Nonalcoholic fatty liver disease is associated with insulin resistance in a young Hispanic population.

OBJECTIVE: To investigate whether nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR) in a young Hispanic population. METHODS: A cross-sectional study was performed in Bogotá, Colombia, during 2006 in 263 males from the Colombian Air Force (age range 29-54 years). Anthropometric measurements and biochemical determinations (glycemia, lipid profile, insulin, and HOMA-IR) were obtained in order to determine the presence of metabolic syndrome (MS) criteria and insulin resistance in this population. In addition, ultrasound studies were performed to evaluate the presence of NAFLD. RESULTS: NAFLD was detected in 26.6% (n=70) of the subjects. Thirty four individuals had complete MS criteria (48.5%). The presence of NAFLD was associated with higher insulin levels (11.0±5.1 vs. 6.6±3.6, p=0.001), and its prevalence increased from 11% (n=8), to 24% (n=17) to 64% (n=45) from the lowest to the highest HOMA-IR tertile. Body mass index, triglycerides and subcutaneous and visceral fat were found to be independent predictors of NAFLD. CONCLUSIONS: These results suggest that NAFLD is associated with insulin resistance and extrahepatic adiposity in nondiabetic young Hispanic population.

Thyroid hormone stimulation of phosphatidylcholine synthesis in cultured fetal rabbit lung.

To investigate the mechanism of thyroid hormone action on pulmonary surfactant synthesis, we characterized the effect of triiodothyronine on phosphatidylcholine synthesis in cultured fetal rabbit lung. Since glucocorticoids stimulate surfactant synthesis and reduce the incidence of Respiratory Distress Syndrome in premature infants, we also examined the interaction of triiodothyronine and dexamethasone. The rate of choline incorporation into phosphatidylcholine was determined in organ cultures of rabbit lung maintained in serum-free Waymouth's medium. In 23-d lung cultured for 72 h, the increase in choline incorporation with triiodothyronine alone, dexamethasone alone, and triiodothyronine plus dexamethasone was 50, 62, and 161%, respectively. Both triiodothyronine and dexamethasone also increased incorporation rates with glucose, glycerol, and acetate as precursors, and stimulation with triiodothyronine plus dexamethasone was at least additive. Dexamethasone, but not triiodothyronine, affected distribution of radioactivity from [3H] acetate among phospholipids. Stimulation was first detected 8-12 h after addition of triiodothyronine, and then increased in a linear fashion. With triiodothyronine plus dexamethasone, stimulation was maximal at 48-72 h, and was supra-additive at all times. Exposure of cultured lung to dexamethasone enhanced the subsequent response to triiodothyronine, but not vice versa. When triiodothyronine was removed from cultures, there was no further stimulation and the triiodothyronine effect was partially reversed within 24 h. Half-maximal stimulation of choline incorporation occurred at a triiodothyronine concentration (0.10 nM) very similar to the dissociation constant for triiodothyronine binding to nuclear receptor (0.11 nM). The relative potencies of thyroid hormone analogs for nuclear binding and stimulation of phosphatidylcholine synthesis were also similar: triiodothyroacetic acid greater than triiodothyronine-proprionic acid greater than L-triiodothyronine approximately D-triiodothyronine much greater than thyroxine much greater than 3,5-diethyl-3'-isopropyl-DL-thyronine approximately 3,5-dimethyl-3'-isopropyl-L-thyronine approximately reverse triiodothyronine. The effect of triiodothyronine was blocked by the presence of either actinomycin D or cycloheximide, inhibitors of ribonucleic acid and protein synthesis, respectively. We conclude that triiodothyronine stimulates phosphatidylcholine synthesis by a process involving nuclear receptors and de novo ribonucleic acid and protein synthesis. These findings support the concept that endogenous triiodothyronine has a physiologic role in lung maturation and suggest that a combined antenatal therapy with thyroid hormone and glucocorticoid may be useful for prevention of Respiratory Distress Syndrome in the premature infant.

Asociación entre la dieta de la población vegana y la autopercepción del estado periodontal en Lima Metropolitana / Association between diet of the vegan population and self-perception of periodontal state in Metropolitan Lima

Objetivo: determinar la asociación entre la dieta vegana y la autopercepción del estado periodontal en una población vegana de Lima Metropolitana, Perú. Materiales y métodos: un total de 240 personas (120 veganas y 120 no veganas) fueron encuestadas en este estudio durante los meses de agosto a diciembre del año 2020 de manera virtual. Para evaluar la autopercepción del estado periodontal y los hábitos de higiene oral se utilizó el autorreporte de enfermedad periodontal, que se encuentra validado con una alfa de Cronbach de 0,77. Además se registraron otras variables como la edad, el sexo, el nivel socioeconómico, el grado de estudio y el consumo de tabaco. Se utilizó la regresión de Poisson con estimador robusto de la varianza para la asociación de las variables y se reportaron razones de prevalencia en un modelo crudo y ajustado. El nivel de confianza fue del 95 % y el de significancia fue de p < 0,05. Resultados y conclusiones: se encontró asociación estadísticamente significativa entre la apariencia de encías rojizas y/o hinchadas (RP = 0,67; IC 95 %: 0,25-0,54) y la mala percepción del estado de las encías (RP = 0,43; IC 95 %: 0,33-0,56) con la dieta vegana. Por último, para la dimensión del sangrado de encías durante el cepillado no se observaron diferencias estadísticamente significativas entre las personas veganas y las no veganas (AU)

Objective: to determine the association between vegan diet and self-perceived periodontal status in a vegan population of Metropolitan Lima, Peru. Materials and methods: a total of 240 people (120 vegans and 120 non-vegans) were surveyed in this study during the months of August to December 2020 in a virtual way. To evaluate self-perception of periodontal status and oral hygiene habits, the self-report of periodontal disease was used, which is validated with a Cronbach's alpha of 0.77. In addition, other variables such as age, sex, socioeconomic level, educational level, and tobacco consumption were registered. A Poisson regression with robust variance estimator was used both for the association of variables, and prevalence ratios were reported in a crude and adjusted model. The confidence level was 95 % and the significance level was p < 0.05. Results and conclusions: a statistically significant association was found between the appearance of reddish and/or swollen gums (PR = 0.67; 95 % CI: 0.25-0.54) and poor perception of the state of the gums (PR = 0.43; 95 % CI: 0.33-0.56) with the vegan diet. Finally, for the gum bleeding dimension during brushing, no statistically significant differences were observed between vegans and non-vegans (AU)

Sustancia P, citocinas proinflamatorias, receptor de potencial transitorio vaniloide tipo 1 y COVID-19: una hipótesis de trabajo / Substance P, proinflammatory cytokines, transient receptor potential vanilloid subtype 1 and COVID-19: A working hypothesis

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Hormonal regulation of cholinephosphate cytidylyltransferase in human fetal lung.

Cytidylyltransferase (CTP: cholinephosphate cytidylyltransferase, EC 2.7.7.15, CYT) is a regulatory enzyme for synthesis of pulmonary surfactant phosphatidylcholine (PC). The effects of glucocorticoid, T3, and cAMP on CYT activity were studied in explants of human fetal lung (18-22 weeks gestation) cultured for 1-6 days in serum-free medium. Dexamethasone (Dex, 10 nM) treatment for 5 days increased homogenate CYT activity (+115%, P < 0.02) when assayed in the presence of added lipid co-factor (L-alpha-phosphatidylglycerol, PG, 1.1 mM) and tended to increase activity in its absence (+77%, P = 0.12). Cytosolic activity was also significantly elevated in the presence of added co-factor (+124%, P < 0.01), but there was no effect of Dex on microsomal specific activity. Dex increased the recovery of CYT activity in the cytosolic fraction (75% vs. 43% (control) of the homogenate activity), but not in the microsomal, nuclear or mitochondrial fractions. Assayed in the presence of added co-factor, stimulation of CYT by Dex was apparent after 48 h exposure and maximal by 5-6 days exposure to < or = 30 nM concentration. T3 or agents that increase endogenous cAMP stimulated cytosolic activity by 40% and 36-74%, respectively, after 4-6 days exposure, but none produced an additive increase in the presence of Dex. We conclude that stimulation of CYT activity contributes to hormonal induction of surfactant lipids by each of these hormones. Glucocorticoids may increase the amount of CYT enzyme as well as activate the enzyme via increased synthesis of lipid co-factor.

Glucocorticoid and cAMP increase fatty acid synthetase mRNA in human fetal lung explants.

During late fetal development, synthesis of surfactant phospholipid requires a large supply of fatty acid precursor. Fatty acid synthetase is a regulatory enzyme for de novo fatty acid synthesis in lung as well as other lipogenic tissues. In this study, we report hormonal induction of FAS mRNA in human fetal lung explants (16-23 week gestation) cultured up to 7 days in Waymouth's medium (no serum) supplemented with dexamethasone (Dex, 10 nM) or agents that increase cAMP (8-Br-cAMP, 0.1 mM; isobutylmethylxanthine, 0.1 mM; forskolin, 0.01 mM; PGE1, 0.01 mM). Exposure of explants to Dex or cAMP agents increased FAS mRNA content by 6 h and maximal stimulation occurred at 72 h for Dex (approx. 3-fold increase) and 24 h for cAMP (approx. 2-fold increase). In the presence of both Dex and cAMP there was a synergistic increase in FAS mRNA content at all times (approx. 11-fold increase at 72 h). Induction of FAS mRNA was specific for steroids with glucocorticoid activity, reversible on removal of hormone, and was half-maximal at 2-3 nM Dex consistent with receptor mediation. Actinomycin D blocked induction by Dex but not by cAMP suggesting a transcriptional effect by glucocorticoid but not by cAMP. T3, which increases phosphatidylcholine synthesis, did not induce FAS mRNA. The findings indicate that both glucocorticoid and cAMP increase FAS gene expression consistent with an important role for FAS in regulating the supply of fatty acid for surfactant phospholipid synthesis.

Transforming growth factor-beta(1) regulation of surfactant protein B gene expression is mediated by protein kinase-dependent intracellular translocation of thyroid transcription factor-1 and hepatocyte nuclear factor 3.

The transforming growth factor-beta (TGF beta) polypeptides control a variety of cellular processes including organogenesis and cellular proliferation and differentiation. In the developing lung, TGF beta(1) treatment inhibits airway branching and expression of the genes for surfactant proteins (SP). Many effects of TGF beta are mediated at the level of gene transcription but there is limited information regarding signaling pathways and target transcription factors. In this study with human pulmonary adenocarcinoma H441 cells, we investigated TGF beta(1) effects on SP-B, a protein which is essential for normal function of pulmonary surfactant. TGF beta(1) (10 ng/ml) reduced SP-B mRNA content in a time-dependent fashion, and transient transfection studies localized responsiveness to the region of the SP-B promoter (-112/-72 bp) containing binding sites for thyroid transcription factor-1 (TTF-1) and hepatocyte nuclear factor 3 (HNF3), transcription factors that are important enhancers of SP gene expression. Using electrophoretic mobility shift assay and immunofluorescence, we demonstrated rapid accumulation of these transcription factors in the cytoplasm and subsequent loss from the nucleus on TGF beta(1) treatment of both adenocarcinoma cells and cultured human fetal lung. TGF beta(1) treatment caused intracellular translocation of protein kinase C and effects of TGF beta(1) were mostly abrogated in the presence of the protein kinase inhibitor calphostin C. We conclude that TGF beta(1), acting via protein phosphorylation, blocks nuclear translocation of TTF-1 and HNF3 which results in down-regulation of the SP-B gene and presumably other pulmonary genes which are transactivated by these factors.

Isolation and characterization of differentiated alveolar type II cells from fetal human lung.

A method has been developed for isolating differentiated type II cells from human lung of 18-24-week gestation. The procedure involves an initial 4-day culture of lung explants in the presence of dexamethasone (10 nM) and triiodothyronine (2 nM). Type II cells (and fibroblasts) are isolated by trypsin digestion of the explants, two differential adherence steps and incubation overnight in primary culture. This method provides a high yield of type II cells ((50 +/- 15) X 10(6) cells/g wet weight of explant) with a purity of 85 +/- 5% in 16 experiments. The type II cells contain numerous perinuclear granules which stain darkly with toluidine blue and Papanicolaou stain; electron microscopy showed these inclusions to be lamellar bodies with tightly stacked, well defined lamellae. Type II cells, but not fibroblasts, were positive by immunofluorescence histology for surfactant apoprotein and binding of Maclura pomifera lectin which binds to the surface of type II but not type I cells in vivo. The rate of both [3H]acetate and [3H]choline incorporation into phosphatidylcholine (PC) was several-fold greater in type II cells than fibroblasts; the saturation of PC was 36.2 and 25.9%, respectively. Release of saturated PC was stimulated by terbutaline, the ionophore A23187, and tetradecanoyl phorbol acetate in type II cells but not fibroblasts. We conclude that differentiated type II cells can be isolated in relatively high yield and purity from hormone-treated explants of fetal human lung.

Glucocorticoid stimulation of fatty acid synthesis in explants of human fetal lung.

We examined the effects of glucocorticoids and thyroid hormone (T3) on fatty acid synthesis, fatty acid composition and fatty acid synthetase activity in explants of human fetal lung (16-23 wk gestation). Explants were cultured 1-7 days in the absence (control) or presence of dexamethasone (10 nM) and/or T3 (2 nM). In control explants fatty acid synthesis and fatty acid synthetase activity increased 200% and 455%, respectively, between 1 and 5 days. Dexamethasone (10 nM) stimulated fatty acid synthesis (tritiated water incorporation) 155% and fatty acid synthetase activity 117% after 5 days in culture. T3 (2 nM) was not stimulatory, either alone or in the presence of dexamethasone. Dexamethasone increased the proportion of newly synthesized fatty acid recovered in phosphatidylcholine from 72% (control) to 90% (P less than 0.02) of total fatty acid. Dexamethasone stimulation of fatty acid synthetase activity was consistent with a receptor-mediated process: (1) stimulation was saturable and dose-dependent (Kd = 1.5 +/- 0.3 nM); (2) the potency of glucocorticoid analogs and other steroids reflected their glucocorticoid activity; (3) stimulation was reversible when cortisol was removed from the medium. Stimulation by dexamethasone was apparent within 24 h of hormone exposure, and increased to a maximum between 4 and 6 days. Fatty acid synthetase activity was higher in Type II cells (3.54 +/- 0.58 nmol malate/min per mg protein) than in fibroblasts from treated explants. Although both cell types responded to hormone treatment the stimulation was greater for Type II cells (200% vs. 75% increase). The fatty acid composition of PC showed increases in 14:0 and 16:1 with culture alone which were further stimulated by dexamethasone but not T3. These results indicate glucocorticoid stimulation of fatty acid synthesis and are consistent with a key role for fatty acid synthetase in the hormonal induction of pulmonary surfactant phosphatidylcholine synthesis in cultured fetal lung.

Synthesis of surfactant components by cultured type II cells from human lung.

We examined the effect of monolayer culture on surfactant phospholipids and proteins of type II cells isolated from human adult and fetal lung. Type II cells were prepared from cultured explants of fetal lung (16-24 weeks gestation) and from adult surgical specimens. Cells were maintained for up to 6 days on plastic tissue culture dishes. Although incorporation of [methyl-3H]choline into phosphatidylcholine (PC) by fetal cells was similar on day 1 and day 5 of culture, saturation of PC fell from 35 to 26%. In addition, there was decreased distribution of labeled acetate into PC, whereas distribution into other phospholipids increased or did not change. The decrease in saturation of newly synthesized PC was not altered by triiodothyronine (T3) and dexamethasone treatment or by culture as mixed type II cell/fibroblast monolayers. The content of surfactant protein SP-A (28-36 kDa) in fetal cells, as measured by ELISA and immunofluorescence microscopy, rose during the first day and then fell to undetectable levels by the fifth. Synthesis of SP-A, as measured by [35S]methionine labeling and immunoprecipitation, was detectable on day 1 but not thereafter. Levels of mRNAs for SP-A and for the two lipophilic surfactant proteins SP-B (18 kDa) and SP-C (5 kDa) fell with half-times of maximally 24 h. In contrast, total protein synthesis measured by [35S]methionine incorporation increased and then plateaued. In adult cells, the content of SP-A and its mRNA decreased during culture, with time-courses similar to those for fetal cells. We conclude that in monolayer culture on plastic culture dishes, human type II cells lose their ability to synthesize both phospholipids and proteins of surfactant. The control of type II cell differentiation under these conditions appears to be at a pretranslational level.

Lamellar bodies of cultured human fetal lung: content of surfactant protein A (SP-A), surface film formation and structural transformation in vitro.

Lamellar bodies were isolated from dexamethasone and T3-treated explant cultures of human fetal lung, using sucrose density-gradient centrifugation. We examined their content of surfactant apoprotein A (SP-A), and their ability to form surface films and to undergo structural transformation in vitro. SP-A measured by ELISA composed less than 2% of total protein within lamellar bodies; this represented, as a minimum estimate, a 2-12-fold enrichment over homogenate. One- and two-dimensional gel electrophoresis also suggested that SP-A was a minor protein component of lamellar bodies. Adsorption of lamellar bodies to an air/water interface was moderately rapid, but accelerated dramatically upon addition of exogenous SP-A in ratios of 1:2-16 (SP-A:phospholipid, w/w). Similar adsorption patterns were seen for lamellar bodies from fresh adult rat and rabbit lung. Lamellar bodies incubated under conditions that promote formation of tubular myelin underwent structural rearrangement only in the presence of exogenous SP-A, with extensive formation of multilamellate whorls of lipid bilayers (but no classical tubular myelin lattices). We conclude that lamellar bodies are enriched in SP-A, but have insufficient content of SP-A for structural transformation to tubular myelin and rapid surface film formation in vitro.

Enhanced distribution of adenovirus-mediated gene transfer to lung parenchyma by perfluorochemical liquid.

Although gene therapy holds great promise for the treatment of inherited and acquired diseases of the lung, a number of issues including efficient delivery and distribution of genes to pulmonary target cells must still be addressed. In this study we evaluated the use of perfluorochemical (PFC) liquid as a vehicle for delivery of recombinant adenovirus (AdCBlacZ) to lungs of juvenile rabbits. Virus was instilled into trachea of rabbits, and 4 days later the lungs were removed, cut into multiple pieces, and assayed for beta-galactosidase (beta-Gal) activity. Total lung expression of the beta-Gal reporter gene was increased two- to three-fold by instillation of the virus (10(11) particles/kg body weight) in saline (1.5 ml/kg) simultaneously with perflubron liquid (15 ml/kg) compared to virus+saline alone (control). Uniformity of beta-Gal activity between lobes was significantly improved by the PFC liquid. In perflubron-treated lungs approximately 45% of the lung pieces had beta-Gal-specific activity values within 50-150% of the mean specific activity for the total lung, compared to only approximately 15% of the pieces in control lungs. More of total lobar beta-Gal activity was recovered in the distal lung tissue (approximately two-fold greater than controls, p < 0.05). Morphological assessment of X-Gal-stained, fresh-frozen lung sections showed increased levels and more complete staining of alveolar wall cells in the PFC group. These data indicate that the PFC liquid perflubron enhances distribution of virus-mediated gene expression to the lung parenchyma in healthy rabbits. PFC liquid may be a useful treatment vehicle for accessing distal spaces of the damaged or diseased lung.

Differentiation of type II cells during explant culture of human fetal lung is accelerated by endogenous prostanoids and adenosine 3',5'-monophosphate.

Explant culture of the fetal lung, in the absence of serum or hormones, results in precocious biochemical and morphological differentiation of alveolar epithelial cells. In this study we tested the hypothesis that these maturational events are induced by endogenous cAMP. During culture of human fetal lung the content of tissue cAMP increased 140% from days 3-6. Treatment with isobutylmethylxanthine caused a further doubling of cAMP content, and indomethacin blocked most of the increase in cAMP. Isobutylmethylxanthine accelerated and indomethacin inhibited the increases during culture in surfactant protein-A (SP-A), SP-A mRNA, SP-B mRNA, phosphatidylcholine content, and activity of fatty acid synthetase. There was no effect of these treatments on the content of SP-C mRNA, which did not increase during culture. Increasing concentrations of prostaglandins E1 and E2 in the presence of indomethacin produced a parallel stimulation of cAMP content, SP-A, and fatty acid synthetase activity. The temporal increase in SP-A was also blocked by inhibitors of protein kinase-A. In morphological studies, indomethacin-treated explants appeared less mature, with decreased intralumenal volume and more columnar epithelial cells. We conclude that increased tissue cAMP levels, stimulated by endogenous prostaglandins, accelerate differentiation of alveolar epithelial cells during explant culture.

Identification and characterization of nuclear 3,5,3'-triiodothyronine-binding sites in fetal human lung.

Thyroid hormones have been implicated in the prenatal lung development of several species. To investigate the possibility that thyroid hormones could play a role in human lung development, we examined nuclei from fetal human lung for the presence of high affinity T3-binding sites. A single class of high affinity (Kd = 35 +/- 3 pM) binding sites for L-T3 was identified in nuclei from fetuses between 12-19 weeks of gestation. The T3-binding capacity increased 65% between 12-13 weeks (binding capacity, 0.227 and 0.282 fmol/micrograms DNA in two experiments) and 16-19 weeks of gestation [binding capacity, 0.420 +/- 0.014 (SEM) fmol/micrograms DNA; n = 8]. Maximal binding was achieved after 4 h of incubation at 20 C. The half-times for dissociation of the T3-receptor complex were 36 h, 10.5 h, 3 h, and 23 min at 2, 20, 25, and 37 C, respectively. The relative order of potency of thyroid hormone analogs in displacing L-T3 from the receptor was: T3-proprionate greater than 3.3'-5-triiodothyroacetic acid greater than L-T3 greater than D-T3 greater than L-T4 greater than 3,5-diethyl-3'-isopropyl-D,L-thyronine greater rT3 greater than 3,5-dimethyl-3'-isopropyl-L-thyronine. Some receptors were released from the nuclei into the supernatant during incubation (7.8 +/- 0.3% after 4 h at 20 C). This release increased with incubation time and temperature, but was independent of T3 concentration, Ca2+, and gestational age. Incubation at 37 C also inactivated some of the receptors, but T3 provided dose-dependent protection from this loss of binding activity. Our results are consistent with the proposal that nuclear receptors mediate a direct effect of thyroid hormones on developing human lung as early as the second trimester of gestation.

Glucocorticoids and thyroid hormones stimulate biochemical and morphological differentiation of human fetal lung in organ culture.

We characterized the stimulatory effects of both glucocorticoids and thyroid hormones on the surfactant system in human fetal lung. Synthesis of phosphatidylcholine (PC) and morphology were examined in explant cultures (15-24 weeks gestation) maintained 1-7 days in serum-free Waymouth's medium in a 95%-air-5% CO2 atmosphere. Control explants (no hormones) had the same rate of choline incorporation into PC between 1 and 7 days, but a significant increase in tissue PC content [82 +/- 21%, (+/- SEM), day 6 vs. 1], consistent with slow turnover of PC. [3H]Choline incorporation was stimulated 36%, 137%, and 192% by T3 (2 nM), dexamethasone (Dex; 10 nM), and T3 plus Dex, respectively, after 6 days of exposure (optimal response) compared to 19%, 38%, and 84% after 2 days of exposure. Thus, a supra-additive response occurred in the presence of both hormones and was greater at a shorter exposure time. Dex increased the percent saturation of newly synthesized PC (28.9 +/- 0.9% vs. 17.8 +/- 0.8% for control), but T3 did not, whereas both hormones increased tissue PC content (74.4 +/- 7.3% and 18.7 +/- 7.8% increase vs. control, respectively). Pulse-chase experiments with [3H]choline suggest that remodeling of unsaturated PC to saturated PC occurred during culture and was stimulated by Dex. Incorporation of [3H]acetate and [3H]glycerol into PC was stimulated by Dex (830% and 77%, respectively), but not by T3; the distribution of incorporated radioactivity among phospholipids was changed by Dex (increased counts per min into PC and phosphatidylglycerol with acetate and glycerol, respectively), but not by T3. Half-maximal stimulation of choline incorporation occurred at concentrations of Dex (2.1 nM) and T3 (0.03 nM) that are similar to the Kd values for receptor binding (5 and 0.05 nM, respectively). The relative potencies of thyroid hormones were T3 greater than T4 greater than rT3, and for corticosteroids, Dex much greater than corticosterone greater than 11-dehydrocorticosterone = cortisol greater than cortisone. Stimulation by either T3 or cortisol was reversed within 24-48 h of hormone removal. Initial treatment of explants with Dex enhanced the subsequent response to T3, but not vice versa. Culture for 4-5 days in the absence of hormones produced some morphological maturation of the epithelial cells, whereas treatment with T3 plus Dex markedly increased the number and size of lamellar bodies in epithelial cells, caused extensive proliferation of apical microvilli, and reduced glycogen deposits. Our findings are consistent with receptor-mediated stimulation of surfactant synthesis in human lung by both glucocorticoids and thyroid hormones.(ABSTRACT TRUNCATED AT 400 WORDS)

Extension of a pulmonary blastoma into the left atrium.

Pulmonary tumors of embryonic origin are rare, and pulmonary blastomas are probably the most uncommon. A thorough literature search disclosed no previous reports of extension of this type of tumor into the heart. We describe a patient whose initial clinical presentation suggested an obstructive left atrial mass; however, clinical and histologic findings indicated the mass was a tumor that originated from a pulmonary blastoma that extended into the left atrium through a pulmonary vein. The unique aspect of this case is that the patient's symptoms were related to the obstructive effects of the atrial mass, not to the primary pulmonary tumor.

Chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease syndrome: ocular manifestations in a recently recognized chronic inflammatory disease of childhood.

OBJECTIVE: To report on the ocular manifestations of the Chronic Infantile Neurological Cutaneous and Articular/Neonatal Onset Multisystem Inflammatory Disease (CINCA/NOMID) syndrome, a rare, recently identified, pediatric multisystem inflammatory disease with chronic cutaneous, neurological, and articular manifestations. DESIGN: Descriptive case-report study. SETTING: International collaborative study based on a questionnaire. RESULTS: We included 31 patients. The mean age at onset of eye manifestations was 4.5 years. Optic disc changes were the most common feature, occurring in 26 patients (83%), including optic disc edema, pseudopapilledema, and optic atrophy. Anterior segment manifestations varying from mild to severe were seen in 13 patients (42%); chronic anterior uveitis, in 17 patients (55%). Moderate to severe visual acuity loss in at least 1 eye was seen in 8 patients (26%) as a consequence of the disease. Posterior synechia, glaucoma, and white iritis were not observed in any patient. CONCLUSION: Ocular manifestations with potentially sight-threatening complications occur commonly in the CINCA/NOMID syndrome. The distinctive nature of these complications may assist the ophthalmologist in recognizing this rare disorder and distinguishing it from juvenile rheumatoid arthritis.

Lung beta-adrenoreceptor blockade affects perinatal surfactant release but not lung water.

We induced beta-adrenergic receptor blockade at 28 days gestation in the fetal rabbit with an irreversible beta-antagonist, bromace-tylalprenolomenthane (BrAlp). There was a marked decrease in concentration of available receptors in lung with increasing doses of BrAlp. BrAlp treatment decreased isoproterenol, but not prostaglandin, stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation in lung minces, and had no effect on activation of adenylate cyclase through non-beta-receptor-mediated components of the cyclase system in particulate preparations. Phospholipid recovery via lung lavage was significantly less from treated fetuses than from controls in groups delivered by cesarean section at 30 days (-31%) or vaginally at 31 days (-34%) and not allowed to air breathe. However, if fetuses from either group were allowed to air breathe, the difference was abolished. BrAlp treatment did not affect the phospholipid composition in lavage fluid, the rate of phosphatidylcholine synthesis, or tissue content of total or saturated phosphatidylcholine. Beta-adrenergic receptor blockade did not produce a significant change in lung water content either at or after birth regardless of the route of delivery. These data indicate that endogenous catecholamines play a role in surfactant secretion in both the fetal and newborn rabbit. We found no effects of BrAlp treatment on lung water, suggesting perhaps a less important role of endogenous catecholamines or that fewer receptors are required for this response than remained after treatment.

Thyroid hormone state and the incorporation of (14C) leucine by brain microsomes in developing rats.

Cell-free incorporation of (14C) leucine into protein was 38% greater for cerebral cortical microsomes from 22-day old neonatally thyroidectomized rats compared to littermate controls. In contrast, incorporation by liver microsomes of hypothyroid rats was 33% lower compared to controls, confirming their deficient hormonal state. Incubation of cerebral microsomes from either hypothyroid or euthyroid rats with both homologous and heterologous pH 5 enzyme fractions clearly implicated the pH 5 fraction as the source of the apparent increase in protein synthetic capacity in the hypothyroid brain. Daily administration of L-thyroxine (20 microgram/100 g body wt) to hypothyroid animals between 22 and 25 days of age produced an additional increase in (14C) leucine incorporation into protein by cerebral microsomes, whereas the cell-free protein synthesis rate of euthyroid rats was unaffected by similar hormonal treatment. Liver preparations from both hypothyroid and euthyroid rats exhibited the expected increase in cell-free protein synthesis following thyroxine administration. The results support the hypothesis that the young hypothyroid brain exhibits delayed maturation and that thyroid hormones play a regulatory role in cerebral protein synthesis during a defined developmental period.