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Biomedical subjects

R M Gonzalez

Publications and source records attributed to R M Gonzalez.

17 recordsLinked to original sources

Inhibition of cholesterol biosynthesis in cultured fibroblasts by D003, a mixture of very long chain saturated fatty acids.

The present study was undertaken to investigate the effects of D003, a mixture of very long chain saturated fatty acids isolated and purified from sugar cane wax, on cholesterol biosynthesis in cultured fibroblasts. Cholesterol biosynthesis is regulated through feedback regulation of at least two sequentially acting enzymes, 3-hydroxy-3-methyl coenzyme A (HMG-CoA) synthase and reductase. They are up-regulated when sterol levels fall and down-regulated when sterol levels rise. The exposure of cultured fibroblasts to a lipid-depleted medium (LDM) and D003 (0.05-50 microg ml(-1)) for 12 h inhibited, in a dose-dependent manner, cholesterol biosynthesis from 14C-labelled acetate (33-68%). The addition of D003 at concentrations inhibiting cholesterol biosynthesis from labelled acetate significantly decreased incorporation of radioactivity from 3H2O into sterols, but not from 14C-mevalonate. These data indicate that D003 inhibits cholesterol biosynthesis by interfering with early steps of cholesterol biosynthetic pathway. We reasoned that D003 acts directly on HMG-CoA reductase, the main regulatory enzyme of cholesterol biosynthetic pathway. However, when enzyme activity was measured in cell extracts in the presence of various concentrations of D003 (0.5-50 microg ml(-1)), reductase activity was not inhibited. Thus, there was no evidence for a competitive or non-competitive inhibition of enzyme activity by D003. Treatment with D003 significantly suppressed (68%) the enzyme up-regulation when cells were cultured in LDM, which suggests a depression of de novo synthesis of HMG-CoA reductase and/or a stimulation of its degradation. However, since the suppressive action of D003 on cholesterol biosynthesis was observed in metabolic conditions under which synthase up-regulation was also enhanced, we cannot rule out a possible effect of D003 on HMG-CoA synthase. Thus, further studies are needed to clarify the precise mechanism of the inhibitory effect of D003 on cholesterol biosynthesis.

Animals↗

The role of state-of-the-art echocardiography in the assessment of myocardial injury during and following cardiac surgery.

Use of intraoperative echocardiography during open heart surgery, transesophageal probes, high-frequency transducers, and color Doppler imaging provide important diagnostic information to surgeons and anesthesiologists. Early detection of myocardial ischemia, assessment of valvular disorders, and the ability to monitor for intracardiac air are among the most important roles of intraoperative transesophageal echocardiography. Large prospective studies are necessary to evaluate whether these changes affect the outcome of patients undergoing coronary artery bypass grafting in terms of morbidity, mortality, hospital length of stay, and functional recovery. The application of new techniques such as contrast-enhanced transesophageal echocardiography helps to assess the adequacy of cardioplegia distribution and, thus, myocardial protection during cardiopulmonary bypass, which has a significant influence on outcomes as well.

Coronary Artery Bypass↗

High recurrence of recombinants in a family with pericentric inversion of chromosome 18.

We report a family in which the father carries a pericentric inversion involving two third of the chromosome 18 (p11.2q22). Of his three children, the proposita and her youngest brother show partial duplication of the short arm and partial deficiency of the long arm; the oldest sister shows the other recombinant (partial duplication of the long arm and partial deficiency of the short arm). In the literature, we found only one family in which both recombinants of a parental pericentric inversion were present in the same offspring and none with three affected and both kinds of recombinants. A review of the reported familial cases reveals that the risk of aneusomy of recombination, at least for chromosome-18 inversion carriers, may be close to 20% and no only 5-10% as previously reported.

Child↗

Effect of policosanol on the hepatic cholesterol biosynthesis of normocholesterolemic rats.

We have suggested previously, measuring 14C-acetate incorporation into free cholesterol, that oral administration of policosanol inhibits hepatic cholesterol biosynthesis in rats. Nevertheless, since acetate has limitations to study cholesterol synthesis in vivo, we now investigate rates of incorporation of labeled water into hepatic sterol after policosanol treatment. Absolute rates of incorporation of 3H-water in sterols were depressed by policosanol by about 20%, giving a more accurate degree of cholesterol biosynthesis inhibition in this species. Since policosanol did not inhibit labeled mevalonate incorporation into cholesterol in rat liver, we also studied the effect of policosanol on hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase. Reductase activity assayed in microsomes treated with policosanol remained unchanged, suggesting that cholesterol synthesis is not inhibited by a direct action of policosanol on this enzyme.

Animals↗

Policosanol inhibits cholesterol biosynthesis and enhances low density lipoprotein processing in cultured human fibroblasts.

Policosanol is a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, that induces cholesterol-lowering effects in experimental models and human beings. When human lung fibroblasts were incubated with policosanol for 48 hours prior to the experiment, a dose dependent inhibition of 14C-acetate incorporation into total cholesterol was observed, whereas labeled mevalonate incorporation was not inhibited. Even when cholesterol synthesis was not strongly inhibited, low density lipoprotein (LDL) processing was markedly enhanced. Thus, LDL binding, internalization and degradation were significantly increased after policosanol treatment. In addition, despite the fact that'cholesterol generation was not inhibited at the lowest dose of policosanol assayed, LDL processing was significantly increased. The current data indicate that policosanol inhibits cholesterol synthesis at the earliest steps of the cholesterol biosynthetic pathway. On the other hand, this study suggests that the increase in LDL processing may be partially explained by the inhibition of cholesterol biosynthesis, even though an sterol-independent mechanism might be responsible for the enhancement of LDL-receptor activity.

Anticholesteremic Agents↗

Ultrastructural study of the cellular types in the pineal organ of Gambusia affinis (teleost).

The pineal organ of Gambusia affinis was studied via light and electron microscopy. The cell types studied included photoreceptor cells, supporting cells, and a third cell type. The photoreceptor cells, which appear to form clusters, are divided into four regions: outer segment, inner segment, cell soma, and synaptic pedicle. Synaptic ribbons are commonly observed in the synaptic pedicle. The supporting cells separate the photoreceptor cells from the thick basal lamina that surrounds the entire pineal organ. The supporting cells show highly organized membrane formations, some lipid-like inclusions, and a diplosome. One of the centrioles gives rise to an invaginated cilium. The third cell type is observed infrequently and appears to be located mainly in the vicinity of the outer segments. The morphological characteristics of this cell type are similar to those of phagocytic cells. The ultrastructural features of the pineal organ of G. affinis are compared with those of other teleosts.

Animals↗

Membrane formations in the pineal cells of the teleost Gambusia affinis.

Highly organized membrane formations in the cytoplasm of photoreceptor and supporting cells of the pineal organ of Gambusia affinis are described. These membranous structures show different characteristics depending on the cell type where they are located. Some of the morphological characteristics of these membranous formations are similar to those of myeloid bodies, but their presence in the photoreceptor cells raises some doubt about their being myeloid bodies. The three-dimensional interpretation of these structures is discussed.

Animals↗

Physiological stresses associated with television camera operators' tasks.

This study was undertaken to evaluate the physiological stresses experienced by news media cameramen on their jobs. The tasks performed by the cameramen were simulated, based on the results of monitoring the field performance of these camera operators for a two-week period. Four male professional camera operators volunteered to participate in this study. Heart rate and oxygen consumption were selected to measure the physiological stresses associated with the camera operator's jobs. The results clearly show that jobs performed by the news media camera operators working for small television stations include very demanding physical tasks. The camera operator's job could be classified, based on physiological costs, as heavy work. A detailed discussion of the results and their implications in the process of camera operator's job redesign is given.

Journal Article↗

Intracellular (Golgi) receptors for insulinlike peptides in rat liver.

An insulinlike peptide (ILAs) has been isolated in our laboratory from human serum. The binding of 123I-labeled ILAs was studied in subcellular fractions from rat liver and found to be much greater in microsomes than purified plasmalemma. The high level of microsomal binding was due to a particular enrichment of binding sites in Golgi elements. Binding to Golgi was time and temperature dependent and was augmented by an increase of either subcellular fraction or 125I-labeled ILAs in accordance with a mass action process. Degradation of 125I-labeled ILAs was greatest in the Golgi vesicle fraction and was reduced by incubation at 4 degrees C. Bound 125I-labeled ILAs could be eluted and was found to retain integrity. Binding was pH dependent with a broad optimum at pH 7.7-8.5. Dissociation of bound 125I-labeled ILAs was time and temperature dependent. It was greater at 37 than 4 degrees C, and was uninfluenced by unlabeled ILAs. The ILAs receptor was stable at 4 degrees C but was markedly decreased by preincubation at 37 degrees C. The binding of 125I-labeled ILAs was inhibited by unlabeled ILAs and related insulinlike peptides (the insulinlike growth factors, IGF-1 and IGF-2) in a dose-dependent manner. Insulin and its analogues had only a partially inhibitory effect, and structurally unrelated peptides were without inhibitory efficacy. In contrast ILAs and IGF-1 and IGF-2 inhibited 125I-labeled insulin binding to its receptors in a dose-dependent fashion. These observations identify a receptor for insulinlike peptides in the Golgi elements of rat liver. It is distinct from the insulin receptor previously observed in these elements. The dual interaction of ILAs and other insulinlike peptides with both the insulin receptor and their own unique receptor constitutes the presumed biochemical basis for the two types of action effected by this family of peptides, namely, an effect on metabolism comparable to insulin and an effect on cellular anabolism and growth.

Animals↗

Serotonergic modulation of yawning.

Yawning induced by intraperitoneal (IP) injection of physostigmine (0.15 mgKg-1), in infant or adult rats is potentiated by Lu 10-171 (0.5-10 mgKg-1), a selective serotonin uptake inhibiting drug, which, by itself does not induce yawning. This effect is counteracted by metergoline (5-10 mgKg-1, IP) which blocks serotonin postsynaptic receptors. It is suggested that serotonin may exert a positivie modulating effect on yawning.

Animals↗

The resistance to carbon dioxide laser ignition of a new endotracheal tube: Xomed Laser-Shield II.

STUDY OBJECTIVE: To assess the resistance of a new endotracheal tube to penetration and ignition by a carbon dioxide (CO2) laser at a clinically relevant power setting. DESIGN: An unblinded, in vitro trial simulating clinical conditions. SETTING: The operating room at a university medical center. PATIENTS: None. INTERVENTIONS: A CO2 laser at 20W with a beam diameter of 1 mm was directed onto the Xomed Laser-Shield II at several points: both perpendicular and tangential to the portion of the tube covered by the protective wrap, to the unwrapped silicone tubing just proximal to the cuff, to the cuff filled with saline and methylene blue, and to the unwrapped silicone tubing distal to the cuff. Trials were performed with or without supplemental oxygen (O2) blown onto the study site and with a 6 L/min flow through the tube containing one of four concentrations of O2 in O2-air admixtures: 21%, 30%, 40%, and 100%. MEASUREMENTS AND MAIN RESULTS: Under all conditions, the laser did not penetrate the protective wrap, but the overlying polytetrafluoroethylene (Teflon) sheet was vaporized to an area equal to the size of beam application. The cuff was penetrated by the laser within 5 seconds. The unprotected silicone protein of the tube was penetrated by the laser in approximately 5 seconds, and time to formation of a blowtorch phenomenon shortened with increasing the percentage of O2 flowing through the tube. CONCLUSIONS: The protective coating of the Xomed Laser-Shield II is laser-resistant, but the unprotected silicone proximal and distal to the cuff is laser-vulnerable and can, under certain conditions, promote a blowtorch phenomenon. This tube would be acceptable for use in oral and pharyngeal laser surgery, but we recommend its use only in well-ventilated areas, out of concern for exposure to the products of the pyrolysis of Teflon, specifically the development of polymer-fume fever.

Equipment Design↗

Large visible gas bubbles in the internal jugular vein: a common occurrence during supine radical neck surgery?

STUDY OBJECTIVE: To establish the frequency of large visible bubbles or collections of bubbles in the jugular vein during radical neck dissection in the supine position. DESIGN: Prospective observation by at least two investigators of random consecutive patients scheduled for radical neck surgery. SETTING: Operating room suite in a university hospital specializing in head and neck cancer surgery. PATIENTS: Twelve consecutive ASA physical status II and III patients undergoing modified radical dissection for cancer. INTERVENTIONS: General anesthesia with fentanyl, oxygen (O2) 30% to 40%, nitrous oxide (N2O) 60% to 70%, and isoflurane 0.5% to 1.5%, with mechanical ventilation. Table position horizontal. Modified radical neck dissections performed by attending surgeons. Surgical field (jugular vein) carefully observed by the surgeons and an independent anesthesiologist investigator for the presence of bubbles during the dissection. MEASUREMENTS AND MAIN RESULTS: Easily visible bubbles were observed in the jugular veins of 42% (5 of 12) of the consecutive radical neck dissection patients studied. Some of the collections of bubbles were large (greater than 2.5 cm in diameter). In one case, the appearance and subsequent disappearance of bubbles was followed by a transient drop in arterial blood pressure (BP) and in end-tidal carbon dioxide (PETCO2), which was suggestive of a diagnosis of central venous air embolization. CONCLUSIONS: We theorize that some unexplained, undesirable intraoperative events (hypotension, arrhythmia, and hypoxemia) during radical neck dissection could be a result of venous air embolus or paradoxical air embolus. The anesthesia community should be aware of the high frequency of these visible bubbles in the jugular veins during radical neck surgery, even in the supine position. At minimum, this phenomenon is a frequent event of intellectual interest. At worst, these bubbles may be harbingers of significant central air embolism.

Adult↗