Metabolism and Functions of Amino Acids in the Skin.

Amino acids are the building blocks of all proteins, including the most abundant fibrous proteins in the skin, as keratins, collagen and elastin. Sagging and wrinkled skin are features of chronic sun-damaged and aged uncared skin, and they are mainly associated with the deterioration of collagen and elastic fibers. The maintenance of skin structures by self-repair processes is essential to skin health. Thus, amino acids significantly impact the appearance of the skin. Amino acids are important nutrients required for (a) wound healing promotion and repair of the damaged skin; (b) acid-base balance and water retention in cellular layers, such as stratum corneum; (c) protection against sunlight damage; (d) maintenance of an appropriate skin microbiome. This review highlights the contribution of all proteinogenic amino acids and some related metabolites to the skin structures as constituents of the main cutaneous proteins or as signaling molecules for the regulation and determination of skin physiology.

Diagnosing pulmonary embolisms: the clinician's point of view. / Diagnóstico de la embolia pulmonar. El punto de vista del médico clínico.

Pulmonary thromboembolism is common and potentially severe. To ensure the correct approach to the diagnostic workup of pulmonary thromboembolism, it is essential to know the basic concepts governing the use of the different tests available. The diagnostic approach to pulmonary thromboembolism is an example of the application of the conditional probabilities of Bayes' theorem in daily practice. To interpret the available diagnostic tests correctly, it is necessary to analyze different concepts that are fundamental for decision making. Thus, it is necessary to know what the likelihood ratios, 95% confidence intervals, and decision thresholds mean. Whether to determine the D-dimer concentration or to do CT angiography or other imaging tests depends on their capacity to modify the pretest probability of having the disease to a posttest probability that is higher or lower than the thresholds for action. This review aims to clarify the diagnostic sequence of thromboembolic pulmonary disease, analyzing the main diagnostic tools (clinical examination, laboratory tests, and imaging tests), placing special emphasis on the principles that govern evidence-based medicine.

Impact of anaemia on health-related quality of life and cardiac remodelling in patients with lower risk myelodysplastic syndromes. Results of GlobQoL study.

The aim of this study was to analyse the eventual changes in health-related quality of life (HRQoL) and left ventricular function (LVF) over a 1-year follow-up period in a cohort of patients with lower risk myelodysplastic syndromes (MDS) receiving standard supportive treatment, in order to identify potential clues for early clinical intervention, as well as to analyse how they relate to haemoglobin levels and other aspects of the disease. A total of 39 adult anaemic patients with lower risk MDS were included in a prospective, observational, multi-centre study. Changes in performance status, functional capacity and HRQoL were collected by using standardised measures (ECOG scale; SPPB, Short Physical Performance Battery; SF-36, Short-Form 36 questionnaire; QLQ-C30, Quality of Life Core Questionnaire; FACT-An, Functional Assessment of Cancer Therapy-Anaemia scale questionnaires respectively). Need for transfusion (Linear Analogue Scale Assessment), as perceived independently by the patient and the haematologist, was also recorded. No changes in HRQoL (or LVF) were found, except for slight reductions in SF-36 physical function (P = 0.034), SPPB gait speed (P = 0.038) and FACT-An score (P = 0.029), all without apparent immediate clinical relevance for HRQoL, that were unrelated to changes in haemoglobin level. Periodical evaluation of gait speed may assist the clinician in early detection of patient's occult functional decline before it becomes clinically relevant.

Comparison of the effects of mesquite pod and Leucaena extracts with phytoestrogens on the reproductive physiology and sexual behavior in the male rat.

Mesquite (Prosopis sp.) and Leucaena leucocephala are widespread legumes, widely used to feed several livestock species and as food source for human populations in several countries. Both mesquite and Leucaena contain several phytoestrogens which might have potential estrogenic effects. Thus, the aim of this study was to evaluate the effects of mesquite pod and Leucaena extracts on several aspects of behavior and reproductive physiology of the male rat. The effects of the extracts were compared with those of estradiol (E2) and of two isoflavones: daidzein (DAI) and genistein (GEN). The following treatments were given to groups of intact male rats: vehicle; mesquite pod extract; Leucaena extract; E2; DAI; GEN. The results indicate that mesquite pod and Leucaena extracts disrupt male sexual behavior in a similar way to DAI and GEN, but less than E2. The main disruptor of sexual behavior was E2, however after 40 and 50days of administration, both extracts and phytoestrogens disrupted sexual behavior in a similar way to E2. The extracts also increased testicular germ cell apoptosis, decreased sperm quality, testicular weight, and testosterone levels, as phytoestrogens did, although these effects were less than those caused by estradiol. The number of seminiferous tubules with TUNEL-positive germ cells increased in extracts treated groups in a similar way to phytoestrogens groups, and E2 caused the greatest effect. The number of TUNEL-positive cells per tubule increased only in Leucaena extract and E2 groups, but not in mesquite- and phytoestrogens-treated groups. Spermatocytes and round spermatids were the TUNEL-positive cells observed in all experimental groups. This effect was associated with smaller testicular weights without atrophy in experimental groups compared with control. Testicular atrophy was only observed in estradiol-treated males. Testosterone decreased in males of all experimental groups, compared with control, this androgen was undetectable in E2 treated males. These results suggest that mesquite pod and Leucaena extracts cause effects similar to those of phytoestrogens in male rat reproduction, these effects were lower than those caused by E2.

Balanço hídrico e excreção renal de metabólitos em ovinos alimentados com palma forrageira (Nopalea cochenillifera Salm Dyck) / Water balance and renal excretion of metabolites in sheep fed forage cactus (Nopalea cochenillifera Salm Dyck)

Objetivou-se avaliar balanço hídrico e excreção renal de metabólitos em borregos sem raça definida, alimentados com diferentes quantidades de palma forrageira (Nopalea cochenillifera Salm Dyck), na forma in natura e em farelo. Foram utilizados 20 borregos, com peso vivo médio inicial de 20 Kg e foram distribuídos no delineamento inteiramente casualizado, sendo cinco tratamentos e quatro repetições. As dietas experimentais consistiram em uma dieta controle à base de feno de tífton, farelo de soja, suplemento mineral e calcário, os demais tratamentos visaram testar níveis diferentes de palma forrageira corrigida com ureia em duas formas: in natura e farelada e em dois níveis de substituição (50 e 100%) da matéria seca do feno de tífton. Amostras de sangue e urina foram coletadas para determinação de diferentes metabólitos e minerais e utilização de equações para obtenção dos índices de excreção urinária destes metabólitos, taxa de depuração endógena de creatinina e reabsorção de água livre de eletrólitos, além do registro de ingestão de água e volume de urina. A ingestão voluntária de água sofreu influência das dietas, sendo que os animais submetidos às dietas contendo farelo de palma e feno e farelo de palma foram superiores aos demais tratamentos. A ingestão de água via alimentos também sofreu influência da dieta, sendo maior nos animais que receberam palma in natura e farelo mais palma in natura. Com relação à ingestão total de água foi maior para os animais alimentados com dietas contendo palma in natura em relação aos demais tratamentos. As dietas experimentais influenciaram na excreção renal de metabólitos derivados purínicos e minerais, sem alterar a função renal. A presença da palma forrageira tanto na condição de farelo como in natura proporciona aumento do volume urinário sem alterar a função renal, além de que deve ser considerado como uma excelente estratégia alimentar no semiárido.

This study aimed to assess fluid balance and renal excretion of metabolites in lambs without defined breed standard, fed different forage cactus (Nopalea cochenillifera Salm Dyck), in natura and bran. 20 lambs were used, with initial body weight of 20 kg and were distributed in a completely randomized design, with five treatments and four repetitions. The experimental diets consisted of a control diet based on Bermuda grass hay, soybean meal, limestone and mineral supplement, other treatments aimed at testing different levels of cactus pear plus urea in two forms: fresh and mash and two levels of substitution (50 and 100%) of dry matter of hay. Blood and urine samples were collected for determination of different metabolites and minerals and use of equations to determine the rates of urinary excretion of these metabolites, rate of endogenous creatinine clearance and electrolyte reabsorption of free water, in addition to recording of water intake and urine volume. The voluntary water intake was influenced by the diets, and the animals subjected to diets containing soybean meal and hay palm and cactus meal were higher than other treatments. Water intake via food was also influenced by diet, being higher in animals fed palm fresh and bran over palm in nature. With respect to total water intake was greater for cows fed diets containing palm in nature compared to the other treatments. The experimental diets influenced the renal excretion of purine metabolites and minerals derived, without changing renal function. The presence of cactus pear both as bran as in nature provides increased urine volume without changing renal function, and to be considered as an excellent food strategy in semiarid.

MDR1 C3435T polymorphism in Mexican patients with breast cancer.

We investigated whether the MDR1 C3435T polymorphism is associated with fibrocystic changes (FCC), infiltrating ductal breast cancer (IDBC), and/or clinical-pathological features of IDBC in Mexican patients. Samples from women who received surgical treatment in 2007 at the Centro Médico de Occidente (México) were included in the analysis. Genotyping was performed by polymerase chain reaction-restricted fragment length polymorphisms in 64 paraffin-embedded breast samples with IDBC, 64 samples with FCC, and 183 peripheral blood samples of healthy females designated as the healthy group (HG). The frequency of the T allele was 41, 45, and 52% for the FCC, IDBC, and HG samples, respectively. Significant differences were only found between the FCC and HG samples [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.43-0.96; P = 0.032]. The prevalence of the T/T genotype was 8, 13, and 24% for FCC, IDBC, and HG samples, respectively. Again, statistical differences were only found between FCC and HG samples for the T/T genotype (OR = 0.28, 95%CI = 0.106-0.77; P = 0.009). Although the T allele and the T/T genotype were less frequent in the IDBC group than in the HG, the differences were not significant. Furthermore, no associations were found between the C3435T polymorphism and clinical-pathological features of the IDBC group. Both the FCC and IDBC groups had a high frequency of the C allele relative to the HG in this sample of women from Western Mexico.

Low transformation growth factor-β1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni

Undernourished mice infected (UI) submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers’ fibrosis in humans. In this report, the effects of the host’s nutritional status on parasite (worm load, egg viability and maturation) and host (growth curves, biology, collagen synthesis and characteristics of the immunological response) were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF)-β1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-β1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.

Low transformation growth factor-ß1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni.

Undernourished mice infected (UI) submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers' fibrosis in humans. In this report, the effects of the host's nutritional status on parasite (worm load, egg viability and maturation) and host (growth curves, biology, collagen synthesis and characteristics of the immunological response) were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF)-ß1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-ß1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.

Chlamydia trachomatis: a major agent of respiratory infections in infants from low-income families.

OBJECTIVES: To determine the prevalence of lower respiratory tract infection (LRTI) due to Chlamydia trachomatis in newborn infants and to describe the clinical, laboratory, and radiological characteristics of the disease. METHODS: A cross-sectional study carried out over a 12-month period. All infants up to 6 months of age admitted consecutively at the Centro Pediátrico Professor Hosannah de Oliveira of the Universidade Federal da Bahia in Salvador, Brazil, and diagnosed with LRTI according to clinical and/or radiological criteria were included in the study. C. trachomatis infection was diagnosed by the enzyme-linked immunosorbent assay (ELISA) for the detection of IgM-class antibodies. The prevalence of LRTI by C. trachomatis was determined and the prevalence ratios for the infection and clinical or laboratory variables were calculated. RESULTS: One hundred and fifty-one infants were submitted to serology for C. trachomatis and 15 (9.9%) tested positive. Chlamydial infection was found only in infants under 5 months of age, mainly in those aged under 2 months. Three of the infants with C. trachomatis infection were born by cesarean section. Conjunctivitis and eosinophilia had occurred in 33.3% of the cases. Chest X rays were abnormal in 92.0% of cases. There was an association between C. trachomatis infection and the duration of hospitalization exceeding 15 days (p = 0.0398) and oxygen therapy (p = 0.0484). CONCLUSIONS: There was a high prevalence of C. trachomatis respiratory infection in the population studied. The infection was associated with a more severe form of the disease, emphasizing the importance of testing pregnant women for this infection to avoid infection in the newborn infant.

Betacyanin and other antioxidants production during growth of Opuntia stricta (Haw.) fruits.

Mature cactus pears from Opuntia stricta have a dark purple color due to high betacyanin concentration, whose biosynthesis is initiated with the amino acid L-tyrosine as a primary precursor. This study followed the maturation and ripening processes of Opuntia stricta fruits to harvest them at high betacyanin and other antioxidant concentrations. Fruits lasted 9 months for final ripening. Physical and compositional changes at different maturation and ripening stages have been determined. Thus, ripe fruits were around 4.72 ± 0.10 cm length, 2.94 ± 0.05 cm diameter and 22.71 ± 0.20 g weight; moisture and pH were maintained at 87.05 ± 0.19 % and 3.37 ± 0.12, respectively. Purple pigment production started in the ovary of immature fruits four months after anthesis (MAA). Concentration of all analyzed metabolites increased from immature (4 MAA) until ripe (9 MAA) stage. In ripe fruits, reducing sugars were 4.72 ± 0.54 g/100 g ff and total phenols 135.17 ± 0.68 mg gallic acid/100 g ff. Metabolites identified by HPLC were the betacyanins: betanin (60.17 ± 1.08 mg/100 g ff), isobetanin (7.58 ± 0.94 mg/100 g ff) and betanidin (13.48 ± 0.87 mg/100 g ff). Also, L-ascorbic acid (35.03 ± 1.06 mg/100 g ff) and L-tyrosine (4.43 ± 0.73 mg/100 g ff) were determined. Furthermore, the addition of L-tyrosine or L-dopa to fruit pulp of moderately ripe fruits, increased betacyanin concentrations 17 (103.3 ± 3.8 mg/100 g) and 32 % (114.3 ± 4.1 mg/100 g), respectively.

Chlamydia trachomatis: um importante agente de infecções respiratórias em lactentes de famílias de baixa renda / Chlamydia trachomatis: a major agent of respiratory infections in infants from low-income families

OBJETIVOS: Determinar a prevalência de infecção do trato respiratório inferior (ITRI) por Chlamydia trachomatis em lactentes internados e descrever as características clínicas, laboratoriais e radiológicas da doença. MÉTODOS: Este foi um estudo do tipo corte transversal, realizado durante um período de 12 meses. Foram incluídos todos os lactentes de até 6 meses internados consecutivamente no Centro Pediátrico Professor Hosannah de Oliveira da Universidade Federal da Bahia, em Salvador, BA, com diagnóstico clínico ou clínico-radiológico de ITRI. O diagnóstico de infecção por C. trachomatis foi realizado através da pesquisa de anticorpos da classe IgM, utilizando-se o ensaio imunoenzimático (ELISA). A prevalência de ITRI por C. trachomatis foi determinada, e foram calculadas as razões de prevalência para essa infecção e variáveis clínicas e laboratoriais. RESULTADOS: Cento e cinquenta e um lactentes realizaram sorologia para C. trachomatis, das quais 15 (9,9%) foram positivas. A infecção por C. trachomatis ocorreu unicamente entre os menores de 5 meses, principalmente naqueles menores de 2 meses. Três crianças com infecção por C. trachomatis nasceram de parto cesáreo. Conjuntivite e eosinofilia ocorreram em 33,3% dos casos. As radiografias de tórax se mostraram alteradas em 92% dos casos. Demonstrou-se associação da infecção por C. trachomatis com duração de internação superior a 15 dias (p = 0,0398) e com oxigenoterapia (p = 0,0484). CONCLUSÕES: Houve alta prevalência de ITRI por C. trachomatis na população estudada. A infecção por esta bactéria foi associada a uma forma mais grave da doença, demonstrando a importância de se investigar essa infecção na gestante de forma a evitar o adoecimento de recém-nascidos.

OBJECTIVES: To determine the prevalence of lower respiratory tract infection (LRTI) due to Chlamydia trachomatis in newborn infants and to describe the clinical, laboratory, and radiological characteristics of the disease. METHODS: A cross-sectional study carried out over a 12-month period. All infants up to 6 months of age admitted consecutively at the Centro Pediátrico Professor Hosannah de Oliveira of the Universidade Federal da Bahia in Salvador, Brazil, and diagnosed with LRTI according to clinical and/or radiological criteria were included in the study. C. trachomatis infection was diagnosed by the enzyme-linked immunosorbent assay (ELISA) for the detection of IgM-class antibodies. The prevalence of LRTI by C. trachomatis was determined and the prevalence ratios for the infection and clinical or laboratory variables were calculated. RESULTS: One hundred and fifty-one infants were submitted to serology for C. trachomatis and 15 (9.9%) tested positive. Chlamydial infection was found only in infants under 5 months of age, mainly in those aged under 2 months. Three of the infants with C. trachomatis infection were born by cesarean section. Conjunctivitis and eosinophilia had occurred in 33.3% of the cases. Chest X rays were abnormal in 92.0% of cases. There was an association between C. trachomatis infection and the duration of hospitalization exceeding 15 days (p = 0.0398) and oxygen therapy (p = 0.0484). CONCLUSIONS: There was a high prevalence of C. trachomatis respiratory infection in the population studied. The infection was associated with a more severe form of the disease, emphasizing the importance of testing pregnant women for this infection to avoid infection in the newborn infant.

Pre-freezing raw hams affects quality traits in cooked hams: potential influence of protein oxidation.

The influence of protein carbonylation and lipid oxidation on colour and texture changes in cooked hams from fresh and pre-frozen (frozen/thawed) raw material was studied. Samples from three muscles, biceps femoris (BF) quadriceps femoris (QF) and semimembranosus (SM) were analysed for the gain of specific protein carbonyls, α-aminoadipic and γ-glutamic semialdehydes, the gain of TBA-RS and their colour and texture properties by instrumental and sensory techniques. The formation of protein carbonyls occurred concomitantly with an intense loss of redness and increase of hardness. Both phenomena were found to be more intense in QF and SM muscles in cooked hams elaborated from frozen material. Lipid oxidation played a negligible role on the impaired quality traits observed in cooked hams as a result of pre-freezing. Plausible mechanisms by which protein carbonylation may be implicated in the loss of quality in cooked hams produced from pre-frozen material are discussed.

Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR).

BACKGROUND: The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice. METHODS: Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n=1345) or a new oral antipsychotic (AP) (n=277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review. RESULTS: At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p<0.0001) and reduction in Clinical Global Impression Severity scores (-1.14 for RLAI versus -0.94 for APs, p=0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p<0.05) and days (18.74 versus 13.02, p<0.01) of hospitalizations at 24 months than oral AP patients. CONCLUSIONS: This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.

Highly skewed inactivation of the wild-type X-chromosome in asymptomatic female carriers of spinal and bulbar muscular atrophy (Kennedy's disease).

We examined families with a history of spinal and bulbar muscular atrophy (SBMA) and found that six out of eight female carriers had a skewed inactivation of the wild-type chromosome. Under these genetic conditions, disease manifestations should be expected and therefore we sought neurological and other symptoms of subclinical SBMA. We did not find either clinical symptoms or electrophysiological signs of mutated AR gene in female carriers, despite skewed methylation of the wild-type allele. These findings suggest that skewed methylation of AR genes are not necessarily associated to clinical manifestations in female carriers of the expanded SBMA allele.

Involvement of a novel copper chaperone in tyrosinase activity and melanin synthesis in Marinomonas mediterranea.

Tyrosinase activity and melanin synthesis in the marine bacterium Marinomonas mediterranea in media with very low copper concentrations are dependent on the presence of a protein (PpoB2) that functions as a chaperone to deliver copper to tyrosinase (PpoB1). Under these conditions, mutants in ppoB2 (such as strain T105) produce PpoB1 as an apoenzyme that can be reconstituted to the active holoenzyme by the addition of cupric ions to cell extracts. To study PpoB2 functionality, a system was developed for genetic complementation in M. mediterranea. Using this approach, melanin synthesis was restored in strain T105 when a wild-type copy of ppoB2 was introduced. PpoB2 is a novel protein since it is believed to be the first to be described that contains several motifs similar to metal binding motifs present separately in other types of copper-related protein. At least three motifs, a His-rich N-terminal region, and the short CxxxC and MxxxMM sequences, are essential for the functionality of PpoB2, since site-directed mutagenesis of these motifs resulted in a non-functional protein. In addition, it was demonstrated that PpoB2 is a membrane copper transporter putatively participating in the delivery of this ion specifically to the tyrosinase of M. mediterranea and not to a second copper oxidase showing laccase activity that this micro-organism also expresses. PpoB2 has similarities with the COG5486 group encoding putative transmembrane metal binding proteins, and is believed to be the first protein in this group to be experimentally characterized. It may constitute the first example of a novel type of protein involved in copper trafficking in bacteria.