PubMed Health⌕ Search

Biomedical subjects

J Genovese

Publications and source records attributed to J Genovese.

17 recordsLinked to original sources
PubMed1998

TGF-beta1 up-regulates the mRNA for the Na+/Ca2+ exchanger in neonatal rat cardiac myocytes.

Northern analyses of neonatal cardiac myocytes demonstrated that TGF-beta1 (5 ng/ml) stimulates and IL-1beta (5 ng/ml) decreases the steady-state levels of the mRNA coding for the Na+/Ca2+ exchanger. This is in agreement with the effects of TGF-beta1 and IL-1beta on beating rate and calcium uptake, suggesting that such effects might be mediated, at least partially, through up-regulation of the Na+/Ca2+ exchanger. Basal and TGF-beta1 stimulated mRNA levels were inhibited by the PKC inhibitors H7 (10 microM) and GF109203X (250 nM). In addition, apigenin (12.5 microM), a MAP kinase inhibitor, was able to inhibit basal mRNA levels for the exchanger. Cycloheximide (35.5 microM) had no effect on basal mRNA levels for the exchanger but steady-state levels were diminished in cells treated with TGF-beta1. Finally, actinomycin D (10 microM) inhibited both basal and TGF-beta1 stimulated mRNA levels, though with a more pronounced effect in the presence of TGF-beta1. These results suggest that a complex mechanism of regulation exists for the exchanger and that PKC and possibly MAP kinases might be involved. The up-regulation of this important protein for calcium extrusion, induced by TGF-beta1, might prepare cells to better overcome the calcium overload which occurs under cellular stress and might explain some of the cytoprotective effects of TGF-beta1.

Animals↗
PubMed1996

Fatality due to acute fluoride poisoning following dermal contact with hydrofluoric acid in a palynology laboratory.

A fatal accident involving concentrated hydrofluoric acid in a palynological laboratory is described. Similar deaths due to dermal exposure to concentrated hydrofluoric acid have been reported in the literature. It is evident that rigorous control measures including proper personal protective equipment and first aid are of utmost importance in the prevention of death and injury when handling hydrofluoric acid. Possible factors that may have contributed to the accident are reviewed.

Accidents, Occupational↗
PubMed1996

A comparison between the acute effects of nitric oxide synthase inhibition and fluid resuscitation on myocardial function and metabolism in entotoxemic dogs.

PURPOSE: Nitric oxide (NO) synthase inhibitors increase mean arterial pressure (MAP) and systemic vascular resistance (SVR) in animal models of sepsis and in humans with septic shock. However, NO synthase inhibitors may cause coronary vessel constriction leading to myocardial ischemia and increased mortality in endotoxemic animals. This study was designed to test the acute effect of NG-nitro-L-arginine (L-NAME) on left ventricular (LV) function and coronary blood flow in a dog model of endotoxemia. METHODS: In open chest, anesthetized dogs endotoxemia was induced intravenously (IV) by Escherichia coli lipopolysaccharide at 2 mg/kg for 60 minutes. This resulted in hypotension, acidosis, and decreased SVR while cardiac index (CI) was maintained. When MAP was < or = 60 mm Hg, animals were resuscitated with either dextran (group I), or L-NAME 30 mg/kg IV bolus (group II). Group III received L-NAME only. A fourth group of dogs was given endotoxin and not resuscitated. Animals were followed up for 30 minutes after intervention. Animals in the fourth group were followed up until the MAP was approximately 30 mm Hg. Heart rate, CI, MAP, LV end systolic and diastolic pressures, dP/dt at a pressure of 40 mm Hg, left anterior descending artery coronary blood flow, regional LV contraction (sonomicrometer crystals), coronary pressures, gas tension, and lactates were continuously recorded. A catheter placed in the coronary sinus allowed measurement of coronary sinus pressure, as well as coronary sinus lactate and gas tensions. Stroke volume index, stroke work index, systemic vascular resistance index (SVRI), coronary vascular resistance, percent myocardial shortening, myocardial oxygen consumption (Mvo2) and net myocardial lactate production were calculated. RESULTS: In Group I, fluid administration increased MAP, stroke work index, coronary blood flow, percent myocardial shortening, and Mvo2. In Group II, L-NAME increased MAP to the same extent as fluid administration without evidence of coronary ischemia or myocardial dysfunction. L-NAME did not alter Mvo2 in either endotoxemic or nonendotoxemic animals. In group III, L-NAME alone resulted in a significant increase in MAP and SVRI, but its effects on coronary blood flow and LV function were not significant. We did not observe net lactate production in any of the groups. Coronary blood flow increased out of proportion to Mvo2 in group I animals. CONCLUSIONS: We conclude that although L-NAME at 30 mg/kg causes vasoconstriction, its effects on coronary blood flow and LV function were not significant.

Animals↗
PubMed1996

Myocardial mechanics and energetics during continuous positive airway pressure in sedated pigs.

OBJECTIVE: To test the hypothesis that increased cardiac output with continuous positive airway pressure (CPAP) leads to increased myocardial metabolic cost. DESIGN: Prospective, repeated-measures, laboratory studies. SETTING: University-affiliated hospital animal research laboratory. SUBJECTS: Eight sedated pigs that had been previously instrumented for collection of hemodynamic data. INTERVENTIONS: Application of CPAP at 0, 5, 10, and 15 cm H2O and recovery under conditions of normal blood volume (normovolemia) and after administration of hetastarch 35 mL/kg (hypervolemia). MEASUREMENTS AND MAIN RESULTS: We measured mean arterial pressure, cardiac output, systemic vascular resistance index, the first derivative of the left ventricular pressure at a left ventricular pressure of 50 mm Hg, rate-pressure product, left ventricular tension-time index, stroke work index, myocardial pressure-myocardial segment length area, coronary artery blood flow and coronary vascular resistance, and myocardial oxygen consumption (four pigs). With normovolemia, cardiac output decreased with CPAP (4.9 +/- 1.2 L/min at CPAP of 0 cm H2O to 4.5 +/- 1.3 L/min at CPAP of 15 cm H2O, p < .005) and systemic vascular resistance index increased (2509 +/- 702 to 3095 +/- 1080 dyne.sec/cm5.m2, p < .01). With hypervolemia, cardiac output increased at low-level CPAP (5.7 +/- 1.4 L/min at CPAP of 0 cm H2O to 6.4 +/- 1.6 L/min at CPAP of 5 cm H2O, p < .05) and systemic vascular resistance index decreased (2412 +/- 552 to 2033 +/- 436 dyne.sec/cm5.m2, p < .01). There were no associated significant changes in myocardial oxygen consumption, or its major correlates when cardiac output increased with CPAP (hypervolemic conditions). CONCLUSIONS: In normal pigs, there is no change in myocardial oxygen demand with CPAP, whatever the change in cardiac output. Thus, increased cardiac output with CPAP carries little extra metabolic cost. Increased cardiac output with low-level CPAP in hypervolemia is associated with systemic vasodilation.

Alfaxalone Alfadolone Mixture↗
PubMed1995

Congestive heart failure and sleep apnoea-possible mechanisms and effect of CPAP therapy.

Sleep-disordered breathing has been associated with increased cardiovascular morbidity and mortality. However, despite several plausible mechanisms whereby obstructive sleep apnoea might be associated with left ventricular dysfunction and congestive heart failure, only limited data exist linking those disorders. These studies are reviewed along with possible mechanisms leading to left ventricular dysfunction in obstructive sleep apnoea. Recent investigations demonstrating improvement in left ventricular function after CPAP therapy in patients with congestive heart failure are reviewed as well. Finally, new data are presented from an animal model of congestive heart failure demonstrating a beneficial effect of CPAP on cardiac index in association with a decline in systematic vascular resistance. Remarkably, these effects persisted even after CPAP was removed. Possible mechanisms whereby CPAP may lead to improvement in cardiac output are discussed.

Journal Article↗
PubMed1995

Effect of CPAP on pericardial pressure and respiratory system mechanics in pigs.

It has been postulated that increased cardiac surface pressure with continuous positive airway pressure (CPAP) results in decreased left-ventricular (LV) transmural pressure. We tested this hypothesis in seven sedated, unanesthetized, and previously instrumented pigs. We measured pericardial (Pperi), LV, airway (P(aw)), and esophageal (Pes) pressures at CPAP values of 0, 4, 8, and 12 cm H2O before and after blood-volume expansion. With normovolemia, CPAP resulted in an increase in Pperi (from -2.0 +/- 7.6 mm Hg at CPAP 0 to 2.3 +/- 5.6 mmHg at CPAP 12, p < 0.05). Baseline end-diastolic Pperi rose with volume expansion from -2.0 +/- 7.6 mm Hg to 5.4 +/- 5.4 mm Hg, p < 0.05. With hypervolemia, CPAP was associated with a decrease in Pperi (from 5.42 +/- 5.4 mm Hg to 2.3 +/- 5.6 mm Hg, p < 0.05). By contrast, Pes rose equally under both conditions with CPAP. LV transmural end-diastolic pressure (TMEDP) fell significantly under normovolemic conditions (from 16.5 +/- 7.4 mm Hg at CPAP 0 to 13.6 +/- 9.0 mm Hg at CPAP 12). The changes in FRC (pneumotachometry) with CPAP were similar under both conditions. We conclude that the CPAP-induced decrease in LV volume under hypervolemic conditions cannot be explained by an increase in cardiac surface pressure. We present a model to explain the decrease in cardiac surface pressure with CPAP.

Animals↗
PubMed1995

Effects of CPAP on cardiac output in pigs with pacing-induced congestive heart failure.

Continuous positive airway pressure (CPAP) may improve left ventricular (LV) function in patients with congestive heart failure (CHF). To understand mechanisms involved, in nine sedated, unanesthetized pigs with pacing-induced CHF we measured cardiac index (CI), heart rate (HR), LV pressures and volumes, ejection fraction (LVEF), and maximal rate of LV pressure rise (dp/dtmax). LV end-systolic transmural pressure (afterload) was estimated as LV end-systolic pressure (LVESP)-CPAP. Measurements were taken at CPAP 0, 5, 10, and 15 cm H2O and during recovery. At CPAP 5 cm H2O, CI increased from 4.23 +/- 1.00 to 4.99 +/- 0.88 L/min/m2 (p < 0.005), LV end-systolic volume decreased from 82.3 +/- 32.1 to 72.7 +/- 30.3 ml (p < 0.04) and LVEF increased from 0.30 +/- 0.09 to 0.36 +/- 0.12 (p < 0.02), and dp/dtmax increased. LVESP-CPAP was unchanged. After CPAP was discontinued, there was a rise in CI (p < 0.03), HR (p < 0.03), LVESP (p < 0.02), dp/dtmax (p < 0.02) and a decrease in total peripheral resistance (p < 0.03). We conclude that in CHF, low levels of CPAP improved CI, at least partly by improving contractility. Increased CI after discontinuing CPAP may be due to sympathoadrenal stimulation or withdrawal of alpha-adrenergic tone.

Animals↗
PubMed1994

Effects of continuous positive airway pressure on cardiac output in normal and hypervolemic unanesthetized pigs.

Continuous positive airway pressure (CPAP) has been used to increase cardiac index (CI) in patients with congestive cardiomyopathy in the presence of elevated pulmonary wedge pressure. We hypothesized that with normovolemia, CPAP would decrease CI because of decreased left ventricular (LV) preload, whereas in hypervolemia CPAP would increase CI because of a decrease in afterload. We tested this hypothesis on nine sedated, unanesthetized pigs instrumented 5 to 10 d before study. We measured CI, heart rate, stroke volume, LV end-diastolic and end-systolic pressures, and LV dimensions at CPAP levels 0, 5, 10, 15, and 20 cm H2O before and after volume expansion with hetastarch (35 ml/kg). From LV dimensions, LV end-diastolic (LVEDV) and LV end-systolic volumes (LVESV) and LV ejection fraction (LVEF) were calculated. With normovolemia, CI and LVEDV decreased with increased CPAP. Volume infusion produced mild cardiac dysfunction as evidenced by increased LV volumes, decreased LVEF, and decreased contractility. With hypervolemia, CPAP produced an increase in CI, decrease in LVEDV and LVESV, and an increase in LVEF. At higher values of CPAP, we observed decreased CI and LVEDV as with normovolemia. We conclude that with normovolemia, CPAP's effects are mainly related to changes in preload. Hypervolemia produced mild cardiac dysfunction. The improvement in CI with CPAP appears predominantly to be secondary to decrease in LV afterload, but a mild preload effect, which parallels the effect seen with normovolemia, was superimposed on afterload changes at higher CPAP values.

Analysis of Variance↗
PubMed1993

Independent test of the fourth rib aging technique.

The sternal surface of the 4th rib has been suggested as a useful predictor of adult age-at-death (Iscan et al.: Journal of Forensic Sciences 29:1094-1104, 1984; American Journal of Physical Anthropology 65:147-156, 1984). We tested its ability to do so in two tests. In the first, we developed a method of seriation and target age assignment for the 4th rib so that inaccuracy and bias of the method could be assessed by decade. We found that the 4th rib shows characteristic changes in morphology with age and can be included in multifactorial age estimates. In the second test, we applied the phase method developed by Iscan et al. (Journal of Forensic Sciences 29:1094-1104, 1984). The results of our three judges were generally similar to those reported by Iscan and Loth (Journal of Forensic Sciences 31:122-132, 1986). Measures of race differences in 4th rib morphology were included in both tests. Americans of African descent (black) showed a non-significant trend for the rib changes to be delayed compared to Americans of European descent (white). This is in contrast to the work of Iscan et al., which predicted that blacks would show a tendency toward accelerated rib changes compared to whites, especially after the early 30s (phases 5-7) (Iscan et al.: Journal of Forensic Sciences 32(2):452-466, 1987).

Adolescent↗
PubMed1986

Mitoxantrone affects topoisomerase activities in human breast cancer cells.

The effects of mitoxantrone, an antineoplastic DNA intercalator, on topoisomerase I and II were studied in two human breast cancer cell lines. A large increase of topoisomerase I activity was found when cells were exposed to various doses of mitoxantrone. Maximal effect was achieved with 20 and 40 ng/mL in T47D and MCF-7 cells respectively. The enhancement on topoisomerase I activity seemed to be reversible, to be dependent on time of exposure to the drug and to require cellular integrity. Type II topoisomerase was inhibited in T47D cells after treatment for one hour with 10 ng/mL of mitoxantrone and enzyme activity was undetectable at higher doses (40 ng/mL). This inhibitory effect did not take place in vitro unless the concentration of the intercalator was increased to 400-500 ng/mL.

Anthraquinones↗
PubMed1984

The effect of maternally derived antibodies on the response of calves to vaccination against foot and mouth disease.

Studies were carried out in South America to assess the effect of maternally derived antibody (MDA) on the responsiveness of calves to FMD vaccination. It was found that calves with MDA did not merely fail to respond to vaccination, but that their serum titres were depressed. This depression was proportional to the level of pre-existing MDA at the time of vaccination and following primary vaccination it persisted for a least 60 days. High MDA titres interfered with both primary and secondary responses. Animals with relatively low MDA titres were able to respond to vaccination, or at least to be sensitized so that on revaccination they showed a satisfactory response. The half-life of MDA was shown to be approximately 22 days, suggesting that under field conditions significant MDA titres are likely to persist for 4-5 months. A trial carried out in Brazil in which the primary course of two inoculations, 4 weeks apart, was initiated when the calves were 5-6 months of age, resulted in the reduction of FMD in the calf population from 11% to 0.9% over a 12-month period. The use of vaccination programmes of this type to lessen the incidence of FMD in young bovines is discussed.

Animals↗