Universal lipid screening in adolescents to identify familial hypercholesterolemia in a large healthcare system.

BACKGROUND: Familial hypercholesterolemia (FH) is an inherited condition that likely affects 1 in 300 people often requiring pharmacologic intervention in childhood. OBJECTIVES: We hypothesized that current strategies for pediatric lipid screening fail to detect and treat most FH, but data analysis may suggest specific methods to improve outcomes. METHODS: We retrospectively searched 392,129 patient records of 11-17-year-olds in Kaiser Permanente Southern California for data related to recommended universal pediatric lipid screening. We categorized subjects as Probable or Possible FH and evaluated FH pharmacotherapy status. RESULTS: 37% of the population received lipid screening with 0.13% (1 in 769) having Probable or Possible FH. Results at each step of the process showed progressive decreases in detection and treatment. We characterized 1 in 3448 subjects as Probable FH which is only 8.7% of cases expected from the prevalence of FH in the population. 45% of Probable FH cases received ongoing pharmacotherapy which is 1 in 7688 of the cohort (3.9% of expected cases). One major correctable reason for this drop-off was using obesity to target screening and treatment decisions rather than following the recommended universal screening. We found a strong association of obesity with screening (risk ratio (RR) 2.74 [confidence interval (CI) 2.71-2.76]), but not with FH (RR 0.72, CI 0.47-1.10). CONCLUSION: This current universal lipid screening strategy, likely typical of US practice, fails to detect and treat the supermajority of FH cases, increasing risk for adult coronary artery disease. To address the specific deficiencies we observed, we suggest improvements to detect and treat FH.

Concentration of biologically active compounds extracted from Ilex paraguariensis St. Hil. by nanofiltration.

The aim of this study was to characterise the bioactive compounds in mate (Ilex paraguariensis St. Hil) extract and in concentrated mate extract obtained by nanofiltration (NF). Also, the impact of NF on the antioxidant activity of both mate extracts was evaluated in vitro and using eukaryotic cells of Saccharomyces cerevisiae (yeast assay). The results showed a significant increase in the contents of total phenolics (338%), chlorogenic acid (483%), theobromine (323%), caffeine (251%), chlorophyll (321%), condensed tannins (278%) and saponins (211%) in the concentrated mate extract. The concentrated mate extract showed higher in vitro antioxidant activity than the mate extract. According to the results obtained, it can be stated that the use of nanofiltration membrane is a valid approach for the concentration of biologically active compounds in aqueous extract of mate.

Sustained antioxidant activity of quercetin-loaded lipid-core nanocapsules.

Lipid-core nanocapsules (LNC) are vesicular nanocarriers prepared by solvent displacement. LNC have been previously prepared using medium-chain triglyceride and sorbitan monostearate as liquid and solid lipophilic components dispersed in the core, surrounded by poly(epsilon-caprolactone) (PCL). Our objective was to investigate the antioxidant activity of LNC containing quercetin (QUE), a radical scavenger, prepared with octyl methoxycinnamate and sorbitan monostearate as lipophilic core components and PCL as the polymer wall. We selected Saccharomyces cerevisae cells as the proposed biological model. QUE-LNC presented z-average diameter of 212 nm, pH of 5.51 and zeta potential of -11 mV. Multiple light scattering analysis (TurbiscanLab) showed a photon path length of 172 microm. Furthermore, a validated turbidimetric study determined that the density of particles in suspension was 1.66 x 10(13). DSC analysis showed that the melting temperature of PCL shifted to lower values when in contact with octyl methoxycinnamate indicating a molecular interaction. After 1 h (7 h), the QUE-LNC formulation and QUE solution incubated with H2O2 showed cell survival of 84.4% (87.7%) and 65.6% (7.3%), respectively. After 35 h of incubation, cell survival was 31.7% and 0.9%, respectively. The QUE-LNC showed sustained antioxidant activity and potential as a nanostructured material to formulate final products.

Pharmacological preconditioning using intraportal infusion of L-arginine protects against hepatic ischemia reperfusion injury.

OBJECTIVE: The present study examined the effects of intraportal infusion of L-arginine on ischemia/reperfusion injury (I/RI) in pig livers, by observing changes in the liver function, liver cell morphology, and changes in the mitochondrial ultrastructure. BACKGROUND: The involvement of the nitric oxide (NO) pathway in the reperfusion-ischemic phenomenon is complex and not fully understood. Likewise, little is known about the possible benefit of intraportal infusion of L-arginine (substrate for the NO synthesis) on liver I/RI. METHODS: A pig model consisting of 90 min of hepatic ischemia and 180 min of reperfusion was employed. Eighteen female hybrid pigs were randomly divided into three groups: sham-operated, non-preconditioned, and pharmacologically preconditioned group (intraportal infusion of L-arginine 400 mg/kg) 10 min before being subjected to ischemia and reperfusion. Serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), thiobarbituric acid reactive substances (TBARS), and the bile flow were measured. Liver biopsies were taken 180 min after reperfusion for histology, caspase-3 immunohistochemistry, and ultrastructural examination of mitochondria. RESULTS: In the pharmacologically preconditioned group, we observed increased bile flow (P < 0.01) and improved serum AST levels (P < 0.01) relative to the non-preconditioned group. Serum concentrations of TBARS did not differ between the groups. Sinusoidal congestion (P = 0.02) was more evident in the non-preconditioned group than in the sham operated group. Infiltrating PMNs (P = 0.01) were more evident in the non-preconditioned group than in the sham and pharmacologically preconditioned group. The pharmacologically preconditioned group showed an approximately 2.5-fold decrease in caspase-3 activity relative to the non-preconditioned group (P < 0.01). Notably, damage to the mitochondrial ultrastructure in the pharmacologically preconditioned group was reduced relative to the other groups (P < 0.01). CONCLUSIONS: Pharmacological preconditioning with intraportal L-arginine provided protection against hepatic I/RI in early phases of the reperfusion period. The mechanisms underlying the protective effect may include preservation of the mitochondrial structure and inhibition of caspase-3 activity.

Ischemic preconditioning protects the pig liver by preserving the mitochondrial structure and downregulating caspase-3 activity.

BACKGROUND DATA: The beneficial effects of ischemic preconditioning (IPC) on hepatic ischemia-reperfusion injury (I/RI) have been described. However, the way in which IPC causes the changes in mitochondrial ultrastructure seen in hepatic I/RI is not well understood. OBJECTIVE: The objective of the present study was to determine whether IPC protects the liver from changes in mitochondrial structure and caspase 3 activity in the early phase of post-ischemic injury. METHODS: A pig model consisting of 90 min of hepatic ischemia and 180 min of reperfusion was employed. Eighteen female pigs were randomly divided into three groups: sham-operated, non-preconditioned, and ischemic preconditioned (10 min ischemia followed by 10 min reperfusion). Serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and thiobarbituric acid reactive substances (TBARS), as well as bile flow, were measured. Liver biopsies were taken after reperfusion for histological, immunohistochemical (anti-caspase 3), and ultrastructural examinations. RESULTS: The IPC procedure increased bile flow (p < 0.01), reduced serum AST level (p < 0.01), and reduced serum concentration of TBARS at 180 min of reperfusion (p = 0.05). Ischemic-preconditioned liver cells had less caspase 3 activity than the non-preconditioning group (p < 0.01), and changes in mitochondrial ultrastructure were reduced (p < 0.01). CONCLUSION: IPC exerts a powerful protective effect against hepatic I/RI in the early phase of reperfusion, which may be mediated by preservation of mitochondrial structure and inhibition of caspase-3 activity.

Multidrug-resistant urinary tract isolates of escherichia coli from Ribeirão Preto, São Paulo, Brazil

Multiple resistances to antimicrobial drugs arising in Escherichia coli isolates may complicate therapeutic management of urinary tract infection (UTI) by this organism. In order to assess the multidrug resistance (MDR) among urinary E. coli isolates, we have tested 11 antimicrobial drugs against 67 isolates from outpatients attended in a tertiary-care teaching hospital and of 78 isolates from a municipal health unit, respectively in Ribeirão Preto, State of São Paulo, Brazil. Seventy-six percent and 22 percent of the isolates from the tertiary-care hospital and the municipal unit, respectively, were resistant to three or more different classes of agents, and were considered to present MDR. Among the isolates from the hospital patients, 73.0 percent, 65.0 percent, 58.0 percent, 58.0 percent and 31.0 percent were resistant to tetracycline, ampicillin, cephalothin, trimethoprim-sulfamethoxazole (TMP/SMX) and norfloxacin, respectively; resistance from the municipal unit patients were 31.0 percent, 37.0 percent, 8.0 percent, 29.0 percent and 12.0 percent respectively, to the same drugs. The predominant phenotype among the MDR isolates presented is ampicillin, TMP/SMX and tetracycline resistance. The high prevalence of drug resistance among UTI patients calls for continuous surveillance to assure effective control of this infection.

Multidrug-resistant urinary tract isolates of escherichia coli from Ribeirão Preto, São Paulo, Brazil.

Multiple resistances to antimicrobial drugs arising in Escherichia coli isolates may complicate therapeutic management of urinary tract infection (UTI) by this organism. In order to assess the multidrug resistance (MDR) among urinary E. coli isolates, we have tested 11 antimicrobial drugs against 67 isolates from outpatients attended in a tertiary-care teaching hospital and of 78 isolates from a municipal health unit, respectively in Ribeirão Preto, State of São Paulo, Brazil. Seventy-six percent and 22% of the isolates from the tertiary-care hospital and the municipal unit, respectively, were resistant to three or more different classes of agents, and were considered to present MDR. Among the isolates from the hospital patients, 73.0%, 65.0%, 58.0%, 58.0% and 31.0% were resistant to tetracycline, ampicillin, cephalothin, trimethoprim-sulfamethoxazole (TMP/SMX) and norfloxacin, respectively; resistance from the municipal unit patients were 31.0%, 37.0%, 8.0%, 29.0% and 12.0% respectively, to the same drugs. The predominant phenotype among the MDR isolates presented is ampicillin, TMP/SMX and tetracycline resistance. The high prevalence of drug resistance among UTI patients calls for continuous surveillance to assure effective control of this infection.

A influência das espécies reativas de oxigênio na infertilidade masculina / The influence of reactive oxigen species on male infertility

A infertilidade masculina é uma entidade multifatorial que abrange uma grande variedade de alterações, podendo ser congênita ou adquirida. A infertilidade idiopática pode ser causada pela excessiva produção de espécies reativas de oxigênio no plasma seminal, levando ao estresse oxidativo. Estudos têm demonstrado que os espermatozóides humanos possuem a capacidade de gerar espécies reativas de oxigênio quando incubados em ambiente aeróbio, sendo que as maiores fontes de espécies reativas de oxigênio no sêmen são leucócitos, espermatozóides com citoplasma residual e espermatozóides imaturos. A membrana plasmática dos espermatozóides é rica em ácidos graxos poliinsaturados sendo vulnerável ao processo de peroxidação lipídica, o que pode prejudicar a estrutura celular, motilidade, sobrevivência e funções metabólicas do espermatozóide. O estresse oxidativo pode induzir dano ao DNA espermático, podendo ser responsável pela aceleração do processo de apoptose da célula germinativa, levando a diminuição da concentração de espermatozóides e à aparente deterioração da qualidade seminal observada nas últimas 4 à 5 décadas. Entretanto dois fatores protegem o DNA espermático do ataque oxidativo: a característica de empacotamento do DNA e os antioxidantes presentes no plasma seminal. Consequentemente, as espécies reativas de oxigênio têm efeitos favoráveis ou prejudiciais sobre a função dos espermatozóides de acordo com sua natureza e concentração, assim como o momento e lugar da exposição. Estes achados mostram a importância do equilíbrio adequado entre antioxidantes e baixos níveis de ERO que são necessários para função espermática normal