Chronic Recurrent Multifocal Osteomyelitis Primarily Affecting the Spine Treated With Anti-TNF Therapy

Study Design. A case report describing chronic recurrent multifocal osteomyelitis (CRMO) with initial presentation limited to spine, successfully treated by anti-TNF-alpha therapy after failure of conventional treatment methods. Objective. To describe an unusual manifestation and treatment of a rare disease. Summary of Background Data. CRMO is a rare inflammatory bone disease that should be differentiated from bacterial osteomyelitis. Rarely, it can affect the spine and in this case the most important differential diagnosis is infectious spondylodiscitis. The disease has an unpredictable course with exacerbations and spontaneous remissions. Although the majority of cases remit spontaneously (or after the use of nonsteroidal anti-inflammatory drugs [NSAIDs]), some progressive and resistant cases have been reported. Methods. We describe a case of CRMO with an unusual clinical presentation emphasizing the importance of this finding as a differential diagnosis of spondylodiscitis and comment on the available treatment alternatives. Results. A 17-year-old man presented with debilitating dorsal spine pain. Magnetic resonance imaging of the spine revealed bone lesions at multiple vertebral levels. After failure of antibiotic treatment, the diagnosis of CRMO was suggested. An initial good response to NSAIDs was followed by a recurrent course and involvement of peripheral joints besides the use of corticosteroids and other drugs. The introduction of infliximab was followed by complete remission of the disease. Conclusion. Our observation highlights the need of awareness for the differential diagnosis in suspected cases of osteomyelitis not responding to antibiotics. Anti-TNF-alpha agents should be considered in CRMO refractory cases.

Increased plasma levels of brain derived neurotrophic factor (BDNF) after multiple sclerosis relapse

Brain derived neurotrophic factor (BDNF) has been related to neuroprotection in a series of central nervous system diseases, although its role in multiple sclerosis (MS) was only partially investigated. In this work, we aimed to evaluate the plasma levels of BDNF from 29 MS patients and 24 control subjects. MS patients had decreased levels of BDNF in comparison with healthy controls. BDNF levels increased significantly after MS relapse. Our results provide some evidence for the involvement of BDNF in the pathogenesis of MS and suggest a role for this neurotrophin during the recovery of acute demyelinating inflammatory lesion. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Use of chewing gum containing 15% of xylitol and reduction in mutans streptococci salivary levels

Frequent use of Xylitol may decrease the S. mutans levels. However, very little is known about whether this effect on the levels of cariogenic bacteria is maintained after the interruption of short-term usage of xylitol. This study aimed at evaluating changes in mutans streptococci (MS) salivary levels after using a chewing gum containing xylitol. Twelve volunteers harboring > 10(5) CFU MS/ml saliva levels were asked to chew Happydent-xylit® for 5 minutes, 5 X/day, for 30 days. Saliva samples were collected at baseline, at 30 days after xylitol usage began, and at 30 days beyond its interruption. MS salivary levels were estimated. The average salivary levels of MS in the ten subjects who completed the study were 13.17 (NL-CFU) at baseline (A). After the 30 days experimental period (B), this average decreased to 9.45 (NL-CFU). Nine of ten subjects studied showed a reduction in MS salivary levels in relation to baseline, whereas salivary levels were maintained in the remaining subject. At thirty days beyond the interruption of xylitol usage (C), the average levels of MS were still reduced to 10.31 (NL-CFU). Multiple sample comparison using the Bonferroni test revealed that the decrease in MS levels observed from baseline (A) to the time immediately after 30 days of xylitol usage (B) was statistically significant (p < 0.05), and those levels were still decreased between baseline and 30 days beyond the interruption of xylitol usage (C). So, the use of xylitol induced a reduction in MS salivary levels after a short period of usage which persisted beyond its interruption.

Cardiac response and anxiety levels in psychopathic murderers

OBJECTIVE: To compare the emotional response and level of anxiety of psychopathic murderers, non-psychopathic murderers, and nonpsychopathic non-criminals. METHOD: 110 male individuals aged over 18 years were divided into three groups: psychopathic murderers (n = 38); non-psychopathic murderers (n = 37) serving sentences for murder convictions in Maximum Security Prisons in the State of Sao Paulo; and non-criminal, non-psychopathic individuals (n = 35) according to the Psychopathy Checklist-Revised. The emotional response of subjects was assessed by heart rate variation and anxiety level (State-Trait Anxiety Inventory) after viewing standardized pictures depicting pleasant, unpleasant and neutral content from the International Affective Picture System. RESULTS: Psychopathic murderers presented lower anxiety levels and smaller heart rate variations when exposed to pleasant and unpleasant stimuli than nonpsychopathic murderers or non-psychopathic non-criminals. The results also demonstrated that the higher the score for factor 1 on the Psychopathy Checklist-Revised, the lower the heart rate variation and anxiety level. CONCLUSION: The results suggest that psychopathic murderers do not present variation in emotional response to different visual stimuli. Although the non-psychopathic murderers had committed the same type of crime as the psychopathic murderers, the former tended to respond with a higher level of anxiety and heart rate variation.

A closer look at multiple-clone Plasmodium vivax infections: detection methods, prevalence and consequences

The naturally occurring clonal diversity among field isolates of the major human malaria parasite Plasmodium vivax remained unexplored until the early 1990s, when improved molecular methods allowed the use of blood samples obtained directly from patients, without prior in vitro culture, for genotyping purposes. Here we briefly review the molecular strategies currently used to detect genetically distinct clones in patient-derived P. vivax samples, present evidence that multiple-clone P. vivax infections are commonly detected in areas with different levels of malaria transmission and discuss possible evolutionary and epidemiological consequences of the competition between genetically distinct clones in natural human infections. We suggest that, when two or more genetically distinct clones are present in the same host, intra-host competition for limited resources may select for P. vivax traits that represent major public health challenges, such as increased virulence, increased transmissibility and antimalarial drug resistance.

Search for cytotoxic agents in multiple Laurencia complex seaweed species (Ceramiales, Rhodophyta) harvested from the Atlantic Ocean with emphasis on the Brazilian State of Espírito Santo

The development of new anti-cancer drugs of algal origin represents one of the least explored frontiers in medicinal chemistry. In this regard, the diversity of micro- and macroalgae found in Brazilian coastal waters can be viewed as a largely untapped natural resource. In this report, we describe a comparative study on the cytotoxic properties of extracts obtained from the Laurencia complex: Laurencia aldingensis, L. catarinensis, L. dendroidea, L. intricata, L. translucida, L. sp, and Palisada flagellifera. All of these species were collected in the coastal waters of the State of Espírito Santo, Brazil. Four out of the twelve samples initially investigated were found to show significant levels of toxicity towards a model tumor cell line (human uterine sarcoma, MES-SA). The highest levels of cytotoxicity were typically associated with non-polar (hexane) algal extracts, while the lowest levels of cytotoxicity were found with the corresponding polar (methanol) extracts. In this report, we also describe a biological model currently in development that will not only facilitate the search for new anti-cancer drug candidates of algal origin, but also permit the identification of compounds capable of inducing the destruction of multi-drug resistant tumors with greater efficiency than the pharmaceuticals currently in clinical use.

Ablation Rate and Morphology of Superficial and Deep Dentin Irradiated with Different Er:YAG Laser Energy Levels

Objective: In this study we evaluated the ablation rate of superficial and deep dentin irradiated with different Er:YAG laser energy levels, and observed the micromorphological aspects of the lased substrates with a scanning electron microscope (SEM). Background Data: Little is known about the effect of Er: YAG laser irradiation on different dentin depths. Materials and Methods: Sixty molar crowns were bisected, providing 120 specimens, which were randomly assigned into two groups ( superficial or deep dentin), and later into five subgroups (160, 200, 260, 300, or 360 mJ). Initial masses of the specimens were obtained. After laser irradiation, the final masses were obtained and mass losses were calculated followed by the preparation of specimens for SEM examination. Mass-loss values were subjected to two-way ANOVA and Fisher's least significant difference multiple-comparison tests (p < 0.05). Results: There was no difference between superficial and deep dentin. A significant and gradual increase in the mass-loss values was reached when energies were raised, regardless of the dentin depth. The energy level of 360 mJ showed the highest values and was statistically significantly different from the other energy levels. The SEM images showed that deep dentin was more selectively ablated, especially intertubular dentin, promoting tubule protrusion. At 360 mJ the micromorphological features were similar for both dentin depths. Conclusion: The ablation rate did not depend on the depth of the dentin, and an energy level lower than 360 mJ is recommended to ablate both superficial and deep dentin effectively without causing tissue damage.

Lepidopteran larva consumption of soybean foliage: basis for developing multiple-species economic thresholds for pest management decisions

BACKGROUND: Defoliation by Anticarsia gemmatalis (Hubner), Pseudoplusia includens (Walker), Spodoptera eridania (Cramer), S. cosmioides (Walker) and S. frugiperda (JE Smith) (Lepidoptera: Noctuidae) was evaluated in four soybean genotypes. A multiple-species economic threshold (ET), based upon the species` feeding capacity, is proposed with the aim of improving growers` management decisions on when to initiate control measures for the species complex. RESULTS: Consumption by A. gemmatalis, S. cosmioides or S. eridania on different genotypes was similar. The highest consumption of P. includens was 92.7 cm(2) on Codetec 219RR; that of S. frugiperda was 118 cm(2) on Codetec 219RR and 115.1 cm(2) on MSoy 8787RR. The insect injury equivalent for S. cosmoides, calculated on the basis of insect consumption, was double the standard consumption by A. gemmatalis, and statistically different from the other species tested, which were similar to each other. CONCLUSIONS: As S. cosmioides always defoliated nearly twice the leaf area of the other species, the injury equivalent would be 2 for this lepidopteran species and 1 for the other species. The recommended multiple-species ET to trigger the beginning of insect control would then be 20 insect equivalents per linear metre. (C) 2010 Society of Chemical Industry

Microbial activity and community composition in saline and non-saline soils exposed to multiple drying and rewetting events

The effects of drying and rewetting (DRW) have been studied extensively in non-saline soils, but little is known about the impact of DRW in saline soils. An incubation experiment was conducted to determine the impact of 1-3 drying and re-wetting events on soil microbial activity and community composition at different levels of electrical conductivity in the saturated soil extract (ECe) (ECe 0.7, 9.3, 17.6 dS m(-1)). A non-saline sandy loam was amended with NaCl to achieve the three EC levels 21 days prior to the first DRW; wheat straw was added 7 days prior to the first DRW. Each DRW event consisted of 1 week drying and 1 week moist (50% of water holding capacity, WHC). After the last DRW, the soils were maintained moist until the end of the incubation period (63 days after addition of the wheat straw). A control was kept moist (50% of WHC) throughout the incubation period. Respiration rates on the day after rewetting were similar after the first and the second DRW, but significantly lower after the third DRW. After the first and second DRW, respiration rates were lower at EC17.6 compared to the lower EC levels, whereas salinity had little effect on respiration rates after the third DRW or at the end of the experiment when respiration rates were low. Compared to the continuously moist treatment, respiration rates were about 50% higher on day 15 (d15) and d29. On d44, respiration rates were about 50% higher at EC9.7 than at the other two EC levels. Cumulative respiration was increased by DRW only in the treatment with one DRW and only at the two lower EC levels. Salinity affected microbial biomass and community composition in the moist soils but not in the DRW treatments. At all EC levels and all sampling dates, the community composition in the continuously moist treatment differed from that in the DRW treatments, but there were no differences among the DRW treatments. Microbes in moderately saline soils may be able to utilise substrates released after multiple DRW events better than microbes in non-saline soil. However, at high EC (EC17.6), the low osmotic potential reduced microbial activity to such an extent that the microbes were not able to utilise substrate released after rewetting of dry soil.

Elevated levels of selenium in the typical diet of Amazonian riverside populations

Selenium (Se) intake is generally from food, whose Se content depends on soil Se and plant accumulation. For humans, adequate Se intake is essential for several selenoenzymes. In the Lower Tapajos region of the Brazilian Amazon, Se status is elevated with large inter-community variability. Se intake in this region, where Hg exposure is among the highest in the world, may be important to counteract mercury (Hg) toxicity. The present study was conducted in 2006 with 155 persons from four communities of the Lower Tapajos. The objectives were: i) to evaluate Se content in their typical diet and drinking water; ii) to compare food Se concentrations with respect to geographic location; and iii) to examine the contribution of consumption of different food items to blood Se. More than 400 local foods and 40 drinking water samples were collected. Participants responded to an interview-administered food frequency questionnaire and provided blood samples. Food, water and blood Se levels were assessed by ICP-MS. Since Brazil nuts may also contain significant levels of barium (Ba) and strontium (Sr), these elements were likewise analyzed in nuts. The highest Se concentrations were found in Brazil nuts, but concentrations were highly variable (median: 13.9 mu g/g; range: 0.4-158.4 mu g/g). Chicken, game meat, eggs and beef also contained considerable levels of Se, with median concentrations from 0.3 to 1.4 mu g/g. There was no particular geographic distribution of food Se. Se concentration in drinking water was very low (<1.4 mu g/L). Blood Se covered a (103-1500 mu g/L), and was positively related to regular consumption of Brazil nuts, domestic chicken and game meat. Brazil nuts were found to contain highly variable and often very high concentrations of Ba (88.0 mu g/g, 1.9-1437 mu g/g) and Sr (38.7 mu g/g, 3.3-173 mu g/g). Further studies should address multiple nutrient/toxic interactions in the diet and related effects on health. (c) 2010 Elsevier B.V. All rights reserved.

Effect of a Pool of Peptides Isolated from Crotalus durissus terrificus (South American Rattlesnake) Venom on Glucose Levels of Mice Fed on a High-Fat Diet

This study investigated the effect of a pool of peptides, isolated from venom of Crotalus durissus terrificus (South American rattlesnake) on glucose concentration in C57BL/6 mice fed on a high-fat diet for 6 weeks. The pool of peptides (molecular mass around of 10 kDa) was obtained using a MidJet apparatus with a cartridge of 10 KDa. The peptide pool was injected intraperitoneally in mice in a single dose (0.5 mg/animal) or multiple doses (0.2 mg/dose). After predetermined times (30, 60, 90 and 120 min) post injections, venous blood samples were collected for enzymatic measurement of serum glucose using a commercial glucose kit (glucose oxidase method). High-fat fed mice showed an increase in blood glucose concentration, in comparison with mice fed on the chow diet. Thirty minutes after a single dose of the peptide pool, high-fat fed animals showed a significant decrease (similar to 47%) in glycemia. However, the glucose level increased again at 60 and 120 min. Conversely, after multiple injections of the pool of peptides administered every 30 min, the blood glucose concentration in the high-fat mice was significantly decreased (similar to 37%) and remained at low levels until 120 min. These results suggest that the tested pool of peptides from Crotalus durissus terrificus contained a peptide (or peptides) with a beneficial role on glucose-lowering action of high-fat fed mice.

Proteomic characterization of the multiple forms of the PLAs from the venom of the social wasp Polybia paulista

The phospholipases A(1) (PLA(1)s) from the venom of the social wasp Polybia paulista occur as a mixture of different molecular forms. To characterize the molecular origin of these structural differences, an experimental strategy was planned combining the isolation of the pool of PLAs from the wasp venom with proteomic approaches by using 2-D, MALDI-TOF-TOF MS and classical protocols of protein chemistry, which included N- and C-terminal sequencing. The existence of an intact form of PLA(1) and seven truncated forms was identified, apparently originating from controlled proteolysis of the intact protein; in addition to this, four of these truncated forms also presented carbohydrates attached to their molecules. Some of these forms are immunoreactive to specific-IgE, while others are not. These observations permit to raise the hypothesis that naturally occurring proteolysis of PLA(1), combined with protein glycosylation may create a series of different molecular forms of these proteins, with different levels of allergenicity. Two forms of PLA(2)s, apparently related to each other, were also identified; however, it was not possible to determine the molecular origin of the differences between both forms, except that one of them was glycosylated. None of these forms were immunoreactive to human specific IgE.

Use of multiple channel pH monitoring for evaluation of ultra-distal reflux in patients after fundoplication for treatment of Barrett`s esophagus

Dysplasia and esophageal adenocarcinoma may arise in patients with Barrett`s esophagus after fundoplication esophageal pH monitoring showing no acid in esophagus. This suggests the need to develop methodology to evaluate the occurrence of ultra-distal reflux (1 cm above the LES). The objective of the study was to compare acid exposition in three different levels: 5 cm above the upper border of the LES, 1 cm above the LES and in the intrasphincteric region. Eleven patients with Barrett`s esophagus after Nissen fundoplication with no clinical, endoscopic and radiologic evidence of reflux were selected. Four-channel pH monitoring took place: channel A, 5 cm above the upper border of the LES; channel B, 1 cm above the LES; channel C, intrasphincteric; channel D, intragastric. The results of channels A, B and C were compared. There was significant increase in number of reflux episodes and a higher fraction of time with pH <4.0 in channel B compared to channel A. There was significant decrease in fraction of time with pH <4.0 in channel B compared to channel C. Two cases of esophageal adenocarcinoma were diagnosed in the studied patients. The region 1 cm above the upper border of the LES is more exposed to acid than the region 5 cm above the upper border of the LES, although this exposure occurred in reduced levels. The region 1 cm above the upper border of the LES is less exposed to acid than the intrasphincteric region.

Modulation of B-1 and B-2 kinin receptors expression levels in the hippocampus of rats after audiogenic kindling and with limbic recruitment, a model of temporal lobe epilepsy

Epileptic seizures are hypersynchronous, paroxystic and abnormal neuronal discharges. Epilepsies are characterized by diverse mechanisms involving alteration of excitatory and inhibitory neurotransmission that result in hyperexcitability of the central nervous system (CNS). Enhanced neuronal excitability can also be achieved by inflammatory processes, including the participation of cytokines, prostaglandins or kinins, molecules known to be involved in either triggering or in the establishment of inflammation. Multiple inductions of audiogenic seizures in the Wistar audiogenic rat (WAR) strain are a model of temporal lobe epilepsy (TLE), due to the recruitment of limbic areas such as hippocampus and amygdata. In this study we investigated the modulation of the B-1 and B-2 kinin receptors expression levels in neonatal WARs as well as in adult WARs subjected to the TLE model. The expression levels of pro-inflammatory (IL-1 beta) and anti-inflammatory (IL-10) cytokines were also evaluated, as well as cyclooxygenase (COX-2). Our results showed that the B-1 and B-2 kinin receptors mRNAs were up-regulated about 7- and 4-fold, respectively, in the hippocampus of kindled WARs. On the other hand, the expressions of the IL-1 beta, IL-10 and COX-2 were not related to the observed increase of expression of kinin receptors. Based on those results we believe that the B, and B2 kinin receptors have a pivotal role in this model of TLE, although their participation is not related to an inflammatory process. We believe that kinin receptors in the CNS may act in seizure mechanisms by participating in a specific kininergic neurochemical pathway. (c) 2007 Elsevier B.V. All rights reserved.

Essential Role of CCR2 in Neutrophil Tissue Infiltration and Multiple Organ Dysfunction in Sepsis

Rationale Sepsis is defined as a systemic inflammatory response to infection, which in its severe form is associated with multiple organ dysfunction syndrome (MODS). The precise mechanisms by Which MODS develops remain unclear. Neutrophils have a pivotal role in the defense against infections; however, overwhelming activation of neutrophils is known to elicit tissue damage. Objectives: We investigated the role of the chemokine receptor CCR2 in driving neutrophil infiltration and eliciting tissue damage in remote organs during sepsis. Methods: Sepsis was induced in wild-type mice treated with CCR2 antagonist (RS504393) or CCR2(-/-) mice by cecal ligation and puncture (CLP) model. Neutrophil infiltration into the organs was measured by myeloperoxidase activity and fluorescence-activated cell sorter. CCR2 expression and chemotaxis were determined in neutrophils stimulated with Toll-like receptor agonists or isolated from septic mice and patients. Measurements and Main Results: CCR2 expression and responsiveness to its ligands was induced in circulating neutrophils during CLP-induced sepsis by a mechanism dependent on Toll-like receptor/nuclear factor-kappa B pathway. Genetic or pharmacologic inhibition of CCR2 protected mice from CLP-induced mortality. This protection was associated with lower infiltration of neutrophils into the lungs, heart, and kidneys and reduced serum biochemical indicators of organ injury and dysfunction. Importantly, neutrophils from septic patients express high levels of CCR2, and the severity of patient illness correlated positively with increasing neutrophil chemotaxis to CCR2 ligands. Conclusions: Collectively, these data identify CCR2 as a key receptor that drives the inappropriate infiltration of neutrophils into remote organs during sepsis. Therefore, CCR2 blockade is a novel potential therapeutic target for treatment of sepsis-induced MODS.