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Facilitating data sharing in scientific research, especially in the domain of animal studies, holds immense value, particularly in mitigating distress and enhancing the efficiency of data collection. This study unveils a meticulously curated collection of neural activity data extracted from six electrophysiological datasets recorded from three parietal areas (V6A, PEc, PE) of two Macaca fascicularis during an instructed-delay foveated reaching task. This valuable resource is now accessible to the public, featuring spike timestamps, behavioural event timings and supplementary metadata, all presented alongside a comprehensive description of the encompassing structure. To enhance accessibility, data are stored as HDF5 files, a convenient format due to its flexible structure and the capability to attach diverse information to each hierarchical sub-level. To guarantee ready-to-use datasets, we also provide some MATLAB and Python code examples, enabling users to quickly familiarize themselves with the data structure.
Assuntos
Macaca fascicularis , Lobo Parietal , Animais , Lobo Parietal/fisiologiaRESUMO
PURPOSE: GH deficit (GHD) could represent an endocrine issue in ß-Thalassemia Major (ßTM) patients. GH/IGF-1 axis has not been extensively explored in ßTM adults, so far. We aim to assess GHD and IGF-1 deficiency prevalence in ßTM adult population, focusing on the relationship with liver disease. METHODS: Cross-sectional multi-centre study conducted on 81 adult ßTM patients (44 males, mean age 41 ± 8 years) on transfusion and chelation therapy. GHD was investigated by GHRH + arginine test. IGF-1 levels, routine biochemical exams, Fibroscan, Hepatic Magnetic Resonance Imaging (MRI) and pituitary MRI were collected. RESULTS: Eighteen patients were affected by GHD and 63 were not (nGHD) according to GHRH + arginine test, while basal GH levels did not differ. GHD was associated with a higher BMI and a worse lipid profile (p < 0.05). No significant differences were observed regarding liver function between the two groups. Pituitary MRI scan was normal except for one case of empty sella. The 94.4% and 93.6% of GHD and nGHD, respectively, presented lower IGF-1 levels than the reference range, and mean IGF-1 SDS was significantly lower in GHD patients. CONCLUSION: GHD is frequent in adult ßTM patients and is associated with higher BMI and worse lipid profile. nGHD patients present lower IGF-1 levels as well. There was no relationship between IGF-1 levels and liver disease. Further, multicentric studies with larger cohorts and standardized diagnostic protocols are needed.
Assuntos
Hormônio do Crescimento Humano , Talassemia beta , Adulto , Arginina , Estudos Transversais , Humanos , Fator de Crescimento Insulin-Like I , Lipídeos , Masculino , Pessoa de Meia-Idade , Talassemia beta/complicações , Talassemia beta/epidemiologiaRESUMO
Abstract Campomanesia phaea (Myrtaceae), popularly known as cambuci, is one of several species of plants producing comestible fruits, largely used in human nutrition. Despite its consumption and economic potential, limited scientific research is available on the Campomanesia, especially those related to its therapeutic benefits. It is reported by traditional medicine the use of the plant in the treatment of different disorders, such as cardiovascular and nervous system disturbances. So, the aim of this study was to carry out the pharmacological evaluation of the hydro-alcoholic extract (HAE) of Campomanesia fruits in rats by screening consisting of tests: a) neuropharmacological observation, b) test on the cardiovascular system. The HAE, prepared from the extraction of fruits with water/ethanol, was concentrated and freeze-dried. Behavioral responses in rats were investigated in open field test and the cardiovascular actions were investigated by a register of indirect blood pressure and the register of spontaneous beating rate right atrium. The results revealed that HAE induced grooming, hypotension and bradycardia. So, this study identified an action on the central nervous system, represented by grooming, and a cardiovascular activity of Campomanesia. The hypotension, attributed in part to bradycardia, was not related to a cholinergic effect, discarding a possible cholinomimetic action of the plant that could justify both cardiovascular and central actions.
Resumo Campomanesia phaea (Myrtaceae), popularmente conhecida como cambuci, é uma das várias espécies de plantas que produzem frutos comestíveis amplamente utilizados na nutrição humana. Apesar de seu consumo e potencial econômico, há poucas pesquisas científicas sobre a Campomanesia, especialmente aquelas relacionadas aos seus benefícios terapêuticos. É relatado pela medicina tradicional o uso da planta no tratamento de diferentes distúrbios, tais como distúrbios do sistema nervoso e cardiovascular. Assim, o objetivo deste estudo foi realizar a avaliação farmacológica do extrato hidroalcoólico (EHA) dos frutos de Campomanesia phaea em ratos através de triagem composta pelos testes: a) observação neurofarmacológica, b) testes no sistema cardiovascular. O EHA, preparado a partir da extração de frutos com água/etanol, foi concentrado e liofilizado. As respostas comportamentais em ratos foram investigadas em teste de campo aberto e as ações cardiovasculares foram investigadas pelo registro da pressão arterial indireta e o registro da taxa de batimentos cardíacos espontâneos em preparações isoladas de átrio direito. Os resultados revelaram que EHA induziu grooming, hipotensão e bradicardia. Assim, este estudo identificou uma ação da Campomanesia sobre o sistema nervoso central, representada por grooming, e uma atividade cardiovascular. A hipotensão, atribuída em parte à bradicardia, não está relacionada a um efeito colinérgico, descartando uma possível ação colinomimética da planta que pudesse justificar tanto as ações cardiovasculares quanto as centrais.
Assuntos
Humanos , Animais , Ratos , Myrtaceae , Frutas , Extratos Vegetais , Ratos Wistar , EtanolRESUMO
Campomanesia phaea (Myrtaceae), popularly known as cambuci, is one of several species of plants producing comestible fruits, largely used in human nutrition. Despite its consumption and economic potential, limited scientific research is available on the Campomanesia, especially those related to its therapeutic benefits. It is reported by traditional medicine the use of the plant in the treatment of different disorders, such as cardiovascular and nervous system disturbances. So, the aim of this study was to carry out the pharmacological evaluation of the hydro-alcoholic extract (HAE) of Campomanesia fruits in rats by screening consisting of tests: a) neuropharmacological observation, b) test on the cardiovascular system. The HAE, prepared from the extraction of fruits with water/ethanol, was concentrated and freeze-dried. Behavioral responses in rats were investigated in open field test and the cardiovascular actions were investigated by a register of indirect blood pressure and the register of spontaneous beating rate right atrium. The results revealed that HAE induced grooming, hypotension and bradycardia. So, this study identified an action on the central nervous system, represented by grooming, and a cardiovascular activity of Campomanesia. The hypotension, attributed in part to bradycardia, was not related to a cholinergic effect, discarding a possible cholinomimetic action of the plant that could justify both cardiovascular and central actions.
Assuntos
Frutas , Myrtaceae , Animais , Etanol , Humanos , Extratos Vegetais , Ratos , Ratos WistarRESUMO
Abstract Campomanesia phaea (Myrtaceae), popularly known as cambuci, is one of several species of plants producing comestible fruits, largely used in human nutrition. Despite its consumption and economic potential, limited scientific research is available on the Campomanesia, especially those related to its therapeutic benefits. It is reported by traditional medicine the use of the plant in the treatment of different disorders, such as cardiovascular and nervous system disturbances. So, the aim of this study was to carry out the pharmacological evaluation of the hydro-alcoholic extract (HAE) of Campomanesia fruits in rats by screening consisting of tests: a) neuropharmacological observation, b) test on the cardiovascular system. The HAE, prepared from the extraction of fruits with water/ethanol, was concentrated and freeze-dried. Behavioral responses in rats were investigated in open field test and the cardiovascular actions were investigated by a register of indirect blood pressure and the register of spontaneous beating rate right atrium. The results revealed that HAE induced grooming, hypotension and bradycardia. So, this study identified an action on the central nervous system, represented by grooming, and a cardiovascular activity of Campomanesia. The hypotension, attributed in part to bradycardia, was not related to a cholinergic effect, discarding a possible cholinomimetic action of the plant that could justify both cardiovascular and central actions.
Resumo Campomanesia phaea (Myrtaceae), popularmente conhecida como cambuci, é uma das várias espécies de plantas que produzem frutos comestíveis amplamente utilizados na nutrição humana. Apesar de seu consumo e potencial econômico, há poucas pesquisas científicas sobre a Campomanesia, especialmente aquelas relacionadas aos seus benefícios terapêuticos. É relatado pela medicina tradicional o uso da planta no tratamento de diferentes distúrbios, tais como distúrbios do sistema nervoso e cardiovascular. Assim, o objetivo deste estudo foi realizar a avaliação farmacológica do extrato hidroalcoólico (EHA) dos frutos de Campomanesia phaea em ratos através de triagem composta pelos testes: a) observação neurofarmacológica, b) testes no sistema cardiovascular. O EHA, preparado a partir da extração de frutos com água/etanol, foi concentrado e liofilizado. As respostas comportamentais em ratos foram investigadas em teste de campo aberto e as ações cardiovasculares foram investigadas pelo registro da pressão arterial indireta e o registro da taxa de batimentos cardíacos espontâneos em preparações isoladas de átrio direito. Os resultados revelaram que EHA induziu grooming, hipotensão e bradicardia. Assim, este estudo identificou uma ação da Campomanesia sobre o sistema nervoso central, representada por grooming, e uma atividade cardiovascular. A hipotensão, atribuída em parte à bradicardia, não está relacionada a um efeito colinérgico, descartando uma possível ação colinomimética da planta que pudesse justificar tanto as ações cardiovasculares quanto as centrais.
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In this work polymorphs of α-aminobenzylpenicillin (ampicillin), a ß-lactamic antibiotic, were prepared and investigated by several experimental and theoretical methods. Amorphous monohydrate and three crystalline forms, the trihydrate, the crystal form I and the crystal form II, were investigated by FT-IR and micro-Raman. Also data obtained by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD) and hot-stage Raman spectroscopy are reported. Finally, quantum mechanical calculations were performed by density functional theory (DFT) to assist the assignment of spectroscopic experimental bands. For the first time, the ampicillin molecule in its zwitterionic form was studied at the B3LYP/aug-cc-pVDZ level and the corresponding theoretical vibrational spectra were computed. In fact, ampicillin in the crystal is in zwitterionic form and concentrations of this same form are quite relevant in solutions at physiological pH. Experimental and theoretical results allowed identification of specific features for polymorph characterization. Bands typical of the different polymorphs are identified both in IR and Raman spectra: in particular in the NH stretching region (IR), in the amide I+δNH region (both techniques), in the 1520-1490cm(-1) region (IR), in the 1320-1300cm(-1) and 1280-1220cm(-1) (IR), in the 1200-1170cm(-1) (Raman), in the amide V region (IR), and, finally, in the 715-640cm(-1) and 220-200cm(-1) (Raman). Interconversion among different polymorphs was investigated by hot-stage Raman spectroscopy and thermal analysis, clarifying the complex pattern of transformations undergone as a function of temperature and heating rate. In particular, DSC scans show how the trihydrate crystals transform into anhydrous forms on heating. Finally, stability tests demonstrated, after a two years period, that no transformation or degradation of the polymorphs occurred.
Assuntos
Ampicilina/química , Antibacterianos/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Simulação por Computador , Cristalização , Cristalografia por Raios X , Estabilidade de Medicamentos , Temperatura Alta , Estrutura Molecular , Transição de Fase , Difração de Pó , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Tecnologia Farmacêutica/métodos , Termogravimetria , Fatores de TempoRESUMO
Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). We correlated the frequencies of islet and extra-pancreatic autoantibodies with genotypes from both loci. The case series comprised 612 T1AD patients and 792 HC. Genotyping of PTPN22 C1858T was performed on 434 T1AD patients and 689 HC. The -448 to +83 base pairs (bp) region of the IL-21 gene was sequenced in 309 Brazilian T1AD and 189 HC subjects. We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR) = 1·94; P < 0·001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. HLA-DR3/DR4 alleles predominated in T1AD patients. A heterozygous allelic IL-21 gene variant (g.-241 T > A) was found in only one patient. In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5'-proximal region of the IL-21 gene were associated with T1AD risk. Patients with T1AD had increased frequencies of anti-islet-cell, anti-thyroid, anti-nuclear, anti-smooth muscle and anti-21-OH autoantibodies. The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies.
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Autoanticorpos/imunologia , Diabetes Mellitus Tipo 1/genética , Interleucinas/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Alelos , Autoanticorpos/genética , Autoanticorpos/metabolismo , Biomarcadores/metabolismo , Brasil , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Feminino , Expressão Gênica , Frequência do Gene , Predisposição Genética para Doença , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/imunologia , Antígeno HLA-DR3/genética , Antígeno HLA-DR3/imunologia , Antígeno HLA-DR4/genética , Antígeno HLA-DR4/imunologia , Humanos , Interleucinas/imunologia , Masculino , Regiões Promotoras Genéticas , Proteína Tirosina Fosfatase não Receptora Tipo 22/imunologia , Risco , Análise de Sequência de DNA , População BrancaRESUMO
The two known propantheline bromide polymorphs (form I and form II) were studied and characterized by a multianalytical approach. In the present work, the identification of propantheline bromide polymorphic forms through vibrational IR spectroscopies are presented and for the first time Raman microscopy and hot stage Raman microscopy (HSRM) studies are reported. Finally, quantum mechanical calculations were performed. For assisting the assignment of the experimental picks, the two IR spectra of the most and least stable representatives of a set of 56 conformers are calculated and studied. DSC thermograms data, are also reported. The surface enhanced Raman scattering (SERS) spectrum was also recorded in a silver colloid; it could be inferred that propantheline bromide is adsorbed on silver colloid through the oxygen atom with the molecular plane perpendicular to the metal surface.
Assuntos
Antiulcerosos/química , Propantelina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Cristalização , Modelos Moleculares , Análise Espectral Raman/métodosRESUMO
In the present work the structural and spectral characteristics of acetazolamide have been studied by methods of infrared, Raman spectroscopy and quantum chemistry. Electrostatic potential surface, optimized geometry, harmonic vibrational frequencies, infrared intensities and activities of Raman scattering were calculated by density functional theory (DFT) employing B3LYP with complete relaxation in the potential energy surface using 6-311++G(d,p) basis set. Based on these results, we have discussed the correlation between the vibrational modes and the structure of the dimers of acetazolamide. The calculated vibrational spectra of three dimers of acetazolamide have been compared with observed spectra, and the assignment of observed bands was carried out using potential energy distribution. The observed spectra agree well with the values computed from the DFT. A comparison of observed and calculated vibrational spectra clearly shows the effect of hydrogen bonding. The frequency shifts observed for the different dimers are in accord with the hydrogen bonding in acetazolamide. Natural bond orbital (NBO) analyses reflect the charge transfer interaction in the individual hydrogen bond units and the stability of different dimers of acetazolamide.
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Acetazolamida/química , Anticonvulsivantes/química , Inibidores da Anidrase Carbônica/química , Ligação de Hidrogênio , Modelos Moleculares , Teoria Quântica , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral RamanRESUMO
BACKGROUND: Age is an important risk factor for perioperative cerebral complications such as stroke, postoperative cognitive dysfunction, and delirium. We explored the hypothesis that intraoperative cerebrovascular autoregulation is less efficient and brain tissue oxygenation lower in elderly patients, thus, increasing the vulnerability of elderly brains to systemic insults such as hypotension. METHODS: We monitored intraoperative cerebral perfusion in 50 patients aged 18-40 and 77 patients >65 yr at two Swiss university hospitals. Mean arterial pressure (MAP) was measured continuously using a plethysmographic method. An index of cerebrovascular autoregulation (Mx) was calculated based on changes in transcranial Doppler flow velocity due to changes in MAP. Cerebral oxygenation was assessed by the tissue oxygenation index (TOI) using near-infrared spectroscopy. End-tidal CO2, O2, and sevoflurane concentrations and peripheral oxygen saturation were recorded continuously. Standardized anaesthesia was administered in all patients (thiopental, sevoflurane, fentanyl, atracurium). RESULTS: Autoregulation was less efficient in patients aged >65 yr [by 0.10 (se 0.04; P=0.020)] in a multivariable linear regression analysis. This difference was not attributable to differences in MAP, end-tidal CO2, or higher doses of sevoflurane. TOI was not significantly associated with age, sevoflurane dose, or Mx but increased with increasing flow velocity [by 0.09 (se 0.04; P=0.028)] and increasing MAP [by 0.11 (se 0.05; P=0.043)]. CONCLUSIONS: Our results do not support the hypothesis that older patients' brains are more vulnerable to systemic insults. The difference of autoregulation between the two groups was small and most likely clinically insignificant.
Assuntos
Encéfalo/metabolismo , Circulação Cerebrovascular , Homeostase , Monitorização Intraoperatória/métodos , Oxigênio/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Encéfalo/irrigação sanguínea , Dióxido de Carbono/metabolismo , Humanos , Fluxometria por Laser-Doppler/métodos , Masculino , Adulto JovemRESUMO
A study of the composition of the remains of ancient ointments from museums was undertaken to enable understanding of the preparation techniques. Comparison of ancient recipes from different historical periods and spectroscopic characteristics of inorganic and/or organic remains recovered in museum vessels enabled preparation of ancient pharmaceutical-cosmetic formulations. Farmacopea Augustana by Occo was one the most important books studied for the 14 formulations prepared in the laboratory. Three formulations are discussed in detail and raw materials and new preparations were proposed for ozone ageing. The most important micro Raman results are discussed. The spectra of the raw materials lipids, beeswax, and resins are discussed; beeswax and pig suet (axungia) Raman spectra were found to be similar, but different from those of the aged oils. SERS was applied to ancient ointments and galbanum and the Raman spectra are reported and discussed for the first time.
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Cosméticos/química , Cosméticos/história , Preparações Farmacêuticas/química , Tecnologia Farmacêutica/história , Animais , História Antiga , Lipídeos/análise , Museus , Resinas Vegetais/análise , Análise Espectral Raman , Suínos , Ceras/análiseRESUMO
Natural organic materials used to prepare pharmaceutical mixtures including ointments and balsams have been characterized by a combined non-destructive spectroscopic analytical approach. Three classes of materials which include vegetable oils (olive, almond and palm tree), gums (Arabic and Tragacanth) and beeswax are considered in this study according to their widespread use reported in ancient recipes. Micro-FTIR, micro-Raman and fluorescence spectroscopies have been applied to fresh and mildly thermally aged samples. Vibrational characterization of these organic compounds is reported together with tabulated frequencies, highlighting all spectral features and changes in spectra which occur following artificial aging. Synchronous fluorescence spectroscopy has been shown to be particularly useful for the assessment of changes in oils after aging; spectral difference between Tragacanth and Arabic gum could be due to variations in origin and processing of raw materials. Analysis of these materials using non-destructive spectroscopic techniques provided important analytical information which could be used to guide further study.
Assuntos
Bálsamos/química , Pomadas/química , Espectrometria de Fluorescência/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise Espectral Raman/métodos , Tecnologia Farmacêutica/história , Goma Arábica/análise , História Antiga , Óleos de Plantas/análise , Ceras/análiseRESUMO
Chemical analysis of ancient residues of pharmaceutical or cosmetic preparations such as balms or ointments is made problematic by the high complexity of these mixtures, composed of organic and inorganic materials. Consequently, a multi-analytical approach and special caution in the interpretation of the results are necessary. In order to contribute to the improvement of analytical strategies for the characterization of complex residues and to reconstruct ancient medical practices, a replica of a pharmaceutical formulation of the seventeenth century was prepared in the laboratory according to a historically documented recipe. In a round robin exercise, a portion of the preparation was analysed as a blind sample by 11 laboratories using various analytical techniques. These included spectroscopic, chromatographic and mass spectrometric methods. None of the laboratories was able to completely reconstruct the complex formulation, but each of them gave partial positive results. The round robin exercise has demonstrated that the application of a multi-analytical approach can permit a complete and reliable reconstruction of the composition. Finally, on the basis of the results, an analytical protocol for the study of residues of ancient medical and pharmaceutical preparations has been outlined.
Assuntos
Pomadas/química , Tecnologia Farmacêutica/história , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , História do Século XVII , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral RamanRESUMO
Proper storage conditions of biological samples are fundamental to avoid microbiological contamination that can cause chemical modifications of the target analytes. A simple liquid chromatography/tandem mass spectrometry (LC/MS/MS) method through direct injection of diluted samples, without prior extraction, was used to evaluate the stability of phase II metabolites of boldenone and testosterone (glucuronides and sulphates) in intentionally poorly stored equine urine samples. We also considered the stability of some deuterated conjugated steroids generally used as internal standards, such as deuterated testosterone and epitestosterone glucuronides, and deuterated boldenone and testosterone sulphates. The urines were kept for 1 day at room temperature, to mimic poor storage conditions, then spiked with the above steroids and kept at different temperatures (-18 degrees C, 4 degrees C, room temperature). It has been possible to confirm the instability of glucuronide compounds when added to poorly stored equine urine samples. In particular, both 17beta- and 17alpha-glucuronide steroids were exposed to hydrolysis leading to non-conjugated steroids. Only 17beta-hydroxy steroids were exposed to oxidation to their keto derivatives whereas the 17alpha-hydroxy steroids were highly stable. The sulphate compounds were completely stable. The deuterated compounds underwent the same behaviour as the unlabelled compounds. The transformations were observed in urine samples kept at room temperature and at a temperature of 4 degrees C (at a slower rate). No modifications were observed in frozen urine samples. In the light of the latter results, the immediate freezing at -18 degrees C of the collected samples and their instant analysis after thawing is the proposed procedure for preventing the transformations that occur in urine, usually due to microbiological contamination.
Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Testosterona/análogos & derivados , Testosterona/urina , Animais , Congelamento , Cavalos , Padrões de Referência , Reprodutibilidade dos Testes , Esteroides/metabolismo , Esteroides/urina , Temperatura , Testosterona/metabolismo , Fatores de TempoRESUMO
A development of a rapid and sensitive LC-MS/MS method for the simultaneous detection of active ingredients of the euthanasic veterinarian drug Tanax mixture is described. The method proposed, with a retention time of few minutes (6 min) was developed for an equine serum sample with solid-phase extraction (S.P.E). This S.P.E. procedure has been revealed useful for the determination of very low concentrations of Tanax analytes (0.05-1 ng/ml). The method was validated in terms of specificity/selectivity, sensitivity, recovery and precision.
Assuntos
Amidas/análise , Amidas/toxicidade , Cromatografia Líquida/veterinária , Eutanásia , Compostos de Amônio Quaternário/análise , Compostos de Amônio Quaternário/toxicidade , Espectrometria de Massas em Tandem/veterinária , Tetracaína/análise , Tetracaína/toxicidade , Amidas/química , Animais , Cicloexanos/análise , Cicloexanos/toxicidade , Combinação de Medicamentos , Estabilidade de Medicamentos , Análise de Injeção de Fluxo/métodos , Cavalos , Estrutura Molecular , Compostos de Amônio Quaternário/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Extração em Fase Sólida/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Tetracaína/química , Fatores de TempoRESUMO
Hypocalcemia due to hypoparathyroidism (HPT) is a late complication of iron-overloaded patients with b-thalassaemia major (TM). The majority of patients have mild disease with parasthesias, while in the more severe form tetany, seizures or cardiac failure may occur. In the last 20 years we observed heart failure in 2 out of 38 (5.2%) TM patients (aged 18 and 22 years) with hypocalcemia secondary to HPT associated to iron overload. Calcium supplementation and vitamin D induced correction of hypocalcemia and resulted in an improvement of cardiac function. Calcium plays a key role in the maintenance and regulation of normal cardiac function. Extra-cellular calcium is indispensable for the contractile process since the sarcoplasmatic reticulum is unable to maintain a sufficient amount of calcium to trigger myocardial contraction. In conclusion, our observations stress the importance of a regular iron chelation therapy, adherence to treatment of endocrine complication and regular follow-up of TM patients with hypocalcemia.
Assuntos
Insuficiência Cardíaca/epidemiologia , Talassemia beta/epidemiologia , Adolescente , Diagnóstico Diferencial , Insuficiência Cardíaca/diagnóstico , Humanos , MasculinoRESUMO
The life expectancy of patients with thalassemia major has significantly increased in recent years, as reported by several groups in different countries. However, complications are still frequent and affect the patients' quality of life. In a recent study from the United Kingdom, it was found that 50% of the patients had died before age 35. At that age, 65% of the patients from an Italian long-term study were still alive. Heart disease is responsible for more than half of the deaths. The prevalence of complications in Italian patients born after 1970 includes heart failure in 7%, hypogonadism in 55%, hypothyroidism in 11%, and diabetes in 6%. Similar data were reported in patients from the United States. In the Italian study, lower ferritin levels were associated with a lower probability of experiencing heart failure and with prolonged survival. Osteoporosis and osteopenia are common and affect virtually all patients. Hepatitis C virus antibodies are present in 85% of multitransfused Italian patients, 23% of patients in the United Kingdom, 35% in the United States, 34% in France, and 21% in India. Hepatocellular carcinoma can complicate the course of hepatitis. A survey of Italian centers has identified 23 such cases in patients with a thalassemia syndrome. In conclusion, rates of survival and complication-free survival continue to improve, due to better treatment strategies. New complications are appearing in long-term survivors. Iron overload of the heart remains the main cause of morbidity and mortality.
Assuntos
Talassemia beta/mortalidade , Adolescente , Adulto , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/etiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Cardiomiopatias/etiologia , Cardiomiopatias/mortalidade , Causas de Morte , Terapia por Quelação , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Intervalo Livre de Doença , Feminino , Ferritinas/análise , Hepatite C/complicações , Hepatite C/epidemiologia , Humanos , Hipogonadismo/epidemiologia , Hipogonadismo/etiologia , Lactente , Recém-Nascido , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/mortalidade , Itália/epidemiologia , Expectativa de Vida , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Mortalidade/tendências , Estudos Multicêntricos como Assunto , Osteoporose/epidemiologia , Osteoporose/etiologia , Gravidez , Complicações Hematológicas na Gravidez , Prevalência , Reação Transfusional , Talassemia beta/complicações , Talassemia beta/terapiaRESUMO
Osteoporosis and osteopenia are frequent complications of thalassemia major (TM) and intermedia (TI). Osteoporosis was found in 23/25 patients with TI and in 115/239 patients with TM. In TM, no association was found with specific polymorphisms in candidate genes (vitamin D receptor, estrogen receptor, calcitonin receptor, and collagen type 1 alpha 1). Osteoporosis in female patients with TM was strongly associated with primary amenorrhea (P < .0001), while in male patients with TM, hypogonadism was not significantly related to bone mineral density (BMD) (P = .0001). Low BMD was also associated with cardiomiopathy (P = .01), diabetes mellitus (P = .0001), chronic hepatitis (P = .0029), and increased ALT (P = .01).
Assuntos
Osteoporose/etiologia , Talassemia beta/complicações , Adulto , Amenorreia/etiologia , Densidade Óssea , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/genética , Cardiomiopatias/etiologia , Colágeno Tipo I/genética , Análise Mutacional de DNA , Diabetes Mellitus/etiologia , Receptor alfa de Estrogênio/genética , Feminino , Predisposição Genética para Doença , Humanos , Hipogonadismo/etiologia , Hipotireoidismo/etiologia , Masculino , Osteoporose/genética , Receptores da Calcitonina/genética , Receptores de Calcitriol/genética , Talassemia beta/genéticaRESUMO
Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in accidental hosts, including humans. Complete genome sequencing of Leptospira interrogans serovar Copenhageni and comparative analysis with the available Leptospira interrogans serovar Lai genome reveal that despite overall genetic similarity there are significant structural differences, including a large chromosomal inversion and extensive variation in the number and distribution of insertion sequence elements. Genome sequence analysis elucidates many of the novel aspects of leptospiral physiology relating to energy metabolism, oxygen tolerance, two-component signal transduction systems, and mechanisms of pathogenesis. A broad array of transcriptional regulation proteins and two new families of afimbrial adhesins which contribute to host tissue colonization in the early steps of infection were identified. Differences in genes involved in the biosynthesis of lipopolysaccharide O side chains between the Copenhageni and Lai serovars were identified, offering an important starting point for the elucidation of the organism's complex polysaccharide surface antigens. Differences in adhesins and in lipopolysaccharide might be associated with the adaptation of serovars Copenhageni and Lai to different animal hosts. Hundreds of genes encoding surface-exposed lipoproteins and transmembrane outer membrane proteins were identified as candidates for development of vaccines for the prevention of leptospirosis.
Assuntos
Genoma Bacteriano , Genômica , Leptospira interrogans/fisiologia , Leptospira interrogans/patogenicidade , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Cricetinae , Humanos , Leptospira interrogans/classificação , Leptospira interrogans/genética , Leptospirose/microbiologia , Camundongos , Dados de Sequência Molecular , Análise de Sequência de DNA , Sorotipagem , Virulência/genéticaRESUMO
OBJECTIVE: To evaluate left ventricular morphology and function in a large population of patients with beta thalassaemia. DESIGN: Echo Doppler assessment of left ventricular function and correlation of cardiovascular data with haematological data. SETTING: Thalassaemia unit in a tertiary referral centre. PATIENTS: 197 young adults with beta thalassaemia, following an adequate transfusional and chelation treatment regimen, without clinical signs of cardiopulmonary involvement. The control group consisted of 213 healthy subjects. RESULTS: Left ventricular volumes, mass index, and mass/volume ratio were increased. Diastolic and systolic shapes were different, the left ventricle maintaining an ellipsoidal shape. The ejection fraction was reduced, and was < 50% in 33 patients. Stroke volume and cardiac index were increased, and systemic vascular resistance was decreased. Fractional shortening and mean velocity of circumferential shortening were decreased. Meridional end systolic and peak systolic stress were increased, as was circumferential end systolic stress. The contractile state was reduced while the functional preload index did not differ. Left ventricular diastolic function, evaluated from the mitral inflow, showed a slightly prolonged isovolumic relaxation time, increased flow velocity integrals, and an increased E/A ratio. Among the haematological data, only serum ferritin showed a weak negative correlation with left ventricular ejection fraction. The patients with the highest serum ferritin (> 2500 ng/ml) had the lowest ejection fraction. CONCLUSIONS: Patients with beta thalassaemia on an adequate transfusion and chelation treatment regimen show abnormal left ventricular remodelling with increased volumes, mass, and mass/volume ratio. Systolic chamber function and contractile state are reduced, with a slightly increased afterload. These findings seem mainly to be related to the increased cardiac output caused by chronic anaemia. Left ventricular performance is better preserved when chelation treatment is adjusted to maintain the serum ferritin concentration at < 1000 ng/ml.