Making DNA without iron: induction of a manganese-dependent ribonucleotide reductase in response to iron starvation

Ribonucleotide reductases supply cells with their deoxyribonucleotides. Three enzyme types are known, classes I, II and III. Class II enzymes are anaerobic whereas class I enzymes are aerobic, and so class I and II enzymes are often produced by the same organism under opposing oxygen regimes. Escherichia coli contains two types of class I enzyme (Ia and Ib) with the Fe-dependent Ia enzyme (NrdAB) performing the major role aerobically, leaving the purpose of the Ib enzyme (NrdEF) unclear. Several papers have recently focused on the class Ib enzymes showing that they are Mn (rather than Fe) dependent and suggesting that the E. coli NrdEF may function under redox-stress conditions. A paper published in this issue of Molecular Microbiology from James Imlay's group confirms that this unexplained NrdEF Ib enzyme is Mn-dependent, but shows that it does not substitute for NrdAB during redox stress. Instead, a role during iron restriction is demonstrated. Thus, the purpose of NrdEF (and possibly other class Ib enzymes) is to enhance growth under aerobic, low-iron conditions, and to functionally replace the Fe-dependent NrdAB when iron is unavailable. This finding reveals a new mechanism by which bacteria adjust to life under iron deprivation.

Solvent-dependent modulation of metal–metal electronic interactions in a dinuclear cyanoruthenate complex: a detailed electrochemical, spectroscopic and computational study

The dinuclear complex [{Ru(CN)4}2(μ-bppz)]4− shows a strongly solvent-dependent metal–metal electronic interaction which allows the mixed-valence state to be switched from class 2 to class 3 by changing solvent from water to CH2Cl2. In CH2Cl2 the separation between the successive Ru(II)/Ru(III) redox couples is 350 mVand the IVCT band (from the UV/Vis/NIR spectroelectrochemistry) is characteristic of a borderline class II/III or class III mixed valence state. In water, the redox separation is only 110 mVand the much broader IVCT transition is characteristic of a class II mixed-valence state. This is consistent with the observation that raising and lowering the energy of the d(π) orbitals in CH2Cl2 or water, respectively, will decrease or increase the energy gap to the LUMO of the bppz bridging ligand, which provides the delocalisation pathway via electron-transfer. IR spectroelectrochemistry could only be carried out successfully in CH2Cl2 and revealed class III mixed-valence behaviour on the fast IR timescale. In contrast to this, time-resolved IR spectroscopy showed that the MLCTexcited state, which is formulated as RuIII(bppz˙−)RuII and can therefore be considered as a mixed-valence Ru(II)/Ru(III) complex with an intermediate bridging radical anion ligand, is localised on the IR timescale with spectroscopically distinct Ru(II) and Ru(III) termini. This is because the necessary electron-transfer via the bppz ligand is more difficult because of the additional electron on bppz˙− which raises the orbital through which electron exchange occurs in energy. DFT calculations reproduce the electronic spectra of the complex in all three Ru(II)/Ru(II), Ru(II)/Ru(III) and Ru(III)/Ru(III) calculations in both water and CH2Cl2 well as long as an explicit allowance is made for the presence of water molecules hydrogen-bonded to the cyanides in the model used. They also reproduce the excited-state IR spectra of both [Ru(CN)4(μ-bppz)]2– and [{Ru(CN)4}2(μ-bppz)]4− very well in both solvents. The reorganization of the water solvent shell indicates a possible dynamical reason for the longer life time of the triplet state in water compared to CH2Cl2.

A novel transport mechanism for MOMP in Chlamydophila pneumoniae and its putative role in immune-therapy

Major outer membrane proteins (MOMPs) of Gram negative bacteria are one of the most intensively studied membrane proteins. MOMPs are essential for maintaining the structural integrity of bacterial outer membranes and in adaptation of parasites to their hosts. There is evidence to suggest a role for purified MOMP from Chlamydophila pneumoniae and corresponding MOMP-derived peptides in immune-modulation, leading to a reduced atherosclerotic phenotype in apoE−/− mice via a characteristic dampening of MHC class II activity. The work reported herein tests this hypothesis by employing a combination of homology modelling and docking to examine the detailed molecular interactions that may be responsible. A three-dimensional homology model of the C. pneumoniae MOMP was constructed based on the 14 transmembrane β-barrel crystal structure of the fatty acid transporter from Escherichia coli, which provides a plausible transport mechanism for MOMP. Ligand docking experiments were used to provide details of the possible molecular interactions driving the binding of MOMP-derived peptides to MHC class II alleles known to be strongly associated with inflammation. The docking experiments were corroborated by predictions from conventional immuno-informatic algorithms. This work supports further the use of MOMP in C. pneumoniae as a possible vaccine target and the role of MOMP-derived peptides as vaccine candidates for immune-therapy in chronic inflammation that can result in cardiovascular events.

Variety matters: adaptive genetic diversity and parasite load in two mouse opossums from the Brazilian Atlantic forest

The adaptive potential of a species to a changing environment and in disease defence is primarily based on genetic variation. Immune genes, such as genes of the major histocompatibility complex (MHC), may thereby be of particular importance. In marsupials, however, there is very little knowledge about natural levels and functional importance of MHC polymorphism, despite their key role in the mammalian evolution. In a previous study, we discovered remarkable differences in the MHC class II diversity between two species of mouse opossums (Gracilinanus microtarsus, Marmosops incanus) from the Brazilian Atlantic forest, which is one of the most endangered hotspots for biodiversity conservation. Since the main forces in generating MHC diversity are assumed to be pathogens, we investigated in this study gastrointestinal parasite burden and functional associations between the individual MHC constitution and parasite load. We tested two contrasting scenarios, which might explain differences in MHC diversity between species. We predicted that a species with low MHC diversity would either be under relaxed selection pressure by low parasite diversity (`Evolutionary equilibrium` scenario), or there was a recent loss in MHC diversity leading to a lack of resistance alleles and increased parasite burden (`Unbalanced situation` scenario). In both species it became apparent that the MHC class II is functionally important in defence against gastrointestinal helminths, which was shown here for the first time in marsupials. On the population level, parasite diversity did not markedly differ between the two host species. However, we did observe considerable differences in the individual parasite load (parasite prevalence and infection intensity): while M. incanus revealed low MHC DAB diversity and high parasite load, G. microtarsus showed a tenfold higher population wide MHC DAB diversity and lower parasite burden. These results support the second scenario of an unbalanced situation.

The Immunomodulatory Action of Sialostatin L on Dendritic Cells Reveals Its Potential to Interfere with Autoimmunity

Sialostatin L (SialoL) is a secreted cysteine protease inhibitor identified in the salivary glands of the Lyme disease vector Ixodes scapularis. In this study, we reveal the mechanisms of SialoL immunomodulatory actions on the vertebrate host. LPS-induced maturation of dendritic cells from C57BL/6 mice was significantly reduced in the presence of SialoL. Although OVA degradation was not affected by the presence of SialoL in dendritic cell cultures, cathepsin S activity was partially inhibited, leading to an accumulation of a 10-kDa invariant chain intermediate in these cells. As a consequence, in vitro Ag-specific CD4(+) T cell proliferation was inhibited in a time-dependent manner by SialoL, and further studies engaging cathepsin S(-/-) or cathepsin L(-/-) dendritic cells confirmed that the immunomodulatory actions of SialoL are mediated by inhibition of cathepsin S. Moreover, mice treated with SialoL displayed decreased early T cell expansion and recall response upon antigenic stimulation. Finally, SialoL administration during the immunization phase of experimental autoimmune encephalomyelitis in mice significantly prevented disease symptoms, which was associated with impaired IFN-gamma and IL-17 production and specific T cell proliferation. These results illuminate the dual mechanism by which a human disease vector protein modulates vertebrate host immunity and reveals its potential in prevention of an autoimmune disease. The Journal of Immunology, 2009, 182: 7422-7429.

Alveolar macrophages from susceptible mice are more competent than those of resistant mice to control initial Paracoccidioides brasiliensis infection

Alveolar macrophages ( AM) are the first host cells to interact with Paracoccidioides brasiliensis (Pb), a primary human pathogen that causes severe pulmonary infections in Latin America. To better understand innate immunity in pulmonary paracoccidioidomycosis, we decided to study the fungicidal and secretory abilities of AM from resistant (A/J) and susceptible (B10.A) mice to infection. Untreated, IFN-gamma and IL-12 primed AM from B10. A and A/J mice were challenged with P. brasiliensis yeasts and cocultured for 72 h. B10. A macrophages presented an efficient fungicidal ability, were easily activated by both cytokines, produced high levels of nitric oxide ( NO), IL-12, and MCP-1 associated with low amounts of IL-10 and GM-CSF. In contrast, A/J AM showed impaired cytokine activation and fungal killing, secreted high levels of IL- 10 and GM-CSF but low concentrations of NO, IL- 12, and MCP-1. The fungicidal ability of B10. A but not of A/J macrophages was diminished by aminoguanidine treatment, although only the neutralization of TGF-beta restored the fungicidal activity of A/J cells. This pattern of macrophage activation resulted in high expression of MHC class II antigens by A/J cells, while B10. A macrophages expressed elevated levels of CD40. Unexpectedly, our results demonstrated that susceptibility to a fungal pathogen can be associated with an efficient innate immunity, while a deficient innate response can ultimately favor the development of a resistant pattern to infection. Moreover, our data suggest that different pathogen recognition receptors are used by resistant and susceptible hosts to interact with P. brasiliensis yeasts, resulting in divergent antigen presentation, acquired immunity, and disease outcomes.

Preventive and curative glycoside kaempferol treatments attenuate the TH2-driven allergic airway disease

Asthma is a chronic respiratory disease characterized by airway inflammation and airway hyperresponsiveness (AHR). One strategy to treat allergic diseases is the development of new drugs. Flavonoids are compounds derived from plants and are known to have antiallergic, anti-inflammatory, and antioxidant properties. To investigate whether the flavonoid kaempferol glycoside 3-O-[beta-D-glycopiranosil-(1 -> 6)-alpha-L-ramnopiranosil]-7-O-alpha-L-ramnopiranosil-kaempferol (GRRK) would be capable of modulating allergic airway disease (AAD) either as a preventive (GRRK P) or curative (GRRK C) treatment in an experimental model of asthma. At weekly intervals, BALB/c mice were subcutaneously (sc) sensitized twice with ovalbumin (OVA)/alum and challenged twice with OVA administered intranasally. To evaluate any preventive effects GRRK was administered 1 h (hour) before each OVA-sensitization and challenge, while to analyze the curative effects mice were first sensitized with OVA, followed by GRRK given at day 18 through 21. The onset: of AAD was evaluated 24 h after the last OVA challenge. Both treatments resulted in a dose-dependent reduction in total leukocyte and eosinophil counts in the bronchoalveolar lavage fluid (BAL). GRRK also decreased CD4(+), B220(+), MHC class II and CD40 molecule expressions in BAL cells. Histology and lung mechanic showed that GRRK suppressed mucus production and ameliorated the AHR induced by OVA challenge. Furthermore, GRRK impaired Th2 cytokine production (IL-5 and IL-13) and did not induce a Th1 pattern of inflammation. These findings demonstrate that GRRK treatment before or after established allergic lung disease down-regulates key asthmatic features. Therefore. GRRK has a potential clinical use for the treatment of allergic asthma. (C) 2009 Elsevier B.V. All rights reserved.

Sugarcane Phosphoribosyl Pyrophosphate Synthetase: Molecular Characterization of a Phosphate-independent PRS

Phosphoribosyl pyrophosphate synthetase (PRS-EC:2.7.6.1) is an important enzyme present in several metabolic pathways, thus forming a complex family of isoenzymes. However, plant PRS enzymes have not been extensively investigated. In this study, a sugarcane prs gene has been characterized from the Sugar Cane Expressed Sequence Tag Genome Project. This gene contains a 984-bp open reading frame encoding a 328-amino acid protein. The predicted amino acid sequence has 77% and 78% amino acid sequence identity to Arabidopsis thaliana and Spinacia oleracea PRS4, respectively. The assignment of sugarcane PRS as a phosphate-independent PRS isoenzyme (Class II PRS) is verified following enzyme assay and phylogenetic reconstruction of PRS homologues. To gain further insight into the structural framework of the phosphate independence of sugarcane PRS, a molecular model is described. This model reveals the formation of two conserved domains elucidating the structural features involved in sugarcane PRS phosphate independence. The recombinant PRS retains secondary structure elements and a quaternary arrangement consistent with known PRS homologues, based on circular dichroism measurements.

Cathepsin S as a biomarker of low-grade inflammation, insulin resistance, and cardiometabolic disease risk

Cathepsin S is a protease important in major histocompatibility complex (MHC) class II antigen presentation and also in degrading the extracellular matrix. Studies, most of them experimental, have shown that cathepsin S is involved in different pathological conditions such as obesity, inflammation, atherosclerosis, diabetes, and cancer.    The overall hypothesis of this report is that high levels of circulating cathepsin S, is a biomarker that reflects pathology induced by inflammation and obesity. The overall aim of this report was to investigate possible associations between circulating cathepsin S, inflammation, glucometabolic disturbance, and its associated diseases in the community. As cathepsin S appears to be a novel risk marker for several pathological conditions, we also wanted to examine the effect of dietary intervention on circulating cathepsin S concentrations.    This thesis is based on data from three community-based cohorts, the Uppsala longitudinal study of adult men (ULSAM), the prospective investigation of the vasculature in Uppsala seniors (PIVUS), and a post-hoc study from the randomized controlled NORDIET trial.    In the first study, we identified a cross-sectional positive association between serum cathepsin S and two markers of cytokine-mediated inflammation, CRP and IL-6. These associations were similar in non-obese individuals. In longitudinal analyses, higher cathepsin S at baseline was associated with higher CRP and IL-6 levels after six years of follow-up. In the second study, we identified a cross-sectional association between increased serum levels of cathepsin S and reduced insulin sensitivity. These associations were similar in non-obese individuals. No significant association was observed between cathepsin S and insulin secretion. In longitudinal analysis, higher cathepsin S levels were associated with an increased risk of developing diabetes during the six-year follow-up. In the third study, we found that higher serum levels of cathepsin S were associated with increased mortality risk. Moreover, in the ULSAM cohort, serum cathepsin S was independently associated with cause-specific mortality from cardiovascular disease and cancer. In the fourth study, we identified that adherence to an ad libitum healthy Nordic diet for 6 weeks slightly decreased the levels of plasma cathepsin S in normal or marginally overweight individuals, relative to the control group. Changes in circulating cathepsin S concentrations were correlated with changes in body weight, LDL-C, and total cholesterol.    Conclusion: This thesis shows that circulating cathepsin S is a biomarker that independently reflects inflammation, insulin resistance, the risk of developing diabetes, and mortality risk. Furthermore, a Nordic diet moderately reduced cathepsin S levels in normal-weight and overweight men and women. This effect may be partially mediated by diet-induced weight loss and possibly by reduced LDL-C concentrations. 

Computational analysis and physico-chemical characterization of an inclusion compound between praziquantel and methyl-beta-cyclodextrin for use as an alternative in the treatment of schistosomiasis

Schistosomiasis is still an endemic disease in many regions, with 250 million people infected with Schistosoma and about 500,000 deaths per year. Praziquantel (PZQ) is the drug of choice for schistosomiasis treatment, however it is classified as Class II in the Biopharmaceutics Classification System, as its low solubility hinders its performance in biological systems. The use of cyclodextrins is a useful tool to increase the solubility and bioavailability of drugs. The aim of this work was to prepare an inclusion compound of PZQ and methyl-beta-cyclodextrin (MeCD), perform its physico-chemical characterization, and explore its in vitro cytotoxicity. SEM showed a change of the morphological characteristics of PZQ:MeCD crystals, and IR data supported this finding, with changes after interaction with MeCD including effects on the C-H of the aromatic ring, observed at 758 cm(-1). Differential scanning calorimetry measurements revealed that complexation occurred in a 1:1 molar ratio, as evidenced by the lack of a PZQ transition temperature after inclusion into the MeCD cavity. In solution, the PZQ UV spectrum profile in the presence of MeCD was comparable to the PZQ spectrum in a hydrophobic solvent. Phase solubility diagrams showed that there was a 5.5-fold increase in PZQ solubility, and were indicative of a type A(L) isotherm, that was used to determine an association constant (K(a)) of 140.8 M(-1). No cytotoxicity of the PZQ:MeCD inclusion compound was observed in tests using 3T3 cells. The results suggest that the association of PZQ with MeCD could be a good alternative for the treatment of schistosomiasis.

Distribuição regional da ventilação pulmonar em indivíduos com insuficiência cardíaca crônica após serem submetidos a um programa de treinamento da musculatura inspiratória e sua correlação com dados funcionais

Introduction: Chagas Disease is a serious public health problem, with 5 million infected individuals in Brazil. Of these, approximately 30% develop chronic Chagas cardiomyopathy (CCC), where the main symptoms are fatigue and dyspnea. Objective: To correlate maximal exercise capacity with pulmonary function, inspiratory muscle strength and quality of life in patients with CCC. Methodology: Twelve individuals suffering from CCC were evaluated (7 men), with a mean age of 54.91± 8.60 years and the following inclusion criteria: functional class II and III according to the New York Heart Association (NYHA); left ventricle ejection fraction below 45%; clinical stability (> 3 months); symptom duration > 1 year, body mass index (BMI) < 35Kg/m2 and non-smokers or ex-smokers with a history of smoking <10 packs/day. All subjects were submitted to spirometry, manometer testing, maximal cardiopulmonary exercise testing (CPX) and a quality of life questionnaire (Minnesota). Results: A negative correlation was observed between VO2máx and MLHFQ scores (r=-0.626; p=0.03) and a positive association with MIP (r=0.713; p=0.009). Positive correlations were also recorded between MIP and spirometric variables [FEV1(r=0.825;p=0.001 ), FVC(r=0.66;p=0.01 and FEF25-75%(r=0.639;p=0.02)]. Conclusion: The present study demonstrated that in patients with CCC: VO2MAX is directly related to inspiratory muscle strength and quality of life, while deteriorating lung function is directly associated with respiratory muscle weakness

O tratamento ortodôntico em uma perspectiva a longo prazo: avaliação da estabilidade oclusal e do grau de satisfação dos pacientes

This study aimed to evaluate factors associated to orthodontic treatment stability and patient satisfaction in the long-term. A total of 209 patients (88 class I and 121 class II) treated with straight wire fixed appliance were selected at least 5 years post treatment. Six hundred twenty seven dental casts were examined with the PAR Index at pretreatment (T1), end of treatment (T2), and at long-term follow up (T3, mean 8.5 years post treatment). At T3, a Dental Impact on Daily Living questionnaire was used to assess patient satisfaction with the dentition in the long-term. Friedman test and multiple regression analysis were used to evaluate changes among the time points and factors associated with stability and patient satisfaction. Predictive factors used to exam the occlusion were: PAR Index at T1 and T2, age at T1, the amount of time without retainer, length of Hawley retainer wear, length of follow-up, sex, extraction and third molar status. To assess patient satisfaction were considered: changes produced by the orthodontic treatment (PAR T2-T1), post treatment stability (PAR T3), age at the start of treatment (T1), length of treatment (T2-T1), gender, and extraction. Orthodontic treatment produced a significant improvement of 94.2% in the PAR Index (T2-T1), but this change was not associated with the level of satisfaction when the patient was questioned at T3. No significant change was observed between T2 and T3. However, when the sample was divided according to the level of finalization (PAR T2), it was observed that well-finished patients experienced some deterioration (P<.001), whereas the less well-finished ones showed some improvement (P<.05). Even with the deterioration, the well-finished patients still had a better PAR Index at T3 compared to the less well-finished ones (PAR T2- T3). Regression analysis showed that PAR Index at T1 and T2, age at T1, and length of retainer wear had a slight association with occlusal stability (R2 = 0.27). Patient satisfaction was significantly associated only with PAR Index at T3 (r2=0.125, P<.0001). We can conclude that, even thought orthodontic treatment is quite stable, not so well-finished treatments tend to show some improvement and well-finished ones deteriorate some in the long-term. Despite of that, well-finished patients still have better occlusal characteristics. Patient satisfaction is not related to the result of orthodontic treatment; nevertheless, there is a slight association with dentition in the long-term

Estudo dos genes do complexo do antígeno leucocitário humano (hla) associados à susceptibilidade ao diabetes mellitus tipo 1

Of all of the genes associated with the development of Diabetes mellitus type 1 (T1D), the largest contribution comes from the genes in the Human Leukocyte Antigen (HLA) region, mostly the class II DR e DQ genes. Specific combinations of alleles DRB1, DQA1 and DQB1 constituting haplotypes, and further, a combination of more than one haplotype, providing multilocus genotypes are associated with susceptibility, protection and neutrality to DM1. Thus, the aim of present study was to verified the association of polymorphisms of HLA genes class II with susceptibility to type 1 diabetes mellitus (T1D). Ninety-two patients with T1D and 100 individuals normoglycemics (NG) aged between 6 and 20 years were studied. Genomic DNA was obtained from peripheral whole blood, collected in EDTA tube, using the extraction kit Illustra Triple Prep®, GE Healthcare. For HLA typing was used DNA LABType system by One Lambda kit applying Luminex® technology to the method of PCRSSO typing reverse. The alleles DRB1*03:01, *04:05, *04:01, *04:02, DQA1*03:01g, *05:01g, DQB1*02:01g, *03:02, the haplotypes DRB1*03:01-DQA1*05:01-DQB1*02:01, DRB1*04:05-DQA1*03:01g-DQB1*03:02, DRB1*04:02-DQA1*03:01g-DQB1*03:02, DRB1*04:01-DQA1*03:01g-DQB1*03:02 and DR3-DQ2/DR4-DQ8 genotype were significantly associated with the chance of developing T1D. The alleles DRB1*11:01, *15:03, *15:01, *13:01, DQA1*01:02, *04:01g, *01:03, DQB1*06:02, *03:01g, *06:03, *04:02, the haplotypes DRB1*11:01-DQA1*05:01-DQB1*03:01, DRB1*13:01-DQA1*01:03-DQB1*06:03 and DRX-DQX/DRX-DQX genotype, formed by other than the DR3-DQ2 or DR4-DQ8 haplotypes, were significantly associated with T1D protection Despite the major racial Brazilian, even at the regional level, these results are similar to the majority of alleles, genotypes and haplotypes of HLA class II-related susceptibility or resistance to T1D, extensively described in the literature for Caucasian population. Children with age at diagnosis less than 5 years of age had significantly higher frequency of the heterozygous genotype DR3-DQ2/DR4-DQ8 compared to children with age at diagnosis than 5 years old. These results also demonstrate strong association of the genetic profile of the class II HLA for this age group, possibly associated with the severity and rapid progression to the onset of T1D. The knowledge of HLA class II genes may be useful in genetic screens that allow the prediction of T1D

Performance of four tomato cultivars, with and without ground cover

The aim of the study was to evaluate the production of four tomato cultivars of determinate growth, in the field, with and without ground cover. The cultivars examined were: 'AP-533', 'AP-529', 'Hypeel 5131 and 'PS-41816', which were cultivated with a spacing of 1 m between rows and 0.4 m between plants. The experimental design utilized was that of subdivided parcels, where parcels were provided with and without a ground cover of black polyethylene, and subparcels consisted of the cultivars; eight repetitions were used. The eight central plants in the parcel were evaluated according to the following characteristics: fresh weight of fruit per plant and number of fruit per plant, separated by size. For the classification of fruit, the same plants were divided into classes based on the diameter of the fruit. The diameter size was as follows: class 1, 3 cm; class II, 4 cm; class III, 4.5 cm; and class IV, 5.5 cm. The results showed that there were no significant differences in production among the cultivars studied. Cultivars 'AP-533' and 'Hypeel 513' demonstrated greater production per plant, when ground cover was used, yielding 1474 and 1404 g/plant, respectively. When black polyethylene ground cover was not used, these cultivars produced 1258 and 1271 g of fruit per plant, respectively. The cultivars 'AP-529' and 'PS41818' showed a greater yield of fruit when cultivated without ground cover, with 1548 and 1663 g/plant, respectively. The cultivar 'Hypeel 513' had the highest percentage of fruit with the largest dimensions. An interaction was appeared between 'AP-529' and ground cover, where the production of this cultivar was lower with black polyethylene ground cover compared to bare ground. It is concluded that there are no significant differences in the cultivation of the tomato hybrids 'AP-533', 'Hypeel 513' and 'PS-41816' with and without ground cover, but that the cultivar 'AP-529' should be planted preferentially in soil without black polyethylene cover.

Carga de trabalho de enfermagem e infecções relacionadas à assistência à saúde na unidade de terapia intensiva

In recent decades, the search for quality care has been widely discussed by the institutions and health professionals. In this context, it is the nurse coordinator of the process of providing nursing staff, reflecting the commitment to quality of care. In this process, it is the appearance of Infections Related to health care and its potential association with the workload in nursing as a valuable indicator of quality of care. Thus, this research contributes to studies to characterize the demand of nursing work to promote a safe healthcare practice. This study aimed to identify the association of nursing workload with the number of cases of Ventilator-Associated Pneumonia, urinary tract infection and central venous catheter infection in the intensive care unit. This is a quantitative research approach, descriptive, cross-sectional and prospective, held at Unimed Hospital in Natal-RN. The study population consisted of all patients treated in the Intensive Care Unit, Hospital for a period of 90 consecutive days in 2011. The convenience sample was compostapelos patients admitted to the ICU during the period of data collection, a total sample of 286 patients. To perform the data analysis software were used: Statistica 6.0, SPPS (Statistical Package for Social Sciences) version 17.0 (2004) and Excel 2007. In the descriptive analysis, we used Measures of Central Tendency and Measures of Dispersion or Variability and the use of nonparametric tests. Of the 286 patients, 88 were from the ICU and 198 ICU II II. Males predominated in the ICU I (51.1%) and female ICU II (57.6%) patients in the ICU I were aged 61-80 years (39.8%) followed by greater than 80 years (39.8%). In the ICU II, most of the patients were aged 61-80 years (38.9%) and then from 41 to 60 years (24.2%). In relation to the class of TISS inlet predominant class II in the two ICUs (59.1%), followed by Class III also in the two units (34.6%). Most patients (70.6%) out of the ICUs belonging to class II TISS. In the ICU I, the average number of forms of the TISS 28 was 6, has in ICU II this value drops to 3.2 forms. The overall mean was 19.9 TISS points in ICU patients I and ICU II.the 17 points in the average hours required to provide adequate nursing care to patients in the ICU I found that is 10 , 7 hours, and the ICU II 9.2 hours. It was found that the time provided by the nursing staff were higher in ICU II, with an average of 19 hours available for nurses in this sector. In the ICU I, which showed higher need of available hours, it was found that the mean value of 12.7 available hours. It was found that only 2.4% of patients had these units Ventilator-Associated Pneumonia, 1.0% were infected central venous catheter and 1.4% of patients had urinary tract infection. Infection associated with health care occurs, on average, on the tenth day of hospitalization. In the ICU II, this average value extends to the twelfth day with an excess of 2.7 hours of nursing care while in ICU I value decays to the ninth day of hospitalization with a deficiency of 12-hour assistance. It is concluded that patients generally showed a need for classification of semi-intensive care and has been assisted in their need to load. As for his association with the Related Infections Health will assist this analysis could not be performed due to the small number of notifications in this period. It is suggested further study how other factors related to infections me a longer period of analysis