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Biomedical subjects

A Ray

Publications and source records attributed to A Ray.

At least 145 records · Page 8Linked to original sources

Improvement of long-term preservation of isolated arrested rat heart: beneficial effect of the antiischemic agent trimetazidine.

Rat hearts, arrested in situ after intracaval injection of a simple mineral cardioplegic solution (St. Thomas), were preserved for 15 h at 4 degrees C either by simple immersion in the cardioplegic solution or low-flow perfusion by the same liquid (0.3 ml/min). Trimetazidine (TMZ) was added to the cardioplegic solution at a concentration of 10(-6) M in two additional groups corresponding to both preservation conditions. The biochemically determined ventricular ATP content was increased in immersed hearts by TMZ (+ 78%). The [ATP]/[Pi] ratio, as calculated from 31P nuclear magnetic resonance (NMR) spectroscopy, was significantly increased in both preservation conditions by TMZ: 0.08 +/- 0.03 versus 0.04 +/- 0.01 in immersed hearts and 0.53 +/- 0.13 versus 0.26 +/- 0.16 in perfused hearts (mean +/- SD). Intracellular pH was increased when TMZ was administered in perfused hearts (7.02 +/- 0.14 vs. 6.67 +/- 0.14, mean +/- SD). Functional recovery, estimated by the pressure developed by the left ventricle (intraventricular isovolumic balloon) when hearts were reperfused with a physiologic solution, was improved by TMZ in both preservation conditions: +137% in immersed hearts and +54% in perfused hearts. These results demonstrate that both the bioenergetic status of the myocardial cell and the functional capabilities of isolated, arrested, stored rat heart can be significantly improved by addition of the antiischemic drug TMZ to the preservation solution.

Adenosine Triphosphate↗

Alteration of cardiac energy state during development of hypertension in rats of the Lyon strain: a 31P-NMR study on the isolated rat heart.

The effect of different chronic blood pressure levels on cardiac energy metabolism was studied by 31P-NMR spectroscopy in perfused hearts from the Lyon strains of hypertensive (LH), normotensive (LN) and hypotensive (LL) rats at the ages of 12 and 21 weeks. The in vivo assessment of haemodynamic parameters measured at 21 weeks in anaesthetized rats with an ultraminiature catheter pressure transducer confirmed that left ventricular systolic pressure and mean aortic pressure were significantly greater (+25%) in LH rats than in LN and LL rats. In the LL animals, left ventricular systolic pressure was slightly reduced (-10%) and cardiac contractility (estimated by LV dP/dtmax) showed a 24% decreased compared to normotensive animals. The energy state of the cardiomyocytes was characterized at different work levels of isolated rat hearts, by determining the concentration of the free phosphorylated compounds at each work level. Changes in workload were induced by varying the calcium concentration in the perfusion fluid. Increasing extracellular calcium concentration resulted in a similar increase in left ventricular developed pressure (LVDP) in all groups studied. Intracellular pH was not influenced by either the age of the animals or the level of cardiac work, in the three groups of animals. ATP content of the LN and LL rats remained constant during the whole perfusion period while the 12 week-old LH rats showed a decreased ATP content with increasing cardiac work. In the older LH rats, ATP content was decreased at the highest work level (corresponding to 2 mM calcium). In response to the increase in work, phosphocreatine (PCr) content diminished and inorganic phosphate (Pi) content increased in both LN, LH and LL animals. PCr degradation and Pi accumulation were higher in the LH rats and less in LL rats compared to the LN. These changes were more important in the younger than in the older hypertensive animals. The relationship between LVDP and [Pi]/[PCr] indicates that oxidative metabolism is maximally activated in the young hypertensive rats and suggests that this maximal activation represents an adaptive phase to the increase in blood pressure. Since the difference between the metabolic pattern of the 21 week-old LH rats and age-matched LN rats was less pronounced, it is likely that a compensatory stage has been reached at that age.

Animals↗

A pharmacological investigation of the contribution of muscarinic receptor-linked potassium channels to the reversal by carbachol of positive inotropic responses of rabbit left atrium to cyclic AMP-generating agents.

The purpose of the present study was to investigate whether the reversal by carbachol of positive inotropic responses of left atria to forskolin and isobutylmethylzanthine (IBMX) is related to the ability of carbachol to open potassium channels. Pretreatment of rabbits with pertussis toxin resulted in complete loss of the ability of carbachol to inhibit isoproterenol-stimulated adenylate cyclase activity and cyclic AMP (cAMP) generation in the left atria. Under these circumstances, negative inotropic responses of the left atria to carbachol in the presence of forskolin and IBMX were only partially attenuated, suggesting that at least part of the reversal by carbachol of the positive inotropic responses to forskolin and IBMX occurs by a cAMP-independent mechanism. The same dose of pertussis toxin had a much greater inhibitory effect on the ability of carbachol to reverse the isoproterenol-stimulated positive inotropic response. The potassium channel blocker, 4-aminopyridine, had no effect on the ability of carbachol to inhibit isoproterenol-induced increases in cAMP levels in atria from saline-treated rabbits. 4-Aminopyridine produced a concentration-dependent attenuation of the inhibitory effect of carbachol on positive inotropic responses to forskolin and IBMX in the left atria from both saline and pertussis toxin pretreated rabbits. These results suggest that the ability of carbachol to open potassium channels contributes to the cAMP-independent component of the negative inotropic response to carbachol in the presence of forskolin and IBMX.

1-Methyl-3-isobutylxanthine↗

[Reoperation after failure of unicompartmental knee prosthesis. Therapeutic strategy and results based on 40 cases].

Forty revisions for failure of unicompartmental knee prostheses were assessed. Twenty-eight women and twelve men (mean age: 67 years) were reoperated. Failure of an medial single-compartment prosthesis was involved in 35 cases, of a lateral prosthesis in 5 cases. The initial prostheses had been cemented in 19 cases and uncemented in 21 cases. Preoperative functional conditions were assessed by Hungerford's functional score and a 200-points score. The radiological study before revision showed 35 cases of varus distortion; in 12 of these, the varus distortion exceeded 10 degrees. Rather than studying the causes for failure of the single-compartment prosthesis, it seemed more useful to try to define the adequate reoperation procedure strategy and analyze its results. Our procedure aimed at solving the following difficulties: surgical approach: the same incision as in the initial operation was performed, the primary prosthesis was removed and a two-stage treatment was justified in cases of infection, metallosis involved complete removal of debris, the problem of bone-recutting and, chiefly, the problem of residual bone defect requiring bone-graft. Bone-recutting was performed with the tibial and femoral elements of the primary prosthesis still in place and using the ancillary equipment of the new prosthesis. Bone defects involved the femur as often (14 cases) as the tibia (12 cases); tibial bone defects occurred more frequently with cemented prostheses (9 cases) than with uncemented prostheses (3 cases). Femoral graft being relatively easier to perform one of the two major difficulties in our strategy was the achievement of a tibial graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Analysis of the promoter element of the serum amyloid A gene and its interaction with constitutive and inducible nuclear factors from rabbit liver.

In an effort to identify regulatory elements of the serum amyloid A (SAA) gene that play a major role in its expression under acute-phase conditions, we studied the expression of a set of chimeric SAA-chloramphenicol acetyltransferase (CAT) plasmids containing a progressively deleted upstream 5' sequence of the SAA gene. Two regulatory regions (-314 to -135 and -135 to -31) capable of driving cytokine-induced transcription have been identified. Gel retardation assays revealed that the regulatory region located between positions -314 and -135 is a major site of interaction for highly inducible and constitutive nuclear proteins in acute-phase rabbit liver. DNase I footprint and competition analyses showed that this region contains two adjacent nuclear protein binding sites (between -191 and -140) with varying affinity for protein binding. Both of these binding sites are capable of driving cytokine-induced transcription of a reporter gene containing a minimal promoter. Detailed analyses of the inducible nuclear proteins that bind to this promoter element showed that they are homologues of the CCAAT/enhancer binding protein (C/EBP) family. Accumulation of the inducible nuclear factors under acute conditions, when maximal transcription activity has been reported, suggests a critical role for these proteins in the expression of the SAA gene.

Animals↗

Aspiration liver biopsy.

BACKGROUND: Traditional and disposable liver biopsy needles are expensive and add to economic burden in developing countries where the prevalence of liver disease requiring liver biopsy is high. AIM: To compare the technique of suction aspiration using a disposable syringe and an ordinary 40 mm long 18 gauge needle (internal diameter 1.27 mm), with Vim-Silverman's needle in obtaining liver tissue in patients with liver disease of various etiology. METHODS: Liver biopsy was performed in 60 patients each using either technique. The size of the biopsy tissue obtained and the number of times a diagnosis was reached with the two techniques were compared. RESULTS: The mean size of tissue obtained by suction aspiration (11.2 mm) was greater than that by the Vim-Silverman technique (6.3 mm) (p = 0.001). The tissue sample was inadequate for opinion in 3 patients in the aspiration group and in 10 patients in the Vim-Silverman group (p = ns). CONCLUSION: Suction aspiration liver biopsy can be done satisfactorily using disposable syringe and 18 gauge needle.

Biopsy, Needle↗

Role of kappa opioid receptors during stress responsiveness in rats.

Effects of kappa opioid agonist, ketocyclazocine (KCZ) and its antagonist, M(r) 2266, were evaluated on some stress responses in rats. KCZ (1 or 10 mg/kg, ip) dose-dependently attenuated cold restraint stress (CRS)-induced gastric ulcer formation. Similar gastric cytoprotection was also seen with KCZ (1 or 10 micrograms/rat, icv). Pretreatment of rats with M(r) 2266 (0.3 mg/kg, ip) clearly antagonized the ulceroprotective effects of both ip and icv KCZ. KCZ effects on the gastric mucosa during CRS were also reduced by naltrexone (5 mg/kg, ip) pretreatment. KCZ (1 or 10 mg/kg, ip) also attenuated the plasma corticosterone response to CRS and these effects were blocked by M(r) 2266 (0.3 mg/kg) pretreatment. These results indicate kappa opioid receptor involvement during stress reactions and also suggest possible opioidergic interactions during CRS.

Animals↗

Identification of novel inducible nuclear factors that interact with the acute phase responsive promoter element of rabbit alpha 1-acid glycoprotein gene.

Alpha 1-acid glycoprotein (alpha 1-AGP) is a major acute phase protein that is highly inducible during hepatic acute-phase response. To identify the promoter element(s) required for increased gene transcription under acute condition a 529 bp 5'-flanking region of alpha 1-AGP gene is fused to the chloramphenicol acetyl transferase (CAT) reporter gene and introduced into BNL liver cells. This DNA fragment is capable of inducing synthesis of the reporter gene-product about ten-fold when transfected cells are exposed to conditioned medium from lipopolysaccharide-stimulated peripheral monocytes. Deletion analyses have shown that sequences located between -224 to -22 are capable of eliciting this inducible promoter function. Using electromobility shift assay we have identified two novel inducible nuclear factors from turpentine-induced acute liver that can interact with this regulatory promoter region. Our results indicate that binding of these two factors to the promoter region of alpha 1-AGP gene is highly specific in nature and the induction of this gene under acute condition may involve their participation.

Animals↗

Cloning and structural characterization of a rabbit genomic DNA for alpha 1 acid glycoprotein.

The gene for rabbit alpha 1 acid glycoprotein (AGP) has been isolated from a lambda EMBL3 genomic DNA library. Isolated clone contains a 12 Kbp fragment of rabbit genomic DNA. Restriction endonuclease mapping has localized the gene within a 4.2 Kbp fragment spanning two EcoRI sites. Southern blot analysis of the rabbit genomic DNA and its comparison with the cloned gene indicates that there is only one gene for AGP present per genome. DNA sequence analysis of the cloned gene indicates that the entire gene, TATA box to the polyadenylation signal, is located within the 4.2 Kbp region and contains six exons representing the full-length cDNA described earlier (1). The 5'-end of alpha 1-AGP gene sequences from rabbit, human, rat and mouse have been compared. Such analysis reveals two conserved regions located between -63 bp and -36 bp and -29 bp and -1 bp of putative transcription start site, which may play a role in transcriptional induction of this gene during acute response. In addition to this conserved domain, DNA sequence upstream of the major transcription start site contains a potential element for Sp1 binding and a 18 bp long palindrome sequence followed by a short repeating dinucleotide sequence, which may be important in the regulation of AGP gene induction.

Animals↗

Role of cAMP in the functional interaction of carbachol with different cAMP elevating agents in rabbit atrium.

The muscarinic agonist carbachol antagonized positive inotropic responses of rabbit left atria to the beta-adrenoceptor agonist isoproterenol, the adenylate cyclase activator forskolin and the phosphodiesterase inhibitor IBMX. Carbachol also reduced cAMP levels elevated by isoproterenol, but had no significant effect on cAMP levels in the presence of either forskolin or IBMX. Pre-treatment of rabbits with a dose of pertussis toxin which completely blocked the reduction by carbachol of isoproterenol-induced increases in cAMP, also blocked the reversal by carbachol of positive inotropic responses to isoproterenol, but only partially attenuated the antagonism by carbachol of inotropic responses to forskolin and IBMX. These data suggest that antagonism by carbachol of forskolin and IBMX-induced increases in cAMP levels does not play an important role in the functional interaction of carbachol with these cAMP-elevating agents.

1-Methyl-3-isobutylxanthine↗

Modulation by naltrexone of stress-induced changes in humoral immune responsiveness and gastric mucosal integrity in rats.

The effects of restraint stress (RS) and the opioid antagonist, naltrexone, were evaluated on humoral immune responsiveness and gastric mucosal integrity in rats. RS for 24 h, but not 6 h, attenuated both the primary (PAR) and secondary antibody response (SAR) to sheep red blood cells (SRBC) after a single exposure to the stressor. Naltrexone (1 or 5 mg/kg) dose-dependently aggravated the effects of RS on anti-SRBC antibody titre in both PAR and SAR studies. Further, in rats sensitized with SRBC, RS (24 h), in addition to lowering the humoral antibody response, also induced gastric mucosal lesions. Both these responses were further aggravated with naltrexone pretreatment. These results are discussed in light of interactions between immune and visceral responses, and their regulation by endogenous opioids, during RS.

Animals↗

Effects of acute and chronic ketocyclazocine and its modulation by oxytocin or vasopressin on food intake in rats.

The effects of acute and chronic ketocyclazocine (KCZ, a kappa receptor agonist) and its interactions with oxytocin (OXY) or vasopressin (AVP) were investigated on food intake in free-fed rats. Acute treatment with KCZ (1 mg/kg) produced a generalized hyperphagia during the light phase (0-6 h) without influencing dark phase (6-24 h) food intake. On chronic administration, tolerance developed to hyperphagic effect during light phase, whereas an enhancement in the food intake was seen during dark phase. OXY or AVP (both at 10 micrograms/kg) per se, did not affect the food intake response during either the light or the dark phase, after acute as well as chronic treatment. In the interaction studies, acute AVP or OXY attenuated the hyperphagia of KCZ during the light phase. On chronic treatment, both AVP and OXY blocked (a) the tolerance, and (b) the "reverse tolerance" to the food intake response to KCZ during light and dark phases, respectively. These results are discussed in light of complex opioid-OXY/AVP interactions during food intake in rats.

Animals↗

Quinalphos-induced suppression of spermatogenesis, plasma gonadotrophins, testicular testosterone production, and secretion in adult rats.

Quinalphos (O,O-diethyl-O-[quinoxalinyl-(2)-thionophosphate]) is a well-known organophosphorus insecticide used extensively in agriculture that adversely interferes with the activity of testicular steroidogenic enzymes in rats. To investigate its effects on spermatogenesis, the other function of testes, quantitative evaluation of different varieties of germ cells at stage VII of the seminiferous epithelium cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatcytes (mPSc), and step 7 spermatids (7Sd), along with the radioimmunoassay of plasma FSH, LH, testosterone, and testicular testosterone, were performed in Wistar rats following treatment with quinalphos (250 micrograms/kg, ip) for approximately one (13 days) and two cycles (26 days) of the seminiferous epithilium. Massive degeneration of all varieties of germ cells at stage VII, remarkable reduction in the sperm count, and significant reductions in plasma concentrations of FSH and testosterone, along with testicular testosterone, were observed after quinalphos treatment. Significant reduction in the plasma concentration of LH was observed only after treatment for two cycles. Administration of human chorionic gonadotrophin for 26 days in rats injected with quinalphos partially prevented the degeneration of germ cells and increased testosterone production. It is suggested that quinalphos may have a suppressive influence on gonadotrophin release but its direct detrimental action at the level of the testes may also be responsible for the observed changes in spermatogenesis and in testicular testosterone production in rats.

Animals↗

Cytokines and their receptors: molecular mechanism of interleukin-6 gene repression by glucocorticoids.

Recent years have seen the discovery and molecular characterization of a bewildering array of cytokines and hematopoietic growth factors--and an even more complex description of their overlapping functions. The molecular cloning of a wide array of the cell-surface receptors for these cytokines has led to the recognition of classes of structurally related receptor superfamilies. The functional receptors for many of these cytokines (e.g., interleukin (IL)-2R and IL-6R) involve two distinct subunits; strikingly, the same beta subunit can interact with distinct alpha subunits to constitute the receptor for different cytokines (e.g., those for IL-3, IL-5, and granulocyte monocyte colony-stimulating factor). Considerable progress has also been made in defining the molecular mechanisms that underlie clinically relevant cytokine-related phenomena. As an example, the molecular mechanism by which glucocorticoids inhibit IL-6 gene expression has been shown to include the occlusion of the inducible enhancer and the basal promoter elements in the IL-6 promoter. Acute rejection episodes in renal transplant patients are accompanied by increases in serum IL-6 levels; the administration of glucocorticoids during these episodes leads to a rapid and marked decrease in IL-6 levels. It appears that the serum IL-6 level may be a useful diagnostic and prognostic indicator in the transplant patient.

Base Sequence↗

Effects of Azadirachta indica A Juss on some biochemical, immunological and visceral parameters in normal and stressed rats.

Effects of A. indica (AI) were evaluated on some biochemical, immunological and visceral parameters in normal and stress rats. AI (100 mg/kg) lowered blood glucose, triglyceride and SGOT levels in normal rats, and attenuated stress-induced elevations of cholesterol and urea levels. In rats immunized with SRBC, AI enhanced the humoral antibody response to the antigen. Further, AI facilitated the footpad thickness response to SRBC in sensitized mice and also enhanced leucocyte migration in immunized rats. In stressed rats, AI significantly attenuated the stress-induced (a) suppression of humoral immune response and (b) gastric ulcerogenesis. These results are discussed in light of the possible mechanisms involved in the effects of AI in normal and stressful situations.

Alanine Transaminase↗