Stability and flocculation of oil droplets in dilute emulsions.
Explore the source record for details and available documents.
Chemical Precipitation↗
SEARCH · Search PubMed
Results for “MIMAE”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Vaginal absorption of a potent luteinizing hormone-releasing hormone analog (leuprolide) in rats I: absorption by various routes and absorption enhancement.
The absorption of a potent luteinizing hormone-releasing hormone analog (leuprolide) through different routes was evaluated by determining the ovulation-inducing activity in diestrous rats. Vaginal administration showed the greatest potency among nonparenteral routes and was followed successively by rectal, nasal, and oral administration. Mixed micellar solution with monoolein-bile acids improved the intestinal absorption of leuprolide, and nasal absorption was enhanced by adding sodium glycocholate, surfactin, or polyoxyethylene 9 lauryl ether, but these bioavailabilities were still insufficient. The vaginal absorption was enhanced by organic acids: citric, succinic, tartaric, and glycocholic; the absolute bioavailability increased to approximately 20%. The vaginal absorption from jellies, as practical dosage forms, yielded sufficient activity of leuprolide, but absorption was slightly reduced with highly polar polymers or with higher concentrations of polymers. It was concluded that vaginal administration of leuprolide can be a rational dosage method for a long-term antitumor therapy.
Absorption↗
Vaginal absorption of a potent luteinizing hormone-releasing hormone analogue (leuprolide) in rats II: mechanism of absorption enhancement with organic acids.
Organic acids such as citric acid enhance the vaginal absorption of luteinizing hormone-releasing hormone, the potent analogue (leuprolide), and insulin. The mechanism of this absorption enhancement was investigated with leuprolide and hydrophilic markers such as phenol red and Evan's blue. The absorption of the analogue was increased by lowering the pH of the solution and increased more by adding citric, succinic, tartaric, and malonic acids. The absolute bioavailability after vaginal administration of the 5% citric acid solution was 16.7% at pH 3.5 and 38.4% at pH 1.8. The enhancing potency of the absorption correlated well with the chelating ability of the organic acids. The vaginal absorption of phenol red was also enhanced with citric acid and edetic acid, but the enhancing effect of edetic acid was eliminated by adding equimolar calcium ion. These results suggest that the acidifying and chelating abilities of the acids may result in a potent enhancement of the vaginal absorption of leuprolide. A leakage experiment using Evan's blue on the vaginal membrane indicated that the blood-vaginal epithelium barrier was loosened with the administration of citric acid; this change was overcome rapidly.
Absorption↗
Vaginal absorption of a potent luteinizing hormone-releasing hormone analogue (leuprolide) in rats III: Effect of estrous cycle on vaginal absorption of hydrophilic model compounds.
The effect of estrous cycle stages on vaginal absorption was determined by the use of insulin, phenolsulfonphthalein, and salicylic acid as hydrophilic model compounds. Absorption of these compounds was markedly affected by the stage, possibly due to the change of transport rate through the pore-like pathways. The absorption of phenolsulfonphthalein during proestrus and estrus is roughly one-tenth of that during metestrus and diestrus. An increase of the nonionized form of salicylic acid, produced by a lowered pH, resulted in an enhancement of absorption during proestrus and diestrus; higher contribution of the transport through the cell membrane possibly reduced an effect of the estrous cycle. However, consecutive daily administration of leuprolide halted the cycle at diestrus and reduced the cycle effect on the vaginal absorption of phenolsulfonphthalein; when the treatment was started at any of the four stages of the cycle, vaginal absorption was enhanced approximately 20%, with less variance than that observed in normal diestrous rats.
Animals↗
Vaginal absorption of a potent luteinizing hormone-releasing hormone analogue (leuprolide) in rats. IV: Evaluation of the vaginal absorption and gonadotropin responses by radioimmunoassay.
The vaginal absorption of leuprolide (a potent luteinizing hormone-releasing hormone analogue), which has the potential for producing regression of hormone-dependent tumors as well as high gonadotropin-releasing and ovulation-inducing activities, was evaluated in rats by radioimmunoassay. Gonadotropin (luteinizing hormone and follicle-stimulating hormone) release was concomitantly determined. Although leuprolide disappeared rapidly from the serum after intravenous administration (the biological half-lives were 8.4 min in the alpha-phase and 33.2 min in the beta-phase), long-lasting serum levels were observed when the analogue was administered vaginally. The vaginal absorption was enhanced by adding citric acid to the test solution. The absolute bioavailability, estimated by the AUC of serum leuprolide levels, was 25.8% over 6 h and 38.0% over 12 h in the 5% citric acid solution (pH 3.5). The sustained release of gonadotropin was also obtained after vaginal administration of the analogue. A linear dose absorption correlation of leuprolide was obtained in the range of 10-1000 micrograms/kg in an aqueous solution or methylcellulose jelly. The release of gonadotropin showed a plateau level at greater than 10 micrograms/kg, which corresponds to an effective dose for antitumor activity. The vaginal absorption of leuprolide varied with the estrous cycle, but this effect was eliminated by prior subcutaneous pretreatment with the analogue.
Absorption↗
Familial cortical myoclonic tremor as a unique form of cortical reflex myoclonus.
Previously it was reported that some patients with tremor had the same electrophysiological findings as those seen in patients with cortical reflex myoclonus, and consequently the tremor was named "cortical tremor." In the present study, we examined six patients from three families with cortical tremor of relatively late onset. The inheritance pattern of cortical tremor was compatible with autosomal dominant trait. Those patients had relatively rhythmic involuntary movements (tremor) in the distal upper and lower limbs, especially during posture and/or fine movements. There was no cerebellar ataxia or dementia, and fits of loss of consciousness occurred only infrequently. Electrophysiologically, they had generalized spikes on electroencephalogram (EEG), giant cortical components of somatosensory evoked potential, an enhanced long-loop reflex (C-reflex), and cortical spikes preceding the rhythmic jerk demonstrable by the jerk-locked back averaging method, thus fulfilling the criteria of cortical reflex myoclonus. Furthermore, they had slow negative EEG shift starting 1-2 s prior to voluntary movements, suggesting that, as opposed to the conventional form of progressive myoclonus epilepsy (PME), the cerebellar efferent input to the motor cortices was normal. These clinical and electrophysiological pictures are distinct from those of familial essential tremor, familial essential myoclonus, or the conventional form of PME, and the term "familial cortical myoclonic tremor" will represent the clinical and electrophysiological features of this unique entity most appropriately.
Adult↗
Electrophysiological studies of early stage corticobasal degeneration.
We conducted electrophysiological studies in two Asian patients with probable corticobasal degeneration (CBD). The duration of illness from onset was 16 and 20 months, respectively. The clinical manifestations were markedly asymmetric and characterized by cortical sensory loss, apraxia, action myoclonus, action tremor, and akinetic-rigid parkinsonism. Neither patient responded to levodopa therapy. Simple photon-emission computed tomography (SPECT) study showed significantly decreased regional cerebral blood flow in the frontoparietal areas and thalamus opposite to the predominantly affected limb. A series of electrophysiological studies failed to identify giant somatosensory evoked potentials (SEPs), enhanced long latency electromyography (EMG) reflex, and cortical spikes preceding myoclonic jerk. However, the earliest cortical component of the median nerve SEP was exclusively enlarged in one patient and preserved with depression of the subsequent components in the other patient. Significantly shorter postmotor-evoked potential (MEP) silent period was found after the transcranial magnetic stimulation of the motor cortex in both patients. CBD is a unique clinical entity characterized by action myoclonus probably the result of the pathologic hyperexcitability of the motor cortex, based on a loss of inhibitory input from the sensory cortex.
Aged↗
Developmental toxicity of caffeine in the larvae of Xenopus laevis.
To examine the developmental toxicity of caffeine, Xenopus larvae just after hatching, were continuously exposed to 100-2,000 mg/L caffeine for 48 hours. Caffeine interfered with development of Xenopus larvae at a concentration of 100 mg/L and above in a concentration-dependent manner. Characteristic external abnormalities, such as shortened body with wavy fins, were observed, the severity of which was clearly concentration dependent. These larvae were frequently accompanied by abnormal body flexure and edema in the fin. Light microscopy revealed that exposure to caffeine induced severe damage in the myotome and neural tube, and at higher concentrations, the epidermal tissue was also affected. Myoblasts showed wide intercellular spaces, and their cytoplasm lost uniform staining. Ultrastructural studies of myoblasts revealed distinct myofibril disorganization and degeneration, and mitochondrial alterations. In the neural tube, cells at the dorsal part of tube showed wide intercellular spaces and some of them were segregated to the peripheral region. Furthermore, vacuole-like structures of various sizes appeared in the white matter. The outer layer of epithelial cells in the epidermis were vacuolated and swollen. With regard to the pathogenesis of myofibril damage, caffeine appeared to cause a disturbance of intracellular calcium regulation, by releasing calcium ions from the sarcoplasmic reticulum, and the mitochondrial changes observed in myotomal cells were considered to be reflective of this increased intracellular calcium ion levels. It is speculated that caffeine interferes with cell adhesion in the myotome and neural tube by affecting calcium ion regulation.
Abnormalities, Drug-Induced↗
An additional limb can be induced from the flank of the chick embryo by FGF4.
To elucidate what initiates formation of the limb, we have attempted to induce an additional limb from the flank of the chick embryo by infecting retrovirus or implanting cells. We report here that an additional limb can be formed from the flank when we implant fibroblast growth factor 4 (Fgf4)-expressing cells into the lateral plate mesoderm at the pre-limb bud stage. In a newly formed limb bud, expressions of both Sonic hedgehog and chick Fgf4, which are authentic morphogenetic signals from the zone of polarizing activity and the apical ectodermal ridge, respectively, are induced by the implanted cells. Thus, it is concluded that the competence for limb development is present along the flank of the chick embryo and that FGF4 applied ectopically at the pre-limb bud stage can alter the developmental fate of flank cells to become limb cells. The present experimental system will contribute to a further elucidation on how the limb is formed.
Animals↗
An in vitro system for identifying agents capable of changing serum lipoprotein(a) concentration by regulating the transcriptional activity of the apolipoprotein(a) gene promoter.
A high serum concentration of lipoprotein(a) [Lp(a)] is a significant and independent risk factor for cardiovascular disease. We examined the effects of agents on the transcriptional activity of the apolipoprotein(a) [apo(a)] gene promoter and determined whether drugs identified by this assay would affect the serum concentration of Lp(a) in vivo. All-trans-retinoic acid (ATRA) and interleukin-6 increased the transcriptional activity of the apo(a) gene promoter 2.1- and 2.5-fold, respectively, whereas danazol reduced activity to 76% of the control value. Triiodothyronine had no effect on transcriptional activity. Treatment of two acute promyelocytic leukemia patients with ATRA induced maximal 2.7- and 3.2-fold increases in serum Lp(a) concentrations, respectively. Thus, the in vitro luciferase assay system is capable of identifying agents that affect the serum concentration of Lp(a) and thus may prove beneficial in the screening of new drugs for treatment of individuals with high serum Lp(a) concentrations.
Adult↗
Dominant and shared T cell receptor beta chain variable regions of T cells inducing synovial hyperplasia in rheumatoid arthritis.
Previously, we demonstrated the presence of at least two distinct subpopulations of patients with rheumatoid arthritis (RA) employing a cell-transfer experiment using severe combined immunodeficient (SCID) mice. One group of patients, whose T cells derived from the rheumatoid joints, induced synovial hyperplasia (SH) in the SCID mice (the positive group). The other group did not display the induction of SH (the negative group). TCR/Vbeta gene usage analysis indicated that some dominant T cell subpopulations were oligoclonally expanding only in the rheumatoid joints, and not in the periphery of the patients of the positive group. Moreover, these T cell subpopulations were not seen in the joints of patients in the negative group or in non-RA patients. In addition, the preferential uses of certain TCR/Vbetas (Vbeta8, Vbeta12, Vbeta13, and Vbeta14) genes were demonstrated in these T cells. In this study, to investigate whether these T cells are driven by a certain antigen(s), the third complementarity determining regions (CDR3s) of TCR/Vbeta, especially Vbeta8 and Vbeta14 PCR products, were cloned and sequenced. As a result, a dominant CDR3 sequence, CASS-PRERAT-YEQ, was found in Vbeta14+ T cells from the rheumatoid joint of a patient (Patient 1) of the positive group with a Vbeta14 skew. The identical CDR3 sequence also predominated in Vbeta14+ T cells from the rheumatoid joint of another patient (Patient 7) of the positive group with a Vbeta14 skew. In addition, in the patients (Patients 4, 7, 8) of the positive group with a Vbeta8 skew, other dominant CDR3 sequences, CASS-ENS-YEQ and CASS-LTEP-DTQ, were found as in the case of Vbeta14. However, no identical CDR3 sequences were detected dominantly in the joints of the patients in the negative group or in non-RA patients. A Vbeta14+ T cell clone (TCL), named G3, with the identical CDR3 sequence, CASS-PRERAT-YEQ, was isolated successfully from Patient 1, and cell transfer of G3 with autologous irradiated peripheral mononuclear cells induced SH in the SCID mice. Taken together, these results suggest that T cells inducing SH, thought to be pathogenic for RA, might be driven by a certain shared antigen(s).
Amino Acid Sequence↗
Tumour necrosis factor alpha (TNF-alpha) interferes with Fas-mediated apoptotic cell death on rheumatoid arthritis (RA) synovial cells: a possible mechanism of rheumatoid synovial hyperplasia and a clinical benefit of anti-TNF-alpha therapy for RA.
To investigate the mechanism of rheumatoid synovial hyperplasia (RASH), the influence of tumour necrosis factor alpha (TNF-alpha) on Fas-mediated apoptotic cell death (Fas-ACD) was examined on cultured rheumatoid synovial cells (RASCs). RASCs were obtained from the synovial tissues of eight patients with rheumatoid arthritis (RA) and SCs from eight patients with osteoarthritis (OA) were used as a control. To examine the influence of TNF-alpha on Fas-ACD, SCs were cultured with anti-Fas antibody (CH11) for 16 h in the absence or presence of different doses of recombinant TNF-alpha. ACD was determined by electron microscopic analysis and the percentage of apoptotic cells was calculated by trypan blue staining. In addition, the expression of Fas and Bcl-2 on RASCs was examined by flow cytometry. As a result, RASCs were more susceptible to Fas-ACD in vitro than OASCs. TNF-alpha interfered with Fas-ACD on RASCs in a dose-dependent manner. Moreover, removal of TNF-alpha activity by a neutralizing anti-TNF-alpha antibody (cA2) restored Fas-ACD. Flow cytometric analysis showed no significant changes in either Fas or Bcl-2 expression on RASCs after the culture with TNFalpha. These results suggest the following: (1) Fas-ACD might be diminished in vivo by local excessive TNF-alpha and this might contribute in part to RASH. (2) The inhibition of Fas-ACD on RASCs by TNF-alpha might not be associated with changes in the expression of Fas or Bcl-2. (3) In addition, considering a magnetic resonance imaging (MRI) finding of marked reduction in the RASH after cA2 treatment, blockade of TNF-alpha activity could restore Fas-ACD in RA synovium, implicating a clinical benefit of anti-TNF-alpha therapy for RA.
Antibodies, Monoclonal↗
FGF can induce outgrowth of somatic mesoderm both inside and outside of limb-forming regions.
In the vertebrate embryo, only somatopleural cells in the limb-forming region are released from the mesodermal layer and undergo outgrowth from the embryonic body to form the limb bud. Molecular signals which regulate limb bud induction are unknown to date. In the present study we examined the ability of fibroblast growth factor (FGF) to induce limb bud formation in chicken embryos. A replication-defective retrovirus encoding FGF type 4 with a reporter, bacterial beta-galactosidase, was microinjected into lateral plate mesoderm inside and outside limb-forming regions. Effects of the ectopic and precocious expression of FGF were assessed at various stages after infection. Here we report that somatic mesodermal cells in both flanks and limb-forming regions can respond to FGF and induce limb bud-like outgrowth. The supernumerary limb bud induced within a limb-forming region differentiated into extralimb structures. These results strongly suggest potential roles of FGF signaling for induction of limb bud formation.
Animals↗
Trabecular myocytes of the embryonic heart require N-cadherin for migratory unit identity.
The myocardial wall of the vertebrate heart changes from a simple epithelium to a trabeculated structure during embryogenesis. This process occurs when epithelioid cardiomyocytes migrate toward the endocardium, which we show is coincident with up-regulation of the cell adhesion molecule, N-cadherin. To study the role of N-cadherin expressed at the trabeculation stage, a replication-defective retrovirus expressing a dominant negative mutant of N-cadherin (delta N-cadherin) was engineered. Control viruses were designed to express beta-galactosidase or a full-length N-cadherin. Viruses were introduced into epithelioid presumptive myocytes at the time they initiate the epithelial-mesenchymal transformation. Individual cells infected with control viruses generated daughter myocytes which migrated toward endocardium as a tight cluster, thereby generating a clone that forms a single or at most two trabeculae. In contrast, myocytes expressing delta N-cadherin were sparsely distributed within the myocardium and failed to form the ridge-shaped clone. Thus, in addition to its known roles in myocyte epithelialization and intercalated disc formation, N-cadherin appears to play a role in homotypic interactions between nonepithelial migratory myocytes during trabecular formation of the embryonic heart.
Animals↗
Generators of movement-related cortical potentials: fMRI-constrained EEG dipole source analysis.
To clarify the precise location and timing of the mo tor cortical activation in voluntary movement, dipole source analysis integrating multiple constraints wa conducted for the movement-related cortical potentia (MRCP). Six healthy subjects performed single self paced extensions of the right index finger at about 15-intervals during EEG and event-related fMRI acquisi tions. EEG was recorded from 58 scalp electrodes, and fMRI of the entire brain was obtained every 2.6 s. Coordinates of the two methods were coregistered us ing anatomical landmarks. During dipole source mod eling, a realistic three-layer head model was used as a volume conductor. To identify the number of uncorre lated source s in the MRCP, principal component (PC analysis was performed, which was consistent with the existence of six sources in the left (Lt SM1) and right (Rt SMI) sensorimotor and medial frontocentral (MFC) areas. After dipoles were seeded at the acti vated spots revealed by fMRI, dipole orientations were fixed based on the interpretation of the topography of distribution of the PC. The strength of the six dipoles (three dipoles in Lt SMI, two in Rt SMI, and one in MFC) was then computed over time. Within the bilat eral SM1, activation of the precentral gyrus occurs bilaterally with similar strength from -1.2 s, followed by that of the precentral bank from -0.5 s with con tralateral preponderance. Subsequently, the postcen tral bank becomes active only on the contralateral side at 0.1 s after movement. Activation of the MFC shows timing similar to that of the bilateral precentral gyri These deduced patterns of activation are consis tent with previous studies of electrocorticography in humans.
Adult↗
Inhibition of overexpression of endothelin-1 by an RNA synthesis inhibitor, doxorubicin, in the rat vasospasm model.
Explore the source record for details and available documents.
Animals↗
Lipocortin-1 fails to ameliorate ischemic brain edema in the cat.
It has been reported that corticosteroids exert their anti-inflammatory action through de novo synthesis of phospholipase-inhibitory proteins called lipocortins (annexins). We postulated that the following may lessen the effectiveness of corticosteroids on acute ischemic brain edema: 1) lipocortins are induced several hours after administration of steroids; 2) de novo synthesis of lipocortins is suppressed in the ischemic brain; and 3) lipocortins induced systemically do not pass through the blood-brain barrier (BBB) to reach the sites of ischemic edema. To test this hypothesis, we examined whether dexamethasone, given long before ischemia or direct administration of recombinant lipocortin-1, combined with or without BBB opening, ameliorate ischemic brain edema. Three hours before occlusion of the middle cerebral artery (MCA) in the cat, 4 mg/kg of dexamethasone was injected intravenously. The animals were subjected to 4 hours of ischemia. Alternatively, 2 ug/ml (total volume 10 ml) of recombinant human lipocortin-1 (annexin-I) was perfused intermittently into the ischemic focus by catheterization into the MCA. Artificial opening of the BBB was performed by intra-arterial mannitol infusion. None of these strategies demonstrated amelioration of ischemic edema. We conclude that: Dexamethasone and recombinant lipocortin-1 seem unlikely to have robust effects on amelioration of acute ischemic edema.
Animals↗
Lipocortin-1 fails to ameliorate cold-injury brain edema in the rat.
Based on evidence that corticosteroids exert their anti-inflammatory action via de novo synthesis of phospholipase A2 inhibitory proteins called lipocortins, we examined effects of high dose dexamethasone and recombinant human lipocortin-1 (annexin-I) on cold-injury brain edema in the rat. Since it takes several hours for lipocortins to be induced, dexamethasone (10 mg/kg) was injected intraperitoneally 3 hours before cold injury. Recombinant lipocortin-1 was administered intraventricularly at three different doses (0.01 mg/kg, 0.05 mg/kg, or 0.1 mg/kg: total volume 20 microliters), or via the internal carotid artery at a dose of 10(-7) M (2 ml). To induce cold injury, a liquid-nitrogen-cooled probe was placed on the exposed dura of male Wistar rats (330-370 kg) for 1 minute. Specific gravimetry and/or a wet-dry weighing method were used for measurement of brain edema at 24 or 48 hours after lesion production. In the present study, dexamethasone and recombinant lipocortin-1 failed to attenuate edema formation. The anti-inflammatory effects of dexamethasone or exogenous lipocortin-1 seemed unlikely to affect cold-injury brain edema.
Animals↗