Albendazole - Ivermectin combination decreases inflammation in experimental neurocysticercosis.

Neurocysticercosis (NCC) is a public health issue in endemic regions and is considered the main preventable cause of neurologic disease. It is caused by the presence of Taenia solium cysticercus in the central nervous system. The current treatment is performed with anthelminthic drugs - albendazole (ABZ) or praziquantel - associated with anti-inflammatory and corticosteroids in order to prevent the negative effects of the inflammatory reaction to the parasite's death. Ivermectin (IVM) is an anthelminthic drug that has been shown to present an anti-inflammatory effect. The aim of this study was to was to evaluate the histopathologic aspects of experimental NCC after in vivo treatment with a combination of ABZ-IVM. Balb/c mice were intracranially inoculated with T. crassiceps cysticerci and after 30 days of infection were treated with a single dose of NaCl 0.9% (control group), ABZ monotherapy (40 mg/kg), IVM monotherapy (0.2 mg/kg) or a combination of ABZ-IVM. 24h after the treatment the animals were euthanized and the brain was removed for histopathologic analysis. The IVM monotherapy and ABZ-IVM combination showed more degenerated cysticerci, less inflammatory infiltration, meningitis and hyperemia than the other groups. Therefore, it is possible to recommend the combination of albendazole and ivermectin as alternative chemotherapy for NCC due to its antiparasitic and anti-inflammatory effects, with potential to decrease the negative effects of the inflammatory burst when the parasite is killed within the CNS.

Polymethylmethacrylate Microspheres are Immunologically Inert in Mouse Tissues.

Nowadays, aesthetic concerns have gained attention, especially by patients looking for a less invasive alternative to minor facial corrections. Polymethylmethacrylate (PMMA) is widely used as a soft tissue filler; the demand for this polymer has increased, and along with it, there are some reports of adverse reactions. Such adverse reactions stem from consequences of immune and inflammatory reactions to PMMA. Some animal models have been used to unravel the causes of these reactions, among other factors involving the management of PMMA. The aim of this study was to determine the immunogenic profile of PMMA implantation in different anatomical planes of mice, over up to 360 experimental days. In this study, BALB/c mice were divided into 30 groups for immune evaluation of the interaction between the organism and the polymer; 2% PMMA was implanted subcutaneously, 10% intramuscularly and 30% in periosteal juxtaposition and followed during five experimental days (7, 30, 90, 180 and 360 days after implantation-DAI). Pro- and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IFN-gamma, TNF, IL-17A, IL-10 and TGF-beta) were quantified in all experimental days. There was no statistical difference between the groups analyzed considering the evaluated parameters. Therefore, at all implanted depths, PMMA behaved inertly in a murine model.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Tissue Remodeling After Implantation with Polymethylmethacrylate: An Experimental Study in Mice.

Polymethylmethacrylate (PMMA) is a filler used for aesthetic and/or repair purposes. The response to the implantation of biomaterials varies according to factors related to the patient, the professional responsible for the application and the material used. In vitro and in vivo experimental models have been used to study aspects such as the organism/biomaterial interface and the role of macrophages, dendritic cells and neutrophils. This study aimed to characterize the inflammatory reactions related to polymer concentration, implantation depth and exposure time. Different concentrations of PMMA were implanted in different anatomical planes in mice. The consequences of contact with PMMA, from structural changes to the inflammatory characteristic of tissue damage, were histologically evaluated. The implantation interfered in the morphological structure of the region where it was implanted, expanding it and due to the inflammatory reaction generated, by the presence of the vehicle in the initial phase and by the collagen produced in the chronic phase. The 30% concentration of PMMA induced a greater presence of foreign body giant cells both subcutaneously, at 7, 30 and 90 days after implantation (DAI), and intramuscular at 30DAI. Tissue remodeling was more expressive in the subcutaneous region with significant density of the extracellular matrix at 90DAI. In conclusion, the foreign body reaction resulting from the implantation process acquires different characteristics depending on the anatomical plane and the concentration of implanted product, where the more superficial the implantation plane, the greater the inflammatory reaction. Moreover, PMMA concentration and the depth of implantation did not influence the collagen production.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266.

Oral Treatment with Angiotensin-(1-7) Attenuates the Kidney Injury Induced by Gentamicin in Wistar Rats.

BACKGROUND: Acute Kidney Injury (AKI), a common disease of the urinary system, can be induced by high doses of gentamicin (GM). The renin-angiotensin system exerts a key role in the progression of the AKI since elevated intrarenal levels of Ang II, and ACE activity is found in this condition. However, it is unknown whether oral administration of angiotensin (Ang)-(1-7), a heptapeptide that evokes opposite effects of Ang II, may attenuate the renal injuries induced by gentamicin. OBJECTIVES: To evaluate the effects of Ang-(1-7) on GM-induced renal dysfunction in rats. METHODS: AKI was induced by subcutaneous administration of GM (80 mg/Kg) for 5 days. Simultaneously, Ang-(1-7) included in hydroxypropyl ß-cyclodextrin (HPßCD) was administered by gavage [46 µg/kg HPßCD + 30 µg/kg Ang-(1-7)]. At the end of the treatment period (sixth day), the rats were housed in metabolic cages for renal function evaluation. Thereafter, blood and kidney samples were collected. RESULTS: Ang-(1-7) attenuated the increase of the plasmatic creatinine and proteinuria caused by GM but did not change the glomerular filtration rate nor tubular necrosis. Ang-(1-7) attenuated the increased urinary flow and the fractional excretion of H2O and potassium observed in GM rats but intensified the elevated excretion of sodium in these animals. Morphological analysis showed that Ang-(1-7) also reduced the tubular vacuolization in kidneys from GM rats. CONCLUSION: Ang-(1-7) promotes selective beneficial effects in renal injuries induced by GM.

In Vivo Treatment with the Combination of Nitazoxanide and Flubendazole Induces Gluconeogenesis and Protein Catabolism in Taenia crassiceps cysticerci.

PURPOSE: Cysticercosis is the presence of Taenia solium larvae in humans or swines tissues. It is a public health problem related to bad hygienic habits and consumption of infected pork. T. crassiceps is a widely used cysticercosis experimental model. The combination of two effective drugs such as nitazoxanide (NTZ) and flubendazole (FBZ) may potentialize their effect. The aim of this study was to use biochemical analysis to determine the metabolic impact of the combination of NTZ and FBZ on cysticerci inoculated intraperitoneally in mice. METHODS: Balb/c mice intraperitoneally infected with T. crassiceps cysticerci received a single oral dose NTZ/FBZ (50 mg/kg). 24 h after the treatment the cysticerci were removed, frozen and analyzed by high performance liquid chromatography regarding the detection of the following metabolic pathways: glycolysis, gluconeogenesis, homolactic fermentation, tricarboxylic acid cycle, proteins catabolism and fatty acids oxidation. RESULTS: The treatment with the drugs combination induced a statistically significant increase in gluconeogenesis and in protein catabolism when compared to the control groups. CONCLUSION: The drugs combination is potentialized and capable of causing greater metabolic stress than the separate treatment with NTZ or FBZ, showing its potential for an alternative cysticercosis treatment.

Facial trauma reconstruction with polymethyl methacrylate-A case report.

BACKGROUND: Polymethyl methacrylate (PMMA) is a dermatologic filler commonly used in esthetic procedures. However, it can also be used in more severe cases such as reconstruction of facial traumas. AIMS: The aim of this report was to describe the use of PMMA in a nasal reconstruction of a patient victim of an automobilist accident which presented previous rejection of autograft. PATIENT: A young female patient, 26 y, victim of automobilist accident, with no bone support due to trauma both in the mandibulum and maxilla, presented fracture of several facial bones. Presented rejection of a bone autograft from the skullcap implanted on the nose. In order to harmonize the facial aspect, a nasal fill with PMMA for the anatomic reconstruction of the nose was performed. RESULTS AND CONCLUSIONS: PMMA promoted the recovery of facial and nasal esthetic characteristics of the patient ensuring a satisfactory result.

Nephroprotective effect of Rudgea viburnoides (Cham.) Benth leaves on gentamicin-induced nephrotoxicity in rats.

RELEVANCE: Rudgea viburnoides, popularly known as "congonha-de-bugre" or "erva de bugre", is used in folk medicine as hypotensive, blood depurative, anti-rheumatic, diuretic and in the treatment of kidney and bladder pain. AIM: Based on the popularly acclaimed nephron-protective effect of R. viburnoides, we investigated, using rats, the protective effect of this plant extract on gentamicin-induced kidney injury. MATERIAL AND METHODS: Urinary volume, water and food intakes were assessed in adult male Wistar rats (naive or gentamicin-induced model of nephrotoxicity) treated with R. viburnoides extract. Also blood and kidney samples were collected for further laboratory and histological analyses. RESULTS: R. viburnoides leaves extract improved renal function. It also improved the renal function impairments caused by gentamicin-induced nephrotoxicity, as revealed by glomerular filtration rate, urine output and proteinuria. CONCLUSION: R. viburnoides exert renoprotective effect, which may support its popular use for renal diseases treatment.

Effects of Pimenta pseudocaryophyllus (Gomes) L. R. Landrum, on melanized and non-melanized Cryptococcus neoformans.

In the present study, the in vitro susceptibility and capsular width from both melanized and non-melanized Cryptococcus neoformans cells in the presence of Pimenta pseudocaryophyllus crude extract were determined. The results were compared with those obtained for voriconazole and amphotericin B. Melanization was obtained in minimal medium broth with the addition of L-dopa, and the antifungal susceptibility tests were performed using the broth microdilution method. Capsular width of 30 cells of each one of the isolates in medium with crude extracts of P. pseudocaryophyllus or voriconazole or amphotericin B at a concentration corresponding to 0.5 times the minimal inhibitory concentration (MIC) was measured, and the mean was calculated. The MICs and minimal fungicidal concentrations (MFCs) for plant extract and voriconazole were identical for both melanized and non-melanized C. neoformans isolates, but for amphotericin, the MFCs for melanized cells were up to 8 times higher than for non-melanized cells. The capsular width of C. neoformans cells was smaller (p < 0.001) in the presence crude extract of P. pseudocaryophyllus and of voriconazole regardless melanization. The findings of capsule alterations of C. neoformans verified in this study provide fertile ways for future research into the effects of antifungal agents on the pathogenesis of cryptococcosis.

Fatty acids oxidation and alternative energy sources detected in Taenia crassiceps cysticerci after host treatment with antihelminthic drugs.

Human cysticercosis caused by Taenia crassiceps is rare however it is considered of zoonotic risk. The treatment of the infected patients was successful when using albendazole or praziquantel. The active forms of albendazole inhibit the glucose uptake and the active forms of praziquantel alter glycogen levels and nutrients absorption. The aim of this study was to analyze the production of organic acids that indicate the oxidation of fatty acids and the use of alternative energy sources from T. crassiceps cysticerci removed from the peritoneal cavity of mice treated with low dosages of albendazole (5.75 and 11.5mg/kg) or praziquantel (3.83 and 7.67 mg/kg). The beta-hydroxibutyrate production was higher by the larval stage cysticerci in all treated groups and the propionate production was higher in final stage cysticerci treated with 11.5mg/kg of albendazole when compared to the control group. The larval stages of cysticerci from the groups treated with 5.75 mg/kg of albendazole and 3.83 mg/kg of praziquantel produced more urea than the initial and final stages which indicate amino acids breakdown. We conclude that it was possible to detect the fatty acid oxidation and amino acids breakdown which indicate the use of alternative energy production sources as the used dosages only cause a partial blockage of the glucose uptake and leads to metabolic alterations in the cysticerci. The metabolic behavior observed after host treatment was different from former descriptions of the in vitro one which indicates great host-parasite interaction.

Lagochilascaris minor: Susceptibility and Resistance to Experimental Infection in Mice Is Independent of H-2 Haplotype and Correlates with the Immune Response in Immunized Animals.

Recently, we demonstrated that C57BL/6 mice are more susceptible to experimental lagochilascariosis than BALB/c mice. To investigate the pattern of infection and the role of the genetic background on susceptibility to infection, we studied experimental lagochilascariosis in H-2(a) identical B10.A and A/J mice. Infected B10.A mice had a lower survival ratio and more severe lesions in the lungs than did A/J mice. Splenocytes of A/J mice immunized with the crude extract of the parasite showed increased proliferation and produced a higher level of interleukin 10 and interferon-gamma in the presence of CE or concanavalin A when compared to B10.A mice. This suggests that resistance of A/J mice may be due to less severe lesions in lungs and other organs and a better immune response to parasite antigens. This paper provides evidence that major histocompatibility complex haplotype does not influence the survival to experimental infection with L. minor.

Freqüência de alterações cérvico-vaginais em mulheres submetidas ao exame citopatológico / Frequency of cervico vaginalis alteration in submitted patients of cytopathological exam / Frecuencia de las alteraciones cervicovaginal en mujeres sometidas al examen citopatógico

O Exame citopatológico é o método de triagem que auxilia na detecção precoce do câncer e de lesões pré-cancerosas da cérvix. No Brasil, o câncer cervical representa a segunda neoplasia maligna mais incidente em mulheres. O objetivo desse estudo foi avaliar a freqüência das alterações citopatológicas de acordo com a faixa etária. A seleção dos casos foi realizada através dos resultados dos exames citopatológicos, de mulheres na faixa etária entre 14 a 80 anos, obtidos no Centro de Atenção Integrada à Saúde da Mulher, Uberaba (MG), no período de 2001 a 2003. Dos 35.220 resultados obtidos, em 3,34% foram descritos alterações no epitélio cérvico-vaginal, sendo mais freqüentes as alterações escamosas e glandulares de significado indeterminado (53,7%) e as infecções pelo HPV (31%). As mulheres mais jovens (< 40 anos) foram significativamente mais acometidas por essas alterações (p<0,005). Neoplasias invasivas acometeram 5,6% das mulheres a partir da quarta década de vida (p<0,005). Os diagnósticos das alterações no epitélio cérvico-vaginal de acordo com a faixa etária das mulheres foram semelhantes aos descritos na literatura, sendo que infecção pelo HPV, principal agente potencialmente carcinogênico, acometeu mulheres mais jovens e as neoplasias invasivas foram mais freqüentes a partir da quarta década de vida.

The cytopathological exam is useful recommended for early diagnoses of neoplastic and of pre-neoplastic lesions of the uterine cervix. In Brazil, cervix neoplasm is the second most frequent malignant neoplasm in women. The aim of this study was evaluate the frequency of cytopathologic alterations and its relationship with age. The cases selection was performed by means of cytopathological exam results in women aged 14 to 80 years old, by the revision in Centro de Atenção Integrado a Saúde da Mulher, Uberaba (MG), during the period of 2001-2003. From de 35.220 reviewed exams, 3.34% tests showed alterations in the cervico vaginalis epithelium, with a higher frequency in the squamous cervical epithelium alterations and glandular epithelium alterations of unknown significance (53.7%) as well as infection by the Human Papillomavirus (HPV) (31%). The infections caused by the HPV and atypical glandular and scamous cells of undetermined significance were more frequent in ages under the 40 (p<0.005), yet the occurrence of cervical carcinoma was more frequent in women over 40 (p<0.005). Therefore, the frequency of cytopathologic alterations of the cervical and vaginal epithelium and its relationship to age were resemblance to described in literature. The HPV infection, the best carcinogenic potential agent attacked younger patients and the invasive neoplasm was more frequent in women over 40 years old.

El exámen citopatológico es un método de triage que ayuda a realizar una detección precoz del cáncer y de lesiones pre-cancerosas del cérvix uterino. En el Brasil, el cáncer cervical representa la segunda neoplasia maligna mas incidente en mujeres. El objetivo del estudio fue avaliar la frecuencia de las alteraciones citopatológicas de acuerdo con el grupo etario. La selección de los casos fue realizada a través de los resultados de los exámenes citopatológicos, de mulheres dentro del grupo etario entre 14 a 80 años, obtenidos del Centro de Atención Integrada a la Salúd de la Mujer, Uberaba (MG), durante el período del 2001 al 2003. De los 35.220 resultados obtenidos, en 3,34% fueron descritas alteraciones en el epitélio cervico-vaginal, siendo mas frecuentes las alteraciones escamosas e glandulares de significado indeterminado (53,7%) y las infecciones por el HPV (31%). Las mulheres más jóvenes (<40 años) fueron significativamente más acometidas por esas alteraciones (p<0,005). Así, las neoplasias invasivas acometieron al 5,6% de las mulheres a partir de la cuarta década de vida (p<0,005). Los diagnósticos de las alteraciones del epitélio cérvico-vaginal de acuerdo con el grupo etario de las mulheres fueron semejantes a otros hallazgos ya descritos en la literatura, siendo que la infección por el VPH, principal agente con potencial carcinogénico, acometió a mulheres más jóvenes y las neoplasias invasivas fueron más frecuentes a partir de la cuarta década de vida.