Dihydroquinoline derivative as a potential anticancer agent: synthesis, crystal structure, and molecular modeling studies.

Cancer is one of the leading causes of death worldwide and requires intense and growing research investments from the public and private sectors. This is expected to lead to the development of new medicines. A determining factor in this process is the structural understanding of molecules with potential anticancer properties. Since the major compounds used in cancer therapies fail to encompass every spectrum of this disease, there is a clear need to research new molecules for this purpose. As it follows, we have studied the class of quinolinones that seem effective for such therapy. This paper describes the structural elucidation of a novel dihydroquinoline by single-crystal X-ray diffraction and spectroscopy characterization. Topology studies were carried through Hirshfeld surfaces analysis and molecular electrostatic potential map; electronic stability was evaluated from the calculated energy of frontier molecular orbitals. Additionally, in silico studies by molecular docking indicated that this dihydroquinoline could act as an anticancer agent due to their higher binding affinity with human aldehyde dehydrogenase 1A1 (ALDH 1A1). Tests in vitro were performed for VERO (normal human skin keratinocytes), B16F10 (mouse melanoma), and MDA-MB-231 (metastatic breast adenocarcinoma), and the results certified that compound as a potential anticancer agent. A Dihydroquinoline derivative was tested against three cancer cell lines and the results attest that compound as potential anticancer agent.

Presence of ascites in bullfrog breeders reared and kept on a frog farm / Presença de ascite em reprodutores de rã-touro criados e mantidos em ranário

Ascites is a pathology characterized by the extravasation of fluid from blood vessels and its accumulation in the abdominal cavity, caused by several associated factors. In this paper, we report the occurrence of this syndrome in breeding male and female Bullfrogs fed a commercial fish feed with 40% crude protein. Liver malformation was already observed due to lack of protein deposition in adult animals from the same spawning. The culture of ascitic fluid showed absence of bacterial growth. Kidney histopathology showed, in both sexes, a large number of tubular structures with strongly eosinophilic hyaline material suggesting colloid growth in both the cortical region and spinal cord. The analysis also revealed granulomas in various stages of development, many showing central necrotic material. The kidneys, glomerular, were mostly hypoplastic, with enlarged Bowman space, and many were hyalinized or hemorrhagic; the parenchyma showed dystrophic calcification, and many tubules containing fibrinoid material. The liver displayed a large amount of melanomacrophages in the parenchyma and foci of mono-lymphocytic hepatitis and marked cytoplasmic rarefaction, as well as several hepatocytes with pyknotic nuclei and necrotic cells and dissociation of the hepatic trabeculae. Ascites may be caused by the lesions observed in these organs.(AU)

A ascite é uma condição patológica que se caracteriza pelo extravasamento do líquido dos vasos sanguíneos e por seu acúmulo na cavidade abdominal provocado por uma somatória de fatores. É considerada uma síndrome de caráter multifatorial e, uma vez desencadeado o processo ascítico, esse se torna, na maioria dos casos, irreversível. O objetivo deste trabalho foi relatar a ocorrência dessa síndrome em machos e fêmeas reprodutores de rã-touro (Lithobates catesbeianus), alimentados com ração comercial para peixes, com 40% de proteína bruta, durante três anos e já sendo observada má formação de fígado, por falta de deposição proteica, em animais adultos da mesma desova. A cultura do líquido ascítico demonstrou ausência de crescimento bacteriano. Na histopatologia, observou-se, para ambos os sexos, nos rins, grande número de estruturas tubulares com material fortemente eosinofílico e hialino, sugerindo coloide, tanto na região cortical como na medular. Visualizaram-se também granulomas em vários estágios de desenvolvimento, muitos apresentando material necrótico central. Ainda se pôde observar que os aparelhos renais, os glomérulos, em sua maioria, estavam hipoplásicos e com aumento do espaço de Bowman, e muitos hialinizados ou hemorrágicos; além de calcificação distrófica no parênquima e nos dos túbulos, havia material fibrinoide no seu interior. No fígado, pôde-se ver grande quantidade de melanomacrófagos no parênquima e focos de hepatite monolinfocitária e acentuada rarefação citoplasmática, assim como vários hepatócitos com núcleo em picnose e células em necrose e dissociação das trabéculas hepáticas. A causa da ascite pode ser devido às lesões observadas nesses órgãos.(AU)

Characterization and analysis of the outcome of adults with acute myeloid leukemia treated in a Brazilian University hospital over three decades

We evaluated the outcome of 227 patients with acute myeloid leukemia during three decades (period 1 - 1980’s, N = 89; period 2 - 1990’s, N = 73; period 3 - 2000’s, N = 65) at a single institution. Major differences between the three groups included a higher median age, rates of multilineage dysplasia and co-morbidities, and a lower rate of clinical manifestations of advanced leukemia in recent years. The proportion of patients who received induction remission chemotherapy was 66, 75, and 85 percent for periods 1, 2, and 3, respectively (P = 0.04). The median survival was 40, 77, and 112 days, and the 5-year overall survival was 7, 13, and 22 percent, respectively (P = 0.01). The median disease-free survival was 266, 278, and 386 days (P = 0.049). Survival expectation for patients with acute myeloid leukemia has substantially improved during this 30-year period, due to a combination of lower tumor burden and a more efficient use of chemotherapy and supportive care.

Characterization and analysis of the outcome of adults with acute myeloid leukemia treated in a Brazilian University hospital over three decades.

We evaluated the outcome of 227 patients with acute myeloid leukemia during three decades (period 1 - 1980's, N = 89; period 2 - 1990's, N = 73; period 3 - 2000's, N = 65) at a single institution. Major differences between the three groups included a higher median age, rates of multilineage dysplasia and co-morbidities, and a lower rate of clinical manifestations of advanced leukemia in recent years. The proportion of patients who received induction remission chemotherapy was 66, 75, and 85% for periods 1, 2, and 3, respectively (P = 0.04). The median survival was 40, 77, and 112 days, and the 5-year overall survival was 7, 13, and 22%, respectively (P = 0.01). The median disease-free survival was 266, 278, and 386 days (P = 0.049). Survival expectation for patients with acute myeloid leukemia has substantially improved during this 30-year period, due to a combination of lower tumor burden and a more efficient use of chemotherapy and supportive care.

Eotaxin-2 in sputum cell culture to evaluate asthma inflammation.

The aim of the present study was to elucidate whether the culture of cells recovered from induced sputum may represent a suitable model to evaluate cytokine and chemokine production by airway inflammatory cells. Sputum induction was performed in 21 normal subjects and 30 asthmatic patients. A total of 21 out of the 30 asthmatic patients were taking inhaled corticosteroids, while the remaining nine were steroid-naive asthmatics. The steroid-naive group was evaluated before and after a 14-day treatment with oral prednisone (40 mg.day(-1)). The supernatant of lysed and centrifuged sputum and the supernatant of sputum cell culture were analysed. Tumour necrosis factor-alpha, interleukin (IL)-8 (CXCL8), IL-1beta, IL-13 and eotaxin-2 (CCL24) concentrations were determined by specific ELISA. Eotaxin-2 production by cell culture was higher in the asthma group (131+/-108 pg.mL(-1)) than in the control group (36+/-41 pg.mL(-1)) and treatment with oral corticosteroids eliminated this difference. In addition, reduction of eotaxin-2 levels by corticosteroid treatment was greater in cell culture (81.3% reduction) than in sputum (26.4%). There was correlation between the decrease in eotaxin-2 production and the decrease in blood eosinophil number and between eotaxin-2 and eosinophils in sputum. Eotaxin-2 may play an important role in asthma and the response to corticosteroid treatment suggests that analysis of sputum cell culture is relevant as an inflammatory parameter.

Do steroids interfere in dyspnoea sensation?

Dyspnoea remains a remarkable clinical problem and a therapeutic challenge, mainly in chronic respiratory conditions. This study investigated the potential effects of steroids on dyspnoea sensation regardless of their pulmonary anti-inflammatory actions. Sixteen healthy men (mean age +/- SD = 22.5 +/- 1.6 years) developed uncomfortable breathing by the use of inspiratory resistors (loads of 0, 7, 14 and 21 cm H2O/l/s) and breathholding 6 h after taking 40 mg of prednisone (Pred) or placebo (Plac). Respiratory discomfort during breathing with loads was evaluated with a 100 mm visual analog scale. The maximum voluntary apnoea time did not differ between the prednisone and placebo days (Plac = 96 +/- 11.8 s x Pred = 105 +/- 12.2 s) and prednisone did not influence the dyspnoea sensation induced by different inspiratory loads (0 cm H2O/l/s: Pred = 2.8 mm x Plac = 1.9 mm; 7 cm H2O/l/s: Pred = 18.3 mm x Plac = 18.6 mm; 14 cm H2O/l/s; Pred = 33.0 mm x Plac = 34.1 mm; 21 cm H2O/l/s: Pred = 48.1 mm x Plac = 49.6 mm). Prednisone intake was associated with a significant increase in minute ventilation during breathing with no inspiratory loads (Pred = 11.91 +/- 1.28 l/min- x Plac = 9.95 +/- 0.86 l/min). Although steroids certainly may improve respiratory conditions due to anti-inflammatory actions, available evidence does not support any specific beneficial effect of these drugs on these perception of dyspnoea itself.

Effect of sulphur inoculated with Thiobacillus on soil salinity and growth of tropical tree legumes.

A greenhouse experiment was carried out with the objective of evaluating the effects of the elementary sulphur inoculated with Thiobacillus, compared with gypsum, in the amendment of a alluvial sodic saline soil from the Brazilian semiarid region, irrigated with saline water and grown with the tropical legumes leucena and mimosa. The treatments consisted of levels of sulphur (0; 300 and 600 kg/ha) and gypsum (1,200 and 2,400 kg/ha), irrigation using different waters containing the salts NaHCO3, MgCl2, CaCl2, NaCl and KCl, with different electrical conductivities (ECs: 0.2. 6.1 and 8.2 dS/m at 25 degrees C). Based on the results it appears that saline water increased exchangeable Na+, K+, Ca2+, Mg2+, and soil pH. Sulphur inoculated with Thiobacillus was more efficient than gypsum in the reduction of the exchangeable sodium of the soil and promoting leaching of salts, especially sodium. Sulphur inoculated with Thiobacillus reduced the EC of the soil saturation extract to levels below that adopted in soil classification of sodic or saline sodic. Leucena was more tolerant to salinity and mimosa more resistant to acidity promoted by sulphur inoculated with Thiobacillus.

Dyspnea scales in the assessment of illiterate patients with chronic obstructive pulmonary disease.

BACKGROUND: Multiple physiological, psychological, social and environmental factors may affect the perception of dyspnea. Although different scales have been used to record the severity of dyspnea in subjects with chronic obstructive pulmonary disease (COPD), none has reported evaluating the properties of such tools in illiterate patients. The objective of this study was to evaluate the reliability and features of concurrent validity of 4 dyspnea scales in illiterate (IL) subjects with COPD. METHODS: One hundred COPD patients submitted to spirometry and were asked to score their breathlessness using a visual analogue scale (VAS), a numerical rating scale (NRS), the Borg scale (BS), and the basal dyspnea index (BDI). Each scale was presented to the patients before and after they had performed spirometry and measurement of residual volume. The obtained scores were analyzed according to the literacy status of the patients. RESULTS: Thirty-three patients were classified as IL and 67 as literate (L). Both groups showed similar respiratory impairment and median scores of dyspnea (VAS, L = 45.0, IL = 49.0; NRS, L = 5.0, IL = 5.0; BS, L = 3.0, IL = 3.0; BDI, L = 5.0, IL = 4.0). No significant differences were found between the dyspnea scores obtained before and after spirometry for all scales in both groups. The degree of correlation between forced expiratory volume in 1 second (FEV1) and usual dyspnea evaluated by BDI did not show a statistical difference between the two groups (L, r = 0.37; IL, r = 0.51). CONCLUSION: The employed dyspnea scales showed comparable reliability in both L and IL COPD subjects.

Use of the polymerase chain reaction in the diagnosis of leprosy.

One of the main limitations for successful epidemiological control of leprosy is the lack of a method for its diagnosis in subclinical cases. Because of the long incubation period of the disease, liberation and spread of Mycobacterium leprae during subclinical stages-principally in cases of untreated multibacillary forms of leprosy-constitute the main source of infection. This report describes the use of the polymerase chain reaction (PCR) for the detection of M. leprae in different types of tissue samples (blood, lymph, nasal secretion and hair) from an individual who was suspected of having leprosy. Although no conclusive diagnosis could be made by traditional diagnostic methods, the individual was found to be infected with M. leprae after amplification of the bacterial DNA.

Immunocytochemistry of mucosal changes in patients infected with the intestinal nematode Strongyloides stercoralis.

AIM: To investigate the immunopathological changes in duodenal tissues induced by strongyloidiasis and to relate these to degrees of clinical severity. METHODS: Tissues taken from 21 patients showing mild, moderate or severe symptoms of strongyloidiasis, and from non-infected controls, were sectioned and stained immunocytochemically for IgA, secretory component (SC) and HLA-DR. Immunopathology was assessed by changes in numbers, intensity and distribution of stained cells. RESULTS: Parasitised individuals showed villous atrophy and crypt hyperplasia. There was notable infiltration of the lamina propria by IgA positive plasma cells and of the epithelium by intraepithelial lymphocytes. Infection was also associated with increased expression of SC and decreased expression of HLA-DR in epithelial cells. Changes in all parameters correlated with degree of clinical severity. CONCLUSIONS: Profound mucosal changes are induced by strongyloidiasis. Some are analogous to those seen in coeliac disease, but others seem quite unusual. It is likely that these changes are functionally related to the immunopathophysiological consequences of infection seen in patients with severe disease.

Immunocytochemical demonstration that human duodenal Brunner's glands may participate in intestinal defence.

The immunocytochemical demonstration of IgA and IgM in some secretory units of human Brunner's glands, associated with the presence of secretory component in all secretory cells, indicates the possibility that these glands assist the function of the intestinal crypts in transporting immunoglobulins into the gut lumen. In addition, the presence of muramidase (lysozyme) in the cells of the secretory units suggests that Brunner's glands continuously secrete bactericidal enzyme, thus reinforcing the function of the Paneth cells as contributors to nonspecific defence (innate immunity) in the intestinal tract.

Evaluation of PCR mediated DNA amplification in non-invasive biological specimens for subclinical detection of Mycobacterium leprae.

DNA from Mycobacterium leprae, present in non-invasive clinical samples from leprosy patients, such as nasal secretion and hair bulbs, was submitted to amplification by the polymerase chain reaction using a M. leprae-specific repetitive sequence as a target. After optimization of sample processing and of the PCR conditions, we were able to detect DNA from M. leprae in both types of clinical samples, even from paucibacillary leprosy patients. The use of hair bulbs and nasal secretion as clinical samples for screening of household contacts and for the evaluation of a risk population, or for the follow-up of patients under chemotherapy, and monitoring of bacterial load is discussed.