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Biomedical subjects

A Ray

Publications and source records attributed to A Ray.

At least 127 records · Page 7Linked to original sources

Study on the activities of testes and accessory sex glands after losulazine treatment in rats.

Losulazine hydrochloride, an antihypertensive agent, was administered intraperitoneally to adult male Wistar rats in doses of 1, 2 and 5 mg/kg/day for 1 seminiferous epithelium cycle to determine its effects on testicular steroidogenesis, spermatogenesis and accessory sex gland function. Administration of low doses of losulazine (1 and 2 mg/kg) resulted in a significant elevation of the steriodogenic key enzymes activity along with significant depletion of cholesterol content in testicular tissue. In addition, a significant rise in acid phosphatase activity in testes and prostate, and fructose content in accessory sex glands was also observed after low doses of losulazine. However, treatment with a higher dose of losulazine (5 mg/kg) significantly reduced the activities of testicular steroidogenic enzymes and acid phosphatase, and the content of fructose in accessory sex glands. Quantitative evaluation of the different varieties of germ cells at stage VII of the seminiferous epithelium cycle and epididymal sperm count in all losulazine-treated rats revealed a persistant prominent detrimental change in spermatogenesis. The results of our present experiment demonstrate an adverse action of losulazine treatment on functional activities of testes and accessory sex glands in adult rats.

17-Hydroxysteroid Dehydrogenases↗

sin 1, a mutation affecting female fertility in Arabidopsis, interacts with mod 1, its recessive modifier.

In Arabidopsis thaliana, a mutation in the SIN 1 gene causes aberrant ovule development and female-specific sterility. The effect of the sin 1 mutation is polymorphic and pleiotropic in different genetic backgrounds. The polymorphism concerns morphology of the mutant ovules. The pleiotropism involves internodal distance and inflorescence initiation time. The particular ovule phenotype and the length of internodes are dependent on an interaction of sin 1 with a second recessive gene, which we term mod 1. The recessive mod 1 allele in a homozygous sin 1 mutant plant reduces internode length and ovule integument size. The mutation sin 1, but not mod 1, has a demonstrable effect on ovule morphology when acting independently. In our crosses mod 1 was inseparably linked to the well known mutation erecta that is known to cause a reduction in internode and pedicle lengths.

Arabidopsis↗

Serum amyloid A gene expression under acute-phase conditions involves participation of inducible C/EBP-beta and C/EBP-delta and their activation by phosphorylation.

Serum amyloid A (SAA) is a plasma protein whose synthesis is markedly increased in the liver during the inflammatory process. Previous analysis of SAA promoter function implicated the involvement of the CCAAT/enhancer-binding protein (C/EBP) in controlling this process. In this study, using antibodies against three C/EBP isoforms in DNA-binding and Western blot (immunoblot) assays, we found that in response to inflammatory signals, both C/EBP-delta and C/EBP-beta are induced and that their interactions with the SAA promoter element are necessary for the increased SAA gene expression. Cotransfections of liver cells with an SAA promoter-linked reporter chloramphenicol acetyltransferase gene and murine sarcoma virus-expressed C/EBP-delta or C/EBP-beta confirm such phenomena. The increased transactivating ability in the presence of the cellular phosphatase inhibitors okadaic acid and sodium orthovanadate, coupled with the observation that dephosphorylation severely inhibits the DNA-binding ability in vitro, implicates a role of phosphorylation in the regulation of the activities of the C/EBP-delta isoform. Consistent with these findings, we have detected higher levels of DNA-binding activity of C/EBP-delta prepared from cells treated with phosphatase inhibitors. We also present evidence that C/EBP-delta is a phosphoprotein. These results suggest that C/EBP-delta is regulated by phosphorylation and, in conjunction with C/EBP-beta, is one of the major proteins responsible for the increased transcription of the SAA gene in response to inflammatory stimuli.

Animals↗

The amygdaloid complex, corticotropin releasing factor and stress-induced gastric ulcerogenesis in rats.

The amygdaloid complex and corticotropin releasing factor (CRF) are both important in stress reactions and we thus evaluated the effects of intra-amygdalar CRF on stress ulceration in rats. Bilateral micro-applications of CRF (0.05, 0.5 or 5.0 micrograms) into the central amygdala (CEA) attenuated cold restraint-induced gastric mucosal lesions in a dose-related manner. Similar gastric cytoprotective effects were seen with intra-CEA noradrenaline (NA; 3.0 micrograms), whereas the NA neurotoxin, DSP-4 (25 micrograms), or the beta-adrenoceptor antagonist, propranolol (1 microgram), aggravated stress ulcer pathology. Intra-CEA pretreatment with DSP-4 or propranolol clearly reversed the ulceroprotective effects of CRF during stress. These results indicate that the CEA is a neural substrate for CRF effects, and CRF-NA interactions in this limbic area are crucial for the regulation of stress ulcerogenesis.

Amygdala↗

Regulation of rabbit alpha 1-acid glycoprotein gene expression in acute-phase liver. Identification of inducible and constitutive proteins like CCAAT-enhancer binding protein that interact with the 5'-proximal promoter elements.

To identify the cis-acting DNA sequences responsible for inducible transcription of rabbit alpha 1-acid glycoprotein gene, 5'-flanking region containing 529 bp of this gene and its various 5'-deletions were linked to the reporter gene coding for the bacterial chloramphenicol acetyltransferase (CAT) and analyzed for their ability to confer cytokine-mediated inducibility to the reporter CAT gene in liver cells. Deletion analysis has identified a 151-bp region from the sequence -186 to -35, that contains the regulatory promoter element(s) responsible for stimulation mediated by cytokines present in the conditioned-medium. Using mobility shift assays, we have identified highly inducible nuclear factors in acute liver nuclear extract that interact with this regulatory promoter region. DNase I footprint analysis has revealed two adjacent nuclear factor binding sites and competition of DNA-binding activity has indicated that the distal element of these two sites has higher affinity for nuclear factors than the proximal one. Both of these two regions have been found to be capable of directing conditioned-medium-induced transcription. Studies on the characterization of nuclear factors binding to these elements have shown that they belong to a class of transcription factors called CCAAT-enhancer binding protein (C/EBP). Our results indicate that binding of C/EBP-like factors to the inducible promoter elements of rabbit alpha 1-acid glycoprotein gene is highly specific and the induction of this gene under acute-phase conditions may involve their participation.

Animals↗

Functional NF-kappa B element in rabbit serum amyloid A gene and its role in acute phase induction.

Serum amyloid A (SAA) protein synthesis is highly induced in acute inflammatory conditions. Such induction process is primarily regulated at the transcriptional level and large amount of SAA mRNA has been found to accumulate in rabbit liver during acute inflammation. To identify the promoter element(s) involved in inducible transcription of SAA, a 5' flanking region of this gene has been fused to a reporter chloramphenicol acetyl transferase (CAT) gene and transfected into BNL liver cells. This DNA is capable of inducing synthesis of the reporter gene in response to lipopolysaccharide-stimulated monocyte-derived conditioned medium. Deletion analyses have shown that a region from -135 to -78 that contains a putative NF-kappa B element is responsible for the inducible function of the promoter. Gel shift assay has detected DNA-binding activity in the induced cells that appear to interact with the potential NF-kappa B element located within -112 to -78 of the SAA gene. Similar factor(s) have also been detected in the lipopolysaccharide-treated rabbit liver which is highly active in transcribing SAA mRNA. Appearance of these factors in acute-phase induced animals and their binding to the NF-kappa B-like element in the SAA proximal promoter region correlated with SAA mRNA synthesis suggests functional role of this promoter element in SAA gene expression under LPS-induced acute-phase condition.

Acute-Phase Proteins↗

Function and energy metabolism of isolated hearts obtained from hyperthyroid spontaneously hypertensive rats (SHR). A 31P-nuclear magnetic resonance study.

It was the aim of this study to evaluate the effects of hyperthyroidism on heart function and cardiac energy metabolism of spontaneously hypertensive (SHR) rats. Hyperthyroidism was induced by daily injections of T3 (0.2 mg/kg s.c.) for 14 days. The hearts were then isolated and perfused in the Langendorff mode. ATP, phosphocreatine (PCr), and inorganic phosphate (Pi) were measured continuously by means of 31P-nuclear magnetic resonance (NMR) spectroscopy. Work load was altered by varying stepwise the Ca++ concentration in the perfusion fluid from 0.5 to 1.0, 1.5, and 2.0 mM, respectively. At every elevation of the Ca++ concentration, the increase in left ventricular developed pressure (LVDP) was higher in the hyperthyroid SHR than in the untreated SHR hearts. The ATP and PCr concentrations were lower in the hyperthyroid SHR compared to the untreated SHR hearts throughout the perfusion period. PCr decreased at every Ca++ elevation in both the untreated and hyperthyroid SHR hearts. The PCr/ATP ratio was not altered at any Ca++ concentration neither in the untreated SHR nor in the hyperthyroid SHR hearts. The Ca(++)-induced stepwise elevation in LVDP was higher at any given PCr/Pi ratio in the hyperthyroid SHR than in the untreated SHR hearts. Thus, the Ca(++)-inducible contractile reserve was greater in the hyperthyroid SHR heart.

Adenosine Triphosphate↗

Effect of age on phosphorylated compounds and mechanical activity of isolated rat heart: a 31P-NMR study.

OBJECTIVE: The aim was to test the hypothesis that aging may change the function and energetics of isolated hearts subjected to an increased work load induced by varying the calcium concentration ([Ca2+]) in the perfusion fluid from 0.5 to 1.0, 1.5, or 2.0 mM. METHODS: Female Wistar rats aged 4, 12-14, and 22-24 months were used. Their hearts were perfused through the aorta and changes in myocardial phosphorylated compound concentration were measured by means of 31P-nuclear magnetic resonance spectroscopy and biochemical analysis. Myocardial contractility was measured in situ in closed heart anaesthetised animals and was followed in vitro during perfusion. RESULTS: The contractile indices measured in situ revealed a decrease with aging of the left ventricular developed pressure and dP/dtmax, while heart rate did not show any significant difference. In all age groups the stepwise increase in [Ca2+] caused a graded increase in left ventricular pressure in the perfused hearts. In aged rats, the left ventricular pressure associated with the different concentrations of Ca2+ was significantly lower than in young rats. In all three groups the myocardial content of inorganic phosphorus (Pi) increased in response to a rise in [Ca2+] and left ventricular pressure. The ATP content of the hearts remained constant in all three groups at each value of [Ca2+] induced left ventricular pressure. However, both ATP and total adenine nucleotide contents of the hearts were lower in aged rats. When the alteration in Pi due to each increase in [Ca2+] was expressed in relation to the rise in left ventricular developed pressure, this relationship was not significantly different in the three groups of hearts. CONCLUSIONS: The reduced mechanical activity of aged rat hearts is not due to a diminished efficiency of the mechanisms transferring high energy phosphates.

Adenosine Triphosphate↗

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↗