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Biomedical subjects

O Gil

Publications and source records attributed to O Gil.

At least 19 recordsLinked to original sources

Depuration of PCBs and DDTs in mullet under captivity clean conditions.

Contaminated mullet (Mugil cephalus) from Douro estuary was allowed to depurate in clean water and fed with uncontaminated food. Levels of PCBs and DDTs in muscle and liver, and ethoxyresorufin O-deethylase (EROD) activity were measured at day 0, 21, 120 and 270. In specimens captured in the estuary total PCB and total DDT concentrations were 311 and 65 ng g(-1) in muscle and 686 and 115 ng g(-1) in liver, respectively. At day 21, after an initial 10-15 days period of starvation, organochlorines levels increased in both analyzed tissues. Thereafter levels of all PCB congeners and DDT compounds decreased in muscle, and at the end of the 270 days were 49 ng g(-1) and 13 ng g(-1), respectively. These decreases were correlated to the lipids consumption. In liver no relationship between those variables was observed, suggesting different elimination processes and eventual exchange of contaminants between muscle and liver. EROD activities decreased in the first days of depuration experiment, but showed no relations with analysed organochlorines.

Animal Feed↗

Usefulness of acr expression for monitoring latent Mycobacterium tuberculosis bacilli in 'in vitro' and 'in vivo' experimental models.

Real-time RT-PCR was used to quantify the expression of genes possibly involved in Mycobacterium tuberculosis latency in in vitro and murine models. Exponential and stationary phase (EP and SP) bacilli were exposed to decreasing pH levels (from 6.5 to 4.5) in an unstirred culture, and mRNA levels for 16S rRNA, sigma factors sigA,B,E,F,G,H and M, Rv0834c, icl, nirA, narG, fpbB, acr, rpoA, recA and cysH were quantified. The expression of acr was the one that best correlated with the CFU decrease observed in SP bacilli. In the murine model, the expressions of icl, acr and sigF tended to decrease when bacillary counts increased and vice versa. Values from immunodepressed mice (e.g. alpha/beta T cells, TNF, IFN-gamma and iNOs knock out strains), with accelerated bacillary growth rate, confirmed this fact. Finally, the expression of acr was maintained in mice following long-term treatment with antibiotics. The quantification of acr expression could be useful for monitoring the presence of latent bacilli in some murine models of tuberculosis.

Animals↗

Organochlorine contaminants in flounder (Platichthys flesus) and mullet (Mugil cephalus) from Douro estuary, and their use as sentinel species for environmental monitoring.

In order to monitor the presence of organic pollutants in Douro estuary (NW Portugal), two sentinel fish species, grey mullet (Mugil cephalus) and flounder (Platichthys flesus), were periodically sampled from May 2001 to April 2002. At all sampling periods, several specimens of both species were allowed to depurate in clean sea water. Levels of PCBs and DDTs were quantified in liver and muscle of both species. The accumulation of PCBs was higher in muscle of mullet, with a maximum of 345 ng/g dw, than in flounder, with a maximum 52ng/g dw. In the liver, flounder showed the highest levels (811 ng/g dw). Of the 18 congeners analysed, CBs 180 (hepta), 153 and 138 (hexachlorobiphenyls) were predominant in the tissue of both species. The maximum concentration of tDDT was measured in flounder liver (301ng/g dw). In contrast, a 10-fold higher tDDT was recorded in mullet muscle (63-69 ng/g dw and 8-16 ng/g dw for mullet and flounder, respectively). The hepatic ethoxyresorufin O-deethylase (EROD) activity was periodically determined. Consistently, a 10-fold higher enzymatic activity was present in mullet in comparison with flounder (1536 pmol/min/mg protein in mullet and 156 pmol/min/mg protein in flounder). In mullet, no correlation could be found between EROD activity and gonado-somatic index (GSI) or hepato-somatic index (HSI). On the contrary, during the reproductive season, female flounder showed a negative correlation between EROD activity and GSI. Despite being in clean sea water for 1 month period, no significant decrease in the tissue content of PCBs and tDDT was found. However, mullet's EROD activity followed a clear pattern, with a decrease enzymatic activity after being in captivity. Female flounder displayed a similar trend during the resting season. Yet, during the reproductive season, an increased EROD activity was recorded after being in captivity for 1 month, which may be associated with a modulation effect of steroids on CYP 1A1. Histological analyses of gonad revealed that 21% of male mullet displayed testis-ova, while no male flounder was found to show gonadal abnormalities. Overall, the study reports the accumulation of significant levels of PCBs and DDTs in the tissues of the studied species. It also provides important evidences supporting the use of grey mullet as a sentinel species for monitoring the presence of organic contaminants and xeno-estrogenic pollution in southern European estuaries.

Analysis of Variance↗

Evidence for polychlorinated biphenyls dechlorination in the sediments of Sado Estuary, Portugal.

Sediment gravity cores and grab samples were collected in the Sado Estuary and in its coastal area. The cores were sliced on board and the percentage of weight loss on ignition was determined in the laboratory, and analysed for polychlorinated biphenyl (PCB) congeners. PCB contents were higher in samples from the North Channel of the estuary, nearby the industrial zone (max. 114 ng g-1 dry weight), while levels in the coastal area were lower than 4.9 ng g-1. The concentrations of the quantified congeners varied irregularly with sediment depth in the estuary, but showed two opposite distribution patterns in cores from the coastal area: the proportions of lower chlorinated congeners increased with depth, while congeners with higher number of chlorines decreased. This suggests a dechlorination of the most chlorinated congeners into less toxic compounds, under reductive conditions of the sediment. Though measurements were done in natural environment it appears that dechlorination was not entirely dependent on chlorine position in the phenyl rings.

Chlorine↗

Neurotrimin expression during cerebellar development suggests roles in axon fasciculation and synaptogenesis.

We investigated the temporal expression of the neural cell adhesion molecule, neurotrimin, in the rat cerebellum and the brainstem from birth to adulthood using immunoreactive labeling. A wave of expression accompanied the development of projection pathways extending from brainstem nuclei (pons/inferior olive) through the cerebellar peduncles into the arbor vitae and disappeared with myelination by P14. Immuno-EM revealed expression of neurotrimin on the surface of unmyelinated axons but not on astrocytes or oligodendroglia. With the development of the molecular and internal granular layers, intense labeling occurred on the surface of parallel fiber bundles, granule cells and mossy fibers. With synaptogenesis, each excitatory junction was labeled by the immunoreaction. By P21, neurotrimin reactivity decreased on the surfaces of neuronal somata, dendrites and axons but remained at excitatory synaptic contact sites in both the molecular and granular layers. The spatial-temporal expression pattern of neurotrimin suggests that this adhesion molecule plays a role in axonal fasciculation of specific cerebellar systems and may also be involved in the formation of excitatory synapses and their stabilization into adulthood.

Afferent Pathways↗

Expression of caveolin-1 and -2 in differentiating PC12 cells and dorsal root ganglion neurons: caveolin-2 is up-regulated in response to cell injury.

Caveolae are cholesterol/sphingolipid-rich microdomains of the plasma membrane that have been implicated in signal transduction and vesicular trafficking. Caveolins are a family of caveolae-associated integral membrane proteins. Caveolin-1 and -2 show the widest range of expression, whereas caveolin-3 expression is restricted to muscle cell types. It has been previously reported that little or no caveolin mRNA species are detectable in the brain by Northern blot analyses or in neuroblastoma cell lines. However, it remains unknown whether caveolins are expressed within neuronal cells. Here we demonstrate the expression of caveolin-1 and -2 in differentiating PC12 cells and dorsal root ganglion (DRG) neurons by using mono-specific antibody probes. In PC12 cells, caveolin-1 expression is up-regulated on day 4 of nerve growth factor (NGF) treatment, whereas caveolin-2 expression is transiently up-regulated early in the differentiation program and then rapidly down-regulated. Interestingly, caveolin-2 is up-regulated in response to the mechanical injury of differentiated PC12 cells; up-regulation of caveolin-2 under these conditions is strictly dependent on continued treatment with NGF. Robust expression of caveolin-1 and -2 is also observed along the entire cell surface of DRG neurons, including high levels on growth cones. These findings demonstrate that neuronal cells express caveolins.

Animals↗

Aortobronchial fistula secondary to chronic post-traumatic thoracic aneurysm.

A few patients with traumatic aortic laceration remain undiagnosed and survive long enough to develop a chronic aneurysm. Such aneurysms are frequently asymptomatic; alternatively, they may manifest themselves in the form of chest pain, dysphonia, dysphagia, bronchial irritation, or sudden death. A case of aortobronchial fistula secondary to a chronic post-traumatic aneurysm of the aortic isthmus is presented. Hemoptysis was the main sign. The affected segment of the thoracic aorta was replaced with a Dacron graft and a left superior lobectomy was performed. Nevertheless, the patient died during the postoperative period due to adult respiratory distress syndrome. Pathogenesis, diagnosis, and management of aortobronchial fistulae are discussed.

Adult↗

[Dynamic cardiomyoplasty. Preliminary experience].

INTRODUCTION AND OBJECTIVES: The purpose of this study is to show our experience in clinical dynamic cardiomyoplasty. PATIENTS, MATERIALS AND METHODS: Six patients with end-stage heart failure and 2 patients with left ventricular aneurysm underwent dynamic cardiomyoplasty using the latissimus dorsi muscle. The latissimus dorsi was electrically conditioned before the procedure through a lead placed under local anesthesia and connected to an external cardiac pace-maker. Surgical technique--including dissection of the latissimus dorsi and encircling of the ventricles with the muscle flap--was performed in general terms as described at the Broussais Hospital. In the first 3 patients a bipolar lead connected to a single impulse generator was used. In the other 5 patients a train of impulses cardiomyostimulator was used. Changes in systolic function were studied through Doppler-echocardiography and radionuclide studies. Changes in diastolic function were evaluated through E wave velocity and deceleration time. RESULTS: Mean follow up was 9 +/- 5.7 months. No early deaths were recorded. One patient underwent emergency surgery, one week after the procedure, because of a tear of the patch used to close the wall defect after left ventricular aneurysm resection. In 2 patients a subcutaneous serous collection secondary to muscle dissection was evacuated. One patient died due to a stroke 4 months after the procedure. Another patient died after an unsuccessful coronary transluminal percutaneous angioplasty 11 months after the procedure. An improved functional class was observed in all patients. No changes in systolic function were observed after surgery when the cardiomyoestimulator was turned-off either with echocardiography (26.7 +/- 8.6 vs 24.8 +/- 5.8% [NS]) or radionuclides (24.5 +/- 9.5 vs 20.2 +/- 8.3% [NS]). When the cardiomyostimulator was turned-on a statistically significant increase of the left ventricular ejection fraction was observed either with echocardiography (24.8 +/- 5.8 vs 37 +/- 10.3%; p < 0.05) or radionuclides (20.2 +/- 8.3 vs 33.3 +/- 12.2%; p < 0.05). This significant increase of the ejection fraction has been observed in subsequent studies. Nevertheless the differences when the cardiomyostimulator is turned-on and turned-off have decreased several months after the procedure. A significant increase of the left ventricular outflow velocity (cm/seg) was observed when the generator was turned-on (57.7 +/- 20.4 vs 75.1 +/- 17.8%; p < 0.01). A significant increase of the dP/dt (mmHg/seg) was observed when the generator was turned-on (706.3 +/- 291.5 vs 592.6 +/- 181.6%; [NS]). No significant changes were observed on E wave velocity. A significant decrease of the deceleration time was observed several months after the procedure (p < 0.05). CONCLUSIONS: We believe that dynamic cardiomyoplasty is a safe and valid surgical procedure for some patients with end stage cardiomyopathies as well as in association with Jatene's technique for the management of left ventricular aneurysms. An improvement in functional class is present and a significant increase of the left ventricular systolic function. Nevertheless it is necessary to find new systolic parameters, independent of volumetric calculations, to evaluate the mechanical support of the muscle as well as to determine the long-term pattern of electrical stimulation.

Adult↗

Use of biventricular circulatory support as bridge to simultaneous heart and kidney transplantation.

A 64-year-old man with dilated cardiomyopathy and chronic renal insufficiency (without dialysis) was admitted in cardiogenic shock urgently requiring a circulatory biventricular assist device (Thoratec). Twenty-nine days later we performed orthotopic cardiac and heterotopic renal transplantations with organs from the same donor. Postoperatively secondary renal insufficiency occurred due to rejection of the graft, bleeding ulcer with hypovolemic shock, and peritonitis due to Streptococcus faecalis and Candida. In the postoperative course only one rejection of the cardiac graft was detected. The patient was discharged after 4 months, resuming a normal life.

Assisted Circulation↗

[Aneurysm of the ascending aorta in patients with a prior aortic valve replacement].

INTRODUCTION AND OBJECTIVES: The purpose of this study is to show our experience in the treatment of aneurysms of the ascending aorta in patients with previous aortic valve surgery. METHODS: We studied retrospectively the clinical characteristics and operative methods of 9 patients who underwent surgery for aneurysm of the ascending aorta after previous aortic valve replacement. RESULTS: Time interval between the first and subsequent reoperation was 8.4 +/- 3.5 years (range 4-15 years). During the first operation there were 5 cases who presented with aortic regurgitation and dilatation of the ascending aorta. Isolated valvular aortic replacement was performed in these patients. Two patients underwent valvular replacement and implantation of supracoronary aortic graft. In two other cases valvular replacement was done with wedge resection of the aortic sinuses. Reoperation was performed because to the following reasons: valvular prosthesis disfunction and aneurysm of the ascending aorta (3), valvular prosthesis disfunction and aneurysm of the aortic remnant located between the prosthesis and the supracoronary aortic graft (2), thrombosis of the prosthesis (1), dissection of the ascending aorta (2) and superior vena cava syndrome (1). There was one hospital death. Another patient died after 26 months because of graft infection. The other 7 patients are in functional class I. CONCLUSIONS: We conclude that an aggressive surgical approach should be adopted in patients with degenerative aortic regurgitation and moderate dilatation of the ascending aorta because of the rapid progression of the aortic disease. We advise complete replacement of the aortic root.

Adult↗

Dynamic cardiomyoplasty in a patient with end-stage cardiomyopathy.

Dynamic cardiomyoplasty is a relatively new surgical procedure by which a transformed fatigue-resistant skeletal muscle wrapped around the heart is stimulated to contract in synchrony with it, thereby augmenting the ventricular functions of a failing heart. We performed a cardiomyoplasty with latissimus dorsii (LD) in a patient who was refused the heart transplant programme because of pulmonary hypertension and psychosocial contraindications. The patient was 34 years old, functional class grade IV of the New York Heart Association (NYHA), with a three-month history, due to ischemic cardiomyopathy with multiple vessels affected, 10% ejection fraction, arteriolar pulmonary resistance of 7.5 U Wood. Cardiomyoplasty was performed after training the LD muscle for four weeks. One week later the pacemaker was programmed in a DDD mode: amplitude 3.75 V, pulse duration 0.50 ms, AV delay 175 ms. The patient reached functional class grade I-II (NYHA). Inotrope support was discontinued and great clinical improvement was noted. The ejection fraction rose from 10% to 30%. Echocardiographic left ventricular outflow tract velocity increased from 0.33 m/s to 0.60 m/s. These values were compared with radionuclide angiocardiography and echocardiography evaluations. The great clinical improvement and positive changes in left ventricular parameters suggest that cardiomyoplasty is useful in the treatment of some cases of dilated or ischemic cardiomyopathy as an alternative to heart transplantation. Long term follow-up is necessary to evaluate this procedure.

Adult↗

Nifedipine blocks calcium-dependent cholinergic depolarization in the guinea pig hippocampus.

The possibility that cholinergic stimulation might directly activate a receptor-operated Ca2+ channel was investigated in the CA1 region of guinea pig hippocampus using intracellular recording techniques. Two cholinergic responses were studied: (1) the plateau depolarization evoked by cholinergic stimulation in the presence of Ba2+; and (2) the Ca2(+)-dependent component of membrane depolarization. Both of these responses were blocked by 1-5 microM of nifedipine, a blocker of voltage-dependent L-type Ca2+ channels. In addition, the plateau response was mimicked by direct postsynaptic depolarization in the presence of Ba2+. We conclude that cholinergic stimulation does not directly activate a Ca2+ conductance in these neurons, but rather leads to the indirect activation of L channels which may be located both pre- and postsynaptically.

Animals↗

Long-term potentiation in rat hippocampus is inhibited by low concentrations of ethanol.

Acute ethanol ingestion impairs memory in humans at concentrations associated with mild intoxication. A possible neurophysiological correlate of this effect is the suppression by ethanol of long-tem potentiation (LTP), a persistent increase in synaptic efficiency which has been proposed as a substrate for memory. However, in previous studies ethanol has been shown to impair LTP only at very high concentrations, near the lethal level in humans. We now report that ethanol can significantly reduce LTP in rat hippocampus at concentrations as low as 5 mM, a level attainable following ingestion of a single alcoholic drink. We also demonstrate that the potency of ethanol in depressing LTP correlates well with its potency in inhibiting the response to N-methyl-D-aspartate, an agonist at the glutamate receptors implicated in LTP induction. The influence of low ethanol concentrations on LTP may contribute to the memory impairment associated with its use in humans.

Animals↗

Cholinergic stimulation enhances long-term potentiation in the CA1 region of rat hippocampus.

The effect of the cholinergic agonist carbachol on a putative substrate for memory (long-term potentiation; LTP) was investigated in slices of rat hippocampus (CA1 region). Carbachol (5 microM) increased LTP when the presynaptic depression of the EPSP was controlled. The results indicate that carbachol enhances the effectiveness of the tetanus, probably through postsynaptic mechanisms. This effect may have implications for the role of acetylcholine in memory and the use of cholinergics in memory disorders.

Animals↗

Pancreatic duct occlusion in the management of acute necrotizing pancreatitis in a canine model.

Based on results reported by others in using prolamine (Ethibloc; Ethicon Gmb H) to treat patients with chronic pancreatitis, without any observed pancreatic complications, we decided to use pancreatic duct occlusion experimentally in dogs in which we induced acute pancreatitis by the injection of calcium chloride into the pancreatic duct. This injection proved to be 100% lethal in the 5 animals constituting the control group, none of which were treated after the injection. Acute pancreatitis was then induced in 57 animals, also by injection of calcium chloride. These dogs were then treated with one of three substances that share the same physical properties: prolamine; Tissucol (Immuno AG, Vienna), a biologic tissue adhesive; silicone (Xantopren, Bayer Dental D-5090 Leverkusen). Thirty-seven dogs were treated with prolamine, 10 dogs with Tissucol, and 10 with silicone. The mortality rate in the 57 treated animals was 12.2%, compared to the 100% rate in the untreated control group. The mechanical action achieved by blocking the pancreatic duct shows how the evolution of acute pancreatitis at different stages could be modified. This specific treatment limits the pathophysiologic process of acute pancreatitis in dogs. These findings provide us with a promising outlook for the treatment of this severe illness.

Acute Disease↗

[Vascular effects of spinal cord electrostimulation. Possible mechanisms of action].

Spinal cord stimulation has been demonstrated to be effective in the treatment of peripheral arteriopathies where neither medical nor surgical treatment is possible. Although there are various theories proposed, the mechanism of action is not yet clear. We studied the changes in transcutaneous PO2 as well as the sympathetic and parasympathetic cardiac activity in 42 patients with peripheral arteriopathies treated with spinal cord stimulation. Transcutaneous PO2 measured in percentage values showed a statistically significant increase 15 minutes (p less than 0.05) and 60 minutes (p less than 0.01) after generator connection. Disconnection produced a gradual decrease of transcutaneous pO2 with a minimal value at 70-180 minutes, maintained for various hours above basal values. The study of the changes in the expiratory/inspiratory quotient of the heart rate during spinal cord stimulation did not show any statistically significant differences with respect to a control group of healthy subjects. This demonstrates a preservation of parasympathetic activity. While studying the changes in heart rate from the decubitus to orthostatic position, the spinal cord stimulation group behaved similar to the group of patients who, for having undergone heart transplantation, had complete cardiac denervation the difference being statistically significant. The results obtained can clear up some questions as to the mechanisms of action of spinal cord stimulation and explain the clinical improvement obtained in this type of treatment for peripheral arteriopathies.

Arm↗