Evaluation of nitazoxanide in the treatment of experimental murine neurotoxoplasmosis

ABSTRACT Toxoplasmosis is a widespread zoonotic disease that poses significant public health concern globally, with neurotoxoplasmosis being a severe complication associated with high mortality rates. The standard therapy for neurotoxoplasmosis involves a combination of sulfadiazine and pyrimethamine, which, despite its efficacy, is often limited by adverse effects leading to treatment discontinuation. This study aimed to evaluate the in vivo efficacy of nitazoxanide in treating neurotoxoplasmosis in mice infected with the Me49 strain. The study comprised two groups: Group I, including subgroups of uninfected, infected and treated with saline, and infected and untreated mice; and Group II, comprising infected mice treated with nitazoxanide at 100 mg/kg/day, nitazoxanide at 150 mg/kg/day, and pyrimethamine combined with sulfadiazine. After 14 days of treatment, the mice were euthanized for organ collection. Histopathological examination of the brains revealed that the highest dose of nitazoxanide reduced parasitic load and cerebral hemorrhages. Biochemical and histopathological analyses of liver and kidney tissues demonstrated toxicological profiles comparable to pyrimethamine and sulfadiazine. However, despite showing efficacy and similar toxicity levels, nitazoxanide treatment was less effective regimen in controlling neurotoxoplasmosis in this experimental model compared to the pyrimethamine and sulfadiazine. Thus, while nitazoxanide presents potential in neurotoxoplasmosis treatment, pyrimethamine combined with sulfadiazine remains the preferred therapeutic choice based on better efficacy observed in this study.

Clinical and Histological Features of Multifocal Canalicular Adenomas of the Upper Lip

Canalicular adenoma (CA) is an uncommon benign salivary gland tumor that mostly occurs in the upper lip. Despite its benign nature, some patients may present multiple nodules and also microscopic growth that can be multifocal with foci of tumor within the adjacent gland. Microscopically, CA can be mistaken for a polymorphous low-grade adenocarcinoma (PLGA) or basal cell adenoma (BCA), and immunohistochemistry can be helpful in differentiating them. Two cases of canalicular adenoma showing tumor foci within the adjacent gland are described. Both cases occurred in the upper lip of white females aged 72 and 79 years. In addition to the histological multifocal aspect, one of the patients presented bi-lateral nodules. Histological examination of both lesions revealed interconnecting and branching canal-like structures composed by uniform columnar and sometimes cuboidal cells, partially encapsulated. Immunohistochemical analysis showed intense expression of cytokeratins (CK) 7, a weak reaction to CK14 and a negative reaction to vimentin. Upon the diagnosis of CA the lesions were excised. In conclusion, it is important to properly diagnose CA and differentiate its multifocal aspect from a malignant behavior.

O adenoma canalicular (AC) é uma rara neoplasia benigna de glândula salivar que ocorre com maior frequência em lábio superior. Apesar de sua natureza benigna, alguns pacientes podem apresentar múltiplos nódulos, além de apresentar microscopicamente um crescimento multifocal com focos de neoplasia na glândula adjacente. Microscopicamente, AC pode ser confundido com adenocarcinoma polimorfo de baixo grau ou adenoma de células basais, sendo a imunohistoquímica útil na diferenciação entre eles. Dois casos de AC com focos de neoplasia dentro da glândula são descritos. Ambos os casos ocorreram em lábio superior de dois indivíduos do sexo feminino com 72 e 79 anos de idade. Além do aspecto histológico multifocal, um dos pacientes apresentou nódulos bilaterais. A análise histológica dos dois casos revelou estruturas canaliculares interligadas, compostas por células colunares uniformes e cuboidais, parcialmente encapsuladas. A análise imunohistoquímica mostrou intensa marcação de citoqueratina (CK) 7, uma fraca expressão para CK14, e reação negativa para vmentina. Após o diagnóstico as lesões foram excisionadas. Conclusão: É importante o correto diagnóstico do AC e a diferenciação do aspecto multifocal de um comportamento maligno.

Diagnóstico de sífilis em lesões orais: estudo comparativo utilizando-se as técnicas histoquímica e imuno-histoquímica / Diagnosis of syphilis in oral lesions: a comparative study using techniques of histochemistry and immunohistochemistry

A sífilis é uma doença infecciosa, cujo agente etiológico é o Treponema pallidum. Pode ser transmitida sexualmente ou verticalmente, via placenta. Seus estágios variam entre sífilis primária, sífilis secundária, sífilis latente e sífilis congênita. Dentre os diagnósticos mais eficazes, encontram-se os testes sorológicos, porém os falsos positivos e falsos negativos no estágio primário levam à procura de uma forma mais eficaz de se determinar, precocemente, a doença. Além disso, por várias razões, nem sempre o profissional clínico suspeita das lesões presentes na mucosa oral, cogitando de outras hipóteses diagnósticas. O objetivo deste trabalho foi avaliar imuno-histoquimicamente e histoquimicamente lesões bucais biopsiadas cujo aspecto histológico levou à suspeita de sífilis, buscando identificar os microorganismos, bem como correlacionar o quadro sorológico quando positivo. Para o estudo foram incluídas 34 lesões suspeitas de sífilis, que foram submetidas à reação imuno-histoquímica com o anticorpo anti-treponema e técnica histoquímica de coloração pela prata. Dos 34 casos avaliados 13 foram positivos para o anticorpo anti-treponema, todos posteriormente diagnosticados como sífilis secundária, com positividade sorológica, exceto por um caso em que a sorologia não foi realizada. Quando se comparou os métodos de diagnóstico, a técnica de coloração por prata obteve sensibilidade de 46,15% e a de imuno-histoquímica foi de 92,3%. Os aspectos histológicos variaram em um grande número de achados, dentre eles: intensa exocitose, infiltrado inflamatório predominantemente plasmocitário (justaepitelial e perivascular), áreas de ulceração, epitélio paraqueratinizado, edema, espongiose e hiperplasia epitelial. A marcação imuno-histoquímica dos treponemas foi, principalmente, epitelial (61,5%) e esse método se mostrou um meio de diagnóstico rápido, simples e eficiente no diagnóstico de lesões orais de Sífilis.

Syphilis is an infectious disease, whose etiologic agent is Treponema pallidum. It can be transmitted sexually or vertically via the placenta. Its stages include primary syphilis, secondary syphilis, latent syphilis and congenital syphilis. Among the diagnoses most effective are the serological tests, but false positives and false negatives in the primary stage lead to demand for a more effective way to determine the disease earlier. In addition, for various reasons, not always the professional clinical suspicion of lesions present in the oral mucosa, thinking in other possible diagnoses. The objective of this study was to identify microorganisms and set the best way forward to a diagnostic framework confirmed positive serology. The results for syphilis lesions in the oral mucosa corresponded to 13 cases, all of secondary iinjuries,with positive serology for syphilis and in only one of them serology had not been held. In a comparison of diagnostic methods, the technique of silver staining achieved sensitivity of 46.15% and immunohistochemistry was 92.3%. The histological features varied in a large number of findings, including: intense exocytosis, inflammatory infiltrate, predominantly plasmacytic (banda-like and infiltrate perivascular), areas of ulceration, parakeratinized epithelium, edema, spongiosis and epithelial hyperplasia. The immunohistochemical staining of treponemes was mainly epithelial (61.5%) and this method was a rapid, simple and efficient means in the diagnosis of oral lesions of syphilis.

Detection of single and mixed colonization of Candida species in patients with denture stomatitis

Aim: To evaluate the profile of the colonization by Candida spp. using presumptive identification to classify the patients with denture stomatitis as having single or mixed colonization, correlating with oral and systemic status. Methods: The CHROMagar Candida™ Medium (CC) for yeast culture and exfoliative cytology was used to identify colonization by Candida spp. and distinguish the different species of the Candida genus from patients with denture stomatitis (DS) and denture wearers without DS (control group). In addition, colonization was correlated with specific habits, such as tobacco and alcohol use, as well as with the use of systemic drugs. Results: Direct swabbing of whole unstimulated saliva (WUS) and palatal mucosa revealed colonization in 97.3% of the patients with DS. In the control group, 55.0% patients presented colonization. The presumptive identification found C. albicans as the most prevalent between both groups, respectively in 89.4% of the DS group and 40.0% from the control group. Regarding the nonalbicans species in the DS group, the most frequent were C. krusei (31.5%), C. glabrata (21.0%) C. tropicalis (15.7%) and Candida spp (2.6%). Smokers presented 90% of mixed isolates, and no C.albicans single colonization in the DS group, with statistically significant difference between smokers and non-smokers (p=0.0051). In the control group, the non-albicans species were C.glabrata (23.0%) and C.tropicalis (23.0%). The results of cytology from the DS group showed positive results in 22.2% of the cases. Conclusions: The use of CC was effective as a complementary method for the diagnosis of colonization by Candida spp. and DS, with the additional advantage of enabling a rapid presumptive identification of the specie. Smoking seemed to play a role in the colonization of oral mucosa by mixed albicans and non-albicans species. Mixed colonization seems to be more prevalent between patients with DS.