Aline Turatti

Exercise Reduces Inflammation and Cell Proliferation in Rat Colon Carcinogenesis

PURPOSES There is evidence that the risk of colon cancer is reduced by appropriate levels of physical exercise. Nevertheless, the mechanisms involved in this protective effect of exercise remain largely unknown. Inflammation is emerging as a unifying link between a range of environment exposures and neoplastic risk. The carcinogen dimethyl-hydrazine (DMH) induces an increase in epithelial cell proliferation and in the expression of the inflammation-related enzyme cyclooxigenase-2 (COX-2) in the colon of rats. Our aim was to verify whether these events could be attenuated by exercise. METHODS Four groups of eight Wistar rats were used in the experiment. The groups G1 and G3 were sedentary (controls), and the groups G2 and G4 were submitted to 8 wk of swimming training, 5 d.wk. The groups G3 and G4 were given subcutaneous injections of DMH immediately after the exercise protocols. Fifteen days after the neoplasic induction, the rats were sacrificed and the colon was processed for histological examination and immunohistochemistry staining of proliferating cell nuclear antigen (PCNA) and COX-2. RESULTS We found a significant increase in the PCNA-labeling index in both DMH-treated groups of rats. However, this increase was significantly attenuated in the training group G4 (P < 0.01). Similar results were observed in relation to the COX-2 expression. CONCLUSIONS From our findings, we conclude that exercise training exerts remarkable antiproliferative and antiinflammatory effects in the rat colonic mucosa, suggesting that this may be an important mechanism to explain how exercise protects against colonic cancer.

Fluoxetine induces preventive and complex effects against colon cancer development in epithelial and stromal areas in rats

Fluoxetine (FLX) is a drug commonly used as antidepressant. However, its effects on tumorigenesis remain controversial. Aiming to evaluate the effects of FLX treatment on early malignant changes, we analyzed serotonin (5-HT) metabolism and recognition, aberrant crypt foci (ACF), proliferative process, microvessels, vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) expression in colon tissue. Male Wistar rats received a daily FLX-gavage (30mgkg(-1)) and, a single dose of 1,2 dimethylhydrazine (DMH; i.p., 125mgkg(-1)). After 6 weeks of FLX-treatment, our results revealed that FLX and nor-fluoxetine (N-FLX) are present in colon tissue, which was related to significant increase in serotonin (5-HT) levels (P<0.05) possibly through a blockade in SERT mRNA (serotonin reuptake transporter; P<0.05) resulting in lower 5-hydroxyindoleacetic acid (5-HIAA) levels (P<0.01) and, 5-HT2C receptor mRNA expressions. FLX-treatment decreased dysplastic ACF development (P<0.01) and proliferative process (P<0.001) in epithelia. We observed a significant decrease in the development of malignant microvessels (P<0.05), VEGF (P<0.001), and COX-2 expression (P<0.01). These findings suggest that FLX may have oncostatic effects on carcinogenic colon tissue, probably due to its modulatory activity on 5-HT metabolism and/or its ability to reduce colonic malignant events.

The Protective Role of Lychnophora ericoides Mart. (Brazilian Arnica) in 1,2-Dimethylhydrazine-Induced Experimental Colon Carcinogenesis

Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.

Overexpression of metallothioneins, stem cell niches and field cancerization in experimental gliomagenesis

INTRODUCAO: celulas-tronco podem originar e perpetuar o crescimento tumoral, porem sao pouco conhecidas na gliomagenese. As metalotioneinas (MTs) sao proteinas envolvidas na oncogenese, e sua a imunopositividade pode ser utilizada como marcador de mutacao de celulas-tronco. Objetivo: estudar a expressao de MT no modelo experimental da ENU e estabelecer um modelo experimental para monitorar as celulas-tronco glioma na oncogenese. METODOS: Trinta e seis ratos machos da raca Wistar foram divididos em dois grupos; o grupo de animais experimental foi tratado dentro de 24 horas apos o nascimento (ratos neonatos) com uma dose unica de N-etil N-nitrosoureia (ENU) (40 mg/kg). Nos animais do grupo controle, injetou-se o mesmo volume de solucao salina. Os animais do grupo experimental foram subdivididos em tres grupos de acordo com o tempo da eutanasia, como se segue: o Grupo 1 (G1) sofreu eutanasia com a idade de 30 dias; o Grupo 2 (G2), com 180 dias e o Grupo 3 (G3) sofreu eutanasia logo apos o surgimento de sinais de existencia de tumor do sistema nervoso, com uma media de idade de 321 dias. A deteccao imunohistoquimica da proteina MT em cortes da medula espinhal fixadas em acetona fria e embebidas em parafina foi realizada pelo metodo do complexo streptavidina-avidina-biotina-imuno peroxidase. RESULTADOS: por meio de modelos experimentais de gliomagenese induzida pela N-etil N-nitrosoureia, foi possivel detectar celulas-tronco de tumor putativo no inicio da oncogenese, analisar um processo de cancerizacao de campo e observar uma relacao morfologica entre celulas positivas para MT e vasos sanguineos. CONCLUSOES: este modelo experimental reprodutivel permite outros estudos sobre a origem, desenvolvimento e fatores reguladores da gliomatogenese.Introduction: stem cells may originate and perpetuate the tumor growth, but they are poorly known in gliomagenesis. Metallothioneins (MTs) are proteins involved in oncogenesis and immunopositivity, for MT may be used as a stem cell mutation marker. Objective: to study the MT expression in the ENU experimental model and to establish an experimental model to track glioma stem cells in early oncogenesis. Methods: Thirtysix male Wistar rats were divided into two groups; the experimental group was treated within 24 hours after birth (neonate rats) with a single dose of subcutaneously injected N-ethyl N-nitrosourea ENU (40 mg/ kg body weight). The control animals were injected with the same volume of saline. These experimental animals were subdivided into three groups according to the euthanize time, as follows: the Group 1 (G1) was euthanized at the age of 30 days; the Group

Anti‐desmogleins autoantibodies detected by ELISA and blotting in bullous pemphigoid: what do they mean?

treat erythrodermic flares of MF/SS because it reduces bacterial colonization and debrides excess scale. It also decreases inflammation and promotes wound cleansing. Moreover, a pilot study showed that whirlpool therapy followed by a quick rinse eradicated more than four times as many bacteria compared with whirlpool therapy alone. In our protocol, the 0.25% acetic acid rinse further decreases the skin bacterial load and reduces skin pH, which inhibits S. aureus colonization. Because the severity of MF/SS is measured by the extent of skin erythema, clinicians must recognize staphylococcal colonization and sepsis in cases of erythroderma. Since the most common cause of death in MF/SS patients is infection, especially from the use of indwelling venous catheters causing line sepsis, treatment of S. aureus is critical. For patients who develop an erythrodermic flare of MF/SS secondary to S. aureus, we recommend the “Duvic regimen” consisting of IV antibiotics, whirlpool therapy, and steroid wet wraps.

Relationship between pemphigus and American tegumentary leishmaniasis: insights from serological and genetic profiles

Background Antibodies against Leishmania peptides (Lbr-peps) and desmogleins (Dsgs) have been reported in pemphigus foliaceus (PF) and leishmaniasis patients, respectively. We aimed to compare serological and genetic features in a Brazilian region endemic for American tegumentary leishmaniasis (ATL) and pemphigus. Methods Commercial anti-Dsg ELISA and in-house ELISA with Lbr-peps were used to determine the serological profile, in addition to immunoblotting (IB) and indirect immunofluorescence (IIF) assays. HLA-DRB1 and -DQA1/DQB1 alleles were characterized by PCR combined with sequence-specific oligonucleotide probes (PCR-SSOP). The serological and genetic profiles were compared using 78 PF, 62 pemphigus vulgaris (PV) and 58 ATL patients against 163 and 1592 healthy controls, respectively. Results Some ATL patients showed positive results for anti-Dsg1 and/or anti-Dsg3 antibodies. They also revealed 130, 160 and/or 230 kDa epidermal peptides in IB. Moreover, some ATL samples exhibited pemphigus or a bullous pemphigoid pattern in IIF. ELISA and IB assays showed Lbr-peps in pemphigus patients. HLA-DQA1*01 and -DQA1*01:02 were protective and susceptibility alleles for ATL, respectively, but the opposite for pemphigus. Conclusions Anti-Dsgs in ATL may represent epiphenomena. Anti-Lbr-pep antibodies in pemphigus suggest a previous infection. A differential association of the HLA profile may contribute to the lack of co-association between pemphigus and ATL.

Herpes simplex virus 1 and cytomegalovirus are associated with pemphigus vulgaris but not with pemphigus foliaceus disease

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are blistering autoimmune diseases that depend on interaction between genetic and environmental factors. Viral infections, like herpes simplex viruses 1 and 2 (HSV1/2), cytomegalovirus (CMV), Epstein‐Barr virus and dengue virus, could trigger or exacerbate pemphigus. IgM and IgG antibodies against these viruses in serum from PV and PF, their relatives and controls were determined. HSV1/2 expression was evaluated by direct immunofluorescence (DIF) and qPCR in affected or not oral mucosa from PV patients compared with uninjured PF mucosa. IgG anti‐HSV1 was higher in the PV group compared with all groups. IgG anti‐CMV resulted higher in PV group compared with PF patients and PV relatives. HSV1 was confirmed by DIF and qPCR on oral samples from patients with PV. Lack of HSV1 expression in the oral mucosa of patients with PF corroborate that immunosuppressive therapy cannot be the main cause for HSV1 replication in PV disease.

Paracoccidioidomycosis and cryptococcosis with localized skin manifestations: report of two cases in the elderly

Distinct cases of Paracoccidioidomycosis and Cryptococcosis with atypical and localized skin manifestation on the upper limbs of two elderly patients are reported. In the 2nd one, he presented asymptomatic pulmonary cancer; the blood tests for fungal infection were negative, and the etiologic agents were seen in skin biopsy samples. This report emphasizes the importance of the differential diagnosis of infectious diseases in elderly patients.

Superexpresión de metalotioneínas, nichos de células madre y campos de cancerización en gliomagénesis experimental

INTRODUCAO: celulas-tronco podem originar e perpetuar o crescimento tumoral, porem sao pouco conhecidas na gliomagenese. As metalotioneinas (MTs) sao proteinas envolvidas na oncogenese, e sua a imunopositividade pode ser utilizada como marcador de mutacao de celulas-tronco. Objetivo: estudar a expressao de MT no modelo experimental da ENU e estabelecer um modelo experimental para monitorar as celulas-tronco glioma na oncogenese. METODOS: Trinta e seis ratos machos da raca Wistar foram divididos em dois grupos; o grupo de animais experimental foi tratado dentro de 24 horas apos o nascimento (ratos neonatos) com uma dose unica de N-etil N-nitrosoureia (ENU) (40 mg/kg). Nos animais do grupo controle, injetou-se o mesmo volume de solucao salina. Os animais do grupo experimental foram subdivididos em tres grupos de acordo com o tempo da eutanasia, como se segue: o Grupo 1 (G1) sofreu eutanasia com a idade de 30 dias; o Grupo 2 (G2), com 180 dias e o Grupo 3 (G3) sofreu eutanasia logo apos o surgimento de sinais de existencia de tumor do sistema nervoso, com uma media de idade de 321 dias. A deteccao imunohistoquimica da proteina MT em cortes da medula espinhal fixadas em acetona fria e embebidas em parafina foi realizada pelo metodo do complexo streptavidina-avidina-biotina-imuno peroxidase. RESULTADOS: por meio de modelos experimentais de gliomagenese induzida pela N-etil N-nitrosoureia, foi possivel detectar celulas-tronco de tumor putativo no inicio da oncogenese, analisar um processo de cancerizacao de campo e observar uma relacao morfologica entre celulas positivas para MT e vasos sanguineos. CONCLUSOES: este modelo experimental reprodutivel permite outros estudos sobre a origem, desenvolvimento e fatores reguladores da gliomatogenese.Introduction: stem cells may originate and perpetuate the tumor growth, but they are poorly known in gliomagenesis. Metallothioneins (MTs) are proteins involved in oncogenesis and immunopositivity, for MT may be used as a stem cell mutation marker. Objective: to study the MT expression in the ENU experimental model and to establish an experimental model to track glioma stem cells in early oncogenesis. Methods: Thirtysix male Wistar rats were divided into two groups; the experimental group was treated within 24 hours after birth (neonate rats) with a single dose of subcutaneously injected N-ethyl N-nitrosourea ENU (40 mg/ kg body weight). The control animals were injected with the same volume of saline. These experimental animals were subdivided into three groups according to the euthanize time, as follows: the Group 1 (G1) was euthanized at the age of 30 days; the Group

A superexpressão de metalotioneínas em células-tronco de áreas cancerígenas na gênese de glioma experimental

INTRODUCAO: celulas-tronco podem originar e perpetuar o crescimento tumoral, porem sao pouco conhecidas na gliomagenese. As metalotioneinas (MTs) sao proteinas envolvidas na oncogenese, e sua a imunopositividade pode ser utilizada como marcador de mutacao de celulas-tronco. Objetivo: estudar a expressao de MT no modelo experimental da ENU e estabelecer um modelo experimental para monitorar as celulas-tronco glioma na oncogenese. METODOS: Trinta e seis ratos machos da raca Wistar foram divididos em dois grupos; o grupo de animais experimental foi tratado dentro de 24 horas apos o nascimento (ratos neonatos) com uma dose unica de N-etil N-nitrosoureia (ENU) (40 mg/kg). Nos animais do grupo controle, injetou-se o mesmo volume de solucao salina. Os animais do grupo experimental foram subdivididos em tres grupos de acordo com o tempo da eutanasia, como se segue: o Grupo 1 (G1) sofreu eutanasia com a idade de 30 dias; o Grupo 2 (G2), com 180 dias e o Grupo 3 (G3) sofreu eutanasia logo apos o surgimento de sinais de existencia de tumor do sistema nervoso, com uma media de idade de 321 dias. A deteccao imunohistoquimica da proteina MT em cortes da medula espinhal fixadas em acetona fria e embebidas em parafina foi realizada pelo metodo do complexo streptavidina-avidina-biotina-imuno peroxidase. RESULTADOS: por meio de modelos experimentais de gliomagenese induzida pela N-etil N-nitrosoureia, foi possivel detectar celulas-tronco de tumor putativo no inicio da oncogenese, analisar um processo de cancerizacao de campo e observar uma relacao morfologica entre celulas positivas para MT e vasos sanguineos. CONCLUSOES: este modelo experimental reprodutivel permite outros estudos sobre a origem, desenvolvimento e fatores reguladores da gliomatogenese.Introduction: stem cells may originate and perpetuate the tumor growth, but they are poorly known in gliomagenesis. Metallothioneins (MTs) are proteins involved in oncogenesis and immunopositivity, for MT may be used as a stem cell mutation marker. Objective: to study the MT expression in the ENU experimental model and to establish an experimental model to track glioma stem cells in early oncogenesis. Methods: Thirtysix male Wistar rats were divided into two groups; the experimental group was treated within 24 hours after birth (neonate rats) with a single dose of subcutaneously injected N-ethyl N-nitrosourea ENU (40 mg/ kg body weight). The control animals were injected with the same volume of saline. These experimental animals were subdivided into three groups according to the euthanize time, as follows: the Group 1 (G1) was euthanized at the age of 30 days; the Group