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Psychometric research on widely used questionnaires aimed at measuring experiential avoidance of chronic pain has led to inconclusive results. To test the structural validity, internal consistency, and construct validity of a recently developed short questionnaire: the Acceptance and Action Questionnaire II-pain version (AAQ-II-P). Cross-sectional validation study among 388 adult patients with chronic nonspecific musculoskeletal pain admitted for multidisciplinary pain rehabilitation in four tertiary rehabilitation centers in the Netherlands. Cronbach’s αwas calculated to analyze internal consistency. Principal component analysis was performed to analyze factor structure. Construct validity was analyzed by examining the association between acceptance of pain and measures of psychological flexibility (two scales and sum), pain catastrophizing (three scales and sum), and mental and physical functioning. Interpretation was based on a-priori defined hypotheses. The compound of the seven items of the AAQ-II-P shows a Cronbach’s αof 0.87. The single component explained 56.2% of the total variance. Correlations ranged from r=−0.21 to 0.73. Two of the predefined hypotheses were rejected and seven were not rejected. The AAQ-II-P measures a single component and has good internal consistency, and construct validity is not rejected. Thus, the construct validity of the AAQ-II-P sum scores as indicator of experiential avoidance of pain was supported.

HYPOTHESIS Mesh repair is generally preferred for surgical correction of inguinal hernia, although the merits of endoscopic techniques over open surgery are still debated. Herein, minimally invasive total extraperitoneal inguinal hernioplasty (TEP) was compared with Lichtenstein repair to determine if one is associated with less postoperative pain, hypoesthesia, and hernia recurrence. DESIGN Prospective multicenter randomized clinical trial. SETTING Academic research. PATIENTS Six hundred sixty patients were randomized to TEP or Lichtenstein repair. MAIN OUTCOME MEASURES The primary outcome was postoperative pain. Secondary end points were hernia recurrence, operative complications, operating time, length of hospital stay, time to complete recovery, quality of life, chronic pain, and operative costs. RESULTS At 5 years after surgery, TEP was associated with less chronic pain (P = .004). Impairment of inguinal sensibility was less frequently seen after TEP vs Lichtenstein repair (1% vs 22%, P < .001). Operative complications were more frequent after TEP vs Lichtenstein repair (6% vs 2%, P < .001), while no difference was noted in length of hospital stay. After TEP, patients had faster time to return to daily activities (P < .002) and less absence from work (P = .001). Although operative costs were higher for TEP, total costs were comparable for the 2 procedures, as were overall hernia recurrences at 5 years after surgery. However, among experienced surgeons, significantly lower hernia recurrence rates were seen after TEP (P < .001). CONCLUSIONS In the short term, TEP was associated with more operative complications, longer operating time, and higher operative costs; however, total costs were comparable for the 2 procedures. Chronic pain and impairment of inguinal sensibility were more frequent after Lichtenstein repair. Although overall hernia recurrence rates were comparable for both procedures, hernia recurrence rates among experienced surgeons were significantly lower after TEP. Patient satisfaction was also significantly higher after TEP. Therefore, TEP should be recommended in experienced hands. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00788554

Seemingly distinct cognitive tasks often activate similar anatomical networks. For example, the right fronto-parietal cortex is active across a wide variety of paradigms suggesting that these regions may subserve a general cognitive function. We utilized fMRI and a GO/NOGO task consisting of two conditions, one with intermittent unpredictive “cues-to-attend” and the other without any “cues-to-attend,” in order to investigate areas involved in inhibition of a prepotent response and top-down attentional control. Sixteen subjects (5 male, ages ranging from 20 to 30 years) responded to an alternating sequence of the letters X and Y and withheld responding when the alternating sequence was broken (e.g., when X followed an X). Cues were rare stimulus font-color changes, which were linked to a simple instruction to attend to the task at hand. We hypothesized that inhibitions and cues, despite requiring quite different responses from subjects, might engage similar top-down attentional control processes and would thus share a common network of anatomical substrates. Although inhibitions and cues activated a number of distinct brain regions, a similar network of right dorsolateral prefrontal and inferior parietal regions was active for both. These results suggest that this network, commonly activated for response inhibition, may subserve a more general cognitive control process involved in allocating top-down attentional resources.

The controlled radical polymerization (CRP) technique reversible addition−fragmentation chain transfer (RAFT) has potential for preparing functional (co)polymers directly in an aqueous environment. Hydrolysis and aminolysis can eliminate the active end groups necessary for maintaining “livingness” in water. These reactions have not previously been evaluated with respect to their effect on aqueous RAFT polymerizations. Herein we determine rate constants of hydrolysis and aminolysis for representative water-soluble chain transfer agents (CTAs) cyanopentanoic acid dithiobenzoate (CTP) and the macro-chain-transfer agents (macro-CTAs) of poly(sodium 2-acrylamido-2-methylpropanesulfonate) (AMPSX) and poly(acrylamide) (AMX) at selected pH values. Rates of hydrolysis and aminolysis both increase with increasing pH and decrease with increasing molecular weight of the dithioester. On the basis of these rate constants, mathematical relationships have been developed to predict the number of living chain ends and the molecular weight with competitive hydrolysis. Utilizing this approach, predictions of molecular weight at specific conversions are in agreement with experimental values determined by SEC/MALLS.

Experimental solution intrinsic viscosity responses to temperature and polymer molecular weight variations were used to test the modeling capability of a simplified intrinsic viscosity equation. The multiple linear equation contains three parameters that are related to the thermodynamic properties of a polymer solution. Simple linear regression was used to produce an intrinsic viscosity equation containing unique fitted parameters for each of three solutions. These parameters describe the polymer coil size at unperturbed conditions and the polymer coil expansion capabilities of the solvent as a function of fluid temperature and molecular weight. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2831–2835, 2003

Ultrafast time-resolved electronic absorption spectroscopy has been used to study the photochemistry of trans-azobenzene and trans-1, a derivative in which azobenzene is capped by an azacrown ether, on UV excitation to the S2(ππ*) state. Excitation of trans-1 results in transient absorption which decays with a dominant component of lifetime ca. 2.6 ps and in bleaching of the ground-state UV absorption band which recovers on a similar time scale. In contrast, excitation of trans-azobenzene results in transient absorption which decays with a dominant component with a shorter lifetime of ca. 1 ps, and in bleaching which recovers on a much longer time scale of ca. 18 ps. The recovery of the ground-state UV absorption band is not complete in either case, and the ultrafast data indicate that the quantum yield of trans-to-cis photoisomerization of 1 is approximately twice that of azobenzene. These observations demonstrate that the restricted rotational freedom of the phenyl groups in trans-1 has a significant effect on the excited-state dynamics and decay mechanism. The differences in lifetime and quantum yield of photoisomerization are attributed to rapid internal conversion from the S2 to S1 excited states of trans-1, which results in photoisomerization by an inversion mechanism in the S1 state, whereas fast rotation in the S2 state of trans-azobenzene populates a “bottleneck” state which delays the recovery of the ground state and which reduces the yield of photoisomerization; this “bottleneck” state is not accessible by trans-1. The results support the proposal that rotation is the dominant pathway for decay of the first-formed S2 state of trans-azobenzene but that inversion is the dominant pathway for decay of the S1 state.

The 10 kA ETA and ATA linear induction accelerators are described. Beam instability is the major concern in these high current machines, and the current status of theoretical understanding, and experimental investigations with the 8 cavity ETA, are reviewed. Modifications to the induction cavities are described that have essentially eliminated the transverse resonant modes seen in the ETA.

Summary: The rheology of a latex paint must be controlled to produce an acceptable coating. Conditions vary as a paint is sequentially taken from storage, applied to a substrate and then cured in place. As shown byTable 1, desirable films are produced only when paint viscosities and yield points are controlled at each process step. Thus, an understanding and control of paint rheology are essential if high quality coatings are to be produced from latex paints.

UV−visible absorption and emission spectroscopy have been used to study the complexation of Ba²⁺ with a benzothiazolium styryl azacrown ether dye and two derivatives, one without an azacrown and one with an alkylsulfonate pendant to the benzothiazolium group. Studies of the thermal cis−trans isomerization on the kilosecond time scale, and of the excited state leading to trans−cis photoisomerization on the picosecond time scale, are reported which enable a quantitative analysis of the kinetics and complexation equilibria to be obtained. The photophysics are interpreted by a scheme which includes rotation around both the olefinic C&dbd;C bond and adjacent C−C bonds in the excited state. A comparison of the data for this dye with those for other derivatives studied here and reported elsewhere indicates that the extent of intramolecular charge transfer in the excited state is a key factor in controlling the properties. An overall mechanism is proposed for the thermal and photochemical reactions of this dye which indicates that it is a good candidate for applications which require the photocontrolled complexation/release of barium cations in solution.

The inversion of 1,4-dioxane has been studied by using ab initio molecular orbital theory at the HF/6-31G* and BLYP/6-31G* levels. A total of 10 stationary points were characterized as energy minima or transition states. Vibrational frequencies were calculated for the chair and two twist-boat conformations. The chair conformation is the lowest in energy, followed by the two twist-boats. The transition state connecting the chair and the twist-boats is a half-chair structure, in which four atoms in the ring are planar. Thermochemical analysis of the chair, twist-boats, and the half-chair structures yields a value of the free energy of activation to ring inversion that is in good agreement with experiment.

The effects of nitroprusside (NP) and D 600 on norepinephrine (NE)- and KCl-induced maximal contractions and unstimulated 45Ca uptake and efflux were delineated in canine renal vein (CRV) and compared with results in renal artery. In CRV, but not in renal artery, NE-induced contractions are usually associated with rhythmic oscillations in developed tension. Corresponding KCl-induced contractions are not associated with rhythmic activity and are depressed by 57 in the presence of phentolamine (PA). The calcium channel blocker, D 600, rapidly and extensively relaxed NE-induced contractions (86) in CRV, but slowly and moderately relaxed similar responses in artery (46). PA-resistant, KCl-induced contractions were equally sensitive to the relaxant effects of D 600 in CRV (73) or artery (72), but the rate of relaxation was much more rapid in CRV. Prior exposure to D 600 inhibited KCl-induced contractions in both CRV and artery (99 versus 91, respectively). Similar prior treatment reduced NE-induced contractions (60) in CRV, and prevented the development of any NE-dependent rhythmic activity. In renal artery, NE-induced contractions were unaffected by prior D 600 exposure. NP relaxed KCl-induced contractions 32 in the presence of PA in CRV, but had little effect on KCl-induced responses in artery (6). Prior exposure to NP inhibited KCl-induced contractions 60–67 in CRV, which is approximately twice the inhibition seen in artery (31). Relaxation of NE-induced contractions with NP in CRV and renal artery are (43 and 38, respectively) approximately equal. In renal artery, responses to NE are less sensitive (1.6-fold) to prior NP exposure than in CRV. Prior exposure to NP or to NP plus D 600 reduced NE-induced contractions in CRV 37 and 96, respectively. NP and D 600 were without effect on unstimulated 45Ca uptake in CRV. In CRV, D 600 had no effect on 45Ca efflux into a O-Casolution, whereas NP decreased the rate of 45Ca efflux in a maintained manner. Thus, NP and D 600 appear to interfere with differing components of Caentry and Carelease in CRV. However, these components are less readily differentiated and more interdependent than similar, well-defined and characterized components in arterial smooth muscle, and appear to be convergent.

The vasoinhibitory action of nitroglycerin was examined on contractile responses to methoxamine and clonidine in isolated rabbit aorta. Nitroglycerin at 10-5M, /ibut not 10-6–10-8M, shifted the concentration response curve for methoxamine to the right. Nitroglycerin (10-8–10-5M), however, noncompetitively inhibited responses to clonidine in a concentration dependent manner. Nitroglycerin (10-5M) had no effect on responses to potassium (10–70 mM), but slightly inhibited responses to Ca2+(0.1–5 mM) in a Ca2+-free medium containing potassium. Nifedipine (10-6and 10-5M), however, almost abolished responses to both potassium and Ca2+but had no effect on responses to either methoxamine or clonidine. Agonist-antagonist interactions using prazosin and yohimbine revealed that responses to both methoxamine and clonidine were due to activation of α1-adrenoceptors. Results with phenoxybenzamine suggested that the aorta has more receptor reserve for methoxamine than for clonidine. Furthermore, in tissues pretreated with phenoxybenzamine, nitroglycerin (10-5M) inhibited the maximal contractile response to methoxamine (3 X 10-4M). /iThe maximal response to clonidine in tissues pretreated with phenoxybenzamine was not affected by nitroglycerin (10-8M). Nitroglycerin (10-9–10-4M) had greater inhibitory effect on residual responses to clonidine (10-5M) than that to methoxamine (10-5M) in a Ca2+-free medium containing EGTA. The contractile responses to Ca2+(2 mM) in a Ca2+-free medium containing EGTA, nifedipine, and either methoxamine (5 X 10-7M) or clonidine (3 X 10-7M) were inhibited by nitroglycerin (10-9–10-5M). The effect of nitroglycerin was greater on responses in the presence of clonidine than methoxamine. The rate of La3+resistant, unidirectional 45Ca influx was increased equally by methoxamine (5 X 10-7M) and clonidine (3 X 10-7M). These increases were inhibited by nitroglycerin (10-6M). These results suggest that nitroglycerin inhibits contractile responses to clonidine much more than those to methoxamine. This differential sensitivity to nitroglycerin is not due to differences in the selective activation of α1- or α2-adrenoceptors but to differences in the amount of receptor reserve. Nitroglycerin interferes with contractile responses due to both intracellular Ca2+mobilization and Ca2+translocation through receptor-activated, nifedipine insensitive channels.

Four binuclear rhenium(I) complexes of the form [Re(CO)3Cl]2BL, where BL is one of the bridging N4-donor ligands 2,3-di(2-pyridyl)quinoxaline, 2,3-di(2-pyridyl)-6-methylquinoxaline, 2,3-di(2-pyridyl)pyrido[2,3-b]pyrazine, or 2,3-di(2-pyridyl)pyrido[3,4-b]pyrazine, have been studied by femtosecond time-resolved UV−visible and infrared absorption spectroscopies. Photolysis at 606 nm, within the metal-to-ligand charge-transfer (MLCT) absorption band of each complex, produces transient features with lifetimes which vary from 100 to 1800 ps, depending on the structure of the bridging ligand. These transient species are assigned to the ³MLCT excited states of the complexes. A detailed analysis of the time-resolved infrared spectra reveals that the three principal ν(CO) bands of the ground state, which arise from two Re(CO)3Cl groups in similar environments, split into two sets of three ν(CO) bands in the ³MLCT excited states. This splitting pattern is attributed to asymmetric charge distribution in the excited state, in which one rhenium center is oxidized and the other is a spectator which senses the reduction of the bridging ligand; i.e., the excited state is a class II mixed-valence state, Re⁺(BL^-)Re. Changes in the transient spectra which occur within ca. 5 ps, and which are observed most clearly as broadening to lower wavenumber of the excited-state infrared bands, are attributed to vibrational relaxation in the excited state. The variation in excited-state lifetime with bridging ligand structure is attributed to changes in the rate constants for nonradiative decay, which correspond qualitatively with changes in the energy of the excited state in accordance with the “energy-gap law” for nonradiative relaxation.

Previous studies have demonstrated that an acute intravenous administration of nitro-L-arginine methyl ester (L-NAME) causes a sustained hypertension and widespread vasoconstriction. However, little information is available regarding the chronic effect of L-NAME on circulatory hemodynamics. Therefore, the purpose of the present study was to characterize both the systemic and regional hemodynamics after the chronic inhibition of endothelium-derived nitric oxide in male Sprague Dawley rats. The rats were divided into two groups: control (n = 8) and L-NAME (n = 8). The rats in the control group received only tap water and the rats in the L-NAME group received oral L-NAME solution at a dose of 0.1 mg/mL in the drinking water ad libitum. Four weeks after L-NAME or tap water treatment the rats were anesthetized with inactin, and mean arterial blood pressure, cardiac output, and individual organ flows were measured. Cardiac output and individual organ flows were measured using radioactive microspheres. Chronic administration of L-NAME resulted in a significant increase in mean arterial blood pressure from a control value of 118 +/- 4 mm Hg to 174 +/- 8 mm Hg (P < .01). Cardiac output decreased from a control value of 29 +/- 2 mL/min/100 g to 20 +/- 2 mL/min/100 g (P < .01) and total peripheral resistance increased from a control value of 4.3 +/- 0.3 mm Hg/mL/min/100 g to 9.7 +/- 1.4 mm Hg/mL/min/100 g (P < .01). In addition, chronic L-NAME treatment resulted in a widespread vasoconstriction and decrease in regional blood flows.(ABSTRACT TRUNCATED AT 250 WORDS)

The action and interactions of three vasoconstrictors, norepinephrine (NE), dopamine (DA) and elevated potassium ion (K+) on contractile responses and associated 45Ca movements were investigated in isolated rabbit and canine renal arteries (RA). Dose-response curves indicate that NE is 39 times more potent than DA in canine RA and 122 times more potent in rabbit RA. Prior exposure to 80 mM K+ did not prevent contractile responses to NE or DA but, conversely, K+ -induced responses did not occur after exposure to NE or DA. Responses to NE persisted after maximum DA-induced contractions but only a small response to DA was observed after a maximum NE-induced contraction. After 30 to 60 min in either a O-Ca or a O-Ca plus 0.05 mM EDTA solution, contractile responses were differentially inhibited (K+ more than DA more than NE). Efflux of 45Ca into a O-Ca plus EDTA solution was qualitatively similar in canine and rabbit RA. Addition of K+, DA or NE decreased the rate of 45Ca efflux in both RA; phentolamine abolished the NE-induced decrease and had no effect on the K+-induced decrease. The observed decrease in 45Ca efflux may reflect an inward shift of 45Ca from membrane binding sites. The mechanisms by which this effect is obtained appear to differ for K+, DA and NE. The differing actions of NE and DA cannot be explained solely by variations in potency at a singel type of receptor.

Administration of nitroprusside (NP) subsequent to induction of contraction in canine renal arterial strips with norepinephrine (NE) yielded a dose-dependent relaxation and with 80 mM potassium (KCl) yielded only a small degree of relaxation. The effect elicited with 0.1 mM NP was significantly greater for responses obtained with NE (68%) than for those with KCl (12%). However, responses of muscles pretreated for 5 min with NP to NE to KCl were reduced by 23 and 31%, respectively. The relaxant effect of NP persisted after incubation with D-600 and/or 30 min of a 0-Ca plus 0.05 mM EDTA solution (low EDTA). Neither D-600 nor NP altered 45Ca uptake in the absence of stimulatory agents. Efflux of 45Ca (into low EDTA solution) was decreased by NP in a maintained manner but was unaffected by D-600. The NE-induced decrease in 45Ca efflux (but not that with KCl) was blocked by NP. However, changes in 45Ca efflux elicited with KCl or NE were not affected by D-600. In contrast to D-600 (which is known to inhibit increased Ca++ entry associated with some stimulatory conditions), NP acts in a manner that is relatively independent of uptake of extracellular Ca++. Thus, these two vasodilators appear to affect Ca++ utilization by different mechanisms and, presumably, in an additive manner.

Summary The following discourse addresses the pharmacologic profile of KT-362, its clinical potential as an antiarrhythmic agent with associated hypotensive effects, as well as its additional related potential in myocardial ischemia and related sequellae, and the specific cellular actions that may be responsible for these potential therapeutic effects. Although these include specific actions on both sodium and calcium entry, the focus is on the relevance of independent effects on calcium release. KT-362 relaxes arterial smooth muscle, concomitantly reducing the total peripheral resistance and mean arterial blood pressure. Vascular relaxing actions are attributed primarily to inhibitory effects on calcium release and secondarily to inhibitory effects on calcium entry via both potential-gated and receptor-linked channels. The “intracellular calcium antagonist” properties are correlated with a decrease in the production of the major second messenger, inositol 1,4,5-trisphosphate, which is responsible for calcium release and a concurrent ryanodine-like action that further decreases the amount of calcium released. Ventricular arrhythmias associated with coronary occlusion, cardiac glycosides, catecholamines, and chloroform are prevented by KT-362. General antiarrhythmic properties are associated with a use-dependent block of the “fast” sodium channel, primarily in the activated state, with ancillary effects on the “slow” calcium current. More selective effects on arrhythmias specifically associated with delayed afterdepolarizations are attributed to effects on calcium release. In myocardial ischemia, KT-362 primarily reduces myocardial oxygen consumption rather than increases oxygen supply. The former is accomplished by depressing myocardial contractility and reducing afterload, while the latter is associated with a limited effect on coronary collateral blood flow. The negative inotropic effect is fundamentally related to its effects on calcium release, with additional contributions from its effects on calcium entry. Thus, the one intrinsic property of KT-362 that consistently emerges as significant and relevant in cardiovascular disease is the capacity to diminish calcium release.

The effects of monensin on coronary blood flow (CBF) and other hemodynamic parameters were studied in anesthetized dogs. A dose-response relationship was established, and it was found that the lowest doses of monensin (5–25 μg/kg) produced a dose-dependent increase (3–5x) in CBF with a concomitant decrease in total peripheral resistance (TPR). Pretreatment with diphenhydramine, atropine, indomethacin, or propranolol resulted in no reduction in peak increase in CBF or in the duration of response to monensin. However, the response was partially blocked by aminophylline. Large doses (100 and 200 μg/kg) produced a dose-dependent increase in cardiac output, aortic pressure, and LV dP/dtmax. The duration of these effects was dose-dependent, ranging from 60 to 120 min or longer. Heart rate remained unchanged with all doses of monensin. Pretreatment with propranolol, H87/07 (a cardioselective β-blocker), and D-600 given alone or in combination significantly reduced, but did not completely abolish, the monensin-induced increase in LV dP/dtmax and aortic pressure responses. The increase in CBF in the left anterior descending coronary artery was not significantly affected by these drug pretreatments. Thus, our studies indicate that monensin has two distinct pharmacological effects—in the lower dose range (< 25 μg/kg) it produces a direct relaxation of the blood vessels resulting in an increase in CBF and a decrease in TPR: at high doses (25 μg/kg) it increases myocardial contractility and aortic blood pressure.

The effects of hyperosmotic mannitol on vascular smooth muscle contractile responses and on 45Ca movements were examined in different isolated canine arteries. Prior exposure to 50 dim mannitol decreased contractile responses elicited with dopamine (DA) in helical strips of canine terminal mesenteric arteries (Tm) and decreased the contractile response elicited with potassium (K) in both isolated left anterior descending (LAD) and circumflex coronary arteries. Tension responses induced by norepinephrine or DA in the Tm and Kand prostaglandin F2αin LAD were relaxed by subsequent exposure to mannitol. Mannitol increased the uptake of 45Ca in Tm arteries. Exposure of the Tm and branches of the LAD to mannitol during the washout of 45Ca resulted in a decrease in the rate of loss of 45Ca; the presence of either K, Mg2, or ethylenediamine tetraacetic acid during the washout did not prevent the observed mannitol-induced decrease in 45Ca efflux. These effects of mannitol on 45Ca efflux without a concomitant major change in net 45Ca uptake could be attributed to an increase in bound Ca2at relevant membrane sites or stores. Thus, hypertonic mannitol may alter contractile responsiveness of selected canine arteries by impeding the release of bound and/or sequestered Ca2and, in this manner, decreasing the Ca2concentration at the contractile elements.

A modified Weibull distribution function is shown to be useful in calibrating the molecular size separation capabilities of both rigid and swellable gel packing materials. Two parameters are used in this function which are related to a packing material's micropore volume distribution. The calibration curves of a set of different packing materials connected in series were predicted from the Weibull calibration functions obtained for each individual packing material.

An on-line viscometer which measures the eluent pressure drop across a long capillary was developed for use in aqueous size exclusion chromatography (SEC). Intrinsic viscosities of several polymer standards were calculated from data collected by the viscometer. These viscosities agree well with the measurements made with a Ubbelohde four-bulb shear dilution viscometer. The on-line viscometer becomes more sensitive as polymer hydro-dynamic volume increases. Therefore, it can be more effective than a refractive index detector for SEC analysis of high molecular weight, water soluble polymers.

Two programs, ACEACQ and ACEANN, provide data acquisition and analysis for Size Exclusion Chromatography (SEC). ACEACQ is used for data logging, real-time smoothing and data reduction by boxcar averaging. ACEACQ requires that traditional SEC hardware be coupled with a Hewlett Packard data logger and microcomputer. A Mettler electronic balance is connected to the computer in a novel fashion to continuously monitor the mass of solvent eluted during an experiment. ACEANN provides analysis for the data collected by ACEACQ. Calculations include molecular weight averages, molecular hydrodynamic diameter averages and column separation efficiency parameters. Significant reductions in analysis time have been realized along with improvements in accuracy of data acquisition, analysis and experimental reproducibility.

Specific receptor-linked Ca++ entry (RLCa++E) was studied separately from Ca++ release and potential-dependent Ca++ entry (PDCa++E) in rabbit aorta after incubation in a Ca++-free solution containing ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid to bind trace levels of Ca++ and including methoxyverapamil (D600) (10(-5) M) to inhibit PDCa++E. Adding norepinephrine (NE) under these conditions resulted in a transient response which was attributed to Ca++ release from a limited cellular store. Subsequent addition of Ca++ results in a sustained contraction that was dependent upon the concentration of agonist and Ca++. This maintained response which by definition was insensitive to D600 was attributed to RLCa++E, was extensively relaxed or inhibited by nitroprusside or nitroglycerin and was partially relaxed by KCl or tetraethylammonium. Contractions due to RLCa++E alone equaled or exceeded the peak tension attained solely as a result of Ca++ release. At higher NE concentrations (greater than 10(-7) M), RLCa++E provided sufficient Ca++ to attain and sustain maximal levels of developed tension without requiring any additional Ca++ from either PDCa++E or Ca++ release. This high flux capacity of these receptor-linked Ca++ channels may partially account for the relative insensitivity of contractile responses to these higher concentrations of NE to D600. The relative contribution of PDCa++E to the elevation of myoplasmic Ca++ and concurrent sensitivity to D600 was increased at lower concentrations of NE because the degree of Ca++ release and RLCa++E were relatively small. Additionally, it appears that RLCA++E may be attenuated by concomitant membrane depolarization.

Contractile and relaxant responses of rabbit aortae in artificial buffered (Tris and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) solutions were compared with those in bicarbonate-buffered solution. EC50 values for responses to KCl in aortae equilibrated in Tris and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid were slightly less than those in bicarbonate; maximum contractions did not differ. There were no significant differences in contractile responses to prostaglandin Fa alpha or histamine in the three buffered solutions. In aortae precontracted with prostaglandin F2 alpha, both acetylcholine and the calcium ionophore, A23187, elicited much less relaxation in artificial buffered solutions than in bicarbonate-buffered solutions. Maximum relaxations to nitroprusside or D600 did not differ among the three solutions. Relaxant responses to isoproterenol were also depressed in artificial buffered solutions. Endothelial damage eliminated relaxant responses to acetylcholine and A23187, as well as the difference in responsiveness to KCl and isoproterenol noted in artificial buffered compared with bicarbonate-buffered solutions. Within the same solution, endothelial damage alone did not alter the responsiveness to KCl or histamine. Total and La -resistant Ca++ binding was similar in all three buffered solutions. Thus, contractile responses are not depressed in Tris- or N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered solutions, whereas endothelium-dependent relaxations are attenuated in similar solutions. Overall, the results imply that, in artificial buffered solutions, the production and/or release of an endothelium derived relaxing factor is attenuated or that its action on aortic smooth muscle is, in some manner, functionally antagonized.

In rabbit aorta, pretreatment with KT-362 (KT; 10(-6) and 10(-5) M) inhibited contractile responses to norepinephrine (NE; 3 X 10(-9)-10(-5) M) and methoxamine (10(-7)-10(-4) M) but failed to affect responses to potassium (10-70 mM). KT (10(-5) M) partially inhibited Ca++-induced contractions in K+-depolarized aorta pre-equilibrated in a Ca++-free medium. After incubation of tissues for 30 min in a Ca++-free medium containing EGTA (0.2 mM), residual responses to NE and methoxamine were inhibited by KT (10(-6)-10(-4) M) and nitroglycerin (10(-5) M), but not by nifedipine, verapamil or diltiazem (all 10(-5) M). The inhibitory action of a combined treatment with KT and nitroglycerin (both 10(-5) M) on the residual response to NE was also much greater than that of either agent alone. In a Ca++-free medium, the residual caffeine-induced contraction of rabbit iliac artery was inhibited by KT (10(-5)-10(-4) M) but not by nifedipine (10(-5) M). The inhibitory action of KT on the residual responses to methoxamine and caffeine in a Ca+-free medium was much greater than that of nitroglycerin. In a Ca++-free medium with low EGTA (0.01 mM), D600 (10(-5) M) and NE (3 X 10(-7) M), the addition of Ca++ (2 mM) resulted in a tonic contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationships between tension responses to norepinephrine (NE) and high potassium (KCl) and high affinity 45Ca binding and mobilization were compared in canine renal arteries and veins. Contractile responses to 80 mM KCl were inhibited 83 (veins) and 88% (arteries) after respective 5-min and 60-min incubation periods in solutions with no added Ca++; responses to 10(-4) M NE were inhibited 87% (veins) and only 44% (arteries) after 60 min in the same solution. In solutions favoring low affinity binding of Ca++ (5.0 mM), uptake of 45Ca was similar in canine renal arteries and veins. However, in solutions favoring high affinity Ca++ binding (0.03 mM Ca++), 45Ca uptake was greater in arteries than in veins. Comparison of 45Ca efflux rates indicates a more rapid efflux and a greater Ca++-45Ca exchangeability in veins. After incubation with 45Ca and subsequent washout in an isosmotic (80.8 mM) La+++-substituted solution at 0.5 degrees C, 45Ca retention (residual Ca++ uptake) was proportionately greater in arteries than in veins at both high and low affinity sites. NE (10(-6) M) significantly increased La+++-resistant 45Ca uptake at both high and low affinity sites in veins but not in arteries. Thus, the NE-induced responses in veins depend upon extracellular Ca++ to a greater degree than in arteries. Even though veins have a lower number of high affinity Ca++ binding sites and this decreases the ability of the veins to retain sufficient Ca++ at these sites to maintain the response to NE, the responsiveness to NE appears to be maintained by an alternate mechanism, uptake of Ca++ at lower NE concentrations.

The effects of 2-nicotinamidoethyl nitrate (SG-75) on norepinephrine (NE)- and KCI-induced responses in rabbit aorta were quantitated, correlated with 45Ca studies and compared with the effects of nifedipine (NIF) on similar parameters. NE- and KCI-induced dose-response relationships were differentially depressed by SG-75 (NE much greater than KCI) and NIF (KCI much greater than NE). Responses to KCI were relatively insensitive to prior SG-75, yet moderately relaxed by subsequent SG-75. Conversely, NIF markedly inhibited and completely relaxed similar responses. Responses to NE were relaxed and inhibited with SG-75, but unaffected by NIF. Responses to NE in La or O-Ca++ + ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid plus D600 (with and without KCI) solutions were phasic, reduced by SG-75 and insensitive to NIF. NE-dependent, Ca++-induced responses in a O-Ca++ + ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid plus D600 solution (with and without KCI) were attenuated by SG-75. Equilibrated (60 min) La -resistant (residual), high apparent affinity Ca++ binding was increased 26% with SG-75 and decreased 34% with NIF, yet neither altered the rate of exchange (10 min). Rate of exchange at low apparent affinity, residual sites was increased 21% by SG-75 without altering equilibrated values, whereas NIF reduced equilibrated values 11%, without affecting rate. NE reduced, SG-75 + NE augmented and NIF + NE decreased, in an additive fashion, high apparent affinity, residual bound Ca++. Residual Ca++ binding at low apparent affinity sites was increased with 160 mM substituted KCI (380%). This increase was only partially inhibited with SG-75, and eliminated by NIF. Net Ca++ efflux was persistently slowed by SG-75 and unaltered by NIF. The primary effects of SG-75 appear to be depression of Ca++ release and inhibition of receptor-operated (potential-independent) Ca++ entry, with limited attenuation of voltage-dependent Ca++ entry. NIF primarily inhibits voltage-dependent Ca++ entry.

A benzothiazolium styryl azacrown ether dye (1) and its photocontrolled complexation with Ba²⁺ in acetonitrile solution have been studied by nanosecond time-resolved UV−visible absorption spectroscopy. Continuous visible irradiation of trans-1 in the presence of Ba²⁺ was used to generate a photostationary-state mixture with “closed” cis-1−Ba²⁺ present in high concentration:  in this form, the barium cation is complexed with both the azacrown and a propylsulfonate group pendant to the benzothiazolium dye. A nanosecond UV photolysis pulse was used to induce photoisomerization of this “closed” cis-1−Ba²⁺ species. Time-resolved UV−visible absorption studies have revealed that the barium cation initially remains complexed to the azacrown in the trans-isomer formed &lt;50 ns after UV photolysis and that the cation is subsequently released from the azacrown on a time scale of ca. 700 ns, consistent with the equilibrium composition of the solution expected from the thermal chemistry under these conditions. Along with time-resolved and steady-state studies of the effect of temperature and cation concentration, these studies have enabled a quantitative mechanism to be proposed for the thermal and photochemical ion-complexing properties of this dye. These direct observations demonstrate that sustained, photocontrolled ion release from an azacrown ether dye can be achieved within 1 μs of photolysis.

Anti-alloantibody whole molecules and subunits have been shown to inhibit specific recognition of foreign antigenic determinants by certain thymus-dependent lymphoid cells. The present investigation was designed to demonstrate whether anti-Fab and anti-Fc alloantibodies raised against Fab and Fc fragments prepared by papain digestion of tumor-enhancing IgG2 could prolong the survival of C3Hf/He (H-2k) fibrosarcoma allografts in TS (H-2s) mice. Prolonged survival of tumor allografts was observed in TS mice that received anti-Fab alloantibody followed one hour later by tumor allotransplantation, whereas anti-Fc alloantibody showed no such effect when assayed under similar conditions. By contrast, no significant difference in allograft survival time was observed between TS mice that received anti-Fc alloantibody and control mice that received 0.15 M NaCl each followed within one hour by tumor allotransplantation. The injection of γ -globulin fraction of alloantisera absorbed with enhancing Fab fragments covalently linked to an insoluble matrix led to tumor allograft rejection complete by 14 days post inoculation. Results of this study are consistent with the concept that immunoglobulin-like molecules act as T-lymphoid cellular receptors in allograft rejection (i.e., a thymus dependent process).