Ocular and systemic bio-distribution of rhodamine-conjugated liposomes loaded with VIP injected into the vitreous of Lewis rats.

PURPOSE: Local delivery of therapeutic molecules encapsulated within liposomes is a promising method to treat ocular inflammation. The purpose of the present study was to define the biodistribution of rhodamine-conjugated liposomes loaded with vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, following their intravitreal (IVT) injection in normal rats. METHODS: Healthy seven- to eight-week-old Lewis male rats were injected into the vitreous with empty rhodamine-conjugated liposomes (Rh-Lip) or with VIP-loaded Rh-Lip (VIP-Rh-Lip; 50 mM of lipids with an encapsulation efficiency of 3.0+/-0.4 mmol VIP/mol lipids). Twenty-four h after IVT injection, the eyes, the cervical, mesenteric, and inguinal lymph nodes (LN), and spleen were collected. The phenotype and distribution of cells internalizing Rh-Lip and VIP-Rh-Lip were studied. Determination of VIP expression in ocular tissues and lymphoid organs and interactions with T cells in cervical LN was performed on whole mounted tissues and frozen tissue sections by immunofluorescence and confocal microscopy. RESULTS: In the eye, 24 h following IVT injection, fluorescent liposomes (Rh-Lip and VIP-Rh-Lip) were detected mainly in the posterior segment of the eye (vitreous, inner layer of the retina) and to a lesser extent at the level of the iris root and ciliary body. Liposomes were internalized by activated retinal Müller glial cells, ocular tissue resident macrophages, and rare infiltrating activated macrophages. In addition, fluorescent liposomes were found in the episclera and conjunctiva where free VIP expression was also detected. In lymphoid organs, Rh-Lip and VIP-Rh-Lip were distributed almost exclusively in the cervical lymph nodes (LN) with only a few Rh-Lip-positive cells detected in the spleen and mesenteric LN and none in the inguinal LN. In the cervical LN, Rh-Lip were internalized by resident ED3-positive macrophages adjacent to CD4 and CD8-positive T lymphocytes. Some of these T lymphocytes in close contact with macrophages containing VIP-Rh-Lip expressed VIP. CONCLUSIONS: Liposomes are specifically internalized by retinal Müller glial cells and resident macrophages in the eye. A limited passage of fluorescent liposomes from the vitreous to the spleen via the conventional outflow pathway and the venous circulation was detected. The majority of fluorescent liposomes deposited in the conjunctiva following IVT injection reached the subcapsular sinus of the cervical LN via conjuntival lymphatics. In the cervical LN, Rh-Lip were internalized by resident subcapsular sinus macrophages adjacent to T lymphocytes. Detection of VIP in both macrophages and T cells in cervical LN suggests that IVT injection of VIP-Rh-Lip may increase ocular immune privilege by modulating the loco-regional immune environment. In conclusion, our observations suggest that IVT injection of VIP-loaded liposomes is a promising therapeutic strategy to dampen ocular inflammation by modulating macrophage and T cell activation mainly in the loco-regional immune system.

The A-kinase anchoring protein (AKAP)-Lbc-signaling complex mediates alpha1 adrenergic receptor-induced cardiomyocyte hypertrophy.

In response to various pathological stresses, the heart undergoes a pathological remodeling process that is associated with cardiomyocyte hypertrophy. Because cardiac hypertrophy can progress to heart failure, a major cause of lethality worldwide, the intracellular signaling pathways that control cardiomyocyte growth have been the subject of intensive investigation. It has been known for more than a decade that the small molecular weight GTPase RhoA is involved in the signaling pathways leading to cardiomyocyte hypertrophy. Although some of the hypertrophic pathways activated by RhoA have now been identified, the identity of the exchange factors that modulate its activity in cardiomyocytes is currently unknown. In this study, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor activity, is critical for activating RhoA and transducing hypertrophic signals downstream of alpha1-adrenergic receptors (ARs). In particular, our results indicate that suppression of AKAP-Lbc expression by infecting rat neonatal ventricular cardiomyocytes with lentiviruses encoding AKAP-Lbc-specific short hairpin RNAs strongly reduces both alpha1-AR-mediated RhoA activation and hypertrophic responses. Interestingly, alpha1-ARs promote AKAP-Lbc activation via a pathway that requires the alpha subunit of the heterotrimeric G protein G12. These findings identify AKAP-Lbc as the first Rho-guanine nucleotide exchange factor (GEF) involved in the signaling pathways leading to cardiomyocytes hypertrophy.

Effect of controlled co-delivery of synergistic neurotrophic factors on early nerve regeneration in rats.

Present interventions to repair severed peripheral nerves provide slow and poor early axonal regeneration, which may cause unsatisfactory functional reinnervation. To improve early axonal regeneration in a 10 mm rat sciatic nerve gap model, we developed collagen nerve conduits loaded with the synergistically acting glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). For controlling the concomitant GDNF and NGF release, the collagen tubes were cross-linked by a dehydro-thermal treatment (110 degrees C; 20 mbar; 5 days) prior to impregnating the tubes with GDNF and NGF and by coating drug-loaded tubes with layers of poly(lactide-co-glycolide). The conduits made of cross-linked collagen released low initial amounts of GDNF and NGF (2% of both during first 3 days) and enhanced significantly the early (2 weeks) nerve regeneration in terms of axonal outgrowth and Schwann cell migration in a 10 mm rat sciatic nerve gap model, as compared to the conduits made of non-cross-linked collagen releasing higher initial amounts of GDNF and NGF (12-16% within 3 days), or those releasing GDNF alone. The enhancement of early axonal regeneration using controlled co-delivery of multiple synergistic neurotrophic factors is an important requisite for eventually establishing functional connections with the target organ.

Conhecimento e percepção dos profissionais a respeito do ruído na unidade neonatal

O objetivo deste estudo foi verificar o conhecimento e a percepção de profissionais de Unidade de Terapia Intensiva Neonatal (UTIN) sobre as repercussões do ruído ao neonato, família e profissionais, antes da implementação de um programa educativo. Trata-se de uma pesquisa descritiva, quantitativa, realizada em Unidade de Terapia Intensiva Neonatal de um hospital de São Paulo, com 101 profissionais. Foram utilizados: questionário para a coleta de dados, e os testes de Qui-quadrado e t de Student para a associação entre as variáveis. Os profissionais identificaram a UTIN como muito ruidosa (44,9%), perceberam os efeitos desse ruído durante e após a jornada de trabalho (67,4%) e utilizaram estratégias para amenizá-lo. Embora os profissionais desconheçam a legislação sobre o ruído no ambiente hospitalar, identificaram repercussões para si, recém-nascido e família. Os resultados apontaram para a necessidade de orientar a equipe quanto à legislação, prevenção de ruído e reorganização das práticas assistenciais e estrutura física da Unidade de Terapia Intensiva Neonatal.

Mortalidade pós-neonatal no território brasileiro: uma revisão da literatura

O presente trabalho trata-se de revisão sistemática, referente ao período de 2004 a 2009, sobre o tema mortalidade pós-neonatal. Teve o objetivo de identificar como se colocam na literatura, as causas da morte e a relação com as condições socioeconômicas. Foram selecionados 27 artigos, 74,4% publicados em periódicos da área da Saúde Pública e 66,7%, de desenho do tipo ecológico. Quase a totalidade versava sobre grupos de causas e seus componentes (66,7%), seguidos pelo terço restante, sobre a identificação dos fatores determinantes dos óbitos. A região Sudeste produziu mais de 37% dos estudos. Na maioria dos municípios e estados brasileiros, a redução superou 50% no final da década de 1990. Dentre os grupos de causas de óbitos, predominou o grupamento diarreia-pneumonia, seguido pelas malformações congênitas. As condições de vida segundo indicadores socioeconômicos - moradia, saneamento básico, educação e acesso à saúde - foram determinantes para os maiores índices de mortalidade pós-neonatal por causas passíveis de redução.

Fatores determinantes da mortalidade neonatal em um município da Região Sul do Brasil

Pesquisa quantitativa do tipo ecológico cujo objetivo foi identificar os fatores de risco que determinaram o óbito neonatal no município de Londrina, Paraná, entre 2000 e 2009. Verificou-se que idade materna, escolaridade, renda familiar, ocupação, situação conjugal, tipo de parto e número de consultas pré-natais não se associaram ao óbito neonatal. Entretanto, o peso ao nascer, a idade gestacional, o índice de Apgar no 1º e 5º minutos e local do parto mostraram-se estatisticamente significativos. Mais de 73,0% dos recém-nascidos evoluíram para óbito no período neonatal precoce. A causa básica predominante foi a afecção perinatal (77,7%), sendo que 72,6% das mortes foram consideradas evitáveis e a maioria, reduzível por controle adequado da gravidez e do parto. Tais resultados reforçam a necessidade de investimentos na prevenção do parto prematuro com assistência antenatal e ao parto equitativa, acessível e integral entre os diferentes níveis de atenção à saúde materno-infantil.

Fatores associados à infecção pelo uso do cateter central de inserção periférica em Unidade de Terapia Intensiva Neonatal

Estudo epidemiológico, longitudinal e analítico, desenvolvido em um hospital de Minas Gerais, com o objetivo de analisar os fatores associados à infecção pelo uso do cateter central de inserção periférica em recém-nascidos internados em unidade de terapia intensiva. A coleta dos dados foi realizada por meio de uma ficha estruturada, preenchida pelos profissionais e verificada pelos pesquisadores. Foram estudados 291 cateteres inseridos em 233 recém-nascidos. Os fatores associados à retirada por suspeita de infecção foram: prematuridade, peso ao nascer até 1.500 gramas, cateter de poliuretano, localização não centralizada do cateter e tempo de uso superior a 30 dias. Após ajuste multivariado, permaneceram independentemente associados: peso inferior a 2.500 gramas na inserção, reparo e tempo de uso do cateter. Conclui-se que fatores relacionados à prática dos profissionais contribuíram para a retirada dos cateteres, sinalizando para a necessidade de intervenções que melhorem a segurança e a eficácia em seu uso.

O processo do cateterismo venoso central em Unidade de Terapia Intensiva Neonatal e Pediátrica

Estudo descritivo, longitudinal e abordagem quantitativa, que objetivou analisar e discutir o processo do cateterismo venoso central nas Unidades de Terapia Intensiva neonatal e pediátrica; descrever as variáveis relacionadas à caracterização da população do estudo (unidade de internação, faixa etária e sexo) e descrever as variáveis relacionadas ao processo do cateterismo venoso central (tipo de cateter, motivo de indicação, número de lumens, sítio de inserção, profissional que realizou o procedimento, terapêutica medicamentosa infundida via cateter, motivo de retirada, tempo de permanência e as complicações mecânicas e infecciosas). A coleta de dados foi realizada em unidade de terapia intensiva neonatal e pediátrica, em 82 prontuários. As indicações dos cateteres foram, em sua maioria, para infusão medicamentosa prolongada e Nutrição Parenteral Total. A remoção foi indicada predominantemente por complicações mecânicas e infecciosas. Esse estudo viabilizou rever a prática assistencial para estabelecer o aprimoramento da assistência prestada à clientela neonatal e pediátrica.

Human milk for neonatal pain relief during ophthalmoscopy

Ophthalmoscopy performed for the early diagnosis of retinopathy of prematurity (ROP) is painful for preterm infants, thus necessitating interventions for minimizing pain. The present study aimed to establish the effectiveness of human milk, compared with sucrose, for pain relief in premature infants subjected to ophthalmoscopy for the early diagnosis of ROP. This investigation was a pilot, quasi-experimental study conducted with 14 premature infants admitted to the neonatal intensive care unit (NICU) of a university hospital. Comparison between the groups did not yield a statistically significant difference relative to the crying time, salivary cortisol, or heart rate (HR). Human milk appears to be as effective as sucrose in relieving acute pain associated with ophthalmoscopy. The study’s limitations included its small sample size and lack of randomization. Experimental investigations with greater sample power should be performed to reinforce the evidence found in the present study.

A manipulacao de prematuros em uma Unidade de Terapia Intensiva Neonatal

Os prematuros são submetidos a diversas manipulações e procedimentos durante internação em unidades neonatais, com consequências deletérias para a saúde. O objetivo do presente estudo foi descrever a manipulação a que são submetidos os prematuros durante as 24 horas em uma unidade de terapia intensiva neonatal (UTIN). Estudo observacional, descritivo, exploratório, realizado com 20 prematuros, filmados continuamente por um período de 24 horas, de setembro de 2008 a março de 2009 numa UTIN. Os prematuros foram submetidos a uma média de 768 manipulações e 1.341 procedimentos. A manipulação durou em média 2 horas e 26 minutos em um período de 24 horas. Cada manipulação agrupou uma média de 2,2 procedimentos, a maioria no turno matutino As manipulações isoladas representaram 65,6% do total de manipulações e a maioria teve duração inferior a um minuto. Conclui-se que nas 24 horas avaliadas, os prematuros foram submetidos a um excesso de manipulações na UTIN.

Intimate Partner Violence Against Pregnant Women: Study About The Repercussions On The Obstetric And Neonatal Results

This observational, descriptive and analytic study aimed to identify the prevalence of IPV cases among pregnant women and classify them according to the type and frequency; identify the obstetric and neonatal results and their associations with the intimate partner violence (IPV) occurrence in the current pregnancy. It was developed with 232 pregnant women who had prenatal care at a public maternity hospital. Data were collected via structured interview and in the patients’ charts and analyzed through the statistic software SAS® 9.0. Among the participants, 15.5% suffered IPV during pregnancy, among that 14.7% suffered psychological violence, 5.2% physical violence and 0.4% sexual violence. Women who did not desire the pregnancy had more chances of suffering IPV (p<0.00; OR=4.32 and 95% CI [1.77 – 10.54]). With regards to the obstetric and neonatal repercussions, there was no statistical association between the variables investigated. Thus, for the study participants there were no negative obstetric and neonatal repercussions related to IPV during pregnancy.

Stimulation by leptin of 3H GDP binding to brown adipose tissue of fasted but not fed rats.

OBJECTIVES: To assess the effects of intracerebroventricular (i.c.v.) leptin administration on rats fed ad libitum or fasted on 3H GDP binding to brown adipose tissue (BAT). SUBJECTS: Groups of 5-6 ten-week-old male Wistar rats. EXPERIMENTAL DESIGN: An i.c.v. cannula was inserted and unilateral denervation of interscapular brown adipose tissue (BAT) was performed 5 d before each study. Thereafter, leptin was infused i.c.v. during 72 h while rats were fed ad libitum or fasted. Vehicle-infused, pair-fed or fasted rats were used as controls. MEASUREMENTS: 3H GDP binding to innervated and denervated BAT mitochondria. RESULTS: 3H GDP binding to innervated or denervated BAT of rats fed ab libitum compared to vehicle-infused, pair-fed rats was not increased by i.c.v. leptin. 3H GDP binding was lower in fasted than in fed rats, and the difference was larger in innervated than denervated BAT. I.c.v. leptin increased 3H GDP binding by 30% in innervated, and by 51% in denervated BAT (P < 0.05) in fasted rats. CONCLUSIONS: I.c.v. leptin does not increase 3H GDP binding to BAT of rats fed ad libitum compared to pair-fed (food-restricted) rats. In contrast, i.c.v. leptin produces a mild stimulation of 3H GDP binding to BAT of fasted rats. This effect is not mediated by the sympathetic nervous system, because it is observed in both innervated and denervated BAT. These results are compatible with the concept that, in fasting rats, the decrease in leptin secretion contributes to the reduction in 3H GDP binding to BAT mitochondria.

Neonatal mortality in infants with low birth weigh

Objective To evaluate the factors associated with neonatal mortality in infant born with low birth weight. Method Cross-sectional study that analyzed data from 771 live births with low birth weight (<2500 g) in the city of Cuiabá, MT, in 2010, of whom 54 died in the neonatal period. We obtained data from the Information System on Live Births and Mortality, by integrated linkage. Results In multiple logistic regression, neonatal mortality was associated with: number of prenatal visits less than 7 (OR=3.80;CI:1,66-8,70); gestational age less than 37 weeks (OR=4.77;CI:1.48-15.38), Apgar score less than 7 at the 1st minute (OR=4.25;CI:1.84-9.81) and the 5th minute (OR=5.72,CI:2.24-14.60) and presence of congenital anomaly (OR=14.39;IC:2.72-76.09). Conclusion Neonatal mortality in infants with low birth weight is associated with avoidable factors through adequate attention to prenatal care, childbirth and infants.


Evaluation of digital educational studenttechnology interaction in neonatal nursing

OBJECTIVE To assess the digital educational technology interface Caring for the sensory environment in the neonatal unit: noise, lighting and handling based on ergonomic criteria. METHODS Descriptive study, in which we used the guidelines and ergonomic criteria established by ISO 9241-11 and an online Likert scale instrument to identify problems and interface qualities. The instrument was built based on Ergolist, which follows the criteria of ISO 9141-11. There were 58 undergraduate study participants from the School of Nursing of Ribeirao Preto, University of Sao Paulo, who attended the classes about neonatal nursing content. RESULTS All items were positively evaluated by more than 70% of the sample. CONCLUSION Educational technology is appropriate according to the ergonomic criteria and can be made available for teaching nursing students.

Blood pressure and renin-angiotensin system resetting in transgenic rats with elevated plasma Val5-angiotensinogen.

OBJECTIVE: : Increases in plasma angiotensinogen (Ang-N) due to genetic polymorphisms or pharmacological stimuli like estrogen have been associated with a blood pressure (BP) rise, increased salt sensitivity and cardiovascular risk. The relationship between Ang-N, the resetting of the renin-angiotensin system, and BP still remains unclear. Angiotensin (Ang) II-induced genetic hypertension should respond to lisinopril treatment. METHODS: : A new transgenic rat line (TGR) with hepatic overexpression of native (rat) Ang-N was established to study high plasma Ang-N. The transgene contained a mutation producing Val-Ang-II, which was measured separately from nontransgenic Ile-Ang-II in plasma and renal tissue. RESULTS: : Male homozygous TGR had increased plasma Ang-N (∼20-fold), systolic BP (ΔBP + 26 mmHg), renin activity (∼2-fold), renin activity/concentration (∼5-fold), total Ang-II (∼2-fold, kidney 1.7-fold) but decreased plasma renin concentrations (-46%, kidney -85%) and Ile-Ang-I and II (-93%, -94%) vs. controls. Heterozygous TGR exhibited ∼10-fold higher plasma Ang-N and 17 mmHg ΔBP. Lisinopril decreased their SBP (-23 vs. -13 mmHg in controls), kidney Ang-II/I (∼3-fold vs. ∼2-fold) and Ile-Ang-II (-70 vs. -40%), and increased kidney renin and Ile-Ang-I (>2.5-fold vs. <2.5-fold). Kidney Ang-II remained higher and renin lower in TGR compared with controls. CONCLUSION: : High plasma Ang-N increases plasma and kidney Ang-II levels, and amplifies the plasma and renal Ang-II response to a given change in renal renin secretion. This enzyme-kinetic amplification dominates over the Ang-II mediated feedback reduction of renin secretion. High Ang-N levels thus facilitate hypertension via small increases of Ang II and may influence the effectiveness of renin-angiotensin system inhibitors.