Exercise and the multidisciplinary holistic approach to adolescent dysautonomia.

AIM: To determine whether an eight-week strength training programme as part of a multidisciplinary approach would minimise symptoms and improve quality of life in patients with dysautonomia. METHODS: Adolescents referred to a tertiary-level cardiology service from May 2014-December 2015 with symptoms of dysautonomia were eligible. Participants completed an exercise test and a quality of life (QoL) questionnaire (PedsQL) prior to the intervention. Participants were asked to complete exercises five times per week. After eight weeks, participants returned for follow-up testing. Parents completed a proxy report of their child's QoL at both time points. RESULTS: A total of 17 participants completed the study protocol with an adherence rate of up to 50%. Post-intervention, QoL scores improved across all levels in the participants [total 65.2 (50.4-74.7) vs 48.9 (37.5-63.0); p = 0.006; psychosocial 65.8 (56.1-74.6) vs 50.0 (41.7-65.8); p = 0.010; physical 62.5 (37.5-76.6) vs 43.8 (25-68.5); p = 0.007] and their parent proxy reports [total 63.5 (48.7-81.3) vs 50.0 (39.3-63.0); p = 0.004; psychosocial 62.1 (52.1-81.3) vs 50.0 (39.6-59.2); p = 0.001; physical 62.5 (51.6-80.0) vs 50.0 (27.5-70.3); p = 0.003]. Treadmill time also improved (9.1 vs 8.0 minutes; p = 0.005). CONCLUSION: Following an eight-week strength training programme, dysautonomia patients report a significant improvement in both their quality of life and endurance time.

The effect of hormones on endometriosis development.

Endometriosis is a common gynecological condition in which tissue that is histologically similar to the endometrium with glands and/or stroma grows outside the uterine cavity and can lead to pelvic pain, dysmenorrhea and infertility. Many aspects of female reproductive function are strongly influenced by genetic factors and numerous studies have attempted to identify susceptibility genes for disorders affecting female fertility such as endometriosis. The importance of steroid hormones on endometriosis is unquestionable. The disease is most prevalent in women of reproductive age and regresses after menopause and its occurrence before menarche has not been reported. Sex steroids, estrogen and progesterone, are mainly produced in the ovaries and they regulate the growth of endometrial tissue, basically by stimulating and inhibiting cell proliferation, respectively. In addition, estrogen plays an important role in the regulation of cyclic gonadotropin release and in folliculogenesis. Numerous studies have been conducted to demonstrate the interaction of hormone and their receptors with endometriosis with conflict results. Besides, environmental chemicals, known as endocrine disruptors, have the capacity to mimic, block or modulate the endocrine system through the interaction with steroidal receptors. Recently evidences have proposed a putative role for ubiquitous environmental contaminants in the occurrence of endometriosis. Here, we reviewed significant articles regarding the interaction among endometriosis, hormones and genetic polymorphic variants.

Characterization and partial isolation of ouabain-insensitive Na(+) -ATPase in MDCK I cells.

We show that MDCK I cells express, besides the classical (Na(+)+K(+))ATPase, a Na(+)-stimulated ATPase activity with the following characteristics: (1) K(0.5) for Na(+) 7.5+/-1.5 mM and V(max) 23.12+/-1.1 nmol Pi/mg per min; (2) insensitive to 1 mM ouabain and 30 mM KCl; and (3) inhibited by furosemide and vanadate (IC(50) 42.1+/-8.0 and 4.3+/-0.3 microM, respectively). This enzyme forms a Na(+)-stimulated, furosemide- and hydroxylamine-sensitive ATP-driven acylphosphate phosphorylated intermediate with molecular weight of 100 kDa. Immunoprecipitation of the (Na(+)+K(+))ATPase with monoclonal anti-alpha(1) antibody reduced its activity in the supernatant by 90%; the Na(+)-ATPase activity was completely maintained. In addition, the formation of the Na(+)-stimulated, furosemide- and hydroxylamine-sensitive ATP-driven acylphosphate intermediate occurred at the same magnitude as that observed before immunoprecipitation. These data suggest that Na(+)-ATPase and (Na(+)+K(+))ATPase activities are independent, with Na(+)-ATPase belonging to a different enzyme entity.

Analysis of worldwide sequence mutations in Zika virus proteins E, NS1, NS3 and NS5 from a structural point of view.

Zika virus (ZIKV) is an emergent arbovirus that has attracted attention in the last year as a possible causative agent of congenital malformation; it shows a remarkably increased microcephaly risk during otherwise healthy pregnancies. We present here an analysis of all ZIKV sequences available in Genbank up to April 2016, studying the mutations in the whole polyprotein and their possible structural implications for the proteins E, NS1, NS3 and NS5. This study suggests that microcephaly is not a consequence of any particular amino acid substitution but, conceivably, is a feature of ZIKV itself. Moreover, the structural analysis of ZIKV proteins, together with the mutational landscape of ZIKV and a structure-sequence comparison with other flaviviruses, allows the suggestion of regions that could be exploited as anti-ZIKV targets, including some allosteric sites found in the NS3 and NS5 proteins of DENV.

Protein kinase C-induced phosphorylation modulates the Na(+)-ATPase activity from proximal tubules.

This study describes the modulation of the ouabain-insensitive Na(+)-ATPase activity from renal proximal tubule basolateral membranes (BLM) by protein kinase C (PKC). Two PKC isoforms were identified in BLM, one of 75 kDa and the other of 135 kDa. The former correlates with the PKC isoforms described in the literature but the latter seems to be a novel isoform, not yet identified. Both PKC isoforms of BLM are functional since a protein kinase C activator, TPA, increased the total hydroxylamine-resistant 32P(i) incorporation from [gamma-32P]ATP into the BLM. In parallel, TPA stimulated the Na(+)-ATPase activity from BLM in a dose-dependent manner, the effect being reversed by the PKC inhibitor sphingosine. The stimulatory effect of TPA on Na(+)-ATPase involved an increase in the V(max) (from 13.4+/-0.6 nmol P(i) mg(-1) min(-1) to 25.2+/-1.4 nmol P(i) mg(-1) min(-1), in the presence of TPA, P<0.05) but did not change the apparent affinity for Na(+) (K(0.5)=14.5+/-2.1 mM in control and 10.0+/-2.1 mM in the presence of TPA, P>0.07). PKC involvement was further confirmed by stimulation of the Na(+)-ATPase activity by the catalytic subunit of PKC (PKC-M). Finally, the phosphorylation of an approx. 100 kDa protein in the BLM (the suggested molecular mass of Na(+)-ATPase [1]) was induced by TPA. Taken together, these findings indicate that PKCs resident in BLM stimulate Na(+)-ATPase activity which could represent an important mechanism of regulation of proximal tubule Na(+) reabsorption.

Angiotensin II and angiotensin-(1-7) inhibit the inner cortex Na+ -ATPase activity through AT2 receptor.

In the present paper, the modulation of the basolateral membrane (BLM) Na+ -ATPase activity of inner cortex from pig kidney by angiotensin II (Ang II) and angiotensin-(1-7) (Ang-(1-7)) was evaluated. Ang II and Ang-(1-7) inhibit the Na+ -ATPase activity in a dose-dependent manner (from 10(-11) to 10(-5) M), with maximal effect obtained at 10(-7) M for both peptides. Pharmacological evidences demonstrate that the inhibitory effects of Ang II and Ang-(1-7) are mediated by AT2 receptor: The effect of both polypeptides is completely reversed by 10(-8) M PD 123319, a selective AT2 receptor antagonist, but is not affected by either (10(-12) - 10(-5) M) losartan or (10(-10)-10(-7) M) A779, selective antagonists for AT1 and AT(1-7) receptors, respectively. The following results suggest that a PTX-insensitive, cholera toxin (CTX)-sensitive G protein/adenosine 3',5'-cyclic monophosphate (cAMP)/PKA pathway is involved in this process: (1) the inhibitory effect of both peptides is completely reversed by 10(-9) M guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS; an inhibitor of the G protein activity), and mimicked by 10(-10) M guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS; an activator of the G protein activity); (2) the effects of both peptides are mimicked by CTX but are not affected by PTX; (3) Western blot analysis reveals the presence of the Gs protein in the isolated basolateral membrane fraction; (4) (10(-10)-10(-6) M) cAMP has a similar and non-additive effect to Ang II and Ang-(1-7); (5) PKA inhibitory peptide abolishes the effects of Ang II and Ang-(1-7); and (6) both angiotensins stimulate PKA activity.

Nature of plant stimulators in the production of Acetobacter xylinum ("tea fungus") biofilm used in skin therapy.

Caffeine and related xanthines were identified as potent stimulators for the bacterial cellulose production in A. xylinum. These compounds are present in several plants whose infusions are useful as culture-medium supplements for this acetobacterium. The proposed target for these native purine-like inhibitory substances is the novel diguanyl nucleotide phosphodiesterase(s) that participate(s) in the bacterial cellulogenic complex. A better understanding of this feature of A. xylinum physiology may facilitate the preparation of bacterial cellulose pellicles, which are applied as a biotechnological tool in the treatment of skin burns and other dermal injuries.

Acetobacter cellulose pellicle as a temporary skin substitute.

A bacterial strain with morphological and biochemical properties close to Acetobacter xylinum has been cultured in nonagitated, inverted sucrose- and yeast water-based medium for the production of thick, smooth, and floating cellulosic pellicles. The cellulose content (greater than 90%, dry weight, depending on the efficiency of water washing) and the beta-D-homopolyglucan nature of these pellicles were assessed by physical, chemical, and enzymatic methods. The apyrogenic bacterial biomass, a minor component of the dried biofilm (BioFill), is inactivated by ethylene dioxide. Once applied on exudating or bloody tissues, this biofilm displays several advantages as a biological dressing, and hence, it is valuable as a temporary skin substitute in the treatment of skin wounds, such as burns, ulcers, grafts, and as an adjuvant in dermal abrasions.

[Immunoenzymatic test for the detection of anti-Cysticercus cellulosae antibodies in cerebrospinal fluid of patients with meningitis of unknown etiology]. / Teste imunoenzimático para pesquisa de anticorpos anti-Cysticercus cellulosae em líquidos cefalorraquianos de pacientes com meningites de etiologia indeterminada.

The enzyme-linked-immunosorbent assay using a new type of support consisting of discs of synthetic fabric-resin (ELISA-d) with antigenic components of Cysticercus cellulosae covalently bound, was employed with the purpose of investigating the presence of specific antibodies to the cysticerci (neurocysticercosis) in the cerebrospinal fluid (CSF) of patients with meningitis without etiological agent determined by the conventional methods. The test was performed in 277 CSF samples (128 children and 149 adults). The mean of optical density values (OD) obtained for 22 CSF normal patients (the diagnostic hyphotesis of meningitis was discarded) was of 0.03. The 44 CSF of patients with meningitis caused by other agents but C. cellulosae, showed OD of 0.05. The cut off determined with these two groups (control group) was 0.13 (OD + 3 SD). The group of 13 CSF of neurocysticercotic meningitis presented OD of 0.41 (0.10 to 0.91). Among the 198 CSF samples of indetermined meningitis, 23 (11.6%) presented OD above the cut off, which suggests the possibility that Cysticercus cellulosae was the etiological agent in this meningitis episode. The ELISA-d test has proved to be efficient for the immunodiagnosis of neurocysticercosis when conducted on CSF samples. The alterations observed in the 23 CSF reactive on ELISA-d were: increased number of lymphomononuclear cells in five, of polymorphonuclear cells in 13 and both cells in five samples.

Visceral larva migrans: a seroepidemiological survey in five municipalities of São Paulo state, Brazil.

An enzyme-linked immunosorbent assay (ELISA), employing antigens from Toxocara canis larvae and the absortion of suspected sera with Ascaris lumbricoides extracts was used in a seroepidemiological study performed in five municipalities of São Paulo State, Brazil (São Paulo, Campinas, Santos, Marília and Presidente Prudente) in order to determine the frequency of antibodies to Toxocara. In 2,025 blood samples collected, 806 proceeded from male subjects and 1,219 from females; 483 samples were collected from subjects under 15 years of age and the remaining 1,542 from subjects aged 15 years or over. Among the 2,025 sera investigated, 3.60% had antibodies to Toxocara at significant levels. A moderate predominance of infection with Toxocara among male subjects (3.72%) was observed, although the difference was not statistically significant when this rate was compared with that for female (3.28%). Related to age, a higher frequency of positive results was detected among subjects under 15 years (6.41%) against the older group (2.53%). A trend of more elevated rates of infection was observed in municipalities with high demographic densities (São Paulo, Campinas and Santos). Nevertheless, such findings only appeared to be statistically significant in subjects younger than 15 years.

[Immunodiagnosis of human leptospirosis by ELISA-IgM, employing different antigenic preparations from prevalent serovars of Leptospira interrogans]. / Imunodiagnóstico da leptospirose humana através do teste ELISA-IgM, empregando-se diferentes preparações antigênicas a partir de sorotipos prevalentes de Leptospira interrogans.

A comparative study among different serovars of Leptospira interrogans was performed in order to prepare antigens to detect IgM antibodies by ELISA in early and late phase of human leptospirosis. Ten serovars were chosen among the most prevalent detected by microscopic seroagglutination (SAM) in São Paulo city. Using ELISA-IgM five of them showed better results (canicola, hebdomadis, icterohaemorrhagiae, cynopteri and brasiliensis). These ones were also studied in a pool. The non-treated antigens showed higher reactivity than the Triton X-100 (4%/50 degrees C/4h). ELISA-IgM using individually or pool of non-treated antigens proved to be reliable with high sensitivity and should be used for an earlier diagnosis of leptospirosis, as a trial test. Faster diagnostic elucidation can be useful to detect epidemic situations, so, allowing epidemiological surveillance interventions.

[Leptospirosis in patients with anti-HIV antibodies: report of 2 cases]. / Leptospirose em doentes com anticorpos anti-HIV: relato de dois casos.

Two patients with concomitant leptospirosis and the acquired immunodeficiency syndrome (AIDS) are reported. In these cases different clinical aspects that can be attributed to simultaneity of these pathologies was not observed.

[Cognitive performance in patients with surgically treated cerebral aneurysms]. / Desempenho cognitivo em pacientes operados de aneurisma cerebral.

Twenty five patients with cerebral aneurysms submitted to surgery were evaluated with cognitive tests to quantify late disorders in language, praxis, orientation, logics, comprehension, memory, depression, dementia and visual gnosis. Results were correlated with age, Hunt-Hess scale, blood at CT (Fisher), angiographic vasospasm (George), side, site, and size of aneurysm. Delayed cognitive disorder was absent in 8 (32%), slight in 5 (20%), moderate in 6 (24%) and severe in 6 (24%). Logics was more affected with 7 severe and moderate patients (28%), praxis was similarly affected in 6 (24%), orientation in 5 (20%), language and memory in 4 (16%); visual gnosis abnormalities, dementia and depression were rarely seen. Patients aged 25-50 years had best cognitive results with sequels absent or slight in 9 patients (75%). Aneurysms of right posterior communicating artery had cognitive sequels absent or slight in 5 (71.42%), right medium cerebral artery in 2 (66.66%). Aneurysms of left medium cerebral artery had the worse results with severe and moderate disabilities in 5 patients (71.42%). Delayed post operative cognitive results in patients operated with cerebral aneurysms are directly related to Hunt-Hess scale, amount of blood at CT, angiographic vasospasm and site of the aneurysm.

[Rett phenotype in patient with XXY karyotype: case report]. / Fenótipo Rett em paciente com cariótipo XXY. Relato de caso.

We report the case of a XXY boy who presents progressive neurological disorder which has started around eleven months of age, with developmental stagnation followed by regression. The child presents as well stereotypic hand movements, loss of purposeful hands use and microcephalia. Presence of any defined systemic or neurological condition which could be pointed out as the possible etiological factor for the case was not found out by investigations. It deals with a boy with phenotypic alterations very similar to those considered typical for Rett syndrome which associated with chromosomal alteration (XYY karotype) constitute evident scientific interest.

[IQ in hydrocephalus and myelomeningocele. Implications of surgical treatment]. / QI em pacientes com hidrocefalia e mielomeningocele. Implicações do tratamento cirúrgico.

Myelomeningocele occurs in 0.4 for 1000 neonates and is associated with hydrocephalus in 85-90%, and reports on cognition are sparsely found in literature. Forty five children with treated hydrocephalus and myelomeningocele were studied in regard of IQ, and statistically correlated to functional motor level, age of the first shunt, number of revisions of shunt, infection of the shunt and circumference of the head. The medium age was of 7.5 years (3-15 years), 16 males and 29 females. Three (6.6%) had a IQ score > 110, 11 (24.4%) had a score between 100-110, 8 between 85-100 (17.7%), 16 (35.5%) between 85-100 (17.7%) and 7 (15.5%) between 50-70. IQ directly correlated with motor level, having better cognitive results the children with minor functional motor disabilities. Cognition was best in children operated until the seven day of life (t 0.0099), with progressive worse results in children operated after the first month of life, no significance was observed in children operated in the period 7 to 31 days (t 0.1013). Worse results were observed in the group of patients with infection of shunts (t 0.0146). Results were progressively worse with reoperations. The best results in relation of the circumference of the head were seen with children in the medium range (t 0.0115); intermediate results were seen in patients between the medium range and-1SD (t 0.00130) and medium range and +1SD. The worse results were seen in patients at the extremes of > 1SD (t 0.0269) and < ISD (t 0.0042). According to cognitive results the surgical treatment of hydrocephalus have to be done until the first month of life, avoiding reoperations and infections that have unfavorable impact in IQ.

[Echocardiographic diagnosis of accessory leaflet of mitral valve]. / Diagnóstico ecocardiográfico de folheto acessório de valva mitral.

The accessory mitral valve leaflet is a rare cardiac congenital anomaly usually associated to complex cardiac congenital malformations. It also represents a rare cause of left ventricular outflow tract obstruction. Its diagnosis has often been ignored by conventional diagnostic methods. This fact may represent a cause for relative surgical failure, when operations for cardiac complex anomalies are performed. Echodopplercardiography is the choice and more accurate method for its diagnosis. In our case, parasternal and apical long axis planes, allowed an unmistakable visualization of a parachute shape fibrous structure, with its concave surface turned up towards the aortic valve. Chordae tendinae proper to the anomalous accessory mitral valve tissue were connected to chordae or to papillary muscles of the mitral valve. A careful echodopplercardiographic study will allow us, not only to diagnose this malformation, as well as to differentiate it from other conditions like tumors, vegetations or other types of subaortic obstruction.

[The dilatation of the residual stenosis due to a Blalock-Taussig anastomosis by percutaneous transluminal angioplasty]. / Dilatação de estenose residual da anastomose Blalock-Taussig modificada pela angioplastia transluminal percutânea.

A ten-months-old white infant had undergone surgical modified Blalock-Taussig anastomosis at 2 months of age. An interposition of bovine mammary artery was anastomosed with the right subclavian artery. A satisfactory clinical follow-up after surgery was achieved, until the last three months when cyanotic spells were observed. A new angiographic study showed tricuspid and pulmonary atresia and severe stenosis (+/- 80%) at the anastomosis between the subclavian artery and the bovine mammary tissue. Percutaneous transluminal angioplasty was successfully performed. An immediate improvement of cyanosis and oxygen saturation were observed.

Growth and hematological studies on Brazilian children of low socioeconomic level.

Anemia and undernutrition are common all over the world, especially in less developed countries. The relationship between low weight, short stature and iron deficiency should be better understood so that appropriate measures might be taken to prevent these problems. A total of 115 institutionalized children aged 12 to 72 months were studied in day-care institutions in the town of Pontal, Southeastern Brazil, during the second semester of 1999. Personal data, weight, height and hematological profile were obtained from all subjects. Food intake was evaluated in 20 children by a direct food-weighing method. The prevalence of low weight for age (2.6%), low weight for height (1.7%) and low height for age (4.3%) was considered low. Anemia was observed in 68.7% of the children. Diet was found to be adequate in terms of the major nutrients evaluated, but food iron supply was of low bioavailability. In conclusion, the population studied revealed a peculiar behavior i.e., the coexistence of fairly good anthropometric nutritional status along with iron-deficiency anemia. The prevention of this kind of malnutrition cannot be limited to an adequate calorie/protein supply but should also be based on the correction of the severe iron deficiency present in this low socioeconomic level preschool children in Brazil.