Nanocomposite functionalized membranes based on silica nanoparticles cross-linked to electrospun nanofibrous support for arsenic(v) adsorption from contaminated underground water.

Nanocomposite functionalized membranes were synthesized using surface functionalized mesoporous silica nanoparticles (MCM-NH2 or MCM-PEI) cross-linked to a modified polyacrylonitrile (mPAN) nanofibrous substrate for the removal of 1 mg L-1 of As(v); a concentration much higher than what has been reported for underground water in Argentina. Adsorption studies were carried out in batch mode at pH 8 with nanoparticles in colloidal form, as well as the nanoparticles supported on the modified PAN membranes (mPAN/MCM-NH2 and mPAN/MCM-PEI). Results indicate a twenty-fold improvement in As(v) adsorption with supported nanoparticles (nanocomposite membranes) as opposed to their colloidal form. The adsorption efficiency could be further enhanced by modifying the nanocomposite membrane surface with Fe3+ (mPAN/MCM-NH2-Fe3+ and mPAN/MCM-PEI-Fe3+) which resulted in more than 95% arsenic being removed within the first 15 minutes and a specific arsenic adsorption capacity of 4.61 mg g-1 and 5.89 mg g-1 for mPAN/MCM-NH2-Fe3+ and mPAN/MCM-PEI-Fe3+ nanocomposite membranes, respectively. The adsorption characteristics were observed to follow a pseudo-first order behavior. The results suggest that the synthesized materials are excellent for quick and efficient reduction of As(v) concentrations below the WHO guidelines and show promise for future applications.

[Expression of B7 molecules and TLR-9 on corneal epithelial cells infected with adenovirus: clinico-pathological implications in viral keratoconjunctivitis]. / Expresión de moléculas B7 y TLR:9 en células epiteliales corneales infectadas con adenovirus: implicaciones clínico-patológicas en la queratoconjuntivitis viral.

PURPOSE: B7 molecules are a family of proteins that co-stimulate T cells during immune activation. Normally the corneal epithelial cells (CEC) do not express these molecules on their cell surface. Toll-like receptors play an important role in the innate immune response to invading pathogens and recently have been demonstrated to be expressed on mice cornea. The objective of this study was to determine whether adenoviral infection induces B7 molecules and TLR9 on human CEC. METHODS: CEC were isolated from human corneas treated with dispase-II, and grown in the presence of supplemented hormonal epithelial medium until confluence. Then CEC were then infected with adenovirus 5 (Ad5) and cultured for different times. The CEC were then recovered and stained against human CD80, CD86, TLR-9 and cytokeratin. All cells were analyzed by flow cytometry. RESULTS: Ad5 infection of CEC induced the expression of B7 molecules and TLR-9 after 24 hours in culture, rising to maximum levels at 72 hours. B7 expression at 72 hours was as follows: CD80 expression on infected CEC was 62% (standard error [SE] 2.6) versus 3% (SE 1.2) on non-infected CEC (p<0.001); CD86 expression on infected CEC was 95% (SE 2.1) versus 5% (SE 1.2) on non-infected CEC (p<0.001). TLR-9 expression at 72 hours was 80% (SE 1.2) on infected CEC versus 5% (SE 1) on non-infected CEC (p<0.001). CONCLUSIONS: Ad5 infection induced the expression of B7 molecules and TLR-9 on CEC.

Expresión de moléculas B7 y TLR:9 en células epiteliales corneales infectadas con adenovirus: implicaciones clínico-patológicas en la queratoconjuntivitis viral / Expression of B7 molecules and TLR-9 on corneal epithelial cells infected with adenovirus: clinico-pathological implications in viral keratoconjunctivitis

Objetivo: Las moléculas B7 son una familia deproteínas que coestimulan al linfocito T durante laactivación inmunitaria, normalmente las célulasepiteliales corneales (CEC) no expresan estas moléculasen superficie. Los receptores tipo Toll jueganun papel importante en la respuesta inmune innatahacia patógenos invasores y recientemente sedemostró su expresión en córneas de ratón. El objetivodel presente estudio fue determinar si la infecciónviral induce moléculas B7 y TLR9 en CEChumanas.Métodos: Las CEC fueron obtenidas de corneashumanas tratadas con dispasa II y crecidas en presenciade medio hormonal epitelial suplementadohasta su confluencia. Posteriormente las células fueron infectadas con adenovirus 5 (Ad5) y cultivadasa diferentes tiempos. Las CEC fueron recuperadasy marcadas contra CD80, CD86, TLR-9 y citoqueratina.Todas las células fueron analizadas porcitometría de flujo.Resultados: La infección de CEC con Ad5 indujola expresión de moléculas B7 y TLR-9 desde las 24h, alcanzando su máximo nivel a las 72 h. La expresiónde moléculas B7 a las 72 h fue como sigue,expresión de CD80 en CEC infectadas 62% errorestándar (ES) 2.6 versus 3 ES 1.2 (p < 0,001) enCEC no infectadas; expresión de CD86 en CECinfectadas 95% ES 2.1 versus 5% ES 1.2 (p <0,001) en CEC no infectadas. La expresión de TLR-9 a las 72 h fue de 80% ES 1.2 en CEC infectadasversus 5% ES 1 en CEC no infectadas (p < 0,001).Conclusiones: La infección por Ad5 induce laexpresión de moléculas B7 y TLR-9 en CEC

Purpose: B7 molecules are a family of proteins that co-stimulate T cells during immune activation. Normally the corneal epithelial cells (CEC) do not express these molecules on their cell surface. Tolllike receptors play an important role in the innate immune response to invading pathogens and recently have been demonstrated to be expressed on mice cornea. The objective of this study was to determine whether adenoviral infection induces B7 molecules and TLR9 on human CEC. Methods: CEC were isolated from human corneas treated with dispase-II, and grown in the presence of supplemented hormonal epithelial medium until confluence. Then CEC were then infected with adenovirus 5 (Ad5) and cultured for different times. The CEC were then recovered and stained against human CD80, CD86, TLR-9 and cytokeratin. All cells were analyzed by flow cytometry. Results: Ad5 infection of CEC induced the expression of B7 molecules and TLR-9 after 24 hours in culture, rising to maximum levels at 72 hours. B7 expression at 72 hours was as follows: CD80 expression on infected CEC was 62% (standard error [SE] 2.6) versus 3% (SE 1.2) on non-infected CEC (p<0.001); CD86 expression on infected CEC was 95% (SE 2.1) versus 5% (SE 1.2) on non-infected CEC (p<0.001). TLR-9 expression at 72 hours was 80% (SE 1.2) on infected CEC versus 5% (SE 1) on non-infected CEC (p<0.001). Conclusions: Ad5 infection induced the expression of B7 molecules and TLR-9 on CEC

The association of incident dementia with mortality in PD.

OBJECTIVE: To evaluate the association of incident dementia with mortality in a cohort of patients with idiopathic PD who were nondemented at baseline evaluation, controlling for extrapyramidal sign (EPS) severity at each study visit. BACKGROUND: The development of dementia has been associated with reduced survival in PD. Because EPS severity is associated with both dementia and mortality in PD, the association of dementia with mortality may be confounded by disease severity. METHODS: A cohort of patients with PD was followed annually with neurologic and neuropsychological evaluations. The association of incident dementia and the total Unified PD Rating Scale (UPDRS) motor score with mortality in PD was examined using Cox proportional hazards models with time-dependent covariates. All analyses were adjusted for age at baseline, sex, years of education, ethnicity, and duration of PD. RESULTS: Of 180 PD patients, 41 (22.8%) died during a mean follow-up period of 3.9 +/- 2.2 years. Among those who died during the study period, 48.8% (20 of 41) became demented during follow-up, as compared to 23.0% (32 of 139) of those who remained alive. Both incident dementia (RR: 2.2, 95% CI: 1.1 to 4.5, p = 0.04) and the total UPDRS motor score at each study visit (RR: 1.04, 95% CI: 1.02 to 1.07, p = 0.001) were associated with mortality in PD when included in the same Cox model. CONCLUSIONS: Incident dementia has an independent effect on mortality when controlling for EPS severity. The development of dementia is associated with a twofold increased mortality risk in PD.

Clinical correlates of action tremor in Parkinson disease.

BACKGROUND: Action tremor is often noted in patients with Parkinson disease (PD), yet the clinical correlates of this type of tremor have been the focus of few studies. It is not clear whether this action tremor is a manifestation of the underlying basal ganglia disease. OBJECTIVE: To determine whether the severity of action tremor in PD is associated with age, age at disease onset, disease duration, levodopa dose, severity of rest tremor, or other motor (ie, bradykinesia, rigidity) and nonmotor manifestations of PD. METHODS: Patients with PD (N = 197) were ascertained as part of a familial aggregation study. All patients underwent a neurological examination. Rest tremor was rated with the Unified Parkinson Disease Rating Scale; and action tremor, with the Washington Heights-Inwood Genetic Study of Essential Tremor Rating Scale. RESULTS: Action tremor was present in 184 (93.4%) of 197 patients. Four patients (2%) met criteria for definite essential tremor. The action tremor score was not associated with age, age at onset, or disease duration. The action tremor score was associated with the rest tremor score (r = 0.37; P<.001), and more strongly with the ipsilateral than contralateral rest tremor score. The association between the action tremor score and the rest tremor score was diminished but still significant (r = 0.21, P<.02) even when we excluded these 63 patients with re-emergent tremor. Neither the action nor the rest tremor score was associated with the bradykinesia or rigidity scores, Hoehn and Yahr scale score, or modified Mini-Mental State Examination score. CONCLUSIONS: Action tremor was associated with rest tremor in PD, suggesting that, at least in part, action tremor is a manifestation of the underlying basal ganglia disease. Neither tremor was associated with other motor and nonmotor manifestations of PD. This in turn suggests that tremor in PD may represent an underlying pathophysiological process different from these other manifestations.

Motor impairment in PD: relationship to incident dementia and age.

OBJECTIVE: To analyze the relationship of specific motor impairment in idiopathic PD to incident dementia. BACKGROUND: The total Unified PD Rating Scale (UPDRS) motor score at baseline has been associated with an increased risk of developing dementia in PD. METHODS: A cohort of 214 nondemented community-dwelling patients with PD was followed annually with neurologic and neuropsychological evaluations. The association of baseline motor impairment with incident dementia was analyzed using Cox proportional hazards models. Facial expression, tremor, rigidity, and bradykinesia were analyzed as part of subscore A (indicative of dopaminergic deficiency); speech and axial impairment were analyzed as part of subscore B (indicative of predominantly nondopaminergic deficiency). The correlation between the six motor domains and age was also analyzed. RESULTS: Of 173 patients followed for at least 1 year, 50 became demented according to the Diagnostic and Statistical Manual of Mental Disorders, revised 3rd edition (DSM III-R) criteria (mean follow-up, 3.6 +/- 2. 2 years). When both subscores A and B were entered into the Cox model, subscore B was associated with incident dementia (relative risk = 1.19; 95% CI, 1.09 to 1.30; p = 0.0001), in addition to gender, age, and education, whereas subscore A was not (relative risk = 1.03; 95% CI, 0.99 to 1.07; p = 0.19). Of the six motor domains, speech and bradykinesia were associated with incident dementia (p < 0.05), and axial impairment approached significance (p = 0.06). Only axial impairment was correlated with age (correlation coefficient = 0.32; p < 0.001). CONCLUSION: The findings suggest that motor impairment mediated predominantly by nondopaminergic systems is associated with incident dementia in PD. Axial impairment may be the result of a combined effect of the disease and the aging process.

Taenia solium: a cysteine protease secreted by metacestodes depletes human CD4 lymphocytes in vitro.

Excreted/secreted products from Taenia solium metacestodes cultured in vitro were analyzed for peptidase activity using peptide substrates Z-Phe-Arg-AFC, Arg-AFC, and Z-Gly-Gly-Arg-AFC and zymography studies. Specific inhibitor profiles revealed mainly cysteine and metalloprotease activities. Hydrolysis of substrate Z-Phe-Arg-AFC was augmented by the addition of L-cysteine and acid pH, consistent with cysteine protease activity. Cysteine protease activity was more prominent in supernatants from living metacestodes cultured in PBS than in either RPMI or RPMI plus fetal calf serum and was proportional to the number of metacestodes. Flow cytometry analysis showed depletion of human T lymphocytes cultured with living T. solium metacestodes. CD4(+) expression was significantly decreased when metacestode E/S products and L-cysteine were added to lymphocyte cultures (P = 0.027). This peptidase activity was inhibited by E-64 indicating that the depletion of CD4(+) cells was due to cysteine protease activity. Thus, T. solium metacestodes produce excretory/secretory proteases. These enzymes may cleave molecules critical for the host immune response allowing the parasites to survive in the host tissues.

Progression of parkinsonian signs in Parkinson disease.

BACKGROUND: Current knowledge about the rate of progression of extrapyramidal signs (EPSs) in Parkinson disease (PD) is derived largely from cross-sectional studies comparing subjects at various stages of illness rather than longitudinal studies in which the subjects were followed up over time. OBJECTIVE: To longitudinally study the progression of EPSs in PD by quantifying the rate of change of EPSs and by examining each EPS (rigidity, bradykinesia, tremor, and postural instability) separately. METHODS: A community-based cohort of 237 patients with PD living in Washington Heights-Inwood in Manhattan, NY, was evaluated at baseline and at yearly intervals. The EPSs were rated using the motor portion of the Unified Parkinson's Disease Rating Scale Motor Examination. Analyses of longitudinal data were performed by applying generalized estimating equations to regression analyses. RESULTS: The total EPS score increased at an annual rate of 1.5 points (1.5%), but, among those who died, the total EPS score increased at an annual rate of 3.6 points (3.6%). Bradykinesia, rigidity, and gait and balance subscores worsened at similar annual rates of 2.0% to 3.1%, whereas the tremor subscore did not clearly worsen with time. Patients with a shorter disease duration (< or =3 years) may have progressed more rapidly than patients with longer disease duration (annual rate of change, 1.9% vs 1.4%, respectively), although this did not reach statistical significance. A high total EPS score was independently associated with dementia, low Activities of Daily Living score, and long disease duration at baseline. CONCLUSIONS: In this cohort, the progression of EPSs in PD occurred at a rate of 1.5% per year and at twice that rate among those who died. Bradykinesia, rigidity, and gait and balance impairment worsened at similar rates, whereas tremor did not, suggesting that tremor may be relatively independent of these other cardinal manifestations of PD.

Risk of Alzheimer's disease in relatives of Parkinson's disease patients with and without dementia.

OBJECTIVE: To determine whether first-degree relatives of PD patients with dementia were at increased risk for the development of AD compared with first-degree relatives of nondemented PD patients and nondemented normal subjects from the community. METHODS: A structured family history interview was administered to 146 nondemented PD patients, 120 patients with PD and dementia, and 903 normal subjects from the community to ascertain the presence of AD among parents and siblings of these subjects. Cox proportional hazards models with double censoring techniques for missing information were used to model the risk of AD among relatives. RESULTS: No increase in risk of AD was found among parents of patients with PD and dementia or parents of nondemented PD patients compared with parents of normal subjects. However, siblings of demented PD patients were three times as likely (relative risk [RR] = 3.2, 95% confidence interval [CI] = 1.1 to 9.4, p < 0.04) as siblings of normal subjects to develop AD. When only siblings >65 years of age were considered, there was a fivefold increase in risk of AD among siblings of demented PD patients compared with siblings of normal subjects (RR = 4.9, 95% CI = 1.1 to 21.4, p < 0.03). The risk of AD was also increased for female relatives, regardless of whether the woman was a relative of a demented PD patient, a nondemented PD patient, or a normal subject. Ethnicity and APOE genotype did not affect dementia status among relatives. CONCLUSIONS: The increased risk of AD in siblings of demented PD patients compared with siblings of normal subjects supports the possibility of familial aggregation of AD and PD with dementia.

Systemic iron metabolism and mortality from Parkinson's disease.

Six measures of systemic iron metabolism were used to predict mortality among 103 patients with Parkinson's disease and 353 controls followed in a longitudinal study. Adjusting for gender, education, ethnicity, presence of dementia, and extrapyramidal signs, transferrin receptor concentration was strongly associated with mortality in patients with PD but not controls. This increase in serum transferrin receptor concentration before death suggests that the previously observed perturbation in iron metabolism continues throughout the disease course.

Postmenopausal estrogen use and Parkinson's disease with and without dementia.

We investigated the effects of estrogen replacement therapy (ERT) on the risk of development of dementia in 87 women with Parkinson's disease without dementia (PDND), 80 women with Parkinson's disease with dementia (PDD), and 989 nondemented healthy women from the same community. ERT was protective for the development of dementia within the setting of PD (OR 0.22, 95% CI 0.05-1.0) and when PDD patients were compared with controls (OR 0.24, 95% CI 0.07-0.78), but did not affect the risk of PD. The results of the study suggest that a randomized clinical trial of ERT may be warranted.

Environmental risk factors for Parkinson's disease in an urban multiethnic community.

Environmental risk factors were examined using univariate and multivariate unconditional logistic regression models in 89 nondemented patients with Parkinson's disease (PD) and 188 control subjects in a multiethnic urban community. Rural living, area farming, and drinking well water were associated with PD only in African-Americans. In Hispanics, area farming was protective, whereas drinking unfiltered water was a risk factor for PD. Consideration of ethnic and cultural origin may add to the epidemiologic study of PD.

Risk of Parkinson's disease among first-degree relatives: A community-based study.

OBJECTIVE: To determine the relative risk (RR) and cumulative incidence of idiopathic Parkinson's disease (PD) in first-degree relatives of PD patients compared with relatives of controls from the same geographic region. DESIGN: A family history questionnaire was used to obtain information on all first-degree relatives of cases and controls. A subset of these first-degree relative was also examined. A Cox proportional hazards model with double-censoring techniques for missing information was used to model the RR for PD, adjusting for gender, ethnicity, and relationship to proband. RESULTS: A total of 1,458 first-degree relatives of 233 PD patients were 2.3 times as likely (95% CI = 1.3 to 4.0) as 7,834 relatives of 1,172 controls to develop PD. The cumulative incidence of PD to age 75 among first-degree relatives of PD patients was 2% compared with 1% among first-degree relatives of controls. The risk in male first-degree relatives was higher than in female relatives (RR = 2.0, 95% CI = 1.1 to 3.4) and the risk in relatives of Caucasians was higher than in African-Americans and Hispanics (RR = 2.4, 95% CI = 1.4 to 4.1). Risk for siblings and parents of probands was similar. CONCLUSIONS: Susceptibility to PD is increased in first-degree relatives of both sporadic and familial cases. The pattern of inheritance and the relationship between genetic and environmental risk factors warrant further study.

The frequency of idiopathic Parkinson's disease by age, ethnic group, and sex in northern Manhattan, 1988-1993.

Sex and ethnic differences in the frequency of Parkinson's disease have become increasingly important, because putative genetic and environmental risk factors have been identified. The authors estimated the prevalence and incidence of Parkinson's disease in a culturally diverse community in New York City over a 4-year period (January 1, 1988-December 31, 1991) using a disease registry substantiated, for older individuals, by a subsequent survey of a random sample of Medicare recipients between January 1, 1992, and December 31, 1993. The prevalence rate was 107 per 100,000 persons, and over a 3-year period the average incidence rate was 13 per 100,000 person-years. Age-adjusted prevalence rates were lower for women than for men in each ethnic group and were lower for blacks than for whites and Hispanics. Incidence rates were highest among black men, but they were otherwise comparable across the sex and ethnic groups. The estimated cumulative incidence of Parkinson's disease up to age 90 years was lower for women than for men, which could partially explain the lower prevalence rate. By ethnic group, the cumulative incidence was higher for blacks than for whites and Hispanics, but more deaths occurred among incident black cases. Discrepant prevalence and incidence rates of Parkinson's disease among blacks and women warrant further investigation. While selective mortality could partially account for this paradox, it is also possible that a delay in diagnosis due to limited access to appropriate health services among these individuals could have resulted in the observed discordant rates of disease.

Successful treatment of New World cutaneous leishmaniasis with a combination of topical paromomycin/methylbenzethonium chloride and injectable meglumine antimonate.

Colombian patients with New World cutaneous leishmaniasis were treated with a combination of a topical formulation (15% paromomycin sulfate/5% methylbenzethonium chloride, twice a day) and parenteral meglumine antimonate (20 mg of antimony [Sb]/kg.d]). Cohort 1 received topical therapy for 10 days and Sb for 7 days; 18 (90%) of the 20 patients were cured (follow-up, 12 months). Other clinical data suggested that neither the topical formulation alone nor the 7-day regimen of Sb alone would have cured many patients. In a subsequent cohort, which received topical therapy for 10 days and Sb for 3 days, the cure rate was 42% (eight of 19 patients). In Colombian cohorts (historical controls) treated with Sb alone for 10-15 days, the cure rate was 31%-36%. Side effects in cohort 1 patients consisted of local reactions to the topical formulation: burning and pruritus in 25% of patients and vesicle formation in 15% of patients. This is the first report that a regimen partially composed of topical antimicrobial agents can be highly effective for treatment of New World cutaneous leishmaniasis.

The apolipoprotein epsilon 4 allele in Parkinson's disease with and without dementia.

The epsilon 4 isoform of apolipoprotein E (Apo-E) may confer genetic susceptibility for familial and sporadic Alzheimer's disease (AD). Because dementia in AD and Parkinson's disease (PD) share many biologic and clinical features, we determined the Apo-E genotypes for 79 patients with PD, 22 of whom were demented, and for 44 age-matched healthy elderly controls from the same community. We hypothesized that if the dementia was similar to AD, there would be a higher allele frequency of apolipoprotein epsilon 4 (Apo epsilon 4) in demented PD patients compared with nondemented PD patients and controls. The epsilon 4 allele frequency for PD without dementia was 0.132, for PD with dementia, 0.068, and for controls, 0.102. There was no association between Apo epsilon 4 and dementia in the PD patients. We conclude that the biologic basis for dementia in PD may differ from that of AD.

Estudio nutricional en la gestación: estudio preliminar / Nutritional status during pregnancy: preliminary study

Proyecto de control nutricional de la madre gestante motivado por el serio problema nutricional en salud pública. Las tasas de desnutrición infantil y de bajo peso al nacer se encuentran en aumento. A pesar de ello, hay pocas referencias a evaluaciones nutricionales en embarazadas