Fabiana Pirani Carneiro

Inhibitory avoidance acquisition in adult rats exposed to a combination of ethanol and methylmercury during central nervous system development.

Previous studies have shown that combined exposure to ethanol (EtOH) and methylmercury (MeHg) in rats during central nervous system development produces several behavioural impairments. This present study was done to investigate inhibitory avoidance acquisition and panic-like disorders in rats in an elevated T-maze (ETM) model of anxiety. Pregnant rats received tap water or EtOH at 22.5% (w/v) (6.5 g/kg per day, by gavage) during pregnancy and lactation. On the 15th day of pregnancy, half of each group received MeHg (8 mg/kg, by gavage). Adult offspring intoxicated by both EtOH + MeHg showed an increase in the ETM re-exposure time. Upon analysis of the enclosed arms latency in baseline and avoidance 1 session it was observed that the rats spent less time inside the arm, suggesting impairment in their short-term memory. The escape latency decreased for EtOH + MeHg and also for EtOH and MeHg groups, suggesting panic-like behaviour. After 24-h and 7-day trials (tests and retests), MeHg and EtOH + MeHg groups had their latency in the enclosed arm reduced with the exception of the EtOH group, revealing memory impairment. Upon analysis of the risk assessment, animals treated with EtOH + MeHg were the only ones to show a decrease in all evaluation stages. This study demonstrates that the exposure to both EtOH and MeHg has an impact on memory and panic-related behaviours, leading to the assertion that this association of toxicants should be studied more in detail to clarify the precise mechanisms of these pharmacological effects.

Foxp3 expression in lesions of the different clinical forms of American tegumentary leishmaniasis.

As the diversity in clinical presentation of American tegumentary leishmaniasis (ATL) is determined mainly by the immune response of host, our aim was to evaluate the in situ expression of Foxp3 [marker of regulatory T (Treg) cell] in lesions of the different clinical forms of ATL. Foxp3+ cells were observed in 39·5% (32/81) of the samples and the number of positive cells was low in all the clinical forms. Even presenting a significantly lower number of CD4+ T cells, diffuse cutaneous leishmaniasis (DCL) showed a higher expression of Foxp3 when compared with localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). In LCL and MCL, the number of Foxp3+ cells correlated positively with the number of apoptotic cells (active caspase‐3+ cells). A positive correlation was also observed between the expression of active caspase‐3 and FasL in these clinical forms. Our data suggest that increased number of Treg cells may be associated to the hyporesponsiveness observed in DCL and also indicate that the apoptosis may be a possible mechanism of action of Foxp3+ Treg cell in LCL and MCL. However, further studies are required to better understand the mechanism of action of Treg cell.

Lobomycosis: diagnosis and management of relapsed and multifocal lesions

We report a case of lobomycosis in the left leg of a patient that had traveled to the endemic Brazilian Amazon region. After surgical resection of the lesion, there was relapse with local dissemination of the disease and the treatment was successfully performed by oral itraconazole and cryosurgery.

Photodynamic therapy mediated by acai oil (Euterpe oleracea Martius) in nanoemulsion: A potential treatment for melanoma.

Melanoma is the most aggressive and lethal form of skin cancer, responsible for >80% of deaths. Standard treatments for late-stage melanoma usually present poor results, leading to life-threatening side effects and low overall survival. Thus, it is necessary to rethink treatment strategies and design new tools for the treatment of this disease. On that ground, we hereby report the use of acai oil in nanoemulsion (NanoA) as a novel photosensitizer for photodynamic therapy (PDT) used to treat melanoma in in vitro and in vivo experimental models. NIH/3T3 normal cells and B16F10 melanoma cell lines were treated with PDT and presented 85% cell death for melanoma cells, while maintaining high viability in normal cells. Flow cytometry indicated that cell death occurred by late apoptosis/necrosis. Tumor bearing C57BL/6 mice treated five times with PDT using acai oil in nanoemulsion showed tumor volume reduction of 82% in comparison to control/tumor group. Necrotic tissue per tumor area reached its highest value in PDT-treated mice, supporting PDT efficacy. Overall, acai oil in nanoemulsion was an effective photosensitizer, representing a promising source of new photosensitizing molecules for PDT treatment of melanoma, a tumor with an inherent tendency to be refractory for this type of therapy.

Study on adhesion formation and the healing of colon anastomosis in rats with induced peritoneal sepsis

PURPOSE To evaluate the effects of abdominal sepsis on adhesion formation and colon anastomosis healing in rats. METHODS Forty rats were distributed in two groups containing 20 rats each for left colon anastomosis in the presence (Group S) or absence (Group N) of induced sepsis by cecal ligation and puncture. Each group was divided into subgroups for euthanasia on the third (N3 and S3) or seventh (N7 or S7) post-operative day. The amount of adhesions was evaluated and a segment of the colon was removed for histopathologic analysis, bursting strength assessment, hydroxyproline and the determination of tissue collagen. RESULTS The subjects which underwent cecal ligation and puncture presented a higher amount of intra-abdominal adherences in both third (p=0,00) and seventh (p=0,00) post-operatory days. Smaller bursting strengths were found in the S3 subgroup, and greater bursting strengths were found in the S7 subgroup. There was no difference in the variations on the concentrations of hydroxyproline, tissue collagen and histopathology. CONCLUSIONS The peritoneal infection which was developed by cecal ligation and puncture raised the amount of intra-cavitary adhesions. There was a decrease in the amount of colonic anastomosis on the third post-operatory day with a following raise on the seventh without any effects on other healing parameters.

Rhinoscleroma causing severe bilateral nasal obstruction

Rhinoscleroma is a chronic, infectious and granulomatous disease of the respiratory tract. There is often a delay in diagnosis due to unfamiliarity with the disease and also because culture is not always positive. We report a case in a 26-year-old woman with granular mass obstructing bilateral nasal cavities and causing breathing difficulty. Histopathological examination showed characteristic Mikulicz histiocytes containing numerous Gram-negative intracellular rod-shaped bacilli consistent with the diagnosis of rhinoscleroma. The patient was treated with gemifloxacin and tetracycline and remains asymptomatic over a year follow-up period. It is important to consider rhinoscleroma in cases of chronic nasal obstruction. As culture is not always positive, histopathological examination may be crucial to the diagnosis.

Association between human papillomavirus infection and cytological abnormalities during early follow-up of invasive cervical cancer†

Considering the limitations of cytology for detection of residual cervical cancer after radiotherapy, the aim of this study was to evaluate the frequency and viral load of high‐risk HPV in cervical and vaginal samples during the early follow‐up of patients treated for invasive cervical cancer and correlate the results with cytological examination. Conventional cytology and hybrid capture test were performed on cervical and vaginal samples of 52 women with invasive cervical carcinoma 3 months after therapy. High‐risk HPV was detected in 46.1% of the samples and the median and the range of the ratio relative light unit (RLU)/cutoff (CO) (estimated viral load) in positive samples was 1.71 (1–2120.03). No significant difference was observed in viral frequency and in median of the ratio RLU/CO between samples of patients at different stages (I–III) and between cervical samples, from patients treated by exclusive radiotherapy with or without chemotherapy, and vaginal samples, from patients who underwent to hysterectomy and radiotherapy with or without chemotherapy. Cytological abnormalities were more frequent significantly in samples with HPV than in samples without HPV. The viral load was also higher significantly in samples with cytological abnormalities when compared with the samples without cytological abnormalities. In conclusion, HPV detection methods may be useful during the early follow‐up as a complement to conventional cytology for the diagnosis of residual cervical cancer after radiotherapy. J. Med. Virol. 84: 1115–1119, 2012.

Effects of carbon dioxide pneumoperitoneum on hepatic and renal morphology of rats after segmental colectomy and colonic anastomosis

PURPOSE To evaluate the effects of increased intraperitoneal pressure caused by carbon dioxide pneumoperitoneum on the hepatic and renal morphology of rats. METHODS Fifty-four adult male rats were randomly divided into three groups (P, PP and C) after anesthesia: P - in 18 animals, pneumoperitoneum was established for 30 minutes immediately before laparotomy; PP - in 18 animals, pneumoperitoneum was established for 60 minutes divided into 30 immediately before laparotomy and 30 after abdominal closure; control group (C) - 18 animals underwent laparotomy without pneumoperitoneum induction. The pneumoperitoneum was maintained at a pressure of 5 mm Hg. Nine animals in each group were killed on the 3(rd) and 7(th) postoperative days, when kidney and liver samples were collected for morphological analysis. The liver specimens were stained with hematoxylin and eosin (HE), and the kidney specimens, with HE and von Kossa. Blinded examiners analyzed the slides. RESULTS No changes in renal morphology were found. Liver samples showed histological signs of degeneration in animals in the pneumoperitoneum groups killed on the 7(th) postoperative day (p=0.029). CONCLUSION The CO(2) pneumoperitoneum did not affect renal morphology but caused hydropic degeneration in the liver of animals killed on the 7(th) postoperative day.

The H63D genetic variant of the HFE gene is independently associated with the virological response to interferon and ribavirin therapy in chronic hepatitis C.

Background Conflicting results have been reported in studies evaluating the relationship between serum markers of iron overload, liver iron deposits, and HFE mutations (C282Y and H63D) in chronic hepatitis C patients, and also their impact on the response to therapy in these patients. Aim To evaluate the role of HFE mutations in the severity of liver disease and in the response to therapy in chronic hepatitis C. Methods Two hundred and sixty-four hepatitis C patients treated with standard interferon and ribavirin were divided into two groups according to type of antiviral response: sustained virological response (SVR) and nonresponse or relapse. We evaluated the relationship between HFE mutation and the type of antiviral response, clinical data, biochemical tests, liver histopathology, virological data, and HFE mutations. Results Of the 264 patients, 88 (32.1%) had SVR whereas 67.9% had nonresponse or relapse. Liver iron deposits were observed in 49.2% of the patients. The factors associated with SVR were hepatitis C virus genotype 2 or 3, transferrin saturation value of 45% or less, and detection of the H63D mutation. HFE mutation was more frequent in patients with iron deposits, but without association with serum iron biochemistry or severity of liver disease. Steatosis was more frequent in patients with liver iron deposits. Conclusion The H63D mutation was an independent factor associated with SVR in chronic hepatitis C patients, as also were hepatitis C virus genotype 2 or 3 and transferrin saturation value of 45% or less. Moreover, the H63D mutation was associated with liver iron deposits.

Role of nicotine on cognitive and behavioral deficits in sepsis-surviving rats.

Sepsis and its complications are important causes of mortality in intensive care units and sepsis survivors may present long-term cognitive and emotional impairments, including memory deficits and anxiety symptoms. In the present study, we investigated whether repeated nicotine administration can affect the behavioral changes in sepsis-surviving rats. Male Wistar rats were divided in two groups: sham-operated and experimental sepsis induced by cecal ligation and puncture (CLP). The animals were injected subcutaneously with nicotine (0.1 mg/kg) or vehicle once a day during 1 week before and/or 1 week after sepsis induction. Thirty minutes after the last administration (i.e., 7 days after surgery), the animals were tested in the open field, elevated plus-maze and step-down inhibitory avoidance tasks. The repeated nicotine treatment did not affect the survival rate in the sepsis group (50%). Moreover, no significant changes on locomotor activity were observed in the sepsis group while the treatment with nicotine during 1 week after surgery reduced the locomotion of sepsis-surviving rats in the open field. It is important to note that both schedules of nicotine treatment (prior and/or after CLP) improved the sepsis-induced anxiogenic-like responses. Interestingly, nicotine was able to improve short- and long-term inhibitory avoidance memory impairments, observed in sepsis survivors, only when administered during 2 consecutive weeks (i.e., prior and after CLP). Taken together, these results indicate that repeated nicotine administration does not alter the survival rate in rats submitted to CLP and provide new evidence that nicotine can improve long-lasting memory impairments and anxiogenic-like responses in sepsis-surviving animals.