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At least 721 records · Page 40Linked to original sources
PubMed1998

Elastase in hyperpnea-induced guinea pig airway constriction.

Aerosolized elastase has been shown to produce airway constriction in guinea pigs. In this study, we examined whether endogenous elastase plays a role in isocapnic hyperpnea-induced airway constriction using an elastase inhibitor, eglin-c. The study was divided into three experiments. In the first experiment, we used an elastase inhibitor, eglin-c, to suppress hyperpnea-induced bronchoconstriction. Twenty-two young male Hartley guinea pigs were divided into three groups: control (n=8), eglin-c(1) (a lower dose of eglin-c, n=7), and eglin-c(2) (a higher dose of eglin-c, n=7). In the second experiment, we tested whether eglin-c affects pulmonary function following 15 min of normal air ventilation in two groups of animals: control (n=8) and eglin-c (n=8). In the third experiment, animals were divided into two groups: control (n=7) and compound 48/80 (a mast cell degranulating agent, n=7). Airway function was examined in the anesthetized-paralyzed animal. In the first and third experiments, 15 min of isocapnic hyperpnea caused marked decreases in dynamic respiratory compliance, forced expiratory flow at 0.1 s and maximal expiratory flow at 50% total lung capacity, demonstrating hyperpnea-induced airway constriction. This bronchoconstriction was significantly attenuated by eglin-c and by pretreatment with compound 48/80. In the second experiment, eglin-c did not significantly affect bronchial function following normal air ventilation. These data suggest that elastase released from mast cells directly or indirectly induces hyperpnea-induced bronchoconstriction.

Animals↗
PubMed1997

Role of the constriction loop in the gating of outer membrane porin PhoE of Escherichia coli.

Porins form voltage-gated channels in the bacterial outer membrane. These proteins are composed of three identical subunits, each forming a 16-stranded beta-barrel. In this study, the role in voltage gating of a loop that forms a constriction within the pore was studied. The channel characteristics of mutant PhoE porins, in which the tip of the constriction loop was connected to the barrel wall, were determined. Whereas the properties of several mutant channels were changed, all of these channels could still be closed at high potential, showing that a gross movement of the constriction loop within the channel is not implicated in voltage gating.

Anti-Bacterial Agents↗
PubMed1997

Airway and tissue constrictions are greater in closed than in open-chest conditions.

We measured lung impedance (ZL) before and after four doses of methacholine (Mch) infusion in five intact chest (with esophageal balloon) and six open-chest dogs from 0.2 to 8 Hz with an optimal ventilator waveform. From ZL, we estimated airway resistance (R(aw)) and inertance (Iaw) and tissue viscance (GL) and elastance (HL). Two-way analysis of variance revealed that: (1) Mch had a strong influence on all parameters (p < 0.001), but small effect on hysteresivity, nL = GL/HL; (2) closed-chest GL and HL were significantly higher and Iaw lower than their open-chest values (p < 0.002, p < 0.05 and p < 0.0001); and (3) at the highest Mch dose, the relative increase in R(aw) was six times higher in the closed-chest condition. The reduced impact of Mch on open-chest mechanics may be due to constrictions superimposed on grossly different lung configurations and/or some humoral effects initiated by the thoracotomy. We conclude that Mch doses that elicit mild constriction in open-chest condition can cause a severe constriction in intact animals.

Airway Resistance↗
PubMed1998

Effect of elastase pretreatment on rat lung strip induced constriction.

On exposure to contractile agonists, peripheral smooth muscle shortens and induces distortion in lung parenchyma. To assess the influence of elastic integrity on lung tissue constriction, 24 rat lung strips were oscillated in organ bath, at a fixed frequency of 1 Hz, and exposed to acetylcholine (Ach) 10(-1) M, before and after incubation with pancreatic porcine elastase (PPE). Before the post-PPE Ach challenge, 11 samples were re-stretched to recover control elastance value. Tissue elastance (Etis), resistance (Rtis), and minimum stress (sigma(min)) were calculated cycle-by-cycle. PPE exposure significantly decreased Etis by 8.50+/-1.91%, and sigma(min) by 33.2+/-3.6%. PPE digestion affected the dynamic of mechanical changes during constriction in non re-stretched samples, but not in re-stretched ones. We conclude that lung tissue damage induced by PPE impairs the transmission of forces generated by lung tissue constriction, challenging mechanical interdependence. The intrinsic properties of contractile machinery seem unaffected by PPE digestion.

Acetylcholine↗
PubMed1997

Effects of the dihydropyridine calcium channel blocker amlodipine on ventricular and atrial protein synthesis in an aortic constriction model of hypertension and, following chronic treatment, in the left ventricle of SHR rats.

The dihydropyridine calcium channel blocking agent amlodipine is an effective anti-hypertensive agent and its use (in doses of 5 or 10 mg/day/kg body weight) was investigated in male Wistar rats with hypertension induced by aortic constriction. Controls were sham-operated and pair-fed. At the end of the study, rates of protein synthesis were measured with radiolabelled phenylalanine to calculate fractional rates of protein synthesis (ks), absolute rates of protein synthesis (Vs) and synthesis rates relative to RNA (kRNA). After 30 days of aortic constriction, weights of the left ventricle and left atrium were significantly increased by hypertension. The weights of the right ventricle and right atrium were relatively unaffected. Hypertension was accompanied by significant increases in the protein and RNA contents of the left ventricle and left atrium. The contractile and non-contractile protein contents were also increased in the left ventricles of hypertensive rats as were total proteins and total RNA. In the myofibrillary fraction, ks decreased. The right ventricle and right atrium were generally unaffected except for a decline in mixed protein ks. Many of these changes in hypertension were ameliorated by treatment with amlodipine, particularly at the higher dose (i.e. 10 mg/kg body weight/day) implicating an effect on protein metabolism. In the left ventricle these included amelioration of the increases in mixed and contractile proteins, total RNA contents, mixed Vs and Vs for sarcoplasmic and stromal proteins. The ameliorating effects of amlodipine were moderate in the left atrium. Furthermore, amlodipine also retarded the hypertension-induced reduction in right ventricule rates of protein synthesis. Although the preceding study emphasises the preventative aspects of amlodipine's efficacy, an additional study was carried out in SHR rats to ascertain the applicability for regression per se. Amlodipine (10 mg/kg/body weight) therapy for 30 weeks caused regression of LV mass, total protein, RNA and DNA contents. We conclude that amlodipine, is an efficient agent in ameliorating the hypertension-induced changes in protein metabolism in an aortic constriction model.

Amlodipine↗
PubMed1999

[Constrictive bronchiolitis obliterans. Apropos of a case].

INTRODUCTION: Constrictive bronchiolitis obliterans is defined histologically as obliteration of the lumina of bronchioles by inflammatory tissue elements and progressive destruction of bronchioles, eventually replaced by fibrotic tissue. Most of the cases, which are not associated with either solid organ or bone marrow transplantation, occur in the development of rheumatoid arthritis. EXEGESIS: We present the case of a 73-year-old woman who developed severe constrictive bronchiolitis obliterans without readily identifiable cause, rapidly fatal despite corticosteroid therapy. The patient had antinuclear antibodies (titer 1/1024) and antiphospholipid antibodies, but there was no anti-DNA, anti-ENA or anti-beta 2GPI antibodies. Tests for rheumatoid factor were negative. Cryoglobulinemia was present (monoclonal IgM Kappa). CONCLUSION: In this case, constrictive bronchiolitis obliterans was associated with serologic abnormalities and cryoglobulinemia. However, were was no clinical evidence of connective tissue disease.

Aged↗
PubMed1997

Effects of intrathecally administered nociceptin, an opioid receptor-like1 (ORL1) receptor agonist, on the thermal hyperalgesia induced by unilateral constriction injury to the sciatic nerve in the rat.

Nociceptin is a 17 amino acid peptide which acts as a potent endogenous agonist of the opioid receptor-like1 (ORL1) receptor. In the spinal cord, nociceptin is reported to depress glutamatergic transmission and to block the spinally mediated facilitation which is thought to be mediated by the activation of N-methyl-D-aspartate (NMDA) receptor. It has been found that NMDA receptor mediated spinal facilitation is crucial in the maintenance of thermal hyperalgesia evoked by a nerve constriction injury. In the present study, we investigated the effect of intrathecally administered nociceptin on the level of thermal hyperalgesia after unilateral constriction injury to the sciatic nerve in the rat. Intrathecally administered nociceptin attenuated the level of thermal hyperalgesia in a dose dependent manner. These data indicate that spinal ORL1 receptor activation by nociceptin inhibits the spinal facilitation evoked by the nerve constriction injury.

Animals↗
PubMed2002

TNP-ATP, a potent P2X3 receptor antagonist, blocks acetic acid-induced abdominal constriction in mice: comparison with reference analgesics.

Exogenous ATP has been shown to be algogenic in both animal and humans. Research has focused on the P2X3 ligand-gated ion channel, as it is preferentially expressed on nociceptive C-fibers. In addition, P2X3 receptor gene disrupted mice show decreased responses to somatic painful stimuli. However, the potential role of P2X receptor activation in visceral pain has not yet been evaluated. In the present study, the systemic administration of suramin, and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, PPADS, both non-selective P2X receptor antagonists, dose-dependently reduced acetic acid-induced abdominal constrictions in mice (ED(50)=34.5 micromol/kg and ED50=70 micromol/kg, respectively). Furthermore, 2'-(or-3')-O-(trinitrophenyl)adenosine 5'- tri-phosphate (TNP-ATP) potently (IC50=10 nM) blocked the functional activation of P2X3 receptors in vitro and attenuated acetic acid-induced visceral pain. In the abdominal constriction assay, TNP-ATP (ED(50)=6.35 micromol/kg, i.p.) was 6-10 fold more potent than suramin and PPADS to reduce nociceptive behavior. In addition, TNP-ATP was 10 fold more potent than TNP-AMP (2'-(or-3')-O-(trinitrophenyl)adenosine 5'-mono-phosphate) (ED50=63.5 micromol/kg, i.p.) at reducing acetic acid-induced nociception. At the highest dose, TNP-ATP completely abolished nociceptive behavior, as did morphine (ED50=3 micromol/kg, i.p.). While TNP-ATP is also a potent antagonist of P2X1 receptors, P2X1 receptor mediated responses have not been shown in dorsal root ganglia and diinosine pentaphosphate, IP5I, a potent and selective P2X1 receptor antagonist, was ineffective at reducing abdominal constrictions. Thus, the antinociceptive effects of TNP-ATP appear to be mediated through activation of homomeric P2X3and/or heteromeric P2X2/3 receptors. Together, these results show that activation of P2X3 containing receptors plays a role in the transmission of inflammatory visceral pain.

Abdomen↗
PubMed2003

Muscimol prevents long-lasting potentiation of dorsal horn field potentials in rats with chronic constriction injury exhibiting decreased levels of the GABA transporter GAT-1.

The inhibitory activity of gamma-aminobutyric acid (GABA) is considered critical in setting the conditions for synaptic plasticity, and many studies support an important role of GABA in the suppression of nociceptive transmission in the dorsal horn. Consequently, any injury-induced modification of the GABA action has the potential to critically modify spinal synaptic plasticity. We have previously reported that chronic constriction injury of the sciatic nerve was accompanied by long-lasting potentiation of superficial spinal dorsal horn field potentials following high-frequency tetanus. In this study we examined whether the GABA-A receptor agonist muscimol would modify post-tetanic responses in rats with chronic constriction injury. In animals exhibiting maximal thermal hyperalgesia as one sign of neuropathic pain 7 days after loose ligation of the sciatic nerve, spinal application of muscimol (5, 10 or 20 microg) before the high-frequency (50 Hz) tetanus produced a long-lasting depression (rather than potentiation) of spinal dorsal horn field potentials. In separate but related Western immunoblot experiments, we also established that the chronic constriction injury was accompanied by significant decreases in the content of the GABA transporter GAT-1. These data demonstrated that GABA-A receptor agonists may effectively influence the expression of long-lasting synaptic plasticity in the spinal dorsal horn, and that an injury-induced loss in GABA transporter content may have contributed to a depletion of GABA from its terminals within the spinal dorsal horn. These data lent further support to the notion that the loss of GABA inhibition may have important consequences for the development of neuropathic pain.

Action Potentials↗
PubMed1998

Afferent activity from myelinated inferior alveolar nerve fibers in ferrets after constriction or section and regeneration.

To investigate possible peripheral mechanisms for post-injury sensory disorders in the trigeminal system, we have made electrophysiological recordings from myelinated fibres in the inferior alveolar nerve (IAN) which have previously sustained an injury. In earlier experiments we have shown that axons in ligature-induced neuromas of the IAN develop spontaneous activity and mechanical sensitivity. The present study has investigated these responses after two different types of injury. In 24 anaesthetised adult male ferrets the left IAN was either chronically constricted by four loose chromic gut ligatures (12 animals) or sectioned and regeneration permitted (12 animals). After recovery periods of 3 days, 1, 3, 6, 12 or 24 weeks, single unit recordings were made from the nerve proximal to the injury site. The proportion of units which were spontaneously active ranged from 0% to 19% after constriction injury and from 0% to 10% after nerve section and regeneration. Both groups revealed a marked variability between individual animals at similar time periods. Mechanical sensitivity was found in 0-42% of units after constriction and 0-25% of units after nerve section; both groups showed a significant negative correlation between mechanical sensitivity and recovery period. None of the fibres which had regained peripheral receptive fields was either spontaneously active or mechanically sensitive. There was no significant difference between the levels of spontaneous activity or mechanical sensitivity in the two groups or that previously found in ligature-induced neuromas. Thus we conclude that widely differing types of peripheral nerve injury are capable of initiating similar raised levels of afferent activity in myelinated inferior alveolar nerve fibres.

Action Potentials↗
PubMed1999

Behavioral manifestations of neuropathic pain and mechanical allodynia, and changes in spinal dorsal horn neurons, following L4-L6 dorsal root constriction in rats.

We investigated behavioral symptoms of neuropathic pain, and associated changes in dorsal horn neurons, in a rat model involving loose ligation of lumbar dorsal roots. The L4-L6 dorsal roots were exposed unilaterally and loosely constricted central to the respective ganglia with one (1-ligation) or two (2-ligation) silk 7-O ligatures. In control groups the dorsal roots were exposed but not ligated (sham-operated), or sutures were placed lengthwise between the dorsal roots (suture control). There was a significant reduction in mechanical withdrawal threshold on the operated side in both 1- and 2-ligation groups which began at 3 days, peaked at 2-5 week, and gradually recovered. A delayed threshold reduction was also seen on the non-operated side. Immediately post-surgery there was a significant increase (hypoalgesia) in thermal paw withdrawal latency (Hargreaves test) in 1- and 2-ligation groups on the operated (but not non-operated) side that recovered after 1 week. Significantly less weight was borne by the operated limb 1-5 weeks post-operatively in 1- and 2-ligation groups. The force of hind limb withdrawals elicited by graded noxious heat pulses (38-52 degrees C) was significantly lower 1 week post-surgery on the operated side (1-ligation group) followed by recovery. Withdrawal forces were higher 5-9 week post-surgery on the non-operated side in 1- and 2-ligation groups. We found no evidence of cold allodynia. Neither sham-operated nor suture controls showed any signs of allodynia or hyperalgesia. Following behavioral testing, rats were anesthetized with halothane for single-unit recordings from lumbar wide dynamic range-type (WDR) neurons. At 22 week post-surgery, the mean area of mechanosensitive receptive fields was significantly larger for units on the operated side in 1- and 2-ligation groups compared with those on the non-operated side or with those from sham-operated rats. Mean stimulus-response functions to graded noxious heat pulses (38-52 degrees C, 5 s) were not significantly different between operated and non-operated sides for 1- or 2-ligation groups, or compared with the 22-week sham-operated group. At 5 week post-surgery, the mean area of cutaneous receptive fields, and stimulus-response functions to graded noxious heat, were not significantly different between units recorded on operated versus non-operated sides, or compared with units from 5-week sham-operated rats. Spontaneous unit activity was significantly higher on the operated versus non-operated side in the 2-ligation (22-week) and sham (5-week) groups. Enlarged cutaneous receptive fields of dorsal horn neurons may contribute to mechanical allodynia associated with dorsal root constriction. However, the slow (>5 week) development of receptive field enlargement does not match the rapid development of allodynia. The lack of effect of dorsal root constriction on thermal sensitivity of dorsal horn units ipsilaterally corresponds to the lack of marked thermal hyperalgesia observed behaviorally.

Animals↗
PubMed1999

Constrictive bronchiolitis obliterans and paraneoplastic pemphigus.

Constrictive bronchiolitis obliterans is rare, and the pathogenesis of the disease often remains unknown. This study reports on the case of a 38 yr-old female with constrictive bronchiolitis obliterans and paraneoplastic pemphigus associated with malignant lymphoma. The patient developed progressive obstructive lung disease. The chest radiograph showed almost normal lungs. Paraneoplastic pemphigus is a newly described syndrome in which patients have autoantibodies binding to some epithelia, including in the respiratory tract. The disease develops in association with non-Hodgkin's lymphomas or other malignant neoplasms. The case presented here suggests that constrictive bronchiolitis obliterans associated with paraneoplastic pemphigus may be one of the facets of autoimmune responses in this context.

Adult↗
PubMed2003

Vigabatrin-associated visual field constriction in a longitudinal series. Reversibility suggested after drug withdrawal.

PURPOSE: To evaluate through a longitudinal study the effects on visual fields of long-term vigabatrin medication in patients with partial epilepsy and to discuss visual field screening strategies. METHODS: A total of 26 patients aged 14-68 years with a mean history of vigabatrin medication of 8.5 years (range 2-14 years) were followed by manual kinetic Goldmann perimetry (objects IV,4 and I,4) for 6-26 months (mean value 12.3 months). At time zero and at follow-up, each patient was assigned a "pooled" averaged value, as a linear percentage of normal isopter position, for the two objects as tested nasally and temporally in the five most horizontal meridians on the Goldmann chart. Twelve eyes from nine adults (age 24-60 years) served as controls. RESULTS: Constrictions were recorded in 24 of 26 patients at baseline. Averaged isopters ranged from 8% to 96% of the controls' averaged isopter positions. Median values of 71.5% and 60.5% for large and small objects, respectively, indicated that the smaller object was more sensitive to visual field constriction. There was no difference in the degree of constriction between nasal and temporal hemifields. Significant improvement in the visual field (mean gain 13.6% units) was seen in the eight patients who underwent full drug withdrawal. No similar improvement was seen in the 12 patients still on full dose or the six with reduced intake. CONCLUSIONS: Most Danish patients on long-term vigabatrin medication have suffered some visual field loss. Contrary to most clinical evidence so far, the present follow-up study indicates some reversibility of visual field loss after drug withdrawal. Kinetic Goldmann perimetry appears to be a fair alternative to computerized static perimetry techniques for screening and following vigabatrin-treated patients.

Adolescent↗
PubMed1982

Inhibition of the pial artery constriction induced by sympathetic stimulation by local microapplication of a cholinomimetic agent.

We studied the effects of microapplications of carbachol plus atropine on cat pial artery diameter in vivo during resting conditions and during stimulation of the cervical sympathetic nerve. The cats were anesthetized with alpha-chloralose and artifically ventilated. The pial surface was exposed by trepanation and protected by a 1-2-cm layer of oil. Calibrated applications of solutions were made by micropipette into the subarachnoid space, while the pial artery diameter was measured by the television image-splitting method. Sympathetic stimulation during 100 s induced a constrictive response of about 10%, which was constant from 60 to 100 s and which remained so during application of inert mock spinal fluid from 65 to 100 s. Application of 10(-5) M carbachol plus 10(-7) M atropine (solution A) or 10(-4) M carbachol plus 10(-6) M atropine (solution B) did not produce any significant changes in diameter during resting conditions. During sympathetic stimulation, application of solution A from 65 to 100 s induced a small nonsignificant reduction of the constriction, whereas application of solution B induced a highly significant reduction of the constriction from 9.63 +/- 1.09% at 60 s to 1.20 +/- 2.40% at 100 s. These results are discussed in terms of the hypothesis that carbachol may act on the sympathetic fibers on the pial arteries by a nonmuscarinic mechanism to reduce the liberation of the transmitter.

Animals↗
PubMed2006

GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission.

Dynamin, a crucial factor in endocytosis, is a member of a family of GTPases that participates in membrane fission. It was initially proposed to act as a machine that constricts and cuts the neck of nascent vesicles in a GTP-hydrolysis-dependent reaction, but subsequent studies suggested alternative models. Here we monitored the effect of nucleotides on dynamin-coated lipid tubules in real time. Addition of GTP, but not of GDP or GTP-gammaS, resulted in twisting of the tubules and supercoiling, suggesting a rotatory movement of the helix turns relative to each other during GTP hydrolysis. Rotation was confirmed by the movement of beads attached to the tubules. Twisting activity produced a longitudinal tension that was released by tubule breakage when both ends of the tubule were anchored. Fission also occurred when dynamin and GTP were added to lipid tubules that had been generated from liposomes by the motor activity of kinesin on microtubules. No fission events were observed in the absence of longitudinal tension. These findings demonstrate a mechanoenzyme activity of dynamin in endocytosis, but also imply that constriction is not sufficient for fission. At the short necks of endocytic vesicles, other factors leading to tension may cooperate with the constricting activity of dynamin to induce fission.

Animals↗
PubMed2001

Three-dimensional reconstruction of dynamin in the constricted state.

Members of the dynamin family of GTPases have unique structural properties that might reveal a general mechanochemical basis for membrane constriction. Receptor-mediated endocytosis, caveolae internalization and certain trafficking events in the Golgi all require dynamin for vesiculation. The dynamin-related protein Drp1 (Dlp1) has been implicated in mitochondria fission and a plant dynamin-like protein phragmoplastin is involved in the vesicular events leading to cell wall formation. A common theme among these proteins is their ability to self-assemble into spirals and their localization to areas of membrane fission. Here we present the first three-dimensional structure of dynamin at a resolution of approximately 20 A, determined from cryo-electron micrographs of tubular crystals in the constricted state. The map reveals a T-shaped dimer consisting of three prominent densities: leg, stalk and head. The structure suggests that the dense stalk and head regions rearrange when GTP is added, a rearrangement that generates a force on the underlying lipid bilayer and thereby leads to membrane constriction. These results indicate that dynamin is a force-generating 'contrictase'.

Animals↗
PubMed2004

The stalk region of dynamin drives the constriction of dynamin tubes.

The GTPase dynamin is essential for numerous vesiculation events including clathrin-mediated endocytosis. Upon GTP hydrolysis, dynamin constricts a lipid bilayer. Previously, a three-dimensional structure of mutant dynamin in the constricted state was determined by helical reconstruction methods. We solved the nonconstricted state by a single-particle approach and show that the stalk region of dynamin undergoes a large conformational change that drives tube constriction.

Dynamins↗
PubMed1991

Posturally induced microvascular constriction in patients with different stages of leg ischaemia: effect of local skin heating.

1. Skin microcirculation was investigated in 12 asymptomatic subjects and 76 patients, grouped according to their ankle-to-brachial systolic blood pressure index, in order to evaluate to what extent posturally induced microvascular constriction is dependent on the stage of leg ischaemia at different local skin temperatures. 2. Skin microcirculation was assessed in the supine and sitting position by using laser Doppler fluxmetry at unheated skin temperature and at 36 degrees C, and transcutaneous oximetry at 37 degrees C and 44 degrees C. 3. Skin perfusion and oxygenation diminished with decreasing ankle-to-brachial systolic blood pressure index. In healthy control subjects, perfusion and oxygenation were reduced when changing from the supine to the sitting position, but were enhanced in patients with severe leg ischaemia (ankle-to-brachial systolic blood pressure less than 30%), indicating disturbed posturally induced vasoconstriction. 4. Increasing the local skin temperature resulted in a higher perfusion and masked the posturally induced vasoconstriction in healthy subjects. In patients with severe leg ischaemia, however, perfusion was unaltered by the temperature increase, apparently because the microvessels were already maximally dilated. The induction of reactive hyperaemia produced no additional increase in perfusion or oxygenation. 5. It is concluded that posturally induced microvascular constriction in the skin is disturbed in patients with severe leg ischaemia (ankle-to-brachial systolic blood pressure index less than 30%). Disturbed microvascular constriction upon dependency was also seen in healthy subjects after local skin heating. This suggests that posturally induced vasoconstriction is mainly regulated by local mechanisms.

Adult↗