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Biomedical subjects

B L Brown

Publications and source records attributed to B L Brown.

At least 73 records · Page 4Linked to original sources
PubMed1988

Involvement of the hypothalamus in opiate-stimulated prolactin secretion.

Administration of opiate agonists to rats is known to elevate plasma prolactin, an effect which is antagonised by the opiate antagonist naloxone. However, this appears not to be a result of a direct action at the pituitary gland. We report here that opiate agonists stimulate prolactin secretion from isolated adenohypophysial cells when they are coincubated with hypothalamic fragments. Both morphine and Met-enkephalin stimulated prolactin secretion by 1.84 fold and 1.50 fold respectively, and this was antagonised by naloxone. These findings support the hypothesis that one site of action of opioid compounds on pituitary hormone secretion is at the level of hypothalamus.

Animals↗
PubMed1988

Diurnal variation in the effect of potassium depolarization on vasoactive intestinal polypeptide release from rat hypothalamus: a possible role for adrenaline.

We have previously reported a lack of effect of a depolarizing concentration of K+ on the release of vasoactive intestinal polypeptide (VIP) from the perifused rat hypothalamus, and suggested that this was due to the presence of an endogenous inhibitor of the release of VIP. In this study we report that the VIP response to K+ was restored if the hypothalami were obtained from animals killed during the dark phase of the light-dark cycle. Adrenaline blocked the K+-stimulated release of VIP when used at a concentration of 0.1 mumol/l; however, at a higher concentration (10 mumol/l) adrenaline stimulated the basal release of VIP. The use of specific receptor antagonists indicated that this dual effect of adrenaline was mediated through two distinct receptors, a stimulatory beta-receptor and an inhibitory alpha 2-receptor. The suggestion that adrenaline might be the endogenous inhibitor of the release of VIP, mediating the diurnal variation in the effect of K+, was supported by studies where 50 mmol K+/l was perifused concomitantly with an alpha 2-antagonist, restoring the VIP response to K+ in light-phase hypothalami. In conclusion, adrenaline has a dual role in the control of VIP release and may function to inhibit the K+-stimulated release of VIP in our system.

Animals↗
PubMed1988

Evidence that angiotensin II is a paracrine agent mediating gonadotrophin-releasing hormone-stimulated inositol phosphate production and prolactin secretion in the rat.

Gonadotrophin-releasing hormone (GnRH) stimulated the accumulation of inositol phosphates and prolactin secretion in anterior pituitary cells from young male rats. Saralasin [( Sar1, Ala8]-angiotensin II; a competitive antagonist of angiotensin II) inhibited the increase in both inositol phosphates and prolactin in a dose-dependent manner. Since angiotensin II has been shown to be a potent stimulus for inositol phosphate accumulation and prolactin secretion in the lactotroph, these findings suggest that angiotensin II acts as a paracrine agent, being released from the gonadotroph in response to GnRH and causing the lactotroph to release prolactin through an effect on phosphoinositide metabolism. The ability of GnRH to promote prolactin release was lost in pituitaries from older rats, and the increase in total inositol phosphate accumulation was less. These findings provide evidence of a physiological role for the presence of the renin-angiotensin system within the pituitary gland.

Angiotensin II↗
PubMed1988

Action of 1,25-dihydroxyvitamin D3 on phospholipid metabolism of human bone cells in culture.

It has recently been proposed that the action of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on bone metabolism may be mediated by changes in phospholipid metabolism. The effects of vitamin D metabolites on the incorporation of radiolabelled precursors into corresponding phospholipid classes were investigated using cells arising from cultured explants of normal human bone with osteoblast-like characteristics. Treatment with 1,25-(OH)2D3 increased the incorporation of serine, measured as the ratio of [3H]serine in phosphatidylserine (PS) to [14C]ethanolamine in phosphatidylethanolamine (PE), in a time- and dose-dependent manner. The maximum effect on PS/PE of 141.6 +/- 5.9% over control (P = 0.022) was observed at a dose of 0.1 nmol 1,25-(OH)2D3/l, maintained for 24 h. Incubations with 25-hydroxyvitamin D3 (0.1 mumol/l) and 24,25-dihydroxyvitamin D3 (10 nmol/l) had no effect. Supraphysiological doses (0.1 mumol/l) of 1,24,25- and 1,25,26-trihydroxyvitamin D3 showed similar effects to those of 1,25-(OH)2D3, emphasizing the importance of 1 alpha-hydroxylation. Incorporation of [14C]choline into phosphatidylcholine, calculated as a ratio to PE, was not affected by treatment with vitamin D metabolites. However, [3H]inositol uptake into phosphatidylinositol was almost doubled when compared with control uptake within 2 h of treatment with 1,25-(OH)2D3 (0.1 mumol/l). This may be of relevance, considering the importance of phosphoinositide metabolism in influencing the intracellular calcium concentration. These results support a role for 1,25-(OH)2D3 in the modulation of phospholipid metabolism in human bone cells, which in turn may be involved in the action of 1,25-(OH)2D3 in bone mineralization.

Bone and Bones↗
PubMed1987

Effect of opioid peptides and potassium on the release of vasoactive intestinal polypeptide and thyrotropin releasing hormone from perifused rat hypothalami.

Opioid peptides have been demonstrated to stimulate prolactin secretion, and it has been postulated that this is mediated, at least in part, by an effect on hypothalamic prolactin releasing and release-inhibiting factors and neurotransmitters. The aim of this study was to investigate the effect of opioid peptides and depolarizing concentrations of K+ on the release of both vasoactive intestinal polypeptide (VIP) and thyrotropin releasing hormone (TRH) from perifused rat hypothalami. Both met-enkephalin and beta-endorphin stimulated the release of VIP significantly whilst not affecting the release of TRH. In addition, leu-enkephalin was found to have no effect on the release of either VIP or TRH. In contrast, depolarizing concentrations of K+ (50 mM) were found to cause the immediate release of TRH, but not VIP, from the same perifusion. The results suggest a role for VIP, but not TRH, in opioid peptide stimulated release of prolactin. In addition, the data indicates that a substance may be released in response to K+ depolarization which is inhibitory to the release of VIP.

Animals↗
PubMed1987

Activation of dopamine receptors does not affect phosphoinositide turnover in NCB-20 cells.

Dopamine inhibits and serotonin stimulates adenylate cyclase activity in a neuroblastoma X Chinese hamster brain explant cell line (NCB-20). The inhibition of cyclic AMP accumulation by dopamine was blocked by pretreatment of the cells with pertussis toxin. Carbachol and bradykinin stimulated the accumulation of water-soluble inositol phosphates whereas thyrotropin-releasing hormone, vasopressin, neurotensin, and phenylephrine were without effect. Dopamine and serotonin had no significant effect on carbachol-induced phosphoinositide hydrolysis or the levels of the parent lipids within the membrane. Forskolin induced a much larger stimulation of cyclic AMP than did serotonin, and caused an increase in the levels of phosphatidylinositol-4-phosphate and phosphatidyl inositol-4,5-bisphosphate in the cell membrane.

Adenylate Cyclase Toxin↗
PubMed1986

Comparison of two dosing schedules of flurbiprofen for patients with rheumatoid arthritis. Twice-daily versus four-times-a-day schedules.

A total daily dose of 200 mg of flurbiprofen (Ansaid, Upjohn) was administered either twice daily (100 mg BID) or four times daily (50 mg QID) to 143 patients with rheumatoid arthritis. Results of this 12-week, randomized, double-blind study showed statistically significant reductions in the number of swollen joints, number of affected joints, duration of morning stiffness, and 50-foot walk time in patients receiving either treatment regimen. Using standard statistical tests, no significant differences between regimens were found. Flurbiprofen treatment was rated as "excellent" or "good" by approximately half of the patients and physicians following both BID or QID dosing.

Adolescent↗
PubMed1986

Flurbiprofen versus naproxen in the treatment of rheumatoid arthritis.

The efficacy and safety of flurbiprofen (Ansaid, Upjohn), 100 mg twice daily, were compared with those of naproxen, 250 mg twice daily, in a six-week, double-blind, randomized study involving 133 patients with rheumatoid arthritis. Patients completing the six-week treatment phase were then treated with flurbiprofen, 100 mg twice daily, during a six-week open-label phase. In the double-blind phase, both treatment groups showed improvement from baseline and, in general, the arthritic condition of all patients was significantly less severe while receiving treatment. In the open-label phase, the patients in whom therapy was switched from naproxen to flurbiprofen reported greater improvement compared with baseline than they did at the end of the double-blind phase. Statistically significant differences between medication groups were few. At weeks four and six, grip strength for the naproxen group increased from baseline by a marginal amount compared with the flurbiprofen group. Global evaluations of disease improvement by patients and physicians and proximal interphalangeal joint size showed trends in favor of flurbiprofen. In the double-blind phase, 29.4 percent of flurbiprofen-treated patients (n = 20) and 23.1 percent of naproxen-treated patients (n = 15) experienced side effects, most of which were gastrointestinal in origin. In the open-label phase, 81.0 percent of the patients (n = 87) satisfactorily completed the six weeks of flurbiprofen treatment. Based on this study, 100 mg of flurbiprofen administered twice daily was as effective as 250 mg of naproxen twice daily in the treatment of rheumatoid arthritis.

Adolescent↗
PubMed1986

Double-blind comparison of flurbiprofen and sulindac for the treatment of osteoarthritis.

In this double-blind, randomized trial involving 143 patients with osteoarthritis of the hip and/or knee, the efficacy and safety of twice-daily dosing with flurbiprofen (Ansaid, Upjohn), which has a half-life of 5.5 hours, were compared with those of sulindac, which has a half-life of 7.8 hours. Patients were treated with flurbiprofen (50 mg orally twice a day) or sulindac (150 mg orally twice a day) for six weeks. Based on evaluations by both patients and physicians, there were no statistically significant differences between the two treatment groups in most of the efficacy parameters studied. In addition, there were no statistically significant differences between the two treatment groups in the incidence or type of side effects, which were primarily gastrointestinal in origin. This study indicates that flurbiprofen, taken as 50 mg twice daily, is equally as effective as 150 mg of sulindac twice a day in the treatment of osteoarthritis.

Adult↗
PubMed1986

The influence of hemodialysis on the pharmacokinetics of ibuprofen and its major metabolites.

The pharmacokinetics of ibuprofen and its two major metabolites, the hydroxy and carboxy derivatives, were studied in seven functionally anephric subjects undergoing hemodialysis therapy. Subjects received ibuprofen 800 mg tid for 14 days. Hemodialysis was performed three times weekly during this period. Arterial and venous blood samples were collected before dialysis and along with dialysate, and during the final dosing interval and dialysis session. No accumulation of ibuprofen plasma concentrations and an absence of intact ibuprofen in dialysate indicated clearance through metabolic pathways. The metabolites did accumulate significantly (mean plasma levels, carboxy 249 micrograms/mL and hydroxy 57 mu/mL); however, both were detected in dialysate. Mean extraction efficiencies were 0.16 (hydroxy) and 0.15 (carboxy). Dialysis clearance calculated by arterial-venous difference was found to agree with actual recovery in dialysate for both metabolites. Side effects were not observed in any subject.

Adult↗
PubMed1986

The effect of interleukin-1 on connective tissue metabolism and its relevance to arthritis.

Interleukin-1 (IL-1) is the name given to a family of related proteins showing a variety of activities. It was originally shown to be produced by monocytes and macrophages but is now known to be produced by numerous cell types, including synovial cells. From the point of view of arthritis, its most interesting activities are those on connective tissue cells in vitro. These include stimulation of production of prostaglandins, plasminogen activator and metalloproteinases such as collagenase and proteoglycanase. IL-1 is also mitogenic for synoviocytes and bone cells, and can alter rates of production of extracellular matrix constituents. The presence of IL-1 in synovial fluids from rheumatoid and osteoarthritic joints and its actions on connective tissues in vitro suggest that IL-1 may play an important role in the pathogenesis of arthritis. There are several potential cellular sources of IL-1 in the inflamed rheumatoid joint and interactions between these cells, T lymphocytes and plasma cells may continually induce IL-1 so contributing to the chronicity of the disease. The mechanism of action of IL-1 on connective tissue cells is at present uncertain though preliminary studies suggest that IL-1 may induce cellular responses by stimulating phosphoinositide turnover and possibly protein kinase C activity.

Arthritis, Rheumatoid↗
PubMed1986

Relative durations of conditioned stimulus and intertrial interval in conditioned suppression.

The effects of the relative durations of the conditional stimulus and the intertrial interval on bar pressing during a conditioned-suppression procedure were examined as a function of two additional variables--type of operant baseline schedule and rate of shock presentation. In Experiment 1, response suppression was compared across components of a multiple fixed-ratio, random-ratio, fixed-interval, random-interval schedule, at relative conditioned-stimulus/intertrial-interval durations of 1/1, 1/4, and 1/9. In Experiment 2, relative conditioned-stimulus/intertrial-interval duration (1/5, 3/3, or 5/1) was manipulated across groups, while shock frequency (2, 6, or 10 shocks/hr) was manipulated within groups. In both experiments, suppression during the signal was virtually complete at all relative durations. Responding was also suppressed during the intertrial interval, but that suppression varied as a function of experimental manipulations. In Experiment 1, intertrial-interval response rates were higher when relative signal duration was 1/9 than when it was 1/1, although both relative signal duration and shock frequency, which covaried, could have contributed to the difference. In Experiment 2, the patterning of response rates between successive shocks was affected by relative duration, absolute rates during the intertrial interval varied as a function of shock frequency, and differences between suppression during the signal and suppression during the intertrial interval were affected by both relative duration and shock frequency. The data support an analysis based upon relationships between shock-correlated and intertrial-interval stimuli and, as assessed by the relative-delay-to-reinforcement metric, are comparable to results that have been reported from experiments using similar manipulations under the autoshaping paradigm.

Animals↗
PubMed1985

Modulation of cyclic AMP accumulation in GH3 cells by a phorbol ester and thyroliberin.

4 beta phorbol-12, 13-dibutyrate (PDBu) stimulated cyclic AMP accumulation in GH3 pituitary tumour cells in the presence of isobutylmethylxanthine. This effect persisted after preincubation of cells with cholera or pertussis toxins. In contrast, vasoactive intestinal polypeptide (VIP)-stimulated cyclic AMP accumulation was inhibited by PDBu in a dose dependent fashion (IC50 = 5.1 nM). Thyroliberin (TRH) had a similar, but non-additive, stimulatory effect on cyclic AMP accumulation with PDBu, however it did not inhibit VIP stimulation. These results suggest that TRH may stimulate cyclic AMP accumulation through protein kinase C and that stimulation of adenylate cyclase by PDBu and TRH may occur distal to the guanine nucleotide binding regulatory proteins, Ns and Ni.

1-Methyl-3-isobutylxanthine↗