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PubMed2003

[Clinical investigation on characteristics of traditional Chinese medical syndrome of hepatocirrhosis].

OBJECTIVE: To explore the characteristics of traditional Chinese medical syndrome (TCM syndrome) of hepatocirrhosis. METHODS: Clinical information from the four diagnosis methods of traditional Chinese medicine (TCM) and related laboratorial indexes were systematically collected from 223 hepatocirrhosis cases, and the multi-statistical methods including systematic cluster analysis, principal component analysis, stepwise discrimination and variance analysis were made with the software SAS 6.11. RESULTS: Multi-analysis showed that there were 3 categories of syndrome characteristics. Type 1 (134 cases): damp heat, blood stasis, deficiency of liver and spleen Qi; Type 2 (62 cases): deficiency of both Qi and Yin with severe deficiency of Qi, heat with severe dampness, blood stasis; Type 3 (27 cases): deficiency of both Qi and Yin with severe deficiency of Yin, stasis and heat or dampness. Analysis of the changes of the related laboratorial indexes among the three types of syndrome showed that Type 1 mainly manifested asthenia syndrome with sthenia syndrome, and its indexes of AST, ALT, GGT levels were markedly higher than those of Type 2 and Type 3, both of which mainly showed sthenia syndrome with asthenia syndrome, and that Type 3 was in active inflammation, deficiency of both Qi and Yin (deficiency of Yin > deficiency of Qi), and its FN, Alb, FV, FVII, PLT, PCT levels were obviously reduced. CONCLUSION: The multi-statistical methods can reveal the characteristics and regularity of TCM syndrome of hepatocirrhosis, and the 3 categories of syndrome characteristics basically conform to clinical manifestations. The result of TCM syndrome distribution and laboratorial indexes infer that damp heat is the pathological basis of hepatocirrhosis, and the degree of liver function disorder and liver damage may be the pathological basis of deficiency of Yin of both liver and kidney.

Adult↗

PubMed2003

[Regulation effects of Gegen Recipe and Guizhi Recipe on expression of IL-1beta, iNOS, TNFalpha, TGFbeta mRNA in degenerated cervical intervertebral disk in rabbits].

OBJECTIVE: To study the effects of Gegen Recipe and Guizhi Recipe regulating the expression of IL-1beta, iNOS, TNFalpha and TGFbeta mRNA in degenerated intervertebral disk caused by stimulation of wind, cold and damp. METHODS: Thirty-six rabbits were randomly separated into six groups, viz. control group, stimulation by wind, cold and damp group, head in low-location group, compound model group (head in low-location plus stimulation of wind, cold and damp), Gegen Recipe group and Guizhi Recipe group. The gene expression of IL-1beta, iNOS, TNFalpha and TGFbeta mRNA in degenerated cervical intervertebral disks were assayed by RT-PCR. RESULTS: Compared with the control group, IL-1beta mRNA and iNOS mRNA expression were up-regulated in each model group(P<0.01). Both Gegen Recipe and Guizhi Recipe down-regulated IL-1beta mRNA, iNOS mRNA expression, which had significant differences compared with the stimulation model group(P<0.01 or <0.05). TNFalpha mRNA expression was significantly enhanced in the compound model group compared with the control group (P<0.01). There was no significant difference between the head in low-location group and the stimulation model group. Gegen Recipe down-regulated TNFalpha mRNA expression compared with the stimulation group(P<0.01),while the effect of Guizhi Recipe was not significant. Compared with the control group, TGFbeta mRNA expression went down in each model group(P<0.01). Gegen Recipe up-regulated TGFbeta mRNA expression(P<0.01), while the effect of Guizhi Recipe on adjusting TGFbeta mRNA was not significant. CONCLUSION: Stimulation by wind, cold and damp, head in low-location, and compound of both can down-regulate the expressions of IL-1beta, iNOS, TNFalpha mRNA, and up-regulate the expression of TGFbeta mRNA. These researches certify that these factors take part in the progression of intervertebral disk degeneration. IL-1beta, iNOS, TNFalpha accelerate the degeneration and TGFbeta defers the degeneration. Gegen Recipe down-regulates the expression of TNFalpha mRNA and up-regulates the expression of TGFbeta mRNA. The effect on regulating the cell factors expressions by Guizhi Recipe is lower than that of Gegen Recipe.

Animals↗

PubMed1993

[Evaluation of the viscoelasticity of the human carotid wall by ultrasonography].

The purpose of this study is to evaluate non-invasively the viscoelastisity of the human carotid wall by ultrasonographic techniques. After mathematical fundamental experimentation using a rubber tube as a vessel wall model, we observed viscoelastic changes in the carotid wall in normal cases in relation to aging and in treated and non-treated cases with hypertension. An amplified single rectangular mechanical impulse with a 0.5 msec duration was applied to the carotid wall percutaneously by using Wilcoxon's vibrator. We converted B-mode images at one point of the carotid wall to ultrasonic variant M-mode images, and damped oscillation waves were thus obtained. The ultrasonic variant M-mode method, which was developed in our department to detect small vibrations of the vocal cord, was used to observe fine impulse excitations of the carotid wall. This ultrasonographic method (variant M-mode) shows the amount of reflected echoes, which are changed to electrical potentials at one point of the carotid wall. Yerzley Resilience (Y.R.) and resonance frequency (R.F.), as well as the Q-value of resonance, (Q.V.) were measured from these damped oscillation waves. It is widely known that Y.R. shows the degree of viscosity of the carotid wall while R.F. and Q.V. show the stiffness of the carotid wall indirectly. A Y.R. of 100% means complete elasticity with lower viscosity and damping degree. When Y.R. comes close to 0%, both viscosity and damping and degree increase. The carotid wall becomes stiffer in proportion to R.F. and Q.V. The following results were obtained: 1) Y.R., R.F. and Q.V. increased with aging. 2) In non-treated cases with hypertention, Y.R. was significantly, while R.F. and Q.V. tended to be, higher than in normal cases of the same generation. 3) In treated cases with hypertention, Y.R., R.F. and Q.V. had a tendency to be lower than in non-treated cases. In conclusion, non-invasive evaluation of carotid wall viscoelastisity appears to be feasible, and further investigation is warranted for applying this ultrasonographic technique to the field of head and neck vessel surgery.

Adult↗

PubMed2002

The role of M2 muscarinic receptor subtypes in mediating contraction of the pig bladder base after cyclic adenosine monophosphate elevation and/or selective M3 inactivation.

PURPOSE: In the bladder body M2 muscarinic receptors predominate but a smaller population of M3 receptors mediates direct detrusor contraction. M2 receptors have an indirect role by inhibiting cyclic adenosine monophosphate mediated relaxation in the bladder body. We investigated whether a similar mechanism also exists in the bladder base. METHODS: Experiments were performed on pig detrusor muscle. In receptor binding studies using l-quinuclidinyl [phenyl-4-(3)H] benzilate ([(3)H]QNB) (NEN Life Science Products, Inc., Boston, Massachusetts) displacement experiments were performed with subtype selective antagonists to determine the M2-to-M3 receptor ratio. In functional studies the affinity of these antagonists against carbachol induced contractions was calculated in normal tissues and in tissues after cyclic adenosine monophosphate elevation by pre-contraction with KCl and relaxation with isoprenaline, and/or selective M3 inactivation by incubation with 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) mustard (Sigma Chemical Co., St. Louis, Missouri) in the presence of methoctramine (Sigma Chemical Co.) to protect M2 receptors. RESULTS: In saturation binding studies receptor density was 130.5 of fmol./mg. protein and the dissociation constant for [(3)H]QNB was 0.27 nM. Displacement of [(3)H]QNB by the M3 selective antagonist 4-DAMP and the M2 antagonist methoctramine indicated an M2-to-M3 ratio of about 3:1. In functional studies 4-DAMP and methoctramine caused competitive antagonism of responses with affinity values of 9.5 and 6.3 in normal tissues, and 9.3 and 6.1, respectively, in cyclic adenosine monophosphate elevated tissues, suggesting the involvement of M3 receptors only. In tissues in which M3 receptors were inactivated and cyclic adenosine monophosphate levels were elevated the affinity of 4-DAMP was significantly reduced to 8.5 but that of methoctramine was significantly increased to 6.5, suggesting the involvement of M2 receptors. CONCLUSIONS: The M3 subtype appears to mediate contraction of the normal and cyclic adenosine monophosphate elevated tissues of the bladder base. Involvement of M2 receptors was only noted after selective M3 inactivation and cyclic adenosine monophosphate elevation.

Animals↗

PubMed2002

Indoor air quality, fungi, and health. How do we stand?

OBJECTIVE: To equip medical practitioners with up-to-date scientific and medical information on the health effects of exposure to fungi in indoor air, clinical evaluation of these health problems, and possible preventive measures. QUALITY OF EVIDENCE: MEDLINE was searched from 1985 to 2000 using the MeSH words mould (mold), fungus, indoor air, and health effects. Nearly all studies were case reports, case-control studies, and cross-sectional studies. Evidence of an association between respiratory problems and the presence of fungi and dampness is strong. MAIN MESSAGE: Recent well designed studies and literature reviews indicate that exposure to dampness and fungi in indoor air brings on or exacerbates asthma and other respiratory complaints. More studies are required, however, before a definite conclusion on other potential effects of such exposure (such as systemic and long-term effects and pulmonary hemorrhage in infants) is possible. The various health problems that can result from exposure to dampness and fungi in indoor air make such exposure unacceptable from a public health perspective. Physicians are important in treating and preventing such problems; various resources are available to help them. CONCLUSION: Even though some scientific issues remain to be resolved concerning the health effects of exposure to dampness and fungi in indoor air, family physicians can identify potential problems and refer patients to appropriate resources.

Air Pollution, Indoor↗

PubMedDate not supplied

Mechanical reaction of the frontal abdominal wall to the impact load during gravidity.

THE AIM OF THE STUDY: Selected parameters of mechanical characteristics of the gravid abdomen under impact load. TYPE OF THE STUDY: Experimental biomechanical study carried out in a human in vivo. METHOD: Damped vibration of the gravid abdomen was detected after a defined impact load using speed cinematographic recording of 103 pictures/sec. A women in 32nd week of gestation, performing toe stand and fall down to the heel, the drop was 0.08 m. The recording was digitalized and the values mathematically analysed. The method used was PAM (polynomial approximation method) of approximation of discrete coordinates. The umbilikus' trajectory in reaction to the impact load was described analytically and interpreted graphically. Parameters of abdomen vibration were detected in horizontal profile by tensometric belt. Impact in interaction of soles with the underlay was detected with the help of tensometric platform Kistler. Ultimate strength point of myometrium was set by tearing experiment in 12 samples. RESULTS: Calculation of characteristics of damped, aperiodic vibration of hydro-viscous elastic system as the outside behaviour of the gravid abdomen. Parameters in vertical direction of umbilicus: impulse in abdominal area - 2,72 Ns, T-period - 0.1299 s, amplitude - 0,009 m, frequency - 7,7 Hz, functional damping - from -6 to +12 Nsm-1. In horizontal direction: frequency 5,4 Hz, damping 123 Nsm-1. Impact in soles' sphere 40 Ns with maximum value 1511 N, which represents level 2,2 G. Ultimate strength point of myometrium is 0,1 - 1,1 MPa. CONCLUSION: The results show one of the possible critical, risky frequencies of the gravid abdomen, that is, in this concrete case, the frequency of the vibrating system of cca 7,7 Hz in vertical direction and cca 5,4 Hz horizontally. This implies that e.g. this frequency is dangerous (possible abruptio placentae) and is necessary to be avoided e.g. when travelling by means of public transportation. The applied analytic methods and presented parameters will be used for e.g. modelling the examined gravid system under impact load of a general character--locomotion, work-load, car accidents, etc.

Abdominal Wall↗

PubMedDate not supplied

Behavioral effects of dibutyryl cyclic 3'5'AMP and biogenic amines in rats.

White male Wistar rats were injected intraventricularly with 200 mug of dibutyryl cyclic 3'5'AMP (DAMP. 30 min later part of animals was injected intraventricularly with 10 mug of dopamine (DA), 10 mug of 5-hydroxytryptamine (5-HT) or 50 mug of acetylcholine (Ach). Immediately after injection of the amines the time of walking, convulsions, immobility and number of jumps during 10 min periods of observation was measured. DAMP induced excitation of animals expressed by convulsions, jumping and short period of immobility. All studied biogenic amines inhibited convulsions and caused periodically stereotypical behavior. 5-HT and Ach increased the time of immobility in animals injected with DAMP. DA increased the number of jumping. These results indicate the interaction between DAMP and DA, 5-HT and Ach on behavioral phenomena in rats.

Acetylcholine↗

PubMed1991

New platinum, titanium, and ruthenium complexes with different patterns of DNA damage in rat ovarian tumor cells.

DNA protein cross-links (DPC), DNA interstrand cross-links (ISCL), and DNA single strand breaks following treatment of experimental ovarian tumor cells (O-342) with five new metal complexes (three platinum, one titanium, one ruthenium compounds) were investigated at 6, 24, and 48 h after drug exposure and compared with their in vitro growth inhibitory potential. cis-Diamminedichloroplatinum(II) (cisplatin, DDP) served as reference drug. The following new compounds were tested: 18-crown-6-tetracarboxybis-diammineplatinum(II) (CTDP), cis-aminotrismethylenephosphonato-diammineplatinum(II) (AMDP), cis-diamminecyclohexano-aminotrismethylenephosphonato-platin um(II) (DAMP), diethoxybis-(1-phenylbutane-1,3-dionato)-titanium(IV) (budotitane), and trans-indazolium-tetrachlorobisindazole-ruthenate(III) (IndCR). At equimolar concentrations DNA cross-linking activity of the platinum agents decreased in the order cisplatin, CTDP, AMDP, DAMP; this was paralleled by growth inhibition in a cell proliferation assay. CTDP-induced interstrand cross-linking occurred more slowly compared to cisplatin (DDP) (6 h: CTDP, 73 +/- 15 versus DDP, 365 +/- 72 rad equivalents), but reached a peak similar to cisplatin 24 h after exposure (CTDP, 317 +/- 68 versus DDP, 392 +/- 116 rad equivalents). At this time point in contrast to DDP no DNA protein cross-links were observed for CTDP (total cross-links: CTDP 310 +/- 71, DDP 1987 +/- 436 rad equivalents). Thus, at 24 h, CTDP was found to be distinctly less reactive to proteins than DDP, and it is suggested that CTDP might be similar in its toxicity pattern to the structurally related compound carboplatin which was also reported to be less reactive to protein than DDP. By 48 h, CTDP- and DDP-induced interstrand cross-links were 65 +/- 21 and 180 +/- 33 rad equivalents, respectively. Although at a lower level, by 24 h, AMDP showed a ratio of ISCL to total cross-links (179 +/- 39 versus 213 +/- 31 rad equivalents), which was comparable to CTDP. The second biphosphonate complex DAMP was the least active platinum compound in terms of DNA damage, effecting only 16 +/- 7 rad equivalents ISCL and 63 +/- 28 rad equivalents total cross-links; similar to DDP, DAMP displayed a higher DPC fraction at 24 h. The titanium complex diethoxybis-(1-phenylbutane-1,3-dionato)-tita-++ +nium(IV) showed dose-dependent inhibition of cell proliferation, while no significant DNA damage could be detected with the alkaline elution technique. These results, together with observations from other authors, indicating that space-filling planar aromatic ring systems are important for its antitumor activity, suggest as possible mechanism of action of diethoxybis-(1-phenylbutane-1,3-dionato)-titanium(IV) intercalation into the DNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMedDate not supplied

Muscarinic receptor subtypes of guinea-pig gallbladder smooth muscle.

The antagonism of acetylcholine-induced contractions of guinea-pig gallbladder and ileum smooth muscle strips via various antagonists has been investigated in order to find out the muscarinic receptor subtype(s) of gallbladder smooth muscle. Atropine, pirenzepine, 4-DAMP and AF-DX 116 were used as nonselective, M1-selective, M1- and smooth muscle M3-selective and cardiac M2-selective muscarinic antagonists, respectively. All the muscarinic antagonists examined displaced the concentration-response curves to the right parallelly in a concentration-dependent manner without affecting the maximum response in both tissues. Schild analysis of data was consistent with competitive antagonism. pA2 values of the antagonists were as follows: a) gallbladder: atropine: 8.43; pirenzepine: 7.81; 4-DAMP: 8.10; AF-DX 116: 6.71; b) ileum: atropine: 9.62; pirenzepine: 6.94; 4-DAMP: 9.41; AF-DX 116: 6.55. It may be concluded that the muscarinic receptors of the guinea-pig gallbladder, which mediate acetylcholine-induced contractions, are not of the cardiac M2-subtype and may be distinguished from ileal smooth muscle M3-receptors because 4-DAMP has a 20.4 times greater affinity for ileal smooth muscle muscarinic receptors.

Acetylcholine↗

PubMed1990

[High-frequency components of occlusal sound in sliding movement].

We postulated that high-frequency components of the occlusal sound occurring due to the characteristic vibration of teeth can be useful data for confirmation of the stability in occlusion, and studied the high-frequency components in the cases both of an experimental sliding movement and a normal occlusion. The results obtained were as follows. 1. A study on high-frequency components of the occlusal sound in an experimental sliding movement. 1) A study on wave type of the occlusal sound revealed one damped oscillation in an impact form and two in a slide form. 2) Spectrum analysis of the damped oscillation showed a similar spectrum pattern with a peak existing between 16KHz or more and 17KHz or less in both impact and slide cases. 2. A study on high-frequency components of the occlusal sound in a normal occlusion case. 1) The wave type in occlusal sound we have observed in a normal occlusion group and in a prosthetic or operative group was as follows: One damped oscillation shown in an impact form and two damped oscillation in a slide form which were the same as those shown in the case where an interference device was attached. 2) Duration of the sliding movement was short in a normal occlusion group, but was prolonged in a prosthetic or operative group. 3) The incidence of the wave type in occlusal sound was 56.7% in a prosthetic or operative group as compared to 87.8% in a normal occlusion group in an impact form. In contrast, the incidence was 43.3% in a prosthetic or operative group as compared to 12.2% in a normal occlusion group in a slide form. Such difference in the incidence between the wave types suggested that high-frequency components of occlusal sound can be an index for judgement of the stability in occlusion.

Dental Occlusion↗

PubMed1990

Regulation of guinea pig ileal electrolyte transport by M3-muscarinic acetylcholine receptors in vitro.

To determine the muscarinic receptor subtype mediating guinea pig ileal mucosal electrolyte secretion, we compared the potencies (Kb) of selective M1 (pirenzepine) (PZ), M2 (AF-DX 116, methoctramine), and M3 [4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), hexahydrosiladifenidol (HHSiD)] antagonists as inhibitors of carbachol-induced reductions in guinea pig atrial heart rate and ileal longitudinal muscle contractions, responses mediated by M2 and M3 receptors, respectively. Pretreatment with all five muscarinic antagonists shifted the carbachol concentration-response curve to the right, in a manner suggesting competitive antagonism. The following affinity profiles (Kb, nM) were obtained for: 1) ileal mucosa: 4-DAMP (2.7) greater than HHSiD (23.0) greater than PZ (110) greater than or equal to methoctramine (395) greater than AF-DX 116 (784); 2) atrial heart rate: 4-DAMP (9.5) congruent to methoctramine (11) greater than AF-DX 116 (63) greater than HHSiD (222) greater than PZ (256); and 3) ileal longitudinal muscle: 4-DAMP (3.1) greater than HHSiD (21) greater than PZ (143) greater than methoctramine (388) greater than or equal to AF-DX 116 (482). The selectivity profiles of these antagonists suggest that muscarinic receptors in the ileal mucosa more closely resemble those in the ileal muscle (M3) than those in atrial muscle (M2). Moreover, M1-muscarinic receptors appear to be relatively unimportant in mediating the effects of carbachol on short circuit current (ISC). Carbachol-induced increases in ISC were also unaffected by pretreatment with 0.5 microM tetrodotoxin, suggesting that electrolyte transport in the guinea pig ileal mucosa may be mediated, in part, by postsynaptic M3-muscarinic receptors on the enterocytes.

Animals↗

PubMed1988

Circadian clock in cell culture: I. Oscillation of melatonin release from dissociated chick pineal cells in flow-through microcarrier culture.

The avian pineal gland contains circadian oscillators that regulate the rhythmic release of melatonin. We have developed a dissociated chick pineal cell culture system in order to begin a cellular analysis of this vertebrate circadian oscillator. Dissociated pineal cells maintained in cyclic light conditions (LD 12:12) released melatonin rhythmically. The release of melatonin was elevated during the dark and low during the light. A circadian oscillation of melatonin release persisted for at least 5 cycles in constant darkness with a period close to 24 hr; however, there was a gradual damping of the amplitude. Analysis of the rhythm revealed that the observed damping was consistent with either desynchronization of multiple oscillators within the cultures or damping of individual oscillators. The circadian oscillation of melatonin release persisted for up to 4 cycles under conditions of constant light; however, the oscillation was strongly damped and the period of the oscillation was lengthened significantly. Thus, dissociated pineal cells express a persistent circadian oscillation of melatonin release in constant darkness, and properties of this oscillation are modulated by light treatment in vitro. This flow-through cell culture method for dissociated chick pineal cells should provide a useful model for the analysis of a vertebrate circadian system at the cellular level.

Animals↗

PubMed1987

Indirect blood pressure monitoring in the postpartum patient.

Direct intra-arterial blood pressure (BP) measurements were compared with simultaneous standard cuff sphygmomanometry and automated inflatable cuff manometry in 12 postpartum patients. An adjustable arterial damping device was used to correct overestimations of systolic values due to distorted pressure waveforms. No significant differences in diastolic pressure with and without arterial damping were noted between noninvasive techniques and direct intra-arterial values. The systolic readings obtained with the standard cuff were significantly lower than the intra-arterial values with or without the arterial damping device (P less than .001 in both cases). However, mean systolic BP by automated cuff did not differ significantly from intra-arterial readings in the presence of the damping device (P = .10, not significant). We recommend indirect BP monitoring by automated cuff manometry in nonobese critically ill patients requiring frequent BP readings, and arterial catheter in situations requiring frequent arterial blood samples or oxygenation assessment.

Blood Pressure Determination↗

PubMed1979

[The correlation between autoregressive power spectrum of EEG and computerized tomography in tuberous sclerosis (author's transl)].

The autoregressive power spectrum and their component analyses of 36 electroencephalograms of 9 patients with tuberous sclerosis and 21 healthy children were studied. The data were recorded on the analog tapes, and the 20 second artifact free segment of records was digitized at 50 samples/sec. The autoregressive power spectrum and their component were calculated by the methods of Sato (1976) with the minicomputer PDP 11/40. The component consisted of the first and the second order elementary processes. The former showed a transient nonscillatory delta wave, whereas the latter showed damped oscillatory waves of delta, theta, alpha and beta rhythms in the EEG. The characteristics of these component rhythms in the EEG were given by the frequency, the time constant of the nonoscillatory delta, the damping time of the oscillatory component waves (time constant of the envelope of the damped oscillation), the mutual information amounts, etc. Thus, the correlation between these characteristics of component and CT-scan in tuberous sclerosis were examined. The results were as follows: 1. Compared with the characteristics of EEG in normal children, the mutual information amount, the damping time and/3r time constant showed significantly lower value in alpha rhythms of frontal-, central-regions and in theta, delta rhythms of occipital region in the patient with tuberous sclerosis. 2. Multiple subependymal high density areas were found in all of these patients on CT. EMI-number of these high density areas were less than that of calcification in younger children below the age of 3 years, but in older children were equivalent to that of calcification. 3. The correlation between the number of subependymal nodule on CT and the mutual information amount in the EEG showed significantly the negative coefficient in theta, delta rhythms of O1 region in older age group of patients. 4. The correlation between EMI-number of these subependymal high density areas and the mutual information amount in the EEG showed significantly thenegative coefficient in theta & delta rhythms of O1 region in all cases of patients. 5. It is considered that the multiple subependymal nodules may influence the background activities of the central and the occipital regions in the EEG of tuberous sclerosis.

Child↗

PubMed1993

Functional role for the M2 muscarinic receptor in smooth muscle of guinea pig ileum.

A functional role for the M2 muscarinic receptor in smooth muscle contraction was investigated in isolated guinea pig ileum. Contractile responses to the muscarinic agonist oxotremorine-M (oxo-M) were measured in isolated ilea that had been pretreated with histamine (0.32 microM) and isoproterenol (0.64 microM) to achieve conditions of elevated cAMP. The resulting concentration-effect curve was biphasic, consisting of high (0-50 nM) and low (> 50 nM) potency components. The reversible M2-selective antagonist AF-DX 116 ([[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11- dihydro-6H-pyrido[2,3b][1,4]benzodiazepine-6-one) (1 and 10 microM) shifted this curve in a manner that was inconsistent with competitive antagonism at a single receptor site; the high affinity component was significantly blocked, whereas there was little effect on the low affinity portion of the curve. To inactivate the M3 muscarinic receptors selectively, ilea were incubated with the irreversible M1/M3-selective muscarinic antagonist 4-DAMP mustard [N-(2-chloroethyl)-4-piperidinyldiphenylacetate] (40 nM) for 1 hr in the presence of AF-DX 116 (1 microM) and were then washed extensively. Under these conditions, the contractile responses to oxo-M, in the presence of histamine and isoproterenol or forskolin, were antagonized by AF-DX 116 (1 microM) in a manner consistent with that mediated by an M2 receptor. AF-DX 116 caused 6.6- and 11-fold increases in the EC50 value for oxo-M for ilea pretreated with isoproterenol and forskolin, respectively, and a significant increase in the Hill coefficient in both cases. Under basal conditions, AF-DX 116 caused only a 1.34-fold increase in the EC50 value and no change in the Hill coefficient. In addition, under basal conditions 4-DAMP mustard treatment shifted the oxo-M contractile response curve to the right approximately 20-fold. However, when histamine was present in combination with isoproterenol or forskolin 4-DAMP mustard treatment shifted the concentration-effect curves for oxo-M to the right only about 3.5-fold. Oxo-M produced an M3-mediated stimulation of phosphoinositide hydrolysis in the longitudinal muscle of rat ileum with an EC50 value of 30 microM. 4-DAMP mustard (10 nM; 1 hr) prevented this response, resulting in a 6.6-fold increase in the EC50 value with a 65% reduction of the maximal response. In contrast, this treatment blocked M2-mediated inhibition of isoproterenol-stimulated adenylate cyclase with only a 2-fold increase in EC50, without affecting maximum inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1999

In vivo human corneal hydration control dynamics: a new model.

PURPOSE: To introduce a new model describing human in vivo corneal deswelling after hypoxic contact lens wear, based on a damped harmonic oscillator, which can describe an overshoot in corneal deswelling, to compare this new model with the currently used exponential model, and also to test whether a diurnal variation in baseline corneal thickness exists that would have to be taken into consideration when calculating corneal deswelling curves. METHODS: In nine healthy young adults, corneal thickness was measured every 30 minutes for 11.5 hours on average using modified optical pachometry (natural test). On another day, corneal deswelling was monitored for 11.1 hours on average after 2 hours of hypoxic contact lens wear (stress test). The damped harmonic oscillator model and the exponential model were used to calculate best-fitting deswelling curves. Natural test data were analyzed for the presence of a trend. Goodness of fit of the curves to the experimental data was analyzed using the F test. RESULTS: In 82% of the deswelling curves the new damped harmonic oscillator model provided a better fit to the data than the exponential model (P < 0.05). An average overshoot in corneal thickness recovery of 5 microm (range, 0-11 microm) was found. In 50% of the natural tests significant trends were found, without any consistent similarities. The overshoot could not be explained by these trends. CONCLUSIONS: The new damped harmonic oscillator model describes corneal deswelling after hypoxic contact lens wear more accurately than the exponential model. No consistent diurnal variation could be demonstrated.

Adult↗

PubMed1999

Characterization of acrylic bone cement using dynamic mechanical analysis.

Dynamic mechanical analysis (DMA) was used to characterize the properties of acrylic bone cement with the addition of tricalcium phosphate (TCP), hydroxyethyl methacrylate (HEMA), and ethylene glycol dimethacrylate (EGDMA). The glass transition temperature of acrylic bone cement is >100 degrees C; the cement has a flat modulus response near human body temperature. The height of the damping peak decreases and becomes broader with increasing TCP content. Thus, TCP is incompatibile with acrylic bone cement. When the frequency is changed from high to low, the damping peak shifts to low temperature. The shift in damping peak with frequency indicates that this relaxation is time-dependent. When acrylic bone cement contains TCP with HEMA and EGDMA, the incompatibility between acrylic bone cement and TCP can be ameliorated.

Biocompatible Materials↗

PubMed1996

Lorentz approach to static magnetic field effects on bound-ion dynamics and binding kinetics: thermal noise considerations.

The present study characterizes an ion-binding site, a molecular cleft in a signalling molecule such as calmodulin or troponin C, as a damped linear isotropic oscillator potential for small displacements about the origin. Quantitative assessments of the effects of thermal noise and exogenous static magnetic fields are made through a statistical mechanical treatment of the Lorentz-Langevin equation for an ion bound in a molecular cleft. Thermal noise causes a bound ion to be ejected from the site after a bound lifetime dependent upon the thermal noise spectral density. It is shown that the Lorentz-Langevin model requires values of the viscous damping parameter many orders of magnitude below those for bulk water in order to characterize the binding site and to obtain realistic lifetimes for a bound ion. The model predicts that milliTesla-range magnetic fields are required for static field effects on dissociation kinetics. The Lorentz equation also yields a classic coherent solution describing precession of the bound-ion oscillator orientation at the Larmor frequency. The bound-ion dynamics described by this coherent solution are sensitive to microTesla-range static magnetic fields in the presence of thermal noise. Numerical integration of the contribution of thermal noise forces to these dynamics is in good agreement with the results of statistical mechanical analysis, also producing realistic bound lifetimes for only very low viscous damping values. The mechanisms by which modulation of precessional motion might enable a signalling molecule such as calmodulin to detect an exogenous magnetic field are presently unclear.

Animals↗