Applicability of ARFI elastography in detecting elasticity changes of the equine superficial digital flexor tendon with induced injury.

The objectives of this prospective, experimental study were to describe changes in the stiffness of the equine superficial digital flexor tendon (SDFT) after induced injury, deep digital flexor tendon (DDFT), accessory ligament (AL-DDFT), and suspensory ligament (SL) during 90 days of healing using acoustic radiation force impulse (ARFI) elastography. Eight healthy horses were selected. Preinjury B mode and ARFI evaluations were performed bilaterally in the palmar metacarpal region. Injury was induced only on the left forelimb (G2) by a single injection of collagenase in SDFT, 15 cm distal to the accessory carpal bone. The right forelimb was used as a control (G1). Evaluations were performed at eight timepoints: one before injury (T0) and seven (T1-T7) after injury (3, 15, 30, 40, 60, 75, and 90 days post-induction). Tendinopathies were visualized as hypoechoic areas with loss of parallel tendon fiber pattern. Injured SDFTs presented mainly cool colors (soft) from T1 to T3, and from T4, there was an increase in warm colors (hard), close to the appearance of tendons of G1. In the first four timepoints, there was a decrease in stiffness compared to G1 (P < 0.001). On T1 and T2, a cutoff value <6.21 m/s to determine tendinopathy of the SDFT was established (75.8% sensitivity and 92.03% specificity). Stiffness changes in the DDFT, AL-DDFT, and SL of injured limbs occurred at different timepoints. Tendinopathy significantly altered the stiffness of the injured tendon and the adjacent tissues. ARFI made it possible to detect these changes, helping to monitor the reparation of this injury.

Treatment with Lycopodium clavatum 200dH Intensifies Kidney and Liver Injury in Mice Infected with Toxoplasma gondii.

The effects of infection with Toxoplasma gondii vary from asymptomatic to the development of alterations in various organs (including the liver and kidneys) which may be irreversible, and lead to the death of the host. Whereas homeopathy is an alternative and effective method for treating various diseases, including those caused by protozoa, we questioned the effect of using Lycopodium clavatum in mice infected with T. gondii. One hundred male Swiss mice, 60 days old, were divided into four groups (n = 25/group): NIC (uninfected and untreated control), IC (infected and treated with un-dynamized 7% alcohol solution [vehicle]), G48 (infected and treated 48 h before infection and treated three more times; at 2, 4, and 6 days post-infection (dpi) with L. clavatum 200dH), and G72 (infected and treated for 3 consecutive days before infection with L. clavatum 200dH). In this study, physiological, histopathological, and immunological parameters were evaluated. The L. clavatum 200dH intensified renal damage in mice infected with T. gondii from 7 dpi, causing severe and progressive alterations during this period, such as various degrees of inflammation, edema, atrophy, and tubular cystic dilation, degenerated tubules with intra-cytoplasmic vacuoles and coalescing spots, severe vascular lesions, glomerulonephritis, and peri-glomerular congestion. In the G72 animals, which received L. clavatum 200dH, more severe cortex damage was observed (91.66-96.66%) as compared to the IC group (55-80%) and more renal corpuscle, and renal tubule injury was observed (80 ± 5 to 96.7% ± 2.89 of the total area) during all periods, as compared to the IC group (p < 0.05). Both groups presented high liver enzyme levels, and the highest values for AST were observable at 60 dpi. We observed significant increases of type I and III collagen, as well as high levels of TGF-ß1 in both organs of the treated animals, the main factor involved in fibrosis in areas damaged by the process. L. clavatum 200dH intensifies kidney and liver alterations in mice infected with T. gondii. Our results reinforce caution when indicating administration schemes and dosages for ultra-diluted drugs.

Histopathological lesions in encephalon and heart of mice infected with Toxoplasma gondii increase after Lycopodium clavatum 200dH treatment.

In many cases, symptoms of toxoplasmosis are mistaken for the ones of other infectious diseases. Clinical signs are rare in immunocompetent people. However, when they arise, in the acute phase of infection, several organs are affected due to the rapid spread of tachyzoites through the bloodstream. In the present study, the reduction of tachyzoites in peripheral blood of mice of G72 (infected 72h after treatment) and G48 (infected 48h after treatment and treated three more times), when compared with IC (infected and non-treated), suggests protective effect exerted by Lycopodium clavatum. If on the one hand L. clavatum brought benefits, reducing parasitemia, on the other hand, the parasitism became exacerbated. Histopathological analysis demonstrated focal, multifocal and diffuse inflammatory infiltrates, ranging from absent, discreet, moderate to intense, in heart and encephalon of mice of NIC (non-infected and non-treated), IC, G48 and G72 groups, respectively. In the perivascular region and meninges, the injuries were enlarged. The presence of tachyzoites was demonstrated through immunohistochemical (IHC) assay in myocardium. Toxoplasma gondii induced increase of collagen fibers in myocardium of mice of G72 and G48 groups, compared with IC (p<0.05) and NIC (p<0.001). The presence of inflammatory infiltrates, as well as the progressive fibrosis, caused myocardial remodeling in animals treated with L. clavatum. Counterstaining with H&E suggests TGF-ß expression by mononuclear cells in the inflammatory infiltrate. Based on our results, we can conclude that the adopted regimen and potency exerted a protective effect, reducing parasitemia. However, it intensified the histopathological lesions in encephalon and heart of mice infected with T. gondii.

The Association of Ponderal Benznidazole with its Ultra-high Diluted Formula Reduces the Toxic Effects and Allows Increasing of Dose in Dose-dependent Protocol in Mice Infected with Trypanosoma cruzi

Although several diseases are treated by toxic drugs, their side effects may hamper adherence to the therapy. The aim of this study is to evaluate the effect of the association of ponderal benznidazole (BZ) with its ultra-high diluted (UHD) formula on clinical and parasitological parameters of mice infected by Trypanosoma cruzi (T. cruzi). 24 non-isogenic Swiss mice were divided into groups: CI – infected animals treated with 7% alcohol; BZp – infected animals treated with BZ (500 mg/ kg) from the beginning of infection; BZp+d – infected animals treated with ponderal BZ and with UHD BZ, which started to be administered four days after the beginning of treatment with ponderal BZ; CNI - group of non-treated and non-infected animals. The UHD medicine was prepared according to Phamacopoeia until 30x. The different treatment schedules were statistically compared through parasitological and clinical parameters. The group BZp+d displayed more favorable clinical evolution than the group BZp, with improvement of mass gain, feed conversion and water intake, presenting data approximated to CNI group. The significant increase of the body temperature of BZp+d group indicates an activation of the immune system which was not observed in the other groups. Moreover, the anti-parasitic effect of the ponderal drug was maintained in all parasitological parameters of this group. By reducing the side effects and maintaining the action of the ponderal drug, the combination of toxic drugs with their UHD formula could be considered a way of improving efficacy of the treatment...

A infecção por Trypanossoma cruzi é um problema de saúde pública e o único medicamento disponível no Brasil é o benznidazol (BZ), com efeitos limitados e tóxicos. Estudos anteriores com BZ na dose de 200 mg/kg indicaram que a administração de BZ diluído (30d) controla os efeitos tóxicos da droga em dose ponderal, sem alterar a sua ação terapêutica. Sob essa perspectiva e considerando a ação do BZ dose dependente, aumentar a quantidade de droga administrada significaria uma melhora na eficácia do tratamento. Portanto, este trabalho teve como objetivo avaliar o efeito do BZ ponderal (BZP), na dose de 500 mg/kg associado com BZ diluído (BZD) nos parâmetros clínicos de camundongos infectados por T. cruzi. Em estudo cego, controlado e randomizado, foram utilizados 23 camundongos suíços, machos, com 8 semanas divididos em grupos: CNI - Não infectados e não tratados; CI - Infectados e tratados com álcool 7 %; BZP - Infectados tratados com BZ (500 mg/kg de peso/ animal) a partir do início da infecção; BZP + BZD - Infectados e tratados com a associação de BZP e BZD. Os medicamentos foram administrados por gavagem (0,2 mL/ dia/ animal). O BZP foi administrado a partir da constatação da infecção. O BZ diluído foi preparado de acordo com a Farmacopeia Homeopática Brasileira e administrado 4 dias após o início do tratamento com BZP. Os parâmetros clínicos, avaliados diariamente, incluíram: peso, consumo de ração e água, temperatura e quantidade de excretas. A análise clínica apontou melhores resultados nos grupos BZP e BZP + BZD, mostrando melhor evolução de peso, consumo de ração, água e excretas quando comparado aos grupos não tratados (p< 0.05)...

The Association of Ponderal Benznidazole with its Ultra-high Diluted Formula Reduces the Toxic Effects and Allows Increasing of Dose in Dose-dependent Protocol in Mice Infected with Trypanosoma cruzi

Although several diseases are treated by toxic drugs, their side effects may hamper adherence to the therapy. The aim of this study is to evaluate the effect of the association of ponderal benznidazole (BZ) with its ultra-high diluted (UHD) formula on clinical and parasitological parameters of mice infected by Trypanosoma cruzi (T. cruzi). 24 non-isogenic Swiss mice were divided into groups: CI – infected animals treated with 7% alcohol; BZp – infected animals treated with BZ (500 mg/ kg) from the beginning of infection; BZp+d – infected animals treated with ponderal BZ and with UHD BZ, which started to be administered four days after the beginning of treatment with ponderal BZ; CNI - group of non-treated and non-infected animals. The UHD medicine was prepared according to Phamacopoeia until 30x. The different treatment schedules were statistically compared through parasitological and clinical parameters. The group BZp+d displayed more favorable clinical evolution than the group BZp, with improvement of mass gain, feed conversion and water intake, presenting data approximated to CNI group. The significant increase of the body temperature of BZp+d group indicates an activation of the immune system which was not observed in the other groups. Moreover, the anti-parasitic effect of the ponderal drug was maintained in all parasitological parameters of this group. By reducing the side effects and maintaining the action of the ponderal drug, the combination of toxic drugs with their UHD formula could be considered a way of improving efficacy of the treatment. (AU)

A infecção por Trypanossoma cruzi é um problema de saúde pública e o único medicamento disponível no Brasil é o benznidazol (BZ), com efeitos limitados e tóxicos. Estudos anteriores com BZ na dose de 200 mg/kg indicaram que a administração de BZ diluído (30d) controla os efeitos tóxicos da droga em dose ponderal, sem alterar a sua ação terapêutica. Sob essa perspectiva e considerando a ação do BZ dose dependente, aumentar a quantidade de droga administrada significaria uma melhora na eficácia do tratamento. Portanto, este trabalho teve como objetivo avaliar o efeito do BZ ponderal (BZP), na dose de 500 mg/kg associado com BZ diluído (BZD) nos parâmetros clínicos de camundongos infectados por T. cruzi. Em estudo cego, controlado e randomizado, foram utilizados 23 camundongos suíços, machos, com 8 semanas divididos em grupos: CNI - Não infectados e não tratados; CI - Infectados e tratados com álcool 7 %; BZP - Infectados tratados com BZ (500 mg/kg de peso/ animal) a partir do início da infecção; BZP + BZD - Infectados e tratados com a associação de BZP e BZD. Os medicamentos foram administrados por gavagem (0,2 mL/ dia/ animal). O BZP foi administrado a partir da constatação da infecção. O BZ diluído foi preparado de acordo com a Farmacopeia Homeopática Brasileira e administrado 4 dias após o início do tratamento com BZP. Os parâmetros clínicos, avaliados diariamente, incluíram: peso, consumo de ração e água, temperatura e quantidade de excretas. A análise clínica apontou melhores resultados nos grupos BZP e BZP + BZD, mostrando melhor evolução de peso, consumo de ração, água e excretas quando comparado aos grupos não tratados (p< 0.05). A associação BZP + BZDobteve melhor evolução de peso, consumo de água e produção de excretas (p< 0.05) quando comparada com o grupo tratado BZP, revelando-se uma alternativa para diminuir os efeitos indesejados do medicamento convencional, permitindo o aumento da dose administrada e maior eficácia do tratamento. A associação destes medicamentos deve ser explorada em outras condições clínicas onde existem poucos medicamentos disponíveis e efeitos colaterais que comprometem a terapêutica