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PubMed2005

Analytical electron microscopy studies of lithium aluminum hydrides with Ti- and V-based additives.

The microstructure of LiAlD(4) with TiCl(3).1/3(AlCl(3)) and VCl(3) additives has been studied during different steps of the decomposition process using electron energy loss spectroscopy and energy-dispersive X-ray spectroscopy in a scanning transmission electron microscope. Energy filtered transmission electron microscopy was used to show elemental distributions in the samples. The spatial distribution of the additives and the main elements within the alanate particles was examined with a resolution of a few nanometers. The analysis of the electron energy loss spectra reveals the chemical state of Al, O, and the additives. Ti and V do not appear to mix chemically with Al to a significant degree. V was found in high concentration in just a few particles, while Ti is more uniformly distributed. All the samples showed evidence of oxidation despite procedures being adopted to avoid exposing the material to air. The additives are oxidized in all the samples, and Al(2)O(3) forms a thin layer at the surface of the particles. This paper gives a comparison between samples at different stages of the decomposition process using different additives.

Journal Article↗
PubMed2005

Group additive values for the gas phase standard enthalpy of formation of hydrocarbons and hydrocarbon radicals.

A complete and consistent set of 95 Benson group additive values (GAV) for the standard enthalpy of formation of hydrocarbons and hydrocarbon radicals at 298 K and 1 bar is derived from an extensive and accurate database of 233 ab initio standard enthalpies of formation, calculated at the CBS-QB3 level of theory. The accuracy of the database was further improved by adding newly determined bond additive corrections (BAC) to the CBS-QB3 enthalpies. The mean absolute deviation (MAD) for a training set of 51 hydrocarbons is better than 2 kJ mol(-1). GAVs for 16 hydrocarbon groups, i.e., C(C(d))(3)(C), C-(C(d))(4), C-(C(t))(C(d))(C)(2), C-(C(t))(C(d))(2)(C), C-(C(t))(C(d))(3), C-(C(t))(2)(C)(2), C-(C(t))(2)(C(d))(C), C-(C(t))(2)(C(d))(2), C-(C(t))(3)(C), C-(C(t))(3)(C(d)), C-(C(t))(4), C-(C(b))(C(d))(C)(H), C-(C(b))(C(t))(H)(2), C-(C(b))(C(t))(C)(H), C-(C(b))(C(t))(C)(2), C(d)-(C(b))(C(t)), for 25 hydrocarbon radical groups, and several ring strain corrections (RSC) are determined for the first time. The new parameters significantly extend the applicability of Benson's group additivity method. The extensive database allowed an evaluation of previously proposed methods to account for non-next-nearest neighbor interactions (NNI). Here, a novel consistent scheme is proposed to account for NNIs in radicals. In addition, hydrogen bond increments (HBI) are determined for the calculation of radical standard enthalpies of formation. In particular for resonance stabilized radicals, the HBI method provides an improvement over Benson's group additivity method.

Journal Article↗
PubMed1995

Addition of methyl thioglycolate and benzylamine to (Z)-ligustilide, a bioactive unsaturated lactone constituent of several herbal medicines. An improved synthesis of (Z)-ligustilide.

(Z)-Ligustilide [1] is a dihydrophthalide purported to be the active ingredient of Ligusticum plant species widely used as herbal medicines in the Orient and in Native American and Hispanic cultures. It readily underwent 1,6-conjugate addition with methyl thioglycolate in the presence of triethylamine. The methyl thioglycolate reaction also yielded a product from addition to the C-6-C-7 double bond and a diadduct from both 1,6-addition and addition to the C-6-C-7 bond. Reaction of 1 with benzylamine did not afford a 1,6-adduct, but yielded instead an N-benzyllactam, presumably formed by rearrangement from initial 1,2-addition to the carbonyl. An improved total synthesis of 1 was developed. (Z)-Ligustilide had weak antiviral properties and weak antimicrobial activity against Gram-positive, Gram-negative, and yeast microorganisms. The broad biological activity of 1 and its electrophilic reactivity are consistent with the use of Ligusticum species in folk medicine.

4-Butyrolactone↗
PubMed2006

Catalytic asymmetric addition of dialkylzinc reagents to alpha-aldiminoesters.

[reaction: see text] The first catalytic, enantioselective addition of organozinc reagents to alpha-aldiminoesters is described. The use of a Lewis acid/Lewis base containing bifunctional catalyst preorganizes both reactive substrates to promote enantioselective addition over the racemic background reaction and alternative addition modes. Alcohol additives were found to enhance the enantioselection. The addition product was also found to cyclize with remaining substrate to provide imidazolidines.

Catalysis↗
PubMed1998

Ring addition of the alpha-amino group of glutathione increases the reactivity of benzoquinone thioethers.

2-(Glutathion-S-yl)-1,4-benzoquinone was found to be remarkably unstable in phosphate buffer (pH 7.4) even in the absence of oxygen. Intramolecular addition of the alpha-amino group of the glutamate residue to the quinone ring yielded ultimately 2,3-(glutathion-N, S-yl)-1,4-benzoquinone and 2,6-(glutathion-N,S-yl)-1,4-benzoquinone in a 3:1 ratio along with 2-(glutathion-S-yl)-1,4-hydroquinone. Kinetic studies indicated that the cyclization reactions proceeded at a rate k1 of 0.093 min-1, while intermolecular reactions followed a second-order kinetics with a k2 of 94 M-1 min-1 (pH 7.4, 37 degreesC), resulting in multiple polymerization products. Both intramolecular amino adducts of 2-(glutathion-S-yl)-1,4-benzoquinone are prone to hydrolysis, leading to the insertion of an additional OH group in the ring. These S-substituted trihydroxybenzene derivatives are particularly susceptible to autoxidation. The model compound 6-(N-acetylcystein-S-yl)-2-hydroxy-1,4-hydroquinone was shown to form readily two atropoisomeric biphenyls upon autoxidation: 2,4'-bis(N-acetylcystein-S-yl)-2',3,3',4,6, 6'-hexahydroxybiphenyl, indicating C-C coupling, presumably via semiquinone radical intermediates. Thus, the sequence of glutathione S-addition, followed by oxidation, N-addition, oxidation, and hydrolysis, constitutes a novel and very effective activation pathway of quinones for eliciting oxidative stress. These data underline the fact that glutathione conjugates of autoxidizable aromatics are no obligatory stable end products of a detoxication reaction. The possible toxicological impacts of intra- and intermolecular addition reactions of quinoid thiol conjugates are discussed.

Acetylcysteine↗
PubMed1998

Additive effect of mifepristone and tamoxifen on apoptotic pathways in MCF-7 human breast cancer cells.

MCF-7 cells growing in culture were used to study the mechanism of the antiproliferative activity of the antiprogestin mifepristone, as compared with the antiestrogen 4-hydroxytamoxifen or the combination of both. These steroid antagonists induced a significant time- and dose-dependent cell growth inhibition (cytotoxicity). This inhibition of cell survival was associated with a significant increase in DNA fragmentation (apoptosis), downregulation of bcl2, and induction of TGFbeta1 protein. Abrogation of the mifepristone- and/or 4-hydroxytamoxifen-induced cytotoxicity by TGFbeta1 neutralizing antibody confirms the correlation between induction of active TGFbeta1 and subsequent cell death. The effect of a combination of mifepristone and 4-hydroxytamoxifen on cell growth inhibition, on the increase in DNA fragmentation, bcl2 downregulation, and induction of TGFbeta1 protein was additive and significantly different (P < 0.05) from the effect of monotherapy. A translocation of protein kinase C (PKC) activity from the soluble to the particulate and/or nuclear fraction appeared to be also additive in cells treated with a combination of both 4-hydroxytamoxifen and mifepristone. These results suggest that the mechanism of the additive antiproliferative activity of mifepristone and tamoxifen could be explained at least in part by an additive induction of apoptosis in both estrogen and progesterone receptor positive MCF-7 breast cancer cells. A bcl2 downregulation, the PKC transduction pathway, and TGFbeta1 expression seem to be involved in this additive mechanism of action. Our data further suggest that a combination of an antiprogestin with tamoxifen may be more effective than tamoxifen monotherapy in the management of human breast cancer.

Apoptosis↗
PubMed1998

Additive effect of latanoprost and dorzolamide in patients with elevated intraocular pressure.

PURPOSE: To evaluate the additive ocular hypotensive effect of latanoprost and dorzolamide in combination, on intraocular pressure reduction in patients with elevated intraocular pressure (IOP). METHODS: Thirty patients with ocular hypertension or early capsular or primary open-angle glaucoma and elevated IOP were randomly assigned to two parallel treatment groups. The treatment period was twenty days. Fifteen patients (Group 1) received latanoprost once daily during the first ten days and, in addition, dorzolamide three times daily during the second ten days. Fifteen patients (Group 2) received dorzolamide three times daily during the first ten days and, in addition latanoprost, once daily during the second ten days. IOP was measured and conjunctival hyperemia was evaluated. RESULTS: In Group 1, the mean IOP on day 0 was 26.8 mm Hg; on day 10, 18.7 mm Hg; and on day 20, 15.9 mm Hg. In Group 2, the mean IOP on day 0 was 26.3 mm Hg; on day 10, 21.2 mm Hg; and on day 20, 16.1 mm Hg. Both groups had clinically significant IOP-lowering effect on day 10 as compared with baseline day (30.2% and 19.4% respectively) (p<0.01). When dorzolamide was added to latanoprost, the additional IOP reduction was 2.8 mm Hg (15%) (p<0.01) compared with 5.1 mm Hg (24.1%) (p<0.01) when latanoprost was added to dorzolamide. No local serious adverse reactions were observed. A mild but statistically significant increase in conjunctival hyperemia was seen in latanoprost applied patients. CONCLUSIONS: The results showed that latanoprost and dorzolamide can be combined successfully to reduce IOP with their additive effects.

Adult↗
PubMed2000

Additivities of compounds that increase the numbers of high affinity [3H]muscimol binding sites by different amounts define more than 9 GABA(A) receptor complexes in rat forebrain: implications for schizophrenia and clozapine research.

BACKGROUND: The numbers of [3H]MUS binding sites were reported to be elevated in layers II and III, but not V or VI, in cingulate cortex of schizophrenic brains post mortem. These increases in [3H]MUS binding sites are probably due to compensatory up-regulation of GABA(A) receptors on pyramidal cells as a consequence of a selective loss of GABAergic interneurons in layer II of cingulate cortex. The number of [3H]flunitrazepam binding sites was reported to be reduced in schizophrenic cingulate cortex, and this may directly reflect the loss of GABAergic interneurons. Chronic administration of clozapine to rats was reported to significantly reduce the numbers of [3H]MUS binding sites in temporal cortex and hippocampus which may be due to selective blockade of GABA(A) receptors on GABAergic interneurons that make synaptic contact with pyramidal cells. Basket cells are GABAergic interneurons that make synaptic contact with pyramidal cells as well as other interneurons. Basket cells can also generate both theta and gamma oscillations. Clozapine increases the power of theta and gamma EEG. Schizophrenic patients show reduced EEG power at 40 Hz (gamma frequency) but not at lower frequencies during auditory stimulation. The GABA(A) receptor blocker bicuculline at 10 nM, but not 10 microM, was reported to increase the amplitude of slow oscillations (< or =1 Hz) in rat hippocampal slices. It therefore seems possible that clozapine, by selectively blocking another GABA(A) receptor, could increase the amplitude of gamma oscillations. FINDINGS: Twenty-six compounds that inhibit [35S]TBPS binding in ways that are reversible by 10 nM R-5135 were found to increase [3H]MUS binding to membranes prepared from rat whole forebrain. In almost all cases the increases in binding were due to increases in the number of binding sites with little effect on affinity (Kd) for [3H]MUS. Concentration-response curves for the compounds revealed maximum increases in [3H]MUS (Esat) binding ranging from 140% (for meclizine) to 313% of control for honokiol. Additivity experiments showed that propofol (44% above control) and diflunisal (50% above control) were almost entirely additive, but there was also a small, but significant overlap, suggesting the existence of three groups of [3H]MUS binding sites defined by propofol and diflunisal. Meclizine was entirely additive with both propofol and diflunisal, indicating the existence of a fourth [3H]MUS binding site. Alphaxalone is also completely additive with meclizine, and has an Esat value significantly larger than that for propofol + diflunisal suggesting a fifth [3H]MUS binding site. The Esat for mefenamate is significantly greater than the Esat for alphaxalone, and mefenamate is also completely additive with meclizine, suggesting the existence of a sixth [3H]MUS binding site. The Esat for magnolol is significantly greater then the Esat, for mefenamate, and the Esat for honokiol is greater than that for magnolol, suggesting, but not proving, the existence of a seventh and an eighth group of [3H]MUS binding sites. The binding of [3H]MUS alone, without enhancers may represent a ninth group of binding sites which is probably heterogeneous as indicated by the very low pseudo Hill coefficients for bicuculline and strychnine in displacing [3H]MUS without enhancer. Altogether, our results suggest the existence of more than 9 different [3H]MUS binding sites. Clozapine was a very weak overall displacer of [3H]MUS (IC50 = 280 microM). However, 5 microM clozapine reduced [3H]MUS binding 6% (P < 0.0001, n = 10) and significantly reduced [3H]MUS binding enhanced by propofol (approximately 14%) or clotrimazole (approximately 17%) but not 17 other compounds tested. TENTATIVE CONCLUSIONS: In the absence of enhancers [3H]MUS may bind preferentially to GABA(A) receptors on pyramidal cells and less to interneurons in cerebral cortex. Conversely, [3H]flunitrazepam may bind preferentially to GABA(A) receptors (allosterically) on interneurons and less to pyramidal cells. Clozapine appears to selectively block a small fraction (10-20%) of [3H]MUS binding sites with an IC50 value in the low micromolar range. This fraction may be preferentially located on certain GABAergic interneurons (basket cells?) that make synaptic contact with pyramidal cells. The blockade of these GABA(A) receptors by clozapine would be expected to increase the firing rate of the interneurons and the release of GABA onto pyramidal cells. Such blockade would also increase the generation of gamma oscillations by the basket cells. Some of these interneurons appear to be destroyed selectively, probably during the second trimester of gestation by a non-paralytic polio virus, in individuals who wil

Animals↗
PubMed1983

Are there limits to binaural additivity of loudness?

In recent years there has been notable interest in additive models of sensory integration. Binaural additivity has emerged as a main hypothesis in the loudness-scaling literature and has recently been asserted by authors using an axiomatic approach to psychophysics. Restrictions of the range of stimuli used in the majority of former experiments, and inherent weaknesses of the axiomatic study by Levelt, Riemersma, and Bunt (1972) are discussed as providing reasons for the present investigation. A limited binaural additivity (LBA) model is proposed that assumes contralateral binaural inhibition for interaural intensity differences that exceed a critical level. Experimental data are reported for 12 subjects in a loudness-matching task designed to test the axioms of cancellation and of commutativity, both necessary to the existence of strict binaural additivity. In a 2 X 2 design, frequencies of 200 Hz and 2 kHz were used, and mean intensity levels were 20 dB apart. Additivity was found violated in 33 out of 48 possible tests. The LBA model is shown to predict the systematic nonadditivity in the loudness judgments and to conform to results from other studies.

Female↗
PubMed2005

Outcome additivity and outcome maximality influence cue competition in human causal learning.

Recent research suggests that outcome additivity pretraining modulates blocking in human causal learning. However, the existing evidence confounds outcome additivity and outcome maximality. Here the authors present evidence for the influence of presenting information about outcome maximality (Experiment 1) and outcome additivity (Experiment 2) on subsequent forward blocking. The results of Experiment 3 confirm that, with outcome maximality controlled, outcome additivity affects backward blocking but not release from overshadowing. Finally, the results of Experiment 4 demonstrate that information about outcome additivity has a similar effect on forward blocking if presented after the blocking training instead of before. The results are compatible with the idea that blocking results from inferential processes at the time of testing and not from a failure to acquire associative strength during training.

Adolescent↗
PubMed2002

Analytical curve or standard addition method: how to elect and design--a strategy applied to copper determination in sugarcane spirits using AAS.

In most instrumental analysis, the analyte concentration is usually obtained the by Analytical Curve Method (ACM) or Standard Addition Method (SAM). Thus, it is important for the analyst to select the most appropriate method, to seek the best conditions of analysis, and to provide parameters of analytical performance. A strategy to do so is proposed in this paper in conjunction with MATLAB software to implement it. The proposed strategy was applied to copper determination by atomic absorption spectrometry in Brazilian sugarcane spirits termed 'Cachaça' and SAM was chosen as the most appropriate method. To select the best experimental design for SAM, the influence of some factors, such as the number of standard additions and concentration levels, the location of the levels and the average concentration of the standard additions were demonstrated. The design with six standard additions, four concentration levels located near the inferior and superior levels and the average concentration of the standard additions closer to zero yielded SAM with an adequate compromise between precision, cost and time of analysis. The uniform distribution of concentration levels, usually used in routine analysis, is not a good design regarding precision. On the other hand, it is adequate when the linear range is unknown. Generally, the proposed strategy can be applied to different instrumental techniques and samples, which aim to improve their analytical performance.

Alcoholic Beverages↗
PubMed1996

Incidence and implication of additional chromosome aberrations in acute promyelocytic leukaemia with translocation t(15;17)(q22;q21): a report on 50 patients.

Acute promyelocytic leukaemia (APL) is characterized by the translocation t(15;17)(q22;q21). Usually t(15;17) is the sole cytogenetic abnormality, but some patients show other chromosome aberrations in addition to t(15;17). The influence of additional chromosome aberrations on the clinical outcome of patients with t(15;17) is unclear. We have analysed 50 cases of APL carrying the translocation t(15;17). Additional chromosome aberrations were observed in 17/47 patients (36%) studied at initial diagnosis and in all three patients studied at relapse. In nine cases (18%) an additional chromosome 8 and in six cases (12%) an isochromosome of the long arm of the derivative chromosome 17 was observed. Various structural rearrangements in addition to t(15;17) were detected in nine patients (18%). Clinical follow-up data were available for 44 patients studied at diagnosis. A complete remission (CR) was achieved in 34 patients (77%). 10 patients (23%) died within 1 month after diagnosis due to infection or bleeding, eight (24%) relapsed within 10-18 months after initial diagnosis. 28 patients are alive 2-93 months after diagnosis (25 in first CR, two in second and one in third CR) (median follow-up 18.5 months). Bone marrow transplantation was performed in six patients (three in first CR, two in second CR, one in third CR), all are alive and in CR. An influence of secondary chromosome anomalies on prognosis was not observed. However, if a higher rate of long-term remission can be reached, specific secondary chromosome aberrations might turn out to be of prognostic value.

Adolescent↗
PubMed2003

The effect of the addition of poly(methyl methacrylate) fibres on some properties of high strength heat-cured acrylic resin denture base material.

The self-reinforcement of acrylic resin with butadiene styrene surface treated poly(methyl methacrylate) fibres has been reported to have the potential to substantially improve the transverse bend strength of conventional heat-cured acrylic resin. The aim of this study was to investigate the effect of the addition of butadiene styrene surface treated poly(methyl methacrylate) fibres in cross-ply arrangement to high impact acrylic resin on the transverse and impact strength. Specimens were prepared as specified in the International Standard Organization and British Standards for the Testing of Denture Base Resins (ISO 1567, 1988; BS 2487, 1989) and the British Standard Specification for Orthodontic resins (BS 6747, 1987) for transverse bend and impact testing. The impact strength was measured using a Zwick pendulum impact tester and the transverse bend strength measured using a Lloyds Instruments testing machine. The results showed that the impact strength was not improved with the addition of fibres, high impact acrylic resin with fibres (LF) 11.1 kJ m-2 and high impact acrylic resin (L) (12.5 kJ m-2). The modulus of rupture was decreased with the addition of fibres (57.8 MPa) for (LF) compared with (60.4 MPa) for (L). The modulus of elasticity was also reduced with the addition of fibres (1834.9 MPa) (LF) and 2086.2 MPa (L) as was the peak load (LF) (50.8 N) and (L) (55.8 N). It was concluded that the addition of surface treated poly(methyl methacrylate) fibres in cross-ply arrangement to high strength acrylic resin did not produce an improvement in the impact or transverse strength and cannot be recommended as a method of reinforcement.

Acrylic Resins↗
PubMed2001

Comparison of two platelet additive solutions.

The use of an additive solution for substitution of plasma for storage of leukodepleted platelet concentrates can have many advantages. In this study, a comparison was made between two platelet additive solutions: one containing citrate and acetate (PAS-II), the other also supplemented with additional salts such as magnesium, and with gluconate (Composol-PS). Donor-dependent differences were avoided by applying a paired experimental design (n = 10). The platelet concentrates were prepared by pooling five buffy coats and the additive solution, and prestorage filtration was utilized to remove leucocytes to well below 1 x 106. Storage of platelet concentrates up to 9 days after blood collection revealed that platelet concentrates in Composol-PS maintained an almost constant pH of on average 6.93 from day 2 through day 7, and at 6.90 at day 9. This was in contrast to PAS-II, which showed a gradually decreasing pH from on average 6.97 at day 1 to 6.86 at day 9. In all units stored in both solutions the swirling effect was present during 9 days of storage. In conclusion, both additive solutions allow storage of platelets, derived from pooled buffy coats, for up to 9 days after collection of the whole blood, with maintenance of good quality in vitro. Composol-PS has a slightly better buffering capacity, reflected as a more constant pH throughout the storage period.

Acetates↗
PubMed2003

Beyond the 12 lead: review of the use of additional leads for the early electrocardiographic diagnosis of acute myocardial infarction.

Despite known limitations, the standard 12 lead ECG is the principal risk stratification device for patients presenting with chest pain to the ED. However, it has a sensitivity of less than 60% for MI. One reason for this is that the standard placement of chest leads fails to interrogate many areas of the myocardium. Various workers have addressed this problem through the use of additional leads or body surface mapping. Additional leads on the posterior and right thoracic surface have been shown to give additional information, which may be important to the emergency physician. This review demonstrates the need for additional leads in the acute setting and makes recommendations about the utility of using additional leads in the ED.

Body Surface Potential Mapping↗
PubMed2003

The innervation of FGF-induced additional limbs in the chick embryo.

Motoneurones that supply the vertebrate limb innervate their muscle targets in a highly reproducible manner. As development proceeds, these limb-specific motoneurones send out axons, which grow towards the developing limb and then congregate at its base to form the plexus. In the plexus, in response to unknown positional cues, these axons rearrange, often changing their original spatial relationships, before sorting out to emerge in the defined nerve trunks that innervate the limb. Several proposals have been put forward to explain how this reproducible innervation pattern is achieved. These include (1) that early differences in the motoneurone identity dictate their future axonal trajectories, (2) that axons actively respond to attractive or repulsive positional cues provided by the limb bud itself, or (3) that motor axons are passively deployed, following pathways of least mechanical resistance. We have addressed the question of the relative roles of motoneurone identity and the signals that the axons encounter on their journey towards the limb bud. Using the developing chick embryo as our experimental model we tested the effect of providing an additional limb target for motor axons leaving the flank level of the spinal cord. To do this we placed FGF-soaked beads in the presumptive flank of 2-day-old chick embryos. This treatment induces an additional limb containing muscles. We investigated whether such additional limbs are innervated and by which neurones. We show that rather than the additional limbs being solely supplied by axons diverted from the two existing limb plexuses, motoneurones that normally supply the flank alter their trajectories to enter the induced limb. Once in the limb, axons respond to positional cues within the bud to generate the stereotypical innervation pattern. Our results show that the tendency of 'flank' motoneurones to innervate flank can be overcome by the presence of an additional limb.

Animals↗
PubMed1994

Photoendocrine transduction in cultured chick pineal cells: IV. What do vitamin A depletion and retinaldehyde addition do to the effects of light on the melatonin rhythm?

Light has at least two distinguishable effects on the circadian rhythm of melatonin output displayed by dispersed chick pineal cells in static culture: acute suppression of melatonin output and entrainment (phase shifts) of the underlying pacemaker. Previous results indicated that these two effects of light are mediated by different mechanistic pathways. The pathways for the acute and phase-shifting effects of light either branch from the same, single photopigment or differ from the outset, starting from separate photopigments. If a single rhodopsin-like photopigment mediates both effects of light, then vitamin A depletion and retinoid addition should affect both responses in parallel, although not proportionately. We therefore compared the effects of vitamin A depletion and retinoid addition on the acute and phase-shifting effects of light under several experimental conditions. When chick pineal cells were depleted of vitamin A, acute responses to light were markedly reduced. Addition of 11-cis-retinaldehyde specifically restored (and enhanced) the acute response. When allowed to free run in constant red light, depleted cells displayed a rhythm of melatonin output with the same period as that of control cells. In contrast to the acute effects, phase shifts in response to 2- or 4-h light pulses did not differ between depleted and control cells. Addition of retinaldehyde to depleted cells did not, by itself, reduce melatonin output or induce phase shifts. Retinaldehyde did increase the acute response to 4-h light pulses but not the ensuing phase shifts. Responses increased with duration of the light pulse: Both the acute effect and the phase shifts induced by 4-h light pulses were considerably larger than those induced by 2-h (or 1-h) light pulses. Addition of retinaldehyde to depleted cells increased the acute effect of 2-h (or 1-h) light pulses to at least that seen with 4-h light pulses but did not increase the size of the ensuing phase shifts. These results strongly confirm previous dissociations of the mechanistic pathways mediating the acute and phase-shifting effects of light on chick pineal cells. They also support a role for rhodopsin-like photopigment in the acute, but not phase-shifting, response. They favor, but do not prove, the conclusion that separate photopigments mediate the acute and entraining effects of light.

Activity Cycles↗
PubMed2002

1alpha,25-dihydroxyvitamin D3 shows strong and additive immunomodulatory effects with cyclosporine A in rat renal allotransplants.

BACKGROUND: Vitamin D3 and its metabolites have long been found to exert immunosuppressive effects both in vivo and in vitro. The present study investigated the effect of 1alpha,25-dihydroxycholecalciferol (1,25DHC) on vascularized renal allografts in rats. METHODS: Three days prior to transplantation, two groups of animals were subjected to 1,25DHC (1 microg/kg/day IP) and a low calcium diet, which was continued until the end of the experiments. Recipient organs were removed and single allografts were transplanted in a high responder strain combination (ACI --> Lewis). Following transplantation, low-dose cyclosporine A (3.2 mg/kg/day CsA) administration was started in two experimental groups of recipients (one group receiving 1,25 DHC additionally) whereas the control allograft recipients received no immunosuppression (control III). Graft survival and renal function was monitored until death or the end of experiments and allograft rejection was assessed histologically using the Banff classification. RESULTS: 1,25DHC significantly prolonged allograft survival in comparison to control III (9.6 +/- 1 vs. 5.7 +/- 0.2 days; P=0.009). In addition, a combination of 1,25DHC and low-dose CsA increased allograft survival compared to CsA administration alone (24 +/- 0.9 vs. 13 +/- 0.3 days; P=0.008). 1,25DHC preserved renal creatinine clearance and decreased proteinuria in comparison to control III, and the combination of 1,25DHC and low-dose CsA again showed an additive effect on preservation of renal function. 1,25DHC and low-dose CsA both decreased interleukin (IL)-2 and IL-12 expression levels in serum and allografts, and a combination treatment produced the strongest attenuation of IL-2 and IL-12 expression. In addition, 1,25DHC increased IL-4 and IL-10 expression levels in allografts, whereas CsA alone did not alter IL-4 and IL-10 expression. In contrast, combination of 1,25DHC and low-dose CsA showed a significant increase in IL-10 expression levels whereas IL-4 expression was not elevated. CONCLUSION: Monotherapy with 1,25DHC significantly prolongs survival of renal allografts and preserves graft function in rats. A combination of 1,25DHC and CsA caused an additive effect on graft survival with differential regulation of pro- and anti-inflammatory cytokines, as compared to 1,25DHC administration alone.

Adjuvants, Immunologic↗