bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulated function of phosphatidylinositol‐3‐kinase in genetically hypertensive rats: a moderator of arterial hypercontractility
Authors: Northcott Carrie A , Hayflick Joel , Watts Stephanie W 
Published: September 2005

SUMMARY1. The growth enzyme phosphatidylinositol 3‐kinase (PI3K) was recently implicated in the mediation of arterial spontaneous tone, an event observed in arteries from hypertensive, but not normotensive, subjects that contributes to changes in total peripheral resistance in the hypertensive state. We have shown this occurrence in experimentally induced models of hypertension. However, because the majority of hypertension is genetically based, it is important to demonstrate a similar change in genetically hypertensive animals.2. Aorta from spontaneously hypertensive rats (SHR; systolic blood pressure = 183 ± 4 mmHg) and Wistar Kyoto (WKY) rats (115 ± 2 mmHg) were isolated for the measurement of isometric contractile force. Aorta from SHR displayed small increases (approximately 5% maximum phenylephrine (PE)‐induced contraction) in spontaneous tone, whereas aorta from WKY rats displayed none. The non‐selective PI3K inhibitor LY294002 (20 µmol/L) and the selective inhibitor of the p110δ catalytic subunit of PI3K IC87114 (20 µmol/L) caused a fall of basal tone in SHR aorta (20 ± 7 and 24 ± 6% of the initial PE contraction, respectively), but did not alter tone in arteries from WKY rats. LY294002, but not IC87114, normalized the increased potency of noradrenaline (NA) observed in aorta from SHR (–log EC50 values for NA in the presence of vehicle in WKY rats and SHR 7.5 ± 0.1 and 7.8 ± 0.1, respectively (P < 0.05); –log EC50 values for NA in the presence of LY294002 in WKY rats and SHR 7.0 ± 0.1 and 7.0 ± 0.1, respectively).3. Biochemical expression of the p110 catalytic and p85 regulator subunits of PI3K in western analyses revealed no difference in expression of the regulatory p85α or p110α protein subunits between WKY rats and SHR; p110γ was not detected. In contrast, p110δ expression was increased greater than 30% in aorta from SHR compared with WKY rats (827.6 ± 88.5 vs 576.8 ± 53.4 arbitrary densitometry units, respectively). Immunohistochemical analyses revealed expression of the p110δ isoform in the smooth muscle of arteries.4. These data underscore the relevance of an enzyme historically classified as one committed to growth/anti‐apoptosis in modifying contractility and supports involvement of PI3K in genetically based hypertension.
Remodelling of mesenteric arteries in genetically hypertensive rats cross‐fostered from birth to normotensive Wistar rats
Authors: Ledingham Janet M , Ashton Nick 
Published: September 2005

SUMMARY1. The effects of cross‐fostering genetically hypertensive (GH) with normotensive (N) Wistar rats on the structure of mesenteric resistance arteries (MRA) in young (6 week old) and adult (18 week old) rats were investigated to see whether the abnormal remodelling known to exist in GH rats could be prevented by changing the maternal environment.2. Genetically hypertensive and normotensive rat pups were reared either by their natural mothers or a foster mother of the opposite strain (NX and GHX) with fostering done within 24 h of birth.3. Blood pressure (BP) was measured from age 6–18 weeks; at 6 and 18 weeks MRA structure was assessed.4. At the time of death, intra‐arterial mean BP was measured (via the femoral artery), after which MRA were fixed by perfusion (at the systolic BP of the rat) via the abdominal aorta, first with 75% Tyrode's solution containing heparin and papaverine, followed by 2% glutaraldehyde in 75% Tyrode's solution. Arteries were dissected out, processed and embedded in Technovit (Heraeus Kulzer, Werheim, Germany) and serial sections were cut and stained with Giemsa.5. Stereological techniques were used to determine media width, lumen diameter and medial cross‐sectional area (CSA); in addition, the ratio of media width to lumen diameter was calculated. Smooth muscle cell density was also calculated.6. In MRA from 6‐week‐old rats, GH rats compared with N rats had increased media width and CSA and an increased ratio of media width to lumen diameter.7. There were no significant changes in structure in the GHX group compared with GH rats. The NX group compared with N rats had increased media width and CSA and lumen diameter, but no change in the ratio of media width to lumen diameter. Smooth muscle cell density, reduced in GH compared with N rats, was increased (P < 0.001) in the NX group, but not changed in the GHX group compared with GH rats.8. In 18‐week‐old GH rats compared with N rats, the MRA had a decreased media width and medial CSA and smaller lumen diameter, but there was no change in the ratio of media width to lumen diameter.9. In the GHX group compared with GH rats, media width and CSA were reduced; in the NX group compared with N rats, media width was increased, lumen decreased and the ratio of media width to lumen diameter increased. Smooth muscle cell density was increased (P < 0.001) in the GHX group, but not in the NX group.10. Changing the maternal environment significantly affected BP in GHX and NX groups up to 9–10 weeks of age but, in adult rats, the BP differences were no longer present. Thus, structural changes were seen at 6 weeks of age in MRA from NX rats and also at 18 weeks in GHX and NX rats (even though the BP differences were no longer significant); structural remodelling occurred independently of BP.
Renal haemodynamics and function in weanling rats treated with enalapril from birth
Authors: Guron Gregor 
Published: September 2005

SUMMARY1. Inhibition of the renin–angiotensin system (RAS) during kidney development produces chronic alterations in renal morphology and function that have been characterized in detail in adult animals. The aim of the present study was to determine the consequences of neonatal angiotensin‐converting enzyme (ACE) inhibition on renal haemodynamics and function in rats at a much earlier age, namely 3–4 weeks.2. Male Wistar pups received daily intraperitoneal injections of enalapril (10 mg/kg) or isotonic saline from birth until 24–28 days of age, when renal haemodynamics and function were assessed using clearance techniques under pentobarbital anaesthesia.3. Enalapril‐treated rats showed significant reductions in glomerular filtration rate (GFR; −44 ± 6%; P < 0.05), effective renal plasma flow (ERPF; −33 ± 6%; P < 0.05) and filtration fraction (−16 ± 3%; P < 0.05) compared with saline‐treated controls. Although mean arterial pressure tended to be lower in enalapril‐treated rats, this group demonstrated a significant increase in renal vascular resistance compared with control rats (RVR; 46 ± 6 vs 32 ± 3 mmHg/mL per·min per g·kidney weight, respectively; P < 0.05). In enalapril‐treated rats, urine osmolality was reduced (−59 ± 5%; P < 0.05) and urine flow rate and fractional urinary excretion rates of sodium and potassium were markedly elevated compared with controls (P < 0.05). Enalapril‐treated rats showed severe renal histological abnormalities, including wall thickening of cortical arterioles, papillary atrophy and tubulointerstitial alterations, mimicking those described previously in similarly treated rats examined in adulthood.4. In conclusion, neonatal ACE inhibition in rats induces pronounced alterations in renal haemodynamics and function, characterized by reductions in ERPF and GFR, increased RVR and impaired tubular sodium and water reabsorption, which are evident at weaning.
Oxygen‐sensing pathway for SK channels in the ovine adrenal medulla
Authors: Keating Damien J , Rychkov Grigori Y , Giacomin Paul , Roberts Michael L 
Published: September 2005

SUMMARY1. The intracellular pathways that modulate the opening of oxygen‐sensitive ion channels during periods of hypoxia are poorly understood. Different tissues appear to use either NADPH oxidase or a rotenone‐sensitive mechanism as an oxygen sensor. The aim of the present study was to identify the oxygen‐sensing pathway in the oxygen‐sensitive sheep adrenal medullary chromaffin cell (AMCC).2. The whole‐cell patch‐clamp technique was used to measure K+ currents in dissociated adult ovine chromaffin cells as well as SK channel currents expressed in the H4IIE cell line.3. Diphenyliodonium, an inhibitor of NADPH oxidase, had no effect on the hypoxia‐evoked closure of K+ channels in primary AMCC, whereas the mitochondrial inhibitor rotenone abolished the hypoxia‐evoked response. Both these compounds significantly reduced K+ current amplitude under normoxic conditions.4. One possible mechanism through which the oxygen sensor may modulate K+ channel activity is by altering the redox state of the cell. In sheep AMCC, altering the redox state by the addition of H2O2 to the extracellular solution increased K+ conductance.5. The oxygen‐sensitive K+ (Ko2) channels in sheep chromaffin cells are from the SK family and the whole‐cell conductance of cells expressing mouse SK2 or SK3, but not human SK1, was increased by H2O2 and decreased by the reducing agent dithiothreitol.6. These studies show that, in sheep AMCC, Ko2 channels are modulated via a rotenone‐sensitive mechanism and that alteration of the cellular redox state mimics the change produced by alterations in Po2. In a heterologous expression system, SK2 and SK3 channels, the channels that initiate hypoxia‐evoked changes in AMCC function, are modulated appropriately by changes in cellular redox state.
Antimutagenic and anti‐oxidant activities of the non‐steroidal anti‐inflammatory drug celecoxib
Authors: Ajith TA , Subin JP , Jacob J , Sanjay PS , Babitha NV 
Published: September 2005

SUMMARY1. Tumors arise and progress through the accumulation of serial genetic changes, including successive mutations, which involve activation of proto‐oncogenes and inactivation of tumour suppressor genes, leading to the uncontrolled proliferation of progeny cells. The human body is continuously and unavoidably exposed to structurally diverse chemicals with established carcinogenic activity in animal models and/or mutagenic activity in short‐term tests.2. Celecoxib, a non‐steroidal anti‐inflammatory drug that specifically inhibits the enzyme cyclo‐oxygenase‐2, has been reported to be effective against certain types of cancers. The in vitro anti‐oxidant and antimutagenic activities of the celecoxib were investigated in the present study using standard procedures.3. The antimutagenic activity of celecoxib was determined using histidine mutant Salmonella typhimurium strains TA98, TA100, TA102 and TA1535 against directly acting mutagens (sodium azide (NaN3), N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG), 4‐nitro‐o‐phenylenediamine (NPDA) and doxorubicin) and mutagens needing activation (2‐acetamidofluorene (2‐AF) and 7,12‐dimethylbenz [a] anthracene (DMBA)).4. Celecoxib inhibited NaN3‐, MNNG‐ and NPDA‐induced mutations of TA100. The antimutagenicity of celecoxib (0.2 mg/plate) against the NaN3‐induced mutation of TA1535 was 39.8% (P < 0.001). The MNNG‐induced mutation of TA1535 was also inhibited by 0.3 mg/plate celecoxib (46.0%; P < 0.05). At concentrations of 0.2 mg/plate, celecoxib significantly inhibited NPDA‐ and doxorubicin‐induced mutations of TA98 by 52.5 and 58.0%, respectively (P < 0.001 and P < 0.05, respectively).5. The antimutagenic activity of 0.3 mg/plate celecoxib against 2‐AF‐ and DMBA‐induced mutations of TA98 was 81.76 and 98.1%, respectively (P < 0.001).6. The anti‐oxidant activity of celecoxib was determined by the inhibition of lipid peroxidation and superoxide and hydroxyl radical‐scavenging activities.7. The IC50 values of celecoxib for hydroxyl radical‐scavenging and the inhibition of lipid peroxidation were 1.97 ± 0.06 and 1.99 ± 0.05 µmol/mL, respectively. Celecoxib had no superoxide radical scavenging‐activity up to a concentration of 2.6 µmol/mL.8. The in vitro antimutagenic and anti‐oxidant activities of celecoxib indicate its possible therapeutic use as a cancer chemopreventive agent.
Operative contractility: A functional concept of the inotropic state
Authors: Curiel Roberto , Perez‐Gonzalez Juan , Torres Edwar , Landaeta Ruben , Cerrolaza Miguel 
Published: September 2005

SUMMARY1. Initial unsuccessful attempts to evaluate ventricular function in terms of the ‘heart as a pump’ led to focusing on the ‘heart as a muscle’ and to the concept of myocardial contractility. However, no clinically ideal index exists to assess the contractile state. The aim of the present study was to develop a mathematical model to assess cardiac contractility.2. A tri‐axial system was conceived for preload (PL), afterload (AL) and contractility, where stroke volume (SV) was represented as the volume of the tetrahedron. Based on this model, ‘operative’ contractility (‘OperCon’) was calculated from the readily measured values of PL, AL and SV. The model was tested retrospectively under a variety of different experimental and clinical conditions, in 71 studies in humans and 29 studies in dogs. A prospective echocardiographic study was performed in 143 consecutive subjects to evaluate the ability of the model to assess contractility when SV and PL were measured volumetrically (mL) or dimensionally (cm).3. With inotropic interventions, OperCon changes were comparable to those of ejection fraction (EF), velocity of shortening (Vcf) and dP/dt‐max. Only with positive inotropic interventions did elastance (Ees) show significantly larger changes. With load manipulations, OperCon showed significantly smaller changes than EF and Ees and comparable changes to Vcf and dP/dt‐max. Values of OperCon were similar when AL was represented by systolic blood pressure or wall stress and when volumetric or dimensional values were used.4. Operative contractility is a reliable, simple and versatile method to assess cardiac contractility.
Primary squamous cell carcinoma of the lacrimal gland
Authors: Hotta Kazuki , Arisawa Takeshi , Mito Hidenori , Narita Makoto 
Published: September 2005

AbstractA 55‐year‐old Japanese woman presented with proptosis of the left eye that showed rapid progression with profound lid oedema and chemosis with pain. Magnetic resonance imaging and helical computed tomography demonstrated a large mass of the upper temporal orbit and extended bony destruction of the frontal and zygomatic bones. She was successfully treated with orbital exenteration. A diagnosis of primary squamous cell carcinoma of the lacrimal gland was made, which was confirmed by characteristic findings seen on histopathological examination.
Acute annular outer retinopathy
Authors: Mitamura Yoshinori , Ito Hiroki , Nakamura Yasushi , Fujiwara Osamutaro , Ohtsuka Kenji 
Published: September 2005

AbstractAcute annular outer retinopathy is an uncommon disorder of uncertain aetiology characterized by a unilateral visual field defect with an irregular annular band of grey‐white, deep retinal opacification in a peripapillary location. Acute annular outer retinopathy is considered to be a variant of acute zonal occult outer retinopathy. The case is reported of acute annular outer retinopathy with spontaneous good visual recovery and no ophthalmoscopic sequelae.
Ocular toxoplasmosis in pregnancy
Authors: Kump Leila I , Androudi Sofia N , Foster CS 
Published: September 2005

AbstractPurpose:  To describe the course of ocular toxoplasmosis during pregnancy.Methods:  This study was a retrospective, non‐comparative case series of four pregnant women who were treated for ocular toxoplasmosis during pregnancy.Results:  All of the participants had severe and treatment‐resistant toxoplasmic retinochoroiditis during pregnancy, leaving three of them with decreased visual acuity in spite of aggressive therapy. Delivery of the infant appeared to help the recovery in two patients.Conclusions:  Pregnant state may provoke the recurrence of ocular toxoplasmosis.
Infliximab for juvenile idiopathic arthritis‐associated uveitis
Authors: Richards Josephine C , Tay‐Kearney Mei‐Ling , Murray Kevin , Manners Prue 
Published: September 2005

AbstractBackground:  Infliximab is a murine–human recombinant antitumour necrosis factor monoclonal antibody recently introduced for the treatment of autoimmune diseases in which tumour necrosis factor is thought to be a key mediator. Its role in the treatment of juvenile idiopathic arthritis‐associated uveitis is as yet undefined.Methods:  Six children with juvenile idiopathic arthritis‐associated uveitis, inadequately controlled on currently available therapy, were treated with infliximab between September 2002 and November 2004. All children were required to remain on low‐dose immunomodulatory treatment in conjunction with the infliximab. A retrospective review of two electronic databases containing details of ophthalmology and rheumatology visits was conducted.Results:  In all six children, institution of infliximab therapy was associated with increased ease of management. Ocular inflammation and intraocular pressure control improved in all. It was also possible to reduce the dose or withdraw some glaucoma, steroid and other immunomodulatory drugs. Two children underwent intraocular surgery without noticeable flare of intraocular inflammation. No patient developed any serious systemic complications attributable to infliximab.Conclusion:  Infliximab may be a useful adjunct to the management of refractory juvenile idiopathic arthritis‐associated uveitis. In our series it was associated with improved uveitis control and simplification of drug use as well as possibly improving safety of surgical intervention. This study suggests that its role is likely to be in conjunction with maintenance immunomodulatory treatment to provide more optimal disease control. Controlled studies are required to confirm its efficacy and safety, and the potential breadth of its use in uveitis and related disorders.
Anaesthesia techniques for cataract surgery: a survey of delegates to the Congress of the International Council of Ophthalmology, 2002
Authors: Eichel Robert , Goldberg Ivan 
Published: September 2005

AbstractBackground:  Cataract surgery is performed using various regional, local, or topical anaesthetic techniques and agents and general anaesthesia. As there is continuous change in the popularity of these techniques, an estimate of current anaesthetic practices for cataract surgery around the world was derived. This allows comparison of techniques and practices internationally and may serve as a baseline for future surveys.Methods:  At the 2002 Congress of the International Council of Ophthalmology held in Sydney, Australia, ophthalmic surgeons from around the world were surveyed with regard to their anaesthetic techniques for cataract surgery.Results:  It was found that almost all cataract surgery was performed using regional anaesthesia. Surgeons performed just over half of the anaesthetics; however, in some countries anaesthetists performed the vast majority of eye anaesthetics. The most frequently employed technique was the peribulbar block, but a substantial minority were performed under topical anaesthesia. An anaesthesia‐trained person monitored most patients during cataract surgery, and the most commonly used local anaesthetic was lignocaine.Conclusion:  Although there is a single most frequent practice in the type of regional block employed for cataract surgery among the delegates, and general anaesthesia is seldom used, individual countries have very different results regarding the anaesthetic used and the role of the anaesthetist.
Iris ischaemic changes and visual outcome after acute primary angle closure
Authors: Loon Seng‐Chee , Chew Paul TK , Oen Francis TS , Chan Yiong‐Huak , Wong Hon‐Tym , Seah Steve KL , Aung Tin 
Published: September 2005

AbstractBackground:  Ischaemic changes in the iris occur frequently after an episode of acute primary angle closure (APAC). The aim of this study was to investigate the significance of such changes with regards to visual outcome.Methods:  Acute primary angle closure cases were treated with medical therapy followed by laser peripheral iridotomy after resolution of the acute episode. Subjects were examined at 1, 4, 8, 12 and 16 weeks post laser peripheral iridotomy. Eyes were examined for signs of iris ischaemic changes (IIC), defined as the presence of iris whorling or stromal atrophy. Iris photographs were also taken at weeks 1, 8 and 16. Subjects requiring glaucoma medication or filtering surgery during the follow‐up period were excluded. The visual acuity and visual field (using automated white‐on‐white threshold perimetry) at week 16 were used in the assessment of visual outcome.Results:  Sixty‐one subjects with APAC completed the study. The majority of subjects were female (82%) and Chinese (92%), and the mean age was 59 ± 8.8 years. More than half the subjects (52.5%) were found to have developed IIC during the study, 65% of whom already had signs of IIC by the first week. Only 13 subjects (41%) with IIC and 6 subjects (21%) without IIC had an abnormal visual field defect at week 16 (P = 0.09). There was also no difference in visual acuity at week 16, the majority of subjects in both groups having visual acuity of 6/12 or better.Conclusions:  The development of iris ischaemic changes after a single episode of APAC may not be associated with an adverse visual outcome.
Prevalence and mechanism of appositional angle closure in acute primary angle closure after iridotomy
Authors: Yeung Barry YM , Ng Philip WC , Chiu Thomas YH , Tsang Chi Wai , Li Felix CH , Chi Chung Chai , Lai Jimmy SM , Tham Clement CY , Lam Dennis SC 
Published: September 2005

AbstractPurpose:  A prospective observational case series to assess the prevalence of appositional angle closure in darkness among iridotomized Chinese eyes after acute primary angle closure (APAC) with the use of both clinical methods and ultrasound biomicroscopy.Methods:  Sixteen Chinese patients who had history of APAC and subsequent successful treatment with laser peripheral iridotomy were examined. Fourteen additional control subjects were studied. Gonioscopy and ultrasound biomicroscopic examination were performed in the dark. Gonioscopic appearance of the angle was assessed, and quantitative measurements of the angle from the ultrasound biomicroscopic images were taken.Results:  Of the APAC eyes 55.6% had appositionally closed angle clinically and in 38.9% only Schwalbe's line was visi‐ble on gonioscopy. Ultrasound biomicroscopy confirmed structurally different anterior segments between eyes with APAC and the control eyes. In particular, the trabecular‐ciliary‐process distances were markedly different between the two groups.Conclusion:  This study documented a high prevalence of appositional closure in iridotomized eyes after APAC in Chinese patients. The anteriorly positioned ciliary body, as documented in these cases by ultrasound biomicroscopy, is the likely mechanism of the angle crowding in this patient population.