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The DDR1 locus is associated with the diagnosis of schizophrenia and with processing speed in patients with schizophrenia and first-episode psychosis. Here, we investigated whether DDR1 variants are associated with bipolar disorder (BD) features. First, we performed a caseâcontrol association study comparing DDR1 variants between patients with BD and healthy controls. Second, we performed linear regression analyses to assess the associations of DDR1 variants with neurocognitive domains and psychosocial functioning. Third, we conducted a mediation analysis to explore whether neurocognitive impairment mediated the association between DDR1 variants and psychosocial functioning in patients with BD. Finally, we studied the association between DDR1 variants and white matter microstructure. We did not find any statistically significant associations in the caseâcontrol association study; however, we found that the combined genotypes rs1264323AA-rs2267641AC/CC were associated with worse neurocognitive performance in patients with BD with psychotic symptoms. In addition, the combined genotypes rs1264323AA-rs2267641AC/CC were associated with worse psychosocial functioning through processing speed. We did not find correlations between white matter microstructure abnormalities and the neurocognitive domains associated with the combined genotypes rs1264323AA-rs2267641AC/CC. Overall, the results suggest that DDR1 may be a marker of worse neurocognitive performance and psychosocial functioning in patients with BD, specifically those with psychotic symptoms.
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Osteoglycin, a fundamental proteoglycan within the vascular extracellular matrix, is expressed in vascular smooth muscle cells (VSMCs). Type 2 diabetes (T2D) is associated with cardiovascular disease (CVD) but the role of osteoglycin in the development of CVD is controversial to date. Therefore, our aims are to determine and compare the level of osteoglycin in T2D patients with/without CVD versus control subjects both at serum and vascular tissue and to analyze in vitro role of osteoglycin in VSMCs under calcified conditions. For this, serum osteoglycin levels were determined by enzyme-linked immunosorbent assay (ELISA) in 117 controls and 129 patients with T2D (46 with CVD and 83 without CVD), revealing a significant increase in patients with T2D compared with controls. Osteoglycin level was not an estimator of CVD but correlated with markers of insulin resistance (triglycerides and triglycerides/high-density lipoprotein cholesterol index) in patients with T2D. At the vascular level, osteoglycin expression was assessed by RT-qPCR and immunohistochemistry, and no significant differences were observed between calcified arteries from patients with T2D and noncalcified arteries from controls. In vitro experiments using VSMCs (mock and overexpressing osteoglycin) under calcifying conditions were performed to analyze the osteoglycin function. The overexpression of osteoglycin in VMSCs under calcifying conditions revealed an increase of cell proliferation without effect on apoptosis and an upregulation of the expression of autotaxin (ATX) involved in inflammatory processes. In conclusion, osteoglycin could play a role in glycemic homeostasis, being a potential biomarker of insulin resistance in patients with T2D. Furthermore, osteoglycin could indirectly participate in the development of atherosclerosis through its regulatory effect on ATX and by proliferating VSMCs.NEW & NOTEWORTHY This study uncovers an increase of serum osteoglycin levels in patients with type 2 diabetes, which does not appear to be associated with the development of atherosclerosis, but rather with insulin resistance in this population. Overexpression of osteoglycin increased proliferation and upregulated the expression of autotaxin in vascular smooth muscle cells within calcified environments. Osteoglycin could be a biomarker of insulin resistance for type 2 diabetes and could be indirectly involved in the development of atherosclerosis.
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Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Músculo Liso Vascular , Aterosclerose/metabolismo , Doenças Cardiovasculares/metabolismo , Biomarcadores/metabolismo , Triglicerídeos/metabolismo , Miócitos de Músculo Liso/metabolismoRESUMO
SIGNIFICANCE: Frequent and effective patient-practitioner communication is essential to ensure that instructions regarding contact lens use, care, and maintenance are understood and followed. Given the relevance of good patient compliance, the responsibility of practitioners to provide adequate information may not be neglected. PURPOSE: This study aimed to determine the content and type of information licensed optometrists in Spain provide their patients during the first contact lens fitting and at follow-up visits. METHODS: A self-reported ad hoc survey was distributed to licensed optometrists in Spain to investigate, among other factors, whether practitioners provided information on several aspects of contact lens use and maintenance, how was this information provided, and whether in-office practical demonstrations were conducted at all contact lens appointments. RESULTS: Respondents of 321 surveys had a median of 20 years of contact lens fitting experience and worked on independent practices (67.6%), and national (29.0%) and regional chains (3.4%). Type of practice influenced continuous education habits ( P = .03). Overall, 28.0% of participants did not always instruct patients on the need to rub contact lenses, 34.3% did not always address contact lens replacement, and 6.8% did not always explain storage case hygiene and replacement. At the follow-up visit, only 8.4% of respondents asked their patients to demonstrate their care routines. Information was mostly oral (48.6%) or oral and written (43.0%). Contact lens-related complications were reported more frequently by participants with less continuous education training ( P = .01), by those not always recommending rubbing ( P = .002), and by those not providing written information about storage case hygiene and replacement ( P = .002). CONCLUSIONS: Patient-practitioner communication was good, albeit several areas were identified where information was insufficient or not provided in a correct and timely format. Precise, written information on rubbing and storage case hygiene and replacement may improve compliance and assist in avoiding complications and dropout.
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Soluções para Lentes de Contato , Lentes de Contato , Humanos , Cooperação do Paciente , Inquéritos e Questionários , HigieneRESUMO
SIGNIFICANCE: Compliance with hygiene and replacement of contact lens (CL) storage cases is key to avoid CL contamination and anterior ocular surface complications. However, compliance levels with these accessories remain low, even in patients with awareness of the risk associated with noncompliance. PURPOSE: This study aimed to determine level of compliance with common practices regarding CL storage case hygiene and replacement, type of information provided by practitioners, and risk perception. METHODS: An ad hoc self-reported survey was used to collect demographic and CL wear details, compliance with storage case care, type of received information, and risk perception (in a 1-to-5 scale). Inferential statistics explored the relationship of demographic details and type of received information with compliance and risk perception. RESULTS: Nondaily disposable wearing participants returned 299 completed surveys, with a median age of 24 years (76.9% females). Monthly replacement silicone hydrogel CLs and multipurpose solutions were predominant. Self-reported compliance with storage case care was poor, with 19.1% of respondents never cleaning their cases, 68.6% exposing them to tap water, and 26.4% failing to replace them within 6 months of acquisition. Two-thirds of respondents received specific information on case maintenance, mainly in oral form. Perceived risk associated with poor-compliance practices was high (median values of 4 and 5), and increased with educational level (P = .02, regarding handwashing; P = .03, regarding case hygiene), with years of CL wear experience (P < .001, regarding handwashing), in those patients provided with specific information on CL case care (P = .01, regarding case replacement). CONCLUSIONS: Compliance with CL storage case hygiene and replacement was generally poor, although awareness of risk associated with noncompliance was high and influenced by factors related to demographic details, CL experience, and patient-practitioner communication. Strategies must be explored to increase risk awareness through education because this may lead to better compliance practices.
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Soluções para Lentes de Contato , Lentes de Contato Hidrofílicas , Adulto , Feminino , Humanos , Higiene , Masculino , Cooperação do Paciente , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: The continued provision of safe food, free of aflatoxin remains a huge challenge in developing countries. Despite several favourable climatic conditions that facilitate aflatoxin contamination in Ethiopia, there is little information showing aflatoxin exposure in children. Therefore, this study assessed aflatoxin exposure among young children in Butajira district, South-Central Ethiopia. METHODS: Community based cross-sectional study stratified by agro-ecology was employed in Health and Demographic Surveillance Site (HDSS) of Butajira. The study included 332 children aged 12-59 months and were selected by simple random sampling technique using the HDSS registration number as a sampling frame. We collected data on dietary practice and aflatoxin exposure. Aflatoxin M1 concentration in urine was measured by Enzyme-Linked Immunosorbent assay (ELISA). The data analysis was carried out using STATA. RESULTS: Detectable urinary Aflatoxin M1 was found in 62.4% (95% CI: 56.9 - 67.5%) of the children at a level ranging from 0.15 to 0.4 ng/ml. Children living in lowland agro-ecological zone had [AOR = 2.11 (95% CI; 1.15, 3.88] odds of being exposed to aflatoxin as compared to children living in highland agro-ecological zone. Children at lower socio-economic status [AOR = 0.27 (95% CI; 0.14, 0.50] and medium socio-economic status [AOR = 0.47 (95% CI; 0.25, 0.87] had 73% and 53% lower odds of being exposed to aflatoxin as compared to children in the higher socio-economic status, respectively. CONCLUSIONS: Aflatoxin exposure among young children was very high in South-Central Ethiopia. This high aflatoxin exposure might emphasize the need for aflatoxin exposure mitigation strategies in Ethiopia. Especially, raising awareness of the community towards aflatoxin exposure is very crucial. In addition, further research is required to assess long-term aflatoxin exposure and its association with child growth and development.
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Aflatoxinas , Aflatoxina M1 , Criança , Pré-Escolar , Estudos Transversais , Dieta , Etiópia/epidemiologia , HumanosRESUMO
BACKGROUND: The interaction of hormonal factors are crucial for good foetal development. During the second trimester of gestation, most of the main physiological processes of foetal development occur. Therefore, the aim of this study was to determine the variations in the physiological levels of cortisol, estriol, estrone sulphate, and progesterone during the second trimester (weeks 12-26) in order to establish normal ranges that can serve as indicators of foetal well-being and good functioning of the foetal-placental unit. METHODS: Saliva samples from 106 pregnant women were collected weekly (from week 12 to week 26 of gestation), and hormonal measurements were assayed by an enzyme immunoassay. The technique used for hormone measurements was highly sensitive and served as a non-invasive method for sample collection. RESULTS: The results revealed a statistically significant (p<0.05) difference between cortisol, progesterone, and oestrogens throughout the second trimester, with a more substantial relationship between oestrogens and progesterone [P4-E3 (r=0.427); P4-E1SO4 (r=0.419)]. By analysing these hormone concentrations, statistically significant (p<0.05) elevations in progesterone, cortisol, and estriol levels were found at the 16th [(P4 (0.78±0.088), C(1.99±0.116), E3(2.513±0.114)]; 18th [(P4 (1.116±0.144), C(3.409±0.137), E3(3.043±0.123)] and 23rd week of gestation [(P4(1.36±0.153), C(1.936±0.11), E3(2.657±0.07)]. Estrone sulphate levels appeared to increase progressively throughout the second trimester [from 1.103±0.03 to 2.244±0.09]. CONCLUSION: The 18th week of gestation seems to constitute a very important week during foetal adrenal development, and the analysis of the main hormones involved in foetal development, provided more precise information regarding the proper functioning of the foetal unit and foetal development.
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Desenvolvimento Fetal , Segundo Trimestre da Gravidez/metabolismo , Adulto , Estriol/metabolismo , Estrona/análogos & derivados , Estrona/metabolismo , Feminino , Humanos , Hidrocortisona/metabolismo , Estudos Longitudinais , Gravidez , Progesterona/metabolismo , Saliva/metabolismoRESUMO
Milk is an important food item in the diet of Kenyans, especially infants. During the last two decades, the dairy sector in Kenya has witnessed important growth in production and improvements in milk quality. The informal marketing channel still prevails, and the Kenya Dairy Board, the regulator of the dairy sector, is currently introducing new regulations to increase registration and licensing of smallholder producers and dairy business operators, improve product hygiene and quality, and safeguard the health of consumers. These new regulations encompass, among others, the requirement to pasteurize milk before it is sold and adopt traceability processes and quality tests; most of these will probably result in higher milk prices at retail level. Using the best-worst scaling approach in this study, we analyzed the potential effects of milk price increase on household milk purchase and allocation to infants (6-48 months of age). The results indicate that an increase in milk price will decrease milk allocation to and intake by children. Households will replace the lost infant milk intake by fruits or porridge that might not be of equivalent nutritional value to milk. Any reforms to policies and regulatory systems aimed at streamlining the dairy sector should account for impacts on milk prices, responsiveness of consumers to price variations and infant nutrition. We recommend that regulatory and development agencies consider interventions that do not increase price for consumers and facilitate access to affordable and safe milk for children and entire households.
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Evidence to support the use of steroids in coronavirus disease 2019 (COVID-19) pneumonia is lacking. We aim to determine the impact of steroid use for COVID-19 pneumonia on hospital mortality. We performed a single-center retrospective cohort study in a university hospital in Madrid, Spain, during March of 2020. To determine the role of steroids in in-hospital mortality, patients admitted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and treated with steroids were compared to patients not treated with steroids, and we adjusted with a propensity score for patients on steroid treatment. Survival times were compared using the log rank test. Different steroid regimens were compared and adjusted with a second propensity score. During the study period, 463 out of 848 hospitalized patients with COVID-19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. The median time to steroid treatment from symptom onset was 10 days (interquartile range [IQR], 8 to 13 days). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67]; hazard ratio [HR], 0.51 [95% confidence interval, 0.27 to 0.96]; P = 0.044). Steroid treatment reduced mortality by 41.8% relative to the mortality with no steroid treatment (relative risk reduction, 0.42 [95% confidence interval, 0.048 to 0.65]). Initial treatment with 1 mg/kg of body weight/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86]; odds ratio [OR], 0.880 [95% confidence interval, 0.449 to 1.726]; P = 0.710). Our results show that the survival of patients with SARS-CoV-2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. Rates of in-hospital mortality were not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.
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Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Interferons/uso terapêutico , Lopinavir/uso terapêutico , Metilprednisolona/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Idoso , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , COVID-19 , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/virologia , Comorbidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/imunologia , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Dislipidemias/tratamento farmacológico , Dislipidemias/imunologia , Dislipidemias/mortalidade , Dislipidemias/virologia , Feminino , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/mortalidade , Neoplasias/virologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudos Retrospectivos , SARS-CoV-2 , Análise de SobrevidaRESUMO
Milk and milk products are essential in the diets of the Borana pastoral community in Ethiopia. Traditional handling and processing of dairy products using basic equipment and infrastructure coupled with a preference for raw milk consumption pose potential health risks to consumers. We tested the effect of an intervention designed to improve the hygienic handling and safe consumption of milk on the knowledge, attitudes, and practices (KAP) of women who produce and sell dairy products. The intervention consisted of 16 h of training on good milk production practices and prevention of milk-borne diseases. A total of 120 women were trained and their KAP assessed at baseline (pretraining), immediately after training, and 6 mo after training. Overall, training increased the knowledge score of the participants from 75.6 to 91.4% in the immediate post-training assessment, and to 90.0% at 6 mo post-training. Compared with pretraining (58.8%), we found a statistically significant difference in the overall attitude score at the immediate post-training evaluation (64.7%) but not 6 mo after (61.4%). We observed a similar increase in the understanding of correct practices from 49.5% at pretraining to 64.7% 6 mo following the training. For some desirable attitudes and practices, the proportion of women reporting adoption at pretraining was low and the change derived from training still left one-third of respondents displaying a negative attitude and a quarter of them reporting wrong practices. We recommend that future training interventions be complemented with locally adaptable technologies, provision of incentives, and creation of an enabling environment including improved access to clean water and sanitation facilities to affect not only knowledge, but also attitudes and ultimately practices in the long term.
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Indústria de Laticínios/normas , Microbiologia de Alimentos , Conhecimentos, Atitudes e Prática em Saúde , Leite/microbiologia , Criação de Animais Domésticos , Animais , Atitude , Camelus , Bovinos , Etiópia , Feminino , Cabras , HumanosRESUMO
Alzheimer's disease has become a public health priority, so an investigation of new therapies is required. Tacrine (TAC) was licensed for treatments; however, its oral administration caused hepatotoxicity, so it is essential to reduce the side effects. PAMAM dendrimer generation 4.0 and 4.5 (DG4.0 and DG4.5) can be used as drug delivery systems and as nanodrugs per se. Our work aims to propose a combined therapy based on TAC and PAMAM dendrimer co-administration. TAC and dendrimer interactions were studied by in vitro drug release, drug stability, and FTIR. The toxicity profile of co-administration was evaluated in human red blood cells, in Neuro-2a cell culture, and in zebrafish larvae. Also, the anti-acetylcholinesterase activity was studied in cell culture. It was possible to obtain DG4.0-TAC and DG4.5-TAC suspensions, without reducing the drug solubility and stability. FTIR and in vitro release studies confirmed that interaction between TAC and DG4.5 was of the electrostatic type. No toxicity effects on human red blood cells were observed, whereas the co-administration with DG4.5 reduced cytotoxicity of TAC on the Neuro-2a cell line. Moreover, in vivo co-administration of both DG4.0-TAC and DG4.5-TAC reduced the morphological and hepatotoxic effects of TAC in zebrafish larvae. The reduction of TAC toxicity was not accompanied by a reduction in its activity since the anti-acetylcholinesterase activity remains when it is co-administrated with dendrimers. In conclusion, the co-administration of TAC with both DG4.0 and DG4.5 is a novel therapy since it was less-toxic, was more biocompatible, and has the same effectiveness than the free drug. Graphical abstract.
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Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/administração & dosagem , Dendrímeros/administração & dosagem , Sistemas de Liberação de Medicamentos , Tacrina/administração & dosagem , Animais , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Estabilidade de Medicamentos , Humanos , Solubilidade , Tacrina/efeitos adversos , Tacrina/química , Peixe-ZebraRESUMO
Livestock-wildlife interactions promote the transmission of a wide range of infectious diseases that constraint livestock production. We used a participatory appraisal approach to find out and rank infectious diseases of concern to pastoralists in a zone of intense wildlife-livestock interaction and another zone with limited interactions. Four villages were selected purposively in areas with intensive cattle-wildlife interactions (zone 1), and another two in areas with low to moderate cattle-wildlife interactions (zone 2). Data were collected in focus group discussions (FGDs) using participatory epidemiological methods (PE); each group had 8-13 participants. Results of impact matrix scoring from all sites indicated that malignant catarrhal fever (MCF), anthrax, foot and mouth disease (FMD), contagious bovine pleuropneumonia (CBPP), east coast fever (ECF) and African animal trypanosomiasis (ATT), in decreasing order, had the highest impact on livestock production. A Kruskal-Wallis test revealed a significant difference in FMD annual prevalence between cattle age groups (p < 0.001) and was the highest in animals > 4 years (median score of 32.5, range, 10-50). FMD had the highest impact on milk production, but based on veterinary costs (treatment costs), it was ranked second to CBPP. The study provides information on disease priorities that occur in the target zones in Mara ecosystem and which the local pastoralists must consider when accessing key ecosystem services such as water and pasture.
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Doenças dos Bovinos/epidemiologia , Meio Ambiente , Criação de Animais Domésticos , Animais , Animais Selvagens , Bovinos , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/virologia , Quênia/epidemiologia , Gado , PrevalênciaRESUMO
Doxorubicin (DOXO) is a chemotherapeutic agent widely used for the treatment of solid tumors and hematologic malignancies in both adults and children. However, DOXO causes short- and long-term cardiotoxicity and others undesirable side effects, such as nephrotoxicity and neurotoxicity. Magnetic nanoparticles (MNPs) allow the delivery of drugs specifically to target place, employing an external magnet. Moreover, they may act as contrast agents in MRI providing information on the diagnostic of diverse pathologies. In this way, two functions may be combined in a unique nanosystem known as theranostic. Also, the MNPs can be modified with folic acid (MNPs@FA) to increase the uptake by cancer cells that overexpress the FA receptors. In previous works, our collaborators obtained and characterized MNPs, MNPs@FA, and MNPs@FA@DOXO. It is essential to study the biosafety of nanotheranostic, and there is no published study of Fe3O4 nanoparticles developmental toxicity. Because of that, this work aimed to study the in vivo toxicity and biocompatibility of DOXO, MNPs@FA, and MNPs@FA@DOXO using zebrafish embryo and larvae as an animal model. Viability, developmental toxicity, changes in spontaneous movement (neurotoxicity), changes in cardiac rhythm (cardiotoxicity), and efficiency of DOXO-uptake were studied. While the 48-h treatment with 50⯵g/mL of DOXO resulted in a 30% larvae death and the development of significant morphological abnormalities, the treatment with MNPs@FA@DOXO and MNPs@FA did not reduce the viability and did not cause developmental abnormalities. Besides, the MNPs@FA@DOXO reduced the cardiotoxicity and promoted a more rapid and significant uptake of DOXO by zebrafish larvae.
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Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/toxicidade , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico/toxicidade , Nanopartículas de Magnetita/toxicidade , Nanomedicina Teranóstica/métodos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/metabolismo , Ácido Fólico/administração & dosagem , Ácido Fólico/metabolismo , Larva/efeitos dos fármacos , Larva/metabolismo , Nanopartículas de Magnetita/administração & dosagem , Peixe-ZebraRESUMO
Doxorubicin (DOX) hydrochloride is a powerful anthracycline antibiotic used for the treatment of various types of malignancies, particularly ovarian and metastatic breast cancer. However, DOX presents severe side effects, such as hepatotoxicity, nephrotoxicity, dose-limiting myelosuppression, brain damage and cardiotoxicity. A liposomal formulation, Doxil®, was approved by the FDA, which has managed to reduce the number of cardiac events in patients with metastatic breast cancer. However, in comparison to free DOX, Doxil® has not shown significant improvements regarding survival. We have previously designed DOX-loaded mixed micelles (MMDOX) composed of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and Tetronic® T1107. To assess the potential toxic effects of this novel formulation, in this work the zebrafish (Danio rerio) model was used to evaluate its in vivo toxicity and teratogenicity. This study evaluated and compared the effects of DOX exposure from different formulations (free DOX, MMDOX and Doxil®) on the swimming activity, morphological alterations, cardiac rhythm, lethality rate and DOX biodistribution. MMDOX showed lower lethal effects, morphological alterations and neurotoxic effects than the free drug. This study shows the potential of the MMDOX to be an effective DOX-delivery system because it could reduce the side effects.
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Doxorrubicina/farmacocinética , Doxorrubicina/toxicidade , Micelas , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Frequência Cardíaca/efeitos dos fármacos , Larva/efeitos dos fármacos , Atividade Motora , Distribuição Tecidual , Peixe-ZebraRESUMO
This article reports novel results about nanotoxicological and teratogenic effects of the PAMAM dendrimers DG4 and DG4.5 in zebrafish (Danio rerio). Zebrafish embryos and larvae were used as a rapid, high-throughput, cost-effective whole-animal model. The objective was to provide a more comprehensive and predictive developmental toxicity screening of DG4 and DG4.5 and test the influence of their surface charge. Nanotoxicological and teratogenic effects were assessed at developmental, morphological, cardiac, neurological and hepatic level. The effect of surface charge was determined in both larvae and embryos. DG4 with positive surface charge was more toxic than DG4.5 with negative surface charge. DG4 and DG4.5 induced teratogenic effects in larvae, whereas DG4 also induced lethal effects in both zebrafish embryos and larvae. However, larvae were less sensitive than embryos to the lethal effects of DG4. The platform of assays proposed and data obtained may contribute to the characterization of hazards and differential effects of these nanoparticles.
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Anormalidades Induzidas por Medicamentos/etiologia , Dendrímeros/toxicidade , Nanopartículas/toxicidade , Nanotecnologia/métodos , Teratogênicos/toxicidade , Toxicologia/métodos , Peixe-Zebra/anormalidades , Animais , Ânions , Cátions , Relação Dose-Resposta a Droga , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Ensaios de Triagem em Larga Escala , Larva/efeitos dos fármacos , Dose Letal Mediana , Fígado/anormalidades , Fígado/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/fisiopatologia , Medição de Risco , Propriedades de SuperfícieRESUMO
A systematic review was conducted by a multidisciplinary team to analyze qualitatively best available scientific evidence on the effect of agricultural intensification and environmental changes on the risk of zoonoses for which there are epidemiological interactions between wildlife and livestock. The study found several examples in which agricultural intensification and/or environmental change were associated with an increased risk of zoonotic disease emergence, driven by the impact of an expanding human population and changing human behavior on the environment. We conclude that the rate of future zoonotic disease emergence or reemergence will be closely linked to the evolution of the agriculture-environment nexus. However, available research inadequately addresses the complexity and interrelatedness of environmental, biological, economic, and social dimensions of zoonotic pathogen emergence, which significantly limits our ability to predict, prevent, and respond to zoonotic disease emergence.
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Agricultura , Mudança Climática , Doenças Transmissíveis Emergentes , Interações Hospedeiro-Patógeno , Modelos Biológicos , Zoonoses , Animais , HumanosRESUMO
INTRODUCTION: The aim of the study was to assess whether the penetration of antibiotics is affected by decreased tissue perfusion in patients with limb ischaemia, thus reducing its concentration in tissues below the minimum inhibitory concentration (MIC) breakpoints of antibiotics for different microorganisms. METHODS: Prospective study. Candidates for major amputation with critical lower limb ischaemia and an infection on antibiotic treatment, were included. Three levels of perfusion in the lower limb were determined by measuring the transcutaneous oxygen pressure (TcPO2). A central line blood specimen, as well as biopsies of the skin, muscle, and bone, were taken at each perfusion level. The antibiotic concentration was determined using HPLC. RESULTS: The total number of cases was 61 (46 patients): 6 clindamycin, 9 vancomycin, 8 linezolid, 18 levofloxacin, 9 ceftazidime, and 11 meropenem. Statistically significant differences were found in TcPO2 at all levels (ANOVA, P=.000). The vancomycin, levofloxacin and ceftazidime skin concentration depends on perfusion. Vancomycin and levofloxacin diffusion in bone is worse than in other tissues. Ceftazidime concentration does not exceed the MIC breakpoint of Pseudomonas aeruginosa in ischaemic tissues. CONCLUSIONS: Meropenem and linezolid diffuse in all tissues, regardless of perfusion, reaching concentrations above the MIC of the target microorganisms, ensuring its effectiveness in ischaemic tissues.
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Antibacterianos/farmacocinética , Isquemia/metabolismo , Extremidade Inferior/irrigação sanguínea , Idoso , Ceftazidima , Cromatografia Líquida de Alta Pressão , Clindamicina/farmacocinética , Feminino , Humanos , Levofloxacino/farmacocinética , Linezolida/farmacocinética , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Pele/metabolismo , Tienamicinas/farmacocinética , Vancomicina/farmacocinéticaRESUMO
Liposomes were developed with bioactive constituents (omega-3, omega-6, tocopherol) incorporated in acid food. They were made of soy phosphatidylcholine (SPC) allowing the encapsulation of antioxidant vitamin C (VC) and tocopherol. Stearic acid (SA) or calcium stearate (CaS) was added as a bilayer stabilizer. The structural and oxidative stability of the liposomes were studied considering the heat effect of pasteurization. Size was analyzed by light scattering; shape and structure were studied by optical and transmission electron microscopy, respectively. Membrane packing was studied with merocyanine 540. Surface charge and oxidative stability were analyzed by zeta potential and ORAC method, respectively. The liposomes showed significant stability in all of the parameters mentioned above and an important protective effect over thermolabile VC. To confirm their applicability in food, the rheological behavior and a sensory evaluation of liposomes with vitamin C and bioactive constituents were studied. The sensory evaluation of liposomes in orange juice was performed by the overall acceptability and triangular tests with 40 and 78 potential consumers, respectively. The incorporation of all liposomal formulation did not change the acceptability of orange juice. Noteworthy, SPC and SPC:SA systems had rheological behavior similar to a Newtonian fluid whereas that SPC:CaS presented a pseudoplastic one, both considered excellent for larger scale production. From all the obtained results, we can conclude that these liposomal formulations are suitable for food industry applications, incorporating bioactive constituents and generating functional orange juice that conserves its bioactivity after pasteurization.
RESUMO
We aimed to estimate the global occurrence of zoonotic tuberculosis (TB) caused by Mycobacterium bovis or M. caprae infections in humans by performing a multilingual, systematic review and analysis of relevant scientific literature of the last 2 decades. Although information from many parts of the world was not available, data from 61 countries suggested a low global disease incidence. In regions outside Africa included in this study, overall median proportions of zoonotic TB of ≤1.4% in connection with overall TB incidence rates ≤71/100,000 population/year suggested low incidence rates. For countries of Africa included in the study, we multiplied the observed median proportion of zoonotic TB cases of 2.8% with the continental average overall TB incidence rate of 264/100,000 population/year, which resulted in a crude estimate of 7 zoonotic TB cases/100,000 population/year. These generally low incidence rates notwithstanding, available data indicated substantial consequences of this disease for some population groups and settings.
Assuntos
Mycobacterium bovis , Tuberculose/epidemiologia , Zoonoses/epidemiologia , África , América , Animais , Austrália , Bovinos , China , Coinfecção , Europa (Continente) , Infecções por HIV/epidemiologia , Humanos , Incidência , Nova ZelândiaRESUMO
BACKGROUND: The therapeutic and diagnostic approach in deep vein thrombosis (DVT) has changed enormously in the last two decades with the introduction of ultrasound, low-molecular-weight heparin (LMWH), and premature motion. The aim of this study is to evaluate these changes and analyze their clinical and economic aspects. METHODS: We registered all inpatients with a diagnosis of DVT during 1994 (n=110) and 2009 (n=75) and their sociodemographic and clinical features in a descriptive observational design. We performed a comparison of diagnostic techniques, length of stay, inpatient complications, and costs thus derived for both series, based on 2009 prices, so that we could get comparable results. RESULTS: Ninety-one percent of inpatients in 1994 were diagnosed by venography, whereas, in 2009, the diagnosis was based on clinical features, D-dimer, and ultrasound in 100% of patients. Inpatient treatment went from 7% LMWH in 1994 to 96% in 2009, and as outpatient from 82% acenocumarol to 90.6% LMWH. Complications decreased by 13.3%. Length of stay was 2.7 higher in 1994. Globally, the cost per patient decreased by 63.39%, based primarily on reduced length of stay. CONCLUSIONS: The current diagnostic and therapeutic approach in DVT allows for effective treatment, fewer complications, and a drastic reduction in inpatient costs.
Assuntos
Anticoagulantes , Heparina de Baixo Peso Molecular , Custos Hospitalares , Pacientes Internados , Tromboembolia Venosa , Adulto , Idoso , Anticoagulantes/economia , Anticoagulantes/uso terapêutico , Biomarcadores/sangue , Redução de Custos , Análise Custo-Benefício , Custos de Medicamentos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Heparina de Baixo Peso Molecular/economia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Flebografia/economia , Valor Preditivo dos Testes , Sistema de Registros , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/economia , Tromboembolia Venosa/terapiaRESUMO
Nanotechnology is an emerging science with the potential to create new materials and strategies involving manipulation of matter at the nanometer scale (<100 nm). With size-dependent properties, nanoparticles have introduced a new paradigm in pharmacotherapy - the possibility of cell-targeted drug delivery with minimal systemic side effects and toxicity. The present review provides a summary of published findings, especially regarding to nanoparticle formulations for lung diseases. The available data have shown some benefits with nanoparticle-based therapy in the development of the disease and lung remodeling in respiratory diseases. However, there is a wide gap between the concepts of nanomedicine and the published experimental data and clinical reality. In addition, studies are still required to determine the potential of nanotherapy and the systemic toxicity of nanomaterials for future human use.