Azathioprine is an immunosuppressive drug for several inflammatory disorders. Due to its clinical relevance, to explore the solid-state properties for excipient compatibility in the product quality review process is essential. Fourier transform infrared spectroscopy, powder X-ray diffraction and thermal analysis (thermogravimetry/derivative thermogravimetry (TG/DTG), differential thermal analysis (DTA), and differential scanning calorimetry (DSC)) were applied. The compatibility studies evidenced that starch pregelatinized, colloidal silicon dioxide, and talc are fully compatible with azathioprine. However, stearic acid, magnesium stearate, and mannitol are incompatible after heat supply at temperatures easily reached by industrial processing. The nonlinear Vyazovkin isoconversional treatment performed the kinetic study of the thermal degradation. The activation energies were determined to clarify the influence of each excipient on the thermal drug stability, an essential procedure in the pharmaceutical development, and all over the commercial live span, in Good Manufacturing Practices.

Abstract Pneumonia in cattle is one of the causes of morbidity rates and economic loss. The host response to lung infections caused by Ureaplasma diversum in bovines is virtually unknown. Here in the immune response was evaluated in a murine model for an experimental pulmonary infection by U. diversum. Therefore, AJ, BALB/C and C57BL/6 mice received intratracheal inoculation of U. diversum and were evaluated after 1, 2, 3, 7 and 14 days and the clinical specimens were collected. In bronchoalveolar lavages (BAL) an increase of inflammatory cells was observed. Neutrophils were the main cells recruited to the site of infection and the infiltration was coincided with the production of pro-inflammatory cytokines. We found a large amount of neutrophil in this initial period, followed by a decrease 7 and 14 days post infection, accompanied by bacterial clearance. Our results evidenced the presence of U. diversum within the neutrophil that suggests a phagocytic role of this cell in the elimination of the infection. The immune response features reported here are the initial evidence that healthy immune systems may control these microorganisms. This may be the first step to design new strategies immune based to control the infections in naturally infected hosts.

Ureaplasma diversum é um patógeno oportunista asso ciado com inflamação uterina, implantação do embrião prejudicada, infertilidade, abortos, nascimento prema turo de bezerros e pneumonia neonatal em gado. Tem sido sugerido que infecções causadas por Ureaplasma diversum podem causar alterações vasculares que impedem o sucesso da gravidez. Portanto, o objetivo desse estudo foi avaliar as alterações intrauterinas em camundongos A/J na fase de estro ou proestro inoculados com Ureaplasma diversum. A infecção foi avaliada após 24, 48 e 72 horas pela metodologia de PCR para detectar Ureaplasma no sítio de inoculação e o perfil de células sanguíneas circulantes. Alterações morfológicas, intensidade da inflamação e a produção de citocinas foram comparadas. Os camundongos infectados mostraram inflamação local pela produção de IFN-γ e TNF-α. Infecções por Ureaplasma diversum no trato reprodutivo dos camundongos estudados mostraram estar associadas com a produção de citocinas pró-inflamatórias no parênquima uterino. As concentrações de TNF-α nos camundongos infectados foram dependentes da carga bacteriana de Ureaplasma inoculado. Infecções uterinas experimentais por Ureaplasma diversum ainda não foram descritas e aqui nós apresentamos o primeiro relato de um modelo de infecção intrauterina em camundongos.

Ureaplasma diversum is an opportunistic pathogen associated with uterine inflammation, impaired embryo implantation, infertility, abortions, premature birth of calves and neonatal pneumonia in cattle. It has been suggested that the intra-uterine infection by Ureaplasma diversum can cause vascular changes that hinder the success of pregnancy. Thus, the aim of this study was to evaluate the changes of intrauterine site of A/J mice in estrus or proestrus phase inoculated with Ureaplasma diversum. The infection was monitored at 24, 48 and 72 hours by the PCR methodology to detect the Ureaplasma in the inoculation site and the profile of circulating blood cells. Morphological changes, intensity of inflammation and the production of cytokines were compared. The infected mice showed local inflammation through the production of IFN-γ and TNF-α. Ureaplasma diversum infections in the reproductive tract of studied mice seemed to be associated with the production of pro-inflammatory cytokines in uterine parenchyma. The levels of TNF-α of infected mice were dependent on the bacterial load of inoculated Ureaplasma. Uterine experimental infections by Ureaplasma diversum have not been mentioned yet and herein we presented the first report of an intrauterine infection model in mice.

O objetivo do presente estudo é avaliar o papel das colinesterases como marcadores inflamatórios nas fases aguda e crônica da infecção por T. evansi em coelhos infectados experimentalmente. Foram utilizados 12 coelhos adultos, fêmeas, da raça Nova Zelândia, divididos em dois grupos: um grupo controle, com seis animais (coelhos 1-6), e um grupo infectado, com seis animais (coelhos 7-12). Os animais pertencentes ao grupo infectados receberam, pela via intraperitoneal, 0,5 mL de sangue de rato contendo 108 tripanossomas por animal. Amostras do sangue utilizado para avaliação das colinesterases foram coletadas nos dias 0, 2, 7, 12, 27, 42, 57, 87, 102 e 118 pós-inoculação (PI). Aumento (P<0,05) na atividade da butirilcolinesterase (BChE) e da acetilcolinesterase foi observado no sangue nos dias 7 e 27 (PI), respectivamente e não foram observadas diferenças na atividade da colinesterase em outros períodos. Nenhuma diferença significativa na atividade da AChE (P>0,05) foi observada nas estruturas encefálicas. O aumento de atividade da AChE e BChE provavelmente tenha finalidade pró-inflamatória, a fim de reduzir as concentrações de acetilcolina, neurotransmissor que apresenta propriedade anti-inflamatória. Portanto, as colinesterases podem ser marcadores inflamatórios na infecção por T. evansi em coelhos.

The aim of this study is to evaluate the role of cholinesterases as an inflammatory marker in acute and chronic infection by Trypanosoma evansi in rabbits experimentally infected. Twelve adult female New Zealand rabbits were used and divided into two groups with 6 animals each: control group (rabbits 1-6) and infected group (rabbits 7-12). Infected group received intraperitoneally 0.5 mL of blood from a rat containing 108 parasites per animal. Blood samples used for cholinesterases evaluation were collected on days 0, 2, 7, 12, 27, 42, 57, 87, 102 and 118 days post-inoculation (PI). Increased activity (P<0.05) of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) were observed in the blood on days 7 and 27, respectively and no differences were observed in cholinesterase activity in other periods. No significant difference in AChE activity (P>0.05) was observed in the encephalic structures. The increased activities of AChE and BChE probably have a pro-inflammatory purpose, attempting to reduce the concentration of acetylcholine, a neurotransmitter which has an anti-inflammatory property. Therefore, cholinesterase may be inflammatory markers in infection with T. evansi in rabbits.

FeBr2 has reacted with an equivalent of mnt2- (mnt = cis-1,2-dicyanoethylene-1,2-dithiolate) and the α-diimine L (L = 1,10'-phenantroline, 2,2'-bipyridine) in THF solution, and followed by adding of t-butyl-isocyanide to give [Fe(mnt)(L)(t-BuNC)2] neutral compound. The products were characterized by infrared, UV-visible and Mössbauer spectroscopy, besides thermogravimetric and conductivity data. The geometry in the equilibrium was calculated by the density functional theory and the electronic spectrum by the time-dependent. The experimental and theoretical results in good agreement have defined an octahedral geometry with two isocyanide neighbours. The π→π* intraligand electronic transition was not observed for cis-isomers in the near-IR spectral region.