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1.
J Antimicrob Chemother ; 79(7): 1668-1672, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38785349

RESUMO

BACKGROUND: Invasive fungal infections (IFIs) are severe and difficult-to-treat infections affecting immunocompromised patients. Antifungal drug penetration at the site of infection is critical for outcome and may be difficult to achieve. Data about antifungal drug distribution in infected human tissues under real circumstances of IFI are scarce. METHODS: Multiple samples were obtained from soft tissue abscesses of a lung transplant patient with Candida albicans invasive candidiasis who underwent recurrent procedures of drainage, while receiving different consecutive courses of antifungal therapy [itraconazole (ITC), fluconazole, caspofungin]. Antifungal drug concentrations were measured simultaneously at the site of infection (surrounding inflammatory tissue and fluid content of the abscess) and in plasma for calculation of the tissue/plasma ratio (R). The concentration within the infected tissue was interpreted as appropriate if it was equal or superior to the MIC of the causal pathogen. RESULTS: A total of 30 tissue samples were collected for measurements of ITC (n = 12), fluconazole (n = 17) and caspofungin (n = 1). Variable concentrations were observed in the surrounding tissue of the lesions with median R of 2.79 (range 0.51-15.9) for ITC and 0.94 (0.21-1.37) for fluconazole. Concentrations ranges within the fluid content of the abscesses were 0.39-1.83 for ITC, 0.66-1.02 for fluconazole and 0.23 (single value) for caspofungin. The pharmacodynamic target (tissue concentration ≥ MIC) was achieved in all samples for all three antifungal drugs. CONCLUSIONS: This unique dataset of antifungal drug penetration in infected human soft tissue abscesses suggests that ITC, fluconazole and caspofungin could achieve appropriate concentrations in soft tissue abscesses.


Assuntos
Abscesso , Antifúngicos , Caspofungina , Infecções dos Tecidos Moles , Humanos , Antifúngicos/farmacocinética , Antifúngicos/uso terapêutico , Antifúngicos/administração & dosagem , Abscesso/tratamento farmacológico , Abscesso/microbiologia , Caspofungina/farmacocinética , Caspofungina/uso terapêutico , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Fluconazol/farmacocinética , Fluconazol/uso terapêutico , Fluconazol/administração & dosagem , Candida albicans/efeitos dos fármacos , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/microbiologia , Testes de Sensibilidade Microbiana , Masculino , Itraconazol/farmacocinética , Itraconazol/uso terapêutico , Itraconazol/administração & dosagem , Pessoa de Meia-Idade , Feminino , Adulto
2.
Rev Med Suisse ; 20(869): 734-738, 2024 Apr 10.
Artigo em Francês | MEDLINE | ID: mdl-38616683

RESUMO

While most episodes of community-acquired pneumonia are caused by Streptococcus pneumoniae and respiratory viruses, other atypical pathogens can also be responsible for lung infections. The Infectious Diseases Service of the Lausanne University Hospital (CHUV) organizes an annual meeting aimed at general practitioners, during which interesting clinical cases are presented. In this article, we summarize five cases of community-aquired respiratory infection due to atypical pathogens that were presented during the 2023 meeting, each with a particular teaching point. Although these infections are rare, expanding the differential diagnosis in cases of suboptimal response to therapy or particular exposures is warranted.


La plupart des épisodes de pneumonie acquise en communauté sont causés par Streptococcus pneumoniae et des virus respiratoires, mais d'autres agents pathogènes atypiques peuvent également être responsables d'infections pulmonaires. Le Service des maladies infectieuses du Centre hospitalier universitaire vaudois (CHUV) organise une réunion annuelle destinée aux médecins généralistes, au cours de laquelle des cas cliniques intéressants sont présentés. Dans cet article, nous résumons cinq cas d'infections respiratoires communautaires dus à des agents pathogènes atypiques présentés lors de la réunion de 2023, chacun avec un enseignement particulier. Bien que ces infections soient rares, élargir le diagnostic différentiel en cas de réponse thérapeutique suboptimale ou d'expositions particulières est justifié.


Assuntos
Infecções Respiratórias , Humanos , Diagnóstico Diferencial , Clínicos Gerais , Hospitais Universitários , Infecções Respiratórias/diagnóstico
3.
BMC Infect Dis ; 23(1): 240, 2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37072705

RESUMO

BACKGROUND: Men who have sex with men (MSM) and transgender women (TGW) are disproportionately affected by HIV, with much higher incidence and prevalence rates than in the general population in different countries. There are several barriers to testing among MSM and TGW, such as low risk perception, anticipation of HIV-related stigma, discrimination of sexual orientation, in addition to difficulties related to care and access to health services. Therefore, analyzing the available evidence of the effectiveness of strategies for scaling up HIV testing among key populations is essential to point out potential knowledge gaps which may need to be addressed and develop public health policies to promote testing and early diagnosis of HIV infection. METHODS: An integrative review was carried out to evaluate strategies for scaling up HIV testing in these populations. Search strategy was performed on eight electronic databases, without language restriction. We included clinical trials, quasi-experimental studies, and non-randomized studies. Study selection and data extraction were both performed independently by pairs and disagreements were solved by a third revisor. The screening of the studies was carried out through the selection of titles/abstracts and the reading of the full texts of the pre-selected studies based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data extraction was performed using a structured form. RESULTS: Thirty-seven publications referring to 35 studies were included, mostly being carried out in the United States of America and Australia. No studies were found evaluating disaggregated data on TGW. The studies were grouped into four types of intervention strategies: self-test distribution system (n = 10), organization of health services (n = 9), peer education (n = 6), and social marketing campaign (n = 10). Strategies that focused on the first three groups, combined or not, were more effective in increasing HIV testing among MSM. CONCLUSIONS: Considering the diversity of interventions and the methodological heterogeneity of the included studies, strategies especially involving self-test distribution systems, associated with new information and communication technologies, should be evaluated in different communities and social contexts. Research evaluating specific studies on TGW population is still needed.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Pessoas Transgênero , Humanos , Masculino , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Teste de HIV
4.
Eur J Neurosci ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35545450

RESUMO

Urethane is a general anaesthetic widely used in animal research. The state of urethane anaesthesia is unique because it alternates between macroscopically distinct electrographic states: a slow-wave state that resembles non-rapid eye movement (NREM) sleep and an activated state with features of both REM sleep and wakefulness. Although it is assumed that urethane produces unconsciousness, this has been questioned because of states of cortical activation during drug exposure. Furthermore, the similarities and differences between urethane anaesthesia and physiological sleep are still unclear. In this study, we recorded the electroencephalogram (EEG) and electromyogram in chronically prepared rats during natural sleep-wake states and during urethane anaesthesia. We subsequently analysed the power, coherence, directed connectivity and complexity of brain oscillations and found that EEG under urethane anaesthesia has clear signatures of unconsciousness, with similarities to other general anaesthetics. In addition, the EEG profile under urethane is different in comparison with natural sleep states. These results suggest that consciousness is disrupted during urethane. Furthermore, despite similarities that have led others to conclude that urethane is a model of sleep, the electrocortical traits of depressed and activated states during urethane anaesthesia differ from physiological sleep states.

5.
Molecules ; 26(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34577031

RESUMO

Cytostatics are toxic pharmaceuticals, whose presence in surfaces puts healthcare workers at risk. These drugs might also end up in hospital effluents (HWW), potentially damaging aquatic ecosystems. Bicalutamide is a cytostatic extensively consumed worldwide, but few analytical methods exist for its quantification and most of them require advanced techniques, such as liquid chromatography mass spectrometry (LC-MS), which are very complex and expensive for large monitoring studies. Therefore, a simple but reliable multi-matrix high performance liquid chromatographic method, with fluorescence detection, was developed and validated to rapidly screen abnormal concentrations of bicalutamide in HWW and relevant contamination levels of bicalutamide in indoor surfaces (>100 pg/cm2), prior to confirmation by LC-MS. The method presents good linearity and relatively low method detection limits (HWW: 0.14 ng/mL; surfaces: 0.28 pg/cm2). Global uncertainty was below 20% for concentrations higher than 25 ng/mL (HWW) and 50 pg/cm2 (surfaces); global uncertainty was little affected by the matrix. Therefore, a multi-matrix assessment could be achieved with this method, thus contributing to a holistic quantification of bicalutamide along the cytostatic circuit. Bicalutamide was not detected in any of the grab samples from a Portuguese hospital, but an enlarged sampling is required to conclude about its occurrence and exposure risks.


Assuntos
Anilidas , Nitrilas , Compostos de Tosil , Cromatografia Líquida de Alta Pressão , Águas Residuárias/química
7.
Clin Nutr ; 41(12): 2996-3006, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34187698

RESUMO

BACKGROUND & AIMS: Prevalence and complications of oropharyngeal dysphagia (OD) and malnutrition (MN) in COVID-19 patients is unknown. Our aim was to assess the prevalence, risk factors and clinical outcomes of OD and MN in a general hospital during the first wave of the COVID-19 pandemic. METHODS: This was a prospective, observational study involving clinical assessment of OD (Volume-Viscosity Swallowing Test), and nutritional screening (NRS2002) and assessment (GLIM criteria) in COVID-19 patients hospitalized in general wards at the Consorci Sanitari del Maresme, Catalonia, Spain. The clinical characteristics and outcomes of patients were assessed at pre-admission, admission and discharge, and after 3 and 6-months follow-up. RESULTS: We included 205 consecutive patients (69.28 ± 17.52 years, Charlson 3.74 ± 2.62, mean hospital stay 16.8 ± 13.0 days). At admission, Barthel Index was 81.3 ± 30.3; BMI 28.5 ± 5.4 kg/m2; OD prevalence 51.7% (44.1% impaired safety of swallow); and 45.5% developed MN with a mean weight loss of 10.1 ± 5.0 kg during hospitalization. OD was an independent risk factor for MN during hospitalization (OR 3.96 [1.45-10.75]), and hospitalization was prolonged in patients with MN compared with those without (21.9 ± 14.8 vs 11.9 ± 8.9 days, respectively; p < 0.0001). OD was independently associated with comorbidities, neurological symptoms, and low functionality. At 6-month follow-up, prevalence of OD was still 23.3% and that of MN only 7.1%. Patients with OD at discharge showed reduced 6-month survival than those without OD at discharge (71.6% vs 92.9%, p < 0.001); in contrast, those with MN at discharge did not show 6-month survival differences compared to those without (85.4% vs 83.8%, p = 0.8). CONCLUSIONS: Prevalence and burden of OD and MN in patients hospitalized in COVID-19 wards is very high. Our results suggest that optimizing the management of MN might shorten the hospitalization period but optimizing the management of OD will likely impact the nutritional status of COVID-19 patients and improve their clinical outcomes and survival after hospital discharge. CLINICALTRIALS: gov Identifier: NCT04346212.


Assuntos
COVID-19 , Transtornos de Deglutição , Desnutrição , Humanos , Transtornos de Deglutição/complicações , Estado Nutricional , COVID-19/epidemiologia , Pandemias , Avaliação Nutricional , Estudos Prospectivos , Desnutrição/diagnóstico , Hospitalização , Prevalência
8.
Nutrients ; 14(12)2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35745228

RESUMO

BACKGROUND: The effect of oropharyngeal dysphagia (OD) and thickened fluid (TF) therapy on hydration status has not been well defined in the literature. We aimed to assess the hydration status in patients with OD and the effect TF therapy has on it. METHODS: Two literature reviews following PRISMA methodology (each one including a systematic and a scoping review) were performed: (R1) hydration status in adult patients with OD; (R2) effect of TF therapy on fluid intake and dehydration. Narrative and descriptive methods summarized both reviews. Quality assessment was assessed by Joanna Briggs Institute tools and GRADE. RESULTS: (R1) Five out of twenty-two studies using analytical parameters or bioimpedance showed poorer hydration status among OD and 19-100% prevalence of dehydration; (R2) two high quality studies (total of 724 participants) showed positive effects of TF on hydration status. Among the articles included, nine out of ten studies that evaluated fluid intake reported a reduced TF intake below basal water requirements. CONCLUSIONS: Dehydration is a highly prevalent complication in OD. There is scientific evidence on the positive effect of TF therapy on the hydration status of patients with OD. However, strict monitoring of fluid volume intake is essential due to the low consumption of TF in these patients.


Assuntos
Transtornos de Deglutição , Adulto , Transtornos de Deglutição/etiologia , Desidratação/epidemiologia , Desidratação/etiologia , Desidratação/terapia , Ingestão de Líquidos , Hidratação/efeitos adversos , Humanos , Prevalência
9.
Hosp Pract (1995) ; 50(1): 75-81, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35040377

RESUMO

OBJECTIVE: Our objective was to estimate the frequency of comorbidities and assess its relationship with exposure factors after long-term ART use. METHODS: A cross-sectional study with PLHIV (≥18 years-old), who initiated ART between 2001 and 2005 and attended an HIV/AIDS public referral center (Belo Horizonte/Brazil), was performed. Demographic, clinical, therapeutic, and lifestyle data were obtained through interviews, medical charts, public database, routine laboratory examinations, and bone densitometry. The outcome was the number of comorbidities: hyperglycemia, dyslipidemia, systemic arterial hypertension (SAH), and low bone mineral density (BMD). Absolute/relative frequencies were calculated. Factors associated with the outcome were assessed by quasi-Poisson regression. RESULTS: Of the 98 participants, 53% were male and 79% and over 43 years-old. Moderate physical activity was observed in 82%, overweight/obesity in 50%, and 58% used ART based on two nucleoside reverse transcriptase inhibitors (NRTIs) plus one non-nucleoside reverse transcriptase inhibitor (NNRTI). After a mean of 15.6 years of ART exposure, 207 comorbidities were identified and 93% participants presented at least one comorbidity (mean = 2.1/participant). The most frequent overlapping constituted two co-occurrences: dyslipidemia + hyperglycemia or dyslipidemia + SAH, n = 36 for each co-occurrence. The quasi-Poisson regression showed an increase of 3% in the number of comorbidities per year of age (OR = 1.03; 95%CI = 1.02-1.04) and 84% among PLHIV on moderate physical activity (ref = heavy physical-activity) (OR = 1.84; 95%CI = 1.08-3.13). CONCLUSIONS: Our study shows that the aging slightly contributed to comorbidities. However, the practice of physical-activities is crucial to prevent chronic-diseases. Treatment and preventive measures should be encouraged to diminish the burden of disease and improve quality of life among PLHIV.


Assuntos
Infecções por HIV , Hipertensão , Adolescente , Adulto , Comorbidade , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Qualidade de Vida
10.
J Hazard Mater ; 440: 129743, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35963086

RESUMO

Over the past decade there has been an increasing concern on the presence of cytostatics (also known as anticancer drugs) in natural waterbodies. The conventional wastewater treatments seem not to be effective enough to remove them, and therefore new processes must be considered. This work investigates the performance of ozonation (O3), catalytic ozonation (O3/Fe2+) and peroxone (O3/H2O2) processes, under dark or UV radiation conditions, for the degradation of cytostatics of worldwide concern. The degradation of bicalutamide (a representative of recalcitrant cytostatics) was firstly assessed in batch and then in a tubular column reactor (continuous flow mode runs) using a wastewater treatment plant (WWTP) secondary effluent. Bicalutamide removal ranged between 66 % (O3) and 98 % (O3/H2O2/UV) in continuous flow mode runs, the peroxone process being the most effective. The performance of these processes was then assessed against a mixture of twelve cytostatics of worldwide concern spiked in the WWTP effluent (25-350 ng/L). After treatment, seven cytostatics were completely removed, whereas the five most recalcitrant ones were eliminated to an extent of 8-92 % in O3/H2O2, and 44-95 % in O3/H2O2/UV. Phytotoxicity tests revealed a noticeable reduction in the effluent toxicity, demonstrating the feasibility of these processes in realistic conditions as tertiary treatment.


Assuntos
Citostáticos , Ozônio , Poluentes Químicos da Água , Purificação da Água , Anilidas , Peróxido de Hidrogênio , Nitrilas , Oxirredução , Compostos de Tosil , Águas Residuárias , Água , Poluentes Químicos da Água/análise
11.
Nutrients ; 13(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34371923

RESUMO

BACKGROUND: Special needs schools (SNS) educate children and young people with major neurological disabilities who are at high risk of oropharyngeal dysphagia (OD) and malnutrition (MN). We aimed to assess the prevalence of OD, MN, dehydration (DH), and oral health (OH) in students at an SNS. METHODS: A cross-sectional observational study was conducted at SNS L'Arboç, Catalonia, Spain. We assessed (a) demographics, health status, comorbidities, and gross motor function classification system (GMFCS), (b) swallowing function, oral-motor evaluation, masticatory capacity, and EDACS classification for eating and drinking abilities, (c) nutritional and DH status (anthropometry, bioimpedance and dietary records), and (d) OH (Oral Hygiene Index Simplified). RESULTS: A total of 33 students (mean age 13.3 years; 39.4% level V of GMFCS) were included. Main diagnosis was cerebral palsy at 57.6%. All students presented OD, 90.6% had impaired safety, 68.7% were at levels II-III of EDACS, and 31.3% required PEG; furthermore, 89.3% had chronic MN, 21.4% had acute MN, 70% presented intracellular DH, and 83.9% presented impaired OH. CONCLUSION: MN, DH, OD, and poor OH are highly prevalent conditions in students with cerebral palsy and other neurological disabilities and must be specifically managed through nutritional and educational strategies. The multidisciplinary team at SNS should include healthcare professionals specifically trained in these conditions.


Assuntos
Paralisia Cerebral/diagnóstico , Transtornos de Deglutição/diagnóstico , Deglutição , Crianças com Deficiência , Desnutrição/diagnóstico , Estado Nutricional , Higiene Bucal , Estado de Hidratação do Organismo , Adolescente , Desenvolvimento do Adolescente , Fenômenos Fisiológicos da Nutrição do Adolescente , Fatores Etários , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/terapia , Criança , Desenvolvimento Infantil , Estudos Transversais , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/terapia , Comportamento Alimentar , Feminino , Humanos , Masculino , Desnutrição/epidemiologia , Desnutrição/fisiopatologia , Desnutrição/terapia , Destreza Motora , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Espanha/epidemiologia
12.
Sci Total Environ ; 795: 148855, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34247083

RESUMO

As the number of cancer patients increases, so does the consumption of cytostatic drugs, which are commonly used in chemotherapy. These compounds are already ubiquitous in wastewater treatment plant (WWTP) effluents and natural water streams, revealing the urgent need for efficient technologies for their removal from the aqueous phase. This work presents the elimination of five cytostatics of concern, found in Portuguese WWTP effluents: bicalutamide (BICA), capecitabine (CAP), cyclophosphamide (CYC), ifosfamide (IFO) and mycophenolic acid (MPA), using non-catalytic ozonation. Experiments were performed starting from trace-level concentrations (1 µM) for all cytostatics at neutral pH (pH: 7.3 ± 0.1) and room temperature (23 ± 1 °C), employing different ozone dosages. Under the studied conditions, CAP and MPA were quickly eliminated by direct ozonation, whereas BICA, CYC and IFO were more slowly degraded, as they undergo a breakdown via hydroxyl radicals generation (HO) exclusively. Increasing the O3 dosage from 1 to 3 mgO3/mgDOC, CAP, MPA and IFO were completely removed, and BICA and CYC were converted more than 90% after 180 min. The presence of both inorganic ions and organic matter in real water matrices (river water, WWTP secondary effluent) did not affect the removal of CAP and MPA. Nonetheless, there was an inefficient and very fast O3 consumption that resulted in only around 30% elimination of BICA, CYC and IFO, even if the reaction time is extended.


Assuntos
Citostáticos , Ozônio , Poluentes Químicos da Água , Purificação da Água , Citostáticos/análise , Humanos , Águas Residuárias/análise , Água , Poluentes Químicos da Água/análise
13.
J Chem Neuroanat ; 105: 101769, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32145304

RESUMO

Hypocretins (Hcrt) 1 and 2 are two neuropeptides synthesized from neurons that are located in the perifornical area of the lateral hypothalamus. These neurons project diffusely throughout the central nervous system, and have been implicated in the generation and maintenance of wakefulness, as well as in critical physiological processes that occur during this behavioral state, such as motivation. The hypocretinergic projections towards the feline midbrain have not been studied before. Therefore, the aim of the present study was to analyze their relationship to the midbrain neurons, that are critically involved in the control of sleep and wakefulness. With this purpose, we examined the distribution of Hcrt1-positive fibers in the midbrain and pontomesencephalic area of the domestic cat (Felis catus), and their relationship with catecholaminergic and cholinergic neurons by means of single and double immunohistochemistry. Hcrtergic axons with distinctive varicosities and buttons were heterogeneously distributed, exhibiting different densities in distinct regions of the midbrain. High Hcrtergic fiber densities were observed in the periaqueductal gray, interpeduncular nucleus, locus coeruleus and cholinergic mesopontine regions. In addition, we studied in detail the Hcrtergic projection towards the dopaminergic nuclei of the midbrain. While very few Hcrt + fibers were observed in the substantia nigra pars compacta, the highest density of Hcrtergic fibers was found in the dopaminergic ventral periaqueductal gray area (also called A10dc area); appositions between Hcrtergic terminals and dopaminergic somata and dendrites were observed within this area. Because this dopaminergic area has been involved in the control of wakefulness, the present anatomical data provides relevant support about the role of the Hcrtergic system in the generation of this behavioral state.


Assuntos
Mesencéfalo/metabolismo , Neurônios/metabolismo , Orexinas/metabolismo , Vigília/fisiologia , Animais , Gatos , Imuno-Histoquímica , Masculino , Fibras Nervosas/metabolismo , Sono/fisiologia
14.
Clocks Sleep ; 2(4): 536-556, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33317018

RESUMO

The sleep-wake cycle is constituted by three behavioral states: wakefulness (W), non-REM (NREM) and REM sleep. These states are associated with drastic changes in cognitive capacities, mostly determined by the function of the thalamo-cortical system, whose activity can be examined by means of intra-cranial electroencephalogram (iEEG). With the purpose to study in depth the basal activity of the iEEG in adult rats, we analyzed the spectral power and coherence of the iEEG during W and sleep in the paleocortex (olfactory bulb), and in neocortical areas. We also analyzed the laterality of the signals, as well as the influence of the light and dark phases. We found that the iEEG power and coherence of the whole spectrum were largely affected by behavioral states and highly dependent on the cortical areas recorded. We also determined that there are night/day differences in power and coherence during sleep, but not in W. Finally, we observed that, during REM sleep, intra-hemispheric coherence differs between right and left hemispheres. We conclude that the iEEG dynamics are highly dependent on the cortical area and behavioral states. Moreover, there are light/dark phases disparities in the iEEG during sleep, and intra-hemispheric connectivity differs between both hemispheres during REM sleep.

15.
Peptides ; 126: 170249, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31911169

RESUMO

Serotonergic neurons of the median raphe nucleus (MnR) and hypothalamic melanin-concentrating hormone (MCH)-containing neurons, have been involved in the control of REM sleep and mood. In the present study, we examined in rats and cats the anatomical relationship between MCH-containing fibers and MnR neurons, as well as the presence of MCHergic receptors in these neurons. In addition, by means of in vivo unit recording in urethane anesthetized rats, we determined the effects of MCH in MnR neuronal firing. Our results showed that MCH-containing fibers were present in the central and paracentral regions of the MnR. MCHergic fibers were in close apposition to serotonergic and non-serotonergic neurons. By means of an indirect approach, we also analyzed the presence of MCHergic receptors within the MnR. Accordingly, we microinjected MCH conjugated with the fluorophore rhodamine (R-MCH) into the lateral ventricle. R-MCH was internalized into serotonergic and non-serotonergic MnR neurons; some of these neurons were GABAergic. Furthermore, we determined that intracerebroventricular administration of MCH induced a significant decrease in the firing rate of 53 % of MnR neurons, while the juxtacellular administration of MCH reduced the frequency of discharge in 67 % of these neurons. Finally, the juxtacellular administration of the MCH-receptor antagonist ATC-0175 produced an increase in the firing rate in 78 % of MnR neurons. Hence, MCH produces a strong regulation of MnR neuronal activity. We hypothesize that MCHergic modulation of the MnR neuronal activity may be involved in the promotion of REM sleep and in the pathophysiology of depressive disorders.


Assuntos
Hormônios Hipotalâmicos/farmacologia , Hipotálamo/efeitos dos fármacos , Melaninas/farmacologia , Fibras Nervosas/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Hormônios Hipofisários/farmacologia , Núcleos da Rafe/efeitos dos fármacos , Receptores do Hormônio Hipofisário/metabolismo , Animais , Gatos , Hipotálamo/metabolismo , Hipotálamo/fisiologia , Fibras Nervosas/metabolismo , Fibras Nervosas/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Núcleos da Rafe/metabolismo , Núcleos da Rafe/fisiologia , Ratos , Ratos Wistar
16.
Nutrients ; 11(2)2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30781630

RESUMO

BACKGROUND: Oropharyngeal dysphagia (OD) and malnutrition are highly prevalent in older patients that are discharged from general hospitals (47% and 30%, respectively). AIMS: To develop a nutritional plan for these patients involving a triple adaptation of their traditional diet: (a) rheological adaptation (texture and viscosity) for safe deglutition, (b) nutritional adaptation (water, calories, and proteins), and (c) organoleptic adaptation to improve compliance. METHODS: Two fluid viscosities (250 and 800 mPa·s) were selected according to previous studies on optimal viscosities in older patients. The British Dietetic Association food texture classification based on common clinical practice selected two food textures (thick purée and fork-mashable. Two levels of calorie protein enrichment were selected according to previous studies using the Mini Nutritional Assessment (MNA®). RESULTS: The daily caloric-protein and hydric needs were established at 1750 kcal, 70 g protein, and 1750 mL water in patients with MNA® ≥ 17; and, 2037 kcal, 90 g protein, and 2000 mL water/day in malnourished patients. Sixteen weekly menus (296 recipes) were developed while using two textures, two levels of viscosity, two nutritional phenotypes (normal/at-risk vs. malnourished), and two seasons of the year (spring/summer-autumn/winter) based on Mediterranean cuisine. CONCLUSION: This concept paper demonstrates that traditional Mediterranean cooking can be adapted to meet the rheological, nutritional, and hydration needs of older patients with OD. The recipes that we have developed meet the needs of patients with varying degrees of OD and malnutrition are reproducible in patient's homes and they could have a major impact on the clinical outcomes of these patients.


Assuntos
Culinária/métodos , Transtornos de Deglutição/dietoterapia , Dieta Mediterrânea , Dieta/métodos , Desnutrição/dietoterapia , Idoso , Deglutição , Transtornos de Deglutição/fisiopatologia , Feminino , Humanos , Masculino , Desnutrição/fisiopatologia , Estado Nutricional , Reologia/métodos , Viscosidade
17.
Peptides ; 104: 50-61, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29680268

RESUMO

Neurons that utilize melanin-concentrating hormone (MCH) as a neuromodulator are localized in the postero-lateral hypothalamus and incerto-hypothalamic area. These neurons project diffusely throughout the central nervous system and have been implicated in critical physiological processes, such as sleep. Unlike rodents, in the order carnivora as well as in humans, MCH exerts its biological functions through two receptors: MCHR-1 and MCHR-2. Hence, the cat is an optimal animal to model MCHergic functions in humans. In the present study, we examined the distribution of MCH-positive fibers in the brainstem of the cat. MCHergic axons with distinctive varicosities and boutons were heterogeneously distributed, exhibiting different densities in distinct regions of the brainstem. High density of MCHergic fibers was found in the dorsal raphe nucleus, the laterodorsal tegmental nucleus, the periaqueductal gray, the pendunculopontine tegmental nucleus, the locus coeruleus and the prepositus hypoglossi. Because these areas are involved in the control of REM sleep, the present anatomical data support the role of this neuropeptidergic system in the control of this behavioral state.


Assuntos
Tronco Encefálico/metabolismo , Hormônios Hipotalâmicos/metabolismo , Melaninas/metabolismo , Hormônios Hipofisários/metabolismo , Sono REM/fisiologia , Animais , Gatos , Imunofluorescência , Imuno-Histoquímica , Masculino , Tegmento Pontino/metabolismo
18.
Environ Sci Pollut Res Int ; 25(28): 27748-27755, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29785599

RESUMO

This paper addresses the removal of four aromatic hydrocarbons typically found in petrochemical wastewater: benzene (B), toluene (T), o-xylene (X), and naphthalene (N), by microwave-assisted catalytic wet peroxide oxidation (MW-CWPO) using activated carbon (AC) as catalyst. Under the studied conditions, complete pollutant elimination (B, 1.28 mM; T, 1.09 mM; X, 0.94 mM; and N, 0.78 mM) was achieved, with more than 90% TOC removal after only 15-min reaction time, working at 120 °C, pH0 = 3, AC at 1 g L-1, and H2O2 at the stoichiometric dose. Furthermore, in the case of toluene, naphthalene, and xylene, the hydroxylation and breakdown of the ring is very rapid and toxic intermediates were not detected. The process follows two steps: (i) pollutant adsorption onto AC followed by (ii) adsorbed compounds oxidation. Thus, MW-CWPO with AC as catalyst appears a promising way for a fast and effective process for B, T, X, and N removal in aqueous phase.


Assuntos
Carvão Vegetal/química , Hidrocarbonetos Aromáticos/análise , Peróxido de Hidrogênio/química , Micro-Ondas , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Catálise , Oxirredução , Águas Residuárias/química
19.
Mol Cell Biol ; 22(22): 7731-43, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12391143

RESUMO

Focal adhesion kinase (FAK) is activated following integrin engagement or stimulation of transmembrane receptors. Autophosphorylation of FAK on Tyr-397 is a critical event, allowing binding of Src family kinases and activation of signal transduction pathways. Tissue-specific alternative splicing generates several isoforms of FAK with different autophosphorylation rates. Despite its importance, the mechanisms of FAK autophosphorylation and the basis for differences between isoforms are not known. We addressed these questions using isoforms of FAK expressed in brain. Autophosphorylation of FAK(+), which is identical to that of "standard" FAK, was intermolecular in transfected cells, although it did not involve the formation of stable multimeric complexes. Coumermycin-induced dimerization of gyrase B-FAK(+) chimeras triggered autophosphorylation of Tyr-397. This was independent of cell adhesion but required the C terminus of the protein. In contrast, the elevated autophosphorylation of FAK(+6,7), the major neuronal splice isoform, was not accounted for by transphosphorylation. Specifically designed immune precipitate kinase assays confirmed that autophosphorylation of FAK(+) was intermolecular, whereas autophosphorylation of FAK(+6,7) or FAK(+7) was predominantly intramolecular and insensitive to the inhibitory effects of the N-terminal domain. Our results clarify the mechanisms of FAK activation and show how alternative splicing can dramatically alter the mechanism of autophosphorylation of a protein kinase.


Assuntos
Processamento Alternativo , Isoenzimas/metabolismo , Proteínas Tirosina Quinases/metabolismo , Aminocumarinas , Animais , Encéfalo/enzimologia , Células COS , Cumarínicos/metabolismo , DNA Girase/genética , DNA Girase/metabolismo , Dimerização , Inibidores Enzimáticos/metabolismo , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Isoenzimas/genética , Modelos Biológicos , Mutagênese Sítio-Dirigida , Novobiocina/metabolismo , Peptídeos/genética , Peptídeos/metabolismo , Fosforilação , Proteínas Tirosina Quinases/genética , Ratos , Transdução de Sinais/fisiologia , Inibidores da Topoisomerase II , Tirosina/metabolismo
20.
Clin Nutr ; 36(4): 1110-1116, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27499393

RESUMO

BACKGROUND: Oropharyngeal dysphagia (OD) is a prevalent risk factor for malnutrition (MN) in older patients and both conditions are related to poor outcome. OBJECTIVE: To explore the nutritional status in older patients with OD in a chronic and an acute clinical situation. DESIGN: We examined 95 older (≥70 years) patients with OD associated to chronic neurological diseases or aging, and 23 older patients with OD and acute community-acquired pneumonia (CAP) with videofluoroscopy; and 15 older people without OD. We collected nutritional status, measured with the Mini Nutritional Assessment (MNA®), anthropometric measurements, and biochemistry and bioimpedance for body composition. Functional status was assessed with the Barthel index. RESULTS: 1) Taking into consideration patients with OD with chronic conditions, 51.1% presented a MNA® ≤23.5; 16.7%, sarcopenia and a) reduced visceral and muscular protein compartments and fat compartment; b) muscular weakness c) intracellular water depletion, and d) reduced body weight. Patients with OD and MNA® ≤23 needed higher levels of nectar viscosity for a safe swallow and had increased oropharyngeal residue at spoon-thick viscosity. 2) Patients with OD and CAP, 69.5%, presented an MNA® ≤23.5 and 29.4% sarcopenia, the inflammatory response of the pneumonia adding to the more severe depletion in visceral protein and muscular mass. CONCLUSIONS: Prevalence of impaired nutritional status (malnutrition risk, and sarcopenia) among older patients with OD associated with either chronic or acute conditions is very high. In patients with OD and chronic diseases, poor nutritional status further impairs OD with an increase in oropharyngeal residue at spoon-thick viscosity. In the acute setting there is inflammation and an additional protein deficiency. These findings will help develop specific products both for OD and nutritional status in each specific clinical situation.


Assuntos
Doença Aguda , Doença Crônica , Transtornos de Deglutição/fisiopatologia , Desidratação/etiologia , Fenômenos Fisiológicos da Nutrição do Idoso , Desnutrição/etiologia , Sarcopenia/etiologia , Doença Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Comorbidade , Estudos Transversais , Transtornos de Deglutição/complicações , Transtornos de Deglutição/epidemiologia , Desidratação/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Desnutrição/epidemiologia , Estado Nutricional , Pneumonia/epidemiologia , Prevalência , Fatores de Risco , Sarcopenia/epidemiologia , Índice de Gravidade de Doença , Espanha/epidemiologia
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