Factors associated with non-treatment of hypertension and gender differences at baseline in the ELSA-Brasil cohort

The treatment of arterial hypertension (AH) contributes to the reduction of morbidity and mortality. Gender differences are likely to play a role, as non-treatment is associated with clinical and sociodemographic aspects. The aim of this study was to investigate the factors associated with non-treatment of AH and gender differences in hypertensive individuals from the ELSA-Brasil cohort. The study was conducted with 5,743 baseline hypertensive cohort participants. AH was considered if there was a previous diagnosis or if systolic blood pressure (SBP) was ≥140 and/or diastolic BP (DBP) was ≥90 mmHg. Sociodemographic and anthropometric data, lifestyle, comorbidities, and use of antihypertensive medications were evaluated through interviews and in-person measurements. Treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) or other antihypertensive medications and non-treatment were evaluated with multivariate logistic regression. Non-treatment was observed in 32.8% of hypertensive individuals. Of the 67.7% treated individuals, 41.1% received RAASi. Non-treatment was associated with alcohol consumption in women (OR=1.41; 95%CI: 1.15-1.73; P=0.001), lowest schooling level in men (OR=1.70; 95%CI: 1.32-2.19; P<0.001), and younger age groups in men and women (strongest association in males aged 35-44 years: OR=4.58, 95%CI: 3.17-6.6, P<0.001). Among those using RAASi, a higher proportion of white, older individuals, and with more comorbidities was observed. The high percentage of non-treatment, even in this civil servant population, indicated the need to improve the treatment cascade for AH. Public health policies should consider giving special attention to gender roles in groups at higher risk of non-treatment to reduce inequities related to AH in Brazil.

Accuracy of orthognathic surgery with customized titanium plates-Systematic review.

This systematic review aimed to evaluate the accuracy of customized titanium plates in orthognathic surgery compared to standard outcome in virtual surgical planning. PRISMA and JBI guidelines were followed. Research protocol was registered in PROSPERO. Six databases and two gray literature repositories were used as sources of research articles. Descriptive clinical studies, that performed orthognathic surgery using custom titanium plates, were included. Risk of bias was assessed by "The Joanna-Briggs Institute Critical Appraisal tools for use in Systematic Reviews Checklist for Case Series". Of the 11,916 studies initially identified, seven met the eligibility criteria and were included. The studies were published between 2015 and 2019. Most of the studies (57%) had a low risk of bias, while one had a high risk of bias. Total sample included 74 patients with 63 bimaxillary surgeries and 11 unimaxillary surgeries. All studies showed acceptable accuracy within previously established clinical parameters. Although the eligible articles assessed the accuracy of the orthognathic surgery with respect to virtual planning, the wide variability of evaluation methodologies made it impossible to calculate a combined accuracy measure. It was not possible to perform a meta-analysis, so a pragmatic recommendation on the use of these plates is not possible.

3D printing of canine hip dysplasia: anatomic models and radiographs / Impressão 3D da displasia coxofemoral canina: modelos anatômicos e radiografias

Canine Hip Dysplasia (CHD) is a highly prevalent articular pathological condition. In this sense, radiography becomes an important diagnostic method to determine the presence and severity of the disease. The objective was to create 3D models and their respective radiographs representing the CHD (3D AMCHD). The research was carried out in the Laboratory of 3D Educational Technologies of UFAC, under no. 23107.007273/2017-49 (CEUA/UFAC). A canine skeleton (hip bone, femurs and patellae) was used without anatomical deformities compatible with DCF (pelvis, femurs and patella), which were scanned in order to obtain the files of the base model. In these files the deformations representing the different degrees of CHD were performed. Subsequently, the 3D AMCHD files were printed, mounted and X-rayed. The 3D AMCHD represented the bone deformations of the different degrees of CHD. In the radiographs of the 3D AMCHD it was possible to observe and determine each of the bones that constituted the hip joints. This allowed to reproduce the correct positioning to represent the CHD diagnosis and establish the precise points to determine the Norberg angle. In this way, it was evidenced that the 3D AMCHD can be a possible tool to be used in the Teaching of Veterinary Medicine.(AU)

A displasia coxofemoral canina (DCF) é uma condição patológica articular de grande prevalência. Nesse sentido, a radiografia torna-se um método de diagnóstico importante para determinar a presença e a gravidade da doença. O objetivo do presente trabalho foi criar modelos 3D e suas respectivas radiografias representando a DCF (MADCF 3D). A pesquisa foi realizada no Laboratório de Tecnologias Educacionais 3D da UFAC, sob o nº. 23107.007273/2017-49 (Ceua/Ufac). Foram utilizados esqueletos caninos (pelve, fêmures e patelas) sem deformidades anatômicas compatíveis com a DCF, os quais foram digitalizados a fim de se obterem os arquivos do modelo base. Nesses arquivos foram realizadas as deformações que representavam os diferentes graus da DCF. Posteriormente, os arquivos dos MADCF 3D foram impressos, montados e radiografados. Os MADCF 3D representaram as deformações ósseas dos diferentes graus da DCF. Nas radiografias dos MADCF 3D, foi possível observar e determinar cada um dos ossos que constituíam as articulações coxofemorais. Isso permitiu reproduzir o posicionamento correto para representação do diagnóstico DCF e estabelecer os pontos precisos para determinar o ângulo de Norberg. Dessa forma, evidenciou-se que os MADCF 3D podem ser uma possível ferramenta a ser empregada no ensino de medicina veterinária.(AU)

Avaliação in vitro do sêmen congelado de carneiros com diluidor suplementado com miricetina / In vitro evaluation of ram sperm frozen with extender supplemented with myricetin

O objetivo deste estudo foi avaliar o efeito da suplementação do diluidor de congelação de sêmen ovino com o flavonoide miricetina contra os danos ocasionados aos espermatozoides. Oito pools de sêmen, obtidos de quatro reprodutores ovinos, foram congelados com diferentes concentrações de miricetina (0, 1, 10, 100 e 1000nM). Após o descongelamento, o sêmen foi avaliado quanto à cinética espermática, à integridade das membranas plasmática e acrossomal, ao potencial de membrana mitocondrial, aos níveis de ROS intracelular, à peroxidação lipídica e à estabilidade de membrana. Amostras tratadas com miricetina 10nM apresentaram menor percentual de células rápidas (P≤0,05), quando comparadas ao grupo miricetina 1000nM. Amostras do grupo controle apresentaram maior (P≤0,05) VAP que o grupo 10nM de miricetina, enquanto amostras criopreservadas com miricetina (10, 100 e 1000nM) evidenciaram maior (P<0,05) BCF, quando comparadas ao grupo controle. O grupo tratado com miricetina 1000nM apresentou maior percentual (P<0,05) de células com peroxidação lipídica, quando comparado ao grupo controle. Em conclusão, a suplementação do diluidor de criopreservação de sêmen ovino com 10 e 100nM de miricetina afeta a cinética espermática sem provocar alterações na estrutura geral do gameta, enquanto 1000nM de miricetina provoca mudanças na cinética associadas à danos peroxidativos.(AU)

The aim of this study was to evaluate the effect of the supplementation of ram semen frozen with extender with the flavonoid myricetin against damage to sperm. Eight pools of semen obtained from four ram breeders, were frozen with different concentrations of myicetin (0, 1, 10, 100 and 1000nM). After thawing, the semen was evaluated for spermatic kinetics, plasma and acrosome membrane integrity, mitochondrial membrane potential, intracellular ROS levels, lipid peroxidation, and membrane stability. Samples treated with 10nM myricetin preserved a lower percentage of rapid cells (P≤0.05) when compared to the 1000nM myricetin group. Samples from the control group presented higher (P≤0.05) VAP than 10nM group of myricetin, while cryopreserved samples with myicetin (10, 100 and 1000nM) showed greater (P<0.05) BCF, when compared to control group. The group treated with 1000nM myricetin had a higher percentage (P<0.05) of cells with lipid peroxidation, when compared to the control group. In conclusion, supplementation of ram semen cryopreservation extender with 10 and 100nM myricetin affects sperm kinetics, without causing changes in the overall structure of the gamete, while 1000nM myricetin causes changes in the kinetics associated with peroxidative damage.(AU)

Fasting: a major limitation for resistance exercise training effects in rodents

Protocols that mimic resistance exercise training (RET) in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1) untrained control rats, 2) untrained rats submitted to fasting periods, and 3) rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks), the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks). After the short-term protocol, cumulative fasting periods promoted loss of weight (P<0.001). After the longer RET protocol, no difference was observed for body mass, extensor digitorum longus (EDL) morphology or skeletal muscle function (P>0.05 for all). Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (P<0.01). Altogether, these data indicate that fasting is a major limitation for RET in rats.

Placebo in sports nutrition: a proof-of-principle study involving caffeine supplementation.

We investigated the effects of supplement identification on exercise performance with caffeine supplementation. Forty-two trained cyclists (age 37 ± 8 years, body mass [BM] 74.3 ± 8.4 kg, height 1.76 ± 0.06 m, maximum oxygen uptake 50.0 ± 6.8 mL/kg/min) performed a ~30 min cycling time-trial 1 h following either 6 mg/kgBM caffeine (CAF) or placebo (PLA) supplementation and one control (CON) session without supplementation. Participants identified which supplement they believed they had ingested ("caffeine", "placebo", "don't know") pre- and post-exercise. Subsequently, participants were allocated to subgroups for analysis according to their identifications. Overall and subgroup analyses were performed using mixed-model and magnitude-based inference analyses. Caffeine improved performance vs PLA and CON (P ≤ 0.001). Correct pre- and post-exercise identification of caffeine in CAF improved exercise performance (+4.8 and +6.5%) vs CON, with slightly greater relative increases than the overall effect of caffeine (+4.1%). Performance was not different between PLA and CON within subgroups (all P > 0.05), although there was a tendency toward improved performance when participants believed they had ingested caffeine post-exercise (P = 0.06; 87% likely beneficial). Participants who correctly identified placebo in PLA showed possible harmful effects on performance compared to CON. Supplement identification appeared to influence exercise outcome and may be a source of bias in sports nutrition.

Correlation between heart rate variability and pulmonary function adjusted by confounding factors in healthy adults

The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincaré plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders.

Correlation between heart rate variability and pulmonary function adjusted by confounding factors in healthy adults.

The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincaré plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders.

Avaliação da atividade larvicida do óleo essencial do Zingiber officinale Roscoe (gengibre) frente ao mosquito Aedes aegypti / Evaluation of the larvicidal effectof the essential oil of Zingiber officinale Roscoe (ginger) against the mosquito Aedes aegypti

RESUMO Este trabalho analisa o efeito larvicida do óleo Zingiber officinale Roscoe contra larvas em terceiro estágio do mosquito Aedes aegypti. Extraiu-se quantitativamente o óleo essencial por hidrodestilação e calculou-se a CL50 do óleo, a partir dos métodos de Reed-Muench e Pizzi, respectivamente. O óleo essencial obteve CL50 de 76,07 (±2,24) μg mL-1 e rendimento de 0,52% m/v. Os resultados indicam que o óleo essencial avaliado é composto por substâncias que propiciam efeito larvicida contra Aedes aegypti.

ABSTRACT This study analyzes the larvicidal effect of the oil of Zingiber officinale Roscoe against larvae in third stage of the mosquito Aedes aegypti (Linnaeus 1792). The essential oil was extracted quantitatively by hydrodistillation and we calculated the oil’s LC50 from Reed-Muench (1938) and Pizzi (1950) methods, respectively. The essential oil obtained LC50 of 76.07 (±2.24) ug mL-1, and yield of 0.52% m/v. The results indicate that the essential oil assessed has substances that provide larvicidal effect against Aedes aegypti.

Intensity and physiological responses to the 6-minute walk test in middle-aged and older adults: a comparison with cardiopulmonary exercise testing

The 6-minute walk test (6MWT) is a simple field test that is widely used in clinical settings to assess functional exercise capacity. However, studies with healthy subjects are scarce. We hypothesized that the 6MWT might be useful to assess exercise capacity in healthy subjects. The purpose of this study was to evaluate 6MWT intensity in middle-aged and older adults, as well as to develop a simple equation to predict oxygen uptake ( V ˙ O 2 ) from the 6-min walk distance (6MWD). Eighty-six participants, 40 men and 46 women, 40-74 years of age and with a mean body mass index of 28±6 kg/m2, performed the 6MWT according to American Thoracic Society guidelines. Physiological responses were evaluated during the 6MWT using a K4b2 Cosmed telemetry gas analyzer. On a different occasion, the subjects performed ramp protocol cardiopulmonary exercise testing (CPET) on a treadmill. Peak V ˙ O 2 in the 6MWT corresponded to 78±13% of the peak V ˙ O 2 during CPET, and the maximum heart rate corresponded to 80±23% of that obtained in CPET. Peak V ˙ O 2 in CPET was adequately predicted by the 6MWD by a linear regression equation: V ˙ O 2 mL·min-1·kg-1 = -2.863 + (0.0563×6MWDm) (R2=0.76). The 6MWT represents a moderate-to-high intensity activity in middle-aged and older adults and proved to be useful for predicting cardiorespiratory fitness in the present study. Our results suggest that the 6MWT may also be useful in asymptomatic individuals, and its use in walk-based conditioning programs should be encouraged.

Correlações genéticas entre algumas características de tipo e intervalo de partos em vacas da raça Holandesa / Genetic correlations for some type traits and calving interval in Holstein cows

Estimaram-se correlações genéticas entre algumas características de tipo e intervalo de partos (IP) em vacas da raça Holandesa no Estado do Paraná. Foram analisados registros de conformação de 23.014 vacas, classificadas no período de 2000 a 2010, oriundas de 248 rebanhos, filhas de 797 touros. Os componentes de variância necessários para obtenção das estimativas das herdabilidades e das correlações genéticas foram obtidos pelo método da Máxima Verossimilhança Restrita (REML), utilizando-se o procedimento MIXED do pacote estatístico SAS. As estimativas de herdabilidade para as características de tipo variaram de 0,09 a 0,24 e para IP foi 0,05. As estimativas de correlação genética entre as características de tipo foram, em geral, de pequena magnitude, sendo o maior valor observado entre largura de peito e profundidade corporal (0,52). As estimativas de correlação genética entre as características de tipo e IP foram, em sua maioria, de pequena magnitude. A baixa correlação genética entre ângulo de garupa e IP (0,02) sugere que a seleção para ângulo de garupa pode não ser efetiva em determinar ganho genético para fertilidade.

Genetic correlations between type traits and calving interval (CI) in Holstein cows in Parana State - Brazil were estimated. The data comprised linear classification of 23,014 cows, from 248 herds, classified from 2000 to 2010, daughters of 797 sires. Variance components for heritability and genetic correlation were estimated with Restricted Maximum Likelihood method (REML), using the MIXED procedure of statistics package SAS. Heritability estimates for type traits ranged from 0.09 to 0.24 and for CI it was 0.05. Genetic correlation estimations among type traits were, in general, of low magnitude, with the higher value between chest width and body depth (0.52). Estimates of genetic correlations between type traits and CI were mostly small. The low genetic correlation between rump angle and CI (0.02) suggests that the selection for rump angle may not be effective in determining genetic gain for fertility.

Respostas do capim-Tifton 85 à aplicação de nitrogênio: cobertura do solo, índice de área foliar e interceptação da radiação solar / Responses of the grass Tifton 85 to the application of nitrogen: soil cover, leaf area index, and solar radiation interception

Estudaram-se os efeitos da adubação nitrogenada sobre o crescimento do capim Tifton 85 (Cynodon spp. cv. Tifton 85), em termos de ocorrência de plantas e altura do dossel, índice de área foliar e interceptação de radiação fotossinteticamente ativa. O estudo foi desenvolvido sobre um planossolo de ocorrência em campo experimental. Os tratamentos consistiram de níveis de N (0; 150; 300; 450 e 600kg/ha de N-ureia, aplicados em duas vezes), arranjados em um desenho experimental de blocos inteiramente ao acaso, com quatro repetições. As avaliações foram realizadas semanalmente, entre 10 e 40 dias após o corte. Tanto a ocorrência de plantas como a altura do dossel responderam à adubação nitrogenada, conforme um padrão de resposta que variou, sazonalmente, em função das doses de N em interação com as condições ambientais. A expansão da área foliar e a interceptação da radiação fotossinteticamente ativa associada, também foram controladas direta e proporcionalmente pelas doses de N aplicadas, sendo maximizadas a valores de índice de área foliar em torno de 4,0.

The effects of nitrogen (N) fertilization levels on the growth patterns of the grass Tifton 85 (Cynodon spp. cv.Tifton 85) were studied in terms of occurrence of plants, sward height, leaf area index, and photosynthetically active radiation interception (PARint). The field trial was made in an experimental area. Treatments consisted of N levels (0; 150; 300; 450; and 600kg/ha N-urea, split in two applications) arranged in an experimental design of entirely randomized blocks with four repetitions. Plots were weekly sampled, from the day 10th to 40th after cutting. Both occurrence of plants as well as sward height were responsive to nitrogen fertilization according to a response pattern that seasonally varied, depending on N rates and environmental conditions; thus, demonstrating their sensitivity as indicators of growth conditions and canopy structure. Leaf expansion and its associated PAR interception were also directly and proportionately controlled by N rates, being maximized to values of leaf area index around 4.0.

Avaliação da atividade antiulcerogênica da Maytenus truncata Reiss (Celastraceae) / Evaluation of antiulcerogenic activity of Maytenus truncata Reiss (Celastraceae)

Maytenus truncata Reiss (Celastraceae) é uma planta nativa da Bahia (Brasil), sendo conhecida como "espinheira-santa". É usada popularmente na forma de decoto das folhas (chás) como antiulcerogênico, similarmente à Maytenus ilicifolia, a verdadeira "espinheira-santa". O objetivo do presente estudo foi avaliar a atividade antiúlcera e cicatrizante, assim como o perfil fitoquímico dos extratos brutos em acetato de etila e metanol da Maytenus truncata. A administração per os desses extratos nas doses de 120 mg/kg e 240 mg/kg reduziu a severidade da lesão gástrica induzida pelo estresse ao frio (-18 °C por 45 minutos) em ratos, com resultados mais significativos para o extrato bruto obtido em metanol. A administração dos extratos provocou o aumento do pH. Os resultados obtidos na administração do extrato bruto em metanol não contrariam seu uso popular, não somente pela atividade observada, mas também por se tratar de um extrato de alta polaridade cujos princípios podem ser obtidos a partir de uma infusão, embora estudos clínicos devam ser realizados para confirmação dessa hipótese.

Maytenus truncata Reiss (Celastraceae) is a native plant from Bahia (Brazil), known as "espinheira-santa". It is popularly used in the form of decoct of leaves (tea) as antiulcerogenic, similarly to Maytenus ilicifolia, the true "espinheira-santa". This study aims to evaluate antiulcerogenic and healing activities, as well as the phytochemical profile, of ethyl acetate and methanol crude extracts of Maytenus truncata. Per os administration of these extracts at 120 mg/kg and 240 mg/kg doses decreased the severity of gastric lesions induced by cold-restraint stress (-18 °C for 45 minutes) in rats, with more significant results for the crude methanol extract. The administration of the extracts caused pH increase. The results obtained with the administration of crude methanol extract are not contrary to its popular use, not only for the activity observed but, also, for its high polarity that enables the obtention of the active principles through infusion, though clinical studies should be performed to confirm this assertion.

Endogenous ligands of carbohydrate recognition domains of the mannose receptor in murine macrophages, endothelial cells and secretory cells; potential relevance to inflammation and immunity.

The macrophage mannose receptor (MR) has an established role in the phagocytosis of a wide range of microbes, and also functions in viral endocytosis, and clearance of a number of endogenous glycoproteins from the circulation. Its broad ligand specificity is mediated by tandemly linked carbohydrate recognition domains (CRDs). Recent studies suggest that binding or internalization of both natural and synthetic ligands of MR CRDs may modulate macrophage (MPhi ) function, for example to increase cidal capacity or cytokine synthesis. To identify endogenous ligands in the normal mouse we used an Fc-fusion protein (CRD4-7Fc) bearing four of the CRDs of MR. CRD4-7Fc recognized endocytic compartments of cultured MPhi, consistent with lysosomal enzymes being major ligands of MR. CRD4-7Fc also recognized MPhi and some endothelial cells in tissues, and intensely labeled secretory cells of the exocrine pancreas, salivary gland and thyroid. Strongly MR-positive interstitial cells were found in close proximity to the ligand-rich secretory cells, suggesting a role for MR in uptake of secretory glycoproteins, including thyroglobulin which was identified as a novel ligand in vitro. Endocytosis of these ligands by MR may have implications for tissue homeostasis and immunity, including antigen presentation, in secretory organs.

Type 1 and type 2 cytokine regulation of macrophage endocytosis: differential activation by IL-4/IL-13 as opposed to IFN-gamma or IL-10.

Cytokine regulation of endocytic activity in primary human macrophages was studied to define ultrastructural changes and mechanisms of pinocytic regulation associated with cytokines secreted by activated T cells. The effects of IFN-gamma (type 1) and IL-4/IL-13 and IL-10 (type 2) cytokines on fluid phase and mannose receptor-mediated endocytosis were assessed by horseradish peroxidase and colloidal gold-BSA uptake and computer-assisted morphometric analysis. IL-4 and IL-13 enhanced fluid phase pinocytosis and mannose receptor-mediated uptake by activation of phosphatidylinositol 3-kinase. Inhibition of actin assembly showed that both cytokines exerted actin-dependent and -independent effects. Ultrastructurally, IL-4 and IL-13 increased tubular vesicle formation underneath the plasma membrane and at pericentriolar sites, concurrent with decreased particle sorting to lysosomes. By contrast, IL-10 or IFN-gamma decreased both fluid phase pinocytosis and mannose receptor-mediated uptake. IFN-gamma stimulated increased particle sorting to perinuclear lysosomes, while IL-10 decreased this activity. In summary, our data document differential effects on macrophage endocytic functions by type 1 or type 2 cytokines associated with induction and effector pathways in immunity.

Class A scavenger receptors and the phagocytosis of apoptotic cells.

Apoptotic cells are rarely seen in situ because of rapid clearance by phagocytes. A number of receptors have been implicated in the recognition and ingestion of dying cells. Class A scavenger receptors (SRs) are multi-domained membrane glycoproteins that can endocytose modified lipoproteins and bind a wide range of ligands. There is growing evidence that they contribute to several biological processes. We present data that suggest class A SRs are involved in the phagocytosis of apoptotic cells.

Lack of p56lck expression correlates with CD4 endocytosis in primary lymphoid and myeloid cells.

In cell lines the endocytic properties of CD4 are regulated through its association with the src-family tyrosine kinase p56lck. In lymphoid cell lines expressing p56lck, CD4 is restricted to the cell surface and undergoes only limited internalization. Phosphorylation of the cytoplasmic domain of CD4 causes p56lck to dissociate and activates an endocytosis signal leading to the internalization of CD4 through clathrin-coated pits. In p56lck-negative transfected cell lines CD4 is constitutively internalized, but internalization is inhibited when p56lck is expressed in these cells. We now demonstrate that these endocytic properties of CD4 determined in transfected cell lines hold true for CD4 naturally expressed on myeloid cell lines (HL-60 and U937), as well as on primary lymphocytes, monocytes and macrophages isolated from human blood. CD4 showed limited internalization on p56lck-positive lymphocytes, but was rapidly internalized in p56lck-negative monocytes and macrophages. Surprisingly, rapid internalization of CD4 was seen with the lymphocytes from one unidentified donor. In these cells we failed to detect p56lck expression by Western blotting.