Antagonists of protein kinase C inhibit rat retinal glutamate transport activity in situ

Neuronal and glial high-affinity transporters regulate extracellular glutamate concentration, thereby terminating synaptic transmission and preventing neuronal excitotoxicity. Glutamate transporter activity has been shown to be modulated by protein kinase C (PKC) in cell culture. This is the first study to demonstrate such modulation in situ, by following the fate of the non-metabolisable glutamate transporter substrate, D-aspartate. In the rat retina, pan-isoform PKC inhibition with chelerythrine suppressed glutamate uptake by GLAST (glutamate/aspartate transporter), the dominant excitatory amino acid transporter localized to the glial Muller cells. This effect was mimicked by rottlerin but not by Go6976, suggesting the involvement of the PKCdelta isoform, but not PKCalpha, beta or gamma. Western blotting and immunohistochemical labeling revealed that the suppression of glutamate transport was not due to a change in transporter expression. Inhibition of PKCdelta selectively suppressed GLAST but not neuronal glutamate transporter activity. These data suggest that the targeting of specific glutamate transporters with isoform-specific modulators of PKC activity may have significant implications for the understanding of neurodegenerative conditions arising from compromised glutamate homeostasis, e.g. glaucoma and amyotrophic lateral sclerosis.

Retinal specializations in the blue marlin: eyes designed for sensitivity to low light levels

The large eyes and well-developed visual system of billfishes suggest that vision is an important sense for the detection and interception of prey and lures. Investigations of visual abilities in these large pelagic fishes are difficult, however anatomical studies of billfish eyes and retinas allow prediction of a number of visual capabilities. From the density of ganglion cells in the blue marlin (Makaira nigricans) retina, visual acuities of less than 10 cycles per degree were derived, a surprisingly low visual resolution given the absolute size of the marlin eye. Cone photoreceptors, on the other hand, were present in high densities, resulting in a presumed summation of cones to ganglion cells at a ratio of 40:1, even in the area of best vision. The optical sensitivity of the marlin eye was high owing to the large dimensions of the cone photoreceptors. These results indicate that the marlin eye is specifically adapted to cope with the low light levels encountered during diving. Since the marlin is likely to use its vision at depth, it is suggested that this line of research could help estimate the limits of vertical distribution based on light level.

A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention

PURPOSE: To determine the effects of aggressive lipid lowering on markers of ischemia, resistance vessel function, atherosclerotic burden, and Symptom status in patients with symptomatic coronary artery disease. METHODS: Sixty consecutive patients with coronary artery disease that was unsuitable for revascularization were assigned randomly to either usual therapy of lipids for patients with a low-density lipoprotein (LDL) cholesterol target level <116 mg/dL, or to a, more aggressive lipid-lowering strategy involving up to 80 mg/d of atorvastatin, with a target LDL cholesterol level <77 mg/dL. The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function.(brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, patients in the aggressive therapy group had a significantly greater decrease in mean (+/- SD) LDL cholesterol level than those in the usual care group (29 +/- 38 mg/dL vs. 7 +/- 24 mg/dL, P = 0.03). Patients in the aggressive therapy group had a reduction in the number of ischemic wall segments (mean between-group difference of 1.3; 95% confidence interval: 0.1 to 2.0; P = 0.04), flow-mediated dilatation (mean between-group difference of 5.9%; 95% confidence interval: 2.5% to 9.4%; P = 0.001), and angina score after 12 weeks. There were no significant changes in atherosclerotic burden in either group. CONCLUSION: Patients with symptomatic coronary artery disease who are treated with aggressive lipid lowering have improvement of symptom status and ischemia that appears to reflect improved vascular function but not atheroma burden. Am J Med. 2003;114:445-453. (C) 2003 by Excerpta Medica Inc.

Parental predictors of poor visual outcome with occlusion treatment for unilateral amblyopia

Aim: Visual acuity outcome of amblyopia treatment depends on the compliance. This study aimed to determine parental predictors of poor visual outcome with occlusion treatment in unilateral amblyopia and identify the relationship between occlusion recommendations and the patient's actual dose of occlusion reported by the parents. Methods: This study comprised three phases: refractive adaptation for a period of 18 weeks after spectacle correction; occlusion of 3 to 6 hours per day during a period of 6 months; questionnaire administration and completion by parents. Visual acuity as assessed using the Sheridan-Gardiner singles or Snellen acuity chart was used as a measure of visual outcome. Correlation analysis was used to describe the strength and direction of two variables: prescribed occlusion reported by the doctor and actual dose reported by parents. A logistic binary model was adjusted using the following variables: severity, vulnerability, self-efficacy, behaviour intentions, perceived efficacy and treatment barriers, parents' and childrens' age, and parents' level of education. Results: The study included 100 parents (mean age 38.9 years, SD approx 9.2) of 100 children (mean age 6.3 years, SD approx 2.4) with amblyopia. Twenty-eight percent of children had no improvement in visual acuity. The results showed a positive mild correlation (kappa = 0.54) between the prescribed occlusion and actual dose reported by parents. Three predictors for poor visual outcome with occlusion were identified: parents' level of education (OR = 9.28; 95%CI 1.32-65.41); treatment barriers (OR = 2.75; 95%CI 1.22-6.20); interaction between severity and vulnerability (OR = 3.64; 95%CI 1.21-10.93). Severity (OR = 0.07; 95%CI 0.00-0.72) and vulnerability (OR = 0.06; 95%CI 0.05-0.74) when considered in isolation were identified as protective factors. Conclusions: Parents frequently do not use the correct dosage of occlusion as recommended. Parents' educational level and awareness of treatment barriers were predictors of poor visual outcome. Lower levels of education represented a 9-times higher risk of having a poor visual outcome with occlusion treatment.

Optimising protocol of acquisition and post-processing procedures in the assessment of coronary artery disease by computed tomography

Coronary artery disease (CAD) is currently one of the most prevalent diseases in the world population and calcium deposits in coronary arteries are one direct risk factor. These can be assessed by the calcium score (CS) application, available via a computed tomography (CT) scan, which gives an accurate indication of the development of the disease. However, the ionising radiation applied to patients is high. This study aimed to optimise the protocol acquisition in order to reduce the radiation dose and explain the flow of procedures to quantify CAD. The main differences in the clinical results, when automated or semiautomated post-processing is used, will be shown, and the epidemiology, imaging, risk factors and prognosis of the disease described. The software steps and the values that allow the risk of developingCADto be predicted will be presented. A64-row multidetector CT scan with dual source and two phantoms (pig hearts) were used to demonstrate the advantages and disadvantages of the Agatston method. The tube energy was balanced. Two measurements were obtained in each of the three experimental protocols (64, 128, 256 mAs). Considerable changes appeared between the values of CS relating to the protocol variation. The predefined standard protocol provided the lowest dose of radiation (0.43 mGy). This study found that the variation in the radiation dose between protocols, taking into consideration the dose control systems attached to the CT equipment and image quality, was not sufficient to justify changing the default protocol provided by the manufacturer.

Acute myocardial infarction in chronic Chagas' cardiomyopathy: report of two cases with no obstructive coronary artery lesions

This report describes two patients with chronic Chagas' Heart Disease who developed clinical and laboratorial signs of myocardial infarction. Both patients presented sudden oppressive chest pain, without precipitating factor. In the first case, the highest MB-CK value was 65 IU, 22 hours after the beginning of the pain. On the second case, it was 77 IU at 18 hours after the beginning of the pain. In both cases ECG changes suggesting non-transmural infarction were present. The 99mTc PYP myocardial scintigram of the first case was positive. Coronary angiograms performed on the 18th and 9th day, respectively, after the acute infarction did not display obstructive lesions. Possible mechanisms causing myocardial infarction with normal coronary arteries in Chagas' Disease may include: embolic event's, particularly when there is associated congestive heart failure; coronary thrombosis and coronary spasms.

Avaliação funcional e farmacológica do corpo carotídeo do rato no envelhecimento

Resumo: O corpo carotídeo gera o quimiorreflexo à hipoxia, tendo por objectivo principal a homeostase dos gases do sangue. Esta tese testou a hipótese da função destes quimiossensores não se deteriorar ao longo da idade. In vivo, em ratos anestesiados, foram estudados os efeitos da idade nas respostas cardiorespiratórias a dois tipos de estímulos diferentes: a isquemia carotídea e a manipulação farmacológica de dois neurotransmissores com efeitos opostos nos quimiorreceptores, a adenosina e a dopamina. O modelo de isquemia carotídea corresponde à oclusão bilateral da artéria carótida comum, durante períodos de 5 a 15 s, o que determina um efeito excitatório na ventilação que é abolido pela secção bilateral dos nervos do seio carotídeo. No estudo farmacológico foram analisadas as respostas cardio-respiratórias à adenosina e à dopamina exógenas na presença e na ausência de antagonistas selectivos para os receptores A2A e D2, respectivamente. In vitro, no corpo carotídeo, foi quantificado o efeito de diferentes concentrações de oxigénio no conteúdo do segundo mensageiro comum à activação dos receptores A2A e D2, o cAMP. Em conjunto, estes resultados demonstraram que no rato o controlo da ventilação pelo corpo carotídeo se mantém inalterado ao longo da idade.--------------------- ABSTRACT: The carotid body initiates reflexes aimed principally at the homeostatic maintenance of blood gas tensions. This thesis tested the hypothesis of the function of these quimiossensores not deteriorate through age. In vivo, in anesthetized rats, we studied the effects of age on cardiorespiratory responses to two different types of stimuli: carotid ischemia and pharmacological manipulation of neurotransmitters with two opposite effects on chemoreceptors, adenosine and dopamine. The model of carotid ischemia corresponded to bilateral occlusion of common carotid artery, during periods of 5 to 15 s, which determines an excitatory effect on ventilation that is abolished by bilateral section of carotid sinus nerve. The pharmacological study analyzed the cardiorespiratory responses to exogenous adenosine and dopamine in the presence and absence of selective antagonists for the A2A and D2 receptors, respectively. In vitro, at the carotid body, it was quantified the effect of different concentrations of oxygen in the content of the common second messenger for the activation of A2A and D2 receptors, the cAMP. Together, these results showed that in rats the control of ventilation by carotid body remains unchanged through age.

Effects of a home-based exercise program in body composition, abdominal fat and lipid profile in patients with coronary artery disease

Introduction: Coronary artery disease and aging seems to be associated with a sedentary lifestyle, contributing to increased abdominal fat and consequently metabolic complications. The exercise can break this cycle by stimulating lipolysis and the use of fatty acids. In Europe there is still a lack of cardiac rehabilitation programmes in hospitals, therefore, this study aims to demonstrate the advantages of implementing home-based exercise programmes, as well as, their effects on cardiovascular prevention. This study analyzed the effects of a home-based exercise programme, in patients with coronary artery disease (myocardial infarction for 1 year), in body composition, abdominal fat, lipid profile. Methods: An ongoing randomized controlled trial with a sample of 20 participants were randomly allocated to intervention (n = 10) and control groups (n = 10). Intervention group performed a specific exercise programme during 8 weeks, consisting of ten home based exercises taking into account flexibility, muscle endurance and strength as well as cardiovascular endurance. Skinfolds thickness were measure to calculate the percentage of total fat: Skinfolds used were suprailiac, abdominal horizontal and vertical. Body mass index calculation and blood tests for lipidic profile were performed. Results: After eight weeks the intervention group decreased significantly the percentage of total fat (p < 0.05), the suprailiac skinfold (p < 0.05), the abdominal horizontal and vertical skinfold (p < 0.05) when compared with control group. In the intervention group it was observed after 8 weeks a significant decrease in body mass index, LDL-cholesterol and triglycerides. Conclusions: Home-based exercise programme influenced body composition, abdominal fat and lipid profile. These results highlight the importance of implementing home based exercises that are easy and cheap to implement in cardiac patients, in order to promote health and reduce cardiovascular risk factors.

Effects of microcurrents and physical exercise on the abdominal fat: a randomized controlled trial in patients with coronary artery disease

Objectives: Coronary artery disease are associated with decreased levels of physical activity, contributing to increases in abdominal fat and consequently the metabolic risk. The use of microcurrents is an innovative and effective method to increase lipolytic rate of abdominal adipocytes. This study aims to investigate the effects of microcurrents with a homebased exercise program on total, subcutaneous and visceral abdominal adipose tissue in subjects with coronary artery disease. Methods: This controlled trial included 44 subjects with myocardial infarction, randomly divided into Intervention Group 1 (IG1; n = 16), Intervention Group 2 (IG2; n = 12) and Control Group (CG; n = 16). IG1 performed a specific exercise program at home during 8 weeks, and IG2 additionally used microcurrents on the abdominal region before the exercise program. All groups were subjected to health education sessions. Computed Tomography was used to evaluate abdominal, subcutaneous and visceral fat, accelerometers to measure habitual physical activity and the semiquantitative Food Frequency Questionnaire for dietary intake. Results: After 8 weeks, IG2 showed a significantly decreased in subcutaneous fat (p ≤ 0.05) when compared to CG. Concerning visceral fat, both intervention groups showed a significant decrease in comparison to the CG (p ≤ 0.05). No significant changes were found between groups on dietary intake and habitual physical activity, except for sedentary activity that decreased significantly in IG2 in comparison with CG (p ≤ 0.05). Conclusions: This specific exercise program showed improvements in visceral fat in individuals with coronary artery disease. Microcurrent therapy associated with a home-based exercise program suggested a decreased in subcutaneous abdominal fat.

Da Disfunção Endotelial à Oclusão Vascular Papel do Sistema Renina - Angiotensina

There is a body of evidence that supports the important role of the renin-angiotensin system (RAS) in atherosclerotic disease and in the cardiovascular disease continuum: from endothelial dysfunction to vascular occlusion. In the earlier stages of vascular disease, the RAS promotes functional changes, of which endothelial dysfunction is the best example. The deposition of atherogenic lipoproteins in the intima, their oxidative modification and the onset and amplification of the inflammatory response strengthens the atherogenic role of the RAS. Inflammatory cells are one of the main sources of angiotensin-converting enzyme (ACE) and angiotensin II (Ang II) in the vascular wall, in a process that leads to structural changes in the artery and progression of atherosclerotic disease. Ang II promotes the migration of vascular smooth muscle cells and their phenotypic differentiation in synthesis that accelerates vascular disease. By modulating the inflammatory response and, in general, all the elements of the plaque, Ang II plays a part in its instability, in the onset of acute events and in the promotion of the local prothrombotic state that leads to infarction.

Miosite Orbitária

Orbital myositis is a subgroup of the nonspecific inflammatory syndrome or orbital pseudotumor and is characterized by a primary inflammation of extraocular muscles. The authors describe a 70-year-old patient with acute proptosis, ocular pain and right ophthalmoplegia, whose orbital computed tomographic scan showed enlargement of the homolateral extraocular muscles. Clinical presentation and complementary tests were compatible with the diagnosis of orbital myositis however, because of the particular aspects, which included retinal central vein occlusion, optic nerve lesion, distension of the superior ophthalmic vein and the homolateral cavernous sinus, the differential diagnosis with cavernous sinus pathology and thyroid ophthalmopathy was considered. The importance of a rapid diagnosis and treatment is stressed.

Intervenção Percutânea Urgente no Enfarte Agudo do Miocárdio por Lesão do Tronco Comum

BACKGROUND: ST-elevation myocardial infarction (STEMI) with the culprit lesion in the left main artery is a rare cardiac emergency with a poor prognosis. OBJECTIVE: Review and prognosis evaluation of primary percutaneous coronary intervention (PCI) performed in the setting of STEMI with left main occlusion in a single high-volume center. METHODS: Of the 483 primary or rescue PCIs performed and followed in our hospital during a 24-month period (August 2004 to July 2006), we retrospectively evaluated those involving left main procedures and analyzed in-hospital mortality and major cardiac events (MACE) in a 12-month follow-up. We found nine patients, age 68 +/- 9 years, five male, seven with multivessel disease and two with isolated left main disease. Rescue PCI was performed in three patients and primary PCI in the others. RESULTS: Seven patients presented in cardiogenic shock and two were classified in Killip class II on admission. Inotropic drugs, intra-aortic balloon pump and abciximab were used in eight patients. Drug-eluting stents were used in six patients, bare-metal stents in two, and isolated balloon angioplasty in one. Five patients (55%) died in the hospital and the four discharged home (two of them aged 81 and 82 years) were still alive and free from MACE at 12-month follow-up. CONCLUSIONS: Clinical presentation of STEMI with the culprit lesion in the left main artery was very severe. During PCI, drug-eluting stents, intra-aortic balloon pump and abciximab were used in almost all patients. This entity had a high mortality rate even though primary PCI was performed. Those who survived had a good mid-term prognosis.

Origem Anómala da Artéria Coronária Esquerda a Partir da Artéria Pulmonar

OBJECTIVE: To assess the frequency and severity of the anomalous origin of the left coronary artery (ALCA) from the pulmonary artery (PA). DESIGN OF THE STUDY: Prospective study of case series between March 1991 and December 1994. SETTING: Referral-based Paediatric Cardiology Department of a Tertiary Care Center. PATIENTS AND METHODS: Five consecutive patients (pts) with anomalous origin of the LCA from the PA; there were three infants aged 4 months and two children one 8 year and one 9 year old. There were three girls and two boys. All pts had clinical and 2D-echo and Doppler investigation prior to cardiac catheterization (CC). Indication for CC was based in the association of symptoms and signs of myocarditis or dilated cardiomyopathy of acute or subacute onset and electrocardiographic (ECG) signs of ischemia in infants. In older patients (pts) diagnosis was suspected mainly from ECG. During CC in all pts, aortograms and when necessary selective coronary angiograms were performed. Surgical correction was performed in all children. In two pts stress exercise ECG and stress Thallium studies before and after surgery were performed. RESULTS: two pts had "adult" an three had "infantile" type of ALCA from the PA. CC was performed and diagnosis was confirmed at surgery in all cases. In one child, correct diagnosis was made by ECO prior to CC and in one case LCA to PA fistula was suspected on Colour-Doppler study. No complications were attributed to CC. Several types of surgery were performed: reimplantation of the ALCA from the PA to the aorta (three pts); tunnel connection of the aorta to the ALCA via the PA (one pt) and left internal mammary to LCA anastomosis (one pt). Two infants died intraoperatively due to extensive myocardial infarction and poor left ventricular function. All the three survivors are asymptomatic after a mean follow up of 34 months. Two oldest pts are currently in New York Heart Association functional class I with normal ECG and improved myocardial perfusion on Thallium scan despite almost total occlusion of LCA at the site of implantation in the aorta as diagnosed on coronary angiogram. CONCLUSIONS: ALCA from PA is associated with major morbidity and mortality. Diagnosis should be suspected in pts with unexplained myocardial ischemia on ECG and even more if it is associated to clinical signs of dilated cardiomyopathy or myocarditis. Careful assessment on ECO and pulsed Doppler and colour flow mapping should make the diagnosis in most cases. Although surgery can be performed based only on ECO diagnosis, we strongly advise for angiography in all cases as in our experience there are false negative diagnosis by ECO. Preoperative Thallium studies can be useful for the selection of the type of surgery as pts with very little viable myocardium will not survive the establishment of a direct systemic to coronary blood flow and may be candidates for heart transplantation.

Effects of the Mediterranean diet and exercise in subjects with coronary artery disease

Introduction The association of the Mediterranean diet and exercise appears to have a protective role, reducing cardiovascular risk. This study investigated the effects of education sessions on the Mediterranean diet and an exercise program in modifying eating behaviors, body composition and abdominal fat. Methods An experimental study was performed on 20 subjects with known coronary heart disease randomly assigned to experimental (n=10) and control (n=10) groups. Both groups received education sessions on the Mediterranean diet, but the experimental group also followed an eight-week program of specific exercises. A semiquantitative food frequency questionnaire was administered to analyze food intake, bioimpedance was used to measure weight, fat mass and lean mass, and waist circumference was measured to calculate waist-to-height ratio. Results After eight weeks, protein (p<0.05) and cholesterol (p<0.05) intake in the experimental group had decreased significantly compared with the control group. Between the beginning and end of the study, there were significant decreases in the control group in carbohydrate (p<0.05) and saturated fat intake (p<0.05). In both groups the percentage of total fat (p<0.05) and fat mass (p<0.05) was significantly decreased. In the experimental group the waist-to-height ratio was significantly reduced (p<0.05). Conclusion The Mediterranean diet reduced carbohydrate and saturated fat intake, reflected in reduced fat mass. The association of the exercise program showed additional benefits in reduction of protein and cholesterol intake and abdominal fat.