Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels

INTRODUCTION: Approximately 30% of hepatitis C virus (HCV) monoinfected patients present persistently normal alanine aminotransferase (ALT) levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive) with known time of HCV infection (intravenous drugs users) were selected. Patients with hepatitis B surface antigen (HBsAg) positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80%) were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26%) patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001) periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001) and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year) significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.

Microvascularização arterial da cóclea

RESUMO: Na descrição deste estudo foi utilizada a terminologia anatómica da Sociedade Brasileira de Anatomia adaptada ao português por J. A. Esperança-Pina de acordo com o tratado Anatomia Humana da Relação. Os actuais estudos sobre hipoacusia sensorioneural implicam um grupo crescente de situações, em que a lesão se situa ao nível da microvascularização coclear, daí que o conhecimento exacto da angiomorfologia normal se torne essencial na fase actual do conhecimento. A autora tem vindo a estudar, desde 1986, a angiomorfologia do ouvido Interno no modelo experimental, o Cobaio, utilizando várias técnicas microvasculares. sendo dado enfâse particular neste estudo à técnica de microscopia electrónica de varrimento em moldes vasculares. Os animais usados no presente estudo pertencem à espécie cavia porcellus, cobaio, por serem considerados na comunidade cientifica internacional como o melhor modelo experimental para estudo do ouvido interno, pelo facto de a morfologia coclear ser muito semelhante à do Homem e por isso ser um modelo fiável para cirurgia experimental e microdissecção. Este estudo foi realizado em 100 cobaios, cavia porcellus, de ambos os sexos com peso médio de 450g. A vascularização do ouvido interno, no cobaio como no homem, faz-se através dos ramos de divisão da artéria auditiva interna ou labiríntica. A artéria labiríntica origina-se como ramo colateral da artéria cerebelosa ântero-inferior a qual tem origem na artéria basilar ou na artéria vertebral. Embora no homem a artéria auditiva interna possa também destacar-se da artéria basilar e até da artéria vertebral, no cobaio em todos os casos estudados a sua origem verificou-se sempre na artéria cerebelosa ântero-inferior. A artéria labiríntica, ao passar abaixo do meato auditivo interno, divide-se na artéria vestibular anterior e na artéria coclear comum.A artéria vestibular anterior dirige-se para o nervo vestibular, emite vasa nervorum para este nervo e vasculariza o utrículo e os canais semicirculares. A artéria coclear comum origina dois ramos principais, a artéria vestíbulo‑coclear ou vestibular posterior no cobaio, a qual se destaca junto à espira basal da cóclea e a artéria coclear, como ramo terminal, que passa a denominar-se de artéria modiolar ou espiralada, após entrar no modíolo. A artéria modiolar ascende no modíolo promovendo através dos seus ramos colaterais e dos seus ramos terminais a microvascularização coclear, numa vascularização de órgão de tipo terminal. Ao longo do seu trajecto verificou‑se de modo constante uma redução gradual de calibre em cada uma das espiras, por emissão de ramos colaterais, sendo que o calibre da artéria na base da cóclea apresenta um valor que diminui gradualmente até ao ápice. A artéria modiolar origina em todo o seu trajecto ramos colaterais, cujo número diminui em valor absoluto da base para o ápice: Arteríolas radiárias internas, arteríolas de trajecto flexuoso que caminham junto às estruturas sensorioneurais da parede interna da cóclea, junto ao lábio timpânico da lâmina espiral óssea e na parede do próprio modíolo, que se relacionam intimamente com este. As arteríolas radiárias internas originam‑se no flanco da artéria modiolar espiralada. Contam‑se dez a doze em cada espira, extraordinariamente flexuosas desde a sua origem. As arteríolas radiárias internas originam como ramos colaterais, vários grupos de arteríolas de menor calibre, que vascularizam distintas regiões da parede interna da cóclea, as arteríolas do gânglio espiral, a rede espiral interna, as arteríolas de origem dos glomérulos de Schwalbe e a arteríola da lâmina basilar. As arteríolas radiárias externas importantes ramos colaterais da artéria modiolar espiralada promovem a vascularização de importantes estruturas da parede externa. Ao atingir o limite externo do ligamento espiral, as arteríolas radiárias externas dividem‑se em vários ramos arteriolares de menor calibre, ao longo da convexidade do limite externo do ligamento espiral, originando a rede capilar pós-estriada que ocupa a porção lateral do ligamento espiral e a rede capilar ad‑ -estriada, na sua porção mais medial em íntima relação com a estria vascular. A espira basal da cóclea apresenta grande riqueza de vascularização, com características particulares apenas a esta espira, a qual é metabolicamente a mais exigente. A arteríola da janela da cóclea aborda a janela da cóclea pela sua convexidade e divide-se numa rica rede vascular da qual emergem arteríolas pré-capilares que se ramificam em capilares, os quais se dirigem em profundidade penetrando a rampa timpânica da cóclea ao nível da espira basal. Importou neste estudo verificar quais as semelhanças em termos de calibre de estruturas análogas, na parede interna e na parede externa da cóclea, com particular incidência na rede capilar. Do estudo estatístico realizado com testes paramétricos de Tamahane e não paramétricos de Mann-Whitney, verifica-se que comparando todas as estruturas consideradas estas têm calibres diferentes, com excepção dos capilares da estria vascular e do ligamento espiral, pertencentes à parede externa da cóclea que têm calibres iguais aos capilares da rede espiral interna e aos capilares da parede interna da cóclea, dependentes das arteríolas da rede espiral interna. As redes capilares dependentes das arteríolas radiárias internas que vascularizam as estruturas sensorioneurais junto á parede interna do modiolo são em tudo semelhantes em termos de calibre às redes capilares da parede externa da cóclea, incluindo os capilares da estria vascular. Esta particularidade traduz num órgão com vascularização de tipo terminal,um mecanismo de controlo do fluxo sanguíneo coclear tão importante na parede interna como na parede externa da cóclea. ------------ ABSTRACT:Current studies on sensorineural hearing loss, imply a growing group of situations in which the lesion is located at the level of the cochlear microvasculature, hence the exact knowledge of normal angiomorfology becomes essential in current state of knowledge. The author has been studying since 1986, the angiomorfology of inner on the experimental model, the guinea pig, using various microvascular techniques being given particular emphasis in this study to the results of the technique of scanning electron microscopy on corrosion casts. The animals used in this study belong to the species cavia porcellus, guinea pig, to be considered in the international scientific community as the best experimental model for the study of the inner ear, the cochlear morphology is very similar to human and therefore a reliable model for experimental surgery and microdissection. This study was performed in 100 guinea pigs of both sexes with average weight of 450g. There shall be a brief description of embryology, anatomy and cochlear physiology in the light of developmental biology, regarding also the spatial location of the cochlea and the determinism of morphogenetic fields in their development and function. The cochlear transduction mechanism converts the sound wave in stimuli sound and so afferent auditory nerve fibres and deafness are closely related to the cochlear microvasculature. Cochlear ischemia is accompanied by immediate hearing loss. The different type of cochlear injury that leads to sensorineural deafness is well studied in presbycusis where an objective link with the audiometric pattern as been established. The sensory type of deafness, is closely related to the degeneracy of the organ of Corti and damage to the outer hair cells at the basal turn of the cochlea. Keeping in mind cochlear tonotopy with location of high frequency sounds at the level of the base of the cochlea, it explains the audiometric pattern with loss in high frequencies. The neural type of deafness, is characterized by neuronal loss with loss of descendant important neuronal afferents, with audiometric translation on a gradually curve with important loss of auditory discrimination. The metabolic type of deafness results in atrophy of the vascular stria, with consequent change in the potential of the endolymph by decreasing the vascular stria cells and changes in K + recycling mechanism. There is also a change in the morphology of the spiral ligament and the audiometric patern as a flattened curve with loss at all frequencies. Bearing in mind cochlear tonotopy and being characterized all types of sensorineural deafness, we may inquire to what extent the cochlear microvasculature, considering not only the cochlea as a whole but different regions of the inner wall and the outer wall of the cochlea, contributes to deafness. We analysed the entire cochlear morphology on scanning electron microscopy with particular emphasis on bone and membranous cochlea. The inner wall of the cochlea and intramodiolar structures such as the spiral ganglion, the morphology of its cell bodies and their axons are analyzed. The morphology of Corti’s organ is described in detail, with description and large detail of the inner and outer hair cells. Is then presented the study of the microvasculature itself. The spiral modiolar artery is observed with the diaphanization technique and the technique of scanning electron microscopy on corrosion vascular casts. After emergence of collateral branches of the greatest importance, the radiating internal and external arterioles, the modiolar artery gives rise to its terminal branches, the arterioles of the cochear apex. Arterial vasa vasorum and vasa nervorum are displayed with a great detail, which was not yet described in such detail in previous microvascular studies. The arterial radiating arterioles originate in the flank of the spiral modiolar artery in number of ten to twelve in each loop, and they vascularize through their branches the inner wall cochlear sensorineural structures located in the modiolus as the spiral ganglion and structures near the organ of Corti. Their caliber is above 20 μm on the basal turn and in the second loop it decreases to values between 12 and 20 μm, decreasing progressively to the apex of the cochlea.They arise near the modiolus or on their way in the spiral lamina forming vascular loops, and divide without presenting vascular constrictions in their divisions, originating new vascular loops of lower caliber. Internal ratiating arterioles originate as collateral branches several groups of smaller caliber arterioles, which vascularize distinct regions of the inner wall of the cochlea namely, the arterioles of the spiral ganglion, the internal spiral network, the arterioles of origin of the glomeruli of Schwalbe and the arterioles of the basilar membrane. The glomeruli of Schwalbe play an important functional role as relay-stations, in hemodynamic terms, to control the cochlear microvasculature. External radiating arterioles have their origin in the spiral modiolar artery, they are directed towards the outer wall of the cochlea and run through the roof of the scala vestibuli. Above the insertion of Reissner’s membrane on the external wall the external radiating arterioles originate the spiral ligament arterioles, which vascularize the spiral ligament, they divide into several arteriolar branches of smaller caliber, along the convexity of the outer edge of the spiral ligament. The connective tissue of the spiral ligament forms a mesh with supporting function of the highly specialized epithelium, where pericytes were identifiable. Next to its base there is the microvascular network of stria vascularis. The adstriated vascular network which is divided into a capillary network, the capillary network of stria vascularis. The stria vascularis, the only vascularized epithelium of the human body, plays an important role, forming an haemato-labyrintine barrier to assure labyrinthine endocochlear potential and transport of ions, essential for the mechanism of transduction of external hair cells. The cochlear basal turn has a special feature on its external wall, the region of the windows, the round windows giving access to scala tympani and the oval window thatleads into scala vestibuli, and so it is metabolic demanding. For their role in cochlear tonotopy the sensorineural structures and those of the external wall of the cochlea, are particularly vulnerable to hypoxia. Although the complementarity of all the techniques was important for three- -dimensional reconstruction of the microvasculature of the cochlea, the scanning electron microscopy technique, especially when we used the system Semafore was fundamental to perform precise morphometric mesures regarding all vascular structures.Regarding the capillaries of the inner and outer wall of the cochlea networks this technique allowed their characterization in morphometric terms. To conclude the capillaries of the inner wall and of the external wall of the cochlea have similar size. So although located at different cochlear regions, with a different functional role, in cochlear physiology these networks consist of capillaries of similar caliber. It seems to translate a cochlear blood flow control mechanism that is so important in the inner wall as in and the external wall of the cochlea to provide for in inner ear homeosthasia.

A segurança ao uso normal na decisão de intervenção em parques edificados

O estado de degradação de edifícios em Portugal tem aumentado significativamente ao longo dos últimos anos, devido, entre outros aspectos, ao envelhecimento e à falta de manutenção. Estes factores aceleram o processo de deterioração dos edifícios, motivando o aparecimento de anomalias. No entanto, existem diversas ferramentas para o levantamento dessas anomalias e para avaliação do estado de conservação de edifícios. Em 2006, foi desenvolvido no Laboratório Nacional de Engenharia Civil (LNEC), o Método de Avaliação do Estado de Conservação de imóveis (MAEC), que permite determinar, de forma expedita, o estado de conservação de edifícios, através da realização de inspecções visuais ao local por técnicos qualificados. Contudo, algumas situações que possam causar riscos na utilização corrente dos edifícios, caso não derivem de anomalias físicas construtivas, não são tomadas em consideração para efeitos de definição de intervenções de reabilitação. Considera-se importante que no momento do levantamento das condições de degradação física, a avaliação da segurança ao uso normal tenha igual relevância, através da identificação de alguns perigos. Em países como o Reino Unido e França são utilizadas metodologias de avaliação que integram em simultâneo estas duas dimensões. Neste sentido, o MAEC poderá ser complementado de forma a concretizar e a viabilizar este tipo de avaliações. Assim, o estudo visa desenvolver uma ferramenta aplicável em inspecções para avaliação das condições de segurança dos imóveis (MACS), integrando o MAEC neste processo de intervenção. Para isso analisaram-se outros métodos de avaliação (nacional e estrangeiros) que serviram de apoio ao desenvolvimento da proposta. Para testar a viabilidade do novo método foi avaliada uma amostra de imóveis no âmbito do MAEC e do MACS, através da inspecção de edifícios de uso habitacional, com épocas construtivas distintas. De uma forma geral, concluiu-se que a metodologia permitiu criar padrões actuais de risco, e a sua aplicação possibilitou a comparação das condições de segurança de diferentes edifícios. Também foi possível identificar os perigos com maior risco de ocorrência de acidentes, permitindo a definição de níveis de urgência de intervenção das situações consideradas perigosas.

Weight concerns scale applied to college students : Comparison between pencil-and-paper and online formats

Online data collection is becoming increasingly common and has some advantages compared to traditional paper-and-pencil formats, such as reducing loss of data, increasing participants' privacy, and decreasing the effect of social desirability. However, the validity and reliability of this administration format must be established before results can be considered acceptable. The aim of this study was to evaluate the validity, reliability, and equivalence of paper-and-pencil and online versions of the Weight Concerns Scale (WCS) when applied to Brazilian university students. A crossover design was used, and the Portuguese version of the WCS (in both paper-and-pencil and online formats) was completed by 100 college students. The results indicated adequate fit in both formats. The simultaneous fit of data for both groups was excellent, with strong invariance between models. Adequate convergent validity, internal consistency, and mean score equivalence of the WCS in both formats were observed. Thus, the WCS presented adequate reliability and validity in both administration formats, with equivalence/stability between answers.

Relationship between plasma creatinine concentration and glomerular filtration in preterm newborn infants

Fluid management and dosage regimens of drugs in preterm infants should be based on the glomerular filtration rate. The current methods to determine glomerular flitration rate are invasive, time-consuming, and expensive. In contrast, creatinine clearance can be easy obtained and quickly determined. The purpose of this study was to compare plasma creatinine on the third and seventh day of life in preterm newborn infants, to evaluate the influence of maternal creatinine, and to demonstrate creatinine clearance can be used as a reliable indicator of glomerular filtration rate. We developed a prospective study (1994) including 40 preterm newborns (gestational age < 37 weeks), average = 34 weeks; birth weight (average) = 1840 g, in the first week of life. Inclusion criteria consisted of: absence of renal and urinary tract anomalies; O2 saturation 3 92%; adequate urine output (>1ml/kg/hr); normal blood pressure; absence of infections and no sympathomimetic amines in use. A blood sample was collected to determine plasma creatinine (enzymatic method) on the third and seventh day of life and creatinine clearance (CrCl) was obtained using the following equation: , k = 0.33 in preterm infant All plasma creatinine determinations showed normal values [third day: 0.78 mg/dl ± 0.24 (mean ± SD)and seventh day: 0.67 mg/dl ± 0.31 - (p>0.05)]. Also all creatinine clearance at third and seventh day of life were normal [third day: 19.5 ml/min ± 5.2 (mean ± SD) and seventh day: 23.8 ml/min ± 7.3 - (p>0,05)]. All preterm infants developed adequate renal function for their respective gestational age. In summary, our results indicate that, for clinical practice, the creatinine clearance, using newborn length, can be used to estimate glomerular filtration rate in preterm newborn infants.

Intraventricular hemorrhage in very low birth weight infants: associated risk factors and outcome in the neonatal period

Intraventricular hemorrhage (IVH) is a severe complication in very low birth weight (VLBW) newborns (NB). With the purpose of studying the incidence of IVH, the associated risk factors, and the outcomes for these neonates, we studied all the VLBW infants born in our neonatal unit. Birth weight, gestational age, presence of perinatal asphyxia, mechanical ventilation, length of hospitalization, apnea crisis, hydrocephalus, and periventricular leukomalacia were analyzed. The diagnosis of IVH was based on ultrasound scan studies (Papile's classification) performed until the tenth day of life and repeated weekly in the presence of abnormalities. Sixty-seven/101 neonates were studied. The mortality rate was 30.6% (31/101) and the incidence of IVH was 29.8% (20/67) : 70% grade I, 20% grade III and 10% grade IV. The incidence of IVH in NB <1,000 g was 53.8% (p = 0.035) and for gestational age <30 weeks was 47.3% (p = 0.04), both considered risk factors for IVH. The length of hospitalization (p = 0.00015) and mechanical ventilation (p = 0.038) were longer in IHV NB. The IVH NB had a relative risk of 2.3 of developing apnea (p = 0.02), 3.7 of hydrocephalus (p = 0.0007), and 7.7 of periventricular leukomalacia (p < 0.00001). The authors emphasize the importance of knowing the risk factors related to IVH so as to introduce prevention schemes to reduce IVH and to improve outcomes of affected newborns.

Hyperhomocyst(e)inemia in chronic stable renal transplant patients

PURPOSE: Hyperhomocyst(e)inaemia is an important risk factor for atherosclerosis, which is currently a major cause of death in renal transplant patients. The aim of this study was to assess the influence of immunosuppressive therapy on homocyst(e)inemia in renal transplant recipients. METHODS: Total serum homocysteine (by high performance liquid chromatography), creatinine, lipid profile, folic acid (by radioimmunoassay-RIA) and vitamin B12 (by RIA) concentrations were measured in 3 groups. Group I patients (n=20) were under treatment with cyclosporine, azathioprine, and prednisone; group II (n=9) were under treatment with azathioprine and prednisone; and group III (n=7) were composed of renal graft donors for groups I and II. Creatinine, estimated creatinine clearance, cyclosporine trough level, lipid profile, folic acid, and vitamin B12 concentrations and clinical characteristics of patients were assessed with the aim of ascertaining determinants of hyperhomocyst(e)inemia. RESULTS: Patient ages were 48.8 ± 15.1 yr (group I), 43.3 ± 11.3 yr (group II); and 46.5 ± 14.8 yr (group III). Mean serum homocyst(e)ine (tHcy) concentrations were 18.07 ± 8.29 mmol/l in renal transplant recipients; 16.55 ± 5.6 mmol/l and 21.44 ± 12.1 mmol/l respectively for group I (with cyclosporine) and group II (without cyclosporine) (NS). In renal donors, tHcy was significantly lower (9.07 ± 3.06 mmol/l; group I + group II vs. group III, p<0.008). There was an unadjusted correlation (p<0.10) between age (r=0.427; p<0.005) body weight (r=0.412; p<0.05), serum creatinine (r=0.427; p<0.05), estimated creatinine clearance (r=0.316; p<0.10), and tHcy in renal recipients (group I +II). Independent regressors (r²=0.46) identified in the multiple regression model were age (coefficient= 0.253; p=0.009) and serum creatinine (coefficient=8.07; p=0.045). We found no cases of hyperhomocyst(e)inemia in the control group. In contrast, 38% of renal recipients had hyperhomocyst(e)inemia: 7 cases (35%) on cyclosporine and 4 (45%) without cyclosporine, based on serum normal levels. CONCLUSIONS: Renal transplant recipients frequently have hyperhomocyst(e)inemia. Hyperhomocyst(e)inemia in renal transplant patients is independent of the scheme of immunosuppression they are taking. The older the patients are and the higher are their serum creatinine levels, the more susceptible they are to hyperhomocyst(e)inemia following renal transplantation.

Normal bone density in male pseudohermaphroditism due to 5alpha- reductase 2 deficiency

Bone is an androgen-dependent tissue, but it is not clear whether the androgen action in bone depends on testosterone or on dihydrotestosterone. Patients with 5alpha-reductase 2 deficiency present normal levels of testosterone and low levels of dihydrotestosterone, providing an in vivo human model for the analysis of the effect of testosterone on bone. OBJECTIVE: To analyze bone mineral density in 4 adult patients with male pseudohermaphroditism due to 5alpha-reductase 2 deficiency. RESULTS: Three patients presented normal bone mineral density of the lumbar column (L1-L4) and femur neck, and the other patient presented a slight osteopenia in the lumbar column. CONCLUSION: Patients with dihydrotestosterone deficiency present normal bone mineral density, suggesting that dihydrotestosterone is not the main androgen acting in bone.

Familial hyperamylasemia

A 7-year-old white boy was referred to us with a history of 3 attacks of hypogastric pain over the previous 2 years and persistently elevated serum amylase concentrations. At physical examination, he was well with no evidence of clinical abnormalities. His weight and height were normal. Laboratory diagnostic investigations were all normal except for the presence of Ascaris lumbricoides in the feces and persistently elevated serum amylase levels. Serum amylase determinations in the family members were normal in his father and maternal grandmother but elevated in his mother, sister, maternal aunt, and uncle, all of whom asymptomatic. Macroamylasemia was excluded in the child and in the mother. The finding of persistently elevated amylasemia in the child and in the other family members spanning 3 generations, and the exclusion of diseases that lead to hyperamilasemia are consistent with the diagnosis of familial hyperamylasemia. Until now, only 1 similar case has been reported. Familial hyperamylasemia must be considered in the differential diagnosis of hyperamylasemias in childhood.

Cystic fibrosis with normal sweat chloride concentration: case report

Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion ofcystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10kb C->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels.

Prevalence of antinuclear autoantibodies in the serum of normal blood dornors

OBJECTIVE:To examine the presence of serum antinuclear autoantibodies in a healthy population. METHODS: Serum of 500 normal blood donors between 18 and 60 years of age were tested for the presence of autoantibodies. Antinuclear antibodies were detected by indirect immunofluorescence technique using HEp-2 epithelial cells as the substrate. The presence of dnaN was detected by indirect immunofluorescence technique using Critidia lucillae as the substrate. Anti-SSA (RO), anti-SSB (LA), anti-Sm, and anti-RNP were determined by double radial immunodiffusion. RESULTS: In the evaluation of the presence of serum antibodies, antinuclear antibodies were detected in 22.6% of the sera. The presence of other antibodies was not significant. The majority of the titers were 1:40. CONCLUSION: The presence of autoantibodies is not necessarily pathologic and has to be related to the age group, gender, and clinical condition of the patient.

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.

Otimização da anisotropia fronto-calosa e ressonância magnética [1,5T] no idoso normal e com risco cérebro-vascular

RESUMO: Os mais recentes métodos de neuro imagem tal como a Ressonância Magnética (RM) permitiram obter imagens detalhadas do cérebro humano in vivo. Essas imagens revelam, muitas vezes, achados imprevistos face ao padrão normal, com elevada propensão para os indivíduos idosos e franca coexistência com fatores de risco vascular, como característica dum processo de envelhecimento normal. Embora na última década tenham surgido várias publicações sobre este assunto, ele continua ainda pouco explicado. Um pouco por todo o mundo têm emergido os programas de prevenção da doença e promoção da saúde desenvolvidos pela Saúde Pública suportadas sobretudo pelo avanço das tecnologias médicas que resultaram, entre outros impactos, num crescimento da população idosa. Estima-se, em 2030, uma composição demográfica com 20% de indivíduos acima dos 65 anos. Neste contexto, a doença microvascular cerebral é a causa mais frequente de comprometimento cognitivo vascular no idoso sendo as características senescentes na imagem por RM do tipo lesões isquémicas da Substância Branca (Leukoaraiosis) e enfartes lacunares (Status lacunar), atrofia cerebral, gliose e acumulação excessiva de ferro nos núcleos da base. Esta tese, considerando a linha de investigação de que deriva – Ciências da Vida - especialização em Medicina Clinica - Biotecnologia, reúne e reflete sobre três vertentes ligadas à RM e interdependentes em relação a uma problemática comum. A primeira trata da caracterização da Tecnologia por Ressonância Magnética existente em Portugal, a qual inclui uma avaliação exploratória da aplicação da técnica de Difusão Anisotrópica nos estudos cerebrais. As dimensões analíticas estudadas foram a Tecnológica, Sociodemográfica e Económica. Na recolha de dados recorreu-se a várias fontes de informação e a uma metodologia exploratória faseada, validada pela triangulação dos resultados. A sua análise obedeceu a critérios de estratificação e agrupamento segundo as mesmas dimensões analíticas. Otimização da anisotropia fronto-calosa e [RM 1,5T] no idoso normal e com risco cérebro-vascular A segunda descreve o estudo anátomo – radiológico que recaiu sobre parâmetros de quantificação assente na temática do cérebro do idoso em cadáver segundo uma metodologia experimental aplicada às métricas da difusão por RM. Na terceira, e última, é apresentado o estudo técnico - radiológico para avaliação e otimização da imagem ponderada em difusão em estudos clínicos associados ao cérebro do idoso “The Usual Brain Aging” ou Envelhecimento Cerebral Normal, com base metodológica assente nos critérios e indicadores estabelecidos pelo Estudo de Imagem de Roterdão (Rotterdam Scan Study - RSS). Como principais resultados obteve-se que não existem em Portugal estruturas para avaliação dos equipamentos pesados ou Agência de Avaliação das Tecnologias da Saúde para desenvolver o importante papel da produção de estudos comparativos entre os equipamentos disponíveis no mercado, a relação preço-qualidade e a sua afetação às necessidades clínico-epidemiológicas. Constatou-se que a implementação de equipamentos de RM está fortemente assente em critérios económicos carecendo de recomendações e diretivas para o uso racionalizado destas tecnologias. Quanto a dados quantitativos concluímos que a maioria dos equipamentos está instalada em instituições privadas (80,2%); a intensidade de campo magnético mais frequente é [1,5T] com 119 equipamentos; os equipamentos estão instalados maioritariamente nos distritos de Lisboa (55 unidades) e do Porto (39 unidades); o rácio médio de equipamentos por habitante em Portugal é de 1 para 65 195 habitantes; a amplitude de gradientes com maior expressão na amostra é 30-39mT/m; a maioria dos equipamentos foi instalada no intervalo temporal [2009-2012] com 59 equipamentos; apenas 6 instituições desenvolvem investigação clinica e a maioria das bobinas para estudos de crânio são do tipo Array. O estudo de otimização da técnica da difusão revelou, quanto à avaliação dos valoresb, que os mais baixos (b=500 s/mm2 e b=1000 s/mm2), apresentam maior IS e SNR sendo esta uma boa medida referente à qualidade de imagem, no entanto, os valores-b mais elevados (b=2000 s/mm2) apresentam maior CNR e CR, face aos anteriores, o Otimização da anisotropia fronto-calosa e [RM 1,5T] no idoso normal e com risco cérebro-vascular que apesar de proporcionar inferior detalhe anatómico e consequentemente inferior qualidade de imagem, num encéfalo normal, pode auxiliar na interpretação e apresentar vantagens na identificação de lesões microvasculares sempre que persistirem dúvidas em relação ao diagnóstico diferencial de doença microvascular do tipo status lacunar ou Hiperintensidades da Substância Branca. As alterações deste parâmetro são particularmente refletidas nas diferenças da avaliação da qualidade de imagem na região fronto-calos Concluímos da avaliação quantitativa da concentração média de ferro (26Fe) em todas as faixas etárias que os núcleos da base que apresentam maior concentração são, por ordem decrescente: Substância Nigra, Globus Pallidus, Putamen, Tálamo, Núcleo Rubro e Núcleo Caudado; que existe uma predominância na concentração de ferro (26Fe) no hemisfério esquerdo e que os indivíduos do género masculino apresentam mais ferro (26Fe) que os do género feminino nas faixas etárias [30-40[, [40-50[ e [50-60[. Como principal conclusão do estudo da concentração média de ferro em relação à idade destacamos que a concentração média de ferro (26Fe) é superior nos grupos etários superiores, logo aumenta com a idade, sobretudo na Substância Nigra e no Núcleo Lenticular. No estudo técnico-radiológico encontrámos evidências do aumento da difusibilidade da água na substância branca subcortical dos sujeitos idosos comparativamente aos mais jovens. Uma relação idêntica foi avaliada nos tálamos. O aumento relacionado com a idade parece ser predominantemente observado em doentes com mais de 65 anos de idade o que pode refletir alterações estruturais ligeiras associados ao envelhecimento normal. Os resultados indicam que a análise quantitativa das imagens ponderadas em difusão fornece informações, sobre a estrutura do cérebro, as quai s não estão disponíveis apenas por inspeção visual, tanto nas imagens ponderadas em difusão como em outras sequências de aplicação clínica de rotina. Para fazer face às desvantagens dos sistemas de quantificação das HSB os quais são dispendiosos, complexos, requererem tecnologia e formação específicas, recomendamos que a aplicação automatizada GUIAL, desenvolvida ao longo do nosso trabalho é de utilização elementar e prática para que seja introduzida nos sistemas de aquisição de imagem por RM com o fim de integrar o processamento de imagem nos indivíduos portadores de fatores de risco vascular. A avaliação do ADC, nesta amostra, permitiu concluir que a variação desta variável é explicada estatisticamente pela existência da condição clínica de status lacunar em ambos os hemisférios ou por outras palavras, o status lacunar influencia o valor de ADC. Embora uma pequena percentagem da variação do ADC seja explicada pelo género, o ADC nos homens foi superior ao das mulheres o que não nos surpreende, pois são também os homens onde a frequência de doença microvascular se revelou mais expressiva. Os valores do ADC, globalmente, entre os hemisférios cerebrais não mostraram alterações exceto na SB entre os idosos e não idosos. A SB da região frontal mostrou valores diminuídos na anisotropia e isotropia face às restantes áreas anatómicas. Os estudos indicam que na idade avançada existe uma maior predisposição para suscetibilidades de estrutura com status de desconexão. A classificação das HSB foi superior em indivíduos mais velhos e com status lacunar, e em menor quantidade (inferior rating de classificação) nos indivíduos idosos sem status lacunar. As alterações volumétricas foram mais frequentes no homem do que na mulher, presumivelmente devido à associação com a elevada classificação de status lacunar. Um aumento do índice de Evan correspondeu, neste estudo, ao aumento das HSB, à diminuição do volume cerebral total, à expansão ventrículo-sulcal frontal e ao aumento da medida do ângulo caloso. Estes resultados foram agravados pela classificação elevada de status lacunar nos indivíduos que apresentaram indícios de doença de pequenos vasos, com manifesto aumento dos espaços de Virchow-Robin,enfartes lacunares ou HSB. Esses resultados foram mais expressivos no género masculino do que no feminino revelando uma maior vulnerabilidade sobretudo na atrofia frontal nos homens. Por sua vez as dimensões do Corpo Caloso tornaram-se reduzidas devido à compressão dos ventrículos laterais e terceiro ventrículo. Estes indicadores tiveram expressão particularmente nos indivíduos com mais de 65 anos. ---------------------------------------------------------------------------------------------ABSTRACT: The latest neuroimaging methods, such as Magnetic Resonance Imaging (MRI), have enabled detailed images of in vivo human brain. These images reveal often unexpected findings related to the normal pattern, with high predisposition for the elderly people with forthright coexistence with vascular risk factors such as characteristics of a normal aging process. Although it has been, in the last decade, several publications on this subject, it is still little explained. All over the world have emerged disease prevention programs and health promotion developed by the Public Health sector, supported mainly by the advancement of medical technologies that have resulted, among other impacts, in a growing of the elderly population. It is estimated, in 2030, a demographic composition with 20% o people over 65 years. In this context, microvascular disease is the most common cause of cognitive vascular impairment in the elderly and senescent characteristics in the MRI trough ischemic lesions of the white matter (Leukoaraiosis) and lacunar infarcts (lacunar status), cerebral atrophy, gliosis and iron accumulation in the basal ganglia in excess.This thesis, considering the research line that stems - Life Sciences - specialization in Clinical Medicine, Biotechnology, gathers and reflects on three aspects linked to MR, interdependent and related to a common problem. The first deals with the Magnetic Resonance Technology characterization in Portugal, which includes an exploratory evaluation of the implementation of Anisotropic Diffusion technique in brain studies. The analytical dimensions studied were the Technologic, Socio-demographic and Economics. Collecting data was supported by different sources of information and was applied an exploratory methodology whose results were validated by triangulation. The research method was grouped and stratified criteria under the same analytical dimensions. The second describes the anatomical study - which was focused on radiological measurement parameters, based on the brain’s specimen under an experimental methodology applied to MRI diffusion metrics. Radiological evaluation and optimization of the weighted image diffusion in clinical studies were associated with the brain of the elderly "The Usual Brain Aging" with methodological basis based on established criteria and indicators by Rotterdam Scan Study (RSS). The main results obtained reveal the inexistence frameworks in Portugal for evaluation of equipments or Agency of Health Technology to produce studies comparing the equipment available on the market, the value for money and its allocation to clinical and epidemiological needs. It was found that the implementation of MRI equipment is strongly based on economic criteria lacking recommendations and guidelines for the rationalized use of these technologies. As the quantitative data we conclude that most of the scanners are located in private clinical institutions (80,2%); the most frequent magnetic field intensity is [1.5T] with 119 scanners; the scanners are mainly installed in Lisbon (55 units) and Porto (39 units) districts; the average ratio of equipment per capita in Portugal is 1 to 65 195 people; the gradient power with higher expression in the sample is 30-39mT / m;most of the scanners were installed in the years range [2009-2012 years] with 59 equipment; only 6 clinical placements develop clinical research and the most coils for brain studies are of Array type. The optimization study of diffusion technique revealed, as the assessment of the bvalues, the lower (b = 500 s / mm2 and b = 1000 s / mm 2), promotes an increase in the SI and SNR being this measure related to a higher image quality, however the highest b values (b = 2000 s / mm 2) have a higher CNR (Contrast to Noise-Ratio) and CR (Contrast Ratio), compared to the previous ones. This may provide less anatomical details and, thus, ower image quality, of a normal brain, however can help the interpretation and have advantages in identifying microvascular injuries when doubts persist regarding the differential diagnosis of microvascular disease of lacunar or WMH (White Matter Hyperintensities) status type. Changes on this parameter are Otimização da anisotropia fronto-calosa e [RM 1,5T] no idoso normal e com risco cérebro-vascular particularly reflected in the differences of image quality evaluation in the frontocallosum anatomical area. We conclude from the quantitative assessment of the average concentration of iron (26Fe), in all age groups to the basal ganglia, that the higher concentrations are, in descending order: Nigral Substantia, Globus pallidus, Putamen, Thalamus, Rubio nucleus and Caudate nucleus; that there is a predominance in the concentration of iron (26Fe) in the left hemisphere and that male gender show higher iron (26Fe) level tha females, in the age groups [30-40 [[40-50 [and [50- 60 [. Regarding a main conclusion of the mean concentration study of iron, in terms of age we point out that the average concentration of iron (26Fe) is higher among older groups and increases with age, especially in Nigral Substantia and Lenticular Nucleus. On the technical and radiological study we found evidence of an increased in water /diffusivity in the ubcortical white matter of the elderly compared with younger subjects. A similar relationship was assessed in the Thalamus. The increase agerelated seems to be predominantly observed in patients over 65 years which may reflect minor structural changes associated with normal aging. The results indicate that quantitative analysis of diffusion weighted imaging can provide information about the structure of the brain which is not reached only by visual inspection or standard sequences applied in clinical routine. To address the disadvantages the systems of quantification of WMH which the authors state that are costly, complex, require specific technology and training, we recommend that the automated application GUIAL, developed over our work is basic and practical to use and to be introduced in MR image systems acquisition in order to integrate image processing in patients with vascular risk factors. The evaluation of the ADC showed that its variation is statistically explained by the existence of the medical condition of lacunar status, in both hemispheres, or in other words, the lacunar status influences the ADC value. Although a small percentage of the ADC variation is explained by gender, the ADC in men was higher than women which Otimização da anisotropia fronto-calosa e [RM 1,5T] no idoso normal e com risco cérebro-vascular do not surprise us, since they are also men where the frequency of microvasculardisease has proved more significant. The values of ADC, overall, between the cerebral hemispheres showed no changes but were different in WM among the elderly and non-elderly subjects.The WM's forehead showed decreased values in anisotropy and isotropy face the other anatomical areas. The studies indicate that in old age there is a greater tendency to higher susceptibility to disconnection- status framework. The classification of WMH was higher in elderly people and lacunar status, and fewer (lower classification rating) in the elderly without lacunar status. volumetric changes were more frequent in men than in women, most probably because of its association with high lacunar status rating. An increase of Evan index corresponded, in this study, to an increase in WMH, to a decreased of total brain volume, to a ventricle sulcal frontal and callous angle expansion. These results were wound up by high ranking of lacunar status in subjects who had small vessel disease, clear increase in spaces of Virchow-Robin, lacunar infarctions or WMH. These results were more significant in males than in females revealing vulnerability particularly in the frontal atrophy in men. In turn the size of Corpus Callosum because reduced due to the compression of the lateral and third ventricles. These indicators had expression particularly in individuals over 65 years.

Comparison of single and multi-objective evolutionary algorithms for robust link-state routing

Traffic Engineering (TE) approaches are increasingly impor- tant in network management to allow an optimized configuration and resource allocation. In link-state routing, the task of setting appropriate weights to the links is both an important and a challenging optimization task. A number of different approaches has been put forward towards this aim, including the successful use of Evolutionary Algorithms (EAs). In this context, this work addresses the evaluation of three distinct EAs, a single and two multi-objective EAs, in two tasks related to weight setting optimization towards optimal intra-domain routing, knowing the network topology and aggregated traffic demands and seeking to mini- mize network congestion. In both tasks, the optimization considers sce- narios where there is a dynamic alteration in the state of the system, in the first considering changes in the traffic demand matrices and in the latter considering the possibility of link failures. The methods will, thus, need to simultaneously optimize for both conditions, the normal and the altered one, following a preventive TE approach towards robust configurations. Since this can be formulated as a bi-objective function, the use of multi-objective EAs, such as SPEA2 and NSGA-II, came nat- urally, being those compared to a single-objective EA. The results show a remarkable behavior of NSGA-II in all proposed tasks scaling well for harder instances, and thus presenting itself as the most promising option for TE in these scenarios.

Designing next generation car washing machines with rotary brushes

Tese de Doutoramento - Leaders for Technical Industries (LTI) - MIT Portugal