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Biomedical subjects

H Khan

Publications and source records attributed to H Khan.

14 recordsLinked to original sources

Interleukin-1 beta stimulates decidual stromal cell cyclo-oxygenase enzyme and prostaglandin production.

The cytokine interleukin-1 (IL-1 beta) increased prostaglandin production by decidual stromal cells in culture in a time and dose dependent manner. Optimum conditions for stimulation were found to be for 24 hours at a concentration of 100 pg IL-1 beta/ml. An apparent increase in cyclo-oxygenase enzyme synthesis accompanied the increase in prostaglandin production, and both changes were inhibited by the protein synthesis inhibitor cycloheximide. This implicates protein synthesis in the stimulatory effects of IL-1 beta, which may be mediated through the increase in cyclo-oxygenase enzyme. A pre-incubation period of 72 hours was found to be necessary to observe the stimulatory effect of IL-1 beta on prostaglandin production, but this did not seem to be due to any change in the sensitivity of the cells to IL-1 beta; the increase in the number of cyclo-oxygenase positive cells was the same if IL-1 beta was added on day 1, day 2 or day 3 of culture, even though prostaglandin production was not stimulated on day 1 or day 2. Cycloheximide increased prostaglandin production on the first two days of culture and had no effect on the third day of culture. This was interpreted as indicating that a factor inhibiting cyclo-oxygenase activity was synthesised during the initial period of culture, which prevented any increase in prostaglandin production following the increase in enzyme synthesis.

Cycloheximide

Effects of platelet-activating factor on prostaglandin E2 production by intact fetal membranes.

OBJECTIVE: The hypothesis tested in this study is that platelet-activating factor increases prostaglandin E2 synthesis from fetal membranes. STUDY DESIGN: Fetal membrane disks obtained before or after labor were incubated with or without platelet-activating factor for time periods of up to 24 hours. The production of prostaglandin E2 and its inactive metabolites was determined by specific radioimmunoassays. RESULTS: Platelet-activating factor (1 to 10 mumol/L) stimulated the production of prostaglandin E2 and its metabolites by intact fetal membranes and chorion-decidua threefold to fourfold after 24 hours of incubation. Platelet-activating factor had far greater effects on the production of prostaglandin E2 by intact fetal membranes obtained after the onset of labor, such that prostaglandin E2 production was increased by tenfold to 100-fold. CONCLUSION: These results suggest that platelet-activating factor mainly stimulates prostaglandin E2 production by the chorion-decidua before labor and that it may act in synergism with other stimulatory factors present in the fetal membranes during labor.

Amnion

Changes in decidual stromal cell function associated with labour.

OBJECTIVE: To determine whether decidual cells produce altered levels of prostaglandins after labour. DESIGN: Decidual stromal cells and macrophages were isolated before and after labour, and the production of prostaglandins E2 and F2 alpha measured. Changes in the numbers of cyclooxygenase enzyme positive cells were assessed by immunocytochemistry. RESULTS: Decidual stromal cells obtained after labour produced 30 times more prostaglandins E2 and F2 alpha in culture than cells obtained before labour. The increased production persisted for up to 72 h of culture, and was associated with an increase in the numbers of cyclooxygenase-positive cells from less than 5% to greater than 95%. No changes in macrophage function were observed. CONCLUSION: Increased levels of prostaglandins E2 and F2 alpha were released from decidual stromal cells after labour, suggesting that these cells may be an important source of prostaglandins in labour.

Decidua

A comparison of two populations of decidual cells by immunocytochemistry and prostaglandin production.

The decidua has been implicated in the control of human labour, particularly through changes in prostaglandin production, but this tissue contains a number of different cell types. A density gradient system was used to obtain two populations of cells from term human decidua, and these populations were characterised. The more dense cells (population B) was a mixed population, predominantly macrophages (80%), but small numbers of T- and B-lymphocytes were also present, as identified by immunocytochemistry. Most of these cell types also contained detectable levels of cyclooxygenase enzyme. The less-dense cell population (population A) did not contain significant numbers of the above cell types and released prolactin, suggesting that they were decidual stromal cells. This preparation of decidual stromal cells may be of use in defining the functions of these cells in labour.

Antibodies, Monoclonal

Calcitonin gene-related peptide and substance P decrease in the rabbit colon during colitis. A time study.

The sensory neuropeptides, substance P and calcitonin gene-related peptide, have been implicated in inflammatory reactions in several tissues. An immune-complex model of colitis was used in rabbits to determine the colonic content (nmol/g protein) of immunoreactive substance P and calcitonin gene-related peptide at various times after induction of inflammation to assess changes in these neuropeptides during the inflammatory response. Calcitonin gene-related peptide content was decreased by 66% 4 hours after induction of inflammation and reached a maximum of 80% at 48 hours. The substance P content was decreased at 8 hours, with a maximum decrease of 64% at 48 hours. Substance P decrease was detected in the muscle layer. The amounts of substance P in the mucosal/submucosal layer extracts were too low to allow accurate measurements. Calcitonin gene-related peptide decreased both in the muscle and the mucosal-submucosal layers. Immunohistochemical analysis showed that calcitonin gene-related peptide and substance P innervation patterns were comparable in normal and inflamed colon, even though there appeared to be a decrease in density and intensity of the staining, particularly for calcitonin gene-related peptide at 48 hours. The early decrease of calcitonin gene-related peptide and substance P during the time course of colitis might be due to release from nerve terminals of the gut during the inflammatory response. The profound changes in colonic calcitonin gene-related peptide and substance P content during colitis may have important implications during inflammation and subsequent tissue repair and may also lead to disturbances in gut motility.

Animals

Quantitative production of prostaglandin E2 and its metabolites by human fetal membranes.

Cultured amnion, choriodecidua and intact fetal membrane produced similar quantities of prostaglandin E2 (PGE2) (1-5 ng/ml). Choriodecidua and intact fetal membrane also produced very high levels of PGE2 metabolites (100-1000 ng/ml). The total production of PGE (PGE2 + PGE2 metabolites) was similar in intact fetal membrane and in choriodecidua, suggesting that the amnion, although a source of PGE2, contributes little to the overall PGE production by fetal membranes.

Amnion

Differential metabolism of intracellular and extracellular arachidonic acid by decidual stromal cells and macrophages.

Term decidual stromal cells metabolized extracellular arachidonic acid to cyclo-oxygenase, lipoxygenase and epoxygenase products. Prostaglandins were the major metabolites from extracellular arachidonic acid. In contrast, intracellular arachidonic acid was metabolized mainly to an epoxygenase product, together with some lipoxygenase products. Decidual macrophages showed similar results, though these cells had higher production rates per cell of most metabolites. The calcium ionophore A23187 increased the levels of arachidonic acid released from the intracellular stores of decidual stromal cells and had variable effects on the production of cyclo-oxygenase, lipoxygenase and epoxygenase metabolites. Less than 15% of the total metabolites released from A23187-stimulated cells were cyclo-oxygenase products, which suggested that the cyclo-oxygenase products released by decidual stromal cells or macrophages may be mainly derived from extracellular arachidonic acid. This implies that the regulation of decidual cyclo-oxygenase may have a major role in determining prostaglandin output from this tissue.

Arachidonic Acids

Limited transfer of prostaglandin E2 across the fetal membrane before and after labor.

The transfer of prostaglandin E2 (PGE2) across intact fetal membranes (amnion-chorion-decidua) obtained before and after the onset of labor was investigated using a novel system for in vitro fetal membrane culture. Studies using physiological concentrations of PGE2 showed that very little PGE2 will cross the membranes without being metabolised, before or after the onset of labor. It was only when pharmacological concentrations of PGE2 were used that the enzyme activity of the chorion was no longer able to prevent transfer of PGE2 without conversion to inactive metabolites. These results suggest that only small amounts of PGE2 from amnion are normally transferred across the chorio-decidua before or after the onset of labor, but the metabolism of PGE2 subsequent to transfer across the fetal membranes requires further assessment.

Arachidonic Acid

Skin barrier properties in the newborn. Transepidermal water loss and carbon dioxide emission rates.

Relative permeabilities of newborn and adult skin to small molecules were determined by measuring emission of carbon dioxide and water vapor through skin. Transepidermal water loss (TEWL) measured on the forearm of 22 term infants was lower than that observed in 30 control adults (0.31 +/- 0.09 vs. 0.39 +/- 0.15 mg/cm2/h). There was no significant difference between newborn carbon dioxide emission rates (CDER) and adults CDER. When environmental temperature was raised from 74 to 80 derees F, large dramatic increases in adult TEWL were observed in contrast to small increases in newborns. This phenomenon suggests diminished eccrine activity in the newborn. No correlation of TEWL or CDER with respect to birth weight, sex, age or gestational age was observed. Similar permeability to carbon dioxide in neonates and adults and a decreased TEWL in neonates compared to adults suggest that even at birth the skin functions as an efficient barrier to these molecules, penetration rates, in adults, of other polar compounds should be similar to those in neonates.

Adult