Antimicrobial Cyanopeptide Action on Bacterial Cells Observed with Atomic Force Microscopy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Cyanobacteria produce oligopeptides that are predominantly synthesized by the non-ribosomal pathway. Among these are the aeruginosin and cyanopeptolin protease inhibitors, which act against enzymes known to cause several human health problems. Atomic force microscopy (AFM) was used to study the effect of cyanopeptides produced by Microcystis aeruginosa NPCD-1 on pathogenic bacterial cell surfaces. The selected strain was characterized based on the 16S rRNA gene sequence and the intergenic spacer region of the phycocyanin operon. PCR amplification was employed to investigate the presence of genes encoding for aeruginosin and cyanopeptolin. Purified extract from M. aeruginosa NPCD-1 cells was screened for bioactive compounds. The effect of purified extract containing protease inhibitors produced by the NPCD-1 strain on bacterial cells was observed using AFM. Aeruginosin and cyanopeptolin genes were confirmed by both PCR amplification and gene sequencing. Mass spectrometry analysis confirmed the production of aeruginosin. The interaction of Bacillus cereus, Escherichia coli and Staphylococcus aureus with cyanopeptides was characterized by examining the loss of surface stiffness and the formation of micelles, most likely originating from the membrane disruption. The AFM results demonstrate the ability of cyanobacterial extract to alter the cellular membrane of bacterial pathogens.91141148Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [FAPESP - 2003/12529-4, 2009/05474-5]CNPq [CNPq 559720/2009-2]CNPq [308299/2009-4, 151931/2010-0]FAPESP [2010/09867-9, 2008/53627-2, 2006/01671-2

CYP1A1, GSTM1 and GSTT1 polymorphisms, tobacco and alcohol status and risk of head and neck squamous cell carcinoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)We examined the influence of the CYP1A1 A4889G and T6235C, GSTM1 and GSTT1 polymorphisms, involved in carcinogen metabolism, on the head and neck (HN) squamous cell carcinoma (SCC) risk. DNA from 142 HNSCC patients and 142 controls was analysed by polymerase chain reaction (PCR)-restriction fragment length polymorphism or multiplex-PCR for the polymorphisms analyses. Excesses of the CYP1A1 4889AG+GG and 4889AG+GG plus GSTT1 null genotype were seen in patients with heavy tobacco habit compared with controls (41.9% versus 26.8%, P=0.03; 26.2% versus 10.3%, P=0.04, respectively). Carriers of the referred genotypes and heavy tobacco consumption were under a 2.0-fold and 2.8-fold increased risks for HNSCC than others, respectively. The CYP1A1 6235TC+CC plus GSTM1 and GSTT1 null genotypes were more common in pharyngeal SCC patients than in controls (5.3% versus 0.7%, P=0.04). Carriers of the combined genotype had 16.0-fold increased risk for the disease than others. The frequency of one null genotype of the GSTM1 or GSTT1 gene was higher in patients with pharyngeal SCC and heavy smoking status than in controls (76.3% versus 57.7%, P=0.04). Carriers of the referred genotype and heavy tobacco status had a 2.4-fold increased risk for pharyngeal SCC than others. In contrast, the CYP1A1 6235TC+CC genotype was more common in controls than in laryngeal SCC patients (35.9% versus 21.6%, P=0.01). Carriers of the genotype had a 0.2-fold decreased risk for the disease than others. Our data present preliminary evidence that inherited combined CYP1A1 A4889G and T6235C abnormalities and GSTM1 and GSTT1 pathways are important determinants of HNSCC, particularly pharyngeal SCC in heavy smoking individuals from southeastern Brazil.32612091215Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financiadora de Estudos e Projetos do Ministerio da Ciencia e Tecnologia do Brasil (FINEP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Risk factors for conjunctival and retinal vessel alterations in sickle cell disease

Purpose: The aim of this study was to clarify whether the clinical, laboratory and genetic aspects of sickle cell disease (SCD) influence the occurrence of vessel alterations in the conjunctiva and retina. Methods: A total of 102 SCD patients underwent biomicroscopical and retinal examination, in addition to evaluations of haemoglobin (Hb) and haematocrit (Ht) levels, fetal haemoglobin (HbF) estimations, serum creatinine and albuminuria levels, glomerular filtration rate (GFR) values, phenotypes, beta-globin gene haplotypes and alpha-thalassaemia. The relationship between ocular vessel alterations and clinical, laboratory and genetic features were evaluated using chi-squared or Fisher tests and logistic regression analysis. In 13 patients on enalapril treatment, a second ophthalmological evaluation was performed after a 12-month period to evaluate the longitudinal effect of the drug on ocular vessels. Results: Conjunctival vessel alteration (CVA) was not influenced by age, gender, HbF estimation, serum creatinine and albuminuria levels, GFR values, beta-globin gene haplotypes or alpha-thalassaemia. However, increased frequencies of CVA were found in patients with Hb <= 9.0 g/dl, Ht <= 26.7% and sickle cell anaemia (SS) phenotype. Retinal vessel alteration (RVA) was identified only in patients aged 17 years or older. Enalapril did not demonstrate ocular vessel amelioration after 12-months of daily use. Conclusion: The results indicate that lower Hb and Ht levels and SS phenotype are risk factors for CVA, and age over 17 years may be risk factors for RVA in SCD patients.84223424

Inherited pericentric inversion of chromosome 16 in chronic phase of chronic myeloid leukaemia

The simultaneous occurrence of two specific acquired chromosomal abnormalities in chronic or acute leukaemias is rare. Inherited chromosomal abnormalities are also rare events in the general population. In chronic myeloid leukaemia (CML), characterised by the t(9;22)(q34;q11), the inv(16)(p13q22) has been described associated with the acceleration of disease or onset of blast crisis. We report on a patient with chronic phase of CML and both acquired t(9;22)(q34;q11) and inherited inv(16)(p13q22), who obtained a complete remission of the disease after bone marrow transplant. Therefore, it is worth to comment that an additional chromosomal abnormality in disease does not obligatory mean transformation of the disease to a more aggressive form, since chromosomal abnormalities are also seen in normal individuals. (c) 2005 Elsevier Ltd. All rights reserved.30111511