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Biomedical subjects

S Bahrami

Publications and source records attributed to S Bahrami.

At least 19 recordsLinked to original sources
PubMed2006

Is third-time heart retransplantation justifiable?

Since repeat heart transplantation traditionally carries higher risk than primary engraftment, we tested the hypothesis that third-time cardiac allograft transplantation is associated with prohibitive mortality and morbidity. The cohort of all third-time cardiac retransplants performed at our institution (n=3) and reported to UNOS from 1987 to 2002 (n=10) was reviewed. The primary endpoints were early and late mortality. Extending the study frame through 2003 captures a total of 5 and 15 third-time heart transplant recipients in UCLA and UNOS databases, respectively. Of the 15 patients undergoing third-time retransplants, preoperatively one was ventricular assist device-dependent, four were on intravenous inotropes, and two had creatinine levels greater than 2.5. Additionally, four were male recipients of female donor hearts and the mean donor ischemic time was 2.6 hours. One patient was diagnosed with acute allograft rejection, 13 with coronary artery vasculopathy/chronic rejection, and one with primary graft failure. At our institution, five patients underwent a third heart transplant. There was no early or hospital mortality. One patient died late from transplant coronary artery disease and another following a fourth allograft. The mortality rate for third-time heart allograft recipients is acceptable. These results are influenced by small sample size, younger age, case selection, and operations at select, high-volume institutions with significant experience.

California↗
PubMed2005

Plasma D-lactate as a potential early marker for colon ischaemia after open aortic reconstruction.

BACKGROUND AND AIM: The breakdown of mucosal barrier function due to intestinal hypo-perfusion is the earliest dysfunction of ischaemic colitis. Severe colon ischaemia after aortic reconstruction is associated with mortality rates up to 90%. Therefore, early detection and treatment of patients with extensive ischaemic colitis is of crucial importance. In experimental studies, both D-lactate and bacterial endotoxin have been reported as markers of intestinal mucosal barrier impairment. However, evidence of their value in clinical practice is lacking. The aim of this pilot prospective cohort study was to assess the association between ischaemia of the colon (assessed histologically) and plasma levels of D-lactate and endotoxin in patients undergoing open aortic reconstruction. PATIENTS AND METHODS: Twelve consecutive patients underwent surgery between February and April 2003. Six patients underwent emergency surgery and six patients elective aortic surgery. D-Lactate and endotoxin levels were measured in blood samples collected according to a standardised protocol. For histological examination biopsies were obtained by sigmoidoscopy on days 4-6 after surgery, or earlier if indicated clinically. RESULTS: As early as 2 h postoperatively, elevated plasma levels of d-lactate were measured in patients with histologically proven ischaemic colitis. The peak of D-lactate elevation was on postoperative days 1 and 2. Concentration of plasma endotoxin was not significantly different in patients with or without ischaemic colitis. CONCLUSION: Our data suggest that plasma D-lactate levels are a useful marker for early detection of ischaemic colitis secondary to aortic surgery.

Aged↗
PubMed2003

Circulating S100B is increased after bilateral femur fracture without brain injury in the rat.

BACKGROUND: S100B is an acknowledged marker of brain damage. However, trauma without brain damage also causes an increase in S100B. S100B concentrations are highest in multiple trauma patients with long bone fractures. Clinically, extensive long bone fractures are associated with haemorrhagic shock and haemorrhagic shock per se is associated with increased S100B. The aim of our experimental study was to verify the S100B increase in long bone fracture without haemorrhagic shock. METHODS: and results. Bilateral femur fracture was carried out in 10 anaesthetized rats. Blood samples were drawn for immuno-luminometrical S100B measurement 5, 15, 30, 120, and 240 min after fracture. Mean arterial pressure (MAP), heart rate, and body temperature were monitored continuously. S100B increased after bilateral femur fracture and reached a peak 30-120 min after fracture (P<0.001). MAP remained at a level which is not associated with shock in rats. Heart rate and body temperature remained unchanged. Autopsy verified open bilateral femur fracture surrounded only by small zones of clotted blood. CONCLUSIONS: S100B is increased in bilateral femur fracture without haemorrhagic shock in rats. This finding suggests that bone marrow is a potential extracerebral source of S100B.

Animals↗
PubMed2001

Experimental evidence suggesting that nitric oxide diffuses from tissue into blood but not from blood into tissue.

The aim of this study was to evaluate in vivo whether nitric oxide (NO) is able to diffuse from blood into tissues and vice versa from tissues into blood. We used an in vivo model of intestinal ischemia (superior mesenteric artery occlusion) selectively increasing NO levels in intestinal tissue and an infusion of L-arginine selectively increasing NO levels in blood. In this model we followed formation of nitrosyl complexes of hemoglobin (Hb-NO) in blood and nitrosyl-diethyldithiocarbamate-iron complexes (DETC--Fe--NO) in ischemic intestine and normoxic tissues by means of electron paramagnetic resonance spectroscopy. NO trapping by DETC--Fe in the tissues resulted in a reduction of Hb--NO levels in blood accompanied by the formation of water-insoluble DETC--Fe-NO complexes in ischemic intestine and normoxic tissues both during ischemia and during reperfusion. Administration of L-arginine increased NO levels in blood but neither in ischemic intestine nor in normoxic tissue. Our data suggest that NO released in blood from endothelial cells does not diffuse into tissue. In contrast, NO formed in tissue diffuses into blood. The latter indicates that NO formed in tissues may exert its biological activities systematically.

Animals↗
PubMed2001

A unique murine monoclonal antibody recognizing HLA-B53, B37, B51, B52, +/-B44.

Monoclonal antibodies have played an important role in studying the biochemistry of the HLA-Class I molecules. Some murine anti-HLA mAbs can identify configurations of HLA epitopes that have never been reported in human allosera. One of these configurations is identified by an IgM mAb designated as: BHA-1441. This antibody was produced using a lymphoblastoid cell line typed as: A*02, A*25; B*38, B*4402/4405; C*0501, C*07, BW4, as the immunogen. A lymphocytotoxicity test of this mAb over a panel of 109 frozen, 452 fresh and, later, 44 DNA typed T cells revealed its specificity as B53, 37, 51, 52, +/- 44. All of the antigens recognized by this mAb share the Bw4 motif at positions 81-83, except for the HLA-B37, which shares only 82L and 83R. Furthermore, while B37 and B44 cross-react due to the aspartic acid (D) substitution at position 156, the reactivity with B53, B5 (51,52), B37 and 60% of B44 cells, makes it unlikely that the target epitope could be due only to the primary amino-acid sequence. The antibody-binding site might involve changes in tertiary structure and peptides bound by the MHC. BHA-1441 is an interesting tool to study and type the HLA-B53 antigen and its cross-reactive epitopes.

Amino Acid Sequence↗
PubMed2001

Endochondral ossification of costal cartilage is arrested after chondrocytes have reached hypertrophic stage of late differentiation.

Late cartilage differentiation during endochondral bone formation is a multistep process. Chondrocytes transit through a differentiation cascade under the direction of environmental signals that either stimulate or repress progression from one step to the next. In human costal cartilage, chondrocytes reach very advanced stages of late differentiation and express collagen X. However, remodeling of the tissue into bone is strongly repressed. The second hypertrophy marker, alkaline phosphatase, is not expressed before puberty. Upon sexual maturity, both alkaline phosphatase and collagen X activity levels are increased and slow ossification takes place. Thus, the expression of the two hypertrophy markers is widely separated in time in costal cartilage. Progression of endochondral ossification in this tissue beyond the stage of hypertrophic cartilage appears to be associated with the expression of alkaline phosphatase activity. Costal chondrocytes in culture are stimulated by parathyroid hormone in a PTH/PTHrP receptor-mediated manner to express the fully differentiated hypertrophic phenotype. In addition, the hormone stimulates hypertrophic development even more powerfully through its carboxyterminal domain, presumably by interaction with receptors distinct from PTH/PTHrP receptors. Therefore, PTH can support late cartilage differentiation at very advanced stages, whereas the same signal negatively controls the process at earlier stages.

Alkaline Phosphatase↗
PubMed2001

Purification and characterization of beta-methylaspartase from Fusobacterium varium.

Beta-methylaspartase (EC 4.3.1.2) was purified 20-fold in 35% yield from Fusobacterium varium, an obligate anaerobe. The purification steps included heat treatment, fractional precipitation with ammonium sulfate and ethanol, gel filtration, and ion exchange chromatography on DEAE-Sepharose. The enzyme is dimeric, consisting of two identical 46 kDa subunits, and requires Mg2+ (Km = 0.27+/-0.01 mM) and K+ (Km = 3.3+/-0.8 mM) for maximum activity. Beta-methylaspartase-catalyzed addition of ammonia to mesaconate yielded two diastereomeric amino acids, identified by HPLC as (2S,3S)-3-methylaspartate (major product) and (2S,3R)-3-methylaspartate (minor product). Optimal activity for the deamination of (2S,3S)-3-methylaspartate (Km = 0.51+/-0.04 mM) was observed at pH 9.7. The N-terminal protein sequence (30 residues) of the F. varium enzyme is 83% identical to the corresponding sequence of the clostridial enzyme.

Amino Acid Sequence↗
PubMed2001

Organ specific formation of nitrosyl complexes under intestinal ischemia/reperfusion in rats involves NOS-independent mechanism(s).

Intestinal ischemia/reperfusion may lead to local and distant organ damage involving nitric oxide (NO). NO rapidly reacts with heme/non-heme-iron-yielding nitrosyl complexes, which can be determined directly by electron paramagnetic resonance spectroscopy. The aim of the present study was to characterize nitrosylation reactions induced by transient intestinal ischemia in blood and tissues. We used electron paramagnetic resonance spectroscopy and reverse transcription polymerase chain reaction analyses to estimate nitrosyl complex levels and inducible NO synthase mRNA expression in rats subjected to superior mesenteric artery occlusion for 60 min followed by the reperfusion. Nitrosyl hemoglobin concentrations in circulating blood were significantly increased during ischemia and reperfusion. Nitrosyl hemoglobin complexes were detected in ischemic intestine, but not in normoxic lung and liver or reperfused intestine. Administration of N-G-monomethyl-L-arginine, a non-specific NO synthase inhibitor, did not affect the formation of circulating nitrosyl complexes. Moreover, inducible NO synthase mRNA was not found in intestinal tissues at 30 min of reperfusion. Our data suggest an organ-specific NO formation indicated by the increased nitrosylation reaction in ischemic intestinal tissue, but not in the distant normoxic organs, in spite of high circulating nitrosyl hemoglobin levels. NO involved in nitrosylation under intestinal ischemia/reperfusion is probably formed by NO synthase-independent mechanism(s).

Animals↗
PubMed2001

Cytokine synthesis in the liver of endotoxin-tolerant and normal rats during hemorrhagic shock.

In the present study the effects of endotoxin tolerance on hemorrhagic shock were investigated with particular focus on hepatic alterations. The following questions were addressed: (i) does hemorrhagic shock induce cytokine formation and heat shock response in the liver; and (ii) does endotoxin tolerance alter these reactions. Endotoxin tolerance was induced by repetitive daily injections of LPS for 5 days. Hemorrhagic shock was induced by hypovolemia (MAP 35 +/- 5 mmHg). After 3 h, the animals were resuscitated by re-infusion of homologous blood. m-RNA was isolated from liver biopsies and the mRNA levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10) and heat shock protein 70 (HSP-70) were determined by RT-PCR. TNF-alpha was measured by ELISA in serum samples and in the supernatants of whole blood cultures. It was found that endotoxin tolerance reduced mortality caused by hemorrhagic shock from 80% to 20%. In parallel, TNF-alpha production in response to LPS in vivo and in vitro was significantly decreased. During hemorrhage and after resuscitation. increased mRNA levels were detected in hepatic biopsies for TNF-alpha, IL-6, IL-10 and HSP-70, with highest levels immediately after re-infusion. Endotoxin-tolerant rats produced significantly lower levels of TNF-alpha, while no differences were found for IL-10 and HSP-70. Within 30 min after reperfusion, significantly higher levels of IL-6 mRNA were found in hepatic biopsies from tolerant rats; these differences disappeared 2 h after reperfusion.

Animals↗
PubMed2000

Periosteally derived osteoblast-like cells differentiate into chondrocytes in suspension culture in agarose.

Pluripotent cells from the periosteal layer adjacent to cortical bone attain an osteoblast-like phenotype in culture when reaching confluence in monolayer. It is unknown whether such newly differentiated osteoblast-like cells preserve the chondrogenic potential characteristics for stem cells derived from the periosteum. Primary osteoprogenitor cells derived from bovine metacarpal periosteum were differentiated into alkaline phosphatase-positive osteoblast-like cells by an established monolayer culture protocol. After transfer into suspension culture in agarose gels, the cells differentiated into chondrocytes demonstrated by the production of collagen II, but not of collagen I, as well as alkaline phosphatase activity was abated. Contrarily, with continuation of monolayer culture, the cells maintained their osteoblast-like phenotype and secreted large amounts of collagen I and a minor quantity of collagen III and V. The alkaline phosphatase activity steadily increased during the entire culture period of 2 weeks. Thus, our culture techniques can serve as useful tools to study mechanisms of differentiation by modulating the phenotypic potential of osteogenic cells. The results presented here support the notion that the extracellular environment strongly influences the cell type and its metabolism.

Alkaline Phosphatase↗
PubMed2000

Protection against endotoxemia in rats by a novel tetrahydrobiopterin analogue.

We studied the effects of a novel pterin antagonist of NO synthase, the 4-amino analogue of tetrahydrobiopterin (4-ABH4), in a rat model of endotoxic shock and compared its properties with those of N(G)-monomethyl L-arginine (L-NMMA). Treatment with a bolus dose of 4-ABH4 at 2 h after LPS challenge significantly improved the 6-day survival rate, compared with the controls treated with saline. L-NMMA treatment did not significantly influence the survival rate. This bolus treatment, using either compound, had no effect on the plasma nitrite + nitrate or plasma IL-6 levels. The continuous infusion of 4-ABH4 efficiently suppressed the enhanced calcium-dependent/independent NO synthase activities induced by endotoxin in lung homogenates and completely suppressed the increase in plasma nitrite + nitrate caused by endotoxin at 5 h, with no significant difference compared with the L- NMMA treatment. Treatment of RAW264.7 murine macrophages with 4-ABH4 but not with L-NMMA suppressed endotoxin-induced tumor necrosis factor-alpha release by the cells, whereas nitrite in the supernatant decreased in a dose-dependent fashion in both assay systems. Our data show that 4-ABH4, an inhibitor of inducible NO synthase, significantly improves survival in a rat model of endotoxic shock when administered in a bolus dose that does not reduce plasma total nitrite + nitrate levels. Because we observed no overt signs of toxicity and no influence on organ-specific tetrahydrobiopterin levels, we conclude that the novel compound 4-ABH4 is a promising drug candidate for protection against endotoxin-related mortality.

Animals↗
PubMed2000

Mitochondria recycle nitrite back to the bioregulator nitric monoxide.

Nitric monoxide (NO) exerts a great variety of physiological functions. L-Arginine supplies amino groups which are transformed to NO in various NO-synthase-active isoenzyme complexes. NO-synthesis is stimulated under various conditions increasing the tissue of stable NO-metabolites. The major oxidation product found is nitrite. Elevated nitrite levels were reported to exist in a variety of diseases including HIV, reperfusion injury and hypovolemic shock. Denitrifying bacteria such as Paracoccus denitrificans have a membrane bound set of cytochromes (cyt cd1, cyt bc) which were shown to be involved in nitrite reduction activities. Mammalian mitochondria have similar cytochromes which form part of the respiratory chain. Like in bacteria quinols are used as reductants of these types of cytochromes. The observation of one-e- divergence from this redox-couple to external dioxygen made us to study whether this site of the respiratory chain may also recycle nitrite back to its bioactive form NO. Thus, the aim of the present study was therefore to confirm the existence of a reductive pathway which reestablishes the existence of the bioregulator NO from its main metabolite NO2-. Our results show that respiring mitochondria readily reduce added nitrite to NO which was made visible by nitrosylation of deoxyhemoglobin. The adduct gives characteristic triplet-ESR-signals. Using inhibitors of the respiratory chain for chemical sequestration of respiratory segments we were able to identify the site where nitrite is reduced. The results confirm the ubiquinone/cyt be1 couple as the reductant site where nitrite is recycled. The high affinity of NO to the heme-iron of cytochrome oxidase will result in an impairment of mitochondrial energy-production. "Nitrite tolerance" of angina pectoris patients using NO-donors may be explained in that way.

Animals↗
PubMed1998

The inflammatory basis of trauma/shock-associated multiple organ failure.

Multiple alterations in inflammatory and immunologic function have been demonstrated in clinical and experimental situations after trauma and hemorrhage, in particular the activation of various humoral (e.g. complement, coagulation) and cellular systems (neutrophils, endothelial cells, macrophages). As a consequence of this activation process there is synthesis, expression and release of numerous mediators (toxic oxygen species, proteolytic enzymes, adherence molecules, cytokines), which may produce a generalized inflammation and tissue damage in the body. Mediators are responsible for ongoing interactions of different cell types and for amplification effects through their networks and feedback cycles, finally leading to a sustained inflammation and multiple organ damage in the body. In the setting of trauma/shock, many activators including bacterial as well as non-bacterial factors may be present that will induce local and systemic inflammatory responses. Although the potential role of bacteria/endotoxin translocation and its clinical relevance remains controversial, many lines of evidence support the concept that the gut may be the reservoir for systemic sepsis and subsequent MOF in a number of pathophysiologic states.

Bacterial Translocation↗
PubMed1998

[Transfusion of plasma of endotoxin tolerant rats improves survival of hemorrhagic shock in the rat model].

To evaluate the protective effect of endotoxin tolerant plasma after hemorrhagic shock, plasma of endotoxin tolerant animals was used for resuscitation of normal rats. The transfusion of plasma of endotoxin tolerant rats improved the survival rate from 20 to 60 per cent. In the sera of endotoxin tolerant animals a TNF inhibitory activity was detected, which could be transferred by the plasma. This effect may be responsible for the protection to hemorrhagic shock.

Animals↗
PubMed1998

[Endotoxin tolerance and hemorrhagic shock in rats].

The aim of the presents study was to investigate the protective capacity of endotoxin tolerance in a hemorrhagic shock model in rats. A pretreatment with low dose endotoxin induces a state of tolerance, which is characterized by decreased TNF alpha production in vivo and in vitro upon subsequent high dose endotoxin challenge. This endotoxin tolerance improves survival after hemorrhagic shock from 22.8% in untreated controls to 68.8 in tolerant rats. The protection was accompanied with the appearance of n TNF alpha inhibitory activity in the serum of endotoxin tolerant animals, which might be responsible for the improved survival after hemorrhagic shock.

Animals↗
PubMed1997

IL-6 release after intestinal ischemia/reperfusion in rats is under partial control of TNF.

Although there is much evidence to substantiate the view that tumor necrosis factor (TNF) plays a pivotal role in the pathogenesis of multiple organ injury subsequent to intestinal ischemia/reperfusion (I/R), it is still unclear whether TNF is involved in triggering the release of other inflammatory mediators in this condition. The current study was designed to determine the potential effects of TNF blockade, by means of monoclonal antibody (TNF MoAb) treatment, on plasma interleukin 6 (IL-6) in rats after acute intestinal I/R injury. Anesthetized rats underwent 75-min occlusion of superior mesenteric artery followed by 6 hr of reperfusion. The animals were treated with TNF MoAb or control protein at a dose of 20 mg/kg i.v. 30 min before the onset of I/R. Similar IL-6 responses in both the portal and the systemic circulation were observed in animals subjected to intestinal I/R, who showed a progressive increase in plasma IL-6 concentration upon release of the clamp. In animals receiving TNF MoAb before I/R, the subsequent IL-6 release following reperfusion was significantly blunted compared to the levels in controls (P < 0.05). The present study demonstrates that the activation and/or release of IL-6 in the setting of acute gut I/R may, at least in part, be mediated via TNF-dependent mechanisms, providing further evidence that a complex interaction exists between TNF and IL-6.

Animals↗