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Blood pressure (BP) control is a key intervention to decrease cardiovascular diseases (CVD), the main cause of death in low and middle-income countries (MIC). Scarce data on the determinants of BP control in Latin America are available. Our objective is to explore the role of gender, age, education, and income as social determinants of BP control in Argentina, a MIC with a universal health care system. We evaluated 1184 persons in two hospitals. Blood pressure was measured using automatic oscillometric devices. We selected those patients treated for hypertension. The average BP of less than 140/90 mmHg was considered a controlled BP. We found 638 hypertensive individuals, of whom 477 (75%) were receiving antihypertensive drugs, and of those, 248 (52%) had controlled BP. The prevalence of low education was more frequent in uncontrolled patients (25.3% vs. 16.1%; P < .01). We did not find association between household income, gender, and BP control. Older patients had less BP control (44% of those older than 75 years vs. 60.9% of those younger than 40; test for trend P < .05). Multivariate regression indicates low education (OR 1.71 95% CI [1.05, 2.79]; P = .03) and older age (OR 1.01; 95% IC [1.00, 1.03]) as independent predictors of the lack of BP control. We conclude that rates of BP control are low in Argentina. In a MIC with a universal health care system low education and old age but not household income are independent predictors of the lack of BP control.

Subclinical atherosclerosis (SCA) occurs in asymptomatic individuals. Blood peripheral monocytes are involved in the development of atherosclerosis. Circulating monocytes acquire pro-inflammatory profiles, and they are involved in the early stages of atherosclerosis development. Low-density lipoprotein Receptor-related Protein 1 (LRP1) is expressed in monocytes, mainly in classical and intermediate subsets. Although LRP1 is highly expressed in macrophages and vascular smooth muscle cells (VSMCs) in atherosclerotic plaque formation, its expression in circulating monocytes has not been studied in SCA. The aim of this study was to characterize the LRP1 expression level in circulating monocytes of individuals with SCA and compared with individuals with low (LR) and intermediate (IR) risk of cardiovascular diseases, both without evidence of atherosclerotic lesions in carotid and coronary arteries. LRP1 and additional markers (CD11b, CD11c, and CD36) at cell surface of monocytes were analyzed by flow cytometry assays, whereas LRP1 and pro-inflammatory factors gene expressions were measured in isolated monocytes by quantitative RT-PCRs. Both LRP1 protein and LRP1 mRNA were significantly reduced in monocytes in SCA and IR respect to LR. Conversely, CD36, CD11b, and CD11c monocytic markers showed no significant changes between the different study groups. Finally, increased gene expressions of TNF- α and IL-1 β were detected in monocytes of SCA, which were associated with decreased LRP1 expression at the cell surface in total monocytes. In summary, we propose that the decreased LRP1 expression at cell surface in total monocytes with pro-inflammatory profile is associated with the development of atherosclerosis in asymptomatic individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Albertini, Nicolas, Actis Dato, Ferrer, Tinti, Capra and Chiabrando.)

Introduction: COVID-19 disease shows a marked heterogeneity in its clinical course, with descriptions of some factors associated with a worse prognosis. Knowledge of the disease behavior in the local scenario is relevant to allow a better approach., Methods: Retrospective study in two hospitals in the city of Córdoba, Argentina, with patients aged 18 years or more, hospitalized for active SARS-CoV-2 infection, from March to October, 2020., Results: 448 patients were included, of which 95.75% corresponded to COVID-19 pneumonia. Most of the episodes occurred in men (63.6%), the median age was 63 years (IQR: 53-75), and the most frequent comorbidities were arterial hypertension (55.1%), obesity (31.7%) and diabetes mellitus (28.1%). 162 patients (36.2%) needed admission to the intensive care unit and 66 (14.7%) were placed on mechanical ventilation. 67 patients (15%) died within the first 30 days of follow-up. In the multivariate analysis, the only independent variable predictive of mortality at 30 days was age (adjusted Odds ratio [aOR] = 1.08, 95% CI = 1.04-1.11, p <0.001). The 4C-Score and CALL-Score prognostic scores showed good discrimination (Area under the curve [AUC] = 0.766, 95% CI = 0.72-0.80 and AUC = 0.785, 95% CI = 0.70-0.85 respectively) and the predicted percentages of mortality were quite close to what was observed in the present study., Conclusions: Most of the patients hospitalized with SARS-CoV-2 infection presented comorbidities and were admitted with pneumonia, associated with high mortality. The prognostic scores with the best performance to predict complications were the 4C-score and the CALL-score., (Universidad Nacional de Córdoba)

The performance of available risk scores to predict cardiovascular risk (CVR) in the Argentinian population is unknown. Our aim was to compare the CVR predicted by several equations with the occurrence of cardiovascular events (CVE) in patients without known cardiovascular disease in an Argentinian hospital. Adults between 40 and 70 years were randomly selected, excluding those with prior history of major CVE, active cancer, lipid lowering treatment and absence of follow-up data. Framingham 2008, SCORE (low and high-risk populations), ATP III, World Health Organization- American B region (WHO-B) and Pooled Cohort equations (PC) risk scores were used to calculate 10-y CVR at time of enrollment. End of follow-up was 10 years ± 6 months, occurrence of fatal myocardial infarction or death from any cause. We used ROC curves to assess discrimination (AUC > 0.75 good discrimination), and Hosmer Lemeshow chi-square to evaluate calibration (Chi > 20 or p value < 0.05 poor calibration). We included 606 patients in our study, 336 women, average age 56.7 ± 8.4 year. Of those, 10 (1.7%) non-cardiovascular deaths, and 5 (0.8%) cardiovascular deaths were observed. 58 (9.8%) a non-fatal CVE were recorded. There was acceptable discrimination for Framingham, ATP-III, and both PC equations. The global calibration was only good with the ATP-III and PC equations. The observed frequency of CVE was low, and the CVR was overestimated by all equations. However, applying ATP-III or PC equations to assess CVR could be considered in our population.

The incidence of acute kidney injury (AKI) in hospitalized patients with COVID-19 is variable, being associated with worse outcomes. The objectives of the study were to evaluate the incidence, risk factors (considering demographic characteristics, comorbidities, initial clinical presentation and associated complications) and impact of AKI in subjects hospitalized for COVID-19 in two third-level hospitals in Córdoba, Argentina. A retrospective cohort study was conducted. We included 448 adults who were consecutively hospitalized for COVID-19 between March 3 and October 31, 2020 and were followed throughout the hospitalization. The incidence of AKI was 19% (n = 85; stage I = 43, stage II = 17, and stage III = 25, 18 required renal replacement therapy). In the multivariate analysis, the variables that were independently associated with AKI were: age (for every 10 years, adjusted odd ratio [95%CI] = 1.30 [1.04-1.63], p = 0.022), history of chronic kidney disease -CKD- (9.92 [4.52-21.77], p < 0.001), blood neutrophil count at admission -BNCA- (for every increase of 1000 BNCA, 1.09 [1.01-1.18], p = 0.037) and requirement for mechanical ventilation -MV- (6.69 [2.24-19.90], p = 0.001). AKI was associated with longer hospitalization, higher admission (63.5 vs. 29.7%; p < 0.001) and longer stay in the intensive care unit, a positive association with respiratory bacterial superinfection, sepsis, respiratory distress syndrome, MV requirement and mortality (mortality without AK I = 12.4% vs with AKI = 47.1%; stage I = 26%, stage II = 41% and stage III = 88%; p < 0.001). AKI was independently associated with higher mortality (3.32 [1.6-6.9], p = 0.001). In conclusion, the incidence of AKI in adults hospitalized for COVID-19 was 19% and had a clear impact on morbidity and mortality. The independent risk factors for AKI were: Age, CKD, BNCA and MV.

Introduction: Urinary Tract Infections (UTI) are an important cause of morbidity in the community, constituting one of the main reasons for hospitalization, and the fourth cause of healthcare-associated infection. The objectives of this study were to determine the frequency of community-acquired UTI (CA-UTI) with need of hospitalization and healthcare-associated UTI (HA-UTI), their risk factors, etiologic agents and their antimicrobial susceptibility spectrum., Methods: A prospective and analytic study was conducted, in which all admissions regarding CA-UTI with need of hospitalization and HA-UTI were evaluated during the period between 2016 and 2017 in two university hospitals., Results: A total of 279 episodes of UTI in hospitalized patients were identified and, among those, 178 episodes corresponded to CA-UTI and 101 to HA-UTI. On average, patients were 60 years old in both groups. HA-UTI were more frequently associated with kidney transplant, recurrent UTI and chronic kidney disease compared with CA-UTI. The instrumentation of urinary tract within the previous month was more frequent in HA-UTI (75.2% vs 32.6%, p<0.001). Escherichia coli was the most frequent isolated microorganism (62.9% in CA-UTI and 56.4% in HA-UTI), followed by Klebsiella pneumoniae and Pseudomonas aeruginosa. A total of 101 multidrug resistant microorganisms were isolated, of which 53.5% were CA-UTI, and were associated with male patients, use of antimicrobials within the previous three months, chronic kidney disease and recurrent UTI., Conclusion: It is of great importance for the institutions to identify the local antimicrobial susceptibility spectrum of UTI in order to stablish adequate empiric treatments., (Universidad Nacional de Córdoba.)

Introduction: Uncomplicated urinary tract infections(UC-UTI) represent a frequent reason for consultation. Most cases are empirically treated, but the antimicrobial susceptibility of the causative microorganisms has changed over the past years. The objectives of this study where to determine UC-UTI causative microorganism and their antimicrobial susceptibility profiles in adult women., Methods: A prospective analytic study was conducted in two hospital in Córdoba, Argentina, between November/2016 and October/2017. From the identification of positive urine cultures, urinary tract infections (UTI) in women ≥18 years without risk factors for complicated UTIs were included, excluding asymptomatic bacteriurias., Results: A total of 610 UC-UTI were identified and 62.6% of them in patients younger than 50 years; 73.3% of cases were cystitis, being more frequent in older women. Escherichia coli was isolated in 89.2% of UTI and negative coagulase Staphylococcus in 4.2%. As regards Escherichia coli, its resistance against ciprofloxacin was 18.8%; 4.4% against ceftriaxone and 1.8% against nitrofurantoin. There was an elevated resistance against ampicillin, trimethoprim–sulfamethoxazole and ampicillin–sulbactam., Main Conclusion: The most frequent isolated microorganism was Escherichia coli, consistent with global epidemiology. This microorganism showed less than 20% total resistance against ciprofloxacin, ceftriaxone and nitrofurantoin., (Universidad Nacional de Córdoba)

Background: The use of stress ulcer prophylaxis (SUP) has risen in recent years, even in patients without a clear indication for therapy., Aim: To evaluate the efficacy of an electronic medical record (EMR)-based alarm to improve appropriate SUP use in hospitalized patients., Methods: We conducted an uncontrolled before-after study comparing SUP prescription in intensive care unit (ICU) patients and non-ICU patients, before and after the implementation of an EMR-based alarm that provided the correct indications for SUP., Results: 1627 patients in the pre-intervention and 1513 patients in the post-intervention cohorts were included. The EMR-based alarm improved appropriate (49.6% vs. 66.6%, p<0.001) and reduced inappropriate SUP use (50.4% vs. 33.3%, p<0.001) in ICU patients only. These differences were related to the optimization of SUP in low risk patients. There was no difference in overt gastrointestinal bleeding between the two cohorts. Unjustified costs related to SUP were reduced by a third after EMR-based alarm use., Conclusions: The use of an EMR-based alarm improved appropriate and reduced inappropriate use of SUP in ICU patients. This benefit was limited to optimization in low risk patients and associated with a decrease in SUP costs., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis characterized by abnormalities in the anchoring fibrils which attach the basal cell layer of the epidermis to the underlying structures. A characteristic feature of this disorder is the presence of recurrent blistering or erosions, the result of even minor traction to these tissues. Patients with RDEB frequently develop chronic renal failure, and require renal replacement therapy being a major cause of morbidity and mortality. The role of renal transplantation in these patients is scarcely known. We present the case of an end-stage renal disease patient with RDEB treated by renal transplantation and his follow-up during a period of 83 months after the transplant. In this period, there were very low frequency of serious infections as well as the absence of skin tumors. Renal transplantation could be an alternative to renal replacement therapy in epidermolysis bullosa patients with end-stage renal disease, reducing the comorbidities associated with this treatment.

Introduction: Nosocomially acquired urinary tract infections (NAUTI) represent an important public health issue, but its characteristics when they are not catheter associated (CA-UTI) or when they take place outside intensive care units (ICU) are poorly understood., Objectives: To determine the patients' characteristics, etiology and antimicrobial susceptibility of NAUTI, both CA-UTI and no CA-UTI, in general ward and ICU., Methods: We conducted a retrospective analytic cross-sectional study, between 2009 and 2013, in a third level universitary hospital. All NAUTI episodes were identified, classifying them as CA-UTI and no CA-UTI., Results: We included 253 episodes of NAUTI, being CA-UTI (60,9%) more frequent than no CA-UTI. A 37,4% of no CA-UTI and 59,7% of CA-UTI were identified in ICU. The most frequently isolated microorganisms were Escherichia coli, Klebsiella pneumoniae and Enterococcus sp. A 19% of extended spectrum betalactamase producing gram negative bacilli were found, without differences between groups., Conclusion: Patients's comorbidities, microorganisms associated to NAUTI and its antimicrobial susceptibility were similar in CA-UTI and no CA-UTI, as in general ward and ICU.

The goal of our study was to use statistical analysis to try to associate cardiovascular disease (CVD) risk scores and the observed prevalence of subclinical atherosclerosis (SA) in a non-elderly adult local population. An observational cross-sectional study was carried out (143 male and 131 female) on non-elderly adults (20-59 years). CVD risk scores included Framingham Risk Scores for 10-year hard (FRS 10 H), 30-year lipid hard or CVD (FRS 30 L H or FRS 30 L CVD), 30 year-body mass index hard or CVD (FRS 30 BMI H or FRS 30 BMI CVD) and Pooled Cohort Risk Equations for either 10 years (PCE 10) or lifetime (PCE LT). The Carotid Ultrasound (CU) study was performed and the Coronary Artery Calcium (CAC) score were obtained to assess SA. The Receiving Operating Characteristic (ROC) curve analysis followed by Youden's index was used to evaluate and adjust the stratification of CVD risk scores. SA was detected in 32.4% of individuals. The risk scores that showed the biggest areas under the ROC curve were FRS 30 L (H and CVD). When the cut-off values for these CVD risk scores were adjusted, the FRS 30 L H increased the negative predictive value for the low risk group from 87.7 to 97.0% and the FRS 30 L CVD increased the positive predictive values for the high risk group from 69.7 to 85.7%. The CVD risk stratification of non-elderly adults using FRS 30 L H and FRS 30 L CVD may be a useful tool for selecting candidate patients for diagnostic imaging studies that assess their SA prevalence.

Our objectives were to determine the etiology and analyze the antibiotic resistance profiles of microorganisms causing uncomplicated urinary tract infections in our setting. An analytical cross-sectional study was conducted. In vitro antimicrobial resistance of urine cultures was analyzed. 580 urine cultures of women over age fifteen were included. 82.6 % of urine cultures corresponded to cystitis and the remaining 17.4 % corresponded to pyelonephritis. 353 urine cultures of women <50 years old (60.9%) and 227 of women = 50 years old (39.1%) were obtained. The most common pathogens were Escherichia coli (85.5 %) and Klebsiella pneumoniae (4.7 %). For Escherichia coli, there was a resistance of 28.6% to trimethoprim-sulfamethoxazole,7.9% to ciprofloxacin and 0.4% to nitrofurantoin. Significant difference (p = 0.005) was seen in the resistance to ciprofloxacin in women = 50 years old. Our data show there is a low in vitro resistance to nitrofurantoin

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma that selectively affects small and medium-sized bloodvessels in the absence oflymph-adenopathy. The central nervous system (CNS) and skin are the organs most commonly affected. We describe the case of a 64-year-old male who presented to the emergency department (ED) complaining of asthenia and bilateral lower extremity edema that progressed rapidly to anasarca. On presentation, laboratory results were significant for elevated erythrocyte sedimentation rate (ESR) and lactate dehydrogenase (LDH) levels. A skin biopsywas performed, which revealed occlusion of blood vessels by atypical immunophenotype B lymphoid cells within the dermis and subcutaneous tissue. The immuno-histochemistry was consistent with IVLB CL. IVLBCL is an aggressive and rapidly fatal neoplasia with varied and nonspecific clinical manifestations, hence, a diagnostic challenge. This case shows an unusual presentation with asthenia and rapidly progressive edema.

Recent studies show that low-level laser therapy (LLLT) has an important anti-inflammatory action in acute lung inflammation. The present work explored if laser therapy is able to antagonize eosinophils and allergic inflammation induced by oxidative stress in Balb/c mice. Forty-eight hours after challenge, the leukocyte counting, ROS and nitrite/nitrate level, RANTES, CCL3, CCL8 as well as eotaxins were measured in the bronchoalveolar lavage fluid (BALF) of laser-treated mice or not. Into the lung, some chemokines receptors, the iNOS activity and mRNA expression, and the activities of superoxide dismutase (SOD), catalase, gluthatione, NADPH oxidase activities and thiobarbituric acid reactive species (T-Bars) were measured. Laser-treated allergic mice presented reduction of both the ICAM-1 and eosinophil in the lungs. RANTES, CCL8, CCL3 and eotaxins were reduced in BALF of laser-treated allergic mice. In allergic mice lung LLLT decreased the CCR1 and CCR3 and restored the oxidative stress balance as well. Laser decreased the lipidic peroxidation in allergic mice lung as much as increased SOD, GPx and GR. It shows that LLLT on allergic lung inflammation involves leukocyte-attractant chemokines and endogenous antioxidant. Based on results, LLLT may ultimately become a non- invasive option in allergic lung disease treatment. The top figure illustrates the laser decreasing the eosinophils migration into BALF and the bottom figure shows the laser upregulating the expression of heme-oxygenase (anti-oxidant enzyme) in lung tissue anti-oxidant., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Venous thromboembolism (VTE) is a major health issue that may result in complications such as post-thrombotic syndrome, pulmonary hypertension, and death. Appropriate thromboprophylaxis in individuals undergoing kidney transplantation remains unclear. The aim of this study was to determine the prevalence of symptomatic VTE and major bleeding within 90 days after renal transplantation (RT)., Methods: This was a retrospective study on consecutive patients undergoing RT at Hospital Privado Córdoba, Argentina, from January 1, 2006, to December 31, 2013. Exclusion criteria were age <18 years and combined organ transplantation. Pharmacologic or mechanical thromboprophylaxis was not used routinely. Symptomatic VTE and major bleeding were documented., Results: A total of 511 RTs were performed; 62 patients received combined organ transplantation, and 8 patients (1.5%) were lost to follow-up. Overall, follow-up was completed on 441 patients, 4 (0.9%) of whom developed deep venous thrombosis and 14 (3%) of whom died. The most frequent causes of death were septic shock and severe hemorrhage. Duration of surgery >4 hours (P = .006) and a history of VTE (P < .001) were associated with VTE. Twenty-three patients (5.2%) had major bleeding, 2 (0.4%) died from bleeding complications, and 17 (3.85%) required a reoperation to control bleeding., Conclusions: This study shows a low prevalence of symptomatic VTE in patients undergoing RT despite not having used thromboprophylaxis routinely. Major bleeding was significant, and despite the high risk of VTE assigned by the Caprini score, which suggests pharmacologic prophylaxis, our data raise questions about the appropriate prophylaxis for these patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this article, we present a flow cytometry assay by which human blood monocyte subpopulations-classical (CD14(++) CD16(-)), intermediate (CD14(++) CD16(+)), and nonclassical (CD14(+) CD16(++)) monocytes-can be determined. Monocytic cells were selected from CD45(+) leukocyte subsets by differential staining of the low-density lipoprotein receptor-related protein 1 (LRP1), which allows reducing the spill-over of natural killer cells and granulocytes into the CD16(+) monocyte gate. Percentages of monocyte subpopulations established by this procedure were significantly comparable with those obtained by a well-standardized flow cytometry assay based on the HLA-DR monocyte-gating strategy. We also demonstrated that LRP1 is differentially expressed at cell surface of monocyte subpopulations, being significantly lower in nonclassical monocytes than in classical and intermediate monocytes. Cell surface expression of LRP1 accounts for only 20% of the total cellular content in each monocyte subpopulation. Finally, we established the within-individual biological variation (bCV%) of circulating monocyte subpopulations in healthy donors, obtaining values of 21%, 20%, and 17% for nonclassical, intermediate, and classical monocytes, respectively. Similar values of bCV% for LRP1 measured in each monocyte subpopulation were also obtained, suggesting that its variability is mainly influenced by the intrinsic biological variation of circulating monocytes. Thus, we conclude that LRP1 can be used as a third pan-monocytic marker together with CD14 and CD16 to properly identify monocyte subpopulations. The combined determination of monocyte subpopulations and LRP1 monocytic expression may be relevant for clinical studies of inflammatory processes, with special interest in atherosclerosis and cardiovascular disease., (© 2014 International Society for Advancement of Cytometry.)

Introduction: The increase in the number of studies has led to greater security in the application of this method and the determination of its effectiveness in adults.. The purpose of the present study was to evaluate heart rate variability in healthy individuals submitted to different levels of positive expiratory pressure using an expiratory positive airway pressure (EPAP) device., Material and Methods: The study involved 27 healthy male individuals ranging in age from 20 to 35 years. Patient histories were taken and the subjects were submitted to a physical examination. The volunteers were monitored using the Polar 810s(®) and submitted to the EPAP experiment. Analyses were performed on variables of the frequency domain. Sympathetic and parasympathetic bands and their relationship with sympathovagal response were also analyzed., Results: The mean value of this variable was 526.89 (55.50) ms(2) in the first period, 2811.0 (721.10) ms(2) in the fourth period and 726.52 (123.41) ms(2) in the fifth period. Regarding the parasympathetic area, significant differences were detected when Periods 1 and 5 (no load) were compared with periods in which the individuals were subjected to the use of the therapy. Sympathetic and parasympathetic areas together, a significant difference was detected regarding the sympathetic/parasympathetic ratio in the comparison between Periods 1 and 4 (p < 0.01) as well as Periods 2 and 4 (p < 0.05)., Conclusions: The findings of the present study suggest that the therapeutic use of EPAP significantly alters the parameters of heart rate variability in the frequency domain, highlighting the importance of monitoring and care during the practice of EPAP.

Vertebroplasty is a minimally invasive technique for the treatment of osteoporotic fractures. Within its complications is pulmonary embolism, which can be asymptomatic or with respiratory distress and may be notes by radiography or computed tomography. At present there is no guide to indicate the routine performance of imaging techniques after treatment, and all agreed on the need to start anticoagulant therapy for 3 months or so with coumarin in symptomatic or asymptomatic central emboli.

Hydatidosis is an endemic disease in different parts of the world. Its causal agent is the cestode from the genus Echinococcus. The most commonly affected organs in humans are liver and lung. Bone hydatid disease is a very rare entity, accounting for 0.5 to 4% of total cases. We report a case of a 58 year-old woman from La Rioja, Argentina, who consulted for left infapatellar pain and walking disability of eight months duration. Imaging studies showed a cystic lesion which involved metaphysis and diaphysis of left proximal tibia. Surgical resection was performed and histopathological study confirmed that it was a hydatid cyst. The patient did well and completed three cycles of treatment with albendazole. Currently, she has no evidence of disease and she recovered motility of her left leg. Primary hydatid bone disease, where there is no evidence of systemic disease, is even more unusual. Tibia involvement occurs in up to 15% of the cases. These lesions clinically manifest when they suffer any type of complications. Preoperative diagnosis is mainly made by imaging studies. Lesions are usually osteolytic and can involve cortical bone and extend to soft tissues. Differential diagnosis with inflammatory processes and bone tumors should is mandatory. Treatment is surgical and prognosis is poor due to its high morbi-mortality rate and recurrence risk from 70 to 80%.

The main physiological characteristics in a burn process are the increase of the capillary permeability and the occurrence of edema and exudation. Light-emitting diode (LED) has been proposed as treatment of burning. This study investigated the effects of LED on the repair process of rat skin submitted to a third-degree burning. The lesions were produced on the dorsal surface of male Wistar rats. Animals were divided into 4 groups (n = 6) as follows: L1 and L2 groups as LED-treated burned rats, and received LED therapy along 7 and 15 days with 48 hours intervals, respectively; C1 and C2 groups as control, non-treated burned rats. A red LED (640 nm, 30 mW) operating with a fluence of 4 J/cm(2) was used. The wound area was measured daily after irradiation. Animals were euthanized at the 8th and 16th days after burning, and the wound fragment was submitted to histology. The inflammatory cells as well as the damaged area at the 8th day after burns were significantly lower for the LED-treated group when compared to control. Furthermore, the LED phototherapy effect on cellular migration was even more pronounced at the 16th day. Our results indicated that the treatment with a LED system was clearly effective in reducing the number of inflammatory cells and improving the healing process in an experimental model of third-degree burnings.

1,3-Butadiene (BD) is a multisite carcinogen in laboratory rodents following lifetime exposure, with greater potency in the mouse than the rat, and is associated with an increase in leukemia mortality in highly exposed workers. Species differences in the formation of reactive metabolites underlie observed species differences in sensitivity to the carcinogenic effects of BD. The modes of action (MOAs) for human leukemia and rodent tumors are both likely related to mutagenic potencies of one or more of these metabolites. However, differences in the nature of genotoxic lesions associated with human leukemia and rodent tumors, along with their implications for risk assessment, require that they be discussed separately. The MOAs for BD are assessed in this review using the modified Hill criteria and human relevance framework. Key events in MOAs for human and rodent cancers are identified, along with important species differences and sources of nonlinearity for each event that can affect extrapolations made from high- to low-dose exposures. Because occupational exposures to BD have also included co-exposures to styrene and dimethyldithiocarbamide (DMDTC), potential interactions with BD carcinogenicity are also discussed. The MOAs for BD carcinogenesis will be used to guide key decisions made in the quantitative cancer dose-response assessment.

The viral RNA-dependent RNA polymerases show a conserved structure where the fingers domain interacts with the top of the thumb domain to create a tunnel through which nucleotide triphosphates reach the active site. We have solved the crystal structures of poliovirus polymerase (3D(pol)) in complex with all four NTPs, showing that they all bind in a common pre-insertion site where the phosphate groups are not yet positioned over the active site. The NTPs interact with both the fingers and palm domains, forming bridging interactions that explain the increased thermal stability of 3D(pol) in the presence of NTPs. We have also examined the importance of the fingers-thumb domain interaction for the function and structural stability of 3D(pol). Results from thermal denaturation experiments using circular dichroism and 2-anilino-6-napthaline-sulfonate (ANS) fluorescence show that 3D(pol) has a melting temperature of only approximately 40 degrees C. NTP binding stabilizes the protein and increases the melting by 5-6 degrees C while mutations in the fingers-thumb domain interface destabilize the protein and reduce the melting point by as much as 6 degrees C. In particular, the burial of Phe30 and Phe34 from the tip of the index finger into a pocket at the top of the thumb and the presence of Trp403 on the thumb domain are key interactions required to maintain the structural integrity of the polymerase. The data suggest the fingers domain has significant conformational flexibility and exists in a highly dynamic molten globule state at physiological temperature. The role of the enclosed active site motif as a structural scaffold for constraining the fingers domain and accommodating conformational changes in 3D(pol) and other viral polymerases during the catalytic cycle is discussed.

The complete time-resolved fluorescence of tryptophan in the proteins monellin and IIA(Glc) has been investigated, using both an upconversion spectrophotofluorometer with 150 fs time resolution and a time-correlated single photon counting apparatus on the 100 ps to 20 ns time scale. In monellin, the fluorescence decay displays multiexponential character with decay times of 1.2 and 16 ps, and 0.6, 2.2, and 4.2 ns. In contrast, IIA(Glc) exhibited no component between 1.2 ps and 0.1 ns. For monellin, surprisingly, the 16 ps fluorescence component was found to have positive amplitude even at longer wavelengths (e.g., 400 nm). In conjunction with quantum mechanical simulation of tryptophan in monellin, the experimental decay associated spectra (DAS) and time-resolved emission spectra (TRES) indicate that this fluorescence decay time should be ascribed to a highly quenched conformer. Recent models (Peon, J.; et al. Proc. Natl.Acad. Sci. U.S.A. 2002, 99, 10964) invoked exchange-coupled relaxation of protein water to explain the fluorescence decay of monellin.