Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA.

Electromyographic Study in Patients With Surgically Treated Facial Fractures

This study, using surface electromyography, analyzed the activity of the masseter muscles of 30 patients with facial bone fractures that were surgically treated. Evaluations were made before surgery and in the 7th, 30th, and 60th days after surgery. The value of each measure and the average of 3 maximum voluntary isometric contractions lasting 5 seconds each were registered, and statistical analyses were performed. Patients had a mean age of 31 years and an average of 1.33 fractures. They were grouped according to the type of fracture as follows: mandibular (50%), zygomatic complex (33%), maxilla (10%), and associated fractures (6.7%). There was a lower masseter activity in the preoperative period, when compared with normal values in all groups of fractures. There was a sharp drop in the masseter activity in the postoperative period of 7 days, and all groups showed recovery of activity in 60 days but still below the normal value referenced in the literature. The mean values of the masseter activity, in descending order, were from the zygomatic complex, mandibular, maxillary, and associated fractures. The unilateral mandibular fractures showed higher values than the bilateral fractures in most of the evaluations. There was a highly significant difference in the comparison of the evolution of the masseter activity on both sides, for mandibular and zygomatic complex fractures, and the pairwise comparison showed significant difference between most groups. It was concluded that facial fractures and surgical procedures had negative effects in the muscle activity as observed using electromyography.

Ethnicity and Cutaneous Melanoma in the City of Sao Paulo, Brazil: A Case-Control Study

Background: Over the last century the incidence of cutaneous melanoma has increased worldwide, a trend that has also been observed in Brazil. The identified risk factors for melanoma include the pattern of sun exposure, family history, and certain phenotypic features. In addition, the incidence of melanoma might be influenced by ethnicity. Like many countries, Brazil has high immigration rates and consequently a heterogenous population. However, Brazil is unique among such countries in that the ethnic heterogeneity of its population is primarily attributable to admixture. This study aimed to evaluate the contribution of European ethnicity to the risk of cutaneous melanoma in Brazil. Methodology/Principal Findings: We carried out a hospital-based case-control study in the metropolitan area of Sao Paulo, Brazil. We evaluated 424 hospitalized patients (202 melanoma patients and 222 control patients) regarding phenotypic features, sun exposure, and number of grandparents born in Europe. Through multivariate logistic regression analysis, we found the following variables to be independently associated with melanoma: grandparents born in Europe-Spain (OR = 3.01, 95% CI: 1.03-8.77), Italy (OR = 3.47, 95% CI: 1.41-8.57), a Germanic/Slavic country (OR = 3.06, 95% CI: 1.05-8.93), or >= 2 European countries (OR = 2.82, 95% CI: 1.06-7.47); eye color-light brown (OR = 1.99, 95% CI: 1.14-3.84) and green/blue (OR = 4.62; 95% CI 2.22-9.58); pigmented lesion removal (OR = 3.78; 95% CI: 2.21-6.49); no lifetime sunscreen use (OR = 3.08; 95% CI: 1.03-9.22); and lifetime severe sunburn (OR = 1.81; 95% CI: 1.03-3.19). Conclusions: Our results indicate that European ancestry is a risk factor for cutaneous melanoma. Such risk appears to be related not only to skin type, eye color, and tanning capacity but also to others specific characteristics of European populations introduced in the New World by European immigrants.

Characterization and in vitro evaluation of bacterial cellulose membranes functionalized with osteogenic growth peptide for bone tissue engineering

The aim of this study was to characterize the physicochemical properties of bacterial cellulose (BC) membranes functionalized with osteogenic growth peptide (OGP) and its C-terminal pentapeptide OGP[10-14], and to evaluate in vitro osteoinductive potential in early osteogenesis, besides, to evaluate cytotoxic, genotoxic and/or mutagenic effects. Peptide incorporation into the BC membranes did not change the morphology of BC nanofibers and BC crystallinity pattern. The characterization was complemented by Raman scattering, swelling ratio and mechanical tests. In vitro assays demonstrated no cytotoxic, genotoxic or mutagenic effects for any of the studied BC membranes. Culture with osteogenic cells revealed no difference in cell morphology among all the membranes tested. Cell viability/proliferation, total protein content, alkaline phosphatase activity and mineralization assays indicated that BC-OGP membranes enabled the highest development of the osteoblastic phenotype in vitro. In conclusion, the negative results of cytotoxicity, genotoxicity and mutagenicity indicated that all the membranes can be employed for medical supplies, mainly in bone tissue engineering/regeneration, due to their osteoinductive properties.

On Disruption of Fear Memory by Reconsolidation Blockade: Evidence from Cannabidiol Treatment

The search for reconsolidation blockers may uncover clinically relevant drugs for disrupting memories of significant stressful life experiences, such as those underlying the posttraumatic stress disorder. Considering the safety of systemically administered cannabidiol (CBD), the major non-psychotomimetic component of Cannabis sativa, to animals and humans, the present study sought to investigate whether and how this phytocannabinoid (3-30 mg/kg intraperitoneally; i.p.) could mitigate an established memory, by blockade of its reconsolidation, evaluated in a contextual fear-conditioning paradigm in rats. We report that CBD is able to disrupt 1- and 7-days-old memories when administered immediately, but not 6 h, after their retrieval for 3 min, with the dose of 10 mg/kg being the most effective. This effect persists in either case for at least 1 week, but is prevented when memory reactivation was omitted, or when the cannabinoid type-1 receptors were antagonized selectively with AM251 (1.0 mg/kg). Pretreatment with the serotonin type-1A receptor antagonist WAY100635, however, failed to block CBD effects. These results highlight that recent and older fear memories are equally vulnerable to disruption induced by CBD through reconsolidation blockade, with a consequent long-lasting relief in contextual fear-induced freezing. Importantly, this CBD effect is dependent on memory reactivation, restricted to time window of <6h, and is possibly dependent on cannabinoid type-1 receptor-mediated signaling mechanisms. We also observed that the fear memories disrupted by CBD treatment do not show reinstatement or spontaneous recovery over 22 days. These findings support the view that reconsolidation blockade, rather than facilitated extinction, accounts for the aforementioned CBD results in our experimental conditions. Neuropsychopharmacology (2012) 37, 2132-2142; doi:10.1038/npp.2012.63; published online 2 May 2012

Homogeneity assessment of a station climate series (1933-2005) in the Metropolitan Area of Sao Paulo: instruments change and urbanization effects

This work assessed homogeneity of the Institute of Astronomy, Geophysics and Atmospheric Sciences (IAG) weather station climate series, using various statistical techniques. The record from this target station is one of the longest in Brazil, having commenced in 1933 with observations of precipitation, and temperatures and other variables later in 1936. Thus, it is one of the few stations in Brazil with enough data for long-term climate variability and climate change studies. There is, however, a possibility that its data may have been contaminated by some artifacts over time. Admittedly, there was an intervention on the observations in 1958, with the replacement of instruments, for which the size of impact has not been yet evaluated. The station transformed in the course of time from rural to urban, and this may also have influenced homogeneity of the observations and makes the station less representative for climate studies over larger spatial scales. Homogeneity of the target station was assessed applying both absolute, or single station tests, and tests relatively to regional climate, in annual scale, regarding daily precipitation, relative humidity, maximum (TMax), minimum (TMin), and wet bulb temperatures. Among these quantities, only precipitation does not exhibit any inhomogeneity. A clear signal of change of instruments in 1958 was detected in the TMax and relative humidity data, the latter certainly because of its strong dependence on temperature. This signal is not very clear in TMin, but it presents non-climatic discontinuities around 1953 and around 1970. A significant homogeneity break is found around 1990 for TMax and wet bulb temperature. The discontinuities detected after 1958 may have been caused by urbanization, as the observed warming trend in the station is considerably greater than that corresponding to regional climate.

Delay in the search for health services for the diagnosis of tuberculosis in Ribeirao Preto, Sao Paulo

The scope of this paper is to analyze delays in locating health services for the diagnosis of tuberculosis in Ribeirao Preto in 2009. An epidemiological and cross-sectional study was conducted with 94 TB patients undergoing treatment. A structured questionnaire, based on the Primary Care Assessment Tool adapted for TB care was used. A median (15 days or more) was established to characterize delay in health attendance. Using the Prevalence Ratio, the variables associated with longer delay were identified. The first healthcare services sought were the Emergency Services (ES) (57.5%). The longest period between seeking assistance occurred among males, aged between 50 and 59, who earned less than five minimum wages, had pulmonary TB, were new cases, were not co-infected with TB/HIV, did not consume alcohol, had satisfactory knowledge about TB before diagnosis (with a statistically significant association with delay) and who did not seek healthcare close to home before developing TB. There is a perceived need for training healthcare professionals about the signs and symptoms of the disease, reducing barriers of access to timely diagnosis of TB and widely disseminating it to the community in general.

REDUCTION AND TIMING OF FUNGICIDE APPLICATION IN THE MANAGEMENT OF SCAB IN PLUM TREES

This work aimed to evaluate the incidence and severity of scab in prune trees under different fungicide management, with two time patterns of application; one at the early fruit formation, up to pit hardening, and another starting after pit hardening, and compare the number of fungicide application reductions with the management adopted by the producer Four experiments, with different treatments, were carried out during the 2004-2005 and 2005-2006 seasons (two experiments,) and that of 2008-2009, using the Harry Pickstone and Reubennel cultivars. The most efficient control of the disease was achieved with the combination of metiram, piraclostrobina e ditianona fungicides from late bloom to pit hardening. Efficient scab control in prune was dependent on the combination of the fungicides used and the application timing. Reduced fungicide management is possible, while spraying initiated after pit hardening was not efficient for scab control.

Rehabilitative treatment of cleft lip and palate: experience of the Hospital for Rehabilitation of Craniofacial Anomalies - USP (HRAC-USP) - Part 3: Oral and Maxillofacial Surgery

This paper presents the treatment protocol of maxillofacial surgery in the rehabilitation process of cleft lip and palate patients adopted at HRAC-USP. Maxillofacial surgeons are responsible for the accomplishment of two main procedures, alveolar bone graft surgery and orthognathic surgery. The primary objective of alveolar bone graft is to provide bone tissue for the cleft site and then allow orthodontic movements for the establishment of an an adequate occlusion. When performed before the eruption of the maxillary permanent canine, it presents high rates of success. Orthognathic surgery aims at correcting maxillomandibular discrepancies, especially anteroposterior maxillary deficiencies, commonly observed in cleft lip and palate patients, for the achievement of a functional occlusion combined with a balanced face.

Delays in the diagnosis of tuberculosis in a town at the triple border of Brazil, Paraguay, and Argentina

Objective. To identify the factors linked to patients and health services in delays in the diagnosis of tuberculosis. Methods. Epidemiological study in Foz do Iguacu, Parana, Brazil, 2009. The Primary Care Assessment Tool, adapted for appraising tuberculosis treatment, was the instrument used. Descriptive statistics techniques were used, such as frequency distributions, central tendency and dispersion measurements (median and interquartile intervals), and odds ratios. Results. There were greater delays in seeking health services for those in the age group 60 years and older, for females, for patients with low levels of education, and for patients with poor knowledge of the disease. Clinical variables (being a new case and HIV infection) and behavioral variables (use of tobacco and alcohol consumption) were not linked with delays in diagnosis. The median time delays before diagnosis attributable to patients and to the health services were 30 days and 10 days, respectively. Emergency 24-hour medical services and primary health care services were not effective in identifying suspicious cases of tuberculosis and requesting tests to confirm the diagnosis, with a high percentage of referrals to the Tuberculosis Control Program clinic. Conclusions. Going to primary health care services for diagnosis increased the time before diagnosis of the disease was reached. The Tuberculosis Control Program clinic was more effective in diagnosis of tuberculosis, due to the training of the staff and to an organized process for receiving patients, including the availability of tests to support the diagnosis.

Interleukin-4 Modulates the Inflammatory Response in Ifosfamide-Induced Hemorrhagic Cystitis

We investigated whether interleukin-4 (IL-4) is present and capable of reducing inflammatory changes seen in ifosfamide-induced hemorrhagic cystitis. Male Swiss mice were treated with saline or ifosfamide alone or ifosfamide with the classical protocol with mesna and analyzed by changes in bladder wet weight (BWW), macroscopic and microscopic parameters, exudate, and hemoglobin quantification. In other groups, IL-4 was administered intraperitoneally 1 h before ifosfamide. In other experimental groups, C57BL/6 WT (wild type) and C57BL/6 WT IL-4 (-/-) knockout animals were treated with ifosfamide and analyzed for changes in BWW. Quantification of bladder IL-4 protein by ELISA in control, ifosfamide-, and mesna-treated groups was performed. Immunohistochemistry to tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) as well as protein identification by Western blot assay for inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was carried out on ifosfamide- and IL-4-treated animals. In other experimental groups, antiserum against IL-4 was given 30 min before ifosfamide. In IL-4-treated animals, the severity of hemorrhagic cystitis was significantly milder than in animals treated with ifosfamide only, an effect that was reverted with serum anti-IL-4. Moreover, knockout animals for IL-4 (-/-) exhibit a worse degree of inflammation when compared to C57BL/6 wild type. Exogenous IL-4 also attenuated TNF-alpha, IL-1 beta, iNOS, and COX-2 expressions in ifosfamide-treated bladders. IL-4, an anti-inflammatory cytokine, attenuates the inflammation seen in ifosfamide-induced hemorrhagic cystitis.

Assessment of nose protector for sport activities: finite element analysis

There has been a significant increase in the number of facial fractures stemming from sport activities in recent years, with the nasal bone one of the most affected structures. Researchers recommend the use of a nose protector, but there is no standardization regarding the material employed. Clinical experience has demonstrated that a combination of a flexible and rigid layer of ethylene vinyl acetate (EVA) offers both comfort and safety to practitioners of sports. The aim of the present study was the investigation into the stresses generated by the impact of a rigid body on the nasal bone on models with and without an EVA protector. For such, finite element analysis was employed. A craniofacial model was constructed from images obtained through computed tomography. The nose protector was modeled with two layers of EVA (1 mm of rigid EVA over 2 mm of flexible EVA), following the geometry of the soft tissue. Finite element analysis was performed using the LS Dyna program. The bone and rigid EVA were represented as elastic linear material, whereas the soft tissues and flexible EVA were represented as hyperelastic material. The impact from a rigid sphere on the frontal region of the face was simulated with a constant velocity of 20 m s-1 for 9.1 mu s. The model without the protector served as the control. The distribution of maximal stress of the facial bones was recorded. The maximal stress on the nasal bone surpassed the breaking limit of 0.130.34 MPa on the model without a protector, while remaining below this limit on the model with the protector. Thus, the nose protector made from both flexible and rigid EVA proved effective at protecting the nasal bones under high-impact conditions.

Intrauterine Undernourishment Alters TH1/TH2 Cytokine Balance and Attenuates Lung Allergic Inflammation in Wistar Rats

IL-4 produced by Th2 cells can block cytokine production by Th1 cells, and Th1 IFN-gamma is known to counterregulate Th2 immune response, inhibiting allergic eosinophilia. As intrauterine undernutrition can attenuate lung inflammation, we investigated the influence of intrauterine undernourishment on the Th1/Th2 cytokine balance and allergic lung inflammation. Intrauterine undernourished offspring were obtained from dams fed 50% of the nourished diet of their counterparts and were immunized at 9 weeks of age. We evaluated the cell counts and cytokine protein expression in the bronchoalveolar lavage, mucus production and collagen deposition, and cytokine gene expression and transcription factors in lung tissue 21 days after ovalbumin immunization. Intrauterine undernourishment significantly reduced inflammatory cell airway infiltration, mucus secretion and collagen deposition, in rats immunized and challenged. Intrauterine undernourished rats also exhibited an altered cytokine expression profile, including higher TNF-alpha and IL-1 beta expression and lower IL-6 expression than well-nourished rats following immunization and challenge. Furthermore, the intrauterine undernourished group showed reduced ratios of the IL-4/IFN-gamma and the transcription factors GATA-3/T-Bet after immunization and challenge. We suggest that the attenuated allergic lung inflammation observed in intrauterine undernourished rats is related to an altered Th1/Th2 cytokine balance resulting from a reduced GATA-3/T-bet ratio. Copyright (C) 2012 S. Karger AG, Basel

Epidemiology and predictors of a poor outcome in elderly patients with candidemia

Background: Candidemia affects patient populations from neonates to the elderly. Despite this, little information is available about the epidemiology of candidemia in elderly patients. Methods: We performed a retrospective analysis of 987 episodes of candidemia in adults (>14 years of age) from the databases of three laboratory-based surveys of candidemia performed at 14 tertiary care hospitals. Patients aged >= 60 years were considered elderly (group 1, n = 455, 46%) and were compared to younger patients (group 2, n = 532, 54%) regarding demographics, underlying diseases, comorbidities, exposure to medical procedures, species, treatment, and outcome. Results: The median APACHE II score was significantly higher in the elderly patients (19 vs. 15, p = 0.03). Variables that were observed significantly more frequently in elderly patients included admission to an intensive care unit, diabetes mellitus, renal failure, cardiac disease, lung disease, receipt of antibiotics or H2 blockers, insertion of a central venous catheter, mechanical ventilation, and candidemia due to Candida tropicalis. The 30-day mortality of elderly patients was significantly higher than that of younger patients (70% vs. 45%, p < 0.001). Factors associated with higher mortality by multivariate analysis included APACHE II score and being in group 1 (elderly). Factors associated with mortality in elderly patients were lung disease and the receipt of mechanical ventilation. Conclusions: Elderly patients account for a substantial proportion of patients with candidemia and have a higher mortality compared to younger patients. (C) 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

HELMINTH PARASITES OF HYPSIBOAS PRASINUS (ANURA: HYLIDAE) FROM TWO ATLANTIC FOREST FRAGMENTS, SAO PAULO STATE, BRAZIL

Seventy-seven males of Hypsiboas prasinus from 2 Atlantic forest fragments in the municipalities of Botucatu and Jundiai, sao Paulo State, Brazil, were examined for endoparasites. The frogs were captured in summer (January until March) and winter (July/August) of 2008 and 2009. Thirty-three males (75%) from Botucatu were infected with Rhabdias cf. fuelleborni, cosmocerciid nematodes, and Cylindrotaenia americana. Twenty-five tree frogs (78.5%) from Jundiai were infected by Rhabdias cf. fuelleborni, Physaloptera sp., and cosmocerciid nematodes. Only cosmocerciid nematodes presented a statistically significance difference in prevalence (z = 4.345; P < 0.001) and mean abundance (t = 562.0; P < 0.001) between Botucatu and Jundiai during the winter. Also, the cosmocerciids exhibited higher mean abundance (t = 196.0; P = 0.034) in winter when compared with summer at the Jundiai site. Moreover, to our knowledge, this is the first report of C. americana in the Brazilian Hylidae. This study presents 4 new records of nematodes in H. prasinus.