Immunomodulation of allergic response in children and adolescents: What we can learn from lymphatic filarial infection.

BACKGROUND: Although it is well known that allergic diseases involve a strong Th2 immune response, with production of high levels of specific IgE allergen, knowledge on the association between filarial infection and allergies, among paediatric patients is scarce. OBJECTIVE: To evaluate the allergic response patterns in cases of filarial infection by comparing peripheral eosinophils, total IgE levels, immediate hypersensitivity and cytokine levels in children and adolescents in Brazil. METHODS: This was an exploratory study with three groups: (I) with filarial infection and without allergic diseases; (II) without filarial infection and with allergic diseases; and (III) without filarial infection and without allergic diseases. The prick test and specific IgE tests for aeroallergens were performed using five antigens. Peripheral eosinophils and total IgE were also evaluated. IL-4 and IL-5 were determined using whole-blood culture stimulated by three antigens. RESULTS: Eosinophilia and elevated levels of total IgE (≥400IU/dl) were observed in all groups. The prick test was positive in 56.6% of the cases. Group I presented hypersensitive responses similar to the allergic disease groups. In the whole-blood culture stimulated by Dermatophagoides pteronyssinus, average IL-4 production did not differ significantly among the groups, but IL5 production resulting from stimulation was greater in the allergic disease groups (p<0.05). CONCLUSIONS: The allergic response pattern in group with filarial infection was similar to that of the groups with and without allergic diseases, but the response to IL-5 in the culture stimulated by D. pteronyssinus was an exclusive characteristic of the allergic group.

Receptor Antagonist of IL-13 Exerts a Potential Negative Regulation During Early Infection of Human Schistosomiasis.

The pathology of schistosomiasis is associated with the formation of granulomas, and this process is associated with liver fibrosis. Studies indicate that Th1 cytokines reduce fibrosis in schistosomiasis, while Th2 cytokines play a part in the progression of fibrosis, and IL-13 has a critical role in this process. The IL-13Rα2 receptor, known as a 'receptor antagonist' binds with high affinity to IL-13, and studies have identified that this plays a part in reducing fibrosis and the size of granulomas. The objective of this study was to evaluate the function of IL-13Rα2 and cellular immune response in hepatic fibrosis. A negative correlation between IL-13Rα2 and IL-13 was found, suggesting an increase in cytokine in early fibrosis. Initially, a negative correlation between IFN-γ and IL-13 was found in patients without fibrosis, and subsequently, this correlation was found to be positive in patients with severe fibrosis, thereby highlighting a new mechanism for regulating the progress of periportal fibrosis. There was a positive correlation between the profiles of Th1 and Th2 cytokines, suggesting the presence of both responses, thus regulating the disease. The results contribute to a better understanding of the immune mechanisms that control the process of hepatic fibrogenesis in schistosomiasis in humans.

[Infectious endocarditis in the intensive care unit]. / Endocarditis infecciosa en la Unidad de Medicina Intensiva.

OBJECTIVE: To study the characteristics, evolution and prognosis of patients with infectious endocarditis requiring treatment in the Intensive Care Unit. DESIGN: A prospective, observational cohort study of patients admitted due to infectious endocarditis. SETTING: Nuestra Señora de Candelaria University Hospital, a third - level center with a recruitment population of 493,145. PATIENTS: All patients consecutively diagnosed with infectious endocarditis in our center according to the Duke criteria, between 1 January 2005 and 31 July 2011. STUDY VARIABLES: Demographic data, clinical severity scores, microbiological and echocardiographic data, hospital mortality and complications. RESULTS: Out of 102 patients diagnosed with endocarditis, 38 (37%) were admitted to Intensive Care. Compared with those patients not admitted to the ICU, these subjects suffered more frequent mitral valve alterations (OR= 7.13; 95%CI: 2.12-24; p= 0.002) and cerebral embolism (OR= 3.89; 95%CI: 1.06-14.3; p= 0.041). In turn, mortality was greater (42.1% vs 18.8%, p= 0.011), as was the proportion of emergency surgeries (45.8% vs 5.9%, p<0.001). The identified mortality predictors were Staphylococcus aureus infection (OR= 3.49; 95%CI 1.02-11.93; p=0.046), heart failure (OR=4.18; 95%CI: 1.17-14.94; p=0.028), cerebral embolism (OR= 8.45; 95%CI: 1.89-37.74; p=0.005) and the SAPS II upon admission (OR=1.09; 95%CI: 1.04-1.15; p<0.001). CONCLUSIONS: A large proportion of patients with endocarditis require admission to the Intensive Care Unit, presenting a much poorer prognosis. Staphylococcus aureus infection, heart failure, cerebral embolism and SAPS II scores are independent predictors of hospital mortality.

Immunological diagnosis of tuberculosis based on recombinant antigens ESAT-6 and CFP-10 in children from an endemic area in northeast Brazil.

Diagnostic tests for tuberculosis (TB) using interferon gamma (IFN-γ) responses produced by T lymphocytes after stimulation by early secretory antigen target 6 (ESAT-6), culture filtrate protein 10 (CFP-10) or purified protein derivate (PPD) were carried out using ELISA (enzyme-linked immunosorbent assay) in whole blood culture supernatants from children with suspected TB disease (n=21), latent TB infection (LTBI; n=17) and negative controls (NC; n=21) from Recife, Pernambuco, Brazil. The results were analysed using the ROC (receiver operating characteristic) curves and the areas under the curve (AUC) generated varied from 0.5 to 1.0 with higher values indicating increased discriminatory ability. Comparisons of AUCs were made using non-parametric assumptions, and the differences were considered significant if P<0.05. The ROC curve showed a statistical difference (P = 0.015) between the LTBI and NC groups with an AUC of 0.731, TB disease and NC (AUC=0.780; P=0.002) and a group with TB (latent infection+disease, n=38) and NC (AUC=0.758; P = 0.001) when the antigen used was ESAT-6. No statistical difference was found between the groups when CFP-10 or PPD was used. In conclusion, the ESAT-6 test may be the most appropriate for diagnosis of childhood TB, both LTBI and TB disease, when associated with epidemiological and clinical data, especially in endemic areas such as Brazil.

Towards bio-inspired robots for underground and surface exploration in planetary environments: An overview and novel developments inspired in sand-swimmers.

Dessert organisms like sandfish lizards (SLs) bend and generate thrust in granular mediums to scape heat and hunt for prey [1]. Further, SLs seems to have striking capabilities to swim in undulatory form keeping the same wavelength even in terrains with different volumetric densities, hence behaving as rigid bodies. This paper tries to recommend new research directions for planetary robotics, adapting principles of sand swimmers for improving robustness of surface exploration robots. First, we summarize previous efforts on bio-inspired hardware developed for granular terrains and accessing complex geological features. Later, a rigid wheel design has been proposed to imitate SLs locomotion capabilities. In order to derive the force models to predict performance of such bio-inspired mobility system, different approaches as RFT (Resistive Force Theory) and analytical terramechanics are introduced. Even in typical wheeled robots the slip and sinkage increase with time, the new design intends to imitate traversability capabilities of SLs, that seem to keep the same slip while displacing at subsurface levels.

Practical document on the management of hyponatremia in critically ill patients. / Documento práctico del manejo de la hiponatremia en pacientes críticos.

Hyponatremia is the most prevalent electrolyte disorder in Intensive Care Units. It is associated with an increase in morbidity, mortality and hospital stay. The majority of the published studies are observational, retrospective and do not include critical patients; hence it is difficult to draw definitive conclusions. Moreover, the lack of clinical evidence has led to important dissimilarities in the recommendations coming from different scientific societies. Finally, etiopathogenic mechanisms leading to hyponatremia in the critical care patient are complex and often combined, and an intensive analysis is clearly needed. A study was therefore made to review all clinical aspects about hyponatremia management in the critical care setting. The aim was to develop a Spanish nationwide algorithm to standardize hyponatremia diagnosis and treatment in the critical care patient.

Use of a reliable PCR assay for the detection of Neisseria gonorrhoeae in Peruvian patients.

Neisseria gonorrhoeae is the most common sexually transmitted disease-causing bacterium worldwide. An in-house PCR assay targeting the carbamoyl-phosphate synthase subunit A (carA) gene was developed for the specific detection of N. gonorrhoeae in clinical specimens. Samples from 605 patients were cultured on selective medium and assayed by PCR in a double-blind fashion. Of 605 urethral/cervical samples analysed, 13 were PCR-positive, of which 11 were culture-positive. The PCR showed a sensitivity and specificity of 100% and 99.7% with these samples. PCR targeting the carA gene appears to be a reliable method for the detection of N. gonorrhoeae in clinical specimens.

Immune factors and immunoregulation in tuberculosis.

Pathogens causing tuberculosis and other chronic infectious diseases of major public health importance commonly have complex mechanisms involved in their persistence in the host despite specific and sometimes strong immune responses. These diseases are also associated with the lack of efficient vaccines, difficult therapeutics and a high mortality rate among susceptible individuals. Here, we will review features of the host immune response that contribute to the occurrence of disease. In addition, we propose that the immune responses observed in tuberculosis cannot be interpreted solely on the basis of a Th1-Th2 counter-regulatory paradigm since there is growing evidence that natural regulatory T cells may play an important role in the regulation of host immune responses against Mycobacterium tuberculosis. Thus, the development of more effective vaccines against this bacterial disease should take into account the role of natural regulatory T cells in the progression to severe disease and persistence of infection. Finally, new treatments based on manipulation of regulatory T cells should be investigated.

Glacial recharge, salinisation and anthropogenic contamination in the coastal aquifers of Recife (Brazil).

Implying large residence times and complex water origins deep coastal aquifers are of particular interest as they are remarkable markers of climate, water use and land use changes. Over the last decades, the Metropolitan Region of Recife (Brazil) went through extensive environmental changes increasing the pressure on water resources and giving rise to numerous environmental consequences on the coastal groundwater systems. We analysed the groundwater of the deep aquifers Cabo and Beberibe that are increasingly exploited. The processes potentially affecting groundwater residence times and flow paths have been studied using a multi-tracer approach (CFCs, SF6, noble gases, 14C, 2H and 18O). The main findings of these investigations show that: (1) Groundwaters of the Cabo and Beberibe aquifers have long residence times and were recharged about 20,000years ago. (2) Within these old groundwaters we can find palaeo-climate evidences from the last glacial period at the tropics with lower temperatures and dryer conditions than the present climate. (3) Recently, the natural slow dynamic of these groundwater systems was significantly affected by mixing processes with contaminated modern groundwater coming from the shallow unconfined Boa Viagem aquifer. (4) The large exploitation of these aquifers leads to a modification of the flow directions and causes the intrusion through palaeo-channels of saline water probably coming from the Capibaribe River and from the last transgression episodes. These observations indicate that the current exploitation of the Cabo and Beberibe aquifers is unsustainable regarding the long renewal times of these groundwater systems as well as their ongoing contamination and salinisation. The groundwater cycle being much slower than the human development rhythm, it is essential to integrate the magnitude and rapidity of anthropogenic impacts on this extremely slow cycle to the water management concepts.

Groundwater contamination in coastal urban areas: Anthropogenic pressure and natural attenuation processes. Example of Recife (PE State, NE Brazil).

In a context of increasing land use pressure (over-exploitation, surface-water contamination) and repeated droughts, identifying the processes affecting groundwater quality in coastal megacities of the tropical and arid countries will condition their long-term social and environmental sustainability. The present study focuses on the Brazilian Recife Metropolitan Region (RMR), which is a highly urbanized area (3,743,854 inhabitants in 2010) on the Atlantic coast located next to an estuarial zone and overlying a multi-layered sedimentary system featured by a variable sediment texture and organic content. It investigates the contamination and redox status patterns conditioning potential attenuation within the shallow aquifers that constitute the interface between the city and the strategic deeper semi-confined aquifers. These latter are increasingly exploited, leading to high drawdown in potenciometric levels of 20-30m and up to 70m in some high well density places, and potentially connected to the surface through leakage. From a multi-tracer approach (major ions, major gases, δ(11)B, δ(18)O-SO4, δ(34)S-SO4) carried out during two field campaigns in September 2012 and March 2013 (sampling of 19 wells and 3 surface waters), it has been possible to assess the contamination sources and the redox processes. The increasing trend for mineralization from inland to coastal and estuarial wells (from 119 to around 10,000µS/cm) is at first attributed to water-rock interactions combined with natural and human-induced potentiometric gradients. Secondly, along with this trend, one finds an environmental pressure gradient related to sewage and/or surface-channel network impacts (typically depleted δ(11)B within the range of 10-15‰) that are purveyors of chloride, nitrate, ammonium and sulfate. Nitrate, ammonium and sulfate (ranging from 0 to 1.70mmol/L, from 0 to 0,65mmol/L, from 0.03 to 3.91mmol/L respectively are also potentially produced or consumed through various redox processes (pyrite oxidation, denitrification, dissimilatory nitrate reduction to ammonium) within the system, as is apparent within a patchwork of biogeochemical reactors. Furthermore, intensive pumping in the coastal area with its high well density punctually leads to temporary well salinization ([Cl] reaching temporarily 79mmol/L). Our results, summarized as a conceptual scheme based on environmental conditions, is a suitable basis for implementing sustainable management in coastal sedimentary hydrosystems influenced by highly urbanized conditions.

Patterns in spontaneous adverse event reporting among branded and generic antiepileptic drugs.

Spontaneous adverse event reports constitute an important source of information on previously unknown adverse reactions to marketed medicines. However, the dynamics of such reporting following generic introduction are poorly understood. Using adverse event reports on five antiepileptic drugs from the US Food and Drug Administration's Adverse Event Reporting System, we describe temporal trends in adverse event reporting before and after generic introduction, and survey the quality of product-identifying information contained therein. The majority of reports were sent by innovator drug manufacturers while few were sent by generic manufacturers, even when generics accounted for >90% of dispensed prescriptions. We manually reviewed narratives from 2,500 reports and found that the suspect product type (brand or generic) could not be determined in 84% of reports, while generic products (16%) were identified more often than brand-name products (<1%). These results suggest that pharmacovigilance stakeholders should act to promote more detailed reporting practices.

Mapping of the N terminus of the Schistosoma mansoni tegumental antigen Sm15 to its predicted precursor protein.

Sm15 is a major Schistosoma mansoni 15 kDa tegumental antigen, resulting from the proteolytic processing of a larger precursor. The amino terminus of Sm15 was identified by direct amino acid sequencing, and the antigen was tentatively mapped to the segment spanning amino acids 362-497 of the precursor. This will allow subsequent studies to elucidate the possible immunological role of proteolytic processing in schistosomiasis.

The use of non-specific immunopotentiators in experimental Trypanosoma cruzi infection.

The effects of levamisole, isoprinosine and Corynebacterium parvum on Trypanosoma cruzi (Y strain) experimental infection of mice were studied. In prophylactic treatment these drugs reduced the peak of parasitaemia, and had no apparent effect on mortality rate or on histopathological and electrocardiographic findings. Levamisole and isoprinosine had no effect when used after infection. Electrocardiograms were obtained from all chronic chagasic mice. The most frequent changes were left atrial overload and first degree atrio-ventricular block. These findings became more frequent the longer the animals survived. The net effect of the non-specific immunopotentiators seems to depend on several factors: host immune state, severity of infection, dose and timing of drug administration. This probably explains the variable published results and the paradoxical findings of different laboratories.

Vaccines against human parasitic diseases: an overview.

There are no vaccines currently available to control the major human parasitic diseases, although there is evidence of acquired immunity and resistance to reinfection in most of the parasitic infections. The present manuscript concentrates on the vaccines for parasitic diseases that are in the most advanced stages of development: malaria, leishmaniasis and schistosomiasis. Vaccines for malaria and leishmaniasis have been taken to clinical trials while vaccines for schistosomiasis are being considered for Phase I (assessment of safety and immune responsiveness in volunteers). We have attempted to give a factual account of the present status of knowledge of vaccines against human parasitic diseases, emphasizing both the successes and setbacks. We do not intend to cover the enormous literature in the field but have concentrated on the most promising antigenic preparations. Finally, some new approaches for the development of vaccines are discussed including nucleic acid vaccines and the use of cytokines as adjuvants.

In vivo leukocyte chemotaxis during the development of acute experimental Trypanosoma cruzi infection.

Five and 15 days after T. cruzi infection, staphylococcal protein A was injected into a connective tissue air pouch of mice and the migration of polymorphonuclear leukocytes into the area was monitored. The PMN leukocyte response of 15-day infected mice was lower than that of uninfected mice (P less than 0.001): The 15-day infected mice also showed a lower PMN leukocyte response when compared to 5-day infected mice (P less than 0.001). These data suggest that the chemotaxis defect developed gradually during the acute phase of infection.

Onset and evolution of nephropathy in rats with spontaneous diabetes mellitus.

The occurrence of renal diabetic complications was studied in diabetic nonobese IIM/FmeSS (eSS) rats. The results were compared with eumetabolic Wistar rats paired by sex and age. Between 6 and 12 months of age, eSS male rats had higher fructosamine values and glucose intolerance as well as increasing proteinuria and uremia. Enhancement in water, calcium and phosphorus fractional excretion with a concomitant lower sodium excretion, was observed from 12 months of age on. 18- and 21-month-old eSS rats exhibited fasting hyperglycaemia and rising values of fructosamine, glucose intolerance and glycosuria. Simultaneously, a notorious worsening of proteinuria as well as alterations in glomerular filtration were verified. Optic microscopy of 12-month-old eSS rat kidneys showed areas of tubular dilatation with protein cylinders. In 21-month-old eSS animals, kidneys appeared overtly damaged. Increased capsular, glomerular and Henle's thin loop diameters were verified in 12- and 21-month-old eSS rats. Glomeruli showed diffuse hypertrophy of mesangial tissue and thickening of the basement membrane. Areas of markedly atrophic and dilated tubules containing acidophilic proteinaceous material were observed. At age of 21 months, kidneys of eumetabolic Wistar control rats presented foci of interstitial and pielic inflammatory infiltrates.

"In vivo" leukocyte chemotaxis in experimental mice Schistosoma mansoni infection.

The "in vivo" chemotaxis was studied in C57Bl/10 mice 10, 30, 50 and 60 days after a Schistosoma mansoni infection in comparison to a control group (uninfected mice). Staphylococcal protein A was injected into a connective tissue air pouch of control and experimental mice and the leukocyte chemotaxis was counted. A decrease in polymorphonuclear (PMN) leukocyte response was found in infected mice in comparison to the control group (p < 0.05). The 10 day infected mice showed a decreased PMN leukocyte response respecting the control group (p < 0.05) and this finding became more evident 30 and 50 days post-infection. Although the PMN leukocyte response of 60 day infected mice increased in comparison to 50 day infected animals, it was still significantly lower the control response. The mononuclear leukocyte response was not significantly different between infected or uninfected mice.

[Effects of non-specific immunopotentiators on experimental Schistosoma mansoni infection. I. Levamisole]. / Efeitos de imunopotenciadores não específicos na infecção experimental pelo Schistosoma mansoni. I. Levamisole.

The effects of levamisole on the histopathological changes, host's resistance and "in vivo" chemotaxis in Schistosoma mansoni experimental infection of C57Bl/10 inbred mice were studied. Prophylactic treatment resulted in an increase in the number of adult worms obtained by perfusion and also increased the mortality rate (p < 0.05). The histopathological changes (liver and intestines) were similar in all the groups. A significant reduction of "in vivo" chemotaxis occurred in infected control mice as well as in those submitted to prophylactic treatment with levamisole. Chemotactic activity reached the same levels of normal control mice (non-infected and non-treated with levamisole), when the curative scheme was used. Levamisole seems to increase the susceptibility of inbred C57Bl/10 mice to the infection with S. mansoni when administered prior to the infection and increase the chemotactic activity to normal levels when given after infection.

Effects of non-specific immunopotentiators in experimental Schistosoma mansoni infection. II. Corynebacterium parvum.

The effects of Corynebacterium parvum on host protection, tissue reaction and "in vivo" chemotaxis in Schistosoma mansoni infected mice were studied. The C. parvum was given intraperitoneally using a dose of 0.7 mg, twice a week (for 4 weeks), thirty days before (prophylactic treatment) or after infection (curative treatment). The host protection was evaluated through the recovery of adult worms by liver perfusion and was lower in the prophylactic group as compared to the control group (p = 0.018), resulting in 44% protection. The "in vivo" leukocyte response in both prophylactic and curative groups was higher as compared to the infected/non treated group (p = 0.009 and p = 0.003, respectively). Tissue reactions were described in the experimental and control groups, but there were not remarkable differences among them. The possible biological implications and relevance of the findings for the defensive response of the host and control of schistosomiasis are discussed.