Predictors and outcomes of disseminated tuberculosis in an intermediate burden setting.

SETTING: University-affiliated hospital located in Porto, North Portugal, an area with a low to intermediate incidence of tuberculosis (TB). OBJECTIVE: To identify predictors and outcomes of disseminated TB (dTB). DESIGN: A cohort of patients diagnosed with TB between 2007 and 2013 was retrospectively analysed. Patients with dTB criteria were characterized and compared to single organ TB cases. Factors independently associated with dTB were determined by multivariate logistic regression analysis. RESULTS: A total of 744 patients were analysed, including 145 with dTB. Independent risk factors for dTB were pharmacological immunosuppression (OR 5.6, 95% CI 2.8-11.3), HIV infection (OR 5.1, 95% CI 3.1-8.3), chronic liver failure or cirrhosis (OR 2.3, 95% CI 1.4-4.1) and duration of symptoms (OR 2.3, 95% CI 1.4-3.8). Compared to single organ TB, the clinical presentation of dTB patients differed by the absence of haemoptysis (OR 3.2, 95% CI 1.3-8.4) and of dyspnoea (OR 1.9, 95% CI 1.2-3.1), presence of weight loss (OR 1.8, 95% CI 1.1-2.9), night sweats (OR 1.7, 95% CI 1.1-2.7) and bilateral lung involvement (OR 4.4, 95% CI 2.8-7.1). Mortality and time until culture conversion were higher for dTB patients, although not reaching statistical significance. CONCLUSION: Immunosuppressive conditions and chronic liver failure or cirrhosis were associated with increased risk of dTB. The haematogenous spread may be dependent on longer symptomatic disease and usually progresses with bilateral lung involvement.

Water management applied to the processing of Atlantic Salmon (Salmo salar) and Dolphinfish (Coryphaena hippurus) in a fish cold storage warehouse in Rio de Janeiro, Brazil / Gerenciamento hídrico aplicado ao beneficiamento de Salmão-do-Atlântico (Salmo salar) e Dourado-do-mar (Coryphaena hippurus) em entreposto de pescado no Rio de Janeiro, Brasil

The high consumption of water and uncontrolled wastewater generation commonly seen in fish processing plants are a matter of concern. Sustainable actions must be taken to addres this issue. The present study aimed to quantify the water used in the processing of Atlantic Salmon (Salmo salar) and Dolphinfish (Coryphaena hippurus) in a fish warehouse in Rio de Janeiro, Brazil, through water balance and mass balance at each development stage. According to the data obtained, the warehouse showed higher total water use, both in general (7,173.28±265.77m3/month), with most water use intended for processing support activities, approximately 45.00% (3,186.82±407.57m3/month); specifically, in the processing of the selected raw materials, with greater consumption of water for obtaining one kg of Dolphinfish fillets and slices, around 4.80 x 103m3/kg in both. This suggests the use of sustainable methodologies that result in decreased water consumption and in reuse of solid waste, since the three processing stages studied generated a high amount of solid waste, with emphasis to filleting in both species, with 55.00% of residual production each. The present study will also serve as the basis to other studies on the same issue in the fishing area.(AU)

Comumente relacionado à indústria de pescado, o alto consumo de água e geração de efluentes de forma não controlada é preocupante. Ações sustentáveis são necessárias diante do problema. Objetivou-se, com o presente estudo, quantificar a água utilizada no processamento de salmão-do-atlântico (Salmo salar) e dourado-do-mar (Coryphaena hippurus), em um entreposto de pescado localizado no Rio de Janeiro, Brasil, por meio dos balanços hídrico e de massa de cada etapa de processamento. Com base nos dados obtidos, observou-se que o entreposto apresentou um elevado uso de água total, tanto de forma geral, 7.173,28±265,77m3/mês, com o maior gasto destinado às atividades de apoio ao processamento, aproximadamente 45,00%, quanto de forma específica, no processamento das matéria-prima selecionada, com o maior consumo de água para obtenção de um kg de filé e um kg de posta de dourado, cerca de 4,80 x 103m3/kg em ambos os processos. Sugere-se a aplicação de metodologias sustentáveis de redução no uso hídrico, além do reaproveitamento de resíduos sólidos, uma vez que os três beneficiamentos estudados geram elevada quantidade de resíduos sólidos, com destaque para a filetagem em ambas as espécies, com produção residual de 55,00% cada. O presente estudo também serve como base para outros de mesma temática na área de pescado.(AU)

Beyond central adiposity: liver fat and visceral fat area are associated with metabolic syndrome in morbidly obese patients.

BACKGROUND: Despite its widespread clinical use, both body mass index (BMI) and waist circumference have been reported as inaccurate methods to measure abdominal obesity. The main objective of this study was to determine the relation between visceral fat area and fatty liver infiltration with the expression of metabolic syndrome (MS) in morbidly obese patients. METHODS: We recruited a random selection of 100 morbidly obese patients on pre-operative evaluation for bariatric surgery. A pre-operative CT slice at L4-L5 level, was performed to measure visceral fat and at T12 level to measure hepatic attenuation. RESULTS: Patients with MS had lower hepatic attenuation values (median 49.9 vs 55.5HU; p = .018) and had more VAT (242 vs 172 cm(2);p = .001). Conventional measures (BMI: p = .729 and waist circumference: p = .356), were not useful in discriminating morbidly obese patients with MS. By multivariable logistic regression, fatty liver infiltration (OR = 5.3; p = .03) and age (OR = 1.08; p = .04) were the only factors independently related to the presence of MS. MS prevalence was 100%, 71% and 55%, respectively for patients with both fatty liver and visceral adiposity; one; or none of this findings (AUC - .715; p = .016). CONCLUSION: CT scan seems to measure 2 important markers of MS: visceral adiposity and hepatic fatty infiltration. In morbidly obese patients, both visceral adiposity and hepatic fatty infiltration increase the risk for the presence of MS.

Role of physical exercise on hepatic insulin, glucocorticoid and inflammatory signaling pathways in an animal model of non-alcoholic steatohepatitis.

AIMS: Pro-inflammatory mediators, glucocorticoids and transforming growth factor (TGF)-ß are implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH)-related insulin resistance. As physical activity is beneficial against NASH, we analyzed the voluntary physical activity (VPA) and endurance training (ET) (preventive and therapeutic strategies) effects on hepatic insulin, pro-inflammatory and glucocorticoid signaling regulators/mediators in high-fat (Lieber-DeCarli) diet (HFD)-induced NASH. MAIN METHODS: Adult male Sprague-Dawley rats were divided in standard diet (SD) or HFD, with sedentary, VPA and ET animals in both diet regimens. Plasma glucose and insulin concentrations were analyzed; plasma insulin sensitivity index (ISI) was calculated. Hepatic insulin, pro-inflammatory and glucocorticoid signaling regulators/mediators were evaluated by Western blot or reverse transcriptase-PCR. KEY FINDINGS: ET improved ISI in both diet regimens. HFD-feeding increased interleukin-1ß and induced a similar pattern on interleukin-6 and TGF-ß, which were globally reduced by physical exercise. ET decreased HFD leukemia inhibitory factor level, SD+VPA animals presenting higher values than HFD+VPA animals. HFD increased the ratio of IRS-1(Ser307)/total IRS-1, which was completely mitigated by physical exercise. Physical exercise reduced total ERK and JNK (total and activated) expression in HFD. In SD vs. HFD, VPA presented higher activated JNK and ET presented higher total JNK. Generally, in HFD, the ratio (activated/total) of AKT, and each separately, decreased with exercise and also for activated AKT in SD. Overall, in both diets, exercise reduced 11ß-hydroxysteroid dehydrogenase type 1. ET increased glucocorticoid receptor and reduced PTP1B in HFD. SIGNIFICANCE: Physical exercise mitigates the expression of pro-inflammatory mediators and positively modulates insulin and glucocorticoid signaling in NASH.

Effects of extracts of selected medicinal plants upon hepatic oxidative stress.

Aqueous extracts of a few medicinal plants traditionally used in Portugal have been assayed for their effects upon hepatic oxidative stress in mice. Previous in vitro studies had allowed characterization of agrimony, sage, savory, and raspberry in terms of overall antioxidant capacity and phenolic content. In the present study, the antioxidant effect and safety of these four plants were evaluated in vivo. For this purpose, mice ingested extracts in aqueous form (or water, used as the control) for 4 weeks; damage to lipids, proteins, and DNA was evaluated by oxidative cell biomarkers by the end of that period. Levels of hepatic glutathione and activities of enzymes involved in metabolism thereof were also determined. Finally, catalase and superoxide dismutase (SOD) activities were quantified, as these enzymes play a crucial role in antioxidant defense. When compared with the control, both raspberry and savory produced significant lipid protection; however, protein damage was significantly lower only in raspberry-treated animals. On the other hand, DNA damage was prevented only by savory. All plants led to a decrease in catalase activity, whereas all but sage also produced a decrease in SOD activity. With regard to glutathione levels and activities of enzymes involved in its metabolism, the aforementioned extracts exhibited different effects. In general, raspberry appeared to be the most promising extract, followed by savory, sage, and agrimony, sorted by decreasing performance in protection; the latter was even slightly toxic. Hence, the plants tested possess compounds with interesting biological activities that may support eventual inclusion in food or feed as functional additives.

Characterization of rat heart alkaline phosphatase isoenzymes and modulation of activity.

Alkaline phosphatase (ALP) is important in calcification and its expression seems to be associated with the inflammatory process. We investigated the in vitro acute effects of compounds used for the prevention or treatment of cardiovascular diseases on total ALP activity from male Wistar rat heart homogenate. ALP activity was determined by quantifying, at 410 nm, the p-nitrophenol released from p-nitrophenylphosphate (substrate in Tris buffer, pH 10.4). Using specific inhibitors of ALP activity and the reverse transcription-polymerase chain reaction, we showed that the rat heart had high ALP activity (31.73 +/- 3.43 nmol p-nitrophenol.mg protein-1.min-1): mainly tissue-nonspecific ALP but also tissue-specific intestinal ALP type II. Both ALP isoenzymes presented myocardial localization (striated pattern) by immunofluorescence. ALP was inhibited a) strongly by 0.5 mM levamisole, 2 mM theophylline and 2 mM aspirin (91, 77 and 84%, respectively) and b) less strongly by 2 mM L-phenylalanine, 100 mL polyphenol-rich beverages and 0.5 mM progesterone (24, 21 to 29 and 11%, respectively). beta-estradiol and caffeine (0.5 and 2 mM) had no effect; 0.5 mM simvastatin and 2 mM atenolol activated ALP (32 and 36%, respectively). Propranolol (2 mM) tended to activate ALP activity and corticosterone activated (18%) and inhibited (13%) (0.5 and 2 mM, respectively). We report, for the first time, that the rat heart expresses intestinal ALP type II and has high total ALP activity. ALP activity was inhibited by compounds used in the prevention of cardiovascular pathology. ALP manipulation in vivo may constitute an additional target for intervention in cardiovascular diseases.

Characterization of rat heart alkaline phosphatase isoenzymes and modulation of activity

Alkaline phosphatase (ALP) is important in calcification and its expression seems to be associated with the inflammatory process. We investigated the in vitro acute effects of compounds used for the prevention or treatment of cardiovascular diseases on total ALP activity from male Wistar rat heart homogenate. ALP activity was determined by quantifying, at 410 nm, the p-nitrophenol released from p-nitrophenylphosphate (substrate in Tris buffer, pH 10.4). Using specific inhibitors of ALP activity and the reverse transcription-polymerase chain reaction, we showed that the rat heart had high ALP activity (31.73 ± 3.43 nmol p-nitrophenol·mg protein-1·min-1): mainly tissue-nonspecific ALP but also tissue-specific intestinal ALP type II. Both ALP isoenzymes presented myocardial localization (striated pattern) by immunofluorescence. ALP was inhibited a) strongly by 0.5 mM levamisole, 2 mM theophylline and 2 mM aspirin (91, 77 and 84 percent, respectively) and b) less strongly by 2 mM L-phenylalanine, 100 mL polyphenol-rich beverages and 0.5 mM progesterone (24, 21 to 29 and 11 percent, respectively). â-estradiol and caffeine (0.5 and 2 mM) had no effect; 0.5 mM simvastatin and 2 mM atenolol activated ALP (32 and 36 percent, respectively). Propranolol (2 mM) tended to activate ALP activity and corticosterone activated (18 percent) and inhibited (13 percent) (0.5 and 2 mM, respectively). We report, for the first time, that the rat heart expresses intestinal ALP type II and has high total ALP activity. ALP activity was inhibited by compounds used in the prevention of cardiovascular pathology. ALP manipulation in vivo may constitute an additional target for intervention in cardiovascular diseases.

Central obesity as a major determinant of increased high-sensitivity C-reactive protein in metabolic syndrome.

INTRODUCTION: Traditional cardiovascular risk factors such as central obesity, high blood pressure and insulin resistance, all constituents of metabolic syndrome, have been associated with increased levels of C-reactive protein (CRP). Therefore, this marker of low-grade inflammation may play a major role in the pathogenesis of cardiovascular diseases. In this study, data from a representative sample of urban adults was used to evaluate the association between CRP and metabolic syndrome, accounting for the type and number of its constituents. METHODS: Using random digit dialing, 1022 participants, aged 18-92 y, were selected. All participants completed a structured questionnaire comprising of information on social, demographic, behavioral and clinical aspects. Anthropometrics and blood pressure were recorded and a fasting blood sample collected. Metabolic syndrome was defined, according to the Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, as the presence of three or more of the following characteristics: waist circumference greater than 102 cm in men and 88 cm in women; triglyceride levels > or = 150 mg/dl; high-density lipoprotein cholesterol levels < 40 mg/dl in men and < 50 mg/dl in women; blood pressure > or = 130/85 mm Hg; and serum glucose > or = 110 mg/dl. High-sensitivity CRP was assessed by immunonephelometric assay. After excluding 65 participants with CRP > or = 10 mg/l, 957 subjects (599 women and 358 men) remained for analysis. Geometric means were compared after adjustment for age, sex, alcohol consumption and smoking. RESULTS: Higher mean levels of CRP (2.34 vs 1.36, P < 0.001) were observed when metabolic syndrome was present. Also, mean CRP levels were significantly higher in the presence of central obesity (2.45 vs 1.24, P < 0.001), high blood pressure (1.76 vs 1.12, P < 0.001), hypertriglyceridemia (2.17 vs 1.32, P < 0.001) and high fasting glucose (1.96 vs 1.46, P = 0.032). We found a significant increasing trend (P < 0.001) in mean levels of CRP as the number of features of metabolic syndrome increased. The major contributing features for high CRP levels were central obesity and high blood pressure. CONCLUSIONS: Present data show that increasing severity of metabolic syndrome is associated with increasing CRP. Additionally, we found that central obesity and high blood pressure are the most important determinants of the low-grade chronic inflammation present in metabolic syndrome.

Renal dopaminergic system activity in the rat remnant kidney.

BACKGROUND: Renal dopamine exerts natriuretic and diuretic effects by activating D1-like receptors. Uninephrectomy results in increased renal dopaminergic activity and dopamine-sensitive enhanced natriuresis. METHODS: The present study evaluated renal adaptations in sodium handling and the role of dopamine in rats submitted to (3/4) nephrectomy: right nephrectomy and excision of both poles of the left kidney ((3/4)nx rats). RESULTS: Two weeks after surgery the absolute urinary levels of dopamine were markedly reduced in (3/4)nx rats whereas the urinary dopamine excretion per % of residual nephrons was significantly increased in the remnant kidney of (3/4)nx rats. The V(max) values for renal aromatic L-amino acid decarboxylase, the enzyme responsible for the synthesis of renal dopamine, were decreased in (3/4)nx rats. Renal catechol-O-methyltransferase activity, the enzyme responsible for the methylation of dopamine, was increased in (3/4)nx rats whereas the renal activities of monoamine oxidases A and B did not differ between (3/4)nx and Sham animals. Volume expansion (5% body weight) resulted in similar natriuretic responses in (3/4)nx and Sham rats. During D1 antagonist administration (Sch-23390, 30 microg x h(-1) x kg(-1)) the natriuretic response to volume expansion was reduced in (3/4)nx rats more pronouncedly than in Sham animals. CONCLUSION: The decrease in absolute renal dopamine output in (3/4)nx rats is related with reduced renal synthesis and enhanced O-methylation of the amine. However, this is accompanied in (3/4)nx rats by increased renal dopamine excretion per residual nephrons and dopamine-sensitive enhanced natriuresis.

Concerted action of dopamine on renal and intestinal Na(+)-K(+)-ATPase in the rat remnant kidney.

The present study evaluated renal and intestinal adaptations in sodium handling in uninephrectomized (Unx) rats and the role of dopamine. Two weeks after uninephrectomy, the remnant kidney in Unx rats weighed 33 +/- 2% more than the corresponding kidney in sham-operated (Sham) animals. This was accompanied by increases in urinary levels of dopamine and major metabolites [3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid] and increases in maximal velocity values (169 vs. 115 nmol. mg protein(-1). 15 min(-1)) for renal aromatic L-amino acid decarboxylase, the enzyme responsible for the synthesis of renal dopamine. High salt (HS) intake increased (P < 0.05) the urinary excretion of dopamine and DOPAC in Unx and Sham rats. However, the urinary levels of L-3,4-dihydroxyphenylalanine, dopamine, and DOPAC in Sham rats during HS intake were lower than in Unx rats. Blockade of dopamine D(1) receptors (Sch-23390, 2 x 30 microg/kg) reduced the urinary excretion of sodium in Unx (31% decrease) more pronouncedly than in Sham (19% decrease) rats. However, inhibition of renal Na(+)-K(+)-ATPase activity by dopamine was of similar magnitude in Unx and Sham rats. In parallel, it was observed that uninephrectomy resulted in a significant reduction in jejunal sodium absorption and Na(+)-K(+)-ATPase activity in jejunal epithelial cells. In jejunal epithelial cells from Sham rats, dopamine (1 microM) failed to inhibit Na(+)-K(+)-ATPase activity, whereas in Unx rats it produced a significant reduction. It is concluded that uninephrectomy results in increased renal dopaminergic activity and dopamine-sensitive enhanced natriuresis. Furthermore, it is suggested that decreased jejunal absorption of sodium may take place in response to partial renal ablation, as an example of renal-intestinal cross talk.

Biliary ascariasis after Roux-en-Y hepaticojejunostomy.

The authors report on a 6-year-old girl with biliary ascariasis after surgical treatment of a choledochal cyst and biliary-digestive tract reconstruction by Roux-en-Y hepaticojejunostomy. A precise diagnosis can be obtained by ultrasonography. Surgical treatment is required when clinical and endoscopic treatments fail. In countries in which this disease is endemic, biliary ascariasis should be considered in the differential diagnosis of cholangitis after surgery for hepaticojejunostomy.

Aging, high salt intake, and renal dopaminergic activity in Fischer 344 rats.

The present study examined renal dopaminergic activity and its response to high salt (HS) intake in adult (6-month-old) and old (24-month-old) Fischer 344 rats. Daily urinary excretion of L-3, 4-dihydroxyphenylalanine (L-DOPA), dopamine, and its metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid was similar in adult and old rats; by contrast, daily urinary excretion of norepinephrine in old rats was almost twice that in adult animals. HS intake (1% NaCl) over a period of 24 hours resulted in a 2-fold increase in the urinary excretion of dopamine, DOPAC, and norepinephrine in adult animals but not in old animals. Norepinephrine and L-DOPA plasma levels did not change during HS intake and were similar in both groups of rats. The natriuretic response to an HS intake in old rats (from 4.7+/-0.4 to 10.7+/-2.0 nmol. kg(-1). d(-1); Delta=6.0+/-0.9 nmol. kg(-1). d(-1)) was less than in adult rats (from 5.2+/-0.4 to 13.5+/-2.5 nmol. kg(-1). d(-1); Delta=8.3+/-0.8 nmol. kg(-1). d(-1)). A diuretic response to HS intake was observed in adult rats (from 20.9+/-2.3 to 37.6+/-2.8 mL. kg(-1). d(-1)) but not in old rats (from 37.7+/-5.7 to 42.3+/-6. 0 mL. kg(-1). d(-1)). Dopamine levels and dopamine/L-DOPA ratios in the renal cortex of old rats were greater than in adult rats. HS intake increased both dopamine levels and dopamine/L-DOPA ratios in the renal cortex of adult rats but not in old rats. Aromatic L-amino acid decarboxylase activity was higher in old rats than in adult rats; HS intake increased L-amino acid decarboxylase activity (nmol. mg protein(-1). l5 min(-1)) in adult rats (from 67+/-1 to 93+/-1) but not in old rats (from 86+/-2 to 87+/-2). Dopamine inhibited Na(+),K(+)-ATPase activity in proximal tubules obtained from adult rats, but it failed to exert such an inhibitory effect in old rats. It is concluded that renal dopaminergic tonus in old rats is higher than in adult rats but fails to respond to HS intake as observed in adult rats. This may be due in part to the inability of dopamine to inhibit Na(+),K(+)-ATPase activity in old rats.

Use of a plastic hemoderivative bag in the treatment of gastroschisis.

The authors report their experience with the use of a polyvinyl chloride (PVC) bag for blood-derivative transfer as a prosthesis for the creation of a silo for surgical treatment of gastroschisis (GS) in seven newborn infants. The bag is sterile, impermeable to micro-organisms, transparent, flexible, resistant, internally smooth, does not adhere to the bowel loops, readily available, and inexpensive, properties that make it an excellent alternative as a prosthesis for staged surgical treatment of congenital anomalies of the abdominal wall such as GS and omphalocele. The importance of a multidisciplinary team for the care of newborns with GS is also emphasized for a good postoperative outcome.

Caco-2 cells in culture synthesize and degrade dopamine and 5-hydroxytryptamine: a comparison with rat jejunal epithelial cells.

To explore the usefulness of Caco-2 cells in the study of intestinal dopaminergic and 5-hydroxytryptaminergic physiology, we have undertaken the study of aromatic L-amino acid decarboxylase (AADC), catechol-O-methyltransferase (COMT) and type A and B monoamine oxidase (MAO-A and MAO-B) activities in these cells using specific substrates. The activity of these enzymes was also evaluated in isolated rat jejunal epithelial cells. The results showed that Vmax values (in nmol mg protein(-1) h(-1)) for AADC, using L-DOPA as the substrate, in rat jejunal epithelial cells (127.3+/-11.4) were found to be 6-fold higher than in Caco-2 cells (22.5+/-2.6). However, Km values in Caco-2 cells (1.24+/-0.37 mM) were similar to those observed in rat jejunal epithelial cells (1.30+/-0.29 mM). Similar results were obtained when AADC activity was evaluated using L-5HTP as substrate; in rat jejunal epithelial cells Vmax values (in nmol mg prot(-1) h(-1)) were found to be 5-fold that in Caco-2 cells (16.3+/-1.0 and 3.0+/-0.2, respectively), and Km values in Caco-2 cells (0.23+/-0.08 mM) were again similar to those observed in rat intestinal epithelial cells (0.09+/-0.03 mM). Caco-2 cells were not able to O-methylate dopamine, in contrast to rat jejunal epithelial cells (Vmax = 8.6+/-0.4 nmol mg protein(-1)(h-1); Km = 516+/-57 microM). Vmax values (in nmol mg protein(-1)(h-1)) for type A and B MAO in Caco-2 cells (19.0+/-0.6 and 5.4+/-0.6, respectively) were found to be significantly lower (P<0.05) than those in rat jejunal epithelial cells (46.9+/-3.1 and 9.6+/-1.2, respectively); however, no significant differences in the Km values were observed between Caco-2 and rat jejunal epithelial cells for both type A and B MAO. In conclusion, Caco-2 cells in culture are endowed with the synthetic and metabolic machinery needed to form and degrade DA and 5-HT, though, no COMT activity could be detected in these cells.