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Constriction of the fetal ductus arteriosus after administration of indomethacin to the pregnant ewe.

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in the fetal pulmonary to systemic arterial mean blood pressure difference across the ductus arteriosus rising significantly, presumably secondary to constriction of the ductus arteriosus. The pressure difference was due to pulmonary arterial hypertension, and not due to a fall in systemic arterial mean blood pressure. Fetal arterial blood gas tensions and pH values were normal throughout. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of PGE1 into the fetal inferior vena cava. Indomethacin was present in fetal blood, and maternal plasma prostaglandin levels were suppressed. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus and fetal pulmonary arterial hypertension which, if severe, may cause rapid fetal death. It is possible that this mechanism may be one cause of persistent pulmonary hypertension or tricuspid insufficiency or both in the newborn infant.

Animals↗

Application of cast iron-platinum keeper to a collapsible denture for a patient with constricted oral opening: a clinical report.

Insertion of a denture is especially difficult for patents with a constricted oral opening. This report describes the fabrication of a collapsible removable partial denture with a cast iron-platinum attachment for a partially edentulous woman with a constricted oral opening resulting from rheumatoid arthritis and a craniotomy for a subarachnoid hemorrhage.

Aged↗

Urethral response during bladder contraction induced by subcutaneous bethanechol chloride: elicitation of a sympathetic reflex urethral constriction.

The responses of the urethra to bladder filling and to subcutaneous bethanechol were studied in a surgically separated bladder-urethra preparation in chloralose anesthetized cats. With the pudendal nerves cut or the neuromuscular junction blocked with gallamine, urethral closure pressure increased during bladder filling and the initial phase of the micturition contraction. It then fell spontaneously or in response to bladder emptying through a vent. With the bladder volume held constant subcutaneous bethanechol induced an increase in basal bladder pressure which culminated in a sustained (reflex) contraction. The urethral constrictor response resembled that seen during the cystometrogram; an increase during the rise in detrusor pressure and a fall during the latter part of the sustained (reflex) contraction. In both cases the urethral response was substantially depressed by hypogastric nerve transection or by intravenous prazosin, implying that the urethral responses were reflexly mediated through the sympathetic system. Intra-arterial bethanechol also produced a urethral constriction, but this response was abolished by atropine and not affected by hypogastric nerve section or prazosin. It is therefore concluded that although bethanechol can produce urethral constriction through a direct muscarinic action on the urethra, it does not do so after subcutaneous administration in a neurally intact cat. The urethral response seen after subcutaneous bethanechol administration is part of the micturition reflex complex and is sympathetically mediated.

Animals↗

Antihyperalgesic effect of simultaneously released hydromorphone and bupivacaine from polymer fibers in the rat chronic constriction injury model.

We aimed to evaluate the antihyperalgesic efficacy of a combination of hydromorphone (HM) and bupivacaine (BP) delivered via controlled release from a biodegradable cylindrical rod. In vivo studies were performed using a rat model of thermal hyperalgesia induced by chronic constriction injury (CCI) of the sciatic nerve with loose ligatures. Poly(lactic-co-glycolic acid) (PLGA) rods (10 mm length, 1 mm diameter) loaded with HM (5 mg per rod), BP (5 mg per rod) or no drug (placebo) were implanted subcutaneously, in single or dual pairs, adjacent to the constriction injury, immediately after nerve ligation. We evaluated the efficacy of two dose levels for each drug, alone or in combination, in attenuating thermal hyperesthesia over a period of 12 days according to a prevention protocol. Plasma levels of drugs released from the rods and also released in an in vitro simulation were evaluated. In vitro studies demonstrated that drug release is maintained for at least 10 days. HM (5 mg) alone and BP (5 mg) alone did not attenuate hyperalgesia. Their combination provided a significant increase in the paw withdrawal latency as compared to single agents or placebo. When the dose in each group was doubled, implanting four rods, significant attenuation of hyperalgesia was observed. Analyses of rods retrieved after termination of experiments (after 12 days) revealed 30% residual HM and 70% residual BP content. Prolonged delivery of HM and BP alone or in combination via locally applied PLGA rods may offer a feasible alternative to provide long-lasting analgesia.

Analgesics, Opioid↗

Age-related changes in adenosine 5'-triphosphate-induced constriction of isolated, perfused mesenteric arteries of rats.

In isolated mesenteric arteries of rats, dose-dependent increase in perfusion pressure by adenosine 5'-triphosphate (ATP, 0.1 approximately 3000 nmole) diminished with age. ATP responses of both 4- and 32-week-old rats were enhanced by indomethacin (5 microM), and further by the combination of indomethacin and N(G)-nitro-L-arginine methyl ester (L-NAME, 5 microM). The enhancement with each of the treatments was less in 32-week-old rats than that in 4-week-old rats, and there was no enhancement in 75-week-old rats. The ATP response was enhanced by removing the endothelium only in 4-week-old rats. The constrictions in response to ATP (1000 nmole) in both 4- and 32-week-old rats were equally enhanced by reactive blue 2 (30 micromole) and were inhibited by pyridoxal-phosphate-6-azophenyl-2',4-disulphonic acid (PPADS, 30 microM) and alpha, beta-methylene ATP (alpha, beta-mATP, 100 nmole) to a similar extent. The increased tone which was produced by the perfusion with physiological solution containing 100 mM potassium chloride was greater in older animals. This age-related change in the vascular tone disappeared when the responses were potentiated by L-NAME. These results demonstrate that in rat mesenteric arteries, ATP-induced constriction decreases with age. The age-related decline of vasoconstriction is not likely to arise from the changes in the contractility of smooth muscle, from the counterbalancing regulation by the endothelium, or from the cooperation of P2 purinoceptor subtypes. The density of purinoceptors and some post-receptor signal transduction mechanisms in the vascular smooth muscle cells may change with age. The enhanced ATP response might have special physiological significance in rats during development.

Adenosine Triphosphate↗

The role of angiotensin II and of its receptor subtypes in the acetic acid-induced abdominal constriction test.

The effects of angiotensin II (AngII), the AngII analogues saralasin--[Sar1, Ala8]AngII, sarmesin--[Sar1Tyr(Me)4]AngII, the nonpeptide AngII receptor antagonists DuP753 (losartan) (for AT1 receptor subtype) and PD123319 (for AT2 receptor subtype), as well as combinations of AngII and each of its analogues and receptor antagonists, administered intracerebroventricularly (ICV), were studied on mice using the acetic acid-induced abdominal constrictions test (acetic acid 1% intraperitoneally, IP). The abdominal constrictions were counted at 5-min intervals for 30 min. AngII at doses of 0.05, 0.1, and 1 microg exerted a dose-dependent antinociceptive effect. Saralasin, sarmesin, losartan, and PD123319 exhibited a dose-dependent effect on nociception: they either increased or decreased it. PD123319 antagonized the antinociceptive effect of AnglI while losartan was ineffective. The importance of AT2 receptor subtype for the nociception reducing effect of AngII is considered.

Acetic Acid↗

Penetration of constricted canals with modified K files.

A technique using K files with modified tips has been developed for the penetration of constricted canals. The tip of a #10 K file was sliced diagonally to make it thinner. Because this modified K file has an especially fine tip and an appropriate stiffness, it followed constricted or sharply curved canals well and had a high penetration potential. The author attempted to penetrate to the apical foramen in all 1844 canals of 977 teeth treated from 1987 to 1994. In 263 canals (14.3%) that could not be penetrated with conventional #10 K files, further attempts were made with the modified K files. As a result, the number of the nonpenetrated canals was reduced to 75 (4.1%). There were 7 file breakages and 14 accidental perforations.

Chi-Square Distribution↗

Involvement of glutamate in transmission of afferent constrictive inputs from the airways to the nucleus tractus solitarius in ferrets.

In this study, we identified the neurons within nucleus tractus solitarius (nTS) activated by stimulation of airway sensory systems and examined the expression of AMPA receptor subtype(s) by these cells. We also investigated the possible involvement of endogenously released glutamate and AMPA receptors in the transmission of excitatory inputs from the sensory system of the respiratory tract to the neurons of the nTS. In these experiments we used: (1) immunodetection of c-fos encoded protein (cFos) expression to identify the nTS neurons activated by the stimulation of the airway sensory system; (2) receptor immunochemistry and confocal microscopy to determine the receptor(s) expressed by activated nTS neurons; (3) microdialysis to measure glutamate release, and (4) physiological measurements to examine the effects of selective receptor blockers, and thereby define the role of the glutamate and AMPA glutamatergic receptor subtype(s) in reflexly induced airway constriction. The results showed that activation of airway sensory receptors, by inhalation of aerosolized histamine or capsaicin, induced cFos expression in a subset of nTS neurons that also expressed the AMPA subtype of glutamate receptors. Furthermore, activation of sensory bronchoconstrictive receptors induced glutamate release within nTS, and blockade of the AMPA receptor subtype within nTS inhibited reflexly increased cholinergic outflow to the airways. These data indicate for the first time that glutamate and AMPA receptor signaling pathways are involved in the transmission of afferent inputs from the airways to the nTS, and in mediating reflex airway constriction.

Aerosols↗

Constrictive paralysis of the posterior interosseous nerve without external compression.

Four cases of constrictive neuropathy of the posterior interosseous nerve (PIN) in the absence of external compression are reported. All patients presented with a history of severe elbow pain with no apparent cause, followed by paralysis of the PIN. There were one or two well-localized constrictions on the PIN proximal to the arcade of Frohse where no obvious external compressive structure was observed. After epineurotomy with or without neurorrhaphy, three patients had a complete return of motor function within 1 year. The remaining patient required tendon transfer after resection of the abnormal segment of nerve.

Adolescent↗

Soluble Alzheimers beta-amyloid constricts the cerebral vasculature in vivo.

Bilateral temporoparietal hypoperfusion has been frequently observed early in the Alzheimer's disease (AD) process. An increased beta-amyloid (Abeta) peptide is believed to play a central role in the pathogenesis of AD. In vitro experiments have shown that freshly solubilized Abeta enhances constriction of cerebral and peripheral vessels. We propose that in vivo the Abeta vasoactive property may contribute to cerebral hypoperfusion of AD patients. To test this hypothesis, we intra-arterially infused freshly solubilized Abeta -40 in rats and observed changes in cerebral blood flow and cerebrovascular resistance using fluorescent microspheres. We found that infusion of Abeta in vivo resulted in a decreased blood flow and increased vascular resistance specifically in cerebral cortex but not in heart or kidneys. These data suggest that Abeta has a direct and specific constrictive effect on cerebral vessels in vivo, which may contribute to the cerebral hypoperfusion observed early in the AD process.

Alzheimer Disease↗

Effect of intrathecal octreotide on thermal hyperalgesia and evoked spinal c-Fos expression in rats with sciatic constriction injury.

This study was designed to determine whether intrathecal octreotide (sandostatin), a synthetic octapeptide derivative of somatostatin, relieved thermal hyperalgesia and reduced the evoked spinal c-Fos expression in rats with chronic constriction injury (CCI) of the sciatic nerve. Intrathecal catheters were implanted in rats 7 days before CCI of the sciatic nerve over the left hind limb. After confirmation of the development of thermal hyperalgesia by decreased paw withdrawal latencies (PWL) to heat stimulation 7 days after CCI, intrathecal sandostatin at 20, 40, and 80 microg was administered, respectively. Rats in the control group received saline injections intrathecally. PWLs were evaluated at 30, 60, 120, 180, and 240 min after drug administration. Detection of Fos-like immunoreactivity (Fos-LI) neurons in the dorsal horn of the spinal cord following drug administration was performed after mechanical stimulation (stroking of the hind paws) on the 14th day after CCI. The reduction of PWL was attenuated significantly in the groups that received intrathecal sandostatin at 20, 40, and 80 g when compared with the saline group. However, PWL did not return to pre-CCI values in all groups. In the 40 microg group, PWL returned up to 76% of pre-CCI values 120 min after drug administration. Stroking of the hind paw in CCI-treated (ipsilateral) limbs induced a significantly greater expression of spinal Fos-LI neurons than that of non-CCI treated (contralateral) limbs in each group. The number of Fos-LI neurons in animals receiving intrathecal sandostatin was dose-dependently reduced. Expression of Fos-LI neurons in the 80 microg group was nearly completely inhibited. These data suggest that intrathecal sandostatin significantly relieved thermal hyperalgesia behaviorally but with limited effects and dose-dependently reduced spinal Fos-LI neurons expression evoked by stroking stimulation, which may reflect mechanical allodynia in rats with sciatic constriction injury. This implies that intrathecal sandostatin was effective in the treatment of neuropathic pain.

Animals↗

Fetal limb deformities due to amniotic constrictions (a possible consequence of preceding amniocentesis).

The nature and origin of circular constrictions and intrauterine amputations can be studied more effectively in the fetus than in the newborn. Two cases of fetal micro- and syndactyly secondary to ring constrictions are discussed with respect to morphological processes. The amniotic membranes display active chorionic proliferation in addition to amniotic rupture and passive string formation. Moreover, association between the origin of amniotic bands and preceding amniocentesis seems to be possible in one case though it is difficult to ascertain.

Amniocentesis↗

Correction of constriction rings.

A refinement in the correction of deep and shallow constriction rings, in which subcutaneous fat and fascial flaps are advanced into the defect to prevent recurrent contour deformities, is presented. A straight-line dorsal closure is preferred, with Z-plasties placed along the side of the digits, forearm, or arm. Long-term follow-up is presented in 58 patients with 116 constriction rings corrected by either traditional serial Z-plasties of skin (n = 61 rings) or this new method of contour correction (n = 55 rings). Specific correction of soft tissue is recommended when tissue is available.

Adipose Tissue↗

Symphalangism associated with constriction rings: syndactyly and brachytelophalangy in a black patient.

A 7-year-old girl presented with symptoms of constriction ring syndrome, syndactyly, and brachytelophalangy in the presence of proximal unilateral symphalangism. Physical findings revealed previous surgical correction of constriction rings of the right index and long fingers, a short right thumb with a hypoplastic distal phalanx, a shortened long finger with a stiff proximal interphalangeal joint and characteristic absence of skin creases, and incomplete syndactyly of the right first, second, and third web spaces. A brief review of symphalangism and a surgical treatment plan are presented. This is believed to be the first case report of symphalangism in a black patient with multiple congenital anomalies.

Abnormalities, Multiple↗

Aseptic tenosynovitis of the digital flexor tendon sheath, fetlock and pastern annular ligament constriction.

The anatomy of the digital flexor tendon sheath and related tendons and ligaments is described. Diagnosis and management of acute tenosynovitis and long-term tenosynovitis and associated tendon injuries are discussed, as well as the syndrome of stenosis of the fetlock canal (or fetlock annular ligament constriction) and palmar annular ligament constriction. Desmitis of the palmar annular ligament is also described.

Animals↗

Serotonin-induced pulmonary responses in the perfused guinea pig lung: evidence for 5HT2 receptor-mediated pulmonary vascular and airway smooth muscle constriction.

The isolated perfused guinea pig lung was used to investigate pharmacologic characteristics of serotonin receptors in pulmonary vascular and airway smooth muscle. Serotonin caused a marked dose-related increase in pulmonary arterial pressure and peak intratracheal pressure when injected into the pulmonary artery. In contrast to serotonin, 5-carboxamidotryptamine, a 5HT1A and 5HT1B receptor agonist, and 2-methylserotonin, a 5HT3 receptor agonist produced only weak vascular and airway responses. Furthermore, vasoconstriction and bronchoconstriction elicited by serotonin were antagonized by the potent 5HT2 receptor antagonists, LY53857, ketanserin, and ritanserin. Antagonist specificity for 5HT2 receptors was demonstrated in the perfused guinea pig lung since similar responses induced by histamine were not blocked. High concentrations of serotonin were tachyphylactic on vascular but not airway constriction. Tachyphylaxis of vascular responses was not observed to an equipotent concentration of leukotriene D4 (LTD4). Thus, both the pulmonary vascular and airway constriction to serotonin were predominantly due to 5HT2 receptor activation. Furthermore, tachyphylaxis of vascular responses to serotonin might prove useful to differentiate 5HT receptor systems in pulmonary blood vessels from those in airways.

Animals↗

Trazodone hydrochloride attenuates thermal hyperalgesia in a chronic constriction injury rat model.

BACKGROUND AND OBJECTIVE: Trazodone hydrochloride is used in the treatment of neuropathic pain. However, the analgesic effects of trazodone on neuropathic pain are controversial. The study was undertaken to determine the analgesic effect of trazodone on a chronic constriction injury model. METHODS: We tested the effect of trazodone on thermal hyperalgesia due to a chronic constriction injury of the sciatic nerve in rats and examined the effects of lesions in the descending and ascending serotonergic system induced by 5,7-dihydroxytriptamine (5,7-DHT). RESULTS: The analgesic effects of trazodone showed a clear dose dependency. Furthermore, the analgesic effect of trazodone was observed in rats injected with 5,7-DHT into the dorsal raphe nucleus and medial raphe nucleus. CONCLUSIONS: The results suggest that a mainly serotonergic descending pain control pathway mediates the analgesic effects of trazodone.

Animals↗

Role of charged residues at the OmpF porin channel constriction probed by mutagenesis and simulation.

The channel constriction of OmpF porin, a pore protein in the bacterial outer membrane, is highly charged due to the presence of three arginines (R42, R82, and R132) and two acidic residues (D113 and E117). The influence of these charges on ion conductance, ion selectivity, and voltage gating has been studied with mutants D113N/E117Q, R42A/R82A/R132A/D113N/E117Q, and V18K/G131K, which were designed to remove or add protein charge at the channel constriction. The crystal structures revealed no or only local changes compared to wild-type OmpF, thus allowing a comparative study. The single-channel conductance of the isosteric D113N/E117Q variant was found to be 2-fold reduced, and that of the pentuple mutant was 70% of the wild-type value, despite a considerably larger pore cross section. Ion selectivity was drastically altered by the mutations with cation/anion permeability ratios ranging from 1 to 12. Ion flow through these and eight other mutants, which have been characterized previously, was simulated by Brownian dynamics based on the detailed crystal structures. The calculated ion selectivity and relative channel conductance values agree well with the experimental data. This demonstrates that ion translocation through porin is mainly governed by pore geometry and charge, the two factors that are properly represented in the simulations.

Amino Acids↗