RESUMO
Background: The population of South America has been severely affected by the COVID-19 pandemic. In this region, during the year 2020, high seroprevalence percentages were reported, which have been associated with the socioeconomic characteristics of the population, mainly in urban areas. However, a relative lack of information on the dynamics of the pandemic in rural areas of these countries, where the population is more vulnerable, is still present. This study determined antibody prevalence against SARS-CoV-2 in urban and rural food producing workers in Colombia. Methods: A total of 1242 workers, urban and rural, linked to poultry, dairy, and meat production and supply chains, were analyzed through a sociodemographic survey and two serological tests against S and N proteins of SARS-CoV-2. Results: 78.7% were male. 50.9% of the participants were rural inhabitants, with an average age of 40.9 years old. 39.2% had IgM and IgG against SARS-CoV-2 S protein and 31.3% against N protein for the same virus; 83.6% had not been tested with an RT-PCR test for COVID-19 and 75.7% did not report symptoms related to the disease. The associated risk factors were low education, OR: 1.46, greater number of cohabitants, OR: 1.36, and contact with people infected with COVID-19, OR: 2.03. Conclusions: The seroprevalences found suggest an important interconnectivity between rural and urban areas, where asymptomatic subjects and sociodemographic factors facilitate the virus' spread in the population.
RESUMO
RESUMEN: En el estudio se utilizó una población de 180 llamas de ambos sexos (machos y hembras) clasificados por edades (dientes de leche; dos dientes y cuatro dientes). Se registraron datos del peso corporal y las siguientes medidas morfométricas: En la cabeza: Longitud de la cabeza (LC); ancho de cabeza (ACa) y longitud de oreja (LO). En el cuello: Longitud del cuello (LCU); Perímetro de cuello anterior (PCuA) y perímetro de cuello posterior (PCuP). En el tronco y extremidades: Altura a la cruz (AC); altura de la grupa (AGRU), diámetro dorso esternal (DDE), perímetro torácico (PT), longitud del cuerpo (LOCU), longitud de la cruz a la grupa (LCG), longitud de grupa (LGRU), perímetro de caña anterior (PCA); perímetro de caña posterior (PCP). Los datos fueron procesados utilizando el software estadístico R. Concluyendo que los rasgos de conformación en llamas (Lama glama) Ch'aku y Q'ara están influenciados por la edad, sexo y raza. Los modelos de regresión simple y múltiple para la predicción del peso corporal fueron significativos.
SUMMARY: The study used a population of 180 llamas of both sexes (males and females) classified by age (milk teeth; two teeth and four teeth). Body weight data and the following morphometric measurements were recorded: Head: Head length (CL); head width (ACa) and ear length (LO). On the neck: Neck length (LCU); anterior neck circumference (PCuA) and posterior neck circumference (PCuP). On the trunk and limbs: Height at withers (AC); height at rump (AGRU), sternal dorsal diameter (DDE), thoracic perimeter (PT), body length (LOCU), length from withers to rump (LCG), rump length (LGRU), anterior canine perimeter (PCA); posterior canine perimeter (PCP). The data were processed using R statistical software. It was concluded that conformation traits in Ch'aku and Q'ara llamas (Lama glama) are influenced by age, sex and breed. Simple and multiple regression models for body weight prediction were significant.
Assuntos
Animais , Masculino , Feminino , Peso Corporal , Camelídeos Americanos/anatomia & histologia , Valor Preditivo dos TestesRESUMO
BACKGROUND: To analyze the trends of oral and oropharyngeal cancer mortality in Uruguay between 1997 and 2014 according to sex and age groups and its possible association with sociodemographic factors. MATERIAL AND METHODS: A time-series ecological study using secondary data was performed. The data about mortality due to oral and oropharyngeal cancers were obtained from the Statistics Vitals Department of the Public Health Ministry of Uruguay. To estimate the mortality trends of the historical series, by sex, anatomical site and age groups, linear regressions generated by the Prais-Winsten procedure were used. RESULTS: The analysis of mortality trends for oral cavity and oropharyngeal cancers in Uruguay indicated that the global mortality rate was stable over the studied period. The women's mortality rate increased from 0.51 per 100,000 in 1997 to 0.65 per 100,000 in 2014 while for men, rates per 100,000 went from 3.22 in 1997 to 2.20 per 100,000 in 2014. Mortality from oral cancer in men decreased between 1997 and 2014. Mortality by oropharyngeal cancer, irrespective of sex, remained stable. Analysis by cancer site revealed decreasing trends tumors situated in the base of the tongue and gum. Years of education, unemployment, smoking and Gini index were not associated with mortality trends. CONCLUSIONS: The overall mortality from oral and oropharyngeal cancer in Uruguay has remained constant in the period between 1997 and 2014. Oral cancer mortality decreased in men and increased in women and decreased at the base of the tongue. It's necessary to continue monitoring the behavior of these diseases.
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Neoplasias Bucais , Neoplasias Orofaríngeas , Feminino , Humanos , Incidência , Masculino , Saúde Pública , UruguaiRESUMO
In Uruguay, groundwater is frequently used for agricultural activities, as well as for human consumption in urban and rural areas. As in many countries worldwide, drinking water microbiological quality is evaluated only according to bacteriological standards and virological analyses are not mentioned in the legislation. In this work, the incidence of human viral (Rotavirus A, Norovirus GII, and human Adenovirus) and bacterial (total and thermotolerant coliform and Pseudomonas aeruginosa) contamination in groundwater in the Salto district, Uruguay, as well as the possible correlation between these groups of microorganisms, was studied. From a total of 134 groundwater samples, 42 (32.1%) were positive for Rotavirus, only 1 (0.7%) for both Rotavirus and Adenovirus, and 96 (72.6%) samples were positive for bacterial indicators. Results also show that Rotavirus presence was not associated with changes in chemical composition of the aquifer water. Bacteriological indicators were not adequate to predict the presence of viruses in individual groundwater samples (well scale), but a deeper spatial-temporal analysis showed that they are promising candidates to assess the viral contamination degree at aquifer scale, since from the number of wells with bacterial contamination the number of wells with viral contamination could be estimated.
Assuntos
Bactérias/crescimento & desenvolvimento , Água Subterrânea/virologia , Vírus/crescimento & desenvolvimento , Microbiologia da Água , Qualidade da Água , Poços de Água , Adenovírus Humanos/crescimento & desenvolvimento , Agricultura , Água Potável/virologia , Água Subterrânea/microbiologia , Humanos , Norovirus/crescimento & desenvolvimento , Rotavirus/crescimento & desenvolvimento , UruguaiRESUMO
The aim of this work was to obtain information concerning the properties of ophthalmic formulations based on hyaluronic-drug ionic complexes, to identify the factors that determine the onset, intensity and duration of the pharmacotherapeutic effect. Dispersions of a complex of 0.5% w/v of sodium hyaluronate (HyNa) loaded with 0.5% w/v of timolol maleate (TM) were obtained and presented a counterionic condensation higher than 75%. For comparison a similar complex obtained with hyaluronic acid (HyH) was also prepared. Although the viscosity of HyNa-TM was significantly higher than that of HyH-TM, in vitro release of TM from both complexes showed a similar extended drug release profile (20-31% over 5h) controlled by diffusion and ionic exchange. Ocular pharmacokinetic study performed in normotensive rabbits showed that HyNa-TM complex exhibited attractive bioavailability properties in the aqueous humor (AUC and Cmax significantly higher and later Tmax) compared to commercial TM eye-drops. Moreover, a more prolonged period of lowered intra-ocular pressure (10h) and a more intense hypotensive activity was observed after instillation of a drop of HyNa-TM as compared to the eye-drops. Such behavior was related to the longer pre-corneal residence times (400%) observed with HyNa-TM complex. No significant changes in rabbit transcorneal permeation were detected upon complexation. These results demonstrate that the ability of HyNa to modulate TM release, together with its mucoadhesiveness related to the viscosity, affected both the pharmacokinetic and pharmacodynamic parameters. The HyNa-TM complex is a potentially useful carrier for ocular drug delivery, which could improve the TM efficacy and reduce the frequency of administration to improve patient compliance.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Timolol/administração & dosagem , Antagonistas Adrenérgicos beta/química , Antagonistas Adrenérgicos beta/farmacocinética , Antagonistas Adrenérgicos beta/farmacologia , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacocinética , Anti-Hipertensivos/farmacologia , Disponibilidade Biológica , Córnea/efeitos dos fármacos , Córnea/metabolismo , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Liberação Controlada de Fármacos , Ácido Hialurônico/química , Ácido Hialurônico/farmacocinética , Ácido Hialurônico/farmacologia , Pressão Intraocular/efeitos dos fármacos , Soluções Oftálmicas , Permeabilidade , Coelhos , Timolol/química , Timolol/farmacocinética , Timolol/farmacologiaRESUMO
The aims of this study were to evaluate the effects of milking method, disinfection practices and other management factors on the bulk tank milk somatic cell count (BTSCC) in tropical dairy herds and to examine potential interactions with time. One hundred and thirty farms in the Northern region of Antioquia, Colombia, were visited once per month for 24 months. A two level linear mixed model for repeated measures was used to assess the impact on log transformed BTSCC (lnBTSCC). The geometric mean of the BTSCC for all herds was 262,330 cells/mL. The two-level linear mixed model showed that lnBTSCCs in hand milked herds were significantly higher than in machine milked herds. Fore-stripping corresponded with a 27% increase in lnBTSCC and failing to post-dip corresponded with a 45% increase in lnBTSCC. The two way interactions of sampling month with milking method, singeing udders and pre-dipping were significant. The lowest predicted lnBTSCC was observed in machine milked herds that practised both pre-dipping and singeing of udders. This study suggests that milking procedures and disinfection practices can interact with time and have substantial effects on lnBTSCC.
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Bovinos/fisiologia , Indústria de Laticínios/métodos , Desinfecção/métodos , Leite/citologia , Animais , Contagem de Células/veterinária , Colômbia , Feminino , Estações do AnoRESUMO
Novel complexes consisting of Eudragit E100-risedronate are presented. The oral bioavailability of risedronate in rats was determined through its percentage excreted in urine after administration of complexed or free risedronate in fed and fasted conditions. The evaluation of the risedronate gastro-duodenal irritation potential was carried out by macroscopic and histological analyses in an experimental rat model. The degree of counterionic condensation between Eudragit E100 and risedronate was assessed by dialysis with, mechanistic information about the interaction with calcium and the release of risedronate from the complexes being obtained using physiological solution and simulated gastric fluid without pepsin. Non-significant differences were observed in the urinary excretion of risedronate when the complex or free risedronate was administered to fasted rats. However, the urinary excretion of risedronate in the complex group was 4-times higher than in the free risedronate group when animals were concomitantly administered with food. This behavior was related to the high degree of counterionic condensation in the complex (86.5%), which led to a reduction in the calcium induced rate and magnitude of risedronate precipitation and resulted in a decrease in the gastroduodenal damage from the complex, as evidenced by a lower frequency of gastric mucosae hemorrhage. A sustained release of risedronate from the complex was observed toward water, simulated gastric fluid or physiological solution, through an ionic-exchange mechanism. In conclusion, complexation with Eudragit E100 could be a useful strategy to overcome the unfavorable properties of risedronate.
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Acrilatos/química , Bloqueadores dos Canais de Cálcio/farmacologia , Química Farmacêutica , Interações Alimento-Droga , Polímeros/química , Ácido Risedrônico/farmacologia , Estômago/efeitos dos fármacos , Administração Oral , Animais , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacocinética , Ingestão de Alimentos , Jejum , Técnicas In Vitro , Masculino , Ratos , Ratos Wistar , Ácido Risedrônico/química , Ácido Risedrônico/farmacocinéticaRESUMO
In the frame of the Argentine BNCT Project a new research line has been started to study the application of BNCT to the treatment of locoregional recurrences of HER2+ breast cancer subtype. Based on former studies, the strategy considers the use of immunoliposomes as boron carriers nanovehicles to target HER2 overexpressing cells. The essential concerns of the current stage of this proposal are the development of carriers that can improve the efficiency of delivery of boron compounds and the dosimetric assessment of treatment feasibility. For this purpose, an specific pool of clinical cases that can benefit from this application was determined. In this work, we present the proposal and the advances related to the different stages of current research.
RESUMO
In the frame of the Argentine BNCT Project a new research line has been started to study the application of BNCT to the treatment of locoregional recurrences of HER2+ breast cancer subtype. Based on former studies, the strategy considers the use of immunoliposomes as boron carriers nanovehicles to target HER2 overexpressing cells. The essential concerns of the current stage of this proposal are the development of carriers that can improve the efficiency of delivery of boron compounds and the dosimetric assessment of treatment feasibility. For this purpose, an specific pool of clinical cases that can benefit from this application was determined. In this work, we present the proposal and the advances related to the different stages of current research.
Assuntos
Pesquisa Biomédica/tendências , Terapia por Captura de Nêutron de Boro/tendências , Neoplasias da Mama/radioterapia , Oncologia/tendências , Recidiva Local de Neoplasia/radioterapia , Argentina , Neoplasias da Mama/metabolismo , Feminino , Humanos , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/prevenção & controle , Receptor ErbB-2/metabolismo , Resultado do TratamentoRESUMO
We report Doxorubicin ionic complexes with hyaluronic acid (HiH-Dx) or its sodium salt (HiNa-Dx) as tumor-targeting delivery system. The complexes were prepared in situ by mixing aqueous solutions of Dx.HCl with HiH or HiNa. Clear colloidal dispersions with a high degree of counterionic condensation (cc) were obtained. Affinity constants (logKcc) of HiNa-Dx and HiH-Dx were 7.96 and 8.08, respectively. Delivery rates of Dx from the complexes were measured in a Franz-type bicompartimental device. In line with the high affinity constants, loaded Dx was slowly released from the complexes. To test the targeting potential of the complexes, carcinogenic A549 cells overexpressing the CD44 receptors were used. HTR8/SVneo cells without overexpression of CD44 were used as control. In A549 cells, cytotoxicity of both HiH-Dx and HiNa-Dx complexes was 3-fold higher than that of the reference solution. However, no differences were observed between the complexes and free Dx solution in HTR8/SVneo cells. Flow cytometry data suggested successful uptake of Dx in cells, with a greater internalization of Dx in A549 cells than in HTR8/SVneo cells when the complexes were used. Similarly, microscopy imagines revealed a higher concentration of Dx in A549 cells with the complexes. This work provides more detailed information in order to contribute to more solid bases to evaluate the potentiality of Hi as an antineoplastic drug carrier convenient for being used in specific therapeutic indications with minimal side effects.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/químicaRESUMO
We have shown that boron neutron capture therapy (BNCT) could be an alternative for the treatment of poorly differentiated thyroid carcinoma (PDTC). Histone deacetylase inhibitors (HDACI) like sodium butyrate (NaB) cause hyperacetylation of histone proteins and show capacity to increase the gamma irradiation effect. The purpose of these studies was to investigate the use of the NaB as a radiosensitizer of the BNCT for PDTC. Follicular thyroid carcinoma cells (WRO) and rat thyroid epithelial cells (FRTL-5) were incubated with 1 mM NaB and then treated with boronophenylalanine ¹°BPA (10 µg ¹°B ml⻹) + neutrons, or with 2, 4-bis (α,ß-dihydroxyethyl)-deutero-porphyrin IX ¹°BOPP (10 µg ¹°B ml⻹) + neutrons, or with a neutron beam alone. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux = (1.0 ± 0.1) × 10¹° n cm⻲ s⻹). Cell survival decreased as a function of the physical absorbed dose in both cell lines. Moreover, the addition of NaB decreased cell survival (p < 0.05) in WRO cells incubated with both boron compounds. NaB increased the percentage of necrotic and apoptotic cells in both BNCT groups (p < 0.05). An accumulation of cells in G2/M phase at 24 h was observed for all the irradiated groups and the addition of NaB increased this percentage. Biodistribution studies of BPA (350 mg kg⻹ body weight) 24 h after NaB injection were performed. The in vivo studies showed that NaB treatment increases the amount of boron in the tumor at 2-h post-BPA injection (p < 0.01). We conclude that NaB could be used as a radiosensitizer for the treatment of thyroid carcinoma by BNCT.
Assuntos
Terapia por Captura de Nêutron de Boro , Ácido Butírico/administração & dosagem , Inibidores de Histona Desacetilases/administração & dosagem , Radiossensibilizantes/administração & dosagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Acetilação , Animais , Compostos de Boro/administração & dosagem , Compostos de Boro/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Histonas/metabolismo , Humanos , Camundongos , Camundongos Nus , Fenilalanina/administração & dosagem , Fenilalanina/análogos & derivados , Fenilalanina/farmacocinética , Doses de Radiação , Neoplasias da Glândula Tireoide/metabolismoRESUMO
Therapeutic agents containing phosphate groups in their molecules have increasing therapeutic impact. The object of this study was to characterize the cationic polyelectrolyte Eudragit E100 (EuE100) as a carrier for drugs containing phosphate groups, using dexamethasone phosphate (DP) as a model. A series of EuE100-DP complexes was obtained by acid-base reaction in which DP neutralized 12.5-75% of the basic groups of EuE100. The solids obtained after solvent evaporation revealed by spectroscopic characterization the complete reaction between the components through the ionic interaction between the amine groups of EuE100 and the phosphate groups of DP. The reversibility of the counterion condensation, evaluated through the proton-withdrawing effect produced by the ionic exchange generated by titration with NaCl, showed a remarkable high affinity between EuE100 and DP. In line, drug delivery in bicompartimental Franz cells toward water as receptor medium was very slow (2% in 6 h). However, it was increased as water was replaced by NaCl solution, which upon diffusion generates ionic exchange. A sustained release of DP with noticeable zero order kinetics accounted for a remarkable high affinity, mainly due to the electrostatic attraction. The release rate remains constant regardless of the saline concentration of the media. Besides, the delivery control is maintained even in gastric simulated fluid, a property not informed previously for EuE100 complexes.
Assuntos
Acrilatos/química , Dexametasona/química , Dimetilaminas/química , Portadores de Fármacos/química , Ésteres/química , Organofosfatos/química , Polímeros/química , Aminas/química , Cátions/química , Cinética , Concentração Osmolar , Cloreto de Sódio/química , Solubilidade , Soluções/química , Solventes/química , Água/químicaRESUMO
The main aim of the present study was to examine the effects of long-term supplementing diets with saturated or unprotected polyunsaturated fatty acids from two different plant oils rich in either n-3 or n-6 fatty acids (FAs) plus docosahexaenoic acid (DHA)-rich algae on mammary gene expression and milk fat composition in lactating dairy cows. Gene expression was determined from mammary tissue and milk epithelial cells. Eighteen primiparous German Holstein dairy cows in mid-lactation were randomly assigned into three dietary treatments that consist of silage-based diets supplemented with rumen-stable fractionated palm fat (SAT; 3.1% of the basal diet dry matter, DM), or a mixture of linseed oil (2.7% of the basal diet DM) plus DHA-rich algae (LINA; 0.4% of the basal diet DM) or a mixture of sunflower oil (2.7% of the basal diet DM) plus DHA-rich algae (SUNA; 0.4% of the basal diet DM), for a period of 10 weeks. At the end of the experimental period, the cows were slaughtered and mammary tissues were collected to study the gene expression of lipogenic enzymes. During the last week, the milk yield and composition were determined, and milk was collected for FA measurements and the isolation of milk purified mammary epithelial cells (MECs). Supplementation with plant oils and DHA-rich algae resulted in milk fat depression (MFD; yield and percentage). The secretion of de novo FAs in the milk was reduced, whereas the secretion of trans-10,cis-12-CLA and DHA were increased. These changes in FA secretions were associated in mammary tissue with a joint down-regulation of mammary lipogenic enzyme gene expression (stearoyl-CoA desaturase, SCD1; FA synthase, FASN) and expression of the regulatory element binding transcription factor (SREBF1), whereas no effect was observed on lipoprotein lipase (LPL) and glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAM). A positive relationship between mammary SCD1 and SREBF1 mRNA abundances was observed, suggesting a similar regulation for these genes. Such data on mammary gene expression in lactating cows presenting MFD contribute to strengthen the molecular mechanisms that govern milk fat synthesis in the mammary glands. In purified MEC, the dietary treatments had no effect on gene expressions. Differences between mammary tissue and milk purified MEC gene expression were attributed to the effect of lipid supplements on the number of milk purified MEC and its RNA quality, which are determinant factors for the analysis of gene expression using milk cells.
Assuntos
Ração Animal/análise , Bovinos/fisiologia , Ácidos Docosa-Hexaenoicos/administração & dosagem , Regulação para Baixo/efeitos dos fármacos , Ácidos Graxos/metabolismo , Óleo de Semente do Linho/administração & dosagem , Lipídeos/biossíntese , Óleos de Plantas/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal , Animais , Arecaceae , Bovinos/genética , Dieta/veterinária , Gorduras na Dieta/administração & dosagem , Suplementos Nutricionais/análise , Células Epiteliais/enzimologia , Células Epiteliais/metabolismo , Ácidos Graxos/análise , Ácidos Graxos Insaturados/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Lactação , Glândulas Mamárias Animais/enzimologia , Glândulas Mamárias Animais/metabolismo , Leite/química , Reação em Cadeia da Polimerase/veterinária , RNA Mensageiro/análise , Rúmen/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Óleo de GirassolRESUMO
Two polymorphic forms of a novel pharmaceutical compound, ciprofloxacin-saccharinate (CIP-SAC), are analyzed using one dimensional (1D) and two dimensional (2D) (1)H nuclear magnetic resonance (NMR) at fast magic angle spinning (MAS). Additionally (15)N spectroscopy and (1)H-(13)C correlation experiments were performed to complement our conclusions. The 1D (1)H NMR spectra of CIP and complexes reveal valuable information about the ionic bonding between ciprofloxacin and saccharine. Additionally, these spectra allow us to perform a clear characterization of each solid form, giving the number of molecules per unit cell in one of the polymorphs. From 2D (1)H-(1)H spectra obtained through double quantum correlations we can arrive at important conclusions about the hydrogen bonding, conformation, and intra and inter-molecular interactions present in these compounds. Comparing and contrasting the (1)H-(1)H correlation data obtained for both polymorphic forms and taking into account the single crystal structure data existing for the solid form CIP-SAC (II) was possible to extract some conclusions on the polymorph CIP-SAC (I) where no single crystal information is available. (1)H MAS NMR is shown to be an important tool in the field of polymorphism and for the characterization of multicomponent pharmaceutical compounds.
Assuntos
Ciprofloxacina/química , Espectroscopia de Ressonância Magnética/métodos , Sacarina/análogos & derivados , Sacarina/química , Cristalografia por Raios X , Teoria QuânticaRESUMO
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of new multisource and reformulated immediate release (IR) solid oral dosage forms containing ciprofloxacin hydrochloride as the only active pharmaceutical ingredient (API) are reviewed. Ciprofloxacin hydrochloride's solubility and permeability, its therapeutic use and index, pharmacokinetics, excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Solubility and BA data indicate that ciprofloxacin hydrochloride is a BCS Class IV drug. Therefore, a biowaiver based approval of ciprofloxacin hydrochloride containing IR solid oral dosage forms cannot be recommended for either new multisource drug products or for major scale-up and postapproval changes (variations) to existing drug products.
Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Ciprofloxacina/administração & dosagem , Ciprofloxacina/farmacocinética , Administração Oral , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Disponibilidade Biológica , Ciprofloxacina/química , Ciprofloxacina/uso terapêutico , Formas de Dosagem , Aprovação de Drogas , Excipientes , Humanos , Absorção Intestinal , Permeabilidade , Solubilidade , Equivalência TerapêuticaRESUMO
A new polymorphic form of ciprofloxacin saccharinate (CIP-SAC II) is presented, and compared with CIP-SAC I, a different polymorph which we had previously reported. The characterization techniques used were single crystal and powder X-ray diffraction, differential scanning calorimetry, thermogravimetry analysis and infrared and (13)C solid-state nuclear magnetic resonance spectroscopy. The results obtained from these techniques are consistent. Differential scanning calorimetry and thermogravimetric analysis showed that the reaction between the precursors is completed and the crystalline forms of both salts obtained (I and II) are highly pure. Infrared spectroscopy gave clear evidence of a salt formation. Solid-state nuclear magnetic resonance spectroscopy would indicate some degree of qualitative similarity in the intermolecular interaction scheme in both polymorphs, while thermal analysis data might indicate a difference in quantitative terms. A thorough single crystal structure determination of the new form CIP-SAC II allowed disclosing the most important inter- and intramolecular interactions.
Assuntos
Ciprofloxacina/química , Cristalização/métodos , Sacarina/química , Ciprofloxacina/síntese química , Cristalografia/métodos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Termogravimetria/métodosRESUMO
A full understanding of the cellular events that occur during in vitro luteinization of bovine granulosa cells, stimulated by LH and by leptin, is a complex goal that has not been completely achieved. The aim of this work was to study the effects of leptin, LH and leptin + LH on progesterone accumulation (P4) and on the expression of LH receptors (LHR) in bovine granulosa cells in culture. The results confirm that this in vitro model is representative of functional and morphological luteinization/differentiation. The pattern of expression of LHR with time of incubation was an important marker of in vitro luteinization, with 50-90% of cells expressing LHR by 96 h in culture. Cytoplasmic lipidic droplets were highly abundant in granulosa cells, suggesting a sufficient source of precursors for steroid hormone synthesis: P4 accumulation ranged between 40 and 550 ng/ml. In addition, a positive correlation (r = 0.58, p < 0.05) between the expression of LHR and accumulation of P4 throughout the time of incubation was observed. The expression of LHR was inhibited by LH and leptin + LH treatment. In conclusion, we found an inverse modulation between the expression of LHR and the concentration of LH, and the expression of LHR could be regulated by P4 produced by the luteinized granulosa cells. These findings are contributing to elucidate further the panoply of interactions during the differentiation of granulosa cells into luteal cells in vitro.
Assuntos
Bovinos/fisiologia , Células da Granulosa/metabolismo , Leptina/administração & dosagem , Luteinização/efeitos dos fármacos , Hormônio Luteinizante/administração & dosagem , Animais , Diferenciação Celular , Células Cultivadas , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Células da Granulosa/citologia , Células da Granulosa/efeitos dos fármacos , Progesterona/biossíntese , Receptores do LH/análise , Receptores do LH/efeitos dos fármacosRESUMO
The objective of this study was to obtain transgenic maize expressing the rabies virus glycoprotein (G) of the Vnukovo strain and to evaluate its immunogenicity in mice, by the oral route. The ubiquitin maize promoter fused to the whole coding region of the rabies virus G gene, and a constitutive promoter from cauliflowermosaic virus (CaMV)were used. Maize embryogenic callus were transformed with the above construct by biolistics. Regenerated maize plants were recovered and grown in a greenhouse. The presence of the G gene and its product was detected by PCR and western blot, respectively. The amount of G protein detected in the grains was approximately 1% of the total soluble plant protein. Transformed kernels containing 50 microg of G protein were given once by the oral route in adult mice (BALB-C strain). Challenge was undertaken at 90-days post-vaccination using a lethal dose of a vampire bat rabies virus (100 LD 50% in mice); vampire bats are one of the main reservoirs in Latin America. The edible vaccine induced viral neutralizing antibodies (VNA) which, protected mice 100% against challenge. The control group did not survive. The G protein of the Vnukovo strain expressed in transgenic maize may be considered as an oral immunogen against rabies, conferring cross-protection.
Assuntos
Glicoproteínas/imunologia , Nucleoproteínas/imunologia , Vacina Antirrábica/administração & dosagem , Proteínas Virais/imunologia , Zea mays , Administração Oral , Animais , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologia , Glicoproteínas/genética , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Nucleoproteínas/biossíntese , Nucleoproteínas/genética , Plantas Geneticamente Modificadas , Vírus da Raiva/genética , Vírus da Raiva/imunologia , Proteínas Virais/biossíntese , Proteínas Virais/genética , Zea mays/genética , Zea mays/virologiaRESUMO
This study was conducted to evaluate if supplementing bypass fat to cows under silvopastoral systems, increases the concentration of unsaturated fatty acids in milk, thus improving the saturated/ unsaturated ratio without a negative effect on total milk yield in fat or protein. Two concentrations of two different sources of bypass fat were evaluated for 40 days, each in a group of 24 multiparous Lucerna (Colombian breed) cows. A cross-over design of 8 Latin squares 3 x 3 was used. The variables submitted to analysis were body condition, daily milk production and milk composition. Body condition, milk yield and milk quality were not different but there was a significant decrease in the amount of saturated fatty acid in both experiments while the unsaturated fat increased significantly in experiment 1 and remained stable in experiment 2. Results, such as these have as far as we know, not been reported previously and they provide an approach for the improvement of milk as a "functional food".
Assuntos
Bovinos/fisiologia , Gorduras na Dieta/administração & dosagem , Ácidos Graxos Insaturados/análise , Ácidos Graxos/análise , Lactação/metabolismo , Proteínas do Leite/análise , Leite/química , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Bovinos/metabolismo , Estudos Cross-Over , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Feminino , Distribuição AleatóriaRESUMO
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing amitriptyline hydrochloride are reviewed. Its therapeutic uses, its pharmacokinetic properties, the possibility of excipient interactions and reported BE/bioavailability (BA) problems are also taken into consideration. Literature data indicates that amitriptyline hydrochloride is a highly permeable active pharmaceutical ingredient (API). Data on the solubility according to the current Biopharmaceutics Classification System (BCS) were not fully available and consequently amitriptyline hydrochloride could not be definitively assigned to either BCS Class I or BCS Class II. But all evidence taken together, a biowaiver can currently be recommended provided that IR tablets are formulated with excipients used in existing approved products and that the dissolution meets the criteria defined in the Guidances.