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1.
Structure ; 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38513659

ABSTRACT

Mollusk hemocyanins, among the largest known proteins, are used as immunostimulants in biomedical and clinical applications. The hemocyanin of the Chilean gastropod Concholepas concholepas (CCH) exhibits unique properties, which makes it safe and effective for human immunotherapy, as observed in animal models of bladder cancer and melanoma, and dendritical cell vaccine trials. Despite its potential, the structure and amino acid sequence of CCH remain unknown. This study reports two sequence fragments of CCH, representing three complete functional units (FUs). We also determined the high-resolution (1.5 Å) X-ray crystal structure of an "FU-g type" from the CCHB subunit. This structure enables in-depth analysis of chemical interactions at the copper-binding center and unveils an unusual, truncated N-glycosylation pattern. These features are linked to eliciting more robust immunological responses in animals, offering insights into CCH's enhanced immunostimulatory properties and opening new avenues for its potential applications in biomedical research and therapies.

2.
Sci Total Environ ; 916: 170326, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38266720

ABSTRACT

Seawater desalination by reverse osmosis is growing exponentially due to water scarcity. Byproducts of this process (e.g. brines), are generally discharged directly into the coastal ecosystem, causing detrimental effects, on benthic organisms. Understanding the cellular stress response of these organisms (biomarkers), could be crucial for establishing appropriate salinity thresholds for discharged brines. Early stress biomarkers can serve as valuable tools for monitoring the health status of brine-impacted organisms, enabling the prediction of long-term irreversible damage caused by the desalination industry. In this study, we conducted laboratory-controlled experiments to assess cellular and molecular biomarkers against brine exposure in two salinity-sensitive Mediterranean seagrasses: Posidonia oceanica and Cymodocea nodosa. Treatments involved exposure to 39, 41, and 43 psu, for 6 h and 7 days. Results indicated that photosynthetic performance remained unaffected across all treatments. However, under 43 psu, P. oceanica and C. nodosa exhibited lipid oxidative damage, which occurred earlier in P. oceanica. Additionally, P. oceanica displayed an antioxidant response at higher salinities by accumulating phenolic compounds within 6 h and ascorbate within 7 d; whereas for C. nodosa the predominant antioxidant mechanisms were phenolic compounds accumulation and total radical scavenging activity, which was evident after 7 d of brines exposure. Finally, transcriptomic analyses in P. oceanica exposed to 43 psu for 7 days revealed a poor up-regulation of genes associated with brassinosteroid response and abiotic stress response, while a high down-regulation of genes related to primary metabolism was detected. In C. nodosa, up-regulated genes were involved in DNA repair, cell cycle regulation, and reproduction, while down-regulated genes were mainly associated with photosynthesis and ribosome assembly. Overall, these findings suggest that 43 psu is a critical salinity-damage threshold for both seagrasses; and despite the moderate overexpression of several transcripts that could confer salt tolerance, genes involved in essential biological processes were severely downregulated.


Subject(s)
Alismatales , Ecosystem , Salts , Antioxidants/metabolism , Alismatales/physiology , Gene Expression Profiling , Mediterranean Sea
3.
Biol Res ; 56(1): 6, 2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36797803

ABSTRACT

BACKGROUND: Despite representing the largest fraction of animal life, the number of insect species whose genome has been sequenced is barely in the hundreds. The order Dermaptera (the earwigs) suffers from a lack of genomic information despite its unique position as one of the basally derived insect groups and its importance in agroecosystems. As part of a national educational and outreach program in genomics, a plan was formulated to engage the participation of high school students in a genome sequencing project. Students from twelve schools across Chile were instructed to capture earwig specimens in their geographical area, to identify them and to provide material for genome sequencing to be carried out by themselves in their schools. RESULTS: The school students collected specimens from two cosmopolitan earwig species: Euborellia annulipes (Fam. Anisolabididae) and Forficula auricularia (Fam. Forficulidae). Genomic DNA was extracted and, with the help of scientific teams that traveled to the schools, was sequenced using nanopore sequencers. The sequence data obtained for both species was assembled and annotated. We obtained genome sizes of 1.18 Gb (F. auricularia) and 0.94 Gb (E. annulipes) with the number of predicted protein coding genes being 31,800 and 40,000, respectively. Our analysis showed that we were able to capture a high percentage (≥ 93%) of conserved proteins indicating genomes that are useful for comparative and functional analysis. We were also able to characterize structural elements such as repetitive sequences and non-coding RNA genes. Finally, functional categories of genes that are overrepresented in each species suggest important differences in the process underlying the formation of germ cells, and modes of reproduction between them, features that are one of the distinguishing biological properties that characterize these two distant families of Dermaptera. CONCLUSIONS: This work represents an unprecedented instance where the scientific and lay community have come together to collaborate in a genome sequencing project. The versatility and accessibility of nanopore sequencers was key to the success of the initiative. We were able to obtain full genome sequences of two important and widely distributed species of insects which had not been analyzed at this level previously. The data made available by the project should illuminate future studies on the Dermaptera.


Subject(s)
Insecta , Animals , Insecta/genetics , Sequence Analysis, DNA , Chile
4.
Biol. Res ; 56: 6-6, 2023. ilus, tab, graf
Article in English | LILACS | ID: biblio-1429907

ABSTRACT

BACKGROUND: Despite representing the largest fraction of animal life, the number of insect species whose genome has been sequenced is barely in the hundreds. The order Dermaptera (the earwigs) suffers from a lack of genomic information despite its unique position as one of the basally derived insect groups and its importance in agroecosystems. As part of a national educational and outreach program in genomics, a plan was formulated to engage the participation of high school students in a genome sequencing project. Students from twelve schools across Chile were instructed to capture earwig specimens in their geographical area, to identify them and to provide material for genome sequencing to be carried out by themselves in their schools. RESULTS: The school students collected specimens from two cosmopolitan earwig species: Euborellia annulipes (Fam. Anisolabididae) and Forficula auricularia (Fam. Forficulidae). Genomic DNA was extracted and, with the help of scientific teams that traveled to the schools, was sequenced using nanopore sequencers. The sequence data obtained for both species was assembled and annotated. We obtained genome sizes of 1.18 Gb (F. auricularia) and 0.94 Gb (E. annulipes) with the number of predicted protein coding genes being 31,800 and 40,000, respectively. Our analysis showed that we were able to capture a high percentage (≥ 93%) of conserved proteins indicating genomes that are useful for comparative and functional analysis. We were also able to characterize structural elements such as repetitive sequences and non-coding RNA genes. Finally, functional categories of genes that are overrepresented in each species suggest important differences in the process underlying the formation of germ cells, and modes of reproduction between them, features that are one of the distinguishing biological properties that characterize these two distant families of Dermaptera. CONCLUSIONS: This work represents an unprecedented instance where the scientific and lay community have come together to collaborate in a genome sequencing project. The versatility and accessibility of nanopore sequencers was key to the success of the initiative. We were able to obtain full genome sequences of two important and widely distributed species of insects which had not been analyzed at this level previously. The data made available by the project should illuminate future studies on the Dermaptera.


Subject(s)
Animals , Insecta/genetics , Chile , Sequence Analysis, DNA
5.
Int J Mol Sci ; 23(13)2022 Jun 30.
Article in English | MEDLINE | ID: mdl-35806287

ABSTRACT

The genome of the marine alga Ulva compressa was assembled using long and short reads. The genome assembly was 80.8 Mb in size and encoded 19,207 protein-coding genes. Several genes encoding antioxidant enzymes and a few genes encoding enzymes that synthesize ascorbate and glutathione were identified, showing similarity to plant and bacterial enzymes. Additionally, several genes encoding signal transduction protein kinases, such as MAPKs, CDPKS, CBLPKs, and CaMKs, were also detected, showing similarity to plants, green microalgae, and bacterial proteins. Regulatory transcription factors, such as ethylene- and ABA-responsive factors, MYB, WRKY, and HSTF, were also present and showed similarity to plant and green microalgae transcription factors. Genes encoding enzymes that synthesize ACC and ABA-aldehyde were also identified, but oxidases that synthesize ethylene and ABA, as well as enzymes that synthesize other plant hormones, were absent. Interestingly, genes involved in plant cell wall synthesis and proteins related to animal extracellular matrix were also detected. Genes encoding cyclins and CDKs were also found, and CDKs showed similarity to animal and fungal CDKs. Few genes encoding voltage-dependent calcium channels and ionotropic glutamate receptors were identified as showing similarity to animal channels. Genes encoding Transient Receptor Potential (TRP) channels were not identified, even though TRPs have been experimentally detected, indicating that the genome is not yet complete. Thus, protein-coding genes present in the genome of U. compressa showed similarity to plant and green microalgae, but also to animal, bacterial, and fungal genes.


Subject(s)
Chlorophyta , Microalgae , Ulva , Animals , Chlorophyta/genetics , Chlorophyta/metabolism , Copper/metabolism , Ethylenes/metabolism , Genes, Fungal , Microalgae/metabolism , Transcription Factors/metabolism
6.
Am J Primatol ; 84(7): e23381, 2022 07.
Article in English | MEDLINE | ID: mdl-35389525

ABSTRACT

In primates, urine washing (UW) is a behavior in which individuals intentionally deposit urine on their bodies. Social and nonsocial hypotheses have been proposed to explain the adaptive function of this behavior. For capuchins, different functions have been assigned for UW, suggesting it as a flexible behavior, but studies have been mainly in captivity. However, no investigations have been performed in urban environments, where these animals can modify their behavior. Our goal was to study UW in a semi-provisioned group of an introduced unknown robust capuchin species (Sapajus sp.) living in a tiny urban fragment in Foz do Iguaçu, Brazil, where they have contact with humans. We assessed the influence of social (sexual, agonistic, and anointing behaviors) and environmental (temperature, relative air humidity, height of the monkeys in the trees, number of people present in the fragment, and human-monkey interactions) variables, the influence of behavior before and after UW, and the influence of sex-age classes, on the frequency of UW. We observed 75 records of UW in 300 h of observations, where urine was mostly deposited on hands and passed on to feet (95%). There were no significant differences in the frequency of the behavior between sex-age classes nor in the behaviors before and after UW. Around 50% of UW took place in the late morning and we found no correlation between UW and temperature, relative air humidity, nor the heights of the monkeys in the trees. However, we found a significant association between UW and the daily number of people in the fragment, but not between UW and human-monkey interactions, anointing, agonisms, and sexual behavior. Our study increases the scope of UW flexibility by identifying the presence of visitors affecting the occurrence of this behavior. We discussed different possibilities through which people could influence the capuchins to display UW.


Subject(s)
Cebus , Sapajus , Animals , Brazil , Haplorhini , Humans
8.
Ind Eng Chem Res ; 61(17): 6052-6056, 2022 May 04.
Article in English | MEDLINE | ID: mdl-37538052

ABSTRACT

This communication proposes a preliminary simplified kinetic model for the hydrogenation of 1-phenyl-1,2-propanedione that can render up to eight compounds, involving regioselectivity and enantioselectivity. The catalytic system comprises two functionalities; the heterogeneous catalyst (Ir/TiO2) plays the role for the hydrogenation, whereas the adsorption/binding to the active site is played by a chiral molecule (cinchonidine), added to the reaction mixture. The reaction occurs at room temperature and total pressure of 40 bar. The product distribution shows competitive parallel and series pathways with up to 12 possible reactions. Despite the complexity of both reaction and catalyst system, a simplified kinetic model was able to predict the concentrations profiles. The model assumes the reactions to be apparent first order in the concentrations of reactant and intermediate products, while the kinetic constants include all other effects (partial pressure of hydrogen, solvent and catalyst effects, and the concentration of the chiral additive). The concentration profiles were well-modeled with low residual values. The errors in the kinetic constants (k-values) were small for all relevant parameters of the main reaction pathways. Two k-values are nil, which is the lower bound imposed in the model, suggesting that these reaction pathways are likely negligible. The positive outcome from this simplified model suggests that the process can be formally treated as a first-order irreversible homogeneous catalyzed reaction, despite a heterogeneous catalyst was employed (with a modifier). Despite the promising results, the model must be extended for a more general applicability, or conditions where it is applicable.

9.
PLoS One ; 16(5): e0250080, 2021.
Article in English | MEDLINE | ID: mdl-33951051

ABSTRACT

As cities expand, human mobility has become a central focus of urban planning and policy making to make cities more inclusive and sustainable. Initiatives such as the "15-minutes city" have been put in place to shift the attention from monocentric city configurations to polycentric structures, increasing the availability and diversity of local urban amenities. Ultimately they expect to increase local walkability and increase mobility within residential areas. While we know how urban amenities influence human mobility at the city level, little is known about spatial variations in this relationship. Here, we use mobile phone, census, and volunteered geographical data to measure geographic variations in the relationship between origin-destination flows and local urban accessibility in Barcelona. Using a Negative Binomial Geographically Weighted Regression model, we show that, globally, people tend to visit neighborhoods with better access to education and retail. Locally, these and other features change in sign and magnitude through the different neighborhoods of the city in ways that are not explained by administrative boundaries, and that provide deeper insights regarding urban characteristics such as rental prices. In conclusion, our work suggests that the qualities of a 15-minutes city can be measured at scale, delivering actionable insights on the polycentric structure of cities, and how people use and access this structure.


Subject(s)
City Planning , Movement , Cities , Humans , Spain , Urban Health , Walking
11.
Br J Sports Med ; 53(6): 328-333, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30049779

ABSTRACT

Various organisations and experts have published numerous statements and recommendations regarding different aspects of sports-related concussion including definition, presentation, treatment, management and return to play guidelines. 1-7 To date, there have been no written consensus statements specific for combat sports regarding management of combatants who have suffered a concussion or for return to competition after a concussion. In combat sports, head contact is an objective of the sport itself. Accordingly, management and treatment of concussion in combat sports should, and must, be more stringent than for non-combat sports counterparts.The Association of Ringside Physicians (an international, non-profit organisation dedicated to the health and safety of the combat sports athlete) sets forth this consensus statement to establish management guidelines that ringside physicians, fighters, referees, trainers, promoters, sanctioning bodies and other healthcare professionals can use in the ringside setting. We also provide guidelines for the return of a combat sports athlete to competition after sustaining a concussion. This consensus statement does not address the management of moderate to severe forms of traumatic brain injury, such as intracranial bleeds, nor does it address the return to competition for combat sports athletes who have suffered such an injury. These more severe forms of brain injuries are beyond the scope of this statement. This consensus statement does not address neuroimaging guidelines in combat sports.


Subject(s)
Athletic Injuries/therapy , Brain Concussion/therapy , Sports Medicine/methods , Athletes , Consensus , Humans , Physicians , Return to Sport , Societies, Medical
12.
AAPS PharmSciTech ; 19(8): 3376-3387, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29934803

ABSTRACT

The buccal mucosa appears as a promissory route for biologic drug administration, and pharmaceutical films are flexible dosage forms that can be used in the buccal mucosa as drug delivery systems for either a local or systemic effect. Recently, thin films have been used as printing substrates to manufacture these dosage forms by inkjet printing. As such, it is necessary to investigate the effects of printing biologics on films as substrates in terms of their physical and mucoadhesive properties. Here, we explored solvent casting as a conventional method with two biocompatible polymers, hydroxypropyl methylcellulose, and chitosan, and we used electrospinning process as an electrospun film fabrication of polycaprolactone fibers due to its potential to elicit mucoadhesion. Lysozyme was used as biologic drug model and was formulated as a solution for printing by thermal inkjet printing. Films were characterized before and after printing by mechanical and mucoadhesive properties, surface, and ultrastructure morphology through scanning electron microscopy and solid state properties by thermal analysis. Although minor differences were detected in micrographs and thermograms in all polymeric films tested, neither mechanical nor mucoadhesive properties were affected by these differences. Thus, biologic drug printing on films was successful without affecting their mechanical or mucoadhesive properties. These results open way to explore biologics loading on buccal films by inkjet printing, and future efforts will include further in vitro and in vivo evaluations.


Subject(s)
Biological Products/chemistry , Drug Delivery Systems , Mouth Mucosa/metabolism , Administration, Buccal , Biological Products/administration & dosage , Drug Delivery Systems/methods , Polymers/chemistry , Printing/methods
13.
J Psychiatr Res ; 45(4): 539-47, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20828718

ABSTRACT

Normal Pressure Hydrocephalus (NPH) is one of the causes of dementia of the elderly characterized by impaired mental function, gait difficulties and urinary incontinence. Previously, it was proposed that some of the NPH patients may develop Alzheimer's disease (AD) like pathology. Aim of this study was to compare levels of different CSF biomarkers, including total secreted ß-amyloid precursor protein (sAPP), sAPP-alpha form (sAPPα), amyloid-beta (Aß) peptide, total-tau protein and hyperphosphorylated-tau protein in subjects from NPH and Non-NPH Control (NNC). CSF was collected from 23 NPH patients and 13 Non-NPH controls by lumber puncture. Western blot analysis was performed to measure levels of sAPP-total. ELISA was used separately to determine levels of sAPPα, Aß peptide, total-tau and phospho-tau proteins. We found a significant decrease in levels of total secreted APP, sAPPα and Aß (1-42) in the CSF sample of NPH patients vs. NNC. We did not observe any change in levels of total-tau or phospho-tau in NPH vs. NNC subjects. Notably, phospho-tau level was significantly increased in the NPH patients, who were suffering from the disease for more than one year, vs. NNC. Among five biomarkers studied, decreased sAPP, sAPPα and Aß (1-42) levels in CSF can be molecular markers to distinguish NPH cases from NNC. Disease severity can also be assessed by increased levels of CSF phospho-tau protein and the ratio of phospho-tau to Aß (1-42), which might be a useful tool for predicting conversion of NPH individuals to other neurodegenerative disorders including Alzheimer's disease (AD).


Subject(s)
Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Protein Precursor/cerebrospinal fluid , Hydrocephalus, Normal Pressure/cerebrospinal fluid , tau Proteins/cerebrospinal fluid , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Peptide Fragments/cerebrospinal fluid , Phosphorylation , Statistics, Nonparametric
14.
Molecules ; 15(5): 3428-40, 2010 May 12.
Article in English | MEDLINE | ID: mdl-20657492

ABSTRACT

The enantioselective hydrogenation of 1-phenyl-1,2-propanedione over Pt colloids stabilized with (R,S)-4,5-dihydro-4,5-diphenyl-2-(6-cyanopyridinyl)imidazoline (CI) supported on a meso-structured ZrO(2) under a pressure of 40 bar of H(2) at 298 K has been investigated(.) The metal loading in all catalysts was 1 wt%. The effect of the amount of chiral modifier on the metal particle size and on the catalytic behavior was analyzed. It was found that as the CI/Pt molar ratio increases from 2.5 to 3.5 the Pt crystal size decreases from 3.0 to 1.8 nm. All catalysts were very active in the studied reaction, with the most active one being the catalyst with smaller Pt particles, whereas the selectivity is higher in those catalysts with larger chiral modified Pt metal particles.


Subject(s)
Chalcones/chemistry , Platinum/chemistry , Catalysis , Colloids/chemistry , Hydrogenation , Particle Size , Stereoisomerism , Zirconium
15.
Int J Geriatr Psychiatry ; 25(4): 419-26, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19670390

ABSTRACT

OBJECTIVE: Rivastigmine, a dual cholinesterase inhibitor (ChEI), is widely approved for the symptomatic treatment of both mild-to-moderate Alzheimer's disease (AD) and Parkinson's disease dementia. Orally administered ChEIs may be associated with gastrointestinal (GI) side effects and add-on therapy with memantine, an N-methyl-d-aspartate receptor antagonist, approved for moderate-to-severe AD, may ameliorate such side effects. This was a 26-week, prospective, multicenter, single-arm, open-label pilot study to assess the safety and tolerability of rivastigmine capsules plus memantine in patients with moderate AD. METHODS: The primary objective was to assess the safety and tolerability of rivastigmine capsules 6-12 mg/day plus memantine (5-20 mg/day) as measured by the incidences of vomiting and nausea compared with those reported in the rivastigmine United States Prescribing Information (US PI). A total of 117 patients were enrolled with 116 receiving at least one dose of study medication. RESULTS: The incidences of nausea and vomiting (30% and 13%, respectively) observed in patients who received 6-12 mg/day rivastigmine plus memantine were lower than those stated in the US PI for rivastigmine monotherapy 6-12 mg/day (47% and 31%, respectively). The most common adverse events were nausea, vomiting, and dizziness. CONCLUSION: Results from this study suggest the combination of rivastigmine capsule and memantine in patients with moderate AD is safe and tolerable. A greater reduction in the GI tolerability of rivastigmine has been established with rivastigmine transdermal patch.


Subject(s)
Alzheimer Disease/drug therapy , Antiparkinson Agents/therapeutic use , Cholinesterase Inhibitors/therapeutic use , Excitatory Amino Acid Antagonists/therapeutic use , Memantine/therapeutic use , Phenylcarbamates/therapeutic use , Activities of Daily Living , Administration, Oral , Aged , Aged, 80 and over , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Antiparkinson Agents/adverse effects , Blood Pressure/drug effects , Capsules , Cholinesterase Inhibitors/adverse effects , Cognition/drug effects , Dizziness/epidemiology , Drug Therapy, Combination , Excitatory Amino Acid Antagonists/adverse effects , Female , Humans , Incidence , Male , Memantine/adverse effects , Middle Aged , Nausea/epidemiology , Phenylcarbamates/adverse effects , Pilot Projects , Prospective Studies , Rivastigmine , Vomiting/epidemiology
16.
Rev. colomb. quím. (Bogotá) ; 38(1): 97-105, abr. 2009. ilus, tab
Article in Spanish | LILACS | ID: lil-636647

ABSTRACT

Se estudió la hidrogenación enantio selectiva de 4-metoxiacetofenona sobre catalizadores de Pt/TiO2 reducidos a 773K y modificados con cinconidina (CD). Los catalizadores se caracterizaron por fisiadsorción de N2, quimiadsorción de H2, DRX y XPS. Las transformaciones se llevaron a cabo en un reactor tipo STR a distintas concentraciones de cinconidina (CD) con el propósito de evaluar la incidencia de algunos parámetros de reacción como el orden de adición del modificador y la presión de hidrógeno. Se demostró que a bajas concentraciones de CD es posible obtener excesos enantioméricos cercanos al 30%. Se encontró que la estructura de la molécula puede afectar el comportamiento observado.


The enantioselective hydrogenation of 4-methoxyacetophenone over Pt/TiO2 catalyst reduced to 773 K in the presence of cinchonidine (CD) was studied. The catalysts were characterized by N2 physisorption, H2 chemisorption, XRD and XPS. The reactions were carried out in a STR reactor at various concentrations of CD. The effect of several reaction parameters was investigated, such as the addition order of the modifier and hydrogen pressure. Lower concentrations of CD can produce an enantiomeric excess near to 30%. The structure of the molecule can influence the behavior observed.


Neste trabalho, foi estudada a hidrogenação enantioselective do 4-metoxiaceto-fenona em catalisadores Pt/TiO2 reduzidos a 773 K e modificados com cinconidina (CD). Os sólidos foram caracterizados por adsorção de nitrogênio a 77K, quimisorção de hidrogênio a temperatura ambiente, DRX, TEM e XPS. As reações foram realizadas em um reator STR a diferentes concentrações de CD. Alem de isso o efeito de vários parâmetros de reação foi estudado, como ordem de adição do modificador e pressão do hidrogênio. Baixas concentrações do CD podem produzir excesso enantiomêricos próximos aos 30%. A estrutura da molécula pode influenciar o comportamento obtido.

17.
Brain Inj ; 23(2): 123-32, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19191091

ABSTRACT

OBJECTIVE: To investigate the safety, tolerability and efficacy of rivastigmine capsules (3-12 mg/day) in a 26-week, multi-centre, open-label extension of a double-blind study. METHODS: Patients with traumatic brain injury (TBI) and persistent cognitive impairment who had received rivastigmine (3-6 mg/day) or placebo for 12 weeks could enter the extension study and receive rivastigmine (< or =12 mg/day). Patients were assessed using a range of cognitive tests including the Hopkins Verbal Learning Test (HVLT) and the Cambridge Neuropsychological Test Automated Battery Rapid Visual Information Processing (CANTAB RVIP) A' sub-test. Safety measures included monitoring of adverse events. RESULTS: In the extension study (n = 127), the mean duration of rivastigmine treatment was 23.8 weeks and the mean final dosage was 7.9 mg/day. Approximately 40% of patients were responders (> or =1.0 SD improvement from baseline) on CANTAB RVIP A' or HVLT total score at week 38 or endpoint. Statistically significant changes from week 12 at week 38 were observed for CANTAB-RVIP A' and HVLT-total word recall for the sub-group of ex-placebo patients with greater severity of initial impairment. The safety profile of rivastigmine capsules was consistent with the label. CONCLUSIONS: Treatment with rivastigmine for up to 38 weeks was safe in patients with TBI and cognitive impairment.


Subject(s)
Brain Injuries/complications , Cognition Disorders/drug therapy , Neuroprotective Agents/administration & dosage , Phenylcarbamates/administration & dosage , Adult , Brain Injuries/physiopathology , Capsules , Cognition Disorders/physiopathology , Double-Blind Method , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Neuroprotective Agents/adverse effects , Neuropsychological Tests , Phenylcarbamates/adverse effects , Rivastigmine , Time , Treatment Outcome
18.
Rev. colomb. quím. (Bogotá) ; 36(2): 183-198, sep.-dic. 2007. ilus, tab
Article in Spanish | LILACS | ID: lil-636608

ABSTRACT

En este trabajo se estudió la hidrogenación selectiva de citronelal sobre sistemas de Ir/TiO2, Ir/SiO2, e Ir soportado en óxidos mixtos (Ir/TiO2-SiO2) reducidos a 473 y 773 K. Se analizó el efecto de la adición de TiO2 al soporte y de las temperaturas de reducción de los catalizadores para evaluar el posible efecto de especies TiOx parcialmente reducidas, sobre la actividad y selectividad de la reacción. Los sólidos resultantes se caracterizaron por quimisorción de hidrógeno a temperatura ambiente, adsorción de nitrógeno a 77 K, DRX, TEM y XPS. Los resultados indican que los catalizadores reducidos a alta temperatura (HT: 773 K) favorecen la producción del alcohol insaturado debido al efecto de interacción fuerte metal-soporte conocido como SMSI. Los catalizadores reducidos a baja temperatura (LT: 473 K) llevan a la ciclización del anillo produciendo isopulegol. Estos catalizadores mostraron una alta actividad y una menor selectividad hacia el alcohol insaturado.


Catalytic hydrogenation of citronellal over Ir/TiO2, Ir/SiO2, and Ir supported on mixed oxides (Ir/TiO2/SiO2) reduced at 473 y 773 K was studied. The effects of the partially reducible support species, the reduction temperatures (473 K or 773 K) and the successive TiO2 addition were analyzed. The catalysts were characterized by H2 chemisorption at room temperature, N2 adsorption at 77 K, XRD, TEM and XPS. The results showed that the high temperature reduction treatment (HT: 773 K) favored the production of the unsaturated alcohol, which can be explained in terms of the so-called strong metalsupport interaction (SMSI) effect. Catalysts reduced at low temperature (LT: 473 K) mainly led to a cyclization reaction producing isopulegol. These catalysts showed high activity but low selectivity to the unsaturated alcohol.


Nesse trabalho, foi estudada a hidrogenação seletiva do citronelal em catalisadores Ir/TiO2, Ir/SiO2 e Ir suportado em óxidos mistos (Ir/TiO2-SiO2) reduzidos a 473 e 773 K. Foi analisado o efeito da adição da TiO2 no suporte e das temperaturas de redução dos catalisadores para evaliar o possível efeito das espécies TiOx parcialmente reduzidas, sobre a atividade e seletividade da reação. Os sólidos resultantes foram caracterizados por quimisorção de hidrogênio a temperatura ambiente, adsorção de nitrogênio a 77 K, DRX, TEM e XPS. Os resultados indican que os catalisadores reduzidos a alta temperatura (HT: 773 K) favorecem a produção do álcool insaturado pelo efeito da interação forte metal-suporte conhecido como SMSI. Os catalisadores reduzidos a baixa temperatura (LT: 473 K) conduzen para a ciclização do anel produzindo isopulegol. Esses catalisadores mostraram uma alta atividade e uma baixa seletividade para álcool insaturado.

19.
J Alzheimers Dis ; 11(4): 481-9, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17656828

ABSTRACT

The 'cholinergic hypothesis', based on the correlation of the reduction of cholinergic activity in Alzheimer's disease (AD) with cognition and memory, is currently the most widely-held view for AD. Drug treatments for AD focus mainly on inhibition of acetylcholinesterase (AChE), and to some extent butyrylcholinesterase (BChE). In addition to changes in AChE in AD, there is a rise in the level of the sister enzyme BChE. However, the role of the two cholinesterases is poorly understood in vivo. We characterized several proteins immunohistochemically in brain sections from AChE nullizygote (AChE-/-) and wild type AChE+/+ mice. Previous studies had shown that AChE-/- mouse tissues are devoid of AChE activity and that the overall cholinesterase activity is significantly decreased in the knockout group [16]. Despite the differences of cholinesterase activity, we found no significant structural alterations between the experimental groups. Immunohistochemical examination revealed no neuronal, dendritic, astrocytic, synaptic, microglial, and endothelial differences between AChE-/- and AChE+/+ mice. Similarly, the histochemical examination showed no morphologic alterations between AChE-/- and AChE+/+ mice. Our studies show that neither the absence of AChE nor the presence exclusively of BChE is associated with neuroglial and vascular pathology.


Subject(s)
Acetylcholinesterase/genetics , Alzheimer Disease/genetics , Brain/pathology , Acetylcholinesterase/metabolism , Alzheimer Disease/pathology , Animals , Astrocytes/pathology , Brain/blood supply , Butyrylcholinesterase/metabolism , Dendrites/pathology , Endothelium, Vascular/pathology , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Mice , Mice, Knockout , Microcirculation/pathology , Microglia/pathology , Microscopy, Fluorescence , Microtubule-Associated Proteins/genetics , Neurons/pathology , Phosphopyruvate Hydratase/genetics , Phosphopyruvate Hydratase/metabolism , Synapses/pathology , Synaptophysin/genetics , Synaptophysin/metabolism
20.
J Neuropathol Exp Neurol ; 61(7): 634-9, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12125742

ABSTRACT

Inhibition of mitochondrial respiratory chain function may contribute to dopaminergic neurodegeneration in the substantia nigra (SN) of patients with Parkinson disease (PD). Since large-scale structural changes (e.g. deletions and rearrangements in mitochondrial DNA [mtDNA]) have been associated with mitochondrial dysfunction, we tested the hypothesis that increased total mtDNA deletions/rearrangements are associated with neurodegeneration in PD. This study employed a well-established technique, long-extension polymerase chain reaction (LX-PCR), to detect the multiple mtDNA deletions/rearrangements in the SN of patients with PD, multiple system atrophy (MSA), dementia with Lewy bodies (DLB), Alzheimer disease (AD), and age-matched controls. We also compared the total mtDNA deletions/rearrangements in different brain regions of PD patients. The results demonstrated that both the number and variety of mtDNA deletions/rearrangements were selectively increased in the SN of PD patients compared to patients with other movement disorders as well as patients with AD and age-matched controls. In addition, increased mtDNA deletions/rearrangements were observed in other brain regions in PD patients, indicating that mitochondrial dysfunction is not just limited to the SN of PD patients. These data suggest that accumulation of total mtDNA deletions/rearrangements is a relatively specific characteristic of PD and may be one of the contributing factors leading to mitochondrial dysfunction and neurodegeneration in PD.


Subject(s)
DNA Damage/genetics , DNA, Mitochondrial/genetics , Gene Deletion , Mutation/genetics , Neurons/metabolism , Parkinson Disease/genetics , Parkinson Disease/metabolism , Substantia Nigra/metabolism , Aged , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Brain/metabolism , Brain/pathology , Brain/physiopathology , DNA Mutational Analysis , Female , Humans , Lewy Body Disease/genetics , Lewy Body Disease/metabolism , Lewy Body Disease/pathology , Male , Middle Aged , Multiple System Atrophy/genetics , Multiple System Atrophy/metabolism , Multiple System Atrophy/pathology , Neurons/pathology , Parkinson Disease/pathology , Polymerase Chain Reaction , Substantia Nigra/pathology , Substantia Nigra/physiopathology
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