Cutaneous histoplasmosis disclosing an HIV-infection

Histoplasmosis is a systemic mycosis endemic in extensive areas of the Americas. The authors report on an urban adult male patient with uncommon oral-cutaneous lesions proven to be histoplasmosis. Additional investigation revealed unnoticed HIV infection with CD4+ cell count of 7/mm³. The treatment was performed with amphotericin B, a 2065 mg total dose followed by itraconazole 200mg/daily plus antiretroviral therapy with apparent cure. Histoplasmosis is an AIDS-defining opportunistic disease process; therefore, its clinical diagnosis must drive full laboratory investigation looking for unnoted HIV-infection.     

Comparison of the two-dimensional and multiplanar methods and establishment of a new constant for the measurement of fetal lung volume

Objectives. To compare the two-dimensional (2D) and multiplanar methods in the measurement of lung volume in normal fetuses, to obtain a new constant to be incorporated into the 2D equation, and to apply the new equation in fetuses with pulmonary hypoplasia (PH) confirmed postnatally.

Methods. A cross-sectional study was performed on 51 pregnant women at between 20 and 35 weeks of gestation. The ellipsoid formula (x × y × z × 0.52) was used to calculate lung volume by the 2D method. A sequence of multiple planes with 2.0-mm intervals was used with the multiplanar method. In order to compare the techniques, the intra-class correlation coefficient (ICC) and the Student's t-test (p) were used. First-order linear regressions were used to establish a new constant, with three-dimensional (3D) lung volume as dependent variable and gestational age and 2D volume as independent variables. In order to validate it, the new equation was applied to 11 fetuses with confirmed lethal PH.

Results. The mean volumes obtained by the 2D method were overestimated when compared to the multiplanar method (right lung: 23.87 vs. 18.26 mL, respectively, p < 0.001 and left lung: 16.18 vs. 14.33 mL, respectively, p = 0.008). Using a first-order polynomial regression, new constants were obtained for the right lung (0.152) and for the left lung (0.167). When compared to the traditional formula, the new equation presented higher sensitivity (18.1%) in predicting lethal PH.

Conclusion. The recalculated 2D equation can be a promising alternative to 3D ultrasonography in the prediction of PH.     

Analyses of gait and jump tasks in female obese adolescents

In spite of the advances in knowledge on the multi-factorial nature of obesity, many questions related to the consequences of the disease continue to be unanswered. Several studies have reported biomechanic and kinematic adaptation and alterations in walking and in tasks of every day life, motivated by the additional load of fat mass in children and adults. The main objective of this study was to understand the effect of obesity in the electromyographic activity of four lower extremity muscles during three speeds of walking and during a countermovement jump (CMJ) in twenty two (9 obese and 13 normal weight) female adolescents aged 13. Although electromyographic differences were not observed between groups for normal, slow and fast speeds, data suggests that the preferred pace of the obese is less efficient than that of the normal weight group. In CMJ task, differences in the after-fall jump phase were observed. More studies are needed to explain if the few differences observed between groups are caused by the bigger amount of fat mass.     

Glutathione transferase pi (GSTpi) expression in breast cancer: an immunohistochemical and molecular study

Breast cancer is the most frequent cancer in women worldwide. Prognostic markers are important for diagnosis, allowing therapeutic strategies to be defined more efficiently. The expression of the glutathione S-transferase pi isoenzyme (GSTpi) in tumor cells has been evaluated as a predictor of prognosis and in response to cytotoxic treatments. Its immunoexpression was assessed in 63 women diagnosed with invasive ductal carcinoma in a retrospective study. The results were statistically correlated with clinicopathological parameters of patients. The results showed that high GSTpi expression was related to p53-positive tumors, grade III histology, large tumor size and death (p < 0.05). The 37 patients who received adjuvant treatment, checked separately, showed high expression of GSTpi in relation to local recurrence, metastasis and death (p < 0.05). In addition, high levels of GSTpi expression were significantly associated with a shorter overall survival (p < 0.05). To confirm this suspicion, GSTpi gene expression was checked by Real-time PCR in neoplastic mammary cells cultured and subjected to treatment with doxorubicin. Our results suggest that high levels of GSTpi may be related to the development of resistance to chemotherapy in these tumors, the response of these tumors to treatment and the clinical course of the patients involved.     

An immunohistochemical study of interleukin-8 (IL-8) in breast cancer

The use of prognostic markers for breast cancer is important for routine diagnosis and research. Interleukin-8 is a chemotactic cytokine produced by several cell types in response to inflammation, however, its expression, regulation and function are poorly understood. Recent studies have associated angiogenesis and inflammatory processes with tumor malignancy. The present study investigated the correlation between interleukin-8 expression and breast cancer prognosis. Interleukin-8 expression was assessed in 72 women with mammary neoplasia by immunohistochemistry and the results were statistically correlated with clinical-pathological findings. There was an inverse correlation between interleukin-8 expression and metastasis (p = 0.03) and/or local recurrence (p = 0.02). In the patient group that received post-surgery chemotherapy and radiotherapy, a lower interleukin-8 expression was found in those women that showed local recurrence (p = 0.01). Multivariate logistic regression showed estrogen receptor negativity, progesterone positivity and metastasis with increased risk of death (p < 0.05). The data reflect the complexity of the role of interleukin-8 in tumor microenvironment and support its classification as a possible prognostic marker, although more studies are necessary for its inclusion in clinical practice.     

Harpalycin 2 inhibits the enzymatic and platelet aggregation activities of PrTX-III, a D49 phospholipase A

ABSTRACT: BACKGROUND: Harpalycin 2 (HP-2) is an isoflavone isolated from the leaves of Harpalyce brasiliana Benth., a snakeroot found in northeast region of Brazil and used in folk medicine to treat snakebite. Its leaves are said to be anti-inflammatory. Secretory phospholipases A2 are important toxins found in snake venom and are structurally related to those found in inflammatory conditions in mammals, as in arthritis and atherosclerosis, and for this reason can be valuable tools for searching new anti-phospholipase A2 drugs. METHODS: HP-2 and piratoxin-III (PrTX-III) were purified through chromatographic techniques. The effect of HP-2 in the enzymatic activity of PrTX-III was carried out using 4-nitro-3-octanoyloxy-benzoic acid as the substrate. PrTX-III induced platelet aggregation was inhibited by HP-2 when compared to aristolochic acid and p-bromophenacyl bromide (p-BPB). In an attempt to elucidate how HP-2 interacts with PrTX-III, mass spectrometry, circular dichroism and intrinsic fluorescence analysis were performed. Docking scores of the ligands (HP-2, aristolochic acid and p-BPB) using PrTX-III as target were also calculated. RESULTS: HP-2 inhibited the enzymatic activity of PrTX-III (IC50 11.34 [PLUS-MINUS SIGN] 0.28 mug/mL) although it did not form a stable chemical complex in the active site, since mass spectrometry measurements showed no difference between native (13,837.34 Da) and HP-2 treated PrTX-III (13,856.12 Da). A structural analysis of PrTX-III after treatment with HP-2 showed a decrease in dimerization and a slight protein unfolding. In the platelet aggregation assay, HP-2 previously incubated with PrTX-III inhibited the aggregation when compared with untreated protein. PrTX-III chemical treated with aristolochic acid and p-BPB, two standard PLA2 inhibitors, showed low inhibitory effects when compared with the HP-2 treatment. Docking scores corroborated these results, showing higher affinity of HP-2 for the PrTX-III target (PDB code: 1GMZ) than aristolochic acid and p-BPB. HP-2 previous incubated with the platelets inhibits the aggregation induced by untreated PrTX-III as well as arachidonic acid. CONCLUSION: HP-2 changes the structure of PrTX-III, inhibiting the enzymatic activity of this enzyme. In addition, PrTX-III platelet aggregant activity was inhibited by treatment with HP-2, p-BPB and aristolochic acid, and these results were corroborated by docking scores.     

Skeletal muscle major histocompatibility complex class I and II expression differences in adult and juvenile dermatomyositis

OBJECTIVE:

To analyze major histocompatibility complex expression in the muscle fibers of juvenile and adult dermatomyositis.

METHOD:

In total, 28 untreated adult dermatomyositis patients, 28 juvenile dermatomyositis patients (Bohan and Peter''s criteria) and a control group consisting of four dystrophic and five Pompe''s disease patients were analyzed. Routine histological and immunohistochemical (major histocompatibility complex I and II, StreptoABComplex/HRP, Dakopatts) analyses were performed on serial frozen muscle sections. Inflammatory cells, fiber damage, perifascicular atrophy and increased connective tissue were analyzed relative to the expression of major histocompatibility complexes I and II, which were assessed as negatively or positively stained fibers in 10 fields (200X).

RESULTS:

The mean ages at disease onset were 42.0±15.9 and 7.3±3.4 years in adult and juvenile dermatomyositis, respectively, and the symptom durations before muscle biopsy were similar in both groups. No significant differences were observed regarding gender, ethnicity and frequency of organ involvement, except for higher creatine kinase and lactate dehydrogenase levels in adult dermatomyositis (p<0.050). Moreover, a significantly higher frequency of major histocompatibility complex I (96.4% vs. 50.0%, p<0.001) compared with major histocompatibility complex II expression (14.3% vs. 53.6%, p = 0.004) was observed in juvenile dermatomyositis. Fiber damage (p = 0.006) and increased connective tissue (p<0.001) were significantly higher in adult dermatomyositis compared with the presence of perifascicular atrophy (p<0.001). The results of the histochemical and histological data did not correlate with the demographic data or with the clinical and laboratory features.

CONCLUSION:

The overexpression of major histocompatibility complex I was an important finding for the diagnosis of both groups, particularly for juvenile dermatomyositis, whereas there was lower levels of expression of major histocompatibility complex II than major histocompatibility complex I. This finding was particularly apparent in juvenile dermatomyositis.     

Influence of food restriction on lipid profile and spontaneous glucose levels in male rats subjected to paradoxical sleep deprivation

OBJECTIVES:

The purpose of this study was to determine the paired consequences of food restriction and paradoxical sleep deprivation on lipid profile and spontaneous glucose levels in male rats.

METHOD:

Food restriction began at weaning, with 6 g of food being provided per day, which was subsequently increased by 1 g per week until reaching 15 g per day by the eighth week. At adulthood, both rats subjected to food restriction and those fed ad libitum were exposed to paradoxical sleep deprivation for 96 h or were maintained in their home-cage groups.

RESULTS:

Animals subjected to food restriction exhibited a significant increase in high-density lipoprotein levels compared to animals that were given free access to food. After the paradoxical sleep deprivation period, the food-restricted animals demonstrated reduced concentrations of high-density lipoprotein relative to their respective controls, although the values for the food-restricted animals after sleep deprivation were still higher than those for the ad libitum group. The concentration of low-density lipoproteins was significantly increased in sleep-deprived animals fed the ad libitum diet. The levels of triglycerides, very low-density lipoproteins, and glucose in food-restricted animals were each decreased compared to both ad libitum groups.

CONCLUSION:

These results may help to illustrate the mechanisms underlying the relationship between sleep curtailment and metabolism and may suggest that, regardless of sleep deprivation, dietary restriction can minimize alterations in parameters related to cardiovascular risk.