Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivoantitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

Characterization of new sources of derivative starches as wall materials of essential oil by spray drying

Starch derivatives of taro (Colocasia esculenta L. Schott) and rice were characterized as wall materials of orange oil (d-limonene) by spray drying. Native starches were initially hydrolyzed with HCl and then esterified. Succinylated starches were modified using a conventional method in a slurry and were extruded; whereas, the phosphorylated starches were modified using the extrusion process. Viscosity and solubility of starches reduced after acid hydrolysis, derivatization, and extrusion. The particle size of the wall materials ranged between 20.05 and 31.81 µm. The encapsulation efficiency of the phosphorylated taro, rice, and waxy corn starches was 96.9, 96.8 and 97.1% respectively, and 98.6, 98.1, and 98.8% for succynilated taro, rice, and waxy corn starches, respectively. Starch derivatives of taro and rice could potentially be used as wall materials of orange oil d-limonene.

From restrained golden age to creeping platinum age: A periodization of Latin American development in the Robinsonian tradition

ABSTRACTThis paper analyzes Joan Robinson's growth model, and then adapted in order to provide an exploratory taxonomy of Growth Eras. The Growth Eras or Ages were for Robinson a way to provide logical connections among output growth, capital accumulation, the degree of thriftiness, the real wage and illustrate a catalogue of growth possibilities. This modified taxonomy follows the spirit of Robinson's work, but it takes different theoretical approaches, which imply that some of her classifications do not fit perfectly the ones here suggested. Latin America has moved from a Golden Age in the 1950s and 1960s, to a Leaden Age in the 1980s, having two traverse periods, one in which the process of growth and industrialization accelerated in the late 1960s and early 1970s, which is here referred to as a Galloping Platinum Age, and one in which a process of deindustrialization, and reprimarization and maquilization of the productive structure took place, starting in the 1990s, which could be referred to as a Creeping Platinum Age.

A single method to stain Malassezia furfur and Corynebacterium minutissimum in scales

A single and practical method to slain Malassezia furfur and Corynebacterium minutissimum in lesions' scales is described. The scales are collected by pressing small pieces of scotch tape (about 4 cm lenght and 2 cm width) onto the lesions and following withdrawl the furfuraceous scales will remain on the glue side. These pieces are then immersed for some minutes in lactophenol-cotton blue stain. Following absorption of the stain the scales are washed in current water to remove the excess of blue stain, dried with filter paper, dehydrated via passage in two bottles containing absolute alcohol and then placed in xylene in a centrifugation tube. The xylene dissolves the scotch tape glue and the scales fall free in the tube. After centrifugation and decantation the scales concentrated on the bottom of the tube are collected with a platinum-loop, placed in Canada balsam on a microscopy slide and closed with a cover slip. The preparations are then ready to be submitted to microscopic examination. Other stains may also be used instead of lactophenol-cotton blue. This method is simple, easily performed, and offers good conditions to study these fungi as well as being useful for the diagnosis of the diseases that they cause.

Paracoccidioidomycosis: infiltrated, sarcoid-like cutaneous lesions misinterpreted as tuberculoid leprosy

The authors report a case of paracoccidioidomycosis misinterpreted as tuberculoid leprosy, both on clinical and histological examination. Sarcoid-like cutaneous lesion as the initial presentation is rare in young patient with paracoccidioidomycosis and can simulate other infectious or inflammatory diseases. On histology, tuberculoid granuloma presented similar difficulties. Treatment with dapsone, a sulfonamide derivative, could have delayed the presumed natural clinical course to the classical juvenile type of paracoccidioidomycosis, observed only 24 months after the patient had been treated for leprosy.

ANTHELMINTIC ACTIVITY OF CHLOROPHYLLIN AGAINST DIFFERENT LARVAL STAGES OF Fasciola gigantica

Fasciolosis is a food borne zoonosis, caused by the digenetic trematode Fasciola. Freshwater lymnaeid snails are the intermediate host of the trematodes. Chlorophyllin, a semi-synthetic derivative of chlorophyll and its formulations obtained from freeze dried cow urine (FCU) had their toxicity tested against redia and cercaria larvae of F. gigantica. The larvicidal activity of chlorophyllin and its formulations were found to depend on both, time and concentration used against the larvae. Toxicity of chlorophyllin + FCU (1:1 ratio) in sunlight against redia larva (8 h LC50: 0.03 mg/mL) was more pronounced than using just chlorophyllin (8 h LC50: 0.06 mg/mL). Toxicity of chlorophyllin + FCU in sunlight against redia (8 h LC50: 0.03 mg/mL) was higher than against cercaria (8 h LC50: 0.06 mg/mL). The larvicidal activity of chlorophyllin in sunlight (redia/cercaria larvae: 8 h LC50: 0.06 mg/mL) was more pronounced than under laboratory conditions (redia: 8 h LC50: 22.21 mg/mL/, cercaria 8 h LC50: 96.21 mg/mL). Toxicity of FCU against both larvae was lower than that of chlorophyllin and chlorophyllin + FCU. Chlorophyllin and its formulations + FCU were 357.4 to 1603.5 times more effective against redia/cercaria larvae in sunlight than under laboratory conditions. The present study has shown that chlorophyllin formulations may be used as potent larvicides against fasciolosis.

Prevalence and incidence of Mycobacterium tuberculosis infection in nursing students in Vitória, Espírito Santo

This prospective study evaluated the incidence of Mycobacterium tuberculosis infection among nursing students at the Federal University of Espírito Santo, using the purified protein derivative test. In parallel, we evaluated whether knowledge on tuberculosis transmission mechanisms had any impact on nursing students' attitudes in relation to the risk of tuberculosis infection. The incidence of tuberculin conversion was 10.5% per year (p=0.035, 95% CI = 3.63-17.43), whereas the expected conversion rate in the overall population in Brazil is 0.5% per year. These results indicate nursing students as a group at risk for TB infection. Among the risk factors studied only the use of NIOSH95 masks was associated with protection against infection (RR=0.2). Furthermore there was no statistical difference among students that PPD converted and those who remained negative regarding disease knowledge and the existence of adequate facilities for patient hospitalization. Our data reinforces the need for implementing special biosafety programs targeting this professional group.

The secretory immunoglobulin A response to Mycobacterium tuberculosis in a childhood population

We report on the measurement of saliva anti-Purified Protein Derivative sIgA and 38kDa antibodies from 127 children, of whom 31 were strong tuberculosis suspects and 96 were healthy contact children. The results concerning the percentage of children with antibody reactivity to PPD and 38kDa antigens showed that, of these 2 antigens, 38kDa induced higher reactivity in patients positive and negative for the Tuberculin Skin Test (28% and 16.6%, respectively) in comparison to controls positive and negative for the TST (11.7% and 7.1%, respectively). There was a statistically significant difference between patients positive and controls negative for the TST. In relation to the Purified Protein Derivative antigen, while 14.2% of patients positive for the TST showed antibody reactivity to the PPD antigen, no patients negative for the TST had reactivity to this antigen. The findings suggest that these two antigens seem be associated with a different development of the mucosal defence mechanisms mediated by sIgA against Mycobacterium tuberculosis.

Nosocomial Mycobacterium tuberculosis transmission among healthcare students in a high incidence region, in Vitória, State of Espírito Santo

This open comparative study for evaluating hypersensitivity to tuberculin among medical students (n=441), nursing students (n=178) and economics students (n=230) in Vitória, State of Espírito Santo, had the aim of assessing whether the prevalence of positive tuberculin tests among healthcare students could be used as a sentinel event for nosocomial transmission in localities with high endemicity. There was a significant change in the frequency of purified protein derivative reactivity in the nursing students (20. 3%) and medical students (18. 4%), in comparison with the economics students (6%) (p <0. 001). As expected, the medical and nursing students had more knowledge about tuberculosis than did the economics students (p <0. 001). Our data suggest that the incidence of Mycobacterium tuberculosis infection among nursing and medical students in our region, which has high endemicity of tuberculosis, does not differ from what is found in low-incidence countries. These data reinforce the need for implementing biosafety programs for this target population.

Abnormal spontaneous interleukin 8 receptor expression: a brief report of two cases

Interleukin 8 (CXCL8) is an autocrine chemokine specific for the chemoattraction and activation of granulocytes, NKT cells and T lymphocytes. Patients with tuberculosis and latent Mycobacterium tuberculosis infection were assessed for the spontaneous expression of CXCR1 (CD128) and CXCR2 on lymphocytes and monocytes. Compared with ex vivo profiles, increased spontaneous CXCR2 expression and normal CXCR1 expression were found on lymphocytes in two out of 59 individuals. Monocytes showed normal ex vivo profiles for both receptors. After stimulation with purified protein derivative, the in vitro levels of CXCL8 were below the median levels of all patients with prior tuberculosis. Spontaneous CXCR2 modulation did not cause notable variation in the in vitro levels of CXCL8.

Chemotherapy versus best supportive care in stage IV non-small cell lung cancer, non metastatic to the brain

Stage IV non-small cell lung cancer is a fatal disease, with a median survival of 14 months. Systemic chemotherapy is the most common approach. However the impact in overall survival and quality of life still a controversy. OBJECTIVES: To determine differences in overall survival and quality of life among patients with stage IV non-small cell lung cancer non-metastatic to the brain treated with best supportive care versus systemic chemotherapy. PATIENTS: From February 1990 through December 1995, 78 eligible patients were admitted with the diagnosis of stage IV non-small cell lung cancer . Patients were divided in 2 groups: Group A (n=31 -- treated with best supportive care ), and Group B (n=47 -- treated with systemic chemotherapy). RESULTS: The median survival time was 23 weeks (range 5 -- 153 weeks) in Group A and 55 weeks (range 7.4 -- 213 weeks) in Group B (p=0.0018). In both groups, the incidence of admission for IV antibiotics and need of blood transfusions were similar. Patients receiving systemic chemotherapy were also stratified into those receiving mytomycin, vinblastin, and cisplatinum, n=25 and those receiving other combination regimens (platinum derivatives associated with other drugs, n=22). Patients receiving mytomycin, vinblastin, and cisplatinum, n=25 had a higher incidence of febrile neutropenia and had their cycles delayed for longer periods of time than the other group. These patients also had a shorter median survival time (51 versus 66 weeks, p=0.005). CONCLUSION: In patients with stage IV non-small cell lung cancer, non-metastatic to the brain, chemotherapy significantly increases survival compared with best supportive care.

Effects of lisinopril on experimental ischemia in rats. Influence of infarct size

OBJECTIVE - Angiotensin-converting enzyme inhibitors (ACEIs) have gained importance in preventing or attenuating the process of ventricular remodeling after myocardial infarction. The significance of infarct size in regard to the response to ACEIs, however, is controversial. This study aimed to analyze the effects of lisinopril on mortality rate, cardiac function, degree of cardiac hypertrophy and fibrosis in rats with different infarct sizes. METHODS - Lisinopril (20 mg/kg/day) dissolved in drinking water was administered to rats immediately after coronary artery occlusion. After being sacrificed, the infarcted animals were divided into two groups: one group of animals with small infarcts (< 40% of the left ventricle) and another group of animals with large infarcts (> 40% of the left ventricle). RESULTS - The mortality rate was 31.7% in treated rats and 47% in the untreated rats. There was no statistical difference between the groups with small and large infarcts in regard to myocardial concentration of hydroxyproline. In small infarcts, the treatment attenuated the heart dysfunction characterized by lower levels of blood pressure and lower values of the first derivative of pressure and of the negative derivative of pressure. The degree of hypertrophy was also attenuated in small infarcts. In regard to large infarcts, no differences between the groups were observed. CONCLUSION - Treatment with the ACEIs had no effect on mortality rate and on the amount of fibrosis. The protective effect of lisinopril on heart function and on the degree of hypertrophy could only be detected in small infarcts

Um chronographo de construção simples, permittindo registrar intervallos de tempo de 1 a 60 segundos

Descriptive memorial of a chronograph made from a common chronoscop (Eastman Timer). The chronoscop has been modified in order to permit to adjust distinct cog-wheels, everyone in its turn, to the axis of the seconds hand. Each of these cog-wheels holds a definite number of teeth accordingly with the time interval ones desire to record. A wheel with 20 teeth, for instance, is available for recording time in periods of each three seconds, another wheel with 6 teeth, will reckon time in intervals of 10 seconds and so on. These wheels may be interchanged most easily, which enables, with the same apparatus, to have at hand a time recorder for any time interval between one and sixty seconds. To register the time the apparatus is connected with a dry cell. A wire is attached to a binding post on the metal case of the apparatus, another wire being connected with an isolated binding post placed in front of the cog-wheel and fastened to a platinum point allowing open or shut the circuit, every time one of the cogs of the wheel comes into contact with this platinum point. A signal magnet is placed also in the circuit for writing the time intervals on the revolving drum.

CL 64, 855, a potent do anti-Trypanosoma cruzi drug, is also mutagenic in the salmonella/microsome assay

The nitroimidazole-tiadiazole derivative CL 64,855 (2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole, a potent anti-trypanosomal drug, was assayed in a short-term bacterial mutagenicity test with Salmonella typhimurium strains TA 98, TA 100 and TA 102. Results indicate that CL 64,855 is a potent frameshift mutagen detected by strains TA 98 and TA 102. CL 64,855 was able to revert the indicators strains at concentrations as low as 0.1 µg/plate. Metabolic activation experiments with rat liver microsomal fractions did not increase the mutagenic action of Cl 64,855.

Cell mediated immunity in Chagas' disease: Trypanosoma cruzi antigens induce suppression of the in vitro proliferative response of mononuclear cells

The partial suppression of the cell-mediated immune response by Trypanosoma cruzi antigens in patients with Chagas' disease is demonstrated in a costimulation assay with T. cruzi antigens and Mycobacterium tuberculosis purified protein derivative (PPD) or Tetanus toxoid (TT). ononuclear cells from 13 patients with chagasic infection without evidence of heart disease, 10 patients with chagasic cardiomyopathy and 7 healthy blood donors were stimulated with antigen A (autoclaved epimastigotes), PPD, TT, PPD + A, PPD + TT and TT + A. The average percentage of suppression induced by costimulation of mononuclear cells with PPD and antigen A was 47.1% in patients with chagasic infection without heart disease (INF), 38.8% in patients with chagasic cardiomyopathy (CDM) and 23.3% in healthy controls. Similar values were observed when living trypomastigotes were used. A costimulatory study with PPD and TT, PPD and A and TT and A was carried out in 8 patients with chagasic infection, in order to evaluate the possibility that this difference could be due to a nonspecific inhibitory effect. The mean suppression induced by TT + PPD was -8.9, with TT + A was 52.7 and with PPD + A was 50.1. The data reported show that T. cruzi antigens induce a specific suppression of the proliferative responseof mononuclear cells, that might be relevant to the persistence of the parasite in the host.