Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 284
Filter
1.
J Nutr Health Aging ; 25(6): 727-734, 2021.
Article in English | MEDLINE | ID: mdl-34179925

ABSTRACT

BACKGROUND: Obesity accelerates and exacerbates the age-related changes on muscle function and exercise capacity. In addition, the middle-aged population is often overlooked when talking about the prevention of sarcopenia. This study investigated the effects of exercise alone or in combination with a high-protein diet on muscle function and physical fitness in middle-aged obese adults. MATERIALS AND METHODS: Sixty-nine middle-aged (50-64 years old) obese adults were randomly assigned to one of the following groups: control group (C; n=23), exercise group (E; n=23) or exercise plus high-protein group (EP; n=23). Individuals within the E and EP groups received 12 weeks of exercise training; whereas, the individuals in the EP group also received a high-protein diet intervention (1.6g/kg/day). Individuals within the C group were asked to maintain their lifestyle for 12 weeks. Participants were evaluated before and after the intervention. Outcome measures included maximal exercise capacity, muscle function and functional physical performance. Analysis of covariance was used to determine the effects of the intervention. RESULTS: After the intervention, the E and EP groups had greater maximal work rate, peak oxygen consumption, and muscle power during muscle contractions at 180°/sec than that in the C group (P<0.05). The EP group, but not the E group, showed significant improvement in the sit-to-stand test and climbing stairs test than the C group after the intervention (P<0.05). Within group comparisons showed that the anaerobic threshold only increased in the EP group (+12% from pre-test). CONCLUSIONS: For middle-aged obese adults, exercise with a high-protein diet not only improved muscle power and exercise capacity but also enhanced their functional physical performance.


Subject(s)
Diet, High-Protein , Exercise Tolerance , Obesity , Exercise , Humans , Middle Aged , Muscle, Skeletal , Obesity/diet therapy
2.
Biomed Res Int ; 2016: 4582439, 2016.
Article in English | MEDLINE | ID: mdl-28025646

ABSTRACT

Background. Postoperative sore throat is one of the major complaints of general anesthesia in the postanesthesia care unit. This prospective study investigated the preventive effect of ketorolac tromethamine spray in postendotracheal-intubation-induced sore throat after general anesthesia. Methods. Surgical patients undergoing general anesthesia with endotracheal intubation were recruited from a medical center. Patients were randomly assigned to group K (treated with 5% ketorolac tromethamine spray) or group D (treated with distilled water spray). Before intubation, each endotracheal tube was sprayed with the appropriate solution by physicians over the 20 cm length of the cuff. Each group comprised 95 patients fitting the inclusion and exclusion criteria for whom complete data sets were collected. The intensity of the sore throat was measured at 1, 3, 6, and 24 h after surgery, and data were compared. Results. The two groups had similar characteristics. Postoperative sore throat was significantly less frequent in group K than in group D (p < 0.001) and the pain intensity was significantly lower in group K than in group D at each time point (all p < 0.001). Conclusions. This study demonstrated that preanesthesia 5% ketorolac tromethamine spray could effectively decrease postendotracheal-intubation-induced sore throat in patients undergoing general anesthesia.


Subject(s)
Anesthesia, General/adverse effects , Intubation, Intratracheal/adverse effects , Ketorolac Tromethamine/administration & dosage , Oral Sprays , Pharyngitis/prevention & control , Postoperative Complications/prevention & control , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pharyngitis/etiology
3.
Nuklearmedizin ; 54(1): 36-42, 2015.
Article in English | MEDLINE | ID: mdl-25345433

ABSTRACT

UNLABELLED: Oral hydration with large volume of fluid, high dose of diuretics and maximum bladder distension are frequently required to achieve an adequate urinary FDG clearance in an FDG PET/CT protocol for bladder cancer or pelvic tumour evaluation. Although most patients tolerated these procedures for eliminating urinary FDG activity, these procedures may be still unpleasant. AIM: Is there a more patient-friendly protocol which is less burdensome and yet provides a satisfactory FDG clearance in urine? In this study, we established a patient-friendly FDG PET/CT protocol without compromising urinary FDG clearance. PATIENTS, METHODS: 23 patients with biopsy-proven urinary bladder cancers were recruited to evaluate the effectiveness of this patient-friendly protocol on reducing urinary bladder FDG activity. The patient-friendly protocol includes encouraging patients to take a tolerable amount of fluid, delaying the administration of low dose diuretic, shortening the urine holding time and using delayed imaging. RESULTS: All of the patients tolerated this patient-friendly procedure well. In addition, the patient-friendly protocol was effective in reducing FDG activity in the urine. One hundred percent of primary bladder cancer were visualized on the FDG PET/CT images using this patient-friendly protocol. CONCLUSIONS: This patient-friendly FDG PET/CT protocol is less intrusive yet effective in reducing urinary FDG activity.


Subject(s)
Fluorodeoxyglucose F18 , Multimodal Imaging/methods , Patient Satisfaction , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/metabolism , Urinary Bladder/metabolism , Adult , Aged , Female , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Male , Metabolic Clearance Rate , Middle Aged , Patient-Centered Care/methods , Positron-Emission Tomography/methods , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Sensitivity and Specificity , Tomography, X-Ray Computed/methods , Urination
4.
Technology (Singap World Sci) ; 2(1): 75, 2014 Mar.
Article in English | MEDLINE | ID: mdl-25045720

ABSTRACT

We report here the technology and the underlying science of a new device for inhalation (pulmonary) drug delivery which is capable of fulfilling needs unmet by current commercial devices. The core of the new device is a centimeter-size clog-free silicon-based ultrasonic nozzle with multiple Fourier horns in resonance at megahertz (MHz) frequency. The dramatic resonance effect among the multiple horns and high growth rate of the MHz Faraday waves excited on a medicinal liquid layer together facilitate ejection of monodisperse droplets of desirable size range (2-5 µm) at low electrical drive power (<1.0 W). The small nozzle requiring low drive power has enabled realization of a pocket-size (8.6 × 5.6 × 1.5 cm3) ultrasonic nebulizer. A variety of common pulmonary drugs have been nebulized using the pocket-size unit with desirable aerosol sizes and output rate. These results clearly provide proof-of-principle for the new device and confirm its potential for commercialization.

5.
Acta Clin Belg ; 69(2): 130-1, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24724756

ABSTRACT

The authors report a 74-year-old man with chronic hepatitis C-related cirrhosis and end-stage renal disease undergoing maintenance haemodialysis who was diagnosed with hepatoma. The hepatoma spontaneously regressed with significantly decreased serum alpha-fetoprotein level without any treatment during the subsequent 4-year follow-up period. However, recurrent hepatomas over bilateral hepatic lobes were evident thereafter, and the patient died later due to hepatic failure. Hepatoma with ring calcification is extremely rare and considered poor differentiation with high risk for recurrence. Spontaneous regression of hepatoma is also rare, while spontaneous regression occurring in a hepatoma with ring calcification is never reported. The definite mechanisms causing spontaneous regression of hepatomas remain unclear, but an immune response toward hepatoma induced by alpha-fetoprotein might play an important role.


Subject(s)
Calcinosis/pathology , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Neoplasm Regression, Spontaneous , Aged , Calcinosis/metabolism , Carcinoma, Hepatocellular/metabolism , Humans , Liver Neoplasms/metabolism , Male
6.
J Dent Res ; 93(4): 388-93, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24554538

ABSTRACT

The blocking of advanced glycation end-products (AGE) has been shown to reduce diabetic complications and control periodontitis. This study investigated the pattern of palatal wound-healing after graft harvesting under the administration of aminoguanidine (AG), an AGE inhibitor, or N-phenacylthiazolium bromide (PTB), a glycated cross-link breaker. Full-thickness palatal excisional wounds (5.0 x 1.5 mm(2)) were created in 72 Sprague-Dawley rats. The rats received daily intraperitoneal injections of normal saline (control), AG, or PTB and were euthanized after 4 to 28 days. The wound-healing pattern was assessed by histology, histochemistry for collagen matrix deposition, immunohistochemistry for AGE and the AGE receptor (RAGE), and the expression of RAGE, as well as inflammation- and recovery-associated genes. In the first 14 days following AG or PTB treatments, wound closure, re-epithelialization, and collagen matrix deposition were accelerated, whereas AGE deposition, RAGE-positive cells, and inflammation were reduced. RAGE and tumor necrosis factor-alpha were significantly down-regulated at day 7, and heme oxygenase-1 was persistently down-regulated until day 14. The levels of vascular endothelial growth factor, periostin, type I collagen, and fibronectin were all increased at day 14. In conclusion, anti-AGE agents appeared to facilitate palatal wound-healing by reducing AGE-associated inflammation and promoting the recovery process.


Subject(s)
Glycation End Products, Advanced/antagonists & inhibitors , Palate/drug effects , Alveolar Process/drug effects , Alveolar Process/pathology , Animals , Cell Adhesion Molecules , Cicatrix/pathology , Collagen/drug effects , Collagen Type I/analysis , Down-Regulation , Fibronectins/analysis , Glycation End Products, Advanced/analysis , Guanidines/pharmacology , Heme Oxygenase (Decyclizing)/analysis , Inflammation , Male , Nitric Oxide Synthase/antagonists & inhibitors , Palate/surgery , Rats , Rats, Sprague-Dawley , Re-Epithelialization/drug effects , Receptor for Advanced Glycation End Products , Receptors, Immunologic/analysis , Thiazoles/pharmacology , Time Factors , Tumor Necrosis Factor-alpha/analysis , Vascular Endothelial Growth Factor A , Wound Closure Techniques , Wound Healing/drug effects
8.
Horm Metab Res ; 43(1): 31-6, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20865647

ABSTRACT

Previous studies have demonstrated that plasma calcitonin is lower in hypothyroid patients and that thyroxine stimulates the human thyroid to release calcitonin. Therefore, thyroid hormones may regulate the secretion of calcitonin, but further work is needed to address this possibility in more detail. TT cells, a model of human thyroid C cells, were incubated in a medium containing vehicle, thyroxine, or thyroxine methyl-hemisuccinate-bovine serum albumin (BSA-L-T(4), thyroxine was immobilized and linked to BSA); then, the levels of secreted calcitonin (hCT), calcitonin mRNA, and cAMP were measured. To study links that connect the cAMP-dependent protein kinase A (PKA) pathway to the observed thyroxine effects, cells were treated with either vehicle or thyroxine plus SQ22536 [an adenylyl cyclase (AC) inhibitor], KT5720 (a PKA inhibitor), or 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor). The activity levels of AC and PKA, and secreted calcitonin were then measured. The results indicate that thyroxine increases calcitonin secretion, cellular cAMP accumulation, and the activities of AC and PKA, but does not increase hCT mRNA levels in TT cells. BSA-L-T(4) also increases calcitonin secretion. These effects are inhibited by SQ22536, and KT5720 and suggest that the nongenomic thyroxine effects that stimulate calcitonin secretion from TT cells involve the cAMP-dependent PKA pathway.


Subject(s)
Calcitonin/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Thyroid Gland/enzymology , Thyroxine/metabolism , Cell Line, Tumor , Cyclic AMP-Dependent Protein Kinases/genetics , Humans , Models, Biological , Signal Transduction , Thyroid Gland/metabolism
9.
J Food Sci ; 75(5): T82-90, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20629898

ABSTRACT

Nanotechnology, as a new enabling technology, has the potential to revolutionize food systems. However, much attention has been focused on nanoparticle foods due to their potential physiological properties. This study was aimed to evaluate the mutagenic safety and fatty liver improvement of black soybean in senescence-accelerated mice (SAMP8). The mutagenic activity of black soybeans was investigated using the Ames test (Salmonella Typhimurium TA98, 100, 102, and 1535). Furthermore, senescence-accelerated prone-8 mice (SAMP8) have been reported to display spontaneous fatty liver. Male SAMP8 mice were divided into control and supplemented with 10% micronized or nanonized black soybeans diet and fed for 12 wk. The results revealed that the Ames test of micronized and nanonized black soybeans exhibited no mutagenicity. Administration of black soybeans to mice showed no effects on food intake and body and organ weights. The nanonized black soybean group had a lower degree of spontaneous fatty liver, alanine aminotransferase, and thiobarbituric acid-reactive substance concentrations, and had enhanced superoxide dismutase, catalase, and glutathione peroxidase activities of livers when compared with the SAMP8 control and micronized black soybean groups. The mice fed with black soybeans had significantly lower triglyceride concentrations than the SAMP8 control group. The results of this study suggest that nanonized black soybeans have no side effects and, moreover, may minimize liver lesions in SAMP8 mice.


Subject(s)
Aging, Premature/metabolism , Fatty Liver/diet therapy , Fatty Liver/metabolism , Food Technology/methods , Glycine max/toxicity , Nanotechnology/methods , Plant Extracts/pharmacology , Aging/genetics , Aging/metabolism , Aging, Premature/genetics , Animals , Diet/methods , Disease Models, Animal , Liver/drug effects , Liver/metabolism , Male , Mice , Mutagenicity Tests/methods , Mutagens/toxicity , Nanostructures/chemistry , Nanostructures/toxicity , Phytotherapy/adverse effects , Phytotherapy/methods , Plant Extracts/chemistry , Plant Extracts/toxicity , Glycine max/chemistry
10.
J Laryngol Otol ; 123(6): 656-61, 2009 Jun.
Article in English | MEDLINE | ID: mdl-18845034

ABSTRACT

OBJECTIVE: The study aimed to delineate the relationship between 18F-fluorodeoxyglucose uptake and histological findings in nasopharyngeal carcinoma. METHODS: We conducted a retrospective review of 88 patients referred to our positron emission tomography department with newly diagnosed, biopsy-proved nasopharyngeal carcinoma. Hospital records were reviewed for demographic and clinical data, including age, gender, body weight, histological analysis and clinical tumour stage. RESULTS: Nineteen out of the 88 patients (22 per cent) had nasopharyngeal carcinoma of World Health Organization type I, 39 (44 per cent) had type II and 30 (34 per cent) had type III. The mean standardised uptake value for the primary tumour was 9.4 +/- 5.0, ranging from 2.2 to 27.1. The mean standardised uptake values were 8.0 +/- 3.9 for type I tumours, 9.7 +/- 4.4 for type II tumours and 10.1 +/- 6.3 for type III tumours (p = 0.451). CONCLUSIONS: Our study found that type III nasopharyngeal carcinoma exhibited a higher 18F-fluorodeoxyglucose uptake than either type II or type I nasopharyngeal carcinoma. However, this difference was not statistically significant.


Subject(s)
Carcinoma/diagnostic imaging , Fluorodeoxyglucose F18/pharmacokinetics , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharynx/diagnostic imaging , Radiopharmaceuticals/pharmacokinetics , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma/pathology , Female , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/pathology , Positron-Emission Tomography , Retrospective Studies , World Health Organization , Young Adult
11.
Article in English | MEDLINE | ID: mdl-16459117

ABSTRACT

Changes in expression of gill Na+/K+ -ATPase (NKA) on a short-term (96 h) time-course following hyposmotic shock (direct transfer to fresh water) of the euryhaline, marine milkfish were studied on gene, protein, and cell levels in this paper. Plasma osmolality and [Na+] responded with rapid declines in 3 h post-transfer yet, thereafter, remained constant. Plasma [Cl-] gradually fell to a significantly lower level at 6 h post-transfer. Gills responded to hyposmotic shock by a dual phase enhancement of NKA activity and protein abundance; (a) Before 24 h: NKA activity increased as early as 3 h and reached a maximum level from 6 to 12 h post-transfer coincided with the sustained lower levels of plasma osmolality, [Na+], and [Cl-] since 3 h post-transfer. This was followed by a gradual rise in alpha-subunit protein levels that peaked at 12 h post-transfer. Meanwhile, alpha-mRNA of NKA did no show significant change. (b) After 24 h: NKA activity as well as the amounts of alpha-subunit mRNA and protein increased significantly. Direct freshwater transfer induced a prompt and significant decrease of NKA immunoreactive (NKIR) cell abundance in filaments before 24 h, followed by a significant increase after 24 h due to their development in filaments and lamellae. Increased number of NKIR cells after 24 h of hyposmotic shock may occur in conjunction with rise of NKA activity as well as alpha-subunit mRNA and protein abundance. In conclusion, milkfish is able to avoid an excessive drop in plasma ions immediately upon hyposmotic shock and maintain plasma ions on a marginal lower level in fresh water. Notably, the initial increase in NKA activity (adjustive phase; 3-12 h) and delayed increase in NKA mRNA and protein abundance (regulatory phase; 48-96 h) indicate the importance of a higher level of the gill enzyme in milkfish upon hyposmotic shock.


Subject(s)
Fishes/physiology , Gills/enzymology , Sodium-Potassium-Exchanging ATPase/biosynthesis , Animals , Fresh Water , Immunoblotting , Osmolar Concentration , Osmotic Pressure , Polymerase Chain Reaction , Seawater , Sodium/blood
12.
Nucl Med Commun ; 24(8): 933-7, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12869827

ABSTRACT

Bowel accumulation of gallium-67 frequently complicates the interpretation of gallium-67 scintigrams. This is a drawback, especially when reading gallium renal images. In this study, we evaluated the value of a high-fibre diet in bowel preparation for improving the quality of gallium renal imaging in lupus nephritis. Group A, consisting of 86 patients, was on a regular diet and received bisacodyl the night before imaging. Group B, consisting of 77 patients, was on a high-fibre diet for three consecutive days before imaging and received bisacodyl the night before imaging. Gallium bowel activity was rated on a scale of 0 to III on the basis of anterior and posterior views of delayed 48 h images. Our data revealed that there was a significant difference in image quality between groups A and B. Fifty per cent of group A patients had obvious bowel activity. The percentage decreased significantly to 25% in group B. In conclusion, the application of a high-fibre diet significantly improves the efficacy of bowel preparation for gallium renal scintigraphy in the evaluation of lupus nephritis.


Subject(s)
Bisacodyl , Citrates , Dietary Fiber , Gallium , Image Enhancement/methods , Intestines/drug effects , Intestines/diagnostic imaging , Kidney/diagnostic imaging , Lupus Nephritis/diagnostic imaging , Adult , Artifacts , Cathartics , Female , Humans , Male , Radionuclide Imaging , Radiopharmaceuticals
13.
Int J Cardiol ; 90(1): 57-61, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12821220

ABSTRACT

To establish a noninvasive diagnostic method for early assessment of cardiac involvement in Kawasaki disease (KD), 28 children with KD were included in this study. Two-dimensional echocardiography (2D-Echo) to detect the aneurysms of coronary arteries (CA), as well as rest and dipyridamole-stress technetium-99m tetrofosmin (Tc-TF) myocardial perfusion single photon emission computed tomography (SPECT) to detect abnormal myocardial perfusion were performed in all of the 28 children with KD and to compare each other. The results showed that (1). 42.9% of cases had no aneurysm and 57.1% had significant aneurysms detected by 2D-Echo; (2). 42.9% of cases had normal perfusion and 57.1% of cases had abnormal myocardial perfusion assessed by Tc-TF myocardial perfusion SPECT; (3). 25.0% of cases showed both normal 2D-Echo and Tc-TF myocardial perfusion SPECT findings and 39.3% of cases showed both abnormal 2D-Echo and Tc-TF myocardial perfusion SPECT findings; and (4). there was poor agreement between 2D-Echo and Tc-TF myocardial perfusion SPECT findings (P>0.05). We concluded that poor agreement exists between aneurysms and abnormal myocardial perfusion detected by 2D-Echo and Tc-TF myocardial perfusion SPECT findings in patients with KD.


Subject(s)
Dipyridamole , Echocardiography , Heart Diseases/diagnosis , Mucocutaneous Lymph Node Syndrome/diagnosis , Organophosphorus Compounds , Organotechnetium Compounds , Radiopharmaceuticals , Vasodilator Agents , Adolescent , Child , Child, Preschool , Coronary Circulation/physiology , Female , Heart Diseases/etiology , Heart Diseases/physiopathology , Humans , Infant , Male , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/physiopathology , Reproducibility of Results , Sensitivity and Specificity
14.
Abdom Imaging ; 27(4): 442-7, 2002.
Article in English | MEDLINE | ID: mdl-12066243

ABSTRACT

BACKGROUND: The incidence of postoperative wound infection is higher after colorectal surgery than after other surgical procedures. No studies have evaluated the usefulness of gallium 67 scintigraphy for detecting wound infection after colorectal surgery. We investigated the clinical potential of gallium imaging for detecting wound infection after colorectal surgery. METHODS: Fifty patients who had fever after colorectal surgery were enrolled in this study. All patients had open surgical incisions at the midline of the abdomen. Planar gallium scintigraphy was performed 24 h, and then as needed, after the injection of 111 MBq (3 mCi) Ga 67 citrate. All scans were interpreted by two physicians specializing in nuclear medicine. Intensities of gallium uptake at the surgical wound were recorded as grades 0 (no uptake), 1 (less than liver uptake), 2 (equal to liver uptake), or 3 (greater than liver uptake). When the intensity of gallium uptake was equal to or greater than grade 2, gallium uptake was classified as two patterns: regular and irregular. RESULTS: Eighteen patients were diagnosed with wound infection. When interpretation was based on only gallium-uptake intensity, the diagnostic sensitivity, specificity, and accuracy of the gallium scan were 100%, 75%, and 84%, respectively. When interpretation was based on gallium-uptake intensity and pattern, the diagnostic sensitivity and specificity were 94.4% and 96.9%, respectively. The diagnostic accuracy had increased, from 84% to 96%. CONCLUSION: Planar gallium scan is useful for detecting wound infection after colorectal surgery. Gallium-uptake pattern and intensity are important for interpreting planar gallium scans.


Subject(s)
Citrates , Colon/surgery , Gallium Radioisotopes , Gallium , Radiopharmaceuticals , Rectum/surgery , Surgical Wound Infection/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Colonic Neoplasms/surgery , Female , Humans , Male , Middle Aged , Radionuclide Imaging , Rectal Neoplasms/surgery , Surgical Wound Infection/etiology
15.
Nucl Med Biol ; 29(3): 339-44, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11929704

ABSTRACT

The aim of this study was to investigate the relationships among technetium-99m tetrofosmin (Tc-TF) accumulation in parathyroid adenoma and the expression of P-glycoprotein (Pgp) or multidrug resistance related protein (MRP). Before operation, 33 patients with parathyroid adenomas (larger than 1.5 gm) were studied with parathyroid scintigraphy 10 minutes and 2 hours after intravenous injection of Tc-TF before operation. Immunohistochemical analyses (IHA) were performed on multiple nonconsecutive sections of operative parathyroid specimens to detect Pgp or MRP expression. According to the results of IHA, the 33 parathyroid adenomas were separated into four groups: (1) 2 adenomas with both positive Pgp and positive MRP expression, (2) 1 adenomas with positive Pgp but negative MRP expression, (3) 2 adenomas with negative Pgp but positive MRP expression, and (4) 28 adenomas with both negative Pgp and negative MRP expression. All of 28 adenomas in the group 4 could be detected by Tc-TF parathyroid imaging. All of 5 adenomas in the groups 1 to 3 could not be detected by TcTF parathyroid imaging (p < 0.05). Not only the size of parathyroid adenomas, but also significant Pgp or MRP expression limited the sensitivity of Tc-TF parathyroid imaging to localize parathyroid adenomas before operation.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , Adenoma/diagnostic imaging , Adenoma/metabolism , Gene Expression Regulation, Neoplastic/physiology , Genes, MDR/genetics , Organophosphorus Compounds , Organotechnetium Compounds , Parathyroid Neoplasms/diagnostic imaging , Parathyroid Neoplasms/metabolism , Radiopharmaceuticals , Adult , Female , Humans , Immunohistochemistry , Male , Middle Aged , Organophosphorus Compounds/pharmacokinetics , Organotechnetium Compounds/pharmacokinetics , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics
16.
Proc Natl Acad Sci U S A ; 98(26): 14808-13, 2001 Dec 18.
Article in English | MEDLINE | ID: mdl-11752428

ABSTRACT

As the first structural elucidation of a modular polyketide synthase (PKS) domain, the crystal structure of the macrocycle-forming thioesterase (TE) domain from the 6-deoxyerythronolide B synthase (DEBS) was solved by a combination of multiple isomorphous replacement and multiwavelength anomalous dispersion and refined to an R factor of 24.1% to 2.8-A resolution. Its overall tertiary architecture belongs to the alpha/beta-hydrolase family, with two unusual features unprecedented in this family: a hydrophobic leucine-rich dimer interface and a substrate channel that passes through the entire protein. The active site triad, comprised of Asp-169, His-259, and Ser-142, is located in the middle of the substrate channel, suggesting the passage of the substrate through the protein. Modeling indicates that the active site can accommodate and orient the 6-deoxyerythronolide B precursor uniquely, while at the same time shielding the active site from external water and catalyzing cyclization by macrolactone formation. The geometry and organization of functional groups explain the observed substrate specificity of this TE and offer strategies for engineering macrocycle biosynthesis. Docking of a homology model of the upstream acyl carrier protein (ACP6) against the TE suggests that the 2-fold axis of the TE dimer may also be the axis of symmetry that determines the arrangement of domains in the entire DEBS. Sequence conservation suggests that all TEs from modular polyketide synthases have a similar fold, dimer 2-fold axis, and substrate channel geometry.


Subject(s)
Esterases/chemistry , Membrane Proteins/chemistry , Multienzyme Complexes/chemistry , Amino Acid Sequence , Dimerization , Leucine/chemistry , Molecular Sequence Data , Protein Conformation , Recombinant Proteins/chemistry , Sequence Homology, Amino Acid
18.
Rheumatology (Oxford) ; 40(10): 1106-11, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11600739

ABSTRACT

OBJECTIVES: Systemic lupus erythematosus (SLE) can affect multiple organs. Coronary artery disease has received increasing recognition as a major cause of morbidity and mortality in SLE in recent years. The purpose of this study was to evaluate the utility of technetium-99m sestamibi single-photon emission computed tomography ((99m)Tc-sestamibi SPECT) in the detection of cardiovascular involvement in SLE patients with non-specific clinical chest symptoms such as chest discomfort and/or dyspnoea and/or occasional palpitation. METHODS: Thirty-three SLE female patients (age range: 22-45 yr) with non-specific complaints such as chest discomfort and/or dyspnoea and/or occasional palpitation were investigated using a (99m)Tc-sestamibi myocardial perfusion SPECT scan at rest and after dipyridamole infusion in a stress study. The age- and sex-matched healthy group (24 cases) and SLE patients without any cardiovascular symptoms/signs (28 cases) were also included as controls in this study. The results of the uptake pattern of (99m)Tc-sestamibi were classified into four types including normal, persistent perfusion defect, reversible perfusion defect and reverse redistribution. RESULTS: Perfusion abnormalities were detected in 27 cases (seven patients had persistent perfusion defects, 15 patients had reversible perfusion defects, one patient had both persistent and reversible perfusion defects, two patients showed a reverse redistribution pattern and two patients had both reversible perfusion defects and a reverse redistribution pattern). The results of the SPECT in the healthy group were all normal. However, perfusion abnormalities were detected in 12 cases in the group of asymptomatic SLE patients. CONCLUSIONS: (99m)Tc-sestamibi myocardial perfusion SPECT is a useful non-invasive imaging modality to detect cardiovascular involvement in SLE patients with non-specific clinical complaints of heart disease.


Subject(s)
Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/etiology , Coronary Circulation , Lupus Erythematosus, Systemic/complications , Tomography, Emission-Computed, Single-Photon , Adult , Chest Pain/diagnostic imaging , Dyspnea/diagnostic imaging , Female , Humans , Middle Aged , Radiopharmaceuticals , Technetium Tc 99m Sestamibi
19.
Int J Cardiovasc Imaging ; 17(4): 271-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11599866

ABSTRACT

'Syndrome X' describes patients with exertional chest pain and a normal coronary arteriogram. In some patients, acute myocardial ischemia can be demonstrated by regional myocardial perfusion defects on thallium-201 exercise test. However, some patients with typical angina have normal perfusion on thallium-201 heart scintigraphy. It is not clear whether there are different prognoses for patients with normal and abnormal thallium studies. In this study, the clinical features, long term follow-up and clinical results of syndrome X patients with normal and abnormal thallium studies were evaluated to determine the differences between these two groups. Fifty-nine patients (52 males, seven females, mean age 62+/-6 years) with syndrome X were enrolled and divided into two groups on the basis of results of thallium-201 heart scintigraphy. Group I was comprised of 22 patients with normal thallium-201 perfusion scan and group II was comprised of 37 patients with abnormal thallium-201 heart scan. All subjects received coronary arteriography, exercise test, thallium-201 myocardial SPECT, ejection fraction of left ventricle, echocardiography, blood analysis and long term follow-up with questionnaire for 10 years. Lower maximal rate-pressure product and higher angina scores were found in group II. More patients developed cardiomegaly (nine of 33 patients) in group II than in group I (one of 21 patients). Both groups, however, were at low risk for cardiac events (cardiac death or myocardial infarction).


Subject(s)
Cardiomegaly/complications , Cardiomegaly/diagnosis , Cardiomyopathies/diagnostic imaging , Microvascular Angina/complications , Microvascular Angina/diagnosis , Thallium Radioisotopes , Tomography, Emission-Computed, Single-Photon , Aged , Coronary Angiography , Female , Follow-Up Studies , Humans , Hypertension/complications , Hypertension/diagnosis , Male , Middle Aged , Perfusion , Prognosis , Stroke Volume/physiology
20.
J Med Chem ; 44(22): 3746-9, 2001 Oct 25.
Article in English | MEDLINE | ID: mdl-11606139

ABSTRACT

1-Benzyl-3-(5'-hydroxymethyl-2'-furyl)indazole (28, YC-1) was selected as the lead compound for systemic structural modification. After screening for antiplatelet activity, SARs of YC-1 analogues were established. Among these potent active derivatives, compounds 29, 30, 31, 44, and 45 functioned as potent activators of sGC and inhibitors of PDE5 with potency comparable to that of YC-1. In addition, compound 58 was found to be a selective and potent inhibitor of protease-activated receptor type 4 (PAR4)-dependent platelet activation.


Subject(s)
Indazoles/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , 3',5'-Cyclic-GMP Phosphodiesterases/antagonists & inhibitors , Cyclic Nucleotide Phosphodiesterases, Type 5 , Enzyme Activation , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Guanylate Cyclase , Humans , In Vitro Techniques , Indazoles/chemistry , Indazoles/pharmacology , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/pharmacology , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Thrombin/antagonists & inhibitors , Soluble Guanylyl Cyclase , Structure-Activity Relationship
SELECTION OF CITATIONS
SEARCH DETAIL
...