally related genes in PD-L1+ melanomas, involved in CD8+ T cell activation (CD8A, IFNG, PRF1, CCL5), antigen presentation (CD163, TLR3, CXCL1, LYZ), and immunosuppression [PDCD1 (PD-1), CD274(PD-L1), LAG3, IL10]. Functional studies demonstrated that some factors, including IL-10 and IL-32-gamma, induced PD-L1 expression on monocytes but not tumor cells. Conclusions These studies elucidate the complexity of immune checkpoint regulation in the tumor microenvironment, identifying multiple factors likely contributing to coordinated immunosuppression. These factors may provide tumor escape mechanisms from anti-PD-1/PD-L1 therapy, and should be considered for co-targeting in combinatorial immunomodulation treatment strategies. PMID:25944800

Pharmacokinetic-Pharmacodynamic Modeling of Enrofloxacin Against Escherichia coli in Broilers.

PubMed

Sang, KaNa; Hao, HaiHong; Huang, LingLi; Wang, Xu; Yuan, ZongHui

2015-01-01

The purpose of the present study was to establish a pharmacokinetic/pharmacodynamic (PK/PD) modeling approach for the dosage schedule design and decreasing the emergence of drug-resistant bacteria. The minimal inhibitory concentration (MIC) of 929 Escherichia coli isolates from broilers to enrofloxacin and ciprofloxacin was determined following CLSI guidance. The MIC50 was calculated as the populational PD parameter for enrofloxacin against E. coli in broilers. The 101 E. coli strains with MIC closest to the MIC50 (0.05 μg/mL) were submitted for serotype identification. The 13 E. coli strains with O and K serotype were further utilized for determining pathogencity in mice. Of all the strains tested, the E. coli designated strain Anhui 112 was selected for establishing the disease model and PK/PD study. The PKs of enrofloxacin after oral administration at the dose of 10 mg/kg body weights (BW) in healthy and infected broilers was evaluated with high-performance liquid chromatography (HPLC) method. For intestinal contents after oral administration, the peak concentration (C max), the time when the maximum concentration reached (T max), and the area under the concentration-time curve (AUC) were 21.69-31.69 μg/mL, 1.13-1.23 h, and 228.97-444.86 μg h/mL, respectively. The MIC and minimal bactericidal concentration (MBC) of enrofloxacin against E. coli (Anhui 112) in Mueller-Hinton (MH) broth and intestinal contents were determined to be similar, 0.25 and 0.5 μg/mL respectively. In this study, the sum of concentrations of enrofloxacin and its metabolite (ciprofloxacin) was used for the PK/PD integration and modeling. The ex vivo growth inhibition data were fitted to the sigmoid E max (Hill) equation to provide values for intestinal contents of 24 h area under concentration-time curve/MIC ratios (AUC0-24 h/MIC) producing, bacteriostasis (624.94 h), bactericidal activity (1065.93 h) and bacterial eradication (1343.81 h). PK/PD modeling was established to simulate the efficacy of enrofloxacin for different dosage regimens. By model validation, the protection rate was 83.3%, demonstrating that the dosage regimen of 11.9 mg/kg BW every 24 h during 3 days provided great therapeutic significance. In summary, the purpose of the present study was to first design a dosage regimen for the treatment E. coli in broilers by enrofloxacin using PK/PD integrate model and confirm that this dosage regimen presents less risk for emergence of floroquinolone resistance.

Early-life status epilepticus acutely impacts select quantitative and qualitative features of neonatal vocalization behavior: Spectrographic and temporal characterizations in C57BL/6 mice.

PubMed

Reynolds, Conner D; Nolan, Suzanne O; Huebschman, Jessica L; Hodges, Samantha L; Lugo, Joaquin N

2017-07-01

Early-life seizures are known to cause long-term deficits in social behavior, learning, and memory, however little is known regarding their acute impact. Ultrasonic vocalization (USV) recordings have been developed as a tool for investigating early communicative deficits in mice. Previous investigation from our lab found that postnatal day (PD) 10 seizures cause male-specific suppression of 50-kHz USVs on PD12 in 129 SvEvTac mouse pups. The present study extends these findings by spectrographic characterization of USVs following neonatal seizures. On PD10, male C57BL/6 pups were administered intraperitoneal injections of kainic acid or physiological saline. On PD12, isolation-induced recordings were captured using a broad-spectrum ultrasonic microphone. Status epilepticus significantly suppressed USV quantity (p=0.001) and total duration (p<0.05). Seizure pups also utilized fewer complex calls than controls (p<0.05). There were no changes in call latency or inter-call intervals. Spectrographic analysis revealed increased peak amplitude for complex, downward, short, two-syllable, and upward calls, as well as reduced mean duration for short and two-syllable calls in seizure mice. This investigation provides the first known spectrographic characterization of USVs following early-life seizures. These findings also enhance evidence for USVs as an indicator of select communicative impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduction of morbidity related to emergency access to dialysis with very low protein diet supplemented with ketoacids (VLPD+KA).

PubMed

Duenhas, Marta; Gonçalves, Elsa; Dias, Mônica; Leme, Graziela; Laranja, Sandra

2013-05-01

To delay the beginning of the renal replacement therapy (RRT) until the AV fistula is either made and mature or the training for peritoneal dialysis (PD) is given. Prospective study. Nephrology's Ambulatory, Hospital Servidor Público Estadual. 21 patients with chronic kidney disease (CKD) have been followed. For a period of 30 days, a VLPD+KA would be prescribed until the AV fistula was made or the PD training was given The patients were evaluated prior to the beginning of the VLPD+KA, on the 15th and the 30th day, and at the end of the study, with physical and nutritional evaluation, laboratory tests and 24-hour excretion of urinary urea and urinary protein, creatinine and urea residual clearance. 47.6% (10/21) of the patients have initiated HD with matured and suitable AV fistula made in 30 days; 33.3% (7/21) of the patients have been unfit to initiate RRT, even though with sufficient time for the creation of the AV fistula or the training for PD due to AV fistula thrombosis; 14.3% (3/21) of the patients have remained in the study with no need for dialysis, and 4.8% (1/21) have been excluded on the grounds of not having adhered to the VLPD+KA. The anthropometric parameters and the energy intake have not differed from one period to the other. The VLPD+KA is safe to maintain the nutritional status of patients of CKD until the AV fistula is made or the PD training is given.

High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients

PubMed Central

Mizuno, Masashi; Suzuki, Yasuhiro; Higashide, Keiko; Sei, Yumi; Iguchi, Daiki; Sakata, Fumiko; Horie, Masanobu; Maruyama, Shoichi; Matsuo, Seiichi; Morgan, B. Paul; Ito, Yasuhiko

2017-01-01

Background We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis. Methods We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF. Results When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms. Conclusion Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis. PMID:28046064

Periodontitis-associated septic pulmonary embolism caused by Actinomyces species identified by anaerobic culture of bronchoalveolar lavage fluid: a case report.

PubMed

Endo, Shun; Mishima, Eikan; Takeuchi, Yoichi; Ohi, Takashi; Ishida, Masatsugu; Yanai, Masaru; Kiyomoto, Hideyasu; Nagasawa, Tasuku; Ito, Sadayoshi

2015-12-01

Periodontal disease is a less common but important cause of septic pulmonary embolism (SPE). However, the pathogens causing periodontal disease-associated SPE (PD-SPE) have been poorly understood. Actinomyces species are resident microbiota in the oral cavity. Here we report a case of PD-SPE caused by Actinomyces species, which was identified by anaerobic culture of bronchoalveolar lavage fluid (BAL). A 64-year-old Asian man, complicated with severe chronic periodontitis, was admitted with chest pain and fever. Chest CT revealed multiple bilateral pulmonary nodules located subpleurally. We diagnosed the case as SPE associated with periodontitis. Although blood cultures were negative for the usual 5-day incubation, anaerobic culture of the BAL fluid sample yielded Actinomyces species. Antibacterial therapy alone did not ameliorate the symptoms; however, additional dental treatment, including tooth extraction, promptly did. The patient was discharged 23 days after admission. The 3-month follow-up revealed no recurrence of the symptoms and complete resolution of the lung lesions. This case demonstrated that Actinomyces species can cause PD-SPE. Additionally, clinicians should consider performing appropriate anaerobic culture of BAL fluid to identify the pathogen of SPE, and to ordering dental treatment, if necessary, in addition to antibiotics for the initial management of PD-SPE.

Speech Motor Sequence Learning: Acquisition and Retention in Parkinson Disease and Normal Aging.

PubMed

Whitfield, Jason A; Goberman, Alexander M

2017-06-10

The aim of the current investigation was to examine speech motor sequence learning in neurologically healthy younger adults, neurologically healthy older adults, and individuals with Parkinson disease (PD) over a 2-day period. A sequential nonword repetition task was used to examine learning over 2 days. Participants practiced a sequence of 6 monosyllabic nonwords that was retested following nighttime sleep. The speed and accuracy of the nonword sequence were measured, and learning was inferred by examining performance within and between sessions. Though all groups exhibited comparable improvements of the nonword sequence performance during the initial session, between-session retention of the nonword sequence differed between groups. Younger adult controls exhibited offline gains, characterized by an increase in the speed and accuracy of nonword sequence performance across sessions, whereas older adults exhibited stable between-session performance. Individuals with PD exhibited offline losses, marked by an increase in sequence duration between sessions. The current results demonstrate that both PD and normal aging affect retention of speech motor learning. Furthermore, these data suggest that basal ganglia dysfunction associated with PD may affect the later stages of speech motor learning. Findings from the current investigation are discussed in relation to studies examining consolidation of nonspeech motor learning.

Impact of Percutaneous Drainage on Outcome of Intra-abdominal Infection Associated With Pediatric Perforated Appendicitis.

PubMed

Bonadio, William; Langer, Miriam; Cueva, Julie; Haaland, Astrid

2017-10-01

Perforated appendicitis can result in potentially serious complications requiring prolonged medical care. The optimal approach to successfully managing this condition is controversial. Review of 80 consecutive cases of pediatric acute perforated appendicitis with intra-abdominal infection (IAI) medically managed with parenteral antibiotics and percutaneous drainage (PD) during a 7-year period. All patients received broad spectrum parenteral antibiotic therapy. One-third were hospitalized for >2 weeks. IAI was identified on admission in 60% compared with developing during hospitalization in 40% of cases. Before performing PD, the mean duration of antibiotic therapy in those who developed IAI during hospitalization was 6 days. IAI cultures yielded 127 bacterial isolates; polymicrobial infection occurred in 65% of cases. Only 7% of aspirates were sterile. The most common pathogens were Escherichia coli (82%), of which 5 isolates exhibited extended-spectrum β-lactamase production, and streptococci (40%). At the time of PD, 60% were febrile (mean duration of in-hospital fever, 7.5 days); 67% defervesced within 24 hours after the procedure. Posthospitalization abdominal complications (recurrent IAI or appendicitis) occurred in one-third of patients. Children with perforated appendicitis and IAI often have a complicated and prolonged clinical course. Medical management consisting solely of parenteral antibiotic therapy is frequently ineffective in resolving IAI. Rapid clinical improvement commonly follows PD.

EBV+ and MSI Gastric Cancers Harbor High PD-L1/PD-1 Expression and High CD8+ Intratumoral Lymphocytes

PubMed Central

De Rosa, Simona; Tibiletti, Maria Grazia; Magnoli, Francesca; Vanoli, Alessandro; Sessa, Fausto; Chiaravalli, Anna Maria

2018-01-01

Both EBV+ and MSI gastric cancers (GCs) have high lymphoid infiltration which is rare in MSS/EBV− cancers. PD-L1/PD-1 interaction leads to a down-regulated immune response and it is one of the most promising targets for gastric cancer immunotherapy. PD-L1/PD-1 and CD8 expression were immunohistochemically investigated in a series of 169 FFPE GCs, including 33 EBV+, 59 MSI and 77 MSS/EBV− cases. PD-L1 membrane immunoreactivity in more than 5% of tumor cells was present in 31/169 GCs and was associated with high levels of CD8 intraepithelial lymphocytes (TILs; p < 0.001). PD-L1+ cases were mainly poorly differentiated (71%), intestinal type (85%) and high lymphoid response (HLR; 90%) tumors. PD-L1 expression was only present in EBV⁺ (46%), MSI (24%) and rare MSS/EBV− (3%) GCs with high CD8+ TILs (p < 0.001). Despite being associated with a better prognosis both in the whole series (p < 0.05) and in the MSI subset, PD-L1 is not an independent prognostic factor. PD-L1 gene amplification was detected in 3/17 cases, including 2/7 EBV+ and 1/8 MSI GC. PD-1⁺ TILs were significantly higher in EBV⁺ than MSI and MSS/EBV− cases. PD-L1/PD-1 pathway is selectively activated in HLR GCs and could be considered an emerging therapeutic target, particularly for EBV and MSI GCs. PMID:29614789

Impact of a portal/superior mesenteric vein resection during pancreatico-duodenectomy for pancreatic head adenocarcinoma.

PubMed

Dumitrascu, T; Dima, S; Brasoveanu, V; Stroescu, C; Herlea, V; Moldovan, S; Ionescu, M; Popescu, I

2014-12-01

The impact of venous resection (VR) in pancreatico-dudenectomy (PD) for pancreatic adenocarcinoma (PDAC) is controversial. The aim of the study is to comparatively assess the postoperative outcomes after PD with and without VR for PDAC and to identify predictors of morbidity and survival in the subgroup of PD with VR. The data of 51 PD with VR were compared with those of 183 PD without VR. Binary logistic regression and Cox survival analyses were performed. Both the operative time and estimated blood loss was significantly higher in the VR group (P<0.001). A trend towards an increased 90-day mortality (9.8% vs. 5.5%) and severe morbidity (20% vs. 13%) was observed when a VR was performed (P ≥0.264). The median overall survival time after the PD with and without VR was 13 months and 17 months, respectively (P=0.845). The absence of histological tumor invasion of the VR was found as the only independent predictor for a better survival (HR=0.359; 95% CI 0.161-0.803; P=0.013). A PD with VR can be safely incorporated in a pancreatic surgeon armamentarium. However, the trend towards increased mortality and severe morbidity rates should be expected, along with higher operative time and blood loss, compared with PD without VR. Associated VR does not appear to significantly impair the prognosis after PD for PDAC; however, histological tumor invasion of the VR has a negative impact on the survival.

Glucose-6-phosphate dehydrogenase deficiency (G6PD) as a risk factor of male neonatal sepsis.

PubMed

Rostami-Far, Z; Ghadiri, K; Rostami-Far, M; Shaveisi-Zadeh, F; Amiri, A; Rahimian Zarif, B

2016-01-01

Introduction. Neonatal sepsis is a disease process, which represents the systemic response of bacteria entering the bloodstream during the first 28 days of life. The prevalence of sepsis is higher in male infants than in females, but the exact cause is unknown. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway, which leads to the production of NADPH. NADPH is required for the respiratory burst reaction in white blood cells (WBCs) to destroy microorganisms. The purpose of this study was to evaluate the prevalence of G6PD deficiency in neonates with sepsis. Materials and methods. This study was performed on 76 neonates with sepsis and 1214 normal neonates from February 2012 to November 2014 in the west of Iran. The G6PD deficiency status was determined by fluorescent spot test. WBCs number and neutrophils percentages were measured and compared in patients with and without G6PD deficiency. Results. The prevalence of the G6PD deficiency in neonates with sepsis was significantly higher compared to the control group (p=0.03). WBCs number and neutrophils percentages in G6PD deficient patients compared with patients without G6PD deficiency were decreased, but were not statistically significant (p=0.77 and p=0.86 respectively). Conclusions. G6PD deficiency is a risk factor of neonatal sepsis and also a justification for more male involvement in this disease. Therefore, newborn screening for this disorder is recommended.

Characterization of PD-1 upregulation on tumor-infiltrating lymphocytes in human and murine gliomas and preclinical therapeutic blockade.

PubMed

Dejaegher, Joost; Verschuere, Tina; Vercalsteren, Ellen; Boon, Louis; Cremer, Jonathan; Sciot, Raf; Van Gool, Stefaan W; De Vleeschouwer, Steven

2017-11-01

Blockade of the immune checkpoint molecule programmed-cell-death-protein-1 (PD-1) yielded promising results in several cancers. To understand the therapeutic potential in human gliomas, quantitative data describing the expression of PD-1 are essential. Moreover, due the immune-specialized region of the brain in which gliomas arise, differences between tumor-infiltrating and circulating lymphocytes should be acknowledged. In this study we have used flow cytometry to quantify PD-1 expression on tumor-infiltrating T cells of 25 freshly resected glioma cell suspensions (10 newly and 5 relapsed glioblastoma, 10 lower grade gliomas) and simultaneously isolated circulating T cells. A strong upregulation of PD-1 expression in the tumor microenvironment compared to the blood circulation was seen in all glioma patients. Additionally, circulating T cells were isolated from 15 age-matched healthy volunteers, but no differences in PD-1 expression were found compared to glioma patients. In the murine GL261 malignant glioma model, there was a similar upregulation of PD-1 on brain-infiltrating lymphocytes. Using a monoclonal PD-1 blocking antibody, we found a marked prolonged survival with 55% of mice reaching long-term survival. Analysis of brain-infiltrating cells 21 days after GL261 tumor implantation showed a shift in infiltrating lymphocyte subgroups with increased CD8+ T cells and decreased regulatory T cells. Together, our results suggest an important role of PD-1 in glioma-induced immune escape, and provide translational evidence for the use of PD-1 blocking antibodies in human malignant gliomas. © 2017 UICC.

Major Complications of Pneumatic Dilation and Heller Myotomy for Achalasia: Single Center Experience and Systematic Review of the Literature

PubMed Central

Lynch, Kristle L; Pandolfino, John E; Howden, Colin W; Kahrilas, Peter J

2013-01-01

Background & Aims Pneumatic dilation (PD) and laparoscopic Heller myotomy (LHM) can be definitive therapies for achalasia; recent data suggest comparable efficacy. However, risk must also be considered. We reviewed the major complication rate of PD and LHM in a high volume center and reviewed the corresponding literature. Methods We reviewed 12 years of our institution’s achalasia treatment experience. During this interval a consistent technique of PD was used utilizing Rigiflex dilators. Medical records were reviewed for post-procedure complications. We administered a telephone survey and examined medical records to assess efficacy of treatment. We also performed a systematic review of the literature for comparable clinical data and examined 80 reports encompassing 12,494 LHM and PD procedures. Results At our center, 463 achalasia patients underwent 567 PD or LHM procedures. 78% of the PDs used a 30 mm Rigiflex dilator. 157/184 (85%) patients underwent 1 or 2 PD without any subsequent treatment. There were seven clinically significant perforations; one from PD and 6 from LHM. There were no resultant deaths from these perforations; two deaths occurred within 30 days of LHM from unrelated causes. Complications and deaths post-PD were significantly fewer than those post-LHM (p=.02). Conclusions Esophageal perforation from PD at our high-volume center was less common than often reported and lower than that associated with LHM. We conclude that, in the hands of experienced operators using conservative technique, PD has fewer major complications and deaths than LHM. PMID:23032978

Risk factors of severe peritoneal sclerosis in chronic peritoneal dialysis patients.

PubMed

Alatab, Sudabeh; Najafi, Iraj; Pourmand, Gholamreza; Hosseini, Mostafa; Shekarchian, Soroosh

2017-11-01

Peritoneal dialysis (PD) offers the healthiest way for starting renal replacement therapy (RRT) in End Stage Renal Disease patients, however exposes long-term PD patients to a dangerous complication named encapsulating peritoneal sclerosis (EPS). In this study, we searched for possible risk factors of EPS. Data were collected from two PD centers covering period 1995-2012 and comprised 464 patients. Control group defined as PD patients stayed on PD >42 month (n = 122), and case group was 12 confirmed EPS patients. Associations were analyzed using linear regression analysis. Prevalence and incidence of EPS were 2.59% and 8.9% with an incidence of 0.7% patient-years, respectively. The age at start of PD in EPS patients (32.75 ± 10.8 year) was significantly lower compared with control group (49.61 ± 16.18 year, p = .0001). The mean duration of PD in EPS and control group were 2494.4 ± 940.9 and 1890.2 ± 598.8 days (p = .002). Control group had 145 episodes of peritonitis during total duration of 7686 patient months (peritonitis rate of 1/53). This was 1/26 with a total 38 episodes of peritonitis during the total duration of 997 patient months (p = .01) for EPS group. In regression analysis, PD duration, age at PD start and duration of Ultrafiltration failure (UFF) were associated with EPS. Longer time being on PD, younger age, and higher UFF duration were the risk factors for EPS development.

The Effects of Biocompatible Compared with Standard Peritoneal Dialysis Solutions on Peritonitis Microbiology, Treatment, and Outcomes: the balANZ Trial

PubMed Central

Johnson, David W.; Brown, Fiona G.; Clarke, Margaret; Boudville, Neil; Elias, Tony J.; Foo, Marjorie W.Y.; Jones, Bernard; Kulkarni, Hemant; Langham, Robyn; Ranganathan, Dwarakanathan; Schollum, John; Suranyi, Michael G.; Tan, Seng H.; Voss, David

2012-01-01

♦ Background: A multicenter, multi-country randomized controlled trial (the balANZ study) recently reported that peritonitis rates significantly improved with the use of neutral-pH peritoneal dialysis (PD) solutions low in glucose degradation products (“biocompatible”) compared with standard solutions. The present paper reports a secondary outcome analysis of the balANZ trial with respect to peritonitis microbiology, treatment, and outcomes. ♦ Methods: Adult incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. ♦ Results: The safety population analysis for peritonitis included 91 patients in each group. The unadjusted geometric mean peritonitis rates in those groups were 0.30 [95% confidence interval (CI): 0.22 to 0.41] episodes per patient-year for the biocompatible group and 0.49 (95% CI: 0.39 to 0.62) episodes per patient-year for the control group [incidence rate ratio (IRR): 0.61; 95% CI: 0.41 to 0.90; p = 0.01]. When specific causative organisms were examined, the rates of culture-negative, gram-positive, gram-negative, and polymicrobial peritonitis episodes were not significantly different between the biocompatible and control groups, although the biocompatible group did experience a significantly lower rate of non-pseudomonal gram-negative peritonitis (IRR: 0.41; 95% CI: 0.18 to 0.92; p = 0.03). Initial empiric antibiotic regimens were comparable between the groups. Biocompatible fluid use did not significantly reduce the risk of peritonitis-associated hospitalization (adjusted odds ratio: 0.80; 95% CI: 0.48 to 1.34), but did result in a shorter median duration of peritonitis-associated hospitalization (6 days vs 11 days, p = 0.05). Peritonitis severity was more likely to be rated as mild in the biocompatible group (37% vs 10%, p = 0.001). Overall peritonitis-associated technique failures and peritonitis-related deaths were comparable in the two groups. ♦ Conclusions: Biocompatible PD fluid use was associated with a broad reduction in gram-positive, gram-negative, and culture-negative peritonitis that reached statistical significance for non-pseudomonal gram-negative organisms. Peritonitis hospitalization duration was shorter, and peritonitis severity was more commonly rated as mild in patients receiving biocompatible PD fluids, although other peritonitis outcomes were comparable between the groups. PMID:22991015

Artistic productivity and creative thinking in Parkinson's disease.

PubMed

Canesi, M; Rusconi, M L; Isaias, I U; Pezzoli, G

2012-03-01

Creative drive and enhanced artistic-like production may emerge in patients with Parkinson's disease (PD) during dopaminergic therapy. However, it has not been described to date whether this artistic-like production results from dopaminergic drugs triggering innate skills or it could be considered as a repeated behavior possibly associated with impulse control disorders (ICDs). We investigated creative drive in a cohort of cognitively preserved patients with PD by means of the Torrance Test of Creative Thinking (TTCT). We also investigated a putative association between creative drive and ICDs in 36 PD patients with (PD-c) or without (PD-nc) increased artistic-like production and 36 healthy controls (HC). We considered artistic-like productivity to be enhanced if patients reported working on any form of art more than 2h per day after the introduction of dopaminergic treatment. The TTCT, the Barratt Impulsiveness Scale (BIS-11A), the Minnesota Impulsive Disorders Interview (MIDI), and the Punding Rating Scale were applied. Mean TTCT score of PD-c was found to be similar to HC (169.4±51.6 vs. 170.2±69.7, respectively), and both PD-c and HC had significantly higher TTCT scores than patients with PD-nc (125.4±46.1 P<0.05). TTCT did not correlate with any demographic or clinical data in both PD subgroups. No correlation was found between TTCT, BIS-11A, and MIDI. Our study suggests that newly acquired artistic-like production in patients with PD is not associated with impulsivity or ICDs. Artistic-like production might represent the emerging of innate skills in a subset of predisposed patients with PD on dopaminergic therapy. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

Impaired frontal lobe functions in patients with Parkinson's disease and psychosis.

PubMed

Thota, Naveen; Lenka, Abhishek; George, Lija; Hegde, Shantala; Arumugham, Shyam Sundar; Prasad, Shweta; Stezin, Albert; Kamble, Nitish; Yadav, Ravi; Pal, Pramod Kumar

2017-12-01

Patients with Parkinson's disease (PD) may develop several non-motor symptoms (NMS). Psychosis is one of the debilitating NMS of PD. The neurobiology of psychosis is not fully understood. This study aims to compare the frontal lobe functions of PD patients with and without psychosis using the Frontal Assessment Battery (FAB). This study included 69 patients with PD; 34 with psychosis (PD-P) and 35 without psychosis (PD-NP). Mini Mental Status Examination (MMSE) was used to screen for cognitive impairment. Unified Parkinson's disease Rating scale part-III (UPDRS-III) was used to measure the severity and Hoehn and Yahr score (H&Y) was used to measure the stage of PD. Frontal lobe functions were assessed by FAB. The PD-P and PD-NP groups were comparable for age (58.7±8.4 vs 55.7±8.2, p=0.14), age at onset of symptoms (51.4±8.1 vs 50.0±8.8, p=0.48), gender distribution (men: 88%vs 80%, p=0.51), MMSE (28.2±1.9 vs 28.7±1.2 p=0.12), levodopa equivalent dose/day (736.0±376.3 vs 625.2±332.2, p=0.19), UPDRS-III OFF-score (36.7±8.8 vs 35.4±13.2, p=0.64), UPDRS-III ON-score (13.2±5.4 vs 12.4±6.6, p=0.44) and H&Y stage (2.3±0.3 vs 2.3±0.3, p=0.07). PD-P group had lower total FAB score compared to PD-NP group (13.9±2.2 vs 16.5±1.8, p<0.01). On the FAB, PD-P group had lower scores compared to PD-NP in lexical fluency (FAB-2), programming (FAB-3), sensitivity to interference (FAB-4) and inhibitory control (FAB-5). Patients with PD-P had significant frontal lobe dysfunction compared to PD-NP. FAB may be a simple and useful bedside tool to assess frontal dysfunction in patients with PD in a busy neurological set up. Copyright © 2017 Elsevier B.V. All rights reserved.

GFORCE-PD still going strong in 2016

PubMed Central

Parmar, Malin; Takahashi, Jun; Studer, Lorenz; Barker, Roger A

2017-01-01

In 2014, a new initiative was undertaken by groups working on plans for the transplantation of stem-cell-based derived dopaminergic neurons for treating Parkinson’s disease patients. This GForce-PD group held its annual meeting on 18–19 April 2016 in Chicago at Rush University to discuss their progress and the challenges that the translation of this experimental therapy still faces. Over 2 days, the key issues were discussed around the cell lines that will be used, the differentiation protocols, preclinical testing, GMP-adaptation, and cell manufacturing to allow first in human clinical trials, which are anticipated to start in 2017–2018. GForce-PD members also discussed how they can improve outreach and be of better service to the Parkinson's disease (PD) community and help them to make the best possible decisions when pursuing stem cell treatments.

Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration

PubMed Central

Xiong, Jing; Zhang, Xiaowei; Huang, Jinsha; Chen, Chunnuan; Chen, Zhenzhen; Liu, Ling; Zhang, Guoxin; Yang, Jiaolong; Zhang, Zhentao; Zhang, Zhaohui; Lin, Zhicheng

2017-01-01

Fenpropathrin is one of the widely used pyrethroids in agriculture and household and also reported to have neurotoxic effects in rodent models. In our Parkinson’s disease (PD) clinic, there was a unique patient with a history of daily exposure to fenpropathrin for 6 months prior to developing Parkinsonian symptoms progressively. Since whether fenpropathrin is related to any dopaminergic degeneration was unknown, we aimed in this study to evaluate the neurotoxic effects of fenpropathrin on the dopaminergic system and associated mechanisms in vitro and in vivo. In cultured SH-SY5Y cells, fenpropathrin caused cell death, reactive oxygen species generation, Lewy body-associated proteins aggregation, and Lewy body-like intracytoplasmic inclusions formation. In rodent animals, two different injections of fenpropathrin were used for administrations, intraperitoneal (i.p), or stereotaxical (ST). The rats exhibited lower number of pokes 60 days after first i.p injection, while the rats in ST group showed a significant upregulation of apomorphine-evoked rotations 60 days after first injection. Dcreased tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT2) immunoreactivity, while increased dopamine transporter (DAT) immunoreactivity were observed in rats of either i.p or ST group 60 days after the last exposure to fenpropathrin. However, the number of TH-positive cells in the substantia nigra was more reduced 120 days after the first i.p injection than those of 60 days. Our data demonstrated that exposure to fenpropathrin could mimic the pathologic and pathogenetic features of PD especially in late onset cases. These results imply fenpropathrin as a DA neurotoxin and a possible environmental risk factor for PD. PMID:25575680

Treadmill Exercise Prevents Increase of Neuroinflammation Markers Involved in the Dopaminergic Damage of the 6-OHDA Parkinson's Disease Model.

PubMed

Real, Caroline Cristiano; Garcia, Priscila Crespo; Britto, Luiz R G

2017-09-01

Parkinson's disease (PD) involves loss of dopaminergic neurons in the substantia nigra (SN), which can be correlated to neuroinflammatory changes with the aging of the nervous system. On the other hand, exercise can reduce the deleterious effects promoted by age, but the mechanism involved is still unclear. This study investigated the preventive exercise-induced changes on neuroinflammatory processes in a rat model of PD induced by unilateral striatal injections of 6-hydroxydopamine (6-OHDA). Adult male Wistar rats were divided into two groups: (1) sedentary (SED) or (2) exercised (EX), animals that did treadmill exercise three times per week, every other day, for 4 weeks prior to 6-OHDA or saline injection. The rats were then divided into four sub-groups: (1) sedentary saline (SED), (2) sedentary 6-OHDA (SED + 6-OHDA), (3) exercised saline (EX), and (4) exercised 6-OHDA (EX + 6-OHDA). Seven and 30 days after surgery, brains were collected for immunohistochemistry and immunoblotting for dopaminergic and neuroinflammatory markers into SN and striatum. The SED + 6-OHDA animals presented an increase in the astrocyte, microglial, and oxidative species activation. On the other hand, EX + 6-OHDA animals did not present neuroinflammatory responses and performed better apormorphine test. Our data suggest that treadmill exercise throughout life can markedly reduce the chances of dopamine decrease, reinforcing studies that showed a lower incidence of Parkinson's disease in patients who were active during life.

Treatment of complicated parapneumonic pleural effusion and pleural parapneumonic empyema

PubMed Central

Suárez, Pedro Rodríguez; Gilart, Jorge Freixinet; Pérez, José María Hernández; Serhal, Mohamed Hussein; Artalejo, Antonio López

2012-01-01

Summary Background We performed this observational prospective study to evaluate the results of the application of a diagnostic and therapeutic algorithm for complicated parapneumonic pleural effusion (CPPE) and pleural parapneumonic empyema (PPE). Material/Methods From 2001 to 2007, 210 patients with CPPE and PPE were confirmed through thoracocentesis and treated with pleural drainage tubes (PD), fibrinolytic treatment or surgical intervention (videothoracoscopy and posterolateral thoracotomy). Patients were divided into 3 groups: I (PD); II (PD and fibrinolytic treatment); IIIa (surgery after PD and fibrinolysis), and IIIb (direct surgery). The statistical study was done by variance analysis (ANOVA), χ 2 and Fisher exact test. Results The presence of alcohol or drug consumption, smoking and chronic obstructive pulmonary disease (COPD) were strongly associated with a great necessity for surgical treatment. The IIIa group was associated with increased drainage time, length of stay and complications. No mortality was observed. The selective use of PD and intrapleural fibrinolysis makes surgery unnecessary in more than 75% of cases. Conclusions The selective use of PD and fibrinolysis avoids surgery in more than 75% of cases. However, patients who require surgery have more complications, longer hospital stay, and more days on PD and they are more likely to require admittance to the Intensive Care Unit. PMID:22739734

[Comparative study of two treatment methods for acute periodontal abscess].

PubMed

Jin, Dong-mei; Wang, Wei-qian

2012-10-01

The aim of this short-term study was to compare the clinical efficacy of 2 different methods to treat acute periodontal abscesses. After patient selection, 100 cases of acute periodontal abscess were randomly divided into two groups. The experimental group was treated by supra- and subgingival scaling, while the control group was treated by incision and drainage. A clinical examination was carried out to record the following variables: subjective clinical variables including pain, edema, redness and swelling; objective clinical variables including gingival index(GI), bleeding index(BI), probing depth(PD),suppuration, lymphadenopathy and tooth mobility. The data was analyzed with SPSS 19.0 software package. RESULES: Subjective clinical variables demonstrated statistically significant improvements with both methods from the first day after treatment and lasted for at least 30 days(P<0.05), but the results of experimental group showed much better than the control group 1 day and 7 days after treatment. 30 days after treatment, there was no significant difference between the two groups in pain and swelling improvement(P>0.05), but the experimental group showed more improvement in edema and redness than the control group(P<0.05).On improving objective variables, the experimental group showed significant improvement in GI,BI,PD and suppuration 1 day after treatment(P<0.05).After 7 days, all objective clinical variables in the experimental group improved significantly(P<0.05) in the control group, there were significant improvements in GI,suppuration,lymphadenopathy and tooth mobility(P<0.05) but the four variables of the experimental group showed more improvement than the control group(P<0.05).After 30 days, all objective clinical variables improved significantly in both groups as compared to baseline, but in the experimental group, improvements were more significant regarding to GI,BI,PD,suppuration and tooth mobility(P<0.05). The method of supra- and subgingival scaling was rapid and effective in treatment of acute periodontal abscesses.

Prevalence of Convergence Insufficiency-Type Symptomatology in Parkinson's Disease.

PubMed

Law, Caroline; Chriqui, Estefania; Kergoat, Marie-Jeanne; Leclerc, Bernard-Simon; Panisset, Michel; Irving, Elizabeth L; Postuma, Ronald B; Chouinard, Sylvain; Kergoat, Hélène

2017-09-01

Individuals with Parkinson's disease (PD) often present with visual symptoms (e.g., difficulty in reading, double vision) that can also be found in convergence insufficiency (CI). Our objective was to estimate the prevalence of CI-type visual symptomatology in individuals with PD, in comparison with controls. Participants ≥50 years with (n=300) and without (n=300) PD were recruited. They were administered the Convergence Insufficiency Symptom Survey (CISS-15) over the phone. A score of ≥21 on the CISS-15, considered positive for CI-type symptomatology, served as the cutoff. Data from individuals (n=87 with, n=94 without PD) who were approached but who reported having a known oculovisual condition were analysed separately. Student's t test and chi-square at the 0.05 level were employed for statistical significance. A total of 29.3% of participants with versus 7.3% without PD presented with a score of ≥21 on the CISS-15 (p=0.001). Of the participants having a known oculovisual condition, 39.1% with versus 19.1% without PD presented with a score of ≥21 on the CISS-15 (p=0.01). The prevalence of CI-type visual symptoms is higher in individuals with versus without PD whether or not they have a coexisting oculovisual condition. These results suggest that PD per se places individuals with the disease at greater risk of visual symptomatology. These results further underline the importance of providing regular eye exams for individuals with PD.

Hemolysis and Mediterranean G6PD mutation (c.563 C>T) and c.1311 C>T polymorphism among Palestinians at Gaza Strip.

PubMed

Sirdah, Mahmoud; Reading, N Scott; Perkins, Sherrie L; Shubair, Mohammad; Aboud, Lina; Prchal, Josef T

2012-04-15

The G6PD c.563 C>T deficient mutation is endemic among Mediterranean populations but its clinical significance is not well delineated. We set up to estimate the proportion of G6PD deficient children presenting with hemolytic anemia at Al Nasser Pediatric Hospital at Gaza Strip, Palestine. We then established the prevalence of c.563T Mediterranean mutation and its linkage to c.1311 C>T polymorphism in this population. G6PD deficiency was identified in children presenting with hemolytic anemia at Al Nasser Pediatric Hospital by spectrophotometric measurement of G6PD activity. G6PD exon 6 and exon 11 were amplified from genomic DNA and evaluated for c.563T mutation by sequencing and the c.1311T polymorphism by restriction fragment analysis. Seventy X-chromosomes (60 males and 5 females) from G6PD deficient patients and 40 X-chromosomes from a control group known to be not G6PD deficient were tested. Over 80% of these children presenting with hemolytic anemia were G6PD deficient and 34% of these had the Mediterranean G6PD deficient variant. The allelic frequencies of Mediterranean c.563T and c.1311T polymorphisms among G6PD deficient patients were 0.33 and 0.38 respectively. The c.1311T polymorphism was linked in 95.2% of patients with the Mediterranean mutation, an allele frequency of 0.87, compared to the control non-G6PD deficient group with an allele frequency of 0.18. We conclude that G6PD deficiency accounts for majority of hemolytic anemia encountered in Gaza children treated at Al Nasser Pediatric Hospital Emergency department. The Mediterranean mutation c.563T, while not accounting for a majority of G6PD deficiency, is common among G6PD deficient Gaza Strip Palestinians and is frequently, but not always, linked to the c.1311T polymorphism. This work provides a foundation for the population screening of Palestinians for G6PD deficiency and for investigations of ancestral origin of the Mediterranean variant in world populations. Copyright © 2012 Elsevier Inc. All rights reserved.

Nociceptive Response to L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats.

PubMed

Nascimento, G C; Bariotto-Dos-Santos, K; Leite-Panissi, C R A; Del-Bel, E A; Bortolanza, M

2018-04-02

Non-motor symptoms are increasingly identified to present clinical and diagnostic importance for Parkinson's disease (PD). The multifactorial origin of pain in PD makes this symptom of great complexity. The dopamine precursor, L-DOPA (L-3,4-dihydroxyphenylalanine), the classic therapy for PD, seems to be effective in pain threshold; however, there are no studies correlating L-DOPA-induced dyskinesia (LID) and nociception development in experimental Parkinsonism. Here, we first investigated nociceptive responses in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease to a hind paw-induced persistent inflammation. Further, the effect of L-DOPA on nociception behavior at different times of treatment was investigated. Pain threshold was determined using von Frey and Hot Plate/Tail Flick tests. Dyskinesia was measured by abnormal involuntary movements (AIMs) induced by L-DOPA administration. This data is consistent to show that 6-OHDA-lesioned rats had reduced nociceptive thresholds compared to non-lesioned rats. Additionally, when these rats were exposed to a persistent inflammatory challenge, we observed increased hypernociceptive responses, namely hyperalgesia. L-DOPA treatment alleviated pain responses on days 1 and 7 of treatment, but not on day 15. During that period, we observed an inverse relationship between LID and nociception threshold in these rats, with a high LID rate corresponding to a reduced nociception threshold. Interestingly, pain responses resulting from CFA-induced inflammation were significantly enhanced during established dyskinesia. These data suggest a pro-algesic effect of L-DOPA-induced dyskinesia, which is confirmed by the correlation founded here between AIMs and nociceptive indexes. In conclusion, our results are consistent with the notion that central dopaminergic mechanism is directly involved in nociceptive responses in Parkinsonism condition.

Temporal Dissociation of Striatum and Prefrontal Cortex Uncouples Anhedonia and Defense Behaviors Relevant to Depression in 6-OHDA-Lesioned Rats.

PubMed

Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Takahashi, Reinaldo N; Bertoglio, Leandro J; Cunha, Rodrigo A; Prediger, Rui D

2016-08-01

The dorsolateral striatum (DLS) processes motor and non-motor functions and undergoes extensive dopaminergic degeneration in Parkinson's disease (PD). The nigrostriatal dopaminergic degeneration also affects other brain areas including the pre-frontal cortex (PFC), which has been associated with the appearance of anhedonia and depression at pre-motor phases of PD. Using behavioral, neurochemical, and electrophysiological approaches, we investigated the temporal dissociation between the role of the DLS and PFC in the appearance of anhedonia and defense behaviors relevant to depression in rats submitted to bilateral DLS lesions with 6-hydroxydopamine (6-OHDA; 10 μg/hemisphere). 6-OHDA induced partial dopaminergic nigrostriatal damage with no gross motor impairments. Anhedonic-like behaviors were observed in the splash and sucrose consumption tests only 7 days after 6-OHDA lesion. By contrast, defense behaviors relevant to depression evaluated in the forced swimming test and social withdrawal only emerged 21 days after 6-OHDA lesion when anhedonia was no longer present. These temporally dissociated behavioral alterations were coupled to temporal- and structure-dependent alterations in dopaminergic markers such as dopamine D1 and D2 receptors and dopamine transporter, leading to altered dopamine sensitivity in DLS and PFC circuits, evaluated electrophysiologically. These results provide the first demonstration of a dissociated involvement of the DLS and PFC in anhedonic-like and defense behaviors relevant to depression in 6-OHDA-lesioned rats, which was linked with temporal fluctuations in dopaminergic receptor density, leading to altered dopaminergic system sensitivity in these two brain structures. This sheds new light to the duality between depressive and anhedonic symptoms in PD.

Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats.

PubMed

Glenn, Melissa J; Adams, Raven S; McClurg, Lauren

2012-03-14

Perinatal choline supplementation in rats is neuroprotective against insults such as fetal alcohol exposure, seizures, and advanced age. In the present study we explored whether dietary choline supplementation may also confer protection from psychological challenges, like stress, and act as a natural buffer against stress-linked psychological disorders, like depression. We previously found that choline supplementation increased adult hippocampal neurogenesis, a function compromised by stress, lowered in depression, and boosted by antidepressants; and increased levels of growth factors linked to depression, like brain-derived neurotrophic factor. Together, these were compelling reasons to study the role of choline in depressed mood. To do this, we treated rats with a choline supplemented diet (5 mg/kg choline chloride in AIN76A) prenatally on embryonic days 10-22, on postnatal days (PD) 25-50, or as adults from PD75 onward. Outside of these treatment periods rats were fed a standard diet (1.1 mg/kg choline chloride in AIN76A); control rats consumed only this diet throughout the study. Starting on PD100 rats' anxiety-like responses to an open field, learning in a water maze, and reactivity to forced swimming were assessed. Rats given choline supplementation during pre- or post-natal development, but not adult-treated rats, were less anxious in the open field and less immobile in the forced swim test than control rats. These effects were not mediated by a learning deficit as all groups performed comparably and well in the water maze. Thus, we offer compelling support for the hypothesis that supplemental dietary choline, at least when given during development, may inoculate an individual against stress and major psychological disorders, like depression. Copyright © 2012 Elsevier B.V. All rights reserved.

Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats

PubMed Central

Glenn, Melissa J.; Adams, Raven S.; McClurg, Lauren

2012-01-01

Perinatal choline supplementation in rats is neuroprotective against insults such as fetal alcohol exposure, seizures, and advanced age. In the present study we explored whether dietary choline supplementation may also confer protection from psychological challenges, like stress, and act as a natural buffer against stress-linked psychological disorders, like depression. We previously found that choline supplementation increased adult hippocampal neurogenesis, a function compromised by stress, lowered in depression, and boosted by antidepressants; and increased levels of growth factors linked to depression, like brain-derived neurotrophic factor. Together, these were compelling reasons to study the role of choline in depressed mood. To do this, we treated rats with a choline supplemented diet (5 mg/kg choline chloride in AIN76A) prenatally on embryonic days 10–22, on postnatal days (PD) 25–50, or as adults from PD75 onward. Outside of these treatment periods rats were fed a standard diet (1.1 mg/kg choline chloride in AIN76A); control rats consumed only this diet throughout the study. Starting on PD100 rats’ anxiety-like responses to an open field, learning in a water maze, and reactivity to forced swimming were assessed. Rats given choline supplementation during pre- or post-natal development, but not adult-treated rats, were less anxious in the open field and less immobile in the forced swim test than control rats. These effects were not mediated by a learning deficit as all groups performed comparably and well in the water maze. Thus, we offer compelling support for the hypothesis that supplemental dietary choline, at least when given during development, may inoculate an individual against stress and major psychological disorders, like depression. PMID:22305146

Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis.

PubMed

Ishibashi, Naoya; Watanabe, Tatsuaki; Kanehira, Masahiko; Watanabe, Yui; Hoshikawa, Yasushi; Notsuda, Hirotsugu; Noda, Masafumi; Sakurada, Akira; Ohkouchi, Shinya; Kondo, Takashi; Okada, Yoshinori

2018-03-15

Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.

Chronic prenatal ethanol exposure increases adiposity and disrupts pancreatic morphology in adult guinea pig offspring.

PubMed

Dobson, C C; Mongillo, D L; Brien, D C; Stepita, R; Poklewska-Koziell, M; Winterborn, A; Holloway, A C; Brien, J F; Reynolds, J N

2012-12-17

Ethanol consumption during pregnancy can lead to a range of adverse developmental outcomes in children, termed fetal alcohol spectrum disorder (FASD). Central nervous system injury is a debilitating and widely studied manifestation of chronic prenatal ethanol exposure (CPEE). However, CPEE can also cause structural and functional deficits in metabolic pathways in offspring. This study tested the hypothesis that CPEE increases whole-body adiposity and disrupts pancreatic structure in guinea pig offspring. Pregnant guinea pigs received ethanol (4 g kg(-1) maternal body weight per day) or isocaloric-sucrose/pair-feeding (control) for 5 days per week throughout gestation. Male and female CPEE offspring demonstrated growth restriction at birth, followed by a rapid period of catch-up growth before weaning (postnatal day (PD) 1-7). Whole-body magnetic resonance imaging (MRI) in young adult offspring (PD100-140) revealed increased visceral and subcutaneous adiposity produced by CPEE. At the time of killing (PD150-200), CPEE offspring also had increased pancreatic adipocyte area and decreased β-cell insulin-like immunopositive area, suggesting reduced insulin production and/or secretion from pancreatic islets. CPEE causes increased adiposity and pancreatic dysmorphology in offspring, which may signify increased risk for the development of metabolic syndrome and type 2 diabetes mellitus.

Association Between Early-Onset Parkinson Disease and 22q11.2 Deletion Syndrome

PubMed Central

Butcher, Nancy J.; Kiehl, Tim-Rasmus; Hazrati, Lili-Naz; Chow, Eva W. C.; Rogaeva, Ekaterina; Lang, Anthony E.; Bassett, Anne S.

2015-01-01

IMPORTANCE Clinical case reports of parkinsonism co-occurring with hemizygous 22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk of early-onset Parkinson disease (PD). The frequency of PD and its neuropathological presentation remain unknown in this common genetic condition. OBJECTIVE To evaluate a possible association between 22q11.2 deletions and PD. DESIGN, SETTING, AND PARTICIPANTS An observational study of the occurrence of PD in the world’s largest cohort of well-characterized adults with a molecularly confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range, 18.1–68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain tissue from individuals with 22q11.2DS and a clinical history of PD was investigated for neurodegenerative changes and compared with that from individuals with no history of a movement disorder. MAIN OUTCOMES AND MEASURES A clinical diagnosis of PD made by a neurologist and neuropathological features of PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD compared with standard population estimates (standardized morbidity ratio = 69.7; 95% CI, 19.0–178.5). All cases showed early onset and typical PD symptom pattern, treatment response, and course. All were negative for family history of PD and known pathogenic PD-related mutations. The common use of antipsychotics in patients with 22q11.2DS to manage associated psychiatric symptoms delayed diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical α-synuclein–positive Lewy bodies were present in the expected distribution in 2 cases but absent in another. CONCLUSIONS AND RELEVANCE These findings suggest that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD with variable neuropathological presentation reminiscent of LRRK2-associated PD neuropathology. Individuals with early-onset PD and classic features of 22q11.2DS should be considered for genetic testing, and those with a known 22q11.2 deletion should be monitored for the development of parkinsonian symptoms. Molecular studies of the implicated genes, including DGCR8, may help shed light on the underlying pathophysiology of PD in 22q11.2DS and idiopathic PD. PMID:24018986

Magnetic characteristics of CoPd and FePd antidot arrays on nanoperforated Al2O3 templates

NASA Astrophysics Data System (ADS)

Maximenko, A.; Fedotova, J.; Marszałek, M.; Zarzycki, A.; Zabila, Y.

2016-02-01

Hard magnetic antidot arrays show promising results in context of designing of percolated perpendicular media. In this work the technology of magnetic FePd and CoPd antidot arrays fabrication is presented and correlation between surface morphology, structure and magnetic properties is discussed. CoPd and FePd antidot arrays were fabricated by deposition of Co/Pd and Fe/Pd multilayers (MLs) on porous anodic aluminum oxide templates with bowl-shape cell structure with inclined intercellular regions. FePd ordered L10 structure was obtained by successive vacuum annealing at elevated temperatures (530 °C) and confirmed by XRD analysis. Systematic analysis of magnetization curves evidenced perpendicular magnetic anisotropy of CoPd antidot arrays, while FePd antidot arrays revealed isotropic magnetic anisotropy with increased out-of-plane magnetic contribution. MFM images of antidots showed more complicated contrast, with alternating magnetic dots oriented parallel and antiparallel to tip magnetization moment.

Impact of preindustrial to present-day changes in short-lived pollutant emissions on atmospheric composition and climate forcing

NASA Astrophysics Data System (ADS)

Naik, Vaishali; Horowitz, Larry W.; Fiore, Arlene M.; Ginoux, Paul; Mao, Jingqiu; Aghedo, Adetutu M.; Levy, Hiram

2013-07-01

We describe and evaluate atmospheric chemistry in the newly developed Geophysical Fluid Dynamics Laboratory chemistry-climate model (GFDL AM3) and apply it to investigate the net impact of preindustrial (PI) to present (PD) changes in short-lived pollutant emissions (ozone precursors, sulfur dioxide, and carbonaceous aerosols) and methane concentration on atmospheric composition and climate forcing. The inclusion of online troposphere-stratosphere interactions, gas-aerosol chemistry, and aerosol-cloud interactions (including direct and indirect aerosol radiative effects) in AM3 enables a more complete representation of interactions among short-lived species, and thus their net climate impact, than was considered in previous climate assessments. The base AM3 simulation, driven with observed sea surface temperature (SST) and sea ice cover (SIC) over the period 1981-2007, generally reproduces the observed mean magnitude, spatial distribution, and seasonal cycle of tropospheric ozone and carbon monoxide. The global mean aerosol optical depth in our base simulation is within 5% of satellite measurements over the 1982-2006 time period. We conduct a pair of simulations in which only the short-lived pollutant emissions and methane concentrations are changed from PI (1860) to PD (2000) levels (i.e., SST, SIC, greenhouse gases, and ozone-depleting substances are held at PD levels). From the PI to PD, we find that changes in short-lived pollutant emissions and methane have caused the tropospheric ozone burden to increase by 39% and the global burdens of sulfate, black carbon, and organic carbon to increase by factors of 3, 2.4, and 1.4, respectively. Tropospheric hydroxyl concentration decreases by 7%, showing that increases in OH sinks (methane, carbon monoxide, nonmethane volatile organic compounds, and sulfur dioxide) dominate over sources (ozone and nitrogen oxides) in the model. Combined changes in tropospheric ozone and aerosols cause a net negative top-of-the-atmosphere radiative forcing perturbation (-1.05 W m-2) indicating that the negative forcing (direct plus indirect) from aerosol changes dominates over the positive forcing due to ozone increases, thus masking nearly half of the PI to PD positive forcing from long-lived greenhouse gases globally, consistent with other current generation chemistry-climate models.

Developing A Directional High-Dose Rate (d-HDR) Brachytherapy Source

NASA Astrophysics Data System (ADS)

Heredia, Athena Yvonne

Conventional sources used in brachytherapy provide nearly isotropic or radially symmetric dose distributions. Optimizations of dose distributions have been limited to varied dwell times at specified locations within a given treatment volume, or manipulations in source position for seed implantation techniques. In years past, intensity modulated brachytherapy (IMBT) has been used to reduce the amount of radiation to surrounding sensitive structures in select intracavitary cases by adding space or partial shields. Previous work done by Lin et al., at the University of Wisconsin-Madison, has shown potential improvements in conformality for brachytherapy treatments using a directionally shielded low dose rate (LDR) source for treatments in breast and prostate. Directional brachytherapy sources irradiate approximately half of the radial angles around the source, and adequately shield a quarter of the radial angles on the opposite side, with sharp gradient zones between the treated half and shielded quarter. With internally shielded sources, the radiation can be preferentially emitted in such a way as to reduce toxicities in surrounding critical organs. The objective of this work is to present findings obtained in the development of a new directional high dose rate (d-HDR) source. To this goal, 103Pd (Z = 46) is reintroduced as a potential radionuclide for use in HDR brachytherapy. 103Pd has a low average photon energy (21 keV) and relatively short half -life (17 days), which is why it has historically been used in low dose rate applications and implantation techniques. Pd-103 has a carrier-free specific activity of 75000 Ci/g. Using cyclotron produced 103Pd, near carrier-free specific activities can be achieved, providing suitability for high dose rate applications. The evolution of the d-HDR source using Monte Carlo simulations is presented, along with dosimetric parameters used to fully characterize the source. In addition, a discussion on how to obtain elemental palladium, Pd(0), will be discussed in detail. Directional HDR has the potential to improve upon current treatments, providing better dose conformality to the target volume, while maintaining the benefits of HDR applications.

Czochralski growth of LaPd2Al2 single crystals

NASA Astrophysics Data System (ADS)

Doležal, P.; Rudajevová, A.; Vlášková, K.; Kriegner, D.; Václavová, K.; Prchal, J.; Javorský, P.

2017-10-01

The present study is focused on the preparation of single crystalline LaPd2Al2 by the Czochralski method. Differential scanning calorimetry (DSC) and energy dispersive X-ray spectroscopy (EDX) analyses reveal that LaPd2Al2 is an incongruently melting phase which causes difficulties for the preparation of single crystalline LaPd2Al2 by the Czochralski method. Therefore several non-stoichiometric polycrystalline samples were studied for its preparation. Finally the successful growth of LaPd2Al2 without foreign phases has been achieved by using a non-stoichiometric precursor with atomic composition 22:39:39 (La:Pd:Al). X-ray powder diffraction, EDX analysis and DSC were used for the characterisation. A single crystalline sample was separated from the ingot prepared by the Czochralski method using the non-stoichiometric precursor. The presented procedure for the preparation of pure single phase LaPd2Al2 could be modified for other incongruently melting phases.

The Association of Palmitoylethanolamide with Luteolin Decreases Neuroinflammation and Stimulates Autophagy in Parkinson's Disease Model.

PubMed

Siracusa, Rosalba; Paterniti, Irene; Impellizzeri, Daniela; Cordaro, Marika; Crupi, Rosalia; Navarra, Michele; Cuzzocrea, Salvatore; Esposito, Emanuela

2015-01-01

Parkinson's disease (PD) is a disorder resulted by degeneration of dopaminergic neurons. To counteract the neuroinflammation and oxidative stress of PD, we decided to test a new composite constituted by palmitoylethanolamide (PEA) and luteolin (Lut), in a mass ratio of 10:1, respectively (co-ultraPEALut). In this study the neuroprotective property of the new compound was investigated. For the in vivo model of PD, mice received four injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). Starting 24 h after the first administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we treated animals with co-ultraPEALut daily until 7 days. On day 8, brains were processed for Western blotting and immunohistochemical analysis. Treatment with co-ultraPEALut reduced the specific markers of PD (tyrosine hydroxylase immunopositive), and the increased levels of activated astrocytes and pro-inflammatory cytokines as well as inducible nitric oxide synthase. Further, the possible association of autophagy with the beneficial effects of coultraPEALut. Western blot analysis and immunofluorescence staining showed that co-ultraPEALut administration increased autophagy process. These data were confirmed by an in vitro model, using SH-SY5Y neuroblastoma cells. Western blot analysis showed that co-ultraPEALut pre-treatment maintained high Beclin-1 and p62 expression, while continued to inhibit the p70S6K expression. Altogether, these results put forward that treatment with co-ultraPEALut is able to modulate both the neuroinflammatory process and the autophagic pathway involved in PD, actions which may underlie its neuroprotective effect.

Silibinin attenuates MPP⁺-induced neurotoxicity in the substantia nigra in vivo.

PubMed

Jung, Un Ju; Jeon, Min-Tae; Choi, Myung-Sook; Kim, Sang Ryong

2014-05-01

Parkinson's disease (PD) is characterized by degeneration of the nigrostriatal dopaminergic (DA) pathway. The cause of neuronal death in PD is largely unknown, but it is becoming clear that inflammation plays a significant role in the pathophysiology of PD. Silibinin is a major flavonoid in milk thistle which has an anti-inflammatory activity. We investigated whether silibinin could have neuroprotective effects on DA neurons in the 1-methyl-4-phenylpyridinium ion (MPP(+))-treated animal model of PD in vivo. To address this question, animals received intraperitoneal (i.p.) injections 10, 50, or 100 mg/kg of silibinin, starting 1 day before MPP(+) injection and continued daily until 6 days post-lesion for tyrosine hydroxylase (TH) staining, or until 1 hour prior to the MPP(+) injection to examine the expression levels of inflammatory proteins. Finally, their brains were harvested at the indicated time points for the analyses. Silibinin treatment with 10 mg/kg had no significantly neuroprotective effects in the substantia nigra (SN). However, 50 and 100 mg/kg of silibinin ameliorated the MPP(+)-induced neurotoxicity in the SN in a dose-dependent manner, and the increased levels of inflammatory molecules such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) by MPP(+) treatment were attenuated by treatment with 100 mg/kg of silibinin. These results indicate that silibinin could be a useful and beneficial natural product offering promise for the prevention of DA neuronal degeneration involved in PD.

Memory deficit and reduced anxiety in young adult rats given repeated intermittent MDMA treatment during the periadolescent period.

PubMed

Piper, Brian J; Meyer, Jerrold S

2004-12-01

3,4-Methylenedioxymethamphetamine (MDMA, or "Ecstasy") is a popular recreational drug among adolescents that is often taken primarily on weekends. The goals of this study were to develop a model of the typical intermittent pattern of human MDMA use in periadolescent rats and to determine the behavioral consequences of MDMA exposure in this model. Male Sprague-Dawley rats received s.c. injections of 10 mg/kg of MDMA or saline twice daily with an interdose interval of 4 h. Treatments were given every fifth day from postnatal day (PD) 35 to PD 60. Beginning at PD 65, the animals were tested for open-field activity, object recognition memory, and anxiety-related behaviors in the elevated plus-maze. Brain tissues were collected at PD 70 for determination of radiolabeled paroxetine binding to the serotonin transporter (SERT) in the neocortex and hippocampus. Repeated MDMA administration led to a reduced rate of weight gain that was evident by PD 50. There was no treatment effect on ambulatory behavior in the open-field. However, the MDMA group displayed an impairment of object recognition memory and reduced anxiety as indicated by a twofold increase in open-arm duration in the elevated plus-maze. Only modest decreases in SERT binding were observed, although there was a significant negative correlation between hippocampal SERT levels and open-arm duration within the MDMA group. These findings demonstrate that intermittent MDMA exposure during the adolescent period of development can influence subsequent cognitive and affective functioning in the absence of severe serotonergic damage.

Pyridostigmine bromide versus fludrocortisone in the treatment of orthostatic hypotension in Parkinson's disease - a randomized controlled trial.

PubMed

Schreglmann, S R; Büchele, F; Sommerauer, M; Epprecht, L; Kägi, G; Hägele-Link, S; Götze, O; Zimmerli, L; Waldvogel, D; Baumann, C R

2017-04-01

Evidence for effective treatment options for orthostatic hypotension (OH) in Parkinson's disease (PD) is scarce. Elevation of cholinergic tone with pyridostigmine bromide has been reported as a way to improve blood pressure (bp) regulation in neurogenic hypotension without causing supine hypertension. This was a double-centre, double-blind, randomized, active-control, crossover, phase II non-inferiority trial of pyridostigmine bromide for OH in PD (clinicaltrials.gov NCT01993680). Patients with confirmed OH were randomized to 14 days 3 × 60 mg/day pyridostigmine bromide or 1 × 0.2 mg/day fludrocortisone before crossover. Outcome was measured by peripheral and central bp monitoring during the Schellong manoeuvre and questionnaires. Thirteen participants were enrolled between April 2013 and April 2015 with nine participants completing each trial arm. Repeated measures comparison showed a significant 37% improvement with fludrocortisone for the primary outcome diastolic bp drop on orthostatic challenge (baseline 22.9 ± 13.6 vs. pyridostigmine bromide 22.1 ± 17.0 vs. fludrocortisone 14.0 ± 12.6 mmHg; P = 0.04), whilst pyridostigmine bromide had no effect. Fludrocortisone caused an 11% peripheral systolic supine bp rise (baseline 128.4 ± 12.8 vs. pyridostigmine bromide 130.4 ± 18.3 vs. fludrocortisone 143.2 ± 10.1 mmHg; P = 0.01) but no central mean arterial supine bp rise (baseline 107.2 ± 7.8 vs. pyridostigmine bromide 97.0 ± 12.0 vs. fludrocortisone 107.3 ± 6.3 mmHg; P = 0.047). Subjective OH severity, motor score and quality of life remained unchanged by both study interventions. Pyridostigmine bromide is inferior to fludrocortisone in the treatment of OH in PD. This trial provides first objective evidence of the efficacy of 0.2 mg/day fludrocortisone for OH in PD, causing minor peripheral but no central supine hypertension. In addition to peripheral bp, future trials should include central bp measurements, known to correlate more closely with cardiovascular risk. © 2017 EAN.

The effects of perinatal choline supplementation on hippocampal cholinergic development in rats exposed to alcohol during the brain growth spurt.

PubMed

Monk, Bradley R; Leslie, Frances M; Thomas, Jennifer D

2012-08-01

Prenatal alcohol exposure leads to long-lasting cognitive and attention deficits, as well as hyperactivity. Using a rat model, we have previously shown that perinatal supplementation with the essential nutrient, choline, can reduce the severity of some fetal alcohol effects, including hyperactivity and deficits in learning and memory. In fact, choline can mitigate alcohol-related learning deficits even when administered after developmental alcohol exposure, during the postnatal period. However, it is not yet known how choline is able to mitigate alcohol-related behavioral alterations. Choline may act by altering cholinergic signaling in the hippocampus. This study examined the effects of developmental alcohol exposure and perinatal choline supplementation on hippocampal M(1) and M(2/4) muscarinic receptors. Sprague-Dawley rat pups were orally intubated with ethanol (5.25 mg/kg/day) from postnatal days (PD) 4-9, a period of brain development equivalent to the human third trimester; control subjects received sham intubations. From PD 4-30, subjects were injected s.c. with choline chloride (100 mg/kg/day) or saline vehicle. Open field activity was assessed from PD 30 through 33, and brain tissue was collected on PD 35 for autoradiographic analysis. Ethanol-exposed subjects were more active compared to controls during the first 2 days of testing, an effect attenuated with choline supplementation. Developmental alcohol exposure significantly decreased the density of muscarinic M(1) receptors in the dorsal hippocampus, an effect that was not altered by choline supplementation. In contrast, developmental alcohol exposure significantly increased M(2/4) receptor density, an effect mitigated by choline supplementation. In fact, M(2/4) receptor density of subjects exposed to alcohol and treated with choline did not differ significantly from that of controls. These data suggest that developmental alcohol exposure can cause long-lasting changes in the hippocampal cholinergic system and that perinatal choline supplementation may attenuate alcohol-related behavioral changes by influencing cholinergic systems. Copyright © 2012 Wiley Periodicals, Inc.

The Effects of Perinatal Choline Supplementation on Hippocampal Cholinergic Development in Rats Exposed to Alcohol During the Brain Growth Spurt

PubMed Central

Monk, Bradley R.; Leslie, Frances M.; Thomas, Jennifer D.

2012-01-01

Prenatal alcohol exposure leads to long-lasting cognitive and attention deficits, as well as hyperactivity. Using a rat model, we have previously shown that perinatal supplementation with the essential nutrient, choline, can reduce the severity of some fetal alcohol effects, including hyperactivity and deficits in learning and memory. In fact, choline can mitigate alcohol-related learning deficits even when administered after developmental alcohol exposure, during the postnatal period. However, it is not yet known how choline is able to mitigate alcohol-related behavioral alterations. Choline may act by altering cholinergic signaling in the hippocampus. This study examined the effects of developmental alcohol exposure and perinatal choline supplementation on hippocampal M1 and M2/4 muscarinic receptors. Sprague-Dawley rat pups were orally intubated with ethanol (5.25 mg/kg/day) from postnatal days (PD) 4-9, a period of brain development equivalent to the human 3rd trimester; control subjects received sham intubations. From PD 4-30, subjects were injected s.c. with choline chloride (100 mg/kg/day) or saline vehicle. Open field activity was assessed from PD 30-33 and brain tissue was collected on PD 35 for autoradiographic analysis. Ethanol-exposed subjects were more active compared to controls during the first two days of testing, an effect attenuated with choline supplementation. Developmental alcohol exposure significantly decreased the density of muscarinic M1 receptors in the dorsal hippocampus, an effect that was not altered by choline supplementation. In contrast, developmental alcohol exposure significantly increased M2/4 receptor density, an effect mitigated by choline supplementation. In fact, M2/4 receptor density of subjects exposed to alcohol and treated with choline did not differ significantly from that of controls. These data suggest that developmental alcohol exposure can cause long-lasting changes in the hippocampal cholinergic system and that perinatal choline supplementation may attenuate alcohol-related behavioral changes by influencing cholinergic systems. PMID:22431326

Neonatal nucleated red blood cells in G6PD deficiency.

PubMed

Yeruchimovich, Mark; Shapira, Boris; Mimouni, Francis B; Dollberg, Shaul

2002-05-01

The objective of this study is to study the absolute number of nucleated red blood cells (RBC) at birth, an index of active fetal erythropoiesis, in infants with G6PD deficiency and in controls. We tested the hypothesis that hematocrit and hemoglobin would be lower, and absolute nucleated RBC counts higher, in the G6PD deficient and that these changes would be more prominent in infants exposed passively to fava bean through maternal diet. Thirty-two term infants with G6PD deficiency were compared with 30 term controls. Complete blood counts with manual differential counts were obtained within 12 hours of life. Absolute nucleated RBC and corrected leukocyte counts were computed from the Coulter results and the differential count. G6PD deficient patients did not differ from controls in terms of gestational age, birth weight, or Apgar scores or in any of the hematologic parameters studied, whether or not the mother reported fava beans consumption in the days prior to delivery. Although intrauterine hemolysis is possible in G6PD deficient fetuses exposed passively to fava beans, our study supports that such events must be very rare.

KSC-05PD-0209

NASA Technical Reports Server (NTRS)

2005-01-01

KENNEDY SPACE CENTER, FLA. At the 1st Space Exploration Conference: Continuing the Voyage of Discovery, being held at Disneys Contemporary Resort in Orlando, the NASA Explorer School team from McNair High School in Dekalb County, Ga., receives the Space Exploration Video Festival award sponsored by Lockheed Martin. Standing with the awards are Trenten Nash, Theo Maxie and Daniel Jackson. Presenting the awards were John Karas (left), with Lockheed, and Adm. Craig Steidle (right), associate administrator, Office of Exploration Systems at NASA. The three- day conference drew attendees from around the world. It presented topics on new missions, technologies and infrastructure needed to turn the vision for space exploration into reality. Keynote speakers at the three-day conference include NASA Administrator Sean O'Keefe, Congressman Dave Weldon, film director James Cameron and NASAs senior Mars scientist James Garvin. The conference has drawn attendees from around the world.

First determination of the levels of platinum group metals in Manta birostris (manta ray) caught along the Ghanaian coastline.

PubMed

Essumang, D K

2010-06-01

Tissues from Manta birostris caught by fishermen from Dixcove in the western part of Ghana were analyzed for their Platinum, palladium and rhodium concentrations (PGM). The use of chondrichthyan fish has permitted the study of trace levels of Platinum group metals (PGMs) which have travelled very far into the sea. The analysis showed that Ghana's coastline is fairly polluted with these platinum group metals (PGMs). PGM concentration in manta ray recorded a range of (0.15-0.85) microg/g for Pt, (0.033-0.67) microg/g for Pd and (0.007-0.145) microg/g for Rh. Comparing these values to the UK dietary intake of 0.2 microg/day for Pt and Rh and 1.0 microg/day for Pd, its indicates that the values obtained from the analysis for Pt was above the required level. This is the first study to show the accumulation of PGM in chondrichthyan fish, although the sources of this pollution are not clear as manta birostris is migratory and therefore need to be investigated further. The presence of the PGM is very significant, since manta ray meat is consumed in Ghana. This may presents a health risk, due to a possible accumulation of PGMs in humans.

Early oral feeding after pancreatoduodenectomy enhances recovery without increasing morbidity

PubMed Central

Gerritsen, Arja; Wennink, Roos A W; Besselink, Marc G H; van Santvoort, Hjalmar C; Tseng, Dorine S J; Steenhagen, Elles; Borel Rinkes, Inne H M; Molenaar, I Quintus

2014-01-01

Objective The aim of this study was to evaluate whether a change in the routine feeding strategy applied after pancreatoduodenectomy (PD) from nasojejunal tube (NJT) feeding to early oral feeding improved clinical outcomes. Methods An observational cohort study was performed in 102 consecutive patients undergoing PD. In period 1 (n = 51, historical controls), the routine postoperative feeding strategy was NJT feeding. This was changed to a protocol of early oral feeding with on-demand NJT feeding in period 2 (n = 51, consecutive prospective cohort). The primary outcome was time to resumption of adequate oral intake. Results The baseline characteristics of study subjects in both periods were comparable. In period 1, 98% (n = 50) of patients received NJT feeding, whereas in period 2, 53% (n = 27) of patients did so [for delayed gastric empting (DGE) (n = 20) or preoperative malnutrition (n = 7)]. The time to resumption of adequate oral intake significantly decreased from 12 days in period 1 to 9 days in period 2 (P = 0.015), and the length of hospital stay shortened from 18 days in period 1 to 13 days in period 2 (P = 0.015). Overall, there were no differences in the incidences of complications of Clavien–Dindo Grade III or higher, DGE, pancreatic fistula, postoperative haemorrhage and mortality between the two periods. Conclusions The introduction of an early oral feeding strategy after PD reduced the time to resumption of adequate oral intake and length of hospital stay without negatively impacting postoperative morbidity. PMID:24308458

Efficacy of rasagiline for the treatment of Parkinson's disease: an updated meta-analysis.

PubMed

Chang, Ying; Wang, Li-Bo; Li, Dan; Lei, Ke; Liu, Song-Yan

2017-08-01

Rasagiline is a second-generation potent selective inhibitor of monoamine oxidase-B. The aim of the study was to analyze the effectiveness of rasagiline in treatment of Parkinson's disease (PD), both as monotherapy and combination therapy. Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 9 March 2016 using the keywords: Rasagiline, Azilect, Parkinson's disease. Randomized controlled trials of patients with PD who were randomized to treatment with rasagiline or placebo were included. Outcomes were unified Parkinson's disease rating scale (UPDRS) and the three subscales. Ten studies fulfilled the inclusion criteria and 2709 patients were evaluated. The overall analysis revealed a significant improvement in change of total UPDRS scores in 1 mg/day and 2 mg/day rasagiline groups compared to placebo. Significant improvement in Part I (Mentation) of UPDRS scores was observed in 1 mg/day, but not in 2 mg/day rasagiline treatment group. Part II (ADL) and Part III (Motor) subscales significantly improved with both doses of rasagiline. Both monotherapy and combination therapy significantly improved total UPDRS scores. Our results confirm the efficacy of rasagiline in PD. Further studies are required to establish the optimal dose of rasagiline, as well as to determine its effectiveness in different combination therapy protocols. KEY MESSAGES Rasagiline treatment was associated with significant improvement of UPDRS scores and the scores of the subscales. Both monotherapy and combination therapy significantly improved total UPDRS scores. Effect of rasagiline on total UPDRS scores was not dose-dependent.

KSC-04PD-1866

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. After his presentation in the Training Auditorium, astronaut Mike Foale greets employees and signs autographs. Foale shared his experiences aboard the International Space Station as commander of the Expedition 8 crew. Foale and Flight Engineer Alexander Kaleri spent 194 days, 18 hours and 35 minutes in space, the second longest expedition to be completed aboard the Station. In February Foale and Kaleri conducted the first spacewalk ever performed from the complex by a two-person crew. Foale has accumulated more time in space than any U.S. astronaut, amassing a total of 374 days, 11 hours and 19 minutes in space from his Expedition 8 mission, a 1997 flight to the Russian Mir Space Station, and four Space Shuttle missions.

KSC-04PD-1867

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. After his presentation in the Training Auditorium, astronaut Mike Foale greets employees and signs autographs. Foale shared his experiences aboard the International Space Station as commander of the Expedition 8 crew. Foale and Flight Engineer Alexander Kaleri spent 194 days, 18 hours and 35 minutes in space, the second longest expedition to be completed aboard the Station. In February Foale and Kaleri conducted the first spacewalk ever performed from the complex by a two-person crew. Foale has accumulated more time in space than any U.S. astronaut, amassing a total of 374 days, 11 hours and 19 minutes in space from his Expedition 8 mission, a 1997 flight to the Russian Mir Space Station, and four Space Shuttle missions.

KSC-04PD-1862

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. In the Training Auditorium, Center Director Jim Kennedy presents a framed photo to astronaut Mike Foale, who spoke to the audience about his experiences aboard the International Space Station as commander of the Expedition 8 crew. Foale and Flight Engineer Alexander Kaleri spent 194 days, 18 hours and 35 minutes in space, the second longest expedition to be completed aboard the Station. In February Foale and Kaleri conducted the first spacewalk ever performed from the complex by a two-person crew. Foale has accumulated more time in space than any U.S. astronaut, amassing a total of 374 days, 11 hours and 19 minutes in space from his Expedition 8 mission, a 1997 flight to the Russian Mir Space Station, and four Space Shuttle missions.

Solid-state synthesis, structural and magnetic properties of CoPd films

NASA Astrophysics Data System (ADS)

Myagkov, V. G.; Bykova, L. E.; Zhigalov, V. S.; Tambasov, I. A.; Bondarenko, G. N.; Matsynin, A. A.; Rybakova, A. N.

2015-05-01

The results of the investigation of the structural and magnetic properties of CoPd films with equiatomic composition have been presented. The films have been synthesized by vacuum annealing of polycrystalline Pd/Co and epitaxial Pd/α-Co(110) and Pd/β-Co(001) bilayer samples. It has been shown that, for all samples, the annealing to 400°C does not lead to the mixing of layers and the formation of compounds. A further increase in the annealing temperature results in the formation of a disordered CoPd phase at the Pd/Co interface, which is fully completed after annealing at 650°C. The epitaxial relationships between the disordered CoPd phase and the MgO(001) substrate are determined as follows: CoPd(110)<

Effect of virtual reality training on walking distance and physical fitness in individuals with Parkinson's disease.

PubMed

de Melo, Gileno Edu Lameira; Kleiner, Ana Francisca Rozin; Lopes, Jamile Benite Palma; Dumont, Arislander Jonathan Lopes; Lazzari, Roberta Delasta; Galli, Manuela; Oliveira, Claudia Santos

2018-04-07

To evaluate the effects of gait training with virtual reality (VR) on walking distance and physical fitness in individuals with Parkinson's Disease (PD). Thirty-seven individuals with PD participated in this prospective, randomized, controlled clinical trial. They were randomly allocated to a control group submitted to conventional training (n = 12), a treadmill group submitted to gait training on a treadmill (n = 13) and a VR group submitted to gait training using the XboxTM (n = 12). Clinical measures, gait variables and the Six-Minute Walk Test (6MWT) were evaluated: pre-intervention, after one intervention session, post-intervention and follow up (30 days after intervention). The VR and treadmill groups travelled longer distances on the 6MWT and had faster gait speed in comparison to the control group. The VR and treadmill groups demonstrated an increase in pre-6MWT HR. The VR group had more intense HR after the first session and throughout training, but these gains were not maintained at the follow-up. The present findings demonstrate that gait training with a VR program is as effective as treadmill training with regard to gains in walking distance and improvements in temporal gait variables in individuals with PD.

Kinesthetic but not visual imagery assists in normalizing the CNV in Parkinson's disease.

PubMed

Lim, Vanessa K; Polych, Melody A; Holländer, Antje; Byblow, Winston D; Kirk, Ian J; Hamm, Jeff P

2006-10-01

This study investigated whether kinesthetic and/or visual imagery could alter the contingent negative variation (CNV) for patients with Parkinson's disease (PD). The CNV was recorded in six patients with PD and seven controls before and after a 10min block of imagery. There were two types of imagery employed: kinesthetic and visual, which were evaluated on separate days. The global field power (GFP) of the late CNV did not change after the visual imagery for either group, nor was there a significant difference between the groups. In contrast, kinesthetic imagery resulted in significant group differences pre-, versus post-imagery GFPs, which was not present prior to performing the kinesthetic imagery task. In patients with PD, the CNV amplitudes post-, relative to pre-kinesthetic imagery, increased over the dorsolateral prefrontal regions and decreased in the ipsilateral parietal regions. There were no such changes in controls. A 10-min session of kinesthetic imagery enhanced the GFP amplitude of the late CNV for patients but not for controls. While the study needs to be replicated with a greater number of participants, the results suggest that kinesthetic imagery may be a promising tool for investigations into motor changes, and may potentially be employed therapeutically, in patients with Parkinson's disease.

Preserved serotonin transporter binding in de novo Parkinson's disease: negative correlation with the dopamine transporter.

PubMed

Strecker, Karl; Wegner, Florian; Hesse, Swen; Becker, Georg-Alexander; Patt, Marianne; Meyer, Philipp M; Lobsien, Donald; Schwarz, Johannes; Sabri, Osama

2011-01-01

Recent imaging and neuropathological studies indicate reduced serotonin transporter (SERT) in advanced Parkinson's disease (PD). However, data on SERT in early PD patients are sparse. Following the hypothesis that the serotonergic system is damaged early in PD, the aim of our study was to investigate SERT availability by means of PET imaging. Since the loss of dopaminergic neurons is the pathologic hallmark of PD and SERT might be associated with psychiatric co-morbidity, we further sought to correlate SERT availability with the availability of dopamine transporter (DAT) and depressive or motor symptoms in early PD. We prospectively recruited nine early PD patients (4 female, 5 male; 42-76 years) and nine age matched healthy volunteers (5 female, 4 male; 42-72 years). Diagnosis of PD was confirmed by the UK brain bank criteria and DAT imaging. SERT availability was measured by means of [11C]DASB PET. For neuropsychiatric assessment done on the day of PET we applied UPDRS parts I, II and III, Beck's Depression Inventory, Hamilton Rating Scale for Depression, Mini-Mental State Examination and Demtect. SERT was not reduced in any of 14 investigated regions of interest in the nine PD patients compared to healthy controls (p>0.13). SERT was negatively associated with DAT in the striatum (r=-0.69; p=0.04) but not within the midbrain. There was no correlation of SERT availability with depressive symptoms. No alteration of SERT binding in our patients suggests that the serotonergic system is remarkably preserved in early PD. Correlation with DAT might point to a compensatory regulation of the serotonergic system in early stages of PD.

Maternal exposure to silver nanoparticles are associated with behavioral abnormalities in adulthood: Role of mitochondria and innate immunity in developmental toxicity.

PubMed

Amiri, Shayan; Yousefi-Ahmadipour, Aliakbar; Hosseini, Mir-Jamal; Haj-Mirzaian, Arya; Momeny, Majid; Hosseini-Chegeni, Heshmat; Mokhtari, Tahmineh; Kharrazi, Sharmin; Hassanzadeh, Gholamreza; Amini, Seyed Mohammad; Jafarinejad, Somayeh; Ghazi-Khansari, Mahmoud

2018-05-01

Silver nanoparticles (Ag-NPs) are currently used in a wide range of consumer products. Considering the small size of Ag-NPs, they are able to pass through variety of biological barriers and exert their effects. In this regard, the unique physicochemical properties of Ag-NPs along with its high application in the industry have raised concerns about their negative effects on human health. Therefore, it investigated whether prenatal exposure to low doses of Ag-NPs is able to induce any abnormality in the cognitive and behavioral performance of adult offspring. We gavaged pregnant NMRI mice with, 1) Deionized water as vehicle, 2) Ag-NPs 10 nm (0.26 mg/kg/day), 3) Ag-NPs 30 nm (0.26 mg/kg/day), and 4) AgNO 3 (0.26 mg/kg/day) from gestational day (GD) 0 until delivery day. At the postnatal day (PD) 1, our results showed that high concentration of silver is present in the brain of pups. Further, we observed mitochondrial dysfunction and upregulation of the genes relevant to innate immune system in the brain. At PD 60, results revealed that prenatal exposure to Ag-NPs provoked severe cognitive and behavioral abnormalities in male offspring. In addition, we found that prenatal exposure to Ag-NPs was associated with abnormal mitochondrial function and significant up-regulation of the genes relevant to innate immunity in the brain. Although the Ag-NPs have been considered as safe compounds at low doses, our results indicate that prenatal exposure to low doses of Ag-NPs is able to induce behavioral and cognitive abnormalities in adulthood. Also, we found that these effects are at least partly associated with hippocampal mitochondrial dysfunction and the activation of sterile inflammation during early stages of life. Copyright © 2018 Elsevier B.V. All rights reserved.

Determining the efficacy of rasagiline in reducing bradykinesia among Parkinson's disease patients: a review.

PubMed

Silver, Dee E; Buck, Philip O

2011-09-01

Bradykinesia has a significant impact on the lives of Parkinson's disease (PD) patients. Consequently, treating this symptom is of particular concern for patients and clinicians. A number of studies have documented the efficacy of rasagiline in reducing the severity of PD symptoms. To summarize studies that specifically examined the impact of rasagiline on bradykinesia symptoms in PD patients across disease severity. The EMBASE database was searched for relevant articles published between 2000 and November 2010. Three studies were identified that explicitly examined the effect of rasagiline on the bradykinesia subscale of the Unified Parkinson's Disease Rating Scale (UPDRS) motor examination. In each, 1 mg/day rasagiline significantly reduced bradykinesia scores in patients. As a monotherapy or an adjunctive therapy, rasagiline is an effective drug for reducing the severity of bradykinesia in PD patients. Copyright © 2011 Informa Healthcare USA, Inc.

Progressive deficit in isolated pontine infarction: the association with etiological subtype, lesion topography and outcome.

PubMed

Gökçal, Elif; Niftaliyev, Elvin; Baran, Gözde; Deniz, Çiğdem; Asil, Talip

2017-09-01

It is important to predict progressive deficit (PD) in isolated pontine infarction, a relatively common problem of clinical stroke practice. Traditionally, lacunar infarctions are known with their progressive course. However, few studies have analyzed the branch atheromatous disease subtype as a subtype of lacunar infarction, separately. There are also conflicting results regarding the relationship with the topography of lesion and PD. In this study, we classified etiological subtypes and lesion topography in isolated pontine infarction and aimed to investigate the association of etiological subtypes, lesion topography and clinical outcome with PD. We analyzed demographics, laboratory parameters, and risk factors of 120 patients having isolated pontine infarction and admitted within 24 h retrospectively. PD was defined as an increase in the National Institutes of Health Stroke scale ≥2 units in 5 days after onset. Patients were classified as following: large artery disease (LAA), basilar artery branch disease (BABD) and small vessel disease (SVD). Upper, middle and lower pontine infarcts were identified longitudinally. Functional outcome at 3 months was determined according to modified Rankin scores. Of 120 patients, 41.7% of the patients were classified as BABD, 30.8% as SVD and 27.5% as LAA. 23 patients (19.2%) exhibited PD. PD was significantly more frequent in patient with BABD (p 0.006). PD was numerically higher in patients with lower pontine infarction. PD was associated with BABD and poor functional outcome. It is important to discriminate the BABD neuroradiologically from other stroke subtypes to predict PD which is associated with poor functional outcome in patients with isolated pontine infarctions.

Early Peritonitis in a Large Peritoneal Dialysis Provider System in Colombia.

PubMed

Vargas, Edgar; Blake, Peter G; Sanabria, Mauricio; Bunch, Alfonso; López, Patricia; Vesga, Jasmín; Buitrago, Alberto; Astudillo, Kindar; Devia, Martha; Sánchez, Ricardo

♦ BACKGROUND: Peritonitis is the most important complication of peritoneal dialysis (PD), and early peritonitis rate is predictive of the subsequent course on PD. Our aim was to calculate the early peritonitis rate and to identify characteristics and predisposing factors in a large nationwide PD provider network in Colombia. ♦ METHODS: This was a historical observational cohort study of all adult patients starting PD between January 1, 2012, and December 31, 2013, in 49 renal facilities in the Renal Therapy Services in Colombia. We studied the peritonitis rate in the first 90 days of treatment, its causative micro-organisms, its predictors and its variation with time on PD and between individual facilities. ♦ RESULTS: A total of 3,525 patients initiated PD, with 176 episodes of peritonitis during 752 patient-years of follow-up for a rate of 0.23 episodes per patient year equivalent to 1 every 52 months. In 41 of 49 units, the rate was better than 1 per 33 months, and in 45, it was better than 1 per 24 months. Peritonitis rates did not differ with age, ethnicity, socioeconomic status, or PD modality. We identified high incidence risk periods at 2 to 5 weeks after initiation of PD and again at 10 to 12 weeks. ♦ CONCLUSION: An excellent peritonitis rate was achieved across a large nationwide network. This occurred in the context of high nationwide PD utilization and despite high rates of socioeconomic deprivation. We propose that a key factor in achieving this was a standardized approach to management of patients. Copyright © 2017 International Society for Peritoneal Dialysis.

Selective loss of dopaminergic neurons in the substantia nigra pars compacta after systemic administration of MPTP facilitates extinction learning.

PubMed

Kinoshita, Ken-ichi; Tada, Yayoi; Muroi, Yoshikage; Unno, Toshihiro; Ishii, Toshiaki

2015-09-15

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc). In PD, thinking and retrieval deficits often arise from cognitive impairments. However, the mechanism of cognitive disorders in PD remains unknown. Therefore, we investigated cognitive function in PD model mice produced by intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which specifically destroys the DAergic neurons in the SNpc. We evaluated the cognitive function of MPTP-treated mice (PD mice) using the contextual fear conditioning test. In the test, each experiment consists of three phases: training, re-exposure, and testing. Mice were trained with a foot shock (a weak unconditioned stimulus: 1mA/2s duration, once, or an intense unconditioned stimulus: 2mA/2s duration, twice), and 24h later, mice were re-exposed to the training context for 3min to determine reconsolidation or 30min to determine extinction. The percentage of time spent freezing was measured during the test session as indexes of memory consolidation, reconsolidation, and extinction. Reconsolidation of PD mice occurred normally but memory extinction was facilitated in PD mice compared to control mice. Moreover, memory retention in PD mice was attenuated earlier than in controls following repeated conditioned stimuli every day. PD mice with selective loss of DAergic neurons in the SNpc showed attenuated memory retention, probably via facilitated extinction learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Personality Traits in Panic Disorder Patients With and Without Comorbidities.

PubMed

Zugliani, Morena M; Martin-Santos, Rocio; Nardi, Antonio Egidio; Freire, Rafael Christophe

2017-11-01

Panic disorder (PD) is often correlated with high neuroticism and low extraversion. This study aims to ascertain whether PD patients differ from healthy controls in regard to personality traits and determine if these traits are correlated with comorbid disorders, anxiety, and depression symptoms. Personality traits of 69 PD patients and 42 controls were compared using the Maudsley Personality Inventory. In PD patients, comorbidities, anxiety, and depression symptoms were also evaluated. PD patients showed higher neuroticism and lower extraversion compared with healthy controls. Patients without comorbidities presented similar results to controls, whereas those with comorbidities presented higher neuroticism and lower extraversion scores. PD per se may be unrelated to deviant personality traits, although comorbidities with major depressive disorder and agoraphobia are probably associated with high neuroticism and low extraversion. These traits show a strong correlation with the accumulation and severity of these disorders.

Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.

PubMed

Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-11-01

The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1-positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Most pleural as well as peritoneal mesotheliomas express PD-L1. Malignant effusions in this disease are characterized by the presence of tumor cells and CD3-positive T cells that highly express PD-L1. In addition, mesothelioma tumor cells are susceptible to ADCC by the anti-PD-L1 antibody avelumab. Published by Elsevier Inc.

Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

PubMed Central

Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-01-01

INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T cells that highly express PD-L1. In addition, mesothelioma tumor cells are susceptible to ADCC by anti-PD-L1 antibody avelumab. PMID:27544053

Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson’s disease patients

PubMed Central

Paul, Gesine; Zachrisson, Olof; Varrone, Andrea; Almqvist, Per; Jerling, Markus; Lind, Göran; Rehncrona, Stig; Linderoth, Bengt; Bjartmarz, Hjalmar; Shafer, Lisa L.; Coffey, Robert; Svensson, Mikael; Mercer, Katarina Jansson; Forsberg, Anton; Halldin, Christer; Svenningsson, Per; Widner, Håkan; Frisén, Jonas; Pålhagen, Sven; Haegerstrand, Anders

2015-01-01

BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson’s disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 μg rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD. TRIAL REGISTRATION. Clinical Trials.gov NCT00866502. FUNDING. Newron Sweden AB (former NeuroNova AB) and Swedish Governmental Agency for Innovation Systems (VINNOVA). PMID:25689258

Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson's disease patients.

PubMed

Paul, Gesine; Zachrisson, Olof; Varrone, Andrea; Almqvist, Per; Jerling, Markus; Lind, Göran; Rehncrona, Stig; Linderoth, Bengt; Bjartmarz, Hjalmar; Shafer, Lisa L; Coffey, Robert; Svensson, Mikael; Mercer, Katarina Jansson; Forsberg, Anton; Halldin, Christer; Svenningsson, Per; Widner, Håkan; Frisén, Jonas; Pålhagen, Sven; Haegerstrand, Anders

2015-03-02

BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 μg rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD. TRIAL REGISTRATION. Clinical Trials.gov NCT00866502. FUNDING. Newron Sweden AB (former NeuroNova AB) and Swedish Governmental Agency for Innovation Systems (VINNOVA).

Interactions of alcohol and postmenopausal hormone use in regards to mammographic breast density.

PubMed

Yaghjyan, Lusine; Colditz, Graham; Eliassen, Heather; Rosner, Bernard; Gasparova, Aleksandra; Tamimi, Rulla M

2018-06-25

We investigated the association of alcohol intake with mammographic breast density in postmenopausal women by their hormone therapy (HT) status. This study included 2,100 cancer-free postmenopausal women within the Nurses' Health Study and Nurses' Health Study II cohorts. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root transformed. Alcohol consumption was assessed with a food frequency questionnaire (0, < 5, and ≥ 5 g/day). Information regarding breast cancer risk factors was obtained from baseline or biennial questionnaires closest to the mammogram date. We used generalized linear regression to examine associations between alcohol and breast density measures in women with no HT history, current, and past HT users. In multivariable analyses, we found no associations of alcohol consumption with PD (p trend = 0.32) and DA (p trend = 0.53) and an inverse association with NDA (β = - 0.41, 95% CI - 0.73, - 0.09 for ≥ 5 g/day, p trend < 0.01). In the stratified analysis by HT status, alcohol was not associated with PD in any of the strata. We found a significant inverse association of alcohol with NDA among past HT users (β = - 0.79, 95% CI - 1.51, - 0.07 for ≥ 5 g/day, p trend = 0.02). There were no significant interactions between alcohol and HT in relation to PD, DA, and NDA (p interaction = 0.19, 0.42, and 0.43, respectively). Our findings suggest that associations of alcohol with breast density do not vary by HT status.

Cost-utility model of rasagiline in the treatment of advanced Parkinson's disease in Finland.

PubMed

Hudry, Joumana; Rinne, Juha O; Keränen, Tapani; Eckert, Laurent; Cochran, John M

2006-04-01

The economic burden of Parkinson's disease (PD) is high, especially in patients experiencing motor fluctuations. Rasagiline has demonstrated efficacy against symptoms of PD in early and advanced stages of the disease. To assess the cost-utility of rasagiline and entacapone as adjunctive therapies to levodopa versus standard levodopa care in PD patients with motor fluctuations in Finland. A 2 year probabilistic Markov model with 3 health states: "25% or less off-time/day," "greater than 25% off-time/day," and "dead" was used. Off-time represents time awake with poor or absent motor function. Model inputs included transition probabilities from randomized clinical trials, utilities from a preference measurement study, and costs and resources from a Finnish cost-of-illness study. Effectiveness measures were quality-adjusted life years (QALYs) and number of months spent with 25% or less off-time/day. Uncertainty around parameters was taken into account by Monte Carlo simulations. Over 2 years from a societal perspective, rasagiline or entacapone as adjunctive therapies to levodopa showed greater effectiveness than levodopa alone at no additional costs. Benefits after 2 years were 0.13 (95% CI 0.08 to 0.17) additional QALYs and 5.2 (3.6 to 6.7) additional months for rasagiline and 0.12 (0.08 to 0.17) QALYs and 5.1 (3.5 to 6.6) months for entacapone, both in adjunct to levodopa compared with levodopa alone. The results of this study support the use of rasagiline and entacapone as adjunctive cost-effective alternatives to levodopa alone in PD patients with motor fluctuations in Finland. With a different mode of action, rasagiline is a valuable therapeutic alternative to entacapone at no additional charge to society.

The G6PD flow-cytometric assay is a reliable tool for diagnosis of G6PD deficiency in women and anaemic subjects.

PubMed

Bancone, Germana; Kalnoky, Michael; Chu, Cindy S; Chowwiwat, Nongnud; Kahn, Maria; Malleret, Benoit; Wilaisrisak, Pornpimon; Rénia, Laurent; Domingo, Gonzalo J; Nosten, Francois

2017-08-29

Glucose-6-phosphate dehydrogenase (G6PD) activity is essential for redox equilibrium of red blood cells (RBCs) and, when compromised, the RBCs are more susceptible to haemolysis. 8-aminoquinolines (primaquine and tafenoquine) are used for the radical curative treatment of Plasmodium vivax malaria and can cause haemolysis in G6PD deficient subjects. Haemolytic risk is dependent on treatment dose and patient G6PD status but ultimately it correlates with the number of G6PD deficient RBCs. The G6PD spectrophotometric assay reliably identifies deficient subjects but is less reliable in heterozygous females, especially when other blood conditions are present. In this work we analysed samples with a range of G6PD phenotypes and haematologic conditions from 243 healthy volunteers of Asian or African-American heritage using both the spectrophotomeric assay and the G6PD flow-cytometric assay. Overall 18.5% of subjects (29.3% of Asian females) presented with anaemia, associated with decreased RBCs volume (MCV) and reticulocytosis; the flow-cytometric assay showed good correlation with the spectrophotometric assay (Pearson's r 0.918-0.957) and was less influenced by haemoglobin concentration, number of RBCs and number of reticulocytes. This resulted in more precise quantification of the number of G6PD deficient RBCs and presumably higher predictive power of drug induced haemolytic risk.

Detecting evidence of luteal activity by least-squares quantitative basal temperature analysis against urinary progesterone metabolites and the effect of wake-time variability.

PubMed

Bedford, Jennifer L; Prior, Jerilynn C; Hitchcock, Christine L; Barr, Susan I

2009-09-01

To assess computerised least-squares analysis of quantitative basal temperature (LS-BT) against urinary pregnanediol glucuronide (PdG) as an indirect measure of ovulation, and to evaluate the stability of LS-QBT to wake-time variation. Cross-sectional study of 40 healthy, normal-weight, regularly menstruating women aged 19-34. Participants recorded basal temperature and collected first void urine daily for one complete menstrual cycle. Evidence of luteal activity (ELA), an indirect ovulation indicator, was assessed using Kassam's PdG algorithm, which identifies a sustained 3-day PdG rise, and the LS-QBT algorithm, by determining whether the temperature curve is significantly biphasic. Cycles were classified as ELA(+) or ELA(-). We explored the need to pre-screen for wake-time variations by repeating the analysis using: (A) all recorded temperatures, (B) wake-time adjusted temperatures, (C) temperatures within 2h of average wake-time, and (D) expert reviewed temperatures. Relative to PdG, classification of cycles as ELA(+) was 35 of 36 for LS-QBT methods A and B, 33 of 34 (method C) and 30 of 31 (method D). Classification of cycles as ELA(-) was 1 of 4 (methods A and B) and 0 of 3 (methods C and D). Positive predictive value was 92% for methods A-C and 91% for method D. Negative predictive value was 50% for methods A and B and 0% for methods C and D. Overall accuracy was 90% for methods A and B, 89% for method C and 88% for method D. The day of a significant temperature increase by LS-QBT and the first day of a sustained PdG rise were correlated (r=0.803, 0.741, 0.651, 0.747 for methods A-D, respectively, all p<0.001). LS-QBT showed excellent detection of ELA(+) cycles (sensitivity, positive predictive value) but poor detection of ELA(-) cycles (specificity, negative predictive value) relative to urinary PdG. Correlations between the methods and overall accuracy were good and similar for all analyses. Findings suggest that LS-QBT is robust to wake-time variability and that expert interpretation is unnecessary. This method shows promise for use as an epidemiological tool to document cyclic progesterone increase. Further validation relative to daily transvaginal ultrasound is required.

Data mining and pathway analysis of glucose-6-phosphate dehydrogenase with natural language processing

PubMed Central

Chen, Long; Zhang, Chunhua; Wang, Yanling; Li, Yuqian; Han, Qiaoqiao; Yang, Huixin; Zhu, Yuechun

2017-01-01

Human glucose-6-phosphate dehydrogenase (G6PD) is a crucial enzyme in the pentose phosphate pathway, and serves an important role in biosynthesis and the redox balance. G6PD deficiency is a major cause of neonatal jaundice and acute hemolyticanemia, and recently, G6PD has been associated with diseases including inflammation and cancer. The aim of the present study was to conduct a search of the National Center for Biotechnology Information PubMed library for articles discussing G6PD. Genes that were identified to be associated with G6PD were recorded, and the frequency at which each gene appeared was calculated. Gene ontology (GO), pathway and network analyses were then performed. A total of 98 G6PD-associated genes and 33 microRNAs (miRNAs) that potentially regulate G6PD were identified. The 98 G6PD-associated genes were then sub-classified into three functional groups by GO analysis, followed by analysis of function, pathway, network, and disease association. Out of the 47 signaling pathways identified, seven were significantly correlated with G6PD-associated genes. At least two out of four independent programs identified the 33 miRNAs that were predicted to target G6PD. miR-1207-5P, miR-1 and miR-125a-5p were predicted by all four software programs to target G6PD. The results of the present study revealed that dysregulation of G6PD was associated with cancer, autoimmune diseases, and oxidative stress-induced disorders. These results revealed the potential roles of G6PD-regulated signaling and metabolic pathways in the etiology of these diseases. PMID:28627690

KSC-03pd0980

NASA Image and Video Library

2003-04-04

KENNEDY SPACE CENTER, FLA. - Workers prepare the shrouded Mars Exploration Rover 2 (MER-2) for mating to the lander. Set to launch in Spring 2003, the MER Mission consists of two identical rovers, landing at different regions of Mars, designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past. The first rover has a launch window opening May 30, and the second rover a window opening June 25.

KSC-03PD-1041

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, technicians prepare to close the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) around the spacecraft prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03PD-1055

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1063

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1035

NASA Image and Video Library

2003-04-09

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, technicians make final preparations to the Mars Exploration Rover 2 (MER-2) before closing the lander petals and attached airbags around the spacecraft prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1056

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1040

NASA Image and Video Library

2003-04-09

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, technicians prepare to close the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) around the spacecraft prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1038

NASA Image and Video Library

2003-04-09

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, technicians prepare to close the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) around the spacecraft prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1062

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1037

NASA Image and Video Library

2003-04-09

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, technicians prepare to close the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) around the spacecraft prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1055

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1054

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1036

NASA Image and Video Library

2003-04-09

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, technicians prepare to close the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) around the spacecraft prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1057

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1039

NASA Image and Video Library

2003-04-09

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, technicians prepare to close the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) around the spacecraft prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1034

NASA Image and Video Library

2003-04-09

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, technicians prepare to close the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) around the spacecraft prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1061

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1051

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1059

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1053

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1052

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1058

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1060

NASA Image and Video Library

2003-04-10

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1033

NASA Image and Video Library

2003-04-09

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, technicians prepare to close the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) around the spacecraft prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03pd1041

NASA Image and Video Library

2003-04-09

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, technicians prepare to close the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) around the spacecraft prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03PD-1063

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03PD-1040

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, technicians prepare to close the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) around the spacecraft prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03PD-1051

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03PD-1062

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03PD-1057

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03PD-1060

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

KSC-03PD-1052

NASA Technical Reports Server (NTRS)

2003-01-01

KENNEDY SPACE CENTER, FLA. -- In the Payload Hazardous Servicing Facility, the lander petals and attached airbags of the Mars Exploration Rover 2 (MER-2) are closed around the spacecraft during testing prior to launch. The MER Mission consists of two identical rovers set to launch in Spring 2003. Landing at different regions of Mars, they are designed to cover roughly 110 yards each Martian day over various terrain. Each rover will carry five scientific instruments that will allow it to search for evidence of liquid water that may have been present in the planet's past.

Rasagiline – a novel MAO B inhibitor in Parkinson’s disease therapy

PubMed Central

Lecht, Shimon; Haroutiunian, Simon; Hoffman, Amnon; Lazarovici, Philip

2007-01-01

Parkinson’s disease (PD) is a progressive neurodegenerative, dopamine deficiency disorder. The main therapeutic strategies for PD treatment relies on dopamine precursors (levodopa), inhibition of dopamine metabolism (monoamine oxidase [MAO] B and catechol-O-methyl transferase inhibitors), and dopamine receptor agonists. Recently, a novel selective and irreversible MAO B propargylamine inhibitor rasagiline (N-propargyl-1-R-aminoindan, Azilect®) was approved for PD therapy. In contrast to selegiline, the prototype of MAO B inhibitors, rasagiline is not metabolized to potentially toxic amphetamine metabolites. The oral bioavailability of rasagiline is 35%, it reaches Tmax after 0.5–1 hours and its half-life is 1.5–3.5 hours. Rasagiline undergoes extensive hepatic metabolism primarily by cytochrome P450 type 1A2 (CYP1A2). Rasagiline is initiated at 1 mg once-daily dosage as monotherapy in early PD patients and at 0.5–1 mg once-daily as adjunctive to levodopa in advanced PD patients. Rasagiline treatment was not associated with “cheese effect” and up to 20 mg per day was well tolerated. In PD patients with hepatic impairment, rasagiline dosage should be carefully adjusted. Rasagiline should not be administered with other MAO inhibitors and co-administration with certain antidepressants and opioids should be avoided. Although further clinical evidence is needed on the neuroprotective effects of rasagiline in PD patients, this drug provides an additional tool for PD therapy. PMID:18488080

Are we missing non-motor seizures in Parkinson's disease? Two case reports.

PubMed

Son, Andre Y; Cucca, Alberto; Agarwal, Shashank; Liu, Anli; Di Rocco, Alessandro; Biagioni, Milton C

2017-01-01

Parkinson's disease (PD) is predominantly recognized for its motor symptoms, but patients struggle from a morbid and heterogeneous collection of non-motor symptoms (NMS-PD) that can affect their quality of life even more. NMS-PD is a rather generalized term and the heterogeneity and non-specific nature of many symptoms poses a clinical challenge when a PD patient presents with non-motor complaints that may not be NMS-PD. We report two patients with idiopathic PD who presented with acute episodes of cognitive changes. Structural brain images, cardiovascular and laboratory assessment were unremarkable. Both patients experienced a considerable delay before receiving an epilepsy-evaluation, at which point electroencephalogram abnormalities supported the diagnosis of focal non-motor seizures with alteration of awareness. Antiepileptic therapy was implemented and was effective in both cases. Diagnosing non-motor seizures can be challenging. However, PD patients pose an even greater challenge given their eclectic non-motor clinical manifestations and other disease-related complications that could confound and mislead adequate clinical interpretation. Our two cases provide examples of non-motor seizures that may mimic non-motor symptoms of PD. Treating physicians should always consider other possible causes of non-motor symptoms that may coexist in PD patients. Epilepsy work-up should be contemplated in the differential of acute changes in cognition, behavior, or alertness.

Urinary sex steroid hormone and placental leucine aminopeptidase concentration differences between live births and stillbirth of Bornean orangutans (Pongo pygmaeus).

PubMed

Kinoshita, Kodzue; Sano, Yusuke; Takai, Akira; Shimizu, Mika; Kobayashi, Toshio; Ouchi, Akihiro; Kuze, Noko; Inoue-Murayama, Miho; Idani, Gen'ichi; Okamoto, Munehiro; Ozaki, Yasuhiko

2017-02-01

Under the environment of pregnancy, the placenta assumes an important steroidogenic role in the maintenance of pregnancy. Urinary placental leucine aminopeptidase (PLAP), estrone-3-glucuronide (E 1 G), and pregnanediol-3-glucuronide (PdG) concentrations were compared among five pregnancies (four live births and one stillbirth) in four orangutans. The gestation period of the stillbirth (223 days) was shorter than that of the live births (239-254 days). In females who gave a live birth, average PLAP and E 1 G concentrations increased until the delivery. Conversely, in the female who gave a stillbirth, PLAP concentration failed to increase, and E 1 G concentration was significantly low in late pregnancy period. Regarding PdG concentrations, there was no significant difference among all pregnancies. This is the first study reporting a change in urinary PLAP, E 1 G, and PdG concentrations during orangutan stillbirth and live birth pregnancies. The findings will assist in developing pregnancy screening tests. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pd and polyaniline nanocomposite on carbon fiber paper as an efficient direct formic acid fuel cell anode

NASA Astrophysics Data System (ADS)

Pandey, Rakesh K.

2018-03-01

Direct formic acid fuel cells are advantageous as portable power generating devices. In the present work, an anode catalyst for direct formic acid fuel cell (DFAFC) is presented which has good catalytic activity for formic acid oxidation. The catalyst is composed of Pd and conducting polymer polyaniline (Pd-PANI) nanocomposite. The catalyst was prepared by using a single step galvanostatic electrochemical deposition method. The Pd-PANI catalyst was electrodeposited at different time durations and a comparison of the catalytic activity at each deposition time was carried out and optimized.

Effect of ball milling on structures and properties of dispersed-type dental amalgam.

PubMed

Chern Lin, Jiin-Huey; Chen, Fred Ying-Yi; Chiang, Hui-Ju; Ju, Chien-Ping

2011-04-01

The purpose of the present study was to investigate the effect of ball milling on the initial mercury vapor release rate and mechanical properties such as compressive strength, diametral tensile strength and creep value, of the dispersed-type dental amalgam, and comparison was made with respect to two commercial amalgam alloys. Ball milling was employed to modify the configuration of the originally spherical-shaped Ag-Cu-Pd dispersant alloy particles. Improvement in mechanical properties while maintaining a low early-stage mercury vapor release rate of the amalgam is attempted. The experimental results show that the amalgam (AmB10) which was made from Ag-Cu-Pd dispersant alloy particles that were ball-milled for 10 min and heat-treated at 300 °C for 2 days exhibited a low initial mercury vapor release rate of 69 pg/mm(2)/s, which was comparable with that of commercial amalgam alloy Tytin (68 pg/mm(2)/s), and was lower than that of Dispersalloy (73 pg/mm(2)/s). As for mechanical properties, amalgam AmB10 exhibited the highest 1h compressive strength (228 MPa), which was higher than that of commercial amalgam alloy Dispersalloy by 72%; while its 24h diametral tensile strength was also the highest (177 MPa), and was higher than that of Dispersalloy by 55%. Furthermore, the creep value of the amalgams made from Ag-Cu-Pd alloy particles with 10 min ball-milling and heat treatment at 300 °C for 2 days was measured to be 0.12%, which was about 20% that of Dispersalloy. It is found that ball milling of the dispersant Ag-Cu-Pd alloy particles for 10 min was able to modify the configuration of the alloy particles into irregular-shapes. Subsequently, heat treatment at 300 °C significantly lowered the initial mercury vapor release rate, increased its 1h compressive strength and 1h diametral tensile strength, and lowered its creep value. Copyright © 2010 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Long-term dysregulation of brain corticotrophin and glucocorticoid receptors and stress reactivity by single early-life pain experience in male and female rats.

PubMed

Victoria, Nicole C; Inoue, Kiyoshi; Young, Larry J; Murphy, Anne Z

2013-12-01

Inflammatory pain experienced on the day of birth (postnatal day 0: PD0) significantly dampens behavioral responses to stress- and anxiety-provoking stimuli in adult rats. However, to date, the mechanisms by which early life pain permanently alters adult stress responses remain unknown. The present studies examined the impact of inflammatory pain, experienced on the day of birth, on adult expression of receptors or proteins implicated in the activation and termination of the stress response, including corticotrophin releasing factor receptors (CRFR1 and CRFR2) and glucocorticoid receptor (GR). Using competitive receptor autoradiography, we show that Sprague Dawley male and female rat pups administered 1% carrageenan into the intraplantar surface of the hindpaw on the day of birth have significantly decreased CRFR1 binding in the basolateral amygdala and midbrain periaqueductal gray in adulthood. In contrast, CRFR2 binding, which is associated with stress termination, was significantly increased in the lateral septum and cortical amygdala. GR expression, measured with in situ hybridization and immunohistochemistry, was significantly increased in the paraventricular nucleus of the hypothalamus and significantly decreased in the hippocampus of neonatally injured adults. In parallel, acute stress-induced corticosterone release was significantly attenuated and returned to baseline more rapidly in adults injured on PD0 in comparison to controls. Collectively, these data show that early life pain alters neural circuits that regulate responses to and neuroendocrine recovery from stress, and suggest that pain experienced by infants in the Neonatal Intensive Care Unit may permanently alter future responses to anxiety- and stress-provoking stimuli. Published by Elsevier Ltd.

Stage- and tissue-expression of genes involved in the biosynthesis and signalling of ethylene in reproductive organs of damson plum (Prunus domestica L. subsp. insititia).

PubMed

Fernández-Otero, C I; de la Torre, F; Iglesias, R; Rodríguez-Gacio, M C; Matilla, A J

2007-01-01

In this work, four cDNA clones (Pd-ACS1,AJ890088; Pd-ETR1 and Pd-ERS1, AJ890092, AJ890091; and Pd-CTR1, AJ890089) encoding an ACC-synthase, two putative ethylene (ET) receptors, and a putative MAPKKK, respectively, were isolated and phylogenetically characterized in Prunus domestica L. subsp. insititia. Their expression was studied by real-time PCR during flower (closed, open and senescent) and fruit (early green, late green, maturation and ripening) development of damson plum, which is climateric. While two peaks of ET production were quantified at early green and ripening stages in whole fruits, the seed was not able to produce it during maturation and ripening stages. All studied genes were differentially expressed during flower and fruit development. In general, the level of transcripts of Pd-ACS1 was higher in fruits than in flowers. However, it was noteworthy that: (1) Pd-ACS1 expression was hardly detected in closed flowers and at low levels during early green stage; and fruit development provoked a notable differential expression in seeds, and pericarp; (2) the results of Pd-ACS1 expression during fruit development suggest a preponderant role of this gene from late green stage onward. The stamen was the only floral organ in which expression of both Pd-ETR1 and Pd-ERS1 receptor genes was not significantly altered during development; however, their expression decreased concomitantly with development of pistil (only floral organ to register a net ET production when fertilized) and during first days of ovary development (the highest ET production during all fruit development). Contrary to Pd-ERS1, the level of Pd-ETR1 mRNA was temporally quite similar in the seed. With regard Pd-ETR1, even its expression was very scarce during maturation of mesocarp, was stimulated during ripening. In the epicarp, Pd-ERS1 and Pd-ETR1 were low expressed during pit hardening increasing onward and decreasing during ripening. Pd-CTR1 expression was in the seed>mesocarp>epicarp. Spatial and temporal levels of Pd-ACS1, Pd-ETR1, Pd-ERS1 and Pd-CTR1 mRNAs described in this work demonstrate that the expression of these genes is not always constitutive and that control of its transcription may play an important role in regulating the development of reproductive organs of damson plum.

Pt-Pd Bimetal Popcorn Nanocrystals: Enhancing the Catalytic Performance by Combination Effect of Stable Multipetals Nanostructure and Highly Accessible Active Sites.

PubMed

Ma, Yanxia; Yin, Lisi; Cao, Guojian; Huang, Qingli; He, Maoshuai; Wei, Wenxian; Zhao, Hong; Zhang, Dongen; Wang, Mingyan; Yang, Tao

2018-04-01

Exploration of highly efficient electrocatalysts is significantly urgent for the extensive adoption of the fuel cells. Because of their high activity and super stability, Pt-Pd bimetal nanocrystals have been widely recognized as one class of promising electrocatalysts for oxygen reduction. This article presents the synthesis of popcorn-shaped Pt-Pd bimetal nanoparticles with a wide composition range through a facile hydrothermal strategy. The hollow-centered nanoparticles are surrounded by several petals and concave surfaces. By exploring the oxygen reduction reaction on the carbon supported Pt-Pd popcorns in perchloric acid solution, it is found that compared with the commercial Pt/C catalyst the present catalysts display superior catalytic performances in aspects of catalytic activity and stability. More importantly, the Pt-Pd popcorns display minor performance degradations through prolonged potential cycling. The enhanced performances can be mainly attributed to the unique popcorn structure of the Pt-Pd components, which allows the appearance and long existence of the high active sites with more accessibility. The present work highlights the key roles of accessible high active sites in the oxygen reduction reaction, which will ultimately guide the design of highly durable Pt-Pd catalysts. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mitigation of postnatal ethanol-induced neuroinflammation ameliorates trace fear memory deficits in juvenile rats.

PubMed

Goodfellow, Molly J; Shin, Youn Ju; Lindquist, Derick H

2018-02-15

Impairments in behavior and cognition are common in individuals diagnosed with fetal alcohol spectrum disorders (FASD). In this study, FASD model rats were intragastrically intubated with ethanol (5g/kg/day; 5E), sham-intubated (SI), or maintained as naïve controls (NC) over postnatal days (PD) 4-9. Ethanol exposure during this human third trimester-equivalent period induces persistent impairments in hippocampus-dependent learning and memory. The ability of ibuprofen (IBU), a non-steroidal anti-inflammatory drug, to diminish ethanol-induced neuroinflammation and rescue deficits in hippocampus-dependent trace fear conditioning (TFC) was investigated in 5E rats. Phosphate buffered saline vehicle (VEH) or IBU was injected 2h following ethanol exposure over PD4-9, followed by quantification of inflammation-related genes in the dorsal hippocampus of PD10 rats. The 5E-VEH rats exhibited significant increases in Il1b and Tnf, but not Itgam or Gfap, relative to NC, SI-VEH, and 5E-IBU rats. In separate groups of PD31-33 rats, conditioned fear (freezing) was significantly reduced in 5E-VEH rats during TFC testing, but not acquisition, compared to SI-VEH and, critically, 5E-IBU rats. Results suggest neuroimmune activation in response to ethanol within the neonate hippocampus contributes to later-life cognitive dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of the hook of Uncaria rhynchophylla on neurotoxicity in the 6-hydroxydopamine model of Parkinson's disease.

PubMed

Shim, Jin Sup; Kim, Hyo Geun; Ju, Mi Sun; Choi, Jin Gyu; Jeong, Seo Young; Oh, Myung Sook

2009-11-12

While the hook of Uncaria rhynchophylla (URH) is a traditional herb used in northeast Asia for the treatment of Parkinson's disease (PD)-like symptoms such as tremor, it has not been experimentally evaluated in a PD model. We investigated the effects of URH on 6-hydroxydapamine (6-OHDA)-induced neurotoxicity in in vitro and in vivo models of PD. The cell viability, anti-oxidative activity, and anti-apoptotic activity of a water extract of URH (URE) were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, reactive oxygen species (ROS), total glutathione (GSH), and caspase-3 assays in PC12 cells stressed by 6-OHDA. We also investigated the behavioral recovery and dopaminergic neuron protection of URE using an apomorphine-induced rotation test and tyrosine hydroxylase immunohistochemistry in the hemi-parkinsonian rat model of the unilateral 6-OHDA lesion of the medial forebrain bundle. In PC12 cells, URE significantly reduced cell death and the generation of ROS, increased GSH levels, and inhibited caspase-3 activity induced by 6-OHDA. In 6-OHDA-lesioned rats, posttreatment with URE (5 mg/kg/day for 14 days) significantly reduced apomorphine-induced rotation, and it lowered dopaminergic neuronal loss in substantia nigra pars compacta. URE possesses neuroprotective activity against 6-OHDA-induced toxicity through anti-oxidative and anti-apoptotic activities in PD models.

Tai Chi for Reducing Dual-task Gait Variability, a Potential Mediator of Fall Risk in Parkinson’s Disease: A Pilot Randomized Controlled Trial

PubMed Central

Vergara-Diaz, Gloria; Osypiuk, Kamila; Hausdorff, Jeffrey M; Bonato, Paolo; Gow, Brian J; Miranda, Jose GV; Sudarsky, Lewis R; Tarsy, Daniel; Fox, Michael D; Gardiner, Paula; Thomas, Cathi A; Macklin, Eric A; Wayne, Peter M

2018-01-01

Objectives To assess the feasibility and inform design features of a fully powered randomized controlled trial (RCT) evaluating the effects of Tai Chi (TC) in Parkinson’s disease (PD) and to select outcomes most responsive to TC assessed during off-medication states. Design Two-arm, wait-list controlled RCT. Settings Tertiary care hospital. Subjects Thirty-two subjects aged 40–75 diagnosed with idiopathic PD within 10 years. Interventions Six-month TC intervention added to usual care (UC) versus UC alone. Outcome Measures Primary outcomes were feasibility-related (recruitment rate, adherence, and compliance). Change in dual-task (DT) gait stride-time variability (STV) from baseline to 6 months was defined, a priori, as the clinical outcome measure of primary interest. Other outcomes included: PD motor symptom progression (Unified Parkinson’s Disease Rating Scale [UPDRS]), PD-related quality of life (PDQ-39), executive function (Trail Making Test), balance confidence (Activity-Specific Balance Confidence Scale, ABC), and Timed Up and Go test (TUG). All clinical assessments were made in the off-state for PD medications. Results Thirty-two subjects were enrolled into 3 sequential cohorts over 417 days at an average rate of 0.08 subjects per day. Seventy-five percent (12/16) in the TC group vs 94% (15/16) in the UC group completed the primary 6-month follow-up assessment. Mean TC exposure hours overall: 52. No AEs occurred during or as a direct result of TC exercise. Statistically nonsignificant improvements were observed in the TC group at 6 months in DT gait STV (TC [20.1%] vs UC [−0.1%] group [effect size 0.49; P = .47]), ABC, TUG, and PDQ-39. UPDRS progression was modest and very similar in TC and UC groups. Conclusions Conducting an RCT of TC for PD is feasible, though measures to improve recruitment and adherence rates are needed. DT gait STV is a sensitive and logical outcome for evaluating the combined cognitive-motor effects of TC in PD.

Inflammatory gastrointestinal diseases associated with PD-1 blockade antibodies.

PubMed

Collins, M; Michot, J M; Danlos, F X; Mussini, C; Soularue, E; Mateus, C; Loirat, D; Buisson, A; Rosa, I; Lambotte, O; Laghouati, S; Chaput, N; Coutzac, C; Voisin, A L; Soria, J C; Marabelle, A; Champiat, S; Robert, C; Carbonnel, F

2017-11-01

Immune check-point blockade agents have shown clinical activity in cancer patients but are associated with immune-related adverse events that could limit their development. The aim of this study was to describe the gastrointestinal immune-related adverse events (GI-irAE) in patients with cancer treated with anti-PD-1. this is a retrospective study of consecutive adult patients who had a suspected GI-irAE due to anti-PD-1 antibodies between 2013 and 2016. Patients were recruited through a pharmacovigilance registry. Patients' data were reviewed by a multidisciplinary committee that included gastroenterologists, oncologists and a pathologist. Quantitative variables are described by median (range), qualitative variable by frequency (percentage). Forty-four patients were addressed to a Gastroenterology unit for a suspected GI-IrAE. Twenty patients had a confirmed GI-irAE related to anti-PD-1, which occurred 4.2 months (0.2; 22.1) after the initiation of anti-PD-1. GI-IrAE incidence rate under anti-PD-1 treatment was estimated to be 1.5%. Among patients with GI-IrAE, main symptoms were diarrhoea (n = 16, 80%), abdominal pain (n = 13, 65%), nausea and vomiting (n = 11, 55%), intestinal obstruction (n = 1, 5%), and haematochezia (n = 2, 10%). No patient had colectomy. Four distinct categories of GI-irAE were observed: acute colitis (n = 8, 40%), microscopic colitis (n = 7, 35%), upper gastrointestinal tract inflammation (n = 4, 20%) and pseudo-obstruction (n = 1, 5%). Response rates to corticosteroids were 87.5% (7/8) in acute colitis, 57% (4/7) in microscopic colitis and 75% (3/4) in upper gastrointestinal tract inflammation. Median time to resolution was 36 days (6-172) in acute colitis, and 98 days (42-226) in microscopic colitis. This study suggests that GI-irAE are different and less frequent with anti PD-1 than with anti CTLA-4. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Suitability of the Depression, Anxiety, and Stress Scale in Parkinson's Disease.

PubMed

Johnson, Andrew R; Lawrence, Blake J; Corti, Emily J; Booth, Leon; Gasson, N; Thomas, Meghan G; Loftus, A M; Bucks, Romola S

2016-05-27

The Depression, Anxiety, and Stress Scale -21 (DASS-21) is a frequently used measure of emotional disturbance symptoms in Parkinson's disease (PD). However, the factor structure of the DASS-21 in PD has yet to be explored. To assess whether the scale is measuring these symptoms in PD in the same way as the general population. The present study fit a series of established DASS-21 factor structures with both confirmatory factor analysis (CFA) and exploratory structural equation modelling (ESEM) using data from 251 participants with PD. The 3-factor ESEM provided the best fit. The depression and stress scales fit well, however, few items on the anxiety subscale loaded clearly, with several items significantly loading onto the depression or stress factors. Whilst the depression and stress subscales appear suitable in PD, poor loadings and internal consistency indicate the anxiety subscale may not accurately assess anxiety symptomology in PD. This may be due to the scale's reliance on physiological symptoms as indicators of anxiety, when many of these are present in PD. Thus, the anxiety subscale of the DASS-21 may not be a suitable measure of anxiety in PD.

Generalized aggressive periodontitis: microbiological composition and clinical parameters in non-surgical therapy.

PubMed

Usin, María M; Tabares, Sandra M; Menso, Julieta; de Albera, Estela R; Sembaj, Adela

2016-12-01

The aim of this study was to determine the variations in periodontal parameters and microbiological composition in periodontal pockets at the baseline and 3 and 6 months post treatmentin patients with Generalized Aggressive Periodontitis(GAP) undergoing non surgical periodontal treatment combined with chlorhexidine and systemic antibiotics. Medical and dental history was taken from 10 subjects, average age 30.6±2.7 years, diagnosed with GAP. A non surgical periodontal treatment combined with 0.12% chlorhexidine, 875 mg amoxicillin and 500 mg metronidazole every 12 hours for ten days was conducted. At each visit, the following measurements wererecorded: bacterial plaque (BP), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), hypermobility, and furcation lesions, and a sample of subgingivalplaque was taken from the site of the deepest probing depth of each sextant to identify Porphyromonas gingivalis, Treponemadenticola, Tannerella forsythia, Prevotella intermedia and Aggregatibacter actinomycetemcomitans using molecular biology techniques. After 6 months, the Wilcoxon test showed an increase of 0.97 mm in CAL (p=0.0047) and 2.54 mm in PD(p=0.009). A healthy site was defined as having a PD <5 mm, negative BOP and no pathogenic bacteria detected at 6 months, indicating significant improvement (p=0.008), with OR (95%CI) =4.7 (1.102220.11).With the treatment protocol used in this study, 6 months after treatment, patients had an approximately 4- fold higher possibility of presenting PD <5 mm and periodontal pockets without periodontal pathogenic bacteria. Sociedad Argentina de Investigación Odontológica.

Dopaminergic Lesion in the Olfactory Bulb Restores Olfaction and Induces Depressive-Like Behaviors in a 6-OHDA Model of Parkinson's Disease.

PubMed

Ilkiw, Jessica L; Kmita, Luana C; Targa, Adriano D S; Noseda, Ana Carolina D; Rodrigues, Lais S; Dorieux, Flávia W C; Fagotti, Juliane; Dos Santos, Patrícia; Lima, Marcelo M S

2018-06-05

Olfactory impairments and depressive behavior are commonly reported by individuals with Parkinson's disease (PD) being observed before motor symptoms. The mechanisms underlying these clinical manifestations are not fully elucidated. However, the imbalance in dopaminergic neurotransmission seems to play an important role in this context. In patients and animal models of PD, an increase in the dopaminergic interneurons of the glomerular layer in olfactory bulb (OB-gl) is observed, which may contribute to the olfactory impairment. In addition, neuronal imbalance in OB is related to depressive symptoms, as demonstrated by chemical olfactory bulbectomy. In view of that, we hypothesized that a reduction in the number or density of dopaminergic neurons present in OB could promote an olfactory improvement and, in contrast, would accentuate the depressive-like behaviors in the 6-hydroxydopamine (6-OHDA) model of PD. Therefore, we performed single or double injections of 6-OHDA within the substantia nigra pars compacta (SNpc) and/or in the OB-gl. We observed that, after 7 days, the group with nigral lesion exhibited olfactory impairment, as well as the group with the lesion in the OB-gl. However, the combination of the lesions prevented the occurrence of hyposmia. In relation to depressive-like behaviors, we observed that the SNpc injury promoted depressive-like behavior, being accentuated after a double injury. Our results demonstrated the importance of the dopaminergic neurons of the OB-gl in different non-motor features of PD, since the selective reduction of these periglomerular neurons was able to induce olfactory impairment and depressive-like behaviors.

Electrochemical biosensor based on glucose oxidase encapsulated within enzymatically synthesized poly(1,10-phenanthroline-5,6-dione).

PubMed

Ciftci, Hakan; Oztekin, Yasemin; Tamer, Ugur; Ramanaviciene, Almira; Ramanavicius, Arunas

2014-11-01

This study is focused on the investigation of electrocatalytic effect of glucose oxidase (GOx) immobilized on the graphite rod (GR) electrode. The enzyme modified electrode was prepared by encapsulation of immobilized GOx within enzymatically formed poly(1,10-phenanthroline-5,6-dione) (pPD) film. The electrochemical responses of such enzymatic electrode (pPD/GOx/GR) vs. different glucose concentrations were examined chronoamperometrically in acetate-phosphate buffer solution (A-PBS), pH 6.0, under aerobic or anaerobic conditions. Amperometric signals of the pPD/GOx/GR electrode exhibited well-defined hyperbolic dependence upon glucose concentration. Amperometric signals at 100mM of glucose were 41.17 and 32.27 μA under aerobic and anaerobic conditions, respectively. Amperometric signals of the pPD/GOx/GR electrode decreased by 6% within seven days. The pPD/GOx/GR electrode showed excellent selectivity in the presence of dopamine and uric acid. Furthermore it had a good reproducibility and repeatability with standard deviation of 9.4% and 8.0%, respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

Coordinated reset neuromodulation for Parkinson's disease: Proof-of-concept study

PubMed Central

Adamchic, Ilya; Hauptmann, Christian; Barnikol, Utako Brigit; Pawelczyk, Norbert; Popovych, Oleksandr; Barnikol, Thomas Theo; Silchenko, Alexander; Volkmann, Jens; Deuschl, Günter; Meissner, Wassilios G; Maarouf, Mohammad; Sturm, Volker; Freund, Hans-Joachim; Tass, Peter Alexander

2014-01-01

Background The discovery of abnormal synchronization of neuronal activity in the basal ganglia in Parkinson's disease (PD) has prompted the development of novel neuromodulation paradigms. Coordinated reset neuromodulation intends to specifically counteract excessive synchronization and to induce cumulative unlearning of pathological synaptic connectivity and neuronal synchrony. Methods In this prospective case series, six PD patients were evaluated before and after coordinated reset neuromodulation according to a standardized protocol that included both electrophysiological recordings and clinical assessments. Results Coordinated reset neuromodulation of the subthalamic nucleus (STN) applied to six PD patients in an externalized setting during three stimulation days induced a significant and cumulative reduction of beta band activity that correlated with a significant improvement of motor function. Conclusions These results highlight the potential effects of coordinated reset neuromodulation of the STN in PD patients and encourage further development of this approach as an alternative to conventional high-frequency deep brain stimulation in PD. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:24976001

Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

PubMed Central

Cui, Yimin; Song, Yan; Wang, Jessie; Yu, Zhigang; Schuster, Alan; Barrett, Yu Chen; Frost, Charles

2013-01-01

Background The pharmacokinetics (PK), pharmacodynamics (PD), and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio) to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9). The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. PMID:24353445

[Pancreatoduodenectomy: results in a large volume center].

PubMed

Chan, Carlos; Franssen, Bernardo; Uscanga, Luis; Robles, Guillermo; Campuzano, Manuel

2006-01-01

Analyze the experience with pancreaticoduodenectomy (PD) at the INCMNSZ. PD has become a popular procedure in hospitals throughout the USA and Europe in the last 25 years, where mortality is < 5% y morbidity remains around 40%. Nonetheless there are very few reports on PD in Latin America. The data of all PD's performed at the INCMNSZ between 1999 and 2005 was gathered prospectively and analyzed retrospectively. 133 PDs where performed; 47.5% where men and 52.5% where women. Median of age was 57.7 years. 81.5% underwent classical resection and 18.5% a pylorus preserving procedure. Intraoperative variables include: blood loss: 940 mL. (1,000). transfusion requirements: 1.9 U, median operative time: 5:49 (+/- 1:02) and median hospital stay: 14 days. Most frequent diagnosis include ampulary adenocarcinoma and pancreatic cancer Mortality in the entire series was 9.2%, decreased to 2.7% in the 2002-2005 period and from April 2003 has remained in 0. A total of 14 portal-superior mesenteric vein resections where performed. To our knowledge this is the largest series of PD in Latin America. Popularity and indications for PD are expanding. Mortality is acceptable and morbidity remains high despite much effort. This procedure is performed with a satisfactory outcome in high volume centers. Involvement of the portal-superior mesenteric vein is not a contraindication of PD.

Handgrip Strength Related to Long-Term Electromyography: Application for Assessing Functional Decline in Parkinson Disease.

PubMed

Jones, Gareth R; Roland, Kaitlyn P; Neubauer, Noelannah A; Jakobi, Jennifer M

2017-02-01

To determine which clinical measures of physical function (ie, gait, balance, and grip strength) best represent long-term electromyography in persons with Parkinson disease (PD) compared with those without PD. Cross-sectional study. Local community. A sample (N=37) of men and women with PD (n=23) and those without PD (n=14), living independently at home, older than 50 years of age, from the local community. Not applicable. Measures of gait, balance, and grip strength were completed, and electromyography was examined in biceps brachii, triceps brachii, vastus lateralis, and biceps femoris during a 6.5-hour day. Muscle activity was quantified through burst in electromyography (>2% of the normalized maximum voluntary exertion with a continuous activity period of >0.1s). Stepwise multiple regression models were used to determine the proportion of variance in burst characteristics explained by clinical measures of physical function in PD. Grip strength was the best predictor of muscle activity in persons with PD (R 2 =.17-.33; P<.04), whereas gait characteristics explained muscle activity in healthy controls (R 2 =.40-.82; P<.04). Grip strength could serve as an effective clinical assessment tool to determine changes in muscle activity, which is a precursor to functional loss in persons with PD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

mTOR and MEK1/2 inhibition differentially modulate tumor growth and the immune microenvironment in syngeneic models of oral cavity cancer

PubMed Central

Cash, Harrison; Shah, Sujay; Moore, Ellen; Caruso, Andria; Uppaluri, Ravindra; Van Waes, Carter; Allen, Clint

2015-01-01

We investigated the effects of mTOR and MEK1/2 inhibition on tumor growth and the tumor microenvironment in immunogenic and poorly immunogenic models of murine oral cancer. In vitro, rapamycin and PD901 inhibited signaling through expected downstream targets, but only PD901 reduced viability and altered function of MOC cells. Following transplantation of MOC cells into immune-competent mice, effects on both cancer and infiltrating immune cells were characterized following rapamycin and/or PD901 treatment for 21 days. In vivo, both rapamycin and PD901 inhibition reduced primary growth of established MOC tumors on treatment. Following withdrawal of PD901, rapid rebound of tumor growth limited survival, whereas durable tumor control was observed following rapamycin treatment in immunogenic MOC1 tumors despite more robust inhibition of oncogenic signaling by PD901. Characterization of the immune microenvironment revealed diminished infiltration and activation of antigen-specific CD8+ T-cells and other immune cells following PD901 but not rapamycin in immunogenic tumors. Subsequent in vitro T-cell assays validated robust inhibition of T-cell expansion and activation following MEK inhibition compared to mTOR inhibition. CD8 cell depletion abrogated rapamycin-induced primary tumor growth inhibition in MOC1 mice. These data have critical implications in the design of combination targeted and immune therapies in oral cancer. PMID:26506415

Population screening for glucose-6-phosphate dehydrogenase deficiencies in Isabel Province, Solomon Islands, using a modified enzyme assay on filter paper dried bloodspots

PubMed Central

2010-01-01

Background Glucose-6-phosphate dehydrogenase deficiency poses a significant impediment to primaquine use for the elimination of liver stage infection with Plasmodium vivax and for gametocyte clearance, because of the risk of life-threatening haemolytic anaemia that can occur in G6PD deficient patients. Although a range of methods for screening G6PD deficiency have been described, almost all require skilled personnel, expensive laboratory equipment, freshly collected blood, and are time consuming; factors that render them unsuitable for mass-screening purposes. Methods A published WST8/1-methoxy PMS method was adapted to assay G6PD activity in a 96-well format using dried blood spots, and used it to undertake population screening within a malaria survey undertaken in Isabel Province, Solomon Islands. The assay results were compared to a biochemical test and a recently marketed rapid diagnostic test. Results Comparative testing with biochemical and rapid diagnostic test indicated that results obtained by filter paper assay were accurate providing that blood spots were assayed within 5 days when stored at ambient temperature and 10 days when stored at 4 degrees. Screening of 8541 people from 41 villages in Isabel Province, Solomon Islands revealed the prevalence of G6PD deficiency as defined by enzyme activity < 30% of normal control was 20.3% and a prevalence of severe deficiency that would predispose to primaquine-induced hemolysis (WHO Class I-II) of 6.9%. Conclusions The assay enabled simple and quick semi-quantitative population screening in a malaria-endemic region. The study indicated a high prevalence of G6PD deficiency in Isabel Province and highlights the critical need to consider G6PD deficiency in the context of P. vivax malaria elimination strategies in Solomon Islands, particularly in light of the potential role of primaquine mass drug administration. PMID:20684792

Population screening for glucose-6-phosphate dehydrogenase deficiencies in Isabel Province, Solomon Islands, using a modified enzyme assay on filter paper dried bloodspots.

PubMed

Kuwahata, Melissa; Wijesinghe, Rushika; Ho, Mei-Fong; Pelecanos, Anita; Bobogare, Albino; Landry, Losi; Bugora, Hugo; Vallely, Andrew; McCarthy, James

2010-08-05

Glucose-6-phosphate dehydrogenase deficiency poses a significant impediment to primaquine use for the elimination of liver stage infection with Plasmodium vivax and for gametocyte clearance, because of the risk of life-threatening haemolytic anaemia that can occur in G6PD deficient patients. Although a range of methods for screening G6PD deficiency have been described, almost all require skilled personnel, expensive laboratory equipment, freshly collected blood, and are time consuming; factors that render them unsuitable for mass-screening purposes. A published WST8/1-methoxy PMS method was adapted to assay G6PD activity in a 96-well format using dried blood spots, and used it to undertake population screening within a malaria survey undertaken in Isabel Province, Solomon Islands. The assay results were compared to a biochemical test and a recently marketed rapid diagnostic test. Comparative testing with biochemical and rapid diagnostic test indicated that results obtained by filter paper assay were accurate providing that blood spots were assayed within 5 days when stored at ambient temperature and 10 days when stored at 4 degrees. Screening of 8541 people from 41 villages in Isabel Province, Solomon Islands revealed the prevalence of G6PD deficiency as defined by enzyme activity < 30% of normal control was 20.3% and a prevalence of severe deficiency that would predispose to primaquine-induced hemolysis (WHO Class I-II) of 6.9%. The assay enabled simple and quick semi-quantitative population screening in a malaria-endemic region. The study indicated a high prevalence of G6PD deficiency in Isabel Province and highlights the critical need to consider G6PD deficiency in the context of P. vivax malaria elimination strategies in Solomon Islands, particularly in light of the potential role of primaquine mass drug administration.

Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade.

PubMed

Lipson, Evan J; Lilo, Mohammed T; Ogurtsova, Aleksandra; Esandrio, Jessica; Xu, Haiying; Brothers, Patricia; Schollenberger, Megan; Sharfman, William H; Taube, Janis M

2017-01-01

Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition.

PD-L1 Expression Promotes Epithelial to Mesenchymal Transition in Human Esophageal Cancer.

PubMed

Chen, Lujun; Xiong, Yuqi; Li, Jing; Zheng, Xiao; Zhou, Qi; Turner, Abbey; Wu, Changping; Lu, Binfeng; Jiang, Jingting

2017-01-01

PD-L1 (Programmed cell death 1 ligand 1, PD-L1), an essential immune checkpoint molecule in the tumor microenvironment, is an important target for cancer immunotherapy. We have previously reported that its expression in human gastric and esophageal cancer tissues is significantly associated with cancer progression and patients' postoperative prognoses. Its expression in cancer cells is well known to inhibit the T cell-mediated anti-tumor response, and this mechanism of action has been targeted for cancer immunotherapy. As of now, the autonomous effect of PD-L1 on cancer cells is not well understood, thus our present study aimed to examine the role of PD-L1 intervention in cellular biological functions, especially epithelial to mesenchymal transition (EMT), of the human esophageal cancer cell line, Eca-109 cells. Immunohistochemistry assay was used to investigate the correlation between expression of PD-L1 and EMT markers in human esophageal cancer tissues. Intervention of PD-L1 by using RNAi and over-expression methods were used to study the role of PD-L1 in regulation of biological behaviors and EMT in Eca-109 cells. Our clinical and pathological data demonstrated that tumor samples in the EMT positive subgroup had higher PD-L1 expression than those in the EMT negative subgroup. By manipulating PD-L1 expression in Eca-109 cells either through ablation or overexpression of wild type and the cytoplasmic domain-truncated mutant, we demonstrated that PD-L1 expression significantly promoted the cell viability, migration and EMT phenotype. Furthermore, our study also indicated that PD-1 fusion protein mediated stimulation of PD-L1 and the cytoplasmic domain of PD-L1 played a critical role in promoting EMT phenotype of Eca-109 cells, thereby suggesting that PD-1 receptor usually by triggering the reverse signaling can effect PD-L1 mediated regulation of esophageal cancer cell response. Our present study reveals a tumor cell-autonomous role of PD-L1 signaling in promoting EMT in human esophageal cancer. © 2017 The Author(s). Published by S. Karger AG, Basel.

Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on the pharmacokinetics of oral contraceptives, warfarin, and digoxin in healthy participants.

PubMed

Devineni, Damayanthi; Manitpisitkul, Prasarn; Vaccaro, Nicole; Bernard, Apexa; Skee, Donna; Mamidi, Rao N V S; Tian, Hong; Weiner, Sveta; Stieltjes, Hans; Sha, Sue; Rothenberg, Paul

2015-01-01

Drug-drug interactions between canagliflozin, a sodium glucose co-transporter 2 inhibitor approved for the management of type-2 diabetes mellitus, and an oral contraceptive (OC), warfarin, and digoxin were evaluated in three phase 1 studies in healthy participants. All studies were open-label; study 1 included a fixed-sequence design, and studies 2 and 3 used a crossover design. Regimens were: study 1: OC (levonorgestrel (150 μg) + ethinyl estradiol (30 μg))/day (day 1), canagliflozin 200 mg/day (days 4 - 8), and canagliflozin with OC (day 9); study 2: canagliflozin 300 mg/day (days 1 - 12) with warfarin 30 mg/day (day 6) in period 1, and only warfarin 30 mg/day (day 1) in period 2, or vice versa; study 3: digoxin alone (0.5 mg/day (day 1) + 0.25 mg/day (days 2 - 7)) in period 1, and with canagliflozin 300 mg/day (days 1 - 7) in period 2, or vice versa. Pharmacokinetics (PK) were assessed at prespecified intervals; OC: days 1 and 9, canagliflozin: days 8 - 9 (study 1); warfarin: days 6 (period 1) and 1 (period 2) (study 2); and digoxin: days 5 - 7 (periods 1 and 2) (study 3). Warfarin's pharmacodynamics (PD; International Normalized Ratio (INR)) was assessed on days 6 (period 1) and 1 (period 2). Canagliflozin increased the plasma exposure of OC (maximum plasma concentration (Cmax): 22%, area under the curve (AUC): 6%) and digoxin (Cmax: 36%, AUC: 20%); but did not alter warfarin'€™s PK and PD. No clinically relevant safety findings (including hypoglycemia) were noted. Canagliflozin can be coadministered with OC, warfarin, or digoxin without dose adjustments. All treatments were well-tolerated.

Is caffeic acid phenethyl ester more protective than doxycycline in experimental periodontitis?

PubMed

Yiğit, Umut; Kırzıoğlu, Fatma Yeşim; Uğuz, Abdülhadi Cihangir; Nazıroğlu, Mustafa; Özmen, Özlem

2017-09-01

Host modulation therapies (anti-inflammatory drugs, bone-stimulating agents, anti-proteinase etc.) target the inhibition or stabilization of tissue breakdown. The aim of the present study was to evaluate the effects of caffeic acid phenethyl ester (CAPE) and/or low dose doxycycline (LDD) administrations on alveolar bone loss (ABL), serum cytokines and gingival apoptosis, as well as the levels of oxidants and anti-oxidants in rats with ligature-induced periodontitis. The animals were randomly divided into five groups: Group C (periodontally healthy), Group PC (Periodontitis+CAPE), Group PD (Periodontitis+LDD), Group PCD (Periodontitis+CAPE+LDD), Group P (Periodontitis). Experimental periodontitis was induced for 14days. Levels of ABL, and the serum cytokines, interleukin (IL)-1 β, IL-6, tumor necrosis factor-α (TNF-α) and IL-10 were assessed as were the levels of the oxidants and anti-oxidants, malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GSH-Px), and levels of gingival apoptosis. The lowest ABL levels was evident in the PC group, among the experimental groups. There was also less inflammatory infiltration in the PC group than the PD group. IL-1β, IL-6, and IL-10 were lower in the PC group and higher in the P group in comparison to the levels in the other experiment groups. TNF-α levels in the PD group were higher than levels in the PC and PCD groups. The PC and PCD groups did not differ from the C group in regard to MDA levels. The highest GSH-Px level was found in the PC group. Gingival apoptosis in the PC group was not only lower than the PD and PCD groups, but also lower than in the C group. The present study suggests that CAPE has more anti-inflammatory, anti-oxidant and anti-apoptotic effects than LDD, with no additive benefits of a CAPE+LDD combination being evident in rats with periodontitis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Space-based but not object-based inhibition of return is impaired in Parkinson's disease.

PubMed

Possin, Katherine L; Filoteo, J Vincent; Song, David D; Salmon, David P

2009-06-01

Impairments in certain aspects of attention have frequently been reported in Parkinson's disease (PD), including reduced inhibition of return (IOR). Recent evidence suggests that IOR can occur when attention is directed at objects or locations, but previous investigations of IOR in PD have not systematically compared these two frames of reference. The present study compared the performance of 18 nondemented patients with PD and 18 normal controls on an IOR task with two conditions. In the "object-present" condition, objects surrounded the cues and targets so that attention was cued to both a spatial location and to a specific object. In the "object-absent" condition, surrounding objects were not presented so that attention was cued only to a spatial location. When participants had to rely on space-based cues, PD patients demonstrated reduced IOR compared to controls. In contrast, when objects were present in the display and participants could use object-based cues, PD patients exhibited normal IOR. These results suggest that PD patients are impaired in inhibitory aspects of space-based attention, but are able to overcome this impairment when their attention can be directed at object-based frames of reference. This dissociation supports the view that space-based and object-based components of attention involve distinct neurocognitive processes.

Effect of pretreatment on pd/Al2O3 catalyst for catalytic oxidation of o-xylene at low temperature.

PubMed

Huang, Shaoyong; Zhang, Changbin; He, Hong

2013-06-01

The effect of pretreatment on Pd/Al2O3 catalysts for the catalytic oxidation of o-xylene at low temperature was studied by changing the pretreatment and testing conditions. The fresh and pretreated Pd/Al2O3 catalysts were characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The results showed that the pretreatment dramatically changed the Pd/PdO ratio and then significantly affected the Pd/Al2O3 activity; while the pretreatment had not much influence on Pd particle size. The Pd/Al2O3 pre-reduced at 300 degrees C/400 degrees C, which has fully reduced Pd species, showed the highest activity; while the fresh Pd/Al2O3, which has fully oxidized Pd species, presented the worst performance, indicating the Pd chemical state plays an important role in the catalytic activity for the o-xylene oxidation. It is concluded that metallic Pd is the active species on the Pd/Al2O3 catalyst for the catalytic oxidation of o-xylene at low temperature.

Primary dysmenorrhea magnitude, associated risk factors, and its effect on academic performance: evidence from female university students in Ethiopia

PubMed Central

Hailemeskel, Solomon; Demissie, Asrate; Assefa, Nigussie

2016-01-01

Background Primary dysmenorrhea (PD) is the most common gynecologic compliant among adolescent females. There is a wide variation in the estimate of PD, which ranges from 50% to 90%, and the disorder is the most common cause of work and school absenteeism in adolescent females. Objective To assess the prevalence and associated risk factors of PD among female university students and understand its effects on students’ academic performance. Methods A cross-sectional study was employed in 440 research participants. A multistage stratified sampling technique was employed to select the study units. Structured and pretested self-administered questionnaires were used and weight and height measurements were conducted. The severity of dysmenorrheal pain was assessed by using a verbal multidimensional scoring system and visual analog scale. The data were double entered in Epi Info version 3.1 and analyzed using SPSS version 17. Descriptive statistics, chi-square test, and logistic regression analysis were performed. Results A total of 440 students participated in this study. The prevalence of PD was 368 (85.4%). Of these, 123 (28.5%) had mild, 164 (38.1%) moderate, and 81 (18.8%) severe primary dysmenorrheal pain. Among students with PD, 88.3% reported that PD had a negative effect on their academic performance. Of these, 80% reported school absence, 66.8% reported loss of class concentration, 56.3% reported class absence, 47.4% reported loss of class participation, 37.8% reported limited sport participation, 31.7% reported limitation in going out with friends, and 21% reported inability to do homework. Based on the multivariate logistic regression, PD was statistically significant with those who had lower monthly stipends, a history of attempt to lose weight, a history of depression or anxiety, disruption of social network of family, friends or people they love, who consumed more than four glasses of tea per day, who drunk one or more Coca-Cola or Pepsi per day, in nullipara, and students with a family history of dysmenorrhea. Conclusion PD is more prevalent among female students attending university. It has a significant negative impact on students’ academic performance. Thus, it needs medical attention. There are various identified associated risk factors and considering them in the management of the disorder is fundamental. It is also wise to recommend future studies to better identify risk factors for PD and lighten its effect on students’ academic performance at a larger scale in the country. PMID:27695366

Primary dysmenorrhea magnitude, associated risk factors, and its effect on academic performance: evidence from female university students in Ethiopia.

PubMed

Hailemeskel, Solomon; Demissie, Asrate; Assefa, Nigussie

2016-01-01

Primary dysmenorrhea (PD) is the most common gynecologic compliant among adolescent females. There is a wide variation in the estimate of PD, which ranges from 50% to 90%, and the disorder is the most common cause of work and school absenteeism in adolescent females. To assess the prevalence and associated risk factors of PD among female university students and understand its effects on students' academic performance. A cross-sectional study was employed in 440 research participants. A multistage stratified sampling technique was employed to select the study units. Structured and pretested self-administered questionnaires were used and weight and height measurements were conducted. The severity of dysmenorrheal pain was assessed by using a verbal multidimensional scoring system and visual analog scale. The data were double entered in Epi Info version 3.1 and analyzed using SPSS version 17. Descriptive statistics, chi-square test, and logistic regression analysis were performed. A total of 440 students participated in this study. The prevalence of PD was 368 (85.4%). Of these, 123 (28.5%) had mild, 164 (38.1%) moderate, and 81 (18.8%) severe primary dysmenorrheal pain. Among students with PD, 88.3% reported that PD had a negative effect on their academic performance. Of these, 80% reported school absence, 66.8% reported loss of class concentration, 56.3% reported class absence, 47.4% reported loss of class participation, 37.8% reported limited sport participation, 31.7% reported limitation in going out with friends, and 21% reported inability to do homework. Based on the multivariate logistic regression, PD was statistically significant with those who had lower monthly stipends, a history of attempt to lose weight, a history of depression or anxiety, disruption of social network of family, friends or people they love, who consumed more than four glasses of tea per day, who drunk one or more Coca-Cola or Pepsi per day, in nullipara, and students with a family history of dysmenorrhea. PD is more prevalent among female students attending university. It has a significant negative impact on students' academic performance. Thus, it needs medical attention. There are various identified associated risk factors and considering them in the management of the disorder is fundamental. It is also wise to recommend future studies to better identify risk factors for PD and lighten its effect on students' academic performance at a larger scale in the country.

The rate and pattern of urea infusion into the rumen of wethers alters nitrogen balance and plasma ammonia.

PubMed

Recavarren, M I; Milano, G D

2014-12-01

Changes in N balance, urinary excretion of purine derivative (PD), urea, creatinine and ammonia and plasma ammonia, glucose, urea, insulin and IGF-1 were examined in four wethers (37 ± 2.6 kg BW). The animals were fitted with permanent ruminal catheters, fed lucerne hay (9.4 MJ/day; 23 g N/day; 7 g soluble N/day, 6 equal meals/day) and treated with contrasting rates of urea infusion into the rumen: first, a continuous infusion (CT), at 3.2 mg urea-N/min for 10 days and then a discontinuous infusion (DT) at 156 mg urea-N/min for 4 min; in 6 daily doses with the meals for 7 days. N balance was calculated from pooled samples of faeces and urine. Jugular blood samples were collected before and 1.5 h after the morning meal (M1) on days CT10, DT2, DT4 and DT6. N retention decreased during DT (p = 0.01) due to a significant increase of N excretion in urine (4 g/day; p = 0.009) and faeces (1 g/day; p = 0.02). Dry matter (p < 0.001) and N digestibility in vivo (p = 0.01) decreased significantly during DT. Urinary urea and PD excretion were not altered by treatment. Significant linear (p = 0.004) and quadratic (p = 0.001) effects were observed for plasma ammonia in M1 (from 170 CT10 to 235 μm DT2 and returned to 120 μm DT6). No changes were observed in plasma glucose, urea, insulin and IGF-1. Results indicate that changes from CT to DT reduced N retention in sheep due to enhanced urinary N excretion, but it was not associated with changes in urinary urea or PD excretion; or plasma concentrations of insulin and IGF-1. As the dry matter (DM) an N digestibility could account a 0.23 of the decrease in N retention; the largest fraction of the reduction in N retention remained unexplained by the results. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

PD-1/PD-L1 inhibitors in multiple myeloma: The present and the future

PubMed Central

Jelinek, T.; Hajek, R.

2016-01-01

ABSTRACT The introduction of PD-1/PD-L1 pathway inhibitors has marked a significant milestone in the treatment of various types of solid tumors. The current situation in multiple myeloma (MM) is rather unclear, as distinct research groups have reported discordant results. This discrepancy dominantly concerns the expression of PD-1/PD-L1 molecules as well as the identification of the responsible immune effector cell population. The results of monotherapy with PD-1/PD-L1 inhibitors have been unsatisfactory in MM, suggesting that a combination approach is needed. The most logical partners are immunomodulatory agents as they possess many synergistic effects. We are also proposing other rational and promising combinations (e.g., daratumumab, ibrutinib, anti-CD137) that warrant further investigation. PMID:28123899

Carbon-Supported Pd and PdFe Alloy Catalysts for Direct Methanol Fuel Cell Cathodes.

PubMed

Rivera Gavidia, Luis M; Sebastián, David; Pastor, Elena; Aricò, Antonino S; Baglio, Vincenzo

2017-05-25

Direct methanol fuel cells (DMFCs) are electrochemical devices that efficiently produce electricity and are characterized by a large flexibility for portable applications and high energy density. Methanol crossover is one of the main obstacles for DMFC commercialization, forcing the search for highly electro-active and methanol tolerant cathodes. In the present work, carbon-supported Pd and PdFe catalysts were synthesized using a sodium borohydride reduction method and physico-chemically characterized using transmission electron microscopy (TEM) and X-ray techniques such as photoelectron spectroscopy (XPS), diffraction (XRD) and energy dispersive spectroscopy (EDX). The catalysts were investigated as DMFC cathodes operating at different methanol concentrations (up to 10 M) and temperatures (60 °C and 90 °C). The cell based on PdFe/C cathode presented the best performance, achieving a maximum power density of 37.5 mW·cm -2 at 90 °C with 10 M methanol, higher than supported Pd and Pt commercial catalysts, demonstrating that Fe addition yields structural changes to Pd crystal lattice that reduce the crossover effects in DMFC operation.

Carbon-Supported Pd and PdFe Alloy Catalysts for Direct Methanol Fuel Cell Cathodes

PubMed Central

Rivera Gavidia, Luis M.; Sebastián, David; Pastor, Elena; Aricò, Antonino S.; Baglio, Vincenzo

2017-01-01

Direct methanol fuel cells (DMFCs) are electrochemical devices that efficiently produce electricity and are characterized by a large flexibility for portable applications and high energy density. Methanol crossover is one of the main obstacles for DMFC commercialization, forcing the search for highly electro-active and methanol tolerant cathodes. In the present work, carbon-supported Pd and PdFe catalysts were synthesized using a sodium borohydride reduction method and physico-chemically characterized using transmission electron microscopy (TEM) and X-ray techniques such as photoelectron spectroscopy (XPS), diffraction (XRD) and energy dispersive spectroscopy (EDX). The catalysts were investigated as DMFC cathodes operating at different methanol concentrations (up to 10 M) and temperatures (60 °C and 90 °C). The cell based on PdFe/C cathode presented the best performance, achieving a maximum power density of 37.5 mW·cm−2 at 90 °C with 10 M methanol, higher than supported Pd and Pt commercial catalysts, demonstrating that Fe addition yields structural changes to Pd crystal lattice that reduce the crossover effects in DMFC operation. PMID:28772937

The role of loss of control eating in purging disorder.

PubMed

Forney, K Jean; Haedt-Matt, Alissa A; Keel, Pamela K

2014-04-01

Purging Disorder (PD), an Other Specified Feeding or Eating Disorder (APA, 2013), is characterized by recurrent purging in the absence of binge eating. Though objectively large binge episodes are not present, individuals with PD may experience a loss of control (LOC) while eating a normal or small amounts of food. The present study sought to examine the role of LOC eating in PD using archival data from 101 women with PD. Participants completed diagnostic interviews and self-report questionnaires. Analyses examined the relationship between LOC eating and eating disorder features, psychopathology, personality traits, and impairment in bivariate models and then in multivariate models controlling for purging frequency, age, and body mass index. Across bivariate and multivariate models, LOC eating frequency was associated with greater disinhibition around food, hunger, depressive symptoms, negative urgency, distress, and impairment. LOC eating is a clinically significant feature of PD and should be considered in future definitions of PD. Future research should examine whether LOC eating better represents a dimension of severity in PD or a specifier that may impact treatment response or course. Copyright © 2013 Wiley Periodicals, Inc.

Chlorogenic Acid Prevents Alcohol-induced Brain Damage in Neonatal Rat.

PubMed

Guo, Zikang; Li, Jiang

2017-01-01

The present investigation evaluates the neuroprotective effect of chlorogenic acid (CA) in alcohol-induced brain damage in neonatal rats. Ethanol (12 % v/v, 5 g/kg) was administered orally in the wistar rat pups on postnatal days (PD) 7-9. Chlorogenic acid (100 and 200 mg/kg, p.o.) was administered continuously from PD 6 to 28. Cognitive function was estimated by Morris water maze (MWM) test. However, activity of acetylcholinesterase, inflammatory mediators, parameters of oxidative stress and activity of caspase-3 enzyme was estimated in the tissue homogenate of cerebral cortex and hippocampus of ethanol-exposed pups. It has been observed that treatment with CA attenuates the altered cognitive function in ethanol-exposed pups. There was a significant decrease in the activity of acetylcholinesterase in the CA treated group compared to the negative control group. However, treatment with CA significantly ameliorates the increased oxidative stress and concentration of inflammatory mediators in the brain tissues of ethanol-exposed pups. Activity of caspase-3 enzyme was also found significantly decreased in the CA treated group compared to the negative control group. The present study concludes that CA attenuates the neuronal damage induced in alcohol exposed neonatal rat by decreasing the apoptosis of neuronal cells.

Blockade of Tumor-Expressed PD-1 promotes lung cancer growth

PubMed Central

Du, Shisuo; McCall, Neal; Park, Kyewon; Guan, Qing; Fontina, Paolo; Ertel, Adam; Zhan, Tingting; Dicker, Adam P.; Lu, Bo

2018-01-01

ABSTRACT Anti-PD-1 immunotherapy is the standard of care for treating many patients with non-small cell lung cancer (NSCLC), yet mechanisms of treatment failure are emerging. We present a case of NSCLC, who rapidly progressed during a trial (NCT02318771) combining palliative radiotherapy and pembrolizumab. Planned tumor biopsy demonstrated PD-1 expression by NSCLC cells. We validated this observation by detecting PD-1 transcript in lung cancer cells and by co-localizing PD-1 and lung cancer-specific markers in resected lung cancer tissues. We further investigated the biological role of cancer-intrinsic PD-1 in a mouse lung cancer cell line, M109. Knockout or antibody blockade of PD-1 enhanced M109 viability in-vitro, while PD-1 overexpression and exposure to recombinant PD-L1 diminished viability. PD-1 blockade accelerated growth of M109-xenograft tumors with increased proliferation and decreased apoptosis in immune-deficient mice. This represents a first-time report of NSCLC-intrinsic PD-1 expression and a potential mechanism by which PD-1 blockade may promote cancer growth. PMID:29632720

Blockade of Tumor-Expressed PD-1 promotes lung cancer growth.

PubMed

Du, Shisuo; McCall, Neal; Park, Kyewon; Guan, Qing; Fontina, Paolo; Ertel, Adam; Zhan, Tingting; Dicker, Adam P; Lu, Bo

2018-01-01

Anti-PD-1 immunotherapy is the standard of care for treating many patients with non-small cell lung cancer (NSCLC), yet mechanisms of treatment failure are emerging. We present a case of NSCLC, who rapidly progressed during a trial (NCT02318771) combining palliative radiotherapy and pembrolizumab. Planned tumor biopsy demonstrated PD-1 expression by NSCLC cells. We validated this observation by detecting PD-1 transcript in lung cancer cells and by co-localizing PD-1 and lung cancer-specific markers in resected lung cancer tissues. We further investigated the biological role of cancer-intrinsic PD-1 in a mouse lung cancer cell line, M109. Knockout or antibody blockade of PD-1 enhanced M109 viability in-vitro, while PD-1 overexpression and exposure to recombinant PD-L1 diminished viability. PD-1 blockade accelerated growth of M109-xenograft tumors with increased proliferation and decreased apoptosis in immune-deficient mice. This represents a first-time report of NSCLC-intrinsic PD-1 expression and a potential mechanism by which PD-1 blockade may promote cancer growth.

Pharmacokinetic–Pharmacodynamic Modeling of Enrofloxacin Against Escherichia coli in Broilers

PubMed Central

Sang, KaNa; Hao, HaiHong; Huang, LingLi; Wang, Xu; Yuan, ZongHui

2016-01-01

The purpose of the present study was to establish a pharmacokinetic/pharmacodynamic (PK/PD) modeling approach for the dosage schedule design and decreasing the emergence of drug-resistant bacteria. The minimal inhibitory concentration (MIC) of 929 Escherichia coli isolates from broilers to enrofloxacin and ciprofloxacin was determined following CLSI guidance. The MIC50 was calculated as the populational PD parameter for enrofloxacin against E. coli in broilers. The 101 E. coli strains with MIC closest to the MIC50 (0.05 μg/mL) were submitted for serotype identification. The 13 E. coli strains with O and K serotype were further utilized for determining pathogencity in mice. Of all the strains tested, the E. coli designated strain Anhui 112 was selected for establishing the disease model and PK/PD study. The PKs of enrofloxacin after oral administration at the dose of 10 mg/kg body weights (BW) in healthy and infected broilers was evaluated with high-performance liquid chromatography (HPLC) method. For intestinal contents after oral administration, the peak concentration (Cmax), the time when the maximum concentration reached (Tmax), and the area under the concentration-time curve (AUC) were 21.69–31.69 μg/mL, 1.13–1.23 h, and 228.97–444.86 μg h/mL, respectively. The MIC and minimal bactericidal concentration (MBC) of enrofloxacin against E. coli (Anhui 112) in Mueller–Hinton (MH) broth and intestinal contents were determined to be similar, 0.25 and 0.5 μg/mL respectively. In this study, the sum of concentrations of enrofloxacin and its metabolite (ciprofloxacin) was used for the PK/PD integration and modeling. The ex vivo growth inhibition data were fitted to the sigmoid Emax (Hill) equation to provide values for intestinal contents of 24 h area under concentration-time curve/MIC ratios (AUC0–24 h/MIC) producing, bacteriostasis (624.94 h), bactericidal activity (1065.93 h) and bacterial eradication (1343.81 h). PK/PD modeling was established to simulate the efficacy of enrofloxacin for different dosage regimens. By model validation, the protection rate was 83.3%, demonstrating that the dosage regimen of 11.9 mg/kg BW every 24 h during 3 days provided great therapeutic significance. In summary, the purpose of the present study was to first design a dosage regimen for the treatment E. coli in broilers by enrofloxacin using PK/PD integrate model and confirm that this dosage regimen presents less risk for emergence of floroquinolone resistance. PMID:26779495

Innovative Procedure for the, in Situ, Measurement of the Resistive Thermal Coefficient of H(D)/Pd during Electrolysis:. Cross-Comparison of New Elements Detected in the Th-Hg-Pd-D(H) Electrolytic Cells

NASA Astrophysics Data System (ADS)

Celani, Francesco; Spallone, A.; Righi, E.; Trenta, G.; Catena, C.; D'Agostaro, G.; Quercia, P.; Andreassi, V.; Marini, P.; di Stefano, V.; Nakamura, M.; Mancini, A.; Sona, P. G.; Fontana, F.; Gamberale, L.; Garbelli, D.; Celia, E.; Falcioni, F.; Marchesini, M.; Novaro, E.; Mastromatteo, U.

2006-02-01

In the framework of cold fusion studies one of the most important parameters is the deuterium (D) to palladium (Pd) ratio, D/Pd. It is well known that the value of this parameter is related to the normalised resistivity (R/R0) of the D-Pd system. When at high D/Pd ratios (i.e. at low R/R0 values) some excess heat occurs, the Pd wire temperature increase and, as a consequence, the apparent R/R0 value also increases. This effect might give raise to ambiguous data interpretation: similar results are in fact expected in case of a Pd wire degassing (i.e. decreasing of D/Pd ratio). To solve this problem, we developed an innovative procedure and a suitable experimental set-up for the in situ measurement of the Resistive Temperature Coefficient (which is affected only by the real D/Pd ratio) during electrolysis. We will report the results on the hydrogen and deuterium loading of thin (50 μm), and long (60cm) Pd wires, immersed in a solution of C2H5OD (or C2H5OH) and D2O (or H2O), with addition of thorium (Th) and mercury (Hg) salts at micromolar concentrations. Evidence of "transmutations" of some elements occasionally present on the Pd surface, and sometimes also in the electrolytic solution, have often been claimed in cold fusion experiments. In the present work, unexpected elements have been detected by high-resolution ICP-MS analysis. Some of these elements have also an isotopic composition different from the natural one.

Effects of disease severity and medication state on postural control asymmetry during challenging postural tasks in individuals with Parkinson's disease.

PubMed

Barbieri, Fabio A; Polastri, Paula F; Baptista, André M; Lirani-Silva, Ellen; Simieli, Lucas; Orcioli-Silva, Diego; Beretta, Victor S; Gobbi, Lilian T B

2016-04-01

The aim of this study was to investigate the effects of disease severity and medication state on postural control asymmetry during challenging tasks in individuals with Parkinson's disease (PD). Nineteen people with PD and 11 neurologically healthy individuals performed three standing task conditions: bipedal standing, tandem and unipedal adapted standing; the individuals with PD performed the tasks in ON and OFF medication state. The participants with PD were distributed into 2 groups according to disease severity: unilateral group (n=8) and bilateral group (n=11). The two PD groups performed the evaluations both under and without the medication. Two force plates were used to analyze the posture. The symmetric index was calculated for various of center of pressure. ANOVA one-way (groups) and two-way (PD groups×medication), with repeated measures for medication, were calculated. For main effects of group, the bilateral group was more asymmetric than CG. For main effects of medication, only unipedal adapted standing presented effects of PD medication. There was PD groups×medication interaction. Under the effects of medication, the unilateral group presented lower asymmetry of RMS in anterior-posterior direction and area than the bilateral group in unipedal adapted standing. In addition, the unilateral group presented lower asymmetry of mean velocity, RMS in anterior-posterior direction and area in unipedal standing and area in tandem adapted standing after a medication dose. Postural control asymmetry during challenging postural tasks was dependent on disease severity and medication state in people with PD. The bilateral group presented higher postural control asymmetry than the control and unilateral groups in challenging postural tasks. Finally, the medication dose was able to reduce postural control asymmetry in the unilateral group during challenging postural tasks. Copyright © 2015 Elsevier B.V. All rights reserved.

Geochemical behaviour of palladium in soils and Pd/PdO model substances in the presence of the organic complexing agents L-methionine and citric acid.

PubMed

Zereini, Fathi; Wiseman, Clare L S; Vang, My; Albers, Peter; Schneider, Wolfgang; Schindl, Roland; Leopold, Kerstin

2016-01-01

Risk assessments of platinum group metal (PGE) emissions, notably those of platinum (Pt), palladium (Pd) and rhodium (Rh), have been mostly based on data regarding the metallic forms used in vehicular exhaust converters, known to be virtually biologically inert and immobile. To adequately assess the potential impacts of PGE, however, data on the chemical behaviour of these metals under ambient conditions post-emission is needed. Complexing agents with a high affinity for metals in the environment are hypothesized to contribute to an increased bioaccessibility of PGE. The purpose of this study is to examine the modulating effects of the organic complexing agents, L-methionine and citric acid, on the geochemical behavior of Pd in soils and model substances (Pd black and PdO). Batch experimental tests were conducted with soils and model substances to examine the impacts of the concentration of complexing agents, pH and length of extraction period on Pd solubility and its chemical transformation. Particle surface chemistry was examined using X-ray photoelectron spectroscopy (XPS) on samples treated with solutions under various conditions, including low and high O2 levels. Pd was observed to be more soluble in the presence of organic complexing agents, compared to Pt and Rh. Pd in soils was more readily solubilized with organic complexing agents compared to the model substances. After 7 days of extraction, L-methionine (0.1 M) treated soil and Pd black samples, for instance, had mean soluble Pd fractions of 12.4 ± 5.9% and 0.554 ± 0.024%, respectively. Surface chemistry analyses (XPS) confirmed the oxidation of metallic Pd surfaces when treated with organic complexing agents. The type of organic complexing agent used for experimental purposes was observed to be the most important factor influencing solubility, followed by solution pH and time of extraction. The results demonstrate that metallic Pd can be transformed into more bioaccessible species in the presence of organic complexing agents which are ubiquitous in the environment.

Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma

PubMed Central

Koirala, Pratistha; Roth, Michael E.; Gill, Jonathan; Piperdi, Sajida; Chinai, Jordan M.; Geller, David S.; Hoang, Bang H.; Park, Amy; Fremed, Michael A.; Zang, Xingxing; Gorlick, Richard

2016-01-01

Osteosarcoma patient survival has remained stagnant for 30 years. Novel therapeutic approaches are needed to improve outcomes. We examined the expression of Programmed Death Ligand 1 (PD-L1) and defined the tumor immune microenvironment to assess the prognostic utility in osteosarcoma. PD-L1 expression in osteosarcoma was examined in two patient cohorts using immunohistochemistry (IHC) (n = 48, n = 59) and expression was validated using quantitative real time PCR (n = 21) and western blotting (n = 9). IHC was used to determine the presence of tumor infiltrating lymphocytes and antigen-presenting cells (APCs) in the tumor. Expression of PD-L1 was correlated with immune cell infiltration and event-free-survival (EFS). The 25% of primary osteosarcoma tumors that express PD-L1 were more likely to contain cells that express PD-1 than PD-L1 negative tumors (91.7% vs 47.2%, p = 0.002). Expression of PD-L1 was significantly associated with the presence of T cells, dendritic cells, and natural killer cells. Although all immune cell types examined were present in osteosarcoma samples, only infiltration by dendritic cells (28.3% vs. 83.9%, p = 0.001) and macrophages (45.5% vs. 84.4%, p = 0.031) were associated with worse five-year-EFS. PD-L1 expression was significantly associated with poorer five-year-EFS (25.0%. vs. 69.4%, p = 0.014). Further studies in osteosarcoma are needed to determine if targeting the PD-L1:PD-1 axis improves survival. PMID:27456063

Asymptomatic Effluent Protozoa Colonization in Peritoneal Dialysis Patients.

PubMed

Simões-Silva, Liliana; Correia, Inês; Barbosa, Joana; Santos-Araujo, Carla; Sousa, Maria João; Pestana, Manuel; Soares-Silva, Isabel; Sampaio-Maia, Benedita

Currently, chronic kidney disease (CKD) is a global health problem. Considering the impaired immunity of CKD patients, the relevance of infection in peritoneal dialysis (PD), and the increased prevalence of parasites in CKD patients, protozoa colonization was evaluated in PD effluent from CKD patients undergoing PD. Overnight PD effluent was obtained from 49 asymptomatic stable PD patients. Protozoa analysis was performed microscopically by searching cysts and trophozoites in direct wet mount of PD effluent and after staining smears. Protozoa were found in PD effluent of 10.2% of evaluated PD patients, namely Blastocystis hominis, in 2 patients, and Entamoeba sp., Giardia sp., and Endolimax nana in the other 3 patients, respectively. None of these patients presented clinical signs or symptoms of peritonitis at the time of protozoa screening. Our results demonstrate that PD effluent may be susceptible to asymptomatic protozoa colonization. The clinical impact of this finding should be further investigated. Copyright © 2016 International Society for Peritoneal Dialysis.

Improving diet recipe and cooking methods attenuates hyperphosphatemia in patients undergoing peritoneal dialysis.

PubMed

Jiang, N; Fang, W; Gu, A P; Yuan, J Z; Yang, X X; Lin, A W; Ni, Z H; Qian, J Q

2015-09-01

Hyperphosphatemia is an independent predictor for cardiovascular and all-cause mortality in patients undergoing peritoneal dialysis (PD). The study aimed to investigate the effect of dietary intervention on reducing serum phosphate concentration in hyperphosphatemic PD patients. In this single-center clinical trial, 97 prevalent PD patients with serum phosphate concentration ≥ 1.6 mmol/l were allocated to the intervention (n = 48) or control (n = 49) group and followed up for 1 year. In addition to phosphate binder (calcium carbonate) therapy, patients in the intervention group were intensively educated to reduce phosphate-rich food intake and improve cooking methods. While stable in the control group (1.97 ± 0.20 to 1.94 ± 0.35 mmol/l, p > 0.05), the serum phosphate concentration decreased significantly in the intervention group (1.98 ± 0.28 to 1.65 ± 0.33 mmol/l, p = 0.015) concurrently with the drop in dietary phosphate intake (13.03 ± 3.39 to 10.82 ± 3.00 mg/kg ideal body weight/day, p = 0.001). Moreover, after 6 months of intervention, fewer patients needed to use calcium carbonate (from 64.6% to 41.5%, p = 0.029) and the medicine dose reduced significantly (from 2.25 (0, 3.94) to 0 (0, 1.50) g/day, p < 0.001). Our data indicated that intensive dietary intervention of reducing phosphate-rich food intake and improving cooking methods attenuated hyperphosphatemia in PD patients. It suggests that regular assessment of dietary phosphate intake and modification of diet recipe and cooking methods are essential for hyperphosphatemia treatment in PD patients in addition to phosphate binder therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Neurorestoration induced by the HDAC inhibitor sodium valproate in the lactacystin model of Parkinson’s is associated with histone acetylation and up-regulation of neurotrophic factors

PubMed Central

Harrison, Ian F; Crum, William R; Vernon, Anthony C; Dexter, David T

2015-01-01

Background and Purpose Histone hypoacetylation is associated with Parkinson's disease (PD), due possibly to an imbalance in the activities of enzymes responsible for histone (de)acetylation; correction of which may be neuroprotective/neurorestorative. This hypothesis was tested using the anti-epileptic drug sodium valproate, a known histone deacetylase inhibitor (HDACI), utilizing a delayed-start study design in the lactacystin rat model of PD. Experimental Approach The irreversible proteasome inhibitor lactacystin was unilaterally injected into the substantia nigra of Sprague–Dawley rats that subsequently received valproate for 28 days starting 7 days after lactacystin lesioning. Longitudinal motor behavioural testing, structural MRI and post-mortem assessment of nigrostriatal integrity were used to track changes in this model of PD and quantify neuroprotection/restoration. Subsequent cellular and molecular analyses were performed to elucidate the mechanisms underlying valproate's effects. Key Results Despite producing a distinct pattern of structural re-modelling in the healthy and lactacystin-lesioned brain, delayed-start valproate administration induced dose-dependent neuroprotection/restoration against lactacystin neurotoxicity, characterized by motor deficit alleviation, attenuation of morphological brain changes and restoration of dopaminergic neurons in the substantia nigra. Molecular analyses revealed that valproate alleviated lactacystin-induced histone hypoacetylation and induced up-regulation of brain neurotrophic/neuroprotective factors. Conclusions and Implications The histone acetylation and up-regulation of neurotrophic/neuroprotective factors associated with valproate treatment culminate in a neuroprotective and neurorestorative phenotype in this animal model of PD. As valproate induced structural re-modelling of the brain, further research is required to determine whether valproate represents a viable candidate for disease treatment; however, the results suggest that HDACIs could hold potential as disease-modifying agents in PD. PMID:26040297

The effect of Zn2+ on glucose 6-phosphate dehydrogenase activity from Bufo arenarum toad ovary and alfalfa plants.

PubMed

Fonovich de Schroeder, Teresa M

2005-02-01

The effect of Zn2+ on glucose 6-phosphate dehydrogenase (G6PD) activity was monitored in samples from Bufo arenarum toad ovary and alfalfa plants, in the search for a possible new bioindicator able to detect levels of exposure through contaminated soils, and also to elucidate possible similarities between the enzyme from animal and plant tissues. The in vivo effect was evaluated after exposure of the toads to the metal in Ringer solution during 30 days and after 10 days of treatment in 6 weeks old plants, cultured under laboratory conditions. In vitro effects were measured in different extracts from control samples and partially purified enzyme from ovarian tissue as well as in different extracts from control alfalfa plants, by addition of the metal to the reaction mixture containing the enzyme. G6PD from toad ovary was noncompetitively inhibited by zinc both in vivo and in vitro, under all the experimental conditions studied. A kinetic analysis of the enzyme activity showed that the Michaelis-Menten constant (Km) was not modified, while maximal velocity (Vmax) decreased as the consequence of treatment. It was not possible to obtain a dose-response curve for the effects of Zn2+ on G6PD from alfalfa whole plants, measured in vivo or in vitro. Only leaf extracts evidenced a possible relationship between treatment with the metal and G6PD activity alteration. The results agree with a possible role for G6PD as a biomarker of effect and exposure to Zn2+ in B. arenarum ovarian tissue but not in alfalfa plants.

Does a specialist unit improve outcomes for hospitalized patients with Parkinson's disease?

PubMed Central

Skelly, Rob; Brown, Lisa; Fakis, Apostolos; Kimber, Lindsey; Downes, Charlotte; Lindop, Fiona; Johnson, Clare; Bartliff, Caroline; Bajaj, Nin

2014-01-01

Objective Suboptimal management of Parkinson's disease (PD) medication in hospital may lead to avoidable complications. We introduced an in-patient PD unit for those admitted urgently with general medical problems. We explored the effect of the unit on medication management, length of stay and patient experience. Methods We conducted a single-center prospective feasibility study. The unit's core features were defined following consultation with patients and professionals: specially trained staff, ready availability of PD drugs, guidelines, and care led by a geriatrician with specialty PD training. Mandatory staff training comprised four 1 h sessions: PD symptoms; medications; therapy; communication and swallowing. Most medication was prescribed using an electronic Prescribing and Administration system (iSOFT) which provided accurate data on time of administration. We compared patient outcomes before and after introduction of the unit. Results The general ward care (n = 20) and the Specialist Parkinson's Unit care (n = 24) groups had similar baseline characteristics. On the specialist unit: less Parkinson's medication was omitted (13% vs 20%, p < 0.001); of the medication that was given, more was given on time (64% vs 50%, p < 0.001); median length of stay was shorter (9 days vs 13 days, p = 0.043) and patients' experience of care was better (p = 0.01). Discussion If replicated and generalizable to other hospitals, reductions in length of stay would lead to significant cost savings. The apparent improved outcomes with Parkinson's unit care merit further investigation. We hope to test the hypothesis that specialized units are cost-effective and improve patient care using a randomized controlled trial design. PMID:25264022