History of insecticide resistance of Triatominae vectors

AbstractIn the last 15 years, different types of Triatominae resistance to different insecticides have been reported; thus, resistance may be more widespread than known, requiring better characterization and delimitation, which was the aim of this review. This review was structured on a literature search of all articles from 1970 to 2015 in the PubMed database that contained the keywords Insecticide resistance and Triatominae . Out of 295 articles screened by title, 33 texts were selected for detailed analysis. Insecticide resistance of Triatomines is a complex phenomenon that has been primarily reported in Argentina and Bolivia, and is caused by different factors (associated or isolated). Insecticide resistance of Triatominae is a characteristic inherited in an autosomal and semi-dominant manner, and is polygenic, being present in both domestic and sylvatic populations. The toxicological profile observed in eggs cannot be transposed to different stages of evolution. Different toxicological profiles exist at macro- and microgeographical levels. The insecticide phenotype has both reproductive and developmental costs. Different physiological mechanisms are involved in resistance. Studies of Triatomine resistance to insecticides highlight three deficiencies in interpreting the obtained results: I) the vast diversity of methodologies, despite the existence of a single guiding protocol; II) the lack of information on the actual impact of resistance ratios in the field; and III) the concept of the susceptibility reference lineage. Research on the biological and behavioral characteristics of each Triatominae species that has evolved resistance is required in relation to the environmental conditions of each region.

Noonan syndrome: a clinical and genetic study of 31 patients

Noonan syndrome is a multiple congenital anomaly syndrome, inherited in an autosomal dominant pattern. We studied 31 patients (18 males and 13 females) affected by this disorder regarding their clinical and genetic characteristics. The most frequent clinical findings were short stature (71%); craniofacial dysmorphisms, especially hypertelorism, ptosis, downslanting of the palpebral fissures; short or webbed neck (87%); cardiac anomalies (65%), and fetal pads in fingers and toes (70%). After studying the probands' first-degree relatives, we made the diagnosis of Noonan syndrome in more than one family member in three families. Therefore, the majority of our cases were sporadic.

New method for evaluation of cutaneous sensibility in diabetic feet: preliminary report

Diabetic neuropathy is an important complication of the disease, responsible for ulceration and amputation of the foot. Prevention of these problems is difficult mainly because there is no method to correctly access sensibility on the skin of the foot. The introduction of the Pressure-Specified Sensory Device (PSSD TM) in the last decade made possible the measurement of pressure thresholds sensed by the patient, such as touch, both static and in movement, on a continuous scale. This paper is the first in Brazil to report the use of this device to measure cutaneous sensibility in 3 areas of the foot: the hallux pulp, the calcaneus, and the dorsum, which are territories of the tibial and fibular nerves. METHOD: Non-diabetic patients were measured as controls, and 2 groups of diabetic patients - with and without ulcers - were compared. The PSSD TM was used to test the 3 areas described above. The following were evaluated: 1 PS (1-point static), 1 PD (1-point dynamic), 2 PS (2-points static), 2 PD (2-points dynamic). RESULTS: The diabetic group had poorer sensibility compared to controls and diabetics with ulcers had poorer sensibility when compared to diabetics without ulcers. The differences were statistically significant (P <.001). CONCLUSION: Due to the small number of patients compared, the results should be taken as a preliminary report.

Weight loss and morphometric study of intestinal mucosa in rats after massive intestinal resection: influence of a glutamine-enriched diet

Short-bowel syndrome is responsible for significant metabolic alterations that compromise nutritional status. Glutamine is considered an essential nutrient for enterocytes, so beneficial effects from supplementation of the diet with glutamine are hypothesized. PURPOSE: In this study, the effect of a diet enriched with glutamine was evaluated in rats undergoing extensive small bowel resection, with analysis of postoperative weight loss and intestinal morphometrics of villi height, crypt depth, and thickness of the duodenal and remnant jejunal mucosa. METHODS: Three groups of male Wistar rats were established receiving the following diets: with glutamine, without glutamine, and the standard diet of laboratory ration. All animals underwent an extensive small bowel resection, including the ileocecal valve, leaving a remnant jejunum of only 25 cm from the pylorus that was anastomosed lateral-laterally to the ascendant colon. The animals were weighed at the beginning and end of the experiment (20th postoperative day). Then they were killed and the remnant intestine was removed. Fragments of duodenal and jejunal mucosa were collected from the remnant intestine and submitted to histopathologic exam. The morphometric study of the intestinal mucosa was accomplished using a digital system (KS 300) connected to an optic microscope. Morphometrics included villi height, crypt depth, and the total thickness of intestinal mucosa. RESULTS: The weight loss comparison among the 3 groups showed no significant loss difference. The morphometric studies showed significantly taller duodenal villi in the glutamine group in comparison to the without glutamine group, but not different from the standard diet group. The measurements obtained comparing the 3 groups for villi height, crypt depth, and thickness of the remnant jejunum mucosa were greater in the glutamine-enriched diet group than for the without-glutamine diet group, though not significantly different from with standard-diet group. CONCLUSIONS: In rats with experimentally produced short-bowel syndrome, glutamine-enrichment of an isonitrogenous test diet was associated with an improved adaptation response by the intestinal mucosa but not reduced weight loss. However, the adaptation response in the group receiving the glutamine-enriched diet was not improved over that for the group fed regular chow.

Marfan's syndrome: early and severe form in siblings

Marfan's syndrome is an inherited disorder of the connective tissue. Cardiologic manifestations, especially aortic dilation, are important causes of morbidity and mortality in the clinical course of the disease in adults and teenagers. In children, the presence of aortic aneurysm and its dissection or rupture is rare, occurring in patients with genetic mutation of the fibrillin gene but not in those who have the familial form of the disease. We describe here 2 patients, from the same family (siblings), diagnosed with gigantic aortic aneurysm early in infancy, one of them successfully undergoing surgery.

Neuropatia autonômica cardiovascular diabética: fatores de risco, impacto clínico e diagnóstico precoce

A neuropatia autonômica cardiovascular (NAC) constitui uma das complicações de maior repercussão clínica do diabete melito (DM) e, ao mesmo tempo, está entre as menos diagnosticadas. Nesta revisão, são discutidos os principais fatores de risco para o desenvolvimento e a progressão da NAC nos pacientes com DM, a história natural da neuropatia autonômica e seu impacto na doença cardiovascular do DM, bem como os testes para o diagnóstico precoce e o estadiamento da NAC na prática clínica. A pesquisa bibliográfica teve como base dois bancos de dados: Medline e Tripdatabase, com os seguintes descritores: diabetic cardiovascular autonomic neuropathy e cardiovascular autonomic neuropathy and diabetes. Os artigos de 1998 a 2007 em inglês e alemão foram selecionados. A NAC em estágios iniciais (precoce e intermediária) pode ser diagnosticada e revertida, porém, nos casos avançados (estágio grave), resta apenas o tratamento sintomático. A NAC está associada a um maior índice de morbidade e mortalidade cardiovasculares e pior qualidade de vida nos indivíduos diabéticos

Investigation of Copy Number Variation in Children with Conotruncal Heart Defects

Background:Congenital heart defects (CHD) are the most prevalent group of structural abnormalities at birth and one of the main causes of infant morbidity and mortality. Studies have shown a contribution of the copy number variation in the genesis of cardiac malformations.Objectives:Investigate gene copy number variation (CNV) in children with conotruncal heart defect.Methods:Multiplex ligation-dependent probe amplification (MLPA) was performed in 39 patients with conotruncal heart defect. Clinical and laboratory assessments were conducted in all patients. The parents of the probands who presented abnormal findings were also investigated.Results:Gene copy number variation was detected in 7/39 patients: 22q11.2 deletion, 22q11.2 duplication, 15q11.2 duplication, 20p12.2 duplication, 19p deletion, 15q and 8p23.2 duplication with 10p12.31 duplication. The clinical characteristics were consistent with those reported in the literature associated with the encountered microdeletion/microduplication. None of these changes was inherited from the parents.Conclusions:Our results demonstrate that the technique of MLPA is useful in the investigation of microdeletions and microduplications in conotruncal congenital heart defects. Early diagnosis of the copy number variation in patients with congenital heart defect assists in the prevention of morbidity and decreased mortality in these patients.

Heart Rate and Systolic Blood Pressure Variability on Recently Diagnosed Diabetics

Background:Diabetes affects approximately 250 million people in the world. Cardiovascular autonomic neuropathy is a common complication of diabetes that leads to severe postural hypotension, exercise intolerance, and increased incidence of silent myocardial infarction.Objective:To determine the variability of heart rate (HR) and systolic blood pressure (SBP) in recently diagnosed diabetic patients.Methods:The study included 30 patients with a diagnosis of type 2 diabetes of less than 2 years and 30 healthy controls. We used a Finapres® device to measure during five minutes beat-to-beat HR and blood pressure in three experimental conditions: supine position, standing position, and rhythmic breathing at 0.1 Hz. The results were analyzed in the time and frequency domains.Results:In the HR analysis, statistically significant differences were found in the time domain, specifically on short-term values such as standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and number of pairs of successive NNs that differ by more than 50 ms (pNN50). In the BP analysis, there were no significant differences, but there was a sympathetic dominance in all three conditions. The baroreflex sensitivity (BRS) decreased in patients with early diabetes compared with healthy subjects during the standing maneuver.Conclusions:There is a decrease in HR variability in patients with early type 2 diabetes. No changes were observed in the BP analysis in the supine position, but there were changes in BRS with the standing maneuver, probably due to sympathetic hyperactivity.

Prevention of bone marrow graft failure by an anti LFA-1 monoclonal antibody

Graft rejection is the major cause of failure of HLA mismatched bone marrow transplantation because of residual host immunity. we have proposed to use a monoclonal murine antibody specific for the LFA-1 molecule (25-3) to prevent graft failure in HLA mismatched bone marrow transplantation (BMT). The rationale for this approach is three fold: LFA-1 deficient patients (3/3) do not reject HLA mismatched BMT; anti LFA-1 blocka in vitro the induction of T cell responses and T/ non T cytotoxic functions; LFA-1 is not expressed by other cells than leucocytes. We have accordingly treated twenty two patients with inherited diseases and 8 with leikemia. The bone marrow was T cells depled by E rosetting of Campath antibody. The antibody was given at days -3, -1, +1, +3, +5 at dose of .1 mg/kg/d for the first 9 and then .2mg/kg/d from day -3 to +6. Engraftment occured in 23/30 patients as shown by at least HLA typing. Hematological recovery was rapid, GVH was limited. Side effects of antibody infusion included fever and possibly an increased incidence of early bacteral infection (sepsis, 1 death). Immunological reconstitution occured slowly leading in six cases to EBV-induced B cell poliferation (1 death and in two others to transient auto immune hemolytic anemia. There has been only one secondary graft rejection. Sisteen patients are alive 3 to 26 months post transplant with functional grafts. Although the number of patients treated is still low the absence of late rejection so far, gives hope for long term maintenance of the graft using anti LFA-1. Since the antibody is an IgG 1 unable to bind human complement, and since it is known to inhibit phagocytosis, there is a good suggestion that 25-3 act through functional blocking of host T and non T luymphocytes at both induction and effector levels.

Onchocerciasis in Ecuador: changes in prevalence of ocular lesions in Onchocerca volvulus infected individuals over the period 1980-1990

Trends in prevalence rates of onchocercal ocular lesions were examined over the period 1980 to 1990 using data from two cross-sectional surveys. There was evidence for increasing prevalence of anterior chamber microfilariae, iridocyclitis, optic atrophy, and chorioretinopathy. Large increases in prevalence, in particular, were seen for posterior segment lesions: optic atrophy increased from 2.7% to 6.4% and chorioretinopathy from 8.8% to 35.6%. Greatest increases in these lesions were seen in the Chachi which was attributed to the large increases in prevalence of microfilariae in the anterior chamber particularly in those aged 30 years or greater. The study findings suggest that ocular onchocerciasis is evolving in parallel with the well documented parasitological changes.

Humoral immune responses induced by Kudoa sp. (Myxosporea: Multivalvulida) antigens in BALB/c mice

The majority of Kudoa species infect the somatic muscle of fish establishing cysts. As there is no effective method to detect infected fish without destroying them these parasited fish reach the consumer. This work was developed to determine whether this parasite contains antigenic compounds capable of provoking an immune response in laboratory animals, in order to consider the possible immunopathological effects in man by the ingestion of Kudoa infected fish. BALB/c mice were injected by the subcutaneous route with the following extracts suspended in aluminium hydroxide: group 1 (black Kudoa sp. pseudocyst extract), group 2 (white Kudoa sp. pseudocyst extract), and group 3 (non-infected hake meat extract). Specific antibody levels were measured by ELISA against homologous and heterologous antigens. The highest responses were obtained from the black Kudoa sp. pseudocyst extract (group 1).The low optic density levels detected in group 3 proved that the results obtained in groups 1 and 2 were a consequence of the parasitic extract injection. The IgG1 was the predominant subclass. IgE detected in groups 1 and 2 showed the possible allergenic nature of some of the components of the parasitic extract. High IgA levels and medium IgG2a and IgG3 levels were obtained in groups 1 and 2. Low IgG2b responses were shown. No cross-reactions between Kudoa sp. pseudocyst extracts and the non-infected hake meat extract were observed.

Use of polymerase chain reaction and enzymatic cleavage in the identification of Helicobacter spp. in gastric mucosa of human beings from North Paraná, Brazil

Helicobacter pylori is the most common gastric bacteria of human beings. Animal-borne helicobacter have been associated with gastritis, ulceration, and gastric mucosa-associated lymphoid-tissue lymphoma in people. We attempted to identify the species of Helicobacter spp. that infect human beings in north Paraná, Brazil. Samples of gastric mucosa from 38 dyspeptic patients were analyzed by optic microscopy on silver stained slides, polimerase chain reaction (PCR), and enzymatic cleavage. Genus and species-specific primers to H. pylori, H. heilmannii, H. felis, and consensual primers to H. bizzozeronii or H. salomonis were used. The PCR products were submitted to enzymatic cleavage by VspI (Helicobacter spp. product) and HinfI (species products) enzymes. Thirty-two out of 38 patients evaluated had 3.2 to 5 µm long bacteria that resembled H. pylori in Warthin-Starry stained slides and were positive to the genus Helicobacter by PCR. In 30 of these patients the bacteria were identified as H. pylori. Two samples positive by silver stain were negative to all species tested by PCR. None of the 38 samples was positive to animal-origin helicobacter species. These results show that PCR and enzymatic restriction are practical methods to identify the species of helicobacters present in gastric mucosa of human beings. People in north Paraná appear to be infected mostly with H. pylori.

The pathogenesis of diabetic complications: the role of DNA injury and poly(ADP-ribose) polymerase activation in peroxynitrite-mediated cytotoxicity

Recent work has demonstrated that hyperglycemia-induced overproduction of superoxide by the mitochondrial electron-transport chain triggers several pathways of injury [(protein kinase C (PKC), hexosamine and polyol pathway fluxes, advanced glycation end product formation (AGE)] involved in the pathogenesis of diabetic complications by inhibiting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. Increased oxidative and nitrosative stress activates the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP). PARP activation, on one hand, depletes its substrate, NAD+, slowing the rate of glycolysis, electron transport and ATP formation. On the other hand, PARP activation results in inhibition of GAPDH by poly-ADP-ribosylation. These processes result in acute endothelial dysfunction in diabetic blood vessels, which importantly contributes to the development of various diabetic complications. Accordingly, hyperglycemia-induced activation of PKC and AGE formation are prevented by inhibition of PARP activity. Furthermore, inhibition of PARP protects against diabetic cardiovascular dysfunction in rodent models of cardiomyopathy, nephropathy, neuropathy, and retinopathy. PARP activation is also present in microvasculature of human diabetic subjects. The present review focuses on the role of PARP in diabetic complications and emphasizes the therapeutic potential of PARP inhibition in the prevention or reversal of diabetic complications.

Estudo de ovos de quatro espécies do gênero Meccus (Hemiptera, Reduviidae, Triatominae), vetores da doença de Chagas

The objective of this work was to analyze the morphological, morphometrical, and histological characteristics of eggs of four triatomine bugs species still not studied, in order to understand phylogenetic aspects and to facilitate parameters used in taxonomy, with the purpose of a specific and generic characterization of these vectors in public health. The eggs of each species had come from the collections of the Laboratory of Triatomine bugs and Culicid mosquitoes of the Faculdade de Saúde Pública - USP (Faculty of Public Health/USP). The morphologic studies were carried out through optic microscopy (OM) and scanning electronic microscopy (SEM). The eggs were measured with the help of the digital paquimeter Starrett® 727. In relation to histological measures, Microtome Leica RM 2145® was used. Similarities were evidenced in the exocorial architecture of the eggs when they were studied by OM and SEM. This similarity among the eggs suggests a recent speciation, probably derived from common ancestry, representing a monophyletic group. Some structures were also detected by the histological cuts. The study has contributed to the magnification and recognition in generic and specific terms of the Triatominae subfamily. These new data will be able to subsidize a better understanding to determine roles for each vector species and to facilitate parameters to be used in taxonomy.

Mycobacterium leprae downregulates the expression of PHEX in Schwann cells and osteoblasts

Neuropathy and bone deformities, lifelong sequelae of leprosy that persist after treatment, result in significant impairment to patients and compromise their social rehabilitation. Phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) is a Zn-metalloendopeptidase, which is abundantly expressed in osteoblasts and many other cell types, such as Schwann cells, and has been implicated in phosphate metabolism and X-linked rickets. Here, we demonstrate that Mycobacterium leprae stimulation downregulates PHEX transcription and protein expression in a human schwannoma cell line (ST88-14) and human osteoblast lineage. Modulation of PHEX expression was observed to a lesser extent in cells stimulated with other species of mycobacteria, but was not observed in cultures treated with latex beads or with the facultative intracellular bacterium Salmonella typhimurium. Direct downregulation of PHEX by M. leprae could be involved in the bone resorption observed in leprosy patients. This is the first report to describe PHEX modulation by an infectious agent.