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1.
Hand Surg Rehabil ; 41(3): 415-417, 2022 06.
Article in English | MEDLINE | ID: mdl-35272068

ABSTRACT

We present a case of neglected trigger thumb in a forty-year-old male. The patient presented to our clinic due to bilateral triggering of his fourth digit. He attested to having pain and limitation of joint movement of his left thumb since his childhood in the former Soviet Union, with occasional triggering. This eventually subsided and the thumb became stuck in relative flexion and could not be fully extended. We performed X-rays of both thumbs wherein the left affected thumb interphalangeal joint showed an aberrant configuration and sclerosis of both joint surfaces. The joint surface curvature was altered on the left side and contact area reduced. This presentation of altered thumb interphalangeal joint biomechanics following an untreated congenital trigger thumb further emphasizes the need for surgical intervention when indicated.


Subject(s)
Trigger Finger Disorder , Adult , Child , Extremities , Humans , Male , Range of Motion, Articular , Thumb/surgery , Trigger Finger Disorder/surgery
2.
J Phys Condens Matter ; 34(15)2022 Feb 10.
Article in English | MEDLINE | ID: mdl-35051919

ABSTRACT

Simultaneous breaking of inversion- and time-reversal symmetry in Josephson junction (JJ) leads to a possible violation of theI(φ) = -I(-φ) equality for the current-phase relation. This is known as anomalous Josephson effect and it produces a phase shiftφ0in sinusoidal current-phase relations. In ballistic JJs with non-sinusoidal current phase relation the observed phenomenology is much richer, including the supercurrent diode effect and the magnetochiral anisotropy (MCA) of Josephson inductance. In this work, we present measurements of both effects on arrays of JJs defined on epitaxial Al/InAs heterostructures. We show that the orientation of the current with respect to the lattice affects the MCA, possibly as the result of a finite Dresselhaus component. In addition, we show that the two-fold symmetry of the Josephson inductance reflects in the activation energy for phase slips.

3.
Climacteric ; 23(1): 75-83, 2020 02.
Article in English | MEDLINE | ID: mdl-31257934

ABSTRACT

Objective: The objective of this study was to evaluate the action of soy isoflavones (ISO) and 17ß-estradiol on collagen I (CollI) and sulfated glycosaminoglycans (GAGs) in the bone matrix of diabetic rats.Methods: Sixty adult female rats (Rattus norvegicus albinus) underwent ovariectomy, and then were randomized into six groups of 10 animals each: GI, sham control ovariectomized animals; GII, sham control diabetic (DM) ovariectomized animals; GIII, control ovariectomized animals receiving propylene glycol vehicle; GIV, control ovariectomized DM animals receiving propylene glycol vehicle; GV, ovariectomized DM animals treated with ISO (150 mg/kg by gavage); and GVI, ovariectomized DM animals treated with estrogen (17ß-estradiol, 10 mg/kg, subcutaneously). 17ß-Estradiol was used as a positive control when compared with ISO. To obtain significant depletion of the estrogen levels and subsequent bone loss, a postsurgical period of 90 days was observed. Treatments occurred during 30 consecutive days. After euthanasia, shafts of the animals' femurs were immersed in liquid nitrogen for molecular biology analysis, and the distal femurs were removed and processed for paraffin embedding.Results: ISO (GV) and 17ß-estradiol (GVI) improved bone formation, increasing GAGs and CollI formation when compared to the control group (GIV) (p < 0.05).Conclusions: ISO and 17ß-estradiol contribute to the decrease of bone loss in diabetic rats.


Subject(s)
Bone and Bones/metabolism , Estradiol/pharmacology , Estrogens/pharmacology , Isoflavones/chemistry , Animals , Collagen Type I/analysis , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1/metabolism , Estradiol/metabolism , Estrogens/metabolism , Female , Glycosaminoglycans/analysis , Humans , Isoflavones/metabolism , Ovariectomy , Postmenopause , Random Allocation , Rats
4.
QJM ; 111(5): 287-294, 2018 May 01.
Article in English | MEDLINE | ID: mdl-29385542

ABSTRACT

BACKGROUND: Despite the evidence that the patient gender is an important component in the intensive care unit (ICU) admission decision, the role of physician gender and the interaction between the two remain unclear. OBJECTIVE: To investigate the association of both the patient and the physician gender with ICU admission rate of critically ill emergency department (ED) medical patients in a hospital with restricted ICU bed capacity operates with 'closed door' policy. METHODS: A retrospective population-based cohort analysis. We included patients above 18 admitted to an ED resuscitation room (RR) of a tertiary hospital during 2011-12. Data on medical, laboratory and clinical characteristics were obtained. We used an adjusted multivariable logistic regression to analyze the association between both the patient and the physician gender to the ICU admission decision. RESULTS: We included 831 RR admissions, 388 (46.7%) were female patients and 188 (22.6%) were treated by a female physicians. In adjusted multivariable analysis (adjusted for age, diabetes, mode of hospital transportation, first pH and patients who were treated with definitive airway and vasso-pressors in the RR), female-female combination (patient-physician, respectively) showed the lowest likelihood to be admitted to ICU (adjusted OR: 0.21; 95% CI: 0.09-0.51) compared to male-male combination, in addition to a smaller decrease among female-male (adjusted OR: 0.53; 95% CI: 0.32-0.86) and male-female (adjusted OR: 0.43; 95% CI: 0.21-0.89) combinations. CONCLUSION: We demonstrated the existence of the possible gender bias where female gender of the patient and treating physician diminish the likelihood of the restricted health resource use.


Subject(s)
Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , Patient Admission/statistics & numerical data , Physician-Patient Relations , Sexism , Adult , Aged , Aged, 80 and over , Clinical Competence , Clinical Decision-Making , Female , Hospital Bed Capacity , Humans , Israel , Kaplan-Meier Estimate , Male , Middle Aged , Patient Admission/standards , Retrospective Studies , Sex Factors
5.
Climacteric ; 20(6): 564-570, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28866964

ABSTRACT

OBJECTIVE: To assess the effects of isoflavones and 17ß-estradiol on the vaginal epithelium extracellular matrix and hyaluronic acid (HA) in the diabetic rat model. METHODS: Sixty adult, virgin, female rats underwent ovariectomy, then randomization into six groups of ten animals each: GI, sham ovariectomized control animals; GII, sham ovariectomized control diabetic animals; GIII, control ovariectomized rats receiving propylene glycol vehicle; GIV, control ovariectomized diabetic animals receiving propylene glycol vehicle; GV, diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage); GVI, ovariectomized diabetic rats treated with estrogen (17ß-estradiol, 10 mg/kg, subcutaneously). Treatment took place over 30 consecutive days. After euthanasia, a portion of the vagina was immersed in liquid nitrogen for RT-qPCR and Western blotting. Another portion was processed for paraffin embedding. Sections were stained with hematoxylin & eosin for histomorphometry and Picro Sirius Red for collagen quantification. RESULTS: Vaginal epithelium histomorphometry in GIII (15.3 ± 1.1 µm) and GIV (14.5 ± 1.8 µm) was thinner than in GV (41.3 ± 1.5 µm) and GVI (74.3 ± 1.6 µm). There was an increase in collagen content in GV (84.1 ± 1.2 µm) and GVI (88.2 ± 1.7 µm). HA quantification was higher in GV (0.38 ± 1.1 µg/mg) and GVI (0.49 ± 1.4 µg/mg) when compared with GIII (0.12 ± 1.1 µg/mg) and GIV (0.10 ± 1.2 µg/mg), p < 0.05. CONCLUSIONS: Soy isoflavones increase hyaluronic acid concentration in the vagina of diabetic ovariectomized rats. Such findings might help to attenuate the effects of vulvovaginal atrophy in women.


Subject(s)
Diabetes Mellitus, Experimental , Glycine max , Hyaluronic Acid/metabolism , Isoflavones/pharmacology , Vagina/drug effects , Animals , Atrophy/prevention & control , Disease Models, Animal , Female , Ovariectomy , Random Allocation , Rats , Vagina/metabolism , Vagina/pathology
6.
Ultrasound Obstet Gynecol ; 50(1): 32-39, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27862503

ABSTRACT

OBJECTIVE: To analyze the diagnostic accuracy of two- (2D) and three- (3D) dimensional saline contrast sonohysterography (SCSH) in the detection of endometrial polyps and submucosal uterine leiomyomas in women of reproductive age with abnormal uterine bleeding compared with gold standard hysteroscopy. METHODS: A systematic review of diagnostic studies that compared 2D- and/or 3D-SCSH with hysteroscopy and anatomopathology was conducted according to PRISMA and SEDATE recommendations. The databases MEDLINE, EMBASE and The Cochrane Library were searched electronically using specific terms with no restriction on language or publication year. Quality assessment of included studies was performed using the QUADAS-2 tool. Meta-analysis was performed with the Meta-DiSk program and data presented as forest plots and summary receiver-operating characteristics (SROC) curves. Pooled sensitivity, specificity and positive (LR+) and negative (LR-) likelihood ratios of SCSH in the detection of uterine cavity abnormalities were calculated. RESULTS: A total of 1398 citations were identified and five studies were included in the systematic review and meta-analysis. Pooled sensitivity and specificity of 2D-SCSH in detecting endometrial polyps were 93% (95% CI, 89-96%) and 81% (95% CI, 76-86%), respectively, with pooled LR+ of 5.41 (95% CI, 2.60-11.28) and LR- of 0.10 (95% CI, 0.06-0.17). In the detection of submucosal uterine leiomyomas, pooled sensitivity and specificity were 94% (95% CI, 89-97%) and 81% (95% CI, 76-86%), respectively, with pooled LR+ of 4.25 (95% CI, 2.20-8.21) and LR- of 0.11 (95% CI, 0.05-0.22). 2D-SCSH had good accuracy in detecting endometrial polyps and submucosal uterine leiomyomas, with areas under the SROC curves of 0.97 ± 0.02 and 0.97 ± 0.03, respectively. Studies that analyzed the diagnostic accuracy of 3D-SCSH could not be compared due to high heterogeneity related to menopausal status, type of technique used and primary outcome being investigation of infertility. CONCLUSIONS: 2D-SCSH proved to be a highly sensitive method for detection of endometrial polyps and submucosal uterine leiomyomas, making it a potential first-line diagnostic method in the work-up for women with abnormal uterine bleeding. More studies are needed on 3D-SCSH in women of reproductive age. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.


Subject(s)
Hysteroscopy , Leiomyoma/diagnostic imaging , Polyps/diagnostic imaging , Uterine Neoplasms/diagnostic imaging , Contrast Media/administration & dosage , Female , Humans , Leiomyoma/complications , Polyps/complications , Randomized Controlled Trials as Topic , Sensitivity and Specificity , Sodium Chloride/administration & dosage , Uterine Hemorrhage/etiology , Uterine Neoplasms/complications
7.
Cephalalgia ; 31(13): 1336-42, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21700645

ABSTRACT

BACKGROUND: The association between migraine and obesity gives the clinician with an exciting possibility to alleviate migraine suffering through weight-reduction gastric-restrictive operations. We hypothesized that bariatric weight-reduction intervention (gastric banding) will be associated with reduction of migraine burden in this population. METHODS: A total of 105 women between 18 and 50 years of age, admitted for bariatric surgery between April 2006 and February 2007, were screened for migraine. Twenty-nine with diagnosis of migraine were enrolled into the prospective phase. We followed the migraine pattern of these patients for 6 months post bariatric surgery. RESULTS: Baseline median migraine frequency was six headache days a month. Post bariatric surgery, the migraine-suffering women reported of a lower frequency of migraine attacks (p < 0.001), shorter duration of the attacks (p = 0.02), lower medication use during the attack (p = 0.005), less non-migraine pain (44.8 vs. 33%, p = 0.05), and post-bariatric surgery reduction in headache-related disability assessed by the MIDAS and HIT-6 scores. There was a reduction in migraine frequency among both episodic (from four to one episodes a month) and chronic (from 16.8 to 8.5 episodes per month) migraine patient cohorts separately and combined. CONCLUSIONS: Among migraine-suffering premenopausal obese women, we found a reduced frequency of migraine attacks and improvement of headache-related disability post bariatric surgery. Our findings should be interpreted cautiously. The absence of a control group and the non-blinded nature of our small study make it difficult to draw firm conclusions about the causal nature of the headache changes observed in this population. Further study is needed to evaluate the possible specific effects of surgical weight loss on migraine in obese women.


Subject(s)
Bariatric Surgery , Migraine Disorders/epidemiology , Obesity, Morbid/complications , Adolescent , Adult , Female , Follow-Up Studies , Humans , Interviews as Topic , Middle Aged , Migraine Disorders/complications , Obesity, Morbid/surgery , Premenopause , Prospective Studies , Quality of Life , Recurrence , Severity of Illness Index , Surveys and Questionnaires , Treatment Outcome , Weight Loss , Young Adult
8.
Water Sci Technol ; 52(5): 187-94, 2005.
Article in English | MEDLINE | ID: mdl-16248195

ABSTRACT

The paper describes the realization of a real-time control for the Vienna sewer system. The project is scheduled for completion for 2004. The 3.5 year project comprises all planning stages starting with the recording of data up to the planning of measuring and controlling units. The concrete steps of the planning stages are explained. A measuring system including 25 rainfall measurements, 40 flow measurements and 20 water level measurements is implemented as an online system. This measuring system is designed to achieve two objectives, on the one hand the real-time control and on the other hand the calibration of the model that is used for the hydrodynamic sewer system simulation. The approx. 53,000 pipes have served to generate a coarse network of no more than approx. 2600 pipes. The area data were derived with high accuracy from available aerial photograph interpretations. With simulation runs of a rule-based control software the system operation was examined. A self-learning system will improve the rule basis. A forecasting model that uses weather observation radar will additionally influence the controlling decisions. The findings from the investigations are immediately considered in the planning of measuring and control units. The simulated results for the first phase of implementation, which demonstrate the benefit of RTC for the Vienna sewer system, are explained.


Subject(s)
Sewage/chemistry , Waste Disposal, Fluid/methods , Austria , Data Collection , Forecasting , Models, Theoretical , Rain , Software , Water Movements
9.
Am J Physiol Heart Circ Physiol ; 281(6): H2680-6, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11709437

ABSTRACT

Several disease states, including hypertension, are associated with elevations in plasma endothelin-1 (ET-1) and variable changes in vascular contraction to ET-1. The spotting lethal (sl) rat carries a deletion of the endothelin-B (ET(B)) receptor gene that prevents expression of functional ET(B) receptors, resulting in elevated plasma ET-1. On a normal diet, these rats are normotensive and thus provide an opportunity to study the vascular effects of chronically elevated ET-1 in the absence of hypertension. Studies were performed in rats homozygous for the ET(B) deficiency (sl/sl; n = 8) and in transgenic rats heterozygous for the ET(B) deficiency (sl/+; n = 8). Plasma ET-1 was elevated in sl/sl rats (3.85 +/- 0.55 pg/ml) compared with sl/+ rats (0.31 +/- 0.11 pg/ml). Mean arterial blood pressure in conscious unrestrained sl/sl and sl/+ rats was 101 +/- 5 and 107 +/- 6 mmHg, respectively. Concentration-dependent contractions to ET-1 (10(-11)-10(-8) M) were reduced in mesenteric small arteries (150-250 microm) from sl/sl rats, as indicated by an approximately 10-fold increase in EC(50). A selective ET(A) antagonist, A-127722 (30 nM), abolished contraction to ET-1 in both groups, whereas a selective ET(B) antagonist had no effect. Also, ET(B) agonists (IRL-1620 and sarafatoxin 6c) produced neither contraction nor relaxation in either group, indicating that contraction to ET-1 in this vascular segment was exclusively ET(A) dependent. Despite increased plasma ET-1, protein expression of ET(A) receptors in membrane protein isolated from mesenteric small arteries was increased in sl/sl compared with sl/+ rats, as shown by Western blotting. These results indicate that, in ET(B)-deficient rats, ET(A)-induced contraction is reduced in vessels normally lacking ET(B)-mediated effects. Reduced contraction may be related to elevated plasma ET-1 and occurs in the presence of increased ET(A) receptor protein expression, suggesting an uncoupling of ET(A) receptor expression from functional activity.


Subject(s)
Endothelin-1/pharmacology , Receptors, Endothelin/genetics , Receptors, Endothelin/metabolism , Vasoconstriction/drug effects , Vasoconstriction/physiology , Animals , Animals, Genetically Modified , Blood Pressure/drug effects , Blood Pressure/physiology , Blotting, Western , Dose-Response Relationship, Drug , Endothelin-1/blood , Heterozygote , Homozygote , Male , Mesenteric Arteries/chemistry , Mesenteric Arteries/physiology , Rats , Receptor, Endothelin A , Receptor, Endothelin B , Receptors, Endothelin/analysis , Vascular Resistance/drug effects , Vascular Resistance/physiology
10.
J Appl Physiol (1985) ; 91(6): 2553-60, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11717218

ABSTRACT

Most of the available data on the nitric oxide (NO) pathway in the vasculature is derived from studies performed with cells isolated from conduit arteries. We investigated the expression and regulation of components of the NO synthase (NOS)-NO-cGMP pathway in endothelial cells from the mesenteric vascular bed. Basally, or in response to bradykinin, cultured mesenteric endothelial cells (MEC) do not release NO and do not express endothelial NOS protein. MEC treated with cytokines, but not untreated cells, express inducible NOS (iNOS) mRNA and protein, increase nitrite release, and stimulate cGMP accumulation in reporter smooth muscle cells. Pretreatment of MEC with genistein abolished the cytokine-induced iNOS expression. On the other hand, exposure of MEC to the microtubule depolymerizing agent colchicine did not affect the cytokine-induced increase in nitrite formation and iNOS protein expression, whereas it inhibited the induction of iNOS in smooth muscle cells. Collectively, our findings demonstrate that MEC do not express endothelial NOS but respond to inflammatory stimuli by expressing iNOS, a process that is blocked by tyrosine kinase inhibition but not by microtubule depolymerization.


Subject(s)
Cyclic GMP/metabolism , Endothelium, Vascular/metabolism , Nitric Oxide Synthase/metabolism , Nitric Oxide/metabolism , Splanchnic Circulation/physiology , Animals , Aorta/cytology , Aorta/metabolism , Bradykinin/pharmacology , Cells, Cultured , Colchicine/pharmacology , Cytokines/pharmacology , Endothelium, Vascular/cytology , Male , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Nitrites/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Rats, Wistar
11.
Arch Mal Coeur Vaiss ; 94(7): 739-42, 2001 Jul.
Article in French | MEDLINE | ID: mdl-11494632

ABSTRACT

The authors report the first case of cardiac sarcoidosis involving only the interatrial septum and the atrioventricular node in a 30 year old man with known lymph node sarcoidosis. The diagnosis was suspected after the finding of an apparently innocent 1st degree atrioventricular block and confirmed by transoesophageal echocardiography and by IMATRON computerised tomography. Isolated atrial involvement of sarcoidosis is rare in the absence of any left ventricular disease. This explains the negative findings at transthoracic echocardiography and radio-isotopic investigations usually recommended for diagnosing cardiac sarcoidosis.


Subject(s)
Cardiomyopathies/diagnosis , Sarcoidosis/diagnosis , Adult , Cardiomyopathies/diagnostic imaging , Diagnosis, Differential , Echocardiography, Transesophageal , Electrocardiography , Heart Atria/diagnostic imaging , Humans , Lymphatic Diseases/diagnosis , Male , Radionuclide Imaging , Sarcoidosis/diagnostic imaging , Tomography, X-Ray Computed
12.
Prostate ; 48(2): 79-92, 2001 Jul 01.
Article in English | MEDLINE | ID: mdl-11433418

ABSTRACT

BACKGROUND: The generation of prostatic cell lines provides in vitro models for experimental studies of the pathogenesis of prostate carcinoma. Therefore, we established and characterized a new human prostate epithelial cell line, PEAZ-1 (prostate epithelial Arizona-1). METHODS: The PEAZ-1 cells were grown from a primary human prostate carcinoma specimen obtained from radical prostatectomy. The isolated cells were characterized by immunobiochemistry, immunohistochemistry, and tumorigenicity studies. RESULTS: PEAZ-1 cells are near diploid, tumorigenic, and androgen independent for cell growth. PEAZ-1 cells express N-cadherin, alpha- and beta-catenins, and p120 at cell-cell contacts, cytoplasmic laminin 5, vinculin, paxillin, and phosphotyrosine at focal adhesions, vimentin, and cytokeratins 8 and 18. They do not express plakoglobin, E-cadherin, and PSA, and do not form desmosomes and hemidesomomes. PEAZ-1 respond to ocadaic acid, a pro-apoptotic agent, by expression of p53. CONCLUSIONS: PEAZ-1 cells is a human prostate cancer cell line that has a number of mesenchymal characteristics.


Subject(s)
Prostatic Neoplasms/pathology , Tumor Cells, Cultured , Androgens/pharmacology , Cadherins/pharmacology , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Integrins/analysis , Male , Prostatectomy , Specimen Handling
13.
Nucl Med Commun ; 22(2): 189-96, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11258406

ABSTRACT

BACKGROUND: 201Tl myocardial scintigraphy (201Tl SPECT) is of strong prognostic value in various populations with suspected or known coronary artery disease. However, its value in patients with coronary artery bypass grafting (CABG) is not fully assessed. METHODS: We examined 115 consecutive patients to determine the relation between clinical data/stress 201Tl SPECT performed 5+/-3 years after CABG, and subsequent cardiac events. RESULTS: Thirteen patients (11%) had stress-induced angina, 22 (19%) had electrical positivity, and 97 (84%) had abnormal scintigraphy, including 62 (54%) with reversible defects. During follow-up (35+/-22 months), there were nine cardiac deaths, seven myocardial infarctions, and 20 revascularization procedures. Multivariate Cox analysis identified the delay between CABG and scintigraphy (P<0.01, relative risk (RR) = 1.01), the extent of stress 201Tl defects (P = 0.04, RR = 1.18), and increased stress 201Tl lung uptake (P = 0.03, RR = 3.56) as significant predictors of cardiac deaths/infarctions. Delay between CABG and scintigraphy (P < 0.001, RR = 1.01), the extent of stress 201Tl defects (P = 0.03, RR = 1.15), and that of reversible defects (P = 0.05, RR = 1.13) were the only significant predictors of total events. CONCLUSIONS: Besides the delay between CABG and scintigraphy, the scintigraphic parameters were the only significant and additive predictors of cardiac events in 115 patients with CABG.


Subject(s)
Coronary Artery Bypass , Heart/diagnostic imaging , Thallium , Adult , Aged , Disease-Free Survival , Exercise Test , Female , Follow-Up Studies , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Predictive Value of Tests , Prognosis , Thallium Radioisotopes , Tomography, Emission-Computed, Single-Photon
14.
Hypertension ; 37(2): 301-7, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11230289

ABSTRACT

Angiotensin II (Ang II) is one of the most potent vasoconstrictor substances, yet paradoxically, Ang II may dilate certain vascular beds via an undefined mechanism. Ang II-induced vasoconstriction is mediated by the AT(1) receptor, whereas the relative expression and functional importance of the AT(2) receptor in regulating vascular resistance and blood pressure are unknown. We now report that Ang II induces relaxation of mesenteric microvessels and that this vasodilatory response was unaffected by losartan, an AT(1) receptor antagonist, but was inhibited by PD123,319, a selective antagonist of AT(2) receptors. In addition, reverse transcriptase-polymerase chain reaction studies revealed high amounts of AT(2) receptor mRNA in smooth muscle from these same microvessels. Ang II-induced relaxation was inhibited by either tetraethylammonium or iberiotoxin, suggesting involvement of the large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channel. Subsequent whole-cell and single-channel patch-clamp studies on single myocytes demonstrated that Ang II increases the activity of BK(Ca) channels. As in our tissue studies, the effect of Ang II on BK(Ca) channels was inhibited by PD123,319, but not by losartan. In light of these consistent findings from tissue physiology, molecular studies, and cellular/molecular physiology, we conclude that Ang II relaxes microvessels via stimulation of the AT(2) receptor with subsequent opening of BK(Ca) channels, leading to membrane repolarization and vasodilation. These findings provide evidence for a novel endothelium-independent vasodilatory effect of Ang II.


Subject(s)
Angiotensin II/pharmacology , Mesenteric Arteries/drug effects , Potassium Channels/metabolism , Receptors, Angiotensin/physiology , Vasodilation/drug effects , Animals , Calcium/physiology , Cells, Cultured , Dose-Response Relationship, Drug , Endothelin-1/pharmacology , Imidazoles/pharmacology , In Vitro Techniques , Losartan/pharmacology , Male , Membrane Potentials/drug effects , Mesenteric Arteries/cytology , Mesenteric Arteries/physiology , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Nitroarginine/pharmacology , Patch-Clamp Techniques , Peptides/pharmacology , Pyridines/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2 , Receptors, Angiotensin/genetics , Tetraethylammonium/pharmacology
15.
J Biotechnol ; 85(2): 175-85, 2001 Feb 13.
Article in English | MEDLINE | ID: mdl-11165362

ABSTRACT

Escherichia coli fed-batch cultivations at 22 m3 scale were compared to corresponding laboratory scale processes and cultivations using a scale-down reactor furnished with a high-glucose concentration zone to mimic the conditions in a feed zone of the large bioreactor. Formate accumulated in the large reactor, indicating the existence of oxygen limitation zones. It is suggested that the reduced biomass yield at large scale partly is due to repeated production/re-assimilation of acetate from overflow metabolism and mixed acid fermentation products due to local moving zones with oxygen limitation. The conditions that generated mixed-acid fermentation in the scale-down reactor also induced a number of stress responses, monitored by analysis of mRNA of selected stress induced genes. The stress responses were relaxed when the cells returned to the substrate limited and oxygen sufficient compartment of the reactor. Corresponding analysis in the large reactor showed that the concentration of mRNA of four stress induced genes was lowest at the sampling port most distant from the feed zone. It is assumed that repeated induction/relaxation of stress responses in a large bioreactor may contribute to altered physiological properties of the cells grown in large-scale bioreactor. Flow cytometric analysis revealed reduced damage with respect to cytoplasmic membrane potential and integrity in cells grown in the dynamic environments of the large scale reactor and the scale-down reactor.


Subject(s)
Bioreactors , Acetic Acid/metabolism , Anaerobiosis , Biomass , Biotechnology , Escherichia coli/genetics , Escherichia coli/growth & development , Escherichia coli/metabolism , Fermentation , Gene Expression , Genes, Bacterial , Glucose/metabolism , RNA, Bacterial/genetics , RNA, Bacterial/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism
16.
J Cardiovasc Pharmacol ; 36(6): 758-63, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11117376

ABSTRACT

Contraction of vascular smooth muscle by endothelin-1 is dependent on extracellular and intracellular Ca2+. However, the role of ryanodine-sensitive Ca2+ stores in endothelin-1-induced contraction is unknown. Vascular contraction was measured in mesenteric small arteries (200-300 microm intraluminal diameter) isolated from Sprague-Dawley rats and maintained at a constant intraluminal pressure of 40 mm Hg. The presence of functional ryanodine receptor Ca2+ release channels (RyRC) was demonstrated by the finding that ryanodine (10 microM), which locks the RyRC in a subconductance state, produced significant contraction of small arteries in the presence of 15 mM KCl. This effect was inhibited by dantrolene (10 microM), a RyRC inhibitor. Dantrolene significantly reduced the ET(A) receptor-mediated contraction to endothelin-1 (10(-11)-10(-9) M). The ability of dantrolene to reverse contraction induced by endothelin-1 was also determined. Dantrolene (1-10 microM) produced concentration-dependent relaxation of vessels precontracted to 38+/-3% of resting diameter with endothelin-1 but had no effect in vessels precontracted to a similar degree with phenylephrine or KCl. Because activation of RyRC may be dependent on production of cyclic ADP-ribose, the effect of nicotinamide (2 mM), an inhibitor of ADP-ribosyl cyclase, on contraction to endothelin-1 was determined. Nicotinamide had an inhibitory effect similar to that produced by dantrolene. A combination of nicotinamide and dantrolene had no greater effect than either agent alone, suggesting a common pathway for cyclic ADP-ribose and RyRC. In summary, endothelin-1 induces contraction of small mesenteric arteries through ET(A) receptor-mediated production of cyclic ADP-ribose and activation of RyRC.


Subject(s)
Adenosine Diphosphate Ribose/analogs & derivatives , Adenosine Diphosphate Ribose/pharmacology , Calcium Channels/drug effects , Endothelin-1/pharmacology , Mesenteric Arteries/drug effects , Muscle, Smooth, Vascular/drug effects , Ryanodine Receptor Calcium Release Channel/drug effects , Animals , Cyclic ADP-Ribose , Dantrolene/pharmacology , Muscle Relaxants, Central/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase Type III , Nitroarginine/pharmacology , Potassium Channel Blockers , Rats , Rats, Sprague-Dawley
17.
Am J Physiol Heart Circ Physiol ; 279(6): H2598-603, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11087210

ABSTRACT

Previously, we showed that development of myocardial necrotic lesions is associated with impaired endothelium-dependent coronary artery relaxation in young cardiomyopathic hamsters. Since active necrosis declines with aging, this study was designed to determine whether coronary artery endothelium-dependent relaxation to ACh is restored and to identify the mechanisms mediating this effect. Intraluminal diameter was recorded in coronary arteries (150-250 micrometer) from control (C, 297 +/- 5 days old) and cardiomyopathic (M, 296 +/- 4 days old) hamsters. Relaxation to ACh (10(-9)-3 x 10(-5) M) was similar in vessels from C and M hamsters. However, mechanisms mediating relaxation to ACh were altered. Inhibition of nitric oxide synthase (NOS) activity with N-nitro-L-arginine (1 mM) had a greater inhibitory effect in vessels from C hamsters, indicating a reduction in NOS-dependent relaxation in vessels from M hamsters. Conversely, inhibition of large Ca(2+)-dependent K(+) (BK(Ca)) channels with charybdotoxin (CTX, 0.1 microM) had a greater inhibitory effect in vessels from M hamsters. In the presence of both N-nitro-L-arginine and CTX, relaxation to ACh was abolished in both groups. CTX (0.1 micrometer) produced a 50 +/- 4 and 30 +/- 3% contraction of vessels from M and C hamsters, respectively, indicating an enhanced role for BK(Ca) channels in regulation of coronary artery tone in M hamsters. Finally, vasodilatory cyclooxygenase products contributed to ACh-induced relaxation in vessels from M, but not C, hamsters. In conclusion, NOS-dependent relaxation of coronary small arteries is reduced in the late stage of cardiomyopathy. An increase in relaxation mediated by BK(Ca) channels and vasodilatory cyclooxygenase products compensates for this effect.


Subject(s)
Cardiomyopathies/metabolism , Coronary Circulation/physiology , Coronary Vessels/enzymology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Potassium Channels, Calcium-Activated , Potassium Channels/physiology , Acetylcholine/pharmacology , Animals , Biological Factors/metabolism , Cardiomyopathies/pathology , Charybdotoxin/pharmacology , Coronary Circulation/drug effects , Cricetinae , Dose-Response Relationship, Drug , Endothelium, Vascular/enzymology , Enzyme Inhibitors/pharmacology , Epoprostenol/metabolism , Large-Conductance Calcium-Activated Potassium Channels , Male , Mesocricetus , Microcirculation/drug effects , Microcirculation/physiology , Nitric Oxide/metabolism , Nitroarginine/pharmacology , Organ Size , Prostaglandin-Endoperoxide Synthases/metabolism , Vasodilation/drug effects , Vasodilation/physiology , Vasodilator Agents/pharmacology
18.
Am J Physiol Regul Integr Comp Physiol ; 279(2): R492-8, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10938237

ABSTRACT

Cyclic nucleotide-dependent vascular relaxation is associated with increases in the phosphorylation of a small heat shock protein (HSP), HSP20. An increase in phosphorylation of another small HSP, HSP27, is associated with impaired cyclic nucleotide-dependent vascular relaxation. Expression of HSPs is altered by exposure to several types of cellular stress in vitro. To determine if behavioral stress in vivo alters vascular expression and phosphorylation of the small HSPs and cyclic nucleotide-dependent vascular relaxation, borderline hypertensive rats were stressed by restraint and exposure to air-jet stress 2 h/day for 10 days or remained in their home cage. Stress impaired relaxation of aorta to forskolin, which activates adenylyl cyclase, and sodium nitroprusside, which activates guanylyl cyclase. This was associated with an increase in the aortic expression and phosphorylation of HSP27, which was localized to the vascular smooth muscle, but a decrease in the amount of phosphorylated (P)-HSP20. To determine if P-HSP27 inhibits phosphorylation of HSP20, P-HSP27 was added to a reaction mixture containing recombinant HSP20 and the catalytic subunit of cAMP-dependent protein kinase. P-HSP27 inhibited phosphorylation of HSP20 in a concentration-dependent manner. These data demonstrate that P-HSP27 can inhibit phosphorylation of HSP20. The increase in P-HSP27 and decrease in P-HSP20 were associated with reduced cyclic nucleotide-dependent vascular smooth muscle relaxation in response to behavioral stress in vivo, an effect similar to that observed previously in response to cellular stress in vitro.


Subject(s)
Heat-Shock Proteins/metabolism , Stress, Physiological/physiopathology , Vasodilation , Animals , Aorta/metabolism , Aorta/physiopathology , Female , HSP20 Heat-Shock Proteins , Hemodynamics , Male , Phosphoproteins/metabolism , Phosphorylation , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Stress, Physiological/metabolism , Tissue Distribution , Vasomotor System/physiopathology
19.
Am J Physiol ; 276(2): R435-40, 1999 02.
Article in English | MEDLINE | ID: mdl-9950922

ABSTRACT

Behavioral stress and aging are associated with an increase in vascular disease. This study determined the mechanisms contributing to changes in endothelium-dependent relaxation of isolated coronary arteries (300-350 micrometers) induced by exposure to 10 days of air-jet stress (2 h/day) in young (3 mo) and old (18 mo) male borderline hypertensive rats (BHR). Aging, alone, did not alter endothelium-dependent relaxation to acetylcholine (ACh) quantitatively but did alter the mechanisms contributing to relaxation to ACh, which was largely dependent on nitric oxide synthase (NOS) in vessels from old, but not young, BHR. Behavioral stress resulted in an enhanced relaxation to ACh that was dependent on NOS in vessels from young stressed compared with young control BHR. Conversely, relaxation to ACh was reduced in coronary arteries from old stressed compared with old control BHR. In vessels from old control BHR, there was an NOS-independent component of relaxation mediated by opening of K+ channels that was absent in vessels from old stressed BHR. The superoxide anion scavenger, tiron, partially restored relaxation, and inhibition of cyclooxygenase largely restored relaxation to ACh in vessels from old stressed BHR. In summary, the effect of behavioral stress was age dependent. ACh-induced relaxation of coronary arteries was enhanced in an NOS-dependent manner in young BHR and was impaired in old BHR due to superoxide anions, vasoconstrictor cyclooxygenase products, and a loss of K+ channel-mediated relaxation.


Subject(s)
Aging/physiology , Coronary Vessels/physiopathology , Hypertension/physiopathology , Stress, Psychological/physiopathology , Vasodilation/physiology , Acetylcholine/pharmacology , Animals , Arteries/physiopathology , Coronary Vessels/drug effects , Enzyme Inhibitors/pharmacology , Female , Male , Nitroarginine/pharmacology , Physical Stimulation , Rats , Rats, Inbred SHR , Rats, Inbred Strains , Rats, Inbred WKY , Vasodilation/drug effects , Vasodilator Agents/pharmacology
20.
J Learn Disabil ; 31(6): 615-24, 1998.
Article in English | MEDLINE | ID: mdl-9813961

ABSTRACT

The original intent of special education pull-out services was to remove students from general education temporarily for intensive, individualized instruction in deficit areas. In many school districts, however, it seems that once students participate in pull-out services, there is little effort to return them to general education. One explanation for this is that not much is known about how best to prepare students for movement up the cascade of services, including reintegration into the mainstream. A promising reintegration approach is transenvironmental programming (TP). Research suggests that supplementing TP with continuous progress monitoring, specifically via curriculum-based measurement (CBM), better prepares students for reintegration than either TP or CBM alone. Findings from the present study provide a possible explanation: Results suggest that special educators using TP who receive CBM information about their students' academic progress are more likely to plan and implement academic interventions in preparation for students' transition than are those special educators who do not receive this information. This supports the hypothesis that the relatively greater success of TP + CBM is due to increased attention to academic preparation. Implications for practice and future research are discussed.


Subject(s)
Curriculum , Education, Special/methods , Learning Disabilities/rehabilitation , Mainstreaming, Education/methods , Adult , Analysis of Variance , Child , Child, Preschool , Education, Special/organization & administration , Female , Humans , Logistic Models , Male , Middle Aged , Reading , Teaching/standards , Teaching/statistics & numerical data , United States
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