Opposing Action Research Articles

Pt/ZrO2/TiO2 catalysts for selective hydrogenation of crotonaldehyde: Tuning the SMSI effect for optimum performance

Gas phase hydrogenation of crotonaldehyde was performed over Pt/ZrO2/TiO2 catalysts with different zirconia loadings, subjected to low- and high-temperature calcination (200 and 400 °C) and a range of reduction temperatures (200–600 °C). Pt/TiO2 was used as reference system. The catalysts were characterised by TPR, XPS, SEM, HR TEM, TOF-SIMS and H2, O2 and CO chemisorption after different stages of thermal pretreatments. The relationship between catalytic activity, selectivity towards crotyl alcohol and physicochemical properties of the catalysts was examined. The catalyst containing 30% ZrO2 in the support, calcined at 200 °C and reduced at 500 °C showed the highest selectivity (50%) while retaining good activity. The explanation of those properties was proposed, involving the mutually opposing action of two factors – presence of ZrO2 and ‘permeability’ of Pt phase for TiOx migration – in controlling of the SMSI effect.

Opposite effects of $gamma;1- and $gamma;2-melanocyte stimulating hormone on regulation of the dopaminergic mesolimbic system in rats*1

By use of the brain microdialysis technique we show that administration of γ1-melanocyte stimulating hormone (γ1-MSH) into the ventral tegmental area of anaesthetized rats causes an increase in the release of extracellular dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the nucleus accumbens, while γ2-MSH causes the opposite effect. Moreover, γ2-MSH pre-treatment considerably reduced the γ1-MSH-induced effects. Our findings suggest an opposing action of two γ-MSH-activated pathways on the mesolimbic dopaminergic system, which could be important in the maintenance of a balanced psychoactivation state.

Opposite effects of γ 1- and γ 2-melanocyte stimulating hormone on regulation of the dopaminergic mesolimbic system in rats

By use of the brain microdialysis technique we show that administration of γ 1-melanocyte stimulating hormone (γ 1-MSH) into the ventral tegmental area of anaesthetized rats causes an increase in the release of extracellular dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the nucleus accumbens, while γ 2-MSH causes the opposite effect. Moreover, γ 2-MSH pre-treatment considerably reduced the γ 1-MSH-induced effects. Our findings suggest an opposing action of two γ-MSH-activated pathways on the mesolimbic dopaminergic system, which could be important in the maintenance of a balanced psychoactivation state.

Interleukin-18 is a novel mitogen of osteogenic and chondrogenic cells.

IL-18 was identified due to its ability to induce interferon-gamma (IFNgamma) production by T cells. It is a pleiotropic factor that shares structural features with IL-1 and functional activities with IL-12. IL-18 has a role in T cell development, where it has been demonstrated to act cooperatively with IL-12 to regulate IFNgamma. In bone, IL-18 is mainly produced by macrophages, but is also expressed by osteoblasts and inhibits osteoclast formation through granulocyte-macrophage colony-stimulating factor (GM-CSF) and not IFNgamma production by T cells. We have investigated the effects of IL-18 on mature osteoclast activity and for potential actions on osteoblasts or chondrocytes. The effects of IL-18 on mature osteoclast activity were determined using two assays: isolated mature osteoclast cell culture and neonatal murine calvarial organ culture. IL-18 did not affect bone resorption in either assay system. The actions of IL-18 on osteogenic cells (primary cell cultures of fetal rat and neonatal mouse osteoblasts, as well as neonatal mouse calvarial organ culture) and primary chondrocytes (canine) were assessed by proliferation assays (quantification of cell numbers and thymidine incorporation). In each assay system, IL-18 acted as a mitogen to the osteogenic and chondrogenic cells. Since IL-18 signal transduction may involve IFNgamma or GM-CSF, we assessed their involvement in the IL-18 response. IL-18 did not induce IFNgamma production by primary osteoblasts, but, of greater significance, IFNgamma had the opposing action to IL-18 in that it inhibited the primary osteoblast cell proliferation. Although IL-18 rapidly induced GM-CSF production by primary osteoblasts, IL-18 was still mitogenic in osteoblast preparations established from GM-CSF-deficient mice. Combined, these studies indicate that IL-18 may have an autocrine/paracrine mitogen role for both osteogenic and chondrogenic cells, independent of the production of IFNgamma or GM-CSF.

Interaction Between Interleukin 10 and Interleukin 6 in Human B-Cell Differentiation

Contrary to their opposing action on human T-lymphocytes and monocytes, both Interleukin (IL-)10 and IL-6 are potent differentiation factors of human B-cells. Both are known to induce immunoglobulin (Ig) production. The precise mechanism of this converging effect of IL-6 and IL-10 remains elusive, however. Here we investigated the role of IL-6 in the IL-10 dependent B-cell differentiation into Ig secreting cells. We found that co-stimulation of SAC-stimulated human peripheral B-lymphocytes with IL-10 and IL-6 exhibited no additive effect on Ig production over stimulation with IL-10 alone, and that IL-6 receptor blockade only mildly inhibited IL-10 induced Ig synthesis. In fact, we could show that stimulation of B-cells with IL-10 somewhat suppressed SAC induced autocrine IL-6 production. Despite this suppression IL-6 levels remained sufficiently high to stimulate its receptor, and IL-6 binding to the B-cell surface was not affected. The failure of IL-6 to exert an additional effect on SAC+IL-10 induced Ig production suggests that IL-10 may recruit components of the IL-6 intracellular pathway for Ig induction. In conclusion we could demonstrate that IL-10 acts on B-cell differentiation independently of autocrine IL-6 and that it had a considerably mild effect on B lymphocytic autocrine IL-6 secretion. This still allows an IL-6 effect in the presence of IL-10 which appears adaptive with a view to the converging effects of these two cytokines on human B lymphocytes. Our study thus adds to the appreciation of the complex cytokine regulation of the immune system.

Modulation of murine melanocyte function in vitro by agouti signal protein.

Molecular and biochemical mechanisms that switch melanocytes between the production of eumelanin or pheomelanin involve the opposing action of two intercellular signaling molecules, alpha-melanocyte-stimulating hormone (MSH) and agouti signal protein (ASP). In this study, we have characterized the physiological effects of ASP on eumelanogenic melanocytes in culture. Following exposure of black melan-a murine melanocytes to purified recombinant ASP in vitro, pigmentation was markedly inhibited and the production of eumelanosomes was decreased significantly. Melanosomes that were produced became pheomelanosome-like in structure, and chemical analysis showed that eumelanin production was significantly decreased. Melanocytes treated with ASP also exhibited time- and dose-dependent decreases in melanogenic gene expression, including those encoding tyrosinase and tyrosinase-related proteins 1 and 2. Conversely, melanocytes exposed to MSH exhibited an increase in tyrosinase gene expression and function. Simultaneous addition of ASP and MSH at approximately equimolar concentrations produced responses similar to those elicited by the hormone alone. These results demonstrate that eumelanogenic melanocytes can be induced in culture by ASP to exhibit features characteristic of pheomelanogenesis in vivo. Our data are consistent with the hypothesis that the effects of ASP on melanocytes are not mediated solely by inhibition of MSH binding to its receptor, and provide a cell culture model to identify novel factors whose presence is required for pheomelanogenesis.

Ro 15-4513 alteration of pentobarbital dependence

This study investigated the ability of the benzodiazepine inverse agonist, Ro 15-4513, to alter the expression of physical dependence on pentobarbital. Male Sprague-Dawley rats were made physically dependent on pentobarbital by continuous, IP, infusion of escalating doses of pentobarbital for 12 days. In Experiment 1, pentobarbital dependent rats received either vehicle or Ro 15-4513, in doses of 5, 10, or 15 mg/kg, IP, periodically during the pentobarbital abstinence period. As expected, Ro 15-4513 produced a significant, dose-dependent, exacerbation of withdrawal signs in the pentobarbital dependent rats. In Experiment 2, either vehicle or Ro 15-4513, at a dose of 15 mg/ kg, was administered, IP, once daily during the 12 days of continuous pentobarbital infusion. During the subsequent pentobarbital abstinence period it was noted that the withdrawal signs were significantly reduced in the rats receiving the daily administration of Ro 15-4513. It is hypothesized that the benzodiazepine inverse agonist, Ro 15-4513, may inhibit the development of physical dependence on pentobarbital through an opposing action on the GABA-A receptor.

Fluoride therapy in osteoporosis: Acute effects on parathyroid and mineral homoeostasis

1. Acute metabolic effects of sodium fluoride therapy were analysed among 41 osteoporotic patients already receiving large calcium supplements, 33 of whom underwent simultaneous metabolic balance studies. 2. Mean serum calcium fell transiently within 24-48 h by 0.03 +/- 0.07 (SD) mmol/l (P less than 0.01) and phosphorus by 0.06 +/- 0.08 (SD) mmol/l (P less than 0.001). In a subgroup, ionized calcium fell and biologically active parathyroid hormone (bio-PTH) rose more than fivefold (P less than 0.01). Urine calcium rose after an insignificant fall. 3. Pretreatment calcium and phosphorus balances were significantly positive and did not change overall during the first 8 days of treatment. However, on analysing balances in two groups relative to serum changes, in patients whose serum levels changed least sodium fluoride increased faecal calcium (P less than 0.025) and phosphorus (P less than 0.01) and reduced calcium balance (P less than 0.01), giving a mean balance difference between the two groups of 2.1 mmol daily (P less than 0.001). 4. Very small changes in serum levels therefore indicate well-marked metabolic responses: sodium fluoride acutely stimulates bio-PTH activity and must also enhance mineral uptake from circulation into tissue(s). By separate and opposing action(s) it inhibits intestinal calcium and phosphorus absorption, predominantly in those whose serum levels remain stable. All these effects may be relevant to long-term therapeutic results.

Ethanol effect on the ionic transfer through isolated human amnion. I. Preventive and antagonistic actions of some nutrients and of their synthetic congeners

The inhibition of the placental transfer of nutrients was studied in the pathogenesis of the fetal alcohol syndrome. Ethanol reduces the ionic transfer through the human amnion. In this study, the preventive and antagonistic actions of natural nutrients (Mg 2+, Ca 2+, taurine, homotaurine, γ-aminobutyric acid) and of their synthetic congeners (Ca 2+-taurinate, Ca 2+-acetyltaurinate, Ca 2+-acetylhomotaurinate) were observed on the amniotic conductance which was modified by ethanol. All the molecules, except Mg, demonstrated protective actions on the fetal side. The effect varied with the molecule and its concentration. An absolute protective effect was obtained on the maternal side with Ca 2+-acetylhomotaurinate and Ca 2+-taurinate. Some molecules, which have protective actions, had no opposing actions (homotaurine), or inversely (Mg 2+), only Ca 2+-acetylhomotaurinate exhibited both a preventive and an opposing action against ethanol. These results show the interest of studying synthetic molecules for prevention of fetal alcoholism.

Body Temperature and Information Processing Capability

Typically, human performance is projected to fluctuate in a circadian manner, usually in association with body temperature rhythm. Such sinusoidal relationships are isomorphic in that they are, under most normal circumstances, phase-locked in environmental time. As body temperature rises so performance is improved. However, increase in temperature above the zenith does not result in increased capability. Rather, such elevation has the dual and opposing action of speeding performance while elevating error rate to produce an overall diminution of efficiency (e.g., Allan and Gibson, 1979; Nunneley, Reader, and Maldonado, 1982). It has been suggested that deep body temperature controls the speed of performance, while skin temperature mediates error through the control of comfort associated with peripheral variation. To overcome distress connected with peripheral increase, yet to utilize the superior speed elicited by alteration of central temperature change, the use of selective head heating has been explored. The present paper synthesizes data from selective heating studies and indicates the potential gains which may be realized in complex machine operation. Results from this paradigm have suggested facilitation in stimulus assimilation, decision making capability and response selection and execution (e.g., Hancock, 1983; Hancock and Dirkin, 1982; Holt and Brainard, 1976). This facilitation is not linear in temperature change. To a 1°C increase there appears a change in decision criterion such that individuals become more conservative in response. Above this threshold value, veridical gains in performance are manifest with a reduction in both task latency and error rate. Simple physiological accounts of such behavior are largely inadequate as the precise physiological effect has yet to be thoroughly documented. An initial outgrowth of this work is the potential usage of fluctuation in head temperature as a dynamic physiological reflection of imposed mental workload (e.g., Hancock, Meshkati, and Robertson, 1984). These performance facilitations under relatively slow temperature changes are contrasted with decrement observed under rapid temperature fluctuation. A potential relationship with the notion of attentional resource capacity is explored.

The action of nitroglycerine on digitalis induced ST depression in patients with coronary disease (author's transl)

The influence of therapeutic digitalisation on ST depression due to myocardial ischemia was investigated in 11 patients, average age 53.6 years, with coronary heart disease, compared with the effectiveness of nitroglycerine. Therapeutic digitalis led to an average increase of ischaemic ST depression from -0.53 to -0.73 mV. The mean pulmonary arterial and pulmonary capillary pressure decreased slightly, the frequency of pectanginous attacks increased. Independent of the digitalis effect nitroglycerine had an opposing action on these parameters. In decompensated patients with coronary heart disease (n = 4) both digitalis and nitroglycerine produced a shift of the left ventricular function curve as an expression of improved cardiac action. This could not be observed in patients with compensated ventricular function (n = 7). In sufficient ventricular function digitalis led to a further increase of myocardial ischaemic ST depression. In ventricular insufficiency no uniform behaviour was apparent. ST depression induced by digitalis could be reversibly influenced by nitroglycerine.

Cyclic GMP breaks pupal diapause in the flesh fly Sarcophaga crassipalpis

Cyclic GMP and derivatives, when injected into diapausing pupae of the flesh fly Sarcophaga crassipalpis, promptly initiate adult development, whereas cyclic AMP and derivatives are inert. By injecting pupae simultaneously with cyclic nucleotides and a low level of ecdysterone, we find an opposing action for the two nucleotides: cyclic GMP + ecdysterone synergistically enhance the breaking of diapause while cyclic AMP antagonizes the effect of an ecdysterone injection. Phosphodiesterase inhibitors (caffeine, aminophylline, papaverine) are moderately effective agents in terminating diapause. Cholera toxin (an adenylate cyclase activator) produces only a slight response at 19 C, but its ability to break diapause is increased when pupae are transferred to 25 C.

A kinetic model for phosphofructokinase based on the paradoxical action of effectors

Effectors of muscle phosphofructokinase show opposing action on the activity of the enzyme depending upon the concentration of phosphoryl donor employed in the assay. Established inhibitors, such as citrate, activate at low ATP or ITP concentrations while known activators, such as AMP, ADP, and cyclic AMP inhibit at low ATP or ITP concentrations. Inorganic phosphate, on the other hand, activates at all substrate concentrations. The paradoxical effects at low substrate concentrations are dependent upon the order of addition of reaction components. A model is proposed to explain these and other regulatory phenomena of phosphofructokinase.

ACTH stimulation and glucocorticoid inhibition of renin release in the rat.

SummaryIn the rat, ACTH effected a transient rise in the level of plasma renin. Pretreatment with glucocorticoids completely inhibited the ACTH-induced renin rise. After adrenalectomy or inhibition of steroidogenesis by aminoglutethimide. ACTH produced a sustained rise in plasma renin level. Thus in the rat, ACTH has a direct effect on the juxtaglomerular apparatus causing a rise in plasma renin activity and glucocorticoids have an opposing action.

Cardiovascular action of 1, 1-dimethyl-4-phenylpiperazinium iodide (DMPP): A ganglion stimulating agent useful in the diagnosis of pheochromocytoma

1. 1. DMPP (1,1-dimethyl-4-phenylpiperazinium iodide) stimulated sympathetic ganglia more powerfully than nicotine and tetramethylammonium iodide and had less ganglion paralyzing action than nicotine in dogs, cats, rabbits and man. It differed from nicotine also in that its vasopressor action was largely independent of carotid and aortic chemoreceptor function. Respiratory stimulation, however, depended in part upon stimulation of these chemoreceptors. 2. 2. The pressor effect of DMPP depended upon release of epinephrine and/or norepinephrine from the adrenal glands and liver and stimulation of sympathetic ganglia with resultant vasoconstriction and cardioacceleration. The drug had no prominent direct action on blood vessels, at least in the perfused denervated dog's leg. 3. 3. Stimulation of parasympathetic ganglia caused initial transient bradycardia and fall in blood pressure that tended to inhibit the pressor action of DMPP. This opposing action was especially prominent after spinal cord section at C 6 and was eliminated by atropine or section of the vagus nerves. 4. 4. Section of the spinal cord at C 6 or paravertebral sympathectomy augmented the pressor action of DMPP, since these procedures also augment the pressor action of epinephrine and nor-epinephrine. 5. 5. TEAC, nicotine and hexamethonium all inhibited the ganglion-stimulating action of DMPP. The adrenergic blocking agents, priscoline, regitine and RO 2-3248, inhibited the pressor action of DMPP to a degree directly dependent on the inhibition of pressor response to nor-epinephrine. 6. 6. Response to DMPP was not altered by production of chronic neurogenic hypertension in dogs by section of the carotid sinus and aortic depressor nerves. But during the acute hypertension immediately following section of the buffer nerves the late sustained pressor action of DMPP was often replaced by a pronounced depressor effect. The significance of this difference is unknown, other than it may be listed with other observations suggesting that the two forms of hypertension depend on different mechanisms. 7. 7. DMPP has proved useful in the diagnosis of pheochromocytoma because of its strong and specific action on ganglia and adrenal medullary tissue. It ensures a high secretory activity of the tumor, the effect of which is specifically inhibited by adrenergic blocking agents.