Understanding the factors influencing pharmacokinetics of tacrolimus

Tacrolimus, a potent calcineurin inhibitor integral to immunosuppressive regimens, exhibits complex pharmacokinetics influenced by diverse factors and understanding these factors is crucial for safety, efficacy and dose optimisation. Genetic variations, particularly in CYP3A enzyme systems and P- Glycoprotein, contribute significantly to inter-individual variability in tacrolimus metabolism. Polymorphisms in these systems alter drug bioavailability, impacting clinical outcomes. Ethnicity further compounds this variability, with distinct genetic profiles leading to differential drug responses. Notably, black patients, often characterized by CYP3A5 expressor status, may have higher drug clearance. Age-related changes in tacrolimus clearance highlights the discrepancies in elderly and paediatric populations. On the other hand, prediction of gender-specific differences is difficult due to lack of evidence. Body composition, specifically variations in fat and muscle mass, significantly impacts drug distribution and clearance. Obesity, associated with altered CYP3A activity, results in decreased drug clearance, emphasizing the importance of accounting for body composition in dosing calculations. Pregnancy -induced physiological changes affect tacrolimus absorption, distribution, metabolism, and excretion, necessitating careful monitoring and dose adjustments in pregnant individuals. Dietary factors and drug interactions, particularly with CYP3A4 and P-glycoprotein, further contribute to the intricate web of variables influencing tacrolimus pharmacokinetics. In conclusion, this review sheds light on the multifaceted factors influencing tacrolimus pharmacokinetics, providing essential insights for clinicians to tailor individualized dosing regimens and enhance therapeutic efficacy while minimizing the risk of adverse events.

A case of Guillain-Barre syndrome presenting at third trimester of pregnancy complicated with pre-eclampsia and acute kidney injury

Guillain-Barre syndrome (GBS) is immune mediated injury of the peripheral nerves. This condition can affect any individuals with some trigger. Here the disease affected the lady in her last trimester of pregnancy which was complicated with pre-eclampsia and acute kidney injury. Later she recovered by multimodal treatment approach, with a prolonged intensive care unit stay. Currently she and her baby are stable with frequent follow up. This case highlights the fact that GBS can affect any trimester of pregnancy and her pregnancy could be a trigger. Further, treatment approach involves multiple specialties including internal medicine, nephrologist, neurologist, physiotherapist and psychiatrist.

Episodic angioedema with eosinophilia (Gleich's syndrome) associated with urticarial vasculitis: a coincidence or a novel clinical entity?

Episodic angioedema with eosinophilia (EAE) is a rare condition characterized by recurrent attacks of angioedema and urticaria accompanied by a marked elevation of peripheral eosinophil count. We report the case of a young female patient diagnosed with EAE associated with urticarial vasculitis. A 40-year-old female patient was admitted to our institution due to recurrent episodes of cheek and eyelid angioedema in the previous year. Episodes of facial angioedema lasted for two months with spontaneous remission afterwards. In addition, she presented pruritic and painful skin eruptions of erythematous circles, which persisted for longer than 24 h, that were palpable, somewhat purplish, and more pronounced on the face, arms, and trunk. Laboratory investigation showed a sustained elevation of white cell counts with marked eosinophilia. Serum IgM, IgE, and IgA were normal; IgG was slightly elevated. C1-esterase inhibitor and tryptase test were normal. Reverse transcriptase-polymerase chain reaction was performed for detection of FIP1L1-PDGFRA and BCR-ABL rearrangements. None of these alterations were found. Skin biopsies were suggestive of urticarial vasculitis. The patient was submitted to esophagogastroduodenoscopy, which showed mild chronic gastritis, with no eosinophilic infiltration. Cardiac dimensions and function were normal. Abdominal ultrasound and total body CT-scan failed to show lymphadenopathy, organomegaly, and tumors. We report the first case of association between episodic angioedema with eosinophilia and urticarial vasculitis. It is possible that both conditions share a physiopathological mechanism, suggesting that it is not just a chance association.

Multicomponent exercise training in cardiovascular complexity in prefrail older adults: a randomized blinded clinical pilot study

The aim of this study was to investigate the effects of multicomponent training on baroreflex sensitivity (BRS) and heart rate (HR) complexity of prefrail older adults. Twenty-one prefrail community-dwelling older adults were randomized and divided into multicomponent training intervention group (MulTI) and control group (CG). MulTI performed multicomponent exercise training over 16 weeks and CG was oriented to follow their own daily activities. The RR interval (RRi) and blood pressure (BP) series were recorded for 15 min in supine and 15 min in orthostatic positions, and calculation of BRS (phase, coherence, and gain) and HR complexity (sample entropy) were performed. A linear mixed model was applied for group, assessments, and their interaction effects in supine position. The same test was used to assess the active postural maneuver and it was applied separately to each group considering assessments (baseline and post-intervention) and positions (supine and orthostatic). The significance level established was 5%. Cardiovascular control was impaired in prefrail older adults in supine position. Significant interactions were not observed between groups or assessments in terms of cardiovascular parameters. A 16-week multicomponent exercise training did not improve HR complexity or BRS in supine rest or in active postural maneuver in prefrail older adults.

Biomass components and structure of massai grass fertilized with nitrogen and grazed by sheep / Componentes da biomassa e estrutura do capim-massai adubado com nitrogênio e pastejado por ovinos

To evaluate the biomass components of massai grass subjected to nitrogen (N) fertilization levels (control - 0; 400; 800 and 1200 kg ha-1 year-1 of N) and under rotational stocking with sheep, this study was undertaken using a completely randomized design with measurements repeated in time. A quadratic response was observed reaching maximum values as the levels of nitrogen fertilization increased for green forage biomass, green leaf biomass, green stem biomass (5,172.9; 4,146.3; 1,033.9 kg ha-1 cycle-1, respectively), forage total density (179.1 kg ha-1 cm-1), canopy height (36.8 cm) and live material/dead material ratio (4.0) at levels 896; 934; 797; 879.2; 751.4 and 1,161 kg ha-1 year-1 of N, respectively. For all variables, oscillation was observed between the grazing cycles studied. Nitrogen fertilization has a positive response on the biomass components and canopy structure of massai grass.(AU)

Objetivou-se avaliar os componentes da biomassa do capim-massai sob lotação rotativa com ovinos e adubado com doses de nitrogênio (controle - 0; 400; 800 e 1200 kg de N ha -1 ano -1 ), em delineamento inteiramente ao acaso, com medidas repetidas no tempo. Constatou-se resposta quadrática, alcançando valores máximos com o incremento das doses de nitrogênio para as produções de biomassa de forragem verde, de lâmina foliar verde, de colmo verde (5172,9; 4146,3; 1033,9 kg ha -1 ciclo -1 , respectivamente) e para a densidade total de forragem (179,1 kg ha -1 cm -1 ), altura do dossel (36,8 cm) e relação material vivo/material morto (4,0) nas doses 896; 934; 797; 879,2; 751,4 e 1161 kg ha -1 ano -1 de N, respectivamente. Para todas as variáveis, verificou-se oscilação entre os ciclos de pastejo estudados. A adubação nitrogenada exerce respostas positivas sobre os componentes da biomassa e a estrutura do dossel do capim-massai.(AU)

Baroreflex sensitivity in frailty syndrome

Frailty is related to a decrease in the physiological reserves, which causes difficulties in maintaining homeostasis. An example of physiological mechanisms for cardiovascular homeostasis is the baroreflex. The aim of this study was to compare baroreflex among frail, prefrail, and nonfrail individuals, in supine and orthostatic positions. Community-dwelling older adults were evaluated and categorized into frail, prefrail, or nonfrail groups, according to frailty phenotype. The RR interval (RRi) and systolic blood pressure (SBP) series were recorded for 15 min in the supine and 15 min in the orthostatic positions. Mean and variance of RRi and SBP, and baroreflex evaluated by phase, gain (α), and coherence (K2) were determined. A two-way repeated measures ANOVA, with Tukey's post hoc, was applied for group, position, and their interaction effects. The significance level established was 5%. Prefrail and frail participants did not present a significant decrease in mean values of RRi after postural challenge (893.43 to 834.20 ms and 925.99 to 857.98 ms, respectively). Frail participants showed a reduction in RRi variance in supine to orthostatic (852.04 to 232.37 ms2). Prefrail and frail participants showed a decrease in K2 after postural change (0.69 to 0.52 and 0.54 to 0.34, respectively). Frail participants exhibited lower values of K2 (0.34) compared to nonfrail and prefrail participants (0.61 and 0.52, respectively). Baroreflex indicated the presence of decoupling between heart period and SBP in frail and prefrail. Thus, reduced K2 might be a marker of the frailty process.

Risk factors, ascribed causes and effects of obstetric fistula among women in northern Ghana: a case control studies

Background: Obstetric fistula is a demoralizing maternal morbidity. In Ghana, majority of the fistula occur in the northern sector. This study sought to identify the risk factors, ascribed causes and effect of obstetric fistula. Methods: A matched case control study was conducted from April to June 2013. The fistula patients were taken from the Fistula Centre in Tamale whiles the controls were from the Tamale Teaching hospital. Eligible cases were confirmed fistula patients admitted for fistula repair while controls were women who have delivered but without obstetric fistula. Cases and controls were matched on year, region and district of index delivery. Results: the following factors were associated with obstetric fistula; age below 20 years, total labour duration more than 24 hours, height 150 cm and below, still birth, operative delivery, residence in a rural area and lack of formal education. Divorce rate among cases over the period was 55.3% while that among the controls was 2.3%. About 20% of cases were likely to be currently using alcoholic beverages compared to 6% in controls (OR=5.3, 95% CI= 1.4 ­19.7). 40% of cases currently have no living child compared to 2% of controls. Majority of fistula patients blame lack of health facilities and an act of God as a cause of fistula. Conclusions: Majority of women who suffer obstetric fistula are young, poor, of short stature, illiterate and resident in remote areas. There is widespread lack of understanding of the causes of Obstetric fistula among women

Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

Considering that osteoarthritis (OA) is the most prevalent joint disease worldwide, multiple pharmacological treatments have been proposed to alter the articular structure with potential benefit in the progression of the disease. The so-called disease-modifying OA drugs have been frequently investigated but conclusive findings are rare. Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects in decreasing the risk of fractures and possible effect in reducing the progression of OA. The objective of this review was to demonstrate the current panorama of knowledge on the use of SrRan in clinical and experimental models, clarifying its mechanisms of action and describing possible anti-nociceptive and anti-inflammatory effects. The systematic review was based on the PRISMA statement and included articles that are indexed in scientific databases. Fifteen studies were included: seven pre-clinical and eight clinical studies. Despite the limited number of studies, the results suggest a positive effect of SrRan in patients with OA, through changes in functional capacity and reduction of progression of morphological parameters and joint degradation, with moderate quality of evidence for those clinical outcomes. Novel studies are necessary to elucidate the molecular targets of SrRan, focusing on anti-inflammatory effects and histological changes promoted by SrRan, which seemed to reduce the progression of OA in the experimental and clinical studies.

Microbiological, chemical, physical, and proteolytic activities of raw milk after thermal processing / Atividade microbiológica, física, química e proteolítica do leite cru após o processamento térmico

The aim was to evaluate the microbiological, chemical- physical, and shelf-life quality of milk samples after pasteurization (HTST) for 10 days or ultra-high temperature (UHT) treatment for 120 days. Raw milk counts of mesophilic aerobic microorganisms, Staphylococcus spp. and thermotolerant coliforms before HTST and UHT processing were 6.73 and 7.77; 2.84 and 4.30, and 4.68 and 4.37log10, respectively. Pseudomonas spp. were found in raw milk samples. No presence of any other microorganisms studied was detected and no microbial inhibitor was found. Processed samples met microbiological legal requirements. However, aerobic mesophilic counts for HTST pasteurized milk samples stored for 5 and 10 days increased to values comparable to those in raw milk. Composition chemical- physical of all samples were within legal limits. These results demonstrate that, although HTST and UHT processed milk comply with the microbiological standards required by Brazilian law, high microbial counts in raw milk are an issue, possibly due to failures in the early stages of the production chain. Increase in casein macropeptide (CMP), probably because of proteases psychrotrophic bacteria. It is concluded that the quality of raw milk directly influences the progressive increase of the CMP values.(AU)

O objetivo da presente pesquisa foi avaliar a qualidade microbiológica, fisco-química e a vida de prateleira de amostras de leite, após o processo de pasteurização rápida (HTST) ou de ultra-alta temperatura (UHT) durante 10 dias, ou de ultra-alta temperatura (UHT) por 120 dias. As contagens de micro-organismos aeróbios mesófilos, Staphylococcus spp. e de coliformes termotolerantes do leite cru utilizado para tratamentos HTST e UHT foram, respectivamente (log10): 6,73 e 7,77; 2,84 e 4,30 e 4,68 e 4,37. Foi constatada a presença de Pseudomonas spp. no leite cru. Não foi detectada a presença de nenhum outro micro-organismo estudado, e as amostras estavam isentas de inibidores microbianos. Após a pasteurização, todas as amostras apresentaram contagens microbianas compatíveis com os limites legais. No entanto, as amostras de leite pasteurizado apresentaram contagens de aeróbios mesófilos semelhantes ao leite cru após cinco e 10 dias de armazenamento. A composição físico-química de todas as amostras estava de acordo com os limites legais. Observou-se acréscimo dos níveis de caseinomacropeptídeo (CMP) no leite UHT, provavelmente em função das proteases de bactérias psicrotróficas. Conclui-se que a qualidade do leite cru influencia diretamente os valores de CMP.(AU)

Nutritional quality of Pilosocereus gounellei using different spine removal and plant storage methods / Qualidade nutritiva de Pilosocereus gounellei em relação a diferentes métodos de retirada dos acúleos e ao armazenamento

This study aimed to evaluate the nutritional quality of Pilosocereus gounellei using different methods of spine removal and plant storage. A total of 600 P. gounellei cacti were randomly selected in 10 hectares of Caatinga. The experimental design was completely randomised using a 2 x 4 factorial arrangement and three replicates. The variables evaluated were the storage conditions (under trees; and ventilated storage facilities) and four types of spine removal techniques assessed 31 days after storage (fresh plants with spines [control]; use of flamethrowers before storage; slash-and-burn ["coivara"] before storage; and use of flamethrowers after storage). The P. gounellei subjected to slash-and-burn during the cladode harvest (cutting) process deteriorated rapidly and exhibited a smooth consistency; dark colour. The burning process resulted in increased in situ degradability of dry matter compared with the control treatment. The results of treatment 4 were similar to those of the control treatment regarding the preservation of the nutritional properties of P. gounellei. Therefore, P. gounellei can be harvested and stored fresh for 31 days without losing their nutritional properties, and spines should be removed using flamethrowers after the storage period, i.e., when using the plants as livestock feed.(AU)

Objetivou-se com o presente trabalho avaliar a qualidade nutritiva do Pilosocereus gounellei em relação a diferentes métodos de retirada dos acúleos e ao armazenamento. Foram selecionadas ao acaso 600 P. gounelleis em 10 hectares de caatinga nativa. O delineamento experimental foi inteiramente ao acaso, em esquema fatorial (2 x 4), com três repetições. Os fatores constaram dos locais de armazenamento (primeiro local: árvore. segundo local: galpão) e de quatro tipos de processamento de eliminação dos acúleos do P. gounellei (tratamento 1: in natura, com acúleo (testemunha); tratamento 2: utilização de lança-chamas por ocasião do armazenamento; tratamento 3: queima em coivara por ocasião do armazenamento; tratamento 4: lança-chamas após o armazenamento), avaliado após 31 dias do armazenamento. O P. gounellei queimado em coivara por ocasião do corte (tratamento 3) degradou-se rapidamente, apresentando consistência lisa e coloração escurecida. Em relação à degradabilidade in situ da matéria seca, os tratamentos com fogo proporcionaram maiores valores que o tratamento 1. O tratamento 4 foi o que apresentou resultados mais próximos ao 1 (P. gounellei in natura), conservando as propriedades nutricionais do P. gounellei. O P. gounellei pode ser colhido e armazenado in natura por 31 dias, sendo preservadas suas qualidades nutricionais, com retirada dos acúleos com lança-chamas após o armazenamento, no momento de fornecer aos animais.(AU)

Fotoperíodo e frequência alimentar na larvicultura do peixe beta / Photoperiod and feeding frequency in the Siamese fighting fish hatchery

Com este trabalho, objetivou-se avaliar o crescimento, a uniformidade e a sobrevivência das larvas de Betta splendens, submetidas a diferentes fotoperíodos e frequências de alimentação. Foram distribuídos aleatoreamente 480 indivíduos (4,53mg ± 0,32 e 5,51 ± 0,58mm) em 48 recipientes plásticos (1L), com densidade de 10 larvas/ L. Foi utilizado um delineamento experimental inteiramente ao acaso, com quatro repetições, em arranjo fatorial 6x2, com seis fotoperíodos (0L:24E, 6L:18E, 12L:12E, 16L:8E, 20L:4E, 24L:0E) e duas frequências de alimentação (duas ou quatro vezes/ dia). Durante um período de 15 dias, as larvas foram alimentadas com náuplios de Artemia, na proporção de 800 náuplios/ larva/ dia. Larvas de beta submetidas aos fotoperíodos de 12L:12E e 16L:8E apresentaram o maior crescimento em peso (P<0,10), enquanto as que foram alimentadas quatro vezes ao dia apresentaram maior crescimento em comprimento e uniformidade (P<0,10). No entanto, os indivíduos que foram alimentados quatro vezes ao dia apresentaram menor sobrevivência quando submetidos aos fotoperíodos de 16L:8E, 20L:4E e 24L:0E (P<0,10). Por outro lado, as larvas submetidas aos fotoperíodos de 12L:12E, 16L:8E e 20L:4E apresentaram maior taxa de sobrevivência quando alimentadas duas vezes ao dia (P<0,10). Portanto, ao se preconizar maior crescimento, uniformidade e sobrevivência das larvas de Betta splendens, recomenda-se a realização da larvicultura dessa espécie sob o fotoperíodo de 12L:12E, com o fornecimento de náuplios de Artemia em duas alimentações diárias.(AU)

The aim of this study was to evaluate the growth, uniformity and survival of Betta splendens larvae, submitted to different photoperiods and feeding frequency. Four hundred and eighty individuals (4.53mg ± 0.32 and 5.51 ± 0.58mm) were randomly distributed into 48 plastic containers (1L) at a density of 10 larvae/L. A completely randomized design was used, with four replications in a factorial 6 x 2, six photoperiods (0L:24D, 6L:18D, 12L:12D, 16L:8D, 20L:4D, 24L:0D) and two feeding frequencies (two or four times a day). The larvae were fed performed with Artemia nauplii at averaging 800/ larvae/ day, for 15 days. Beta larvae subjected to photoperiod 12L:12D and 16L:8E showed the greatest weight gain (P<0.10), while those fed four times daily had greater length growth and uniformity (P<0.10). However, individuals fed four times daily had lower survival when subjected to photoperiod 16L:8E, 20L:4L and 24E:0D (P<0.10). On the other hand, larvae subjected to a photoperiod of 12L:12D, 16L:8L and 20L:4E showed higher survival rate when fed twice a day (P<0.10). Therefore, with the intention of better growth, uniformity and survival of Betta splendens larvae, it is recommended that the hatchery in this species be done under a photoperiod of 12L: 12D with supply of Artemia nauplii twice daily.(AU)

Inflammatory and oxidative stress airway markers in premature newborns of hypertensive mothers

Although oxidative stress and inflammation are important mechanisms in the pathophysiology of preeclampsia and preterm diseases, their contribution to the respiratory prognosis of premature infants of hypertensive mothers is not known. Our objective was to determine the levels of oxidative stress and inflammation markers in the airways of premature infants born to hypertensive and normotensive mothers, in the first 72 h of life, and to investigate whether they are predictors of bronchopulmonary dysplasia (BPD)/death. This was a prospective study with premature infants less than 34 weeks’ gestation on respiratory support who were stratified into 2 groups: 32 premature infants of hypertensive mothers and 41 of normotensive women, with a mean gestational age of 29 weeks. Exclusion criteria were as follows: diabetes mellitus, chorioamnionitis, malformation, congenital infection, and death within 24 h after birth. The outcome of interest was BPD/death. Malondialdehyde (MDA), nitric oxide (NO), and interleukin 8 (IL-8) were measured in airway aspirates from the first and third days of life and did not differ between the groups. Univariate and multivariate statistical analyses were performed. The concentrations of MDA, NO, and IL-8 were not predictors of BPD/death. Premature infants who developed BPD/death had higher levels of IL-8 in the first days of life. The gestational age, mechanical ventilation, and a small size for gestational age were risk factors for BPD/death. In conclusion, the biomarkers evaluated were not increased in premature infants of hypertensive mothers and were not predictors of BPD/death.

Growth of preterm low birth weight infants until 24 months corrected age: effect of maternal hypertension / Crescimento de prematuros de baixo peso até a idade de 24 meses corrigidos: efeito da hipertensão materna

OBJECTIVE: To evaluate the growth pattern of low birth weight preterm infants born to hypertensive mothers, the occurrence of growth disorders, and risk factors for inadequate growth at 24 months of corrected age (CA). METHODS: Cohort study of preterm low birth weight infants followed until 24 months CA, in a university hospital between January 2009 and December 2010. Inclusion criteria: gestational age < 37 weeks and birth weight of 1,500-2,499 g. Exclusion criteria: multiple pregnancies, major congenital anomalies, and loss to follow up in the 2nd year of life. The following were evaluated: weight, length, and BMI. Outcomes: growth failure and risk of overweight at 0, 12, and 24 months CA. Student's t-test, Repeated measures ANOVA (RM-ANOVA), and multiple logistic regression were used. RESULTS: A total of 80 preterm low birth weight infants born to hypertensive mothers and 101 born to normotensive mothers were studied. There was a higher risk of overweight in children of hypertensive mothers at 24 months; however, maternal hypertension was not a risk factor for inadequate growth. Logistic regression showed that being born small for gestational age and inadequate growth in the first 12 months of life were associated with poorer growth at 24 months. CONCLUSION: Preterm low birth weight born infants to hypertensive mothers have an increased risk of overweight at 24 months CA. Being born small for gestational age and inadequate growth in the 1st year of life are risk factors for growth disorders at 24 months CA. .

OBJETIVO: Avaliar o padrão de crescimento de prematuros de baixo peso nascidos de mães hipertensas, a ocorrência de distúrbios de crescimento e os fatores de risco para inadequado crescimento aos 24 meses de idade corrigida (IC). MÉTODOS: Estudo de coorte de prematuros de baixo peso acompanhados até 24 meses IC, em um hospital universitário, entre janeiro de 2009 e dezembro de 2010. Critérios de inclusão: idade gestacional < 37 semanas e peso de nascimento de 1500-2499 g. Excluídas: gestações múltiplas, anomalias congênitas maiores e perda de seguimento no segundo ano de vida. Foram avaliados: peso, comprimento e IMC. Desfechos: falha de crescimento e risco de sobrepeso com 0, 12 e 24 meses de IC. Teste t de Student, X2, Anova-RM e regressão logística múltipla foram usados. RESULTADOS: Foram estudados 80 prematuros de baixo peso nascidos de mães hipertensas e 101 de mães normotensas. Houve maior risco de sobrepeso em crianças de mães hipertensas aos 24 meses, entretanto a hipertensão materna não foi fator de risco para inadequado crescimento. A regressão logística mostrou que nascer pequeno para idade gestacional e ter inadequado crescimento nos primeiros 12 meses de vida associaram-se com pior crescimento aos 24 meses. CONCLUSÃO: Prematuros de baixo peso nascidos de mães hipertensas têm risco aumentado de sobrepeso aos 24 meses de IC. Ser pequeno para idade gestacional e ter inadequado crescimento no primeiro ano são fatores de risco para distúrbios no crescimento aos 24 meses de IC. .

Mammary and extramammary Paget's disease

Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent.

Practices related to late-onset sepsis in very low-birth weight preterm infants / Práticas relacionadas à sepse tardia em prematuros de muito baixo peso

OBJECTIVE: To understand the practices related to late-onset sepsis (LOS) in the centers of the Brazilian Neonatal Research Network, and to propose strategies to reduce the incidence of LOS. METHODS: This was a cross-sectional descriptive multicenter study approved by the Ethics Committee. Three questionnaires regarding hand hygiene, vascular catheters, and diagnosis/treatment of LOS were sent to the coordinator of each center. The center with the lowest incidence of LOS was compared with the others. RESULTS: All 16 centers answered the questionnaires. Regarding hand hygiene, 87% use chlorhexidine or 70% alcohol; alcohol gel is used in 100%; 80% use bedside dispensers (50% had one dispenser for every two beds); practical training occurs in 100% and theoretical training in 70% of the centers, and 37% train once a year. Catheters: 94% have a protocol, and 75% have a line insertion team. Diagnosis/treatment: complete blood count and blood culture are used in 100%, PCR in 87%, hematological scores in 75%; oxacillin and aminoglycosides is the empirical therapy in 50% of centers. Characteristics of the center with lowest incidence of LOS: stricter hand hygiene; catheter insertion and maintenance groups; use of blood culture, PCR, and hematological score for diagnosis; empirical therapy with oxacillin and aminoglycoside. CONCLUSION: The knowledge of the practices of each center allowed for the identification of aspects to be improved as a strategy to reduce LOS, including: alcohol gel use, hand hygiene training, implementation of catheter teams, and wise use of antibiotic therapy. .

OBJETIVO: Conhecer as práticas relacionadas a sepse tardia (ST) nos centros da Rede Brasileira de Pesquisas Neonatais (RBPN) e propor estratégias para redução da ST. MÉTODOS: Estudo transversal, multicêntrico da RBPN, aprovado pelo CEP. Três questionários sobre higienização das mãos, cateteres vasculares e diagnóstico/tratamento da ST foram elaborados e enviados aos coordenadores de cada centro. O centro com a menor incidência de ST foi comparado aos demais. RESULTADOS: Todos os 16 centros responderam aos questionários. Quanto à higienização das mãos: 87% usam chlorhexidine ou álcool 70%; 100% álcool gel; almotolia/leito em 80% (50% dispõem de um dispensador para cada dois leitos); Treinamento prático ocorre em 100%, teórico em 70% dos centros e 37% treinam uma vez/ano. Cateteres: 94% têm protocolo para passagem, 75% grupo de inserção. Diagnóstico/tratamento: hemograma e hemocultura são usados em 100% dos centros; PCR em 87%; 75% usam escores hematológicos; oxacilina e aminoglicosídeo são usados como terapia empírica em 50% dos centros. Características do centro com menor incidência de ST: rigorosa higienização das mãos; grupos de inserção e manutenção de cateteres; uso de hemocultura, PCR e escores hematológicos para diagnóstico da ST; tratamento empírico com oxacilina e aminoglicosídeo. CONCLUSÕES: O conhecimento das práticas de cada centro permitiu identificar aspectos a serem aprimorados como estratégia para a redução da ST incluindo: uso de álcool gel, treinamento em higienização das mãos, implantação de grupos de cateteres e uso racional de antibióticos. .

Potencial inseticida de óleos essenciais sobre Tribolium castaneum em milho armazenado / Insecticidal potential of essential oils on Tribolium castaneum in stored maize

RESUMO O presente trabalho teve como objetivo investigar o potencial inseticida de óleos essenciais de Croton heliotropiifolius, Croton pulegiodorus, Myracrodruon urundeuva e Ocimumbasilicum sobre adultos de Tribolium castaneumem milho armazenado. Para cada óleo foram realizados bioensaios de fumigação, repelência e o efeito sobre a taxa instantânea de crescimento (ri), em cinco concentrações (0; 5; 10; 15 e 20 μL). Os bioensaios foram conduzidos sob condições constantes de temperatura (28±2 ºC), umidade relativa (70±5%) e escoto fase de 24 horas. Nos testes de fumigação diferentes concentrações dos óleos foi aplicado em tiras de papel filtro presas na parte inferior da tampa da câmara de fumigação (1,5L), a qual continha 20 gramas de substrato alimentar e 10 insetos adultos de T. castaneum não sexados. A mortalidade dos insetos foi avaliada após 48 horas de exposição. Os testes de repelência foram efetuados em arenas compostas por dois frascos ligados a uma caixa central. Em um frasco foi depositado o substrato alimentar com diferentes concentrações do óleo essencial, e, no outro, foi depositado apenas alimento (testemunha). Dez insetos adultos foram liberados na caixa central, ficando expostos por 5 dias para avaliação da preferência. Nos bioensaios de fumigação observou-se atividade inseticida do óleo essencial de M. urundeuva sobre adultos de T. castaneum. Nos bioensaios de repelência, todos os óleos testados apresentaram efeito repelente. A emergência de T. castaneumreduziu entre 33 e 100% quando foram criados em pó de milho tratado com os óleos essenciais. Os óleos essenciais de C. pulegiodorus e O. basilicum ocasionaram redução do crescimento populacional de T. castaneum em grãos de milho tratados. Os óleos testados demonstraram ser uma alternativa eficiente de controle para o uso nos programas de manejo de T. castaneum em unidades armazenadoras.

ABSTRACT The current work aimed at to investigate the insecticide potential of essential oils of Croton heliotropiifolius, Croton pulegiodorus, Myracrodruon urundeuva and Ocimum basilicum on adults of Tribolium castaneum in stored maize. For each oil, it were performed fumigation tests, repellency and the effect on the instantaneous rate of increase (ri), in five concentrations (0; 5; 10; 15 e 20 μL). Bioassays were carried out under constant temperature conditions (28±2 °C), relative humidity (70±5%) and scot phase of 24 hours. In fumigation different concentrations of test oils were applied on filter paper strips attached on the bottom of the fumigation chamber cover (1.5 L), which contained 20 grams of food substrate and 10 unsexed adults of T. castaneum. The insect mortality was recorded after 48 hours of exposure. The repellency tests were performed in arenas composed of two pots connected to a central box. In a pot it was deposited feed substrate, with concentrations of the essential oil, in the other pot (control) it was deposited only food. Ten adult insects were released in the central box, being exposed for 5 days to evaluate the preference. In the fumigation tests, insecticide activity of the essential oil of M. urundeuva was observed on adults of T. castaneum. In the repellency tests, all the tested oils presented repellent effect. The emergency of T. castaneumreduced between 33% and 100% when they were in the powdered maize treated with the essential oils. Maize grains treated with C. pulegiodorus and O. basilicum essential oils caused a significant decrease in the populations of T. castaneum. The tested oils proved to be an efficient control alternative for the use in managing programs of T. castaneum in storing units.

Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus / Efeitos da abordagem terapêutica da persistência de canal arterial sobre a evolução neonatal de recém-nascidos de extremo baixo peso

OBJECTIVE: To analyze the effects of treatment approach on the outcomes of newborns (birth weight [BW] < 1,000 g) with patent ductus arteriosus (PDA), from the Brazilian Neonatal Research Network (BNRN) on: death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH III/IV), retinopathy of prematurity requiring surgical (ROPsur), necrotizing enterocolitis requiring surgery (NECsur), and death/BPD. METHODS: This was a multicentric cohort study, retrospective data collection, including newborns (BW < 1000 g) with gestational age (GA) < 33 weeks and echocardiographic diagnosis of PDA, from 16 neonatal units of the BNRN from January 1, 2010 to Dec 31, 2011. Newborns who died or were transferred until the third day of life, and those with presence of congenital malformation or infection were excluded. Groups: G1 - conservative approach (without treatment), G2 - pharmacologic (indomethacin or ibuprofen), G3 - surgical ligation (independent of previous treatment). Factors analyzed: antenatal corticosteroid, cesarean section, BW, GA, 5 min. Apgar score < 4, male gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II), respiratory distress syndrome (RDS), late sepsis (LS), mechanical ventilation (MV), surfactant (< 2 h of life), and time of MV. Outcomes: death, O2 dependence at 36 weeks (BPD36wks), IVH III/IV, ROPsur, NECsur, and death/BPD36wks. Statistics: Student's t-test, chi-squared test, or Fisher's exact test; Odds ratio (95% CI); logistic binary regression and backward stepwise multiple regression. Software: MedCalc (Medical Calculator) software, version 12.1.4.0. p-values < 0.05 were considered statistically significant. RESULTS: 1,097 newborns were selected and 494 newborns were included: G1 - 187 (37.8%), G2 - 205 (41.5%), and G3 - 102 (20.6%). The highest mortality was observed in G1 (51.3%) and the lowest in G3 (14.7%). The highest frequencies of BPD36wks (70.6%) ...

OBJETIVO: Analisar os efeitos da terapêutica adotada para o canal arterial (CA) em recém-nascidos (RN) < 1.000gadmitidos em unidades neonatais (UN) da Rede Brasileira de Pesquisas Neonatais (RBPN), sobre os desfechos: óbito, displasia broncopulmonar (DBP), hemorragia intraventricular grave (HIVIII/IV), retinopatia da prematuridade cirúrgica (ROPcir), enterocolite necrosante cirúrgica (ECNcir) e o desfecho combinado óbito e DBP. MÉTODOS: Estudo multicêntrico, de coorte, coleta de dados retrospectiva, incluindo RN de 16 UN da RBPN de 01/01/2010 a 31/12/2011, PN < 1.000 g, idade gestacional (IG) < 33 semanas e diagnóstico ecocardiográfico de PCA. Excluídos: óbitos ou transferências até o terceiro dia de vida, infecções congênitas ou malformações. Grupos:G1 - conservadora (sem intervenção medicamentosa ou cirúrgica), G2 - farmacológica (indometacina ou ibuprofeno) e G3 - cirúrgico (com ou sem tratamento farmacológico anterior). Analisou-se: uso de esteroide antenatal, parto cesárea, PN, IG, Apgar5' < 4, sexo masculino, SNAPPE II, síndrome do dDesconforto respiratório (SDR), sepse tardia, ventilação mecânica (VM), surfactante < 2 horas de vida, tempo de VM e os desfechos: óbito, dependência de oxigênio com 36 semanas (DBP36s), HIV III/IV, ROPcir, ECNcir e óbito/DBP36s. Estatística: Teste t-Student, Qui-Quadrado ou teste Exato de Fisher. Testes de Regressão Binária Logística e Regressão Múltipla Stepwise Backward. MedCalc (Medical Calculator) software, versão 12.1.4.0.p < 0,05. RESULTADOS: Foram selecionados 1.097 RN e 494 foram incluídos: G1-187 (37,8%), G2-205 (41,5%) e G3-102 (20,6%). Verificou-se: maior mortalidade (51,3%) no G1 e menor no G3(14,7%); maior frequência DBP36s (70,6%) e ROPcir (23,5%) ...

Cinética do P nos tecidos de suínos em crescimento alimentados com dietas formuladas de acordo com o conceito de proteína ideal e suplementadas com enzima fitase / Phosphorus kinetic in growing pigs tissue fed diets formulated according to the ideal protein concept and supplemented with phytase enzyme

O presente estudo foi desenvolvido para avaliar os efeitos da enzima fitase sobre a cinética do P nos tecidos de suínos, alimentados com dietas formuladas de acordo com o conceito de proteína ideal e suplementadas com enzima fitase. Foram utilizados 20 suínos machos castrados, distribuídos em um delineamento em blocos ao acaso, com cinco tratamentos e quatro repetições. Os animais foram alojados em gaiolas metabólicas durante 17 dias, sendo 10 dias para adaptação e sete dias para coletas de fezes e urina. Amostras de sangue foram coletadas por cinco dias. No primeiro dia da fase experimental, cada animal recebeu, por via endovenosa, uma solução radioativa com 7,4MBq de 32P. No final do período experimental, os animais foram sacrificados, e amostras de tecidos do músculo (lombo), coração, fígado, rins e ossos foram coletadas. A enzima fitase interferiu na cinética do 32P, levando a uma menor incorporação nos tecidos dos ossos...

This study was developed to evaluate the kinetic of the P in the pigs' tissues, feed diets formulated according the ideal protein concept and supplemented with phytase enzyme. Twenty male pigs were used, distributed in a randomized blocks experimental design, with five treatments and four replicates. The animals were housed in metabolic cages for 17 days, with 10 days for adaptation and 7 days for collection of feces and urine. Blood samples were collected in 5 days. On first day of the experimental phase, each animal was intravenously injected with 7.4 MBq 32P. At the end of the experiment the animals were slaughtered and samples of muscle (loin), heart, liver, kidney and bones were collected. The enzyme fitase interfered in the kinetics of 32P, leading to a smaller incorporation of bone tissues...

Parâmetros nutricionais e padrões nictemeral do comportamento ingestivo de cordeiros Somalis Brasileira alimentados com diferentes níveis de energia metabolizável / Nutritional parameters and nycterohemeral patterns of ingestive behavior of Brazilian Somali lambs fed different levels of metabolizable energy

O presente estudo foi conduzido para determinar o consumo e a digestibilidade dos nutrientes, bem como o comportamento ingestivo de cordeiros Somalis Brasileira, alimentados com diferentes níveis de energia metabolizável (EM). Foram utilizados 40 animais, não castrados, com peso vivo médio de 13,47±1,76kg. Os animais foram distribuídos em delineamento em blocos ao acaso, com cinco dietas com diferentes níveis de energia metabolizável (1,18; 2,07; 2,25; 2,42 e 2,69Mcal/kg de MS). O consumo de MS, PB, FDN, CF (g/dia), MS (g/kg0,75) e FDN (%PC e g/kg0,75) apresentaram efeito quadrático (P<0,05), assim como os coeficientes de digestibilidade (P<0,05) da PB, da FDN e dos CF. Foi averiguado efeito linear crescente (P<0,05) para digestibilidade da MS, da MO e dos CNF com o aumento da EM na dieta. Os tempos de alimentação e ócio (h/dia) foram influenciados pelos níveis de energia (P<0,05), e as eficiências de alimentação e ruminação (g FDN/h) apresentaram efeito quadrático (P<0,05). Conclui-se que o aumento dos níveis de EM das rações influencia o consumo e a digestibilidade dos nutrientes, bem como o comportamento ingestivo de cordeiros Somalis Brasileira...

The study was conducted to determine the intake, nutrient digestibility and ingestive behavior of Brazilian Somali lambs fed different levels of metabolizable energy (ME). Forty non-castrated Brazilian Somali lambs with average weight of 13.47±1.76kg were used. The animals were assigned to a randomized block design with eight replications per block and five diets with increasing metabolizable energy (1.18, 2.07, 2.25, 2.42 and 2.69 Mcal/kg DM). The quadratic effect (P<0.05) of the ME level was determined for DM, CP, NDF and FC (g/day) and DM (g/kg0,75) and NDF(%PC and g/kg0,75) intake, as well as the digestibility coefficients (P<0.05) for CP, NDF and CF. A linear effect (P<0.05) was observed for digestibility of DM, OM and NFC with the increase of ME in the diet. Eating and idle results (hours/day) were influenced by the energy levels (P<0.05) and efficiencies of feeding and rumination (g NDF/h) showed a quadratic effect (P<0.05). It is concluded that the increase of ME levels in the diet influences intatke, nutrient digestibility and ingestive behavior of Brazilian Somali lambs...

Radioisótopo e modelagem matemática na avaliação da suplementação de fitase em dietas para suínos em crescimento / Radioisotope and mathematical modeling in the assessment of supplementation of Phytase in diets for growing pigs

O objetivo deste trabalho foi avaliar os efeitos da inclusão de níveis crescentes de enzima fitase em dietas para suínos em fase de crescimento, por meio do uso de modelagem matemática. Foram utilizados dados de 20 leitões mestiços, machos castrados, pesando em média, 26,8kg. Os animais ficaram alojados em gaiolas metabólicas individuais para a coleta de fezes e urina, onde permaneceram por um período de 17 dias. Utilizou-se o delineamento experimental de blocos ao acaso, com cinco tratamentos e quatro repetições. A dieta experimental fornecida aos leitões foi à base de milho e farelo de soja, suplementada com cinco níveis crescentes de enzima fitase (0, 250, 500, 750 e 1000UF/kg), correspondendo a 0; 0,01; 0,02; 0,03 e 0,04%, respectivamente. As variáveis avaliadas foram: ingestão, excreção, fluxo e refluxo do P nos compartimentos (trato digestivo, corrente sanguínea, tecidos moles e ossos). A enzima fitase não interferiu no P consumido (P>0,05 (F10), no P excretado na urina (F02), no fluxo e refluxo do P nos ossos (F32 e F23) e nos tecidos moles (F42 e F24), entretanto observou-se redução no P excretado nas fezes (F01) em 8,92%; 26,76%; 22,53% e 28,64% para os níveis 0, 250, 500, 750 e 1000UF/kg, respectivamente, e efeito linear positivo para o P endógeno (F12). Pode-se utilizar dietas à base de milho e farelo de soja com 50% de P por fosfato bicálcico, adicionando-se 250UF/kg de dieta para suínos em crescimento, o que reduz em 27% as excreções de P nas fezes.

The purpose of this study was to evaluate the effects of including increasing levels of phytase enzyme in pig diets for growing pigs, using the mathematical model. Data from 20 crossbred male piglets, castrated and weighing 26.80 kg on average was used. The animals were housed in individual metabolic cages to collect feces and urine in a 17 day period. A randomized block experimental design containing five treatments and four repetitions was used. The experimental diet provided to piglets contained corn and soybean and was supplemented with five increasing levels of phytase enzyme (0, 250, 500, 750 and 1000 UF/kg), corresponding to 0.00 %, 0.01 %, 0.02 %, 0.03 % and 0.04 % respectively. The variables evaluated were: intake, excretion, output flow of P in the digestive tract, bloodstream, bones and soft tissues. The phytase enzyme did not affect the P intake (P>0.05 (F 10), the P excreted in urine (F02) and the output flow of P in the bones (F32 e F23) and soft tissue (F42 e F24) , however, there was a reduction in P excreted in feces (F01) of 8.92 %, 26.76 %, 22.53 % and 28.64 % to the levels 0, 250, 500, 750 e 1000UF/kg, respectively and showed a positive linear effect (P<0.08) for the endogenous P (F12) . Corn and soybean meal based diets can be used with 50% of P by dicalcium phosphate, adding 250UF/kg diet for growing pigs, and may cause a reduction of 27 % of P excretion in feces.