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R Rabinovici

Publications and source records attributed to R Rabinovici.

At least 19 recordsLinked to original sources
PubMed1998

Effect of liposome-encapsulated hemoglobin on the development of endotoxin-induced shock in the rat.

Liposome-encapsulated hemoglobin (LEH) is an experimental oxygen-carrying resuscitation fluid. Because LEH is cleared from the circulation primarily by the reticuloendothelial system, its effect on the development of sepsis remains a major concern. Thus, the present study aimed to evaluate whether LEH modifies consequences of endotoxemia in the conscious normovolemic rat. LEH infusion at 10% of estimated blood volume (n = 10) did not affect mortality (30%, p < .05) and serum tumor necrosis factor-alpha levels (6204 +/- 414, p < .05) induced by 3.6 mg/kg Escherichia coli endotoxin administered (intravenous bolus) 22 h later. In contrast, when a shorter LEH-endotoxin time interval (<12 h, n = 10) or a higher dose of endotoxin (14.4 mg/kg, n = 20) was tested, LEH enhanced endotoxin-induced mortality (90% and 100%, respectively, p < .05) and broadened serum tumor necrosis factor-alpha response without modifying its peak levels. LEH (n = 20) did not exacerbate the endotoxin-induced tachycardia, leukopenia, and thrombocytopenia. Therefore, in this model, the effect of LEH on endotoxin-induced responses was dependent on the time interval between LEH and endotoxin administration as well as the endotoxin dose. The clinical relevance of these results should be further investigated.

Animals↗
PubMed1997

Effect of liposome-encapsulated hemoglobin on triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol measurements.

The present study investigated the effect of liposome-encapsulated hemoglobin (LEH), an experimental oxygen-carrying resuscitation fluid, on triglyceride, total cholesterol, and low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol measurements. In vivo, the intravenous infusion of LEH (5.6 mL/kg, n = 6) elevated serum triglycerides (+92% vs. baseline, P < .05), total cholesterol (+25% vs. baseline, P < .01), LDL cholesterol (+72% vs. baseline, P < .01) and had no effect on serum HDL cholesterol. In addition, LEH did not alter the elevation in serum triglycerides (+302% vs. baseline, P < .01) and LDL cholesterol (+86% vs. baseline, P < .01) induced by lipopolysaccharide (3.6 mg/kg, i.v., n = 6. Ex vivo, measurements of triglycerides and total cholesterol as well as LDL and HDL cholesterol in whole blood from naive rats were not changed by the addition of LEH (0-50%, n = 6). In vitro, the addition of a fixed concentration of LEH (50%, n = 6) to varying concentrations of cholesterol solution (0-50%), or vice versa, had no effect on cholesterol determination. It is therefore concluded that LEH only minimally affects serum levels of triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol and does not interfere with their measurement.

Animals↗
PubMed1997

Candida pericarditis: clinical profile and treatment.

BACKGROUND: Candida pericarditis is a rare medical and surgical emergency which, unless treated, leads to impaired cardiac function and death. To facilitate early diagnosis, the clinical features of this condition should be identified. METHODS: Twenty-five cases of Candida pericarditis reported in the last 30 years along with 1 new case were reviewed with regard to demographics, precipitating factors, diagnosis, treatment, and outcome. RESULTS: The syndrome occurred in immunocompromised (73%), antibiotic-treated (62%), or postpericardiotomy (54%) patients. The clinical presentation was frequently subtle and nonspecific. Nevertheless, unexplained fever, an increasing cardiac shadow on chest roentgenogram, or the development of cardiac tamponade may be suggestive. Positive culture for Candida in pericardial fluid or histologic evidence of yeast forms in pericardial tissue establishes the diagnosis. A combination of pericardiocentesis followed by operative drainage and antifungal agents is the usual treatment. Untreated, Candida pericarditis is 100% lethal, whereas prompt diagnosis and treatment lead to cure (mean follow-up, 19 months). CONCLUSIONS: Fever and evolving cardiac tamponade in immunocompromised or postpericardiotomy patients may be suggestive of Candida pericarditis; the presence of organisms in pericardial fluid is diagnostic. Pericardiocentesis followed by operative drainage and antifungal agents appears to be the treatment that is most likely to be curative.

Adenocarcinoma↗
PubMed1997

The novel chemokine mob-1: involvement in adult respiratory distress syndrome.

BACKGROUND: Using differential display reverse transcriptase-polymerase chain reaction we have recently identified mob-1, the novel rat homologue of the human alpha-chemokine IP-10, as a highly inducible gene in adult respiratory distress syndrome (ARDS) lungs. The present study aimed to further implicate mob-1 in the pathogenesis of ARDS. METHODS: Pulmonary mob-1 mRNA up-regulation was confirmed by Northern blot analysis in three different rat models of ARDS-like lung injury and localized to pulmonary macrophages by using in situ hybridization. Also, Escherichia coli-derived recombinant mob-1 (rmob-1) was tested for its properties in relationship to lung injury. RESULTS: In vivo, intratracheal injection of rmob-1 (50 micrograms/rat) induced pulmonary leukosequestration (myeloperoxidase +93% +/- 8% versus control, p < 0.05) with preferential accumulation of neutrophils in bronchoalveolar lavage fluid (36.0% +/- 1.0% versus 0.1% +/- 0.1% in controls, p < 0.01). In vitro, transwell migration studies demonstrated chemotactic activity of rmob-1 (50 to 100 ng/ml) toward human monocytes (+151% +/- 34% versus rmob-1 vehicle, p < 0.01) and only weak chemotaxis for human neutrophils (+15% +/- 0% versus rmob-1 vehicle, p < 0.01). Utilizing a rat aortic ring model ex vivo, rmob-1 at 100 ng/ml exerted a very potent inhibitory effect on angiogenesis (-78.7% +/- 6.3% versus rmob-1 vehicle, p < 0.01), a major component of the resolution phase of ARDS. CONCLUSIONS: Taken together, these data support the involvement of mob-1 in the pathogenic mechanisms of ARDS possibly through chemotaclic actions on inflammatory cells and modulation of angiogenesis in the recovery phase of the disease.

Animals↗
PubMed1997

Platelet-activating factor and cardiac diseases: therapeutic potential for PAF inhibitors.

Platelet-activating factor (PAF) is a potent phospholipid mediator released from inflammatory cells in response to diverse immunologic and non-immunologic stimuli. Animal studies have implicated PAF as a major mediator involved in coronary artery constriction, modulation of myocardial contractility and the generation of arrhythmias which may bear on cardiac disorders such as ischemia, infarction and sudden cardiac death. PAF effects are induced by direct actions of PAF on cardiac tissue to modify chronotropic and inotropic activity, or indirectly via the release of eicosanoids such as thromboxane A2 (TXA2), leukotrienes (LT) or cytokines (TNF alpha). The development of selective, high affinity PAF receptor antagonists has permitted investigations on the role of PAF in experimental animal models of cardiac injury. In vivo and in vitro studies strongly suggest that PAF receptor antagonists might convey therapeutic benefits in ischemic conditions and certain arrhythmias. In addition, PAF antagonists might have a cardiac allograft-preservation effect. Although clinical studies with PAF receptor antagonists in patients with cardiac diseases have not yet been reported, the experimental results to date suggest that PAF receptor antagonists might be useful in some specific cardiac disorders in humans.

Animals↗
PubMed1997

Liposome-encapsulated hemoglobin modulates lipopolysaccharide-induced tumor necrosis factor-alpha production in mice.

OBJECTIVE: To investigate the effect of liposome-encapsulated hemoglobin, an experimental blood substitute, on the function of the mononuclear phagocytic system in normovolemic mic, in ex vivo murine splenocytes and in a transformed murine monocytic cell line, RAW 264.7. DESIGN: Prospective, randomized trial. SETTING: Center for Biomolecular Science and Engineering, Naval Research Laboratory, and the Thomas Jefferson University. SUBJECTS: Female Balb/c mice (n = 27). INTERVENTIONS: Mice were injected into the tail vein with liposome-encapsulated hemoglobin or liposome vehicle and were killed at varying time points for blood sampling and splenocyte isolation and culture. MEASUREMENTS AND MAIN RESULTS: Injection of liposome-encapsulated hemoglobin in mice (2.2 of lipid/kg and 0.56 g of hemoglobin/kg, n = 9) did not increase serum tumor necrosis factor (TNF)-alpha concentrations at 2, 8, 15, and 24 hrs after administration. In the ex vivo procedure, lipopolysaccharide (1 microgram/mL)-induced TNF-alpha production by splenocytes from mice injected with liposome-encapsulated hemoglobin was attenuated at 2 and 4 hrs (73%, p = .002 at 2 hrs), compared with TNF-alpha production by splenocytes from sham animals challenged with the same concentration of lipopolysaccharide. In the in vitro procedure, simultaneous exposure of liposome-encapsulated hemoglobin (0.88 to 8.8 mg/mL) and lipopolysaccharide (0.125 to 1 microgram/mL) to the murine-derived, peritoneal monocytic RAW 264.7 cell line showed significantly reduced TNF-alpha peptide, but not messenger RNA, 1 to 4 hrs after exposure as compared with cells challenged with lipopolysaccharide alone. This effect correlated with the rapid phagocytosis (1 hr to 4 hrs) of liposome-encapsulated hemoglobin by RAW 264.7 cells. Phagocytic activity in RAW 264.7 cells exposed to both liposome-encapsulated hemoglobin and lipopolysaccharide showed reduced uptake compared with uptake of liposome-encapsulated hemoglobin. The liposome-induced reduction in TNF-alpha peptide production elicited by lipopolysaccharide was countered by extending the time period to an overnight delay between liposome-encapsulated hemoglobin exposure and lipopolysaccharide challenge. Liposome-encapsulated hemoglobin incubated with lipopolysaccharide in vitro, and subsequently washed to remove free lipopolysaccharide, stimulated TNF-alpha expressed by RAW 264.7 cells. Incubation with liposome-encapsulated hemoglobin alone did not evoke TNF-alpha production in these cells. CONCLUSIONS: These data suggest that liposome-encapsulated hemoglobin modulates the response of the mononuclear phagocyte system to endotoxin, possibly through binding of lipopolysaccharide, presentation to macrophages with subsequent phagocytosis, and modulation of cytokine response by a posttranscriptional mechanism. This effect is attenuated by extending the period between exposure to liposome-encapsulated hemoglobin and endotoxin. The clinical relevance of these findings awaits further investigation.

Animals↗
PubMed1997

Platelet-activating factor (PAF) in experimental and clinical sepsis.

Despite considerable progress in understanding the pathogenic mechanisms of Gram-negative sepsis, the outcome of septic patients has not significantly improved. There are ample data that support a role for inflammatory mediators in sepsis that act in synergy with infectious agents to initiate and propagate the disease process. One such mediator is the glycerophospholipid platelet-activating factor (PAF). The objective of the present review is to summarize experimental and clinical evidence implicating PAF as a mediator in the pathomechanism of sepsis. This review is timely because many potent and selective PAF antagonists have matured for clinical development and a careful analysis of the data that support or refute the merit of clinical trials with such compounds may be important for both academic and pharmaceutical applications.

Animals↗
PubMed1996

Hypertonic saline treatment of acid aspiration-induced lung injury.

Airway acid aspiration leads to severe microvascular lung injury and pulmonary edema. Recent studies have demonstrated that other conditions associated with microvascular injury such as sepsis and burns can be effectively treated with low-volume hypertonic saline (HTS). Thus, the present study aimed to test whether HTS attenuates aspiration-induced lung injury in the rat. Intratracheal administration of 0.2 ml of 0.1 N HCl (n = 7) induced pulmonary leukosequestration [myeloperoxidase (MPO) activity +446 +/- 34%, P < 0.05; bronchoalveolar lavage (BAL) fluid neutrophil count + 178 +/- 23%, P < 0.05], edema (division 43 +/- 6%, P < 0.01), and microvascular permeability defect (BAL protein concentration +675 +/- 34%, P < 0.01). These changes were associated with tissue hypoxia (skeletal muscle PO2, 49 +/- 8 mm Hg, P < 0.05) and elevated serum TNF alpha (750 +/- 38 pg/ml, P < 0.01). HTS (2400 mosmole/liter) at 5 ml/kg, administered 20 min after aspiration (n = 7), reduced lung pulmonary edema by 58 +/- 7% (P < 0.05) and improved tissue oxygen tension (PO2, 85 +/- 7 mm Hg, P < 0.05) but failed to alter lung MPO and BAL fluid protein and leukocyte count response. Also, HTS did not reduce TNF alpha response to aspiration. These data point to a potential therapeutic role for low-volume HTS in treating aspiration-induced lung injury. In addition, our data suggest that HTS is acting by rapidly shifting fluid from the pulmonary interstitium to the intravascular compartment because it did not inhibit the inflammatory response to aspiration.

Animals↗
PubMed1996

Locally produced tumor necrosis factor-alpha mediates interleukin-2-induced lung injury.

Interleukin (IL)-2-induced microvascular lung injury is an experimental paradigm commonly used to investigate the pathogenesis of the adult respiratory distress syndrome. Since tumor necrosis factor-alpha (TNF-alpha) is known to induce such an injury in vivo and since TNF-alpha is involved in other models of lung injury, we postulated that it might also mediate pulmonary toxicity after IL-2 administration. The present study tested this hypothesis by evaluating the effect of TNF-alpha inhibition on IL-2-induced lung injury in the rat. Recombinant human IL-2 (10(6) U IV per rat, n = 6) elevated lung water, myeloperoxidase activity, and protein accumulation in bronchoalveolar lavage fluid and induced tissue hypoxia. Also, IL-2 enhanced lung tissue TNF-alpha mRNA and peptide (1543 +/- 496 pg/g lung wet weight) localized to alveolar macrophages by in situ hybridization. In marked contrast, IL-2 failed to affect serum TNF-alpha, which remained at undetectable levels. Pretreatment with anti-TNF-alpha monoclonal antibody (25 mg/kg IV, n = 7) or the TNF-alpha synthesis inhibitor rolipram (200 micrograms/kg IV, n = 7) attenuated lung injury and reverted tissue hypoxia. Furthermore, TNF-alpha inhibition prevented the upregulation of lung tissue IL-1 beta, IL-6, cytokine-induced neutrophil chemoattractant, and E-selectin (ELAM-1) but not intercellular adhesion molecule-1 mRNAs in response to IL-2. These data imply that locally produced TNF-alpha mediates IL-2-induced lung inflammation and tissue injury and point to the potential utilization of TNF-alpha inhibitors in treating the pulmonary toxicity of IL-2 immunotherapy.

Animals↗
PubMed1995

Aspiration-induced lung injury: role of complement.

OBJECTIVES: To examine the role of complement in the development of acid aspiration-induced lung injury in the rat. It was postulated that inhibition or depletion of complement attenuates aspiration-induced lung injury. DESIGN: Controlled animal trial. SETTING: Animal Laboratory, Jefferson Medical College, Philadelphia, PA. SUBJECTS: Anesthetized rats. INTERVENTIONS: Aspiration was induced by the intratracheal administration of 0.2 mL of 0.1 N hydrochloric acid (n = 7) and lung injury was evaluated by determining water content, myeloperoxidase activity, protein concentration, and leukocyte count in bronchoalveolar lavage fluid. Muscle PO2 was directly measured using a thin-film chamber oxygen sensor and serum tumor necrosis factor-alpha was assayed by enzyme-linked immunosorbent assay. The effect of complement inhibition by recombinant human soluble complement receptor type 1 (n = 8) or complement depletion by cobra venom factor (n = 7) on lung injury was evaluated. MEASUREMENTS AND MAIN RESULTS: Acid aspiration induced pulmonary leukosequestration, edema, and a microvascular permeability defect, along with tissue hypoxia. Pretreatment with soluble complement receptor type 1 (complement inhibition) or cobra venom factor (complement depletion) significantly reduced lung edema (-61 +/- 7%; p < .05), eliminated protein accumulation in bronchoalveolar lavage fluid (p < .01), and improved (p < .05) tissue oxygenation. In contrast, there was no effect of soluble complement receptor type 1 or of cobra venom factor on leukosequestration. CONCLUSIONS: Acid aspiration induces lung injury through a complement-dependent mechanism that leads to microvascular permeability defects. Therefore, the possibility that complement inhibitors may have a salutary effect in humans with aspiration-induced lung injury should be investigated.

Animals↗
PubMed1995

Mob-1 expression in IL-2-induced ARDS: regulation by TNF-alpha.

We have recently established an animal model of adult respiratory distress syndrome (ARDS)-like microvascular lung injury elicited by infusion of human interleukin-2 (IL-2). Based on the pronounced, transcriptional upregulation of multiple pro-inflammatory mediators in IL-2-induced ARDS, differential display was applied to search for potentially novel genes in this paradigm of lung injury. Differential display on total lung RNA derived from IL-2-challenged rats presented a highly reproducible 3'-UTR fragment profile in which a band (approximately 250 bp), termed B1, was strongly induced. B1 cDNA sequence exhibited 99.14% homology to the 3'-UTR of mob-1, a recently cloned gene belonging to the C-X-C chemokine superfamily. Furthermore, Northern blot analysis showed that IL-2-induced pulmonary mob-1 mRNA was expressed at time points before the onset of lung injury and suppressed after TNF-alpha inhibition. These data imply that lung mob-1 is a novel, highly inducible gene in a clinically relevant model of ARDS and, based on its identification as a chemokine, could participate in the development of lung injury.

Amino Acid Sequence↗
PubMed1995

Thoracic duct injury in penetrating neck trauma.

Thoracic duct laceration from penetrating neck trauma is a rare injury associated with significant morbidity. Seventy-one cases published in the English literature in the last 50 years, along with one new case, were reviewed in an attempt to characterize the clinical profile, treatment, and outcome.

Adult↗