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Selected AbstractsAssessment of parathyroid autotransplantation for preservation of parathyroid function after total thyroidectomyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2003Magdy I. El-Sharaky MD Abstract Background. Hypoparathyroidism with permanent hypocalcemia is a well-recognized complication after thyroid surgery. Aim. This study was conducted to assess the role of immediate parathyroid autotransplantation in the preservation of parathyroid function after total thyroidectomy. Patients and Methods. Twenty-eight patients had autotransplantation of parathyroid glands resected or devascularized during total thyroidectomy. Data were collected prospectively regarding demographics, indication for surgery, operative procedure, pathologic diagnosis, number of glands transplanted, and subsequent course. Thyroid nodules were evaluated by ultrasonography, radionuclide scanning, and/or fine-needle aspiration cytology. All patients had serum ionized calcium, phosphorus, and intact parathyroid hormone (PTH) levels measured preoperatively and monitored regularly postoperatively for a period of 14 weeks and again at 6 months after operation. Patients were categorized into three groups according to the number of glands transplanted: one (group 1, n = 6), two (group 2, n = 14), or three glands (group 3, n = 8). In three other volunteers, one parathyroid gland was transplanted in the brachioradialis and subjected to electron microscopy 1, 2, and 4 weeks after transplantation. Results. Total thyroidectomy was performed for malignant disease in 16 patients (57.1%) and for benign disease in 12 (42.9%) patients. All patients reverted to asymptomatic normocalcemia without the need for any medications within 4 to 14 weeks. Normal levels of serum markers were regained slower when one gland was transplanted compared with two or three glands (P < .01). Electron microscopic examination showed evidence of ischemic degeneration in the transplanted tissues 1 week postoperatively. Regeneration started by the second week and coincided with normalization of PTH levels. Optimum resting and nearly normal status of parathyroid tissue was achieved by the fourth week. Conclusions. This study showed that active PTH production coincides with regeneration of parathyroid cells and that autotransplantation of at least two resected or devascularized glands during total thyroidectomy nearly eliminates permanent postoperative hypoparathyroidism, thus improving the safety of total thyroidectomy performed for malignant or benign disease. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 799,807, 2003 [source] IFN-, induces apoptosis in mouse embryonic stem cells, a putative mechanism of its embryotoxicityDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 3 2000Gang-Ming Zou It has been reported that interferon (IFN)-, should inhibit in vitro mouse embryo growth by direct cell toxicity. However, the mechanism involved has not been clearly established. In the present study, this question was addressed using the embryonic stem (ES) cell model. It was found that IFN-, induces a dose-dependent apoptosis in ES cells, as assessed by trypan-blue staining, by Annexin-V labeling and DNA analysis. Moreover, IFN-, treatment cooperates with Fas-mediated apoptosis, a phenomenon that has been recently reported. As Bcl-2 oncoprotein functions as a death repressor molecule in an evolutionarily conserved cell death pathway, its expression was analyzed by flow cytometry. It was demonstrated that Bcl-2 is expressed in ES cells. When compared to untreated ES cells, IFN-,-treated, apoptotic cells expressed a lower Bcl-2 level and a normal level of Fas, whereas surviving cells expressed a normal level of Bcl-2 but a lower Fas expression. Altogether, these data suggest that IFN-, may influence early mouse embryo development by promoting apoptosis, which may constitute a novel mechanism of IFN-, embryotoxicity. [source] How many cases of Type 2 diabetes mellitus are due to being overweight in middle age?DIABETIC MEDICINE, Issue 1 2007Evidence from the Midspan prospective cohort studies using mention of diabetes mellitus on hospital discharge or death records Abstract Aims To relate body mass index (BMI) in middle age to development of diabetes mellitus. Methods Participants were 6927 men and 8227 women from the Renfrew/Paisley general population study and 3993 men from the Collaborative occupational study. They were aged 45,64 years and did not have reported diabetes mellitus. Cases who developed diabetes mellitus, identified from acute hospital discharge data and from death certificates in the period from screening in 1970,1976 to 31 March 2004, were related to BMI at screening. Results Of Renfrew/Paisley study men 5.4%, 4.8% of women and 5% of Collaborative study men developed diabetes mellitus. Odds ratios for diabetes mellitus were higher in the overweight group (BMI 25 to < 30 kg/m2) than in the normal weight group (BMI 18.5 to < 25 kg/m2) and highest in the obese group (BMI , 30 kg/m2). Compared with the normal weight group, age-adjusted odds ratios for overweight and obese Renfrew/Paisley men were 2.73 [95% confidence interval (CI) 2.05, 3.64] and 7.26 (95% CI 5.26, 10.04), respectively. Further subdividing the normal, overweight and obese groups showed increasing odds ratios with increasing BMI, even at the higher normal level. Assuming a causal relation, around 60% of cases of diabetes could have been prevented if everyone had been of normal weight. Conclusions Overweight and obesity account for a major proportion of diabetes mellitus, as identified from hospital discharge and death records. With recent increases in the prevalence of overweight, the burden of disease related to diabetes mellitus is likely to increase markedly. Primordial prevention of obesity would be a major strategy for reducing the incidence of diabetes mellitus in populations. [source] Microcystin extracts induce ultrastructural damage and biochemical disturbance in male rabbit testisENVIRONMENTAL TOXICOLOGY, Issue 1 2010Ying Liu Abstract In the present research, the changes of ultrastructures and biochemical index in rabbit testis were examined after i.p. injection with 12.5 ,g/kg microcystin (MC) extracts. Ultrastructural observation showed widened intercellular junction, distention of mitochondria, endoplasmic reticulum, and Golgi apparatus. All these changes appeared at 1, 3, and 12 h, but recovered finally. In biochemical analyses, the levels of lipid peroxidation (MDA) and H2O2 increased significantly at 1 h, indicating MC-caused oxidative stress. Finally, H2O2 decreased to the normal levels, while MDA remained at high levels. The antioxidative enzymes (CAT, SOD, GPx, GST) and antioxidants (GSH) also increased rapidly at 1 h, demonstrating a quick response of the defense systems to the oxidative stress. Finally, the activity of CAT, SOD, and GPX recovered to the normal level, while the activity of GST and the concentration of GSH remained at a high level. This suggests that the importance of MCs detoxification by GST via GSH, and the testis of rabbit contained abundant GSH. The final recovery of ultrastructure and some biochemical indexes indicates that the defense systems finally succeeded in protecting the testis against oxidative damage. In conclusion, these results indicate that the MCs are toxic to the male rabbit reproductive system and the mechanism underlying this toxicity might to be the oxidative stress caused by MCs. Although the negative effects of MCs can be overcome by the antioxidant system of testis in this study, the potential reproductive risks of MCs should not be neglected because of their wide occurrence. © 2009 Wiley Periodicals, Inc. Environ Toxicol 2010. [source] IRAK-4 kinase activity-dependent and -independent regulation of lipopolysaccharide-inducible genesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2008Magdalena Koziczak-Holbro Abstract IRAK-4 kinase inactive (IRAK-4 KD) knock-in mice display defects in TLR- and IL-1 receptor signaling and are resistant to LPS-induced shock. In the present study we examined the LPS-induced response in IRAK-4 KD mice in more detail. We show that IRAK-4 kinase activity is required for certain aspects of TLR-mediated signaling but not for others. We found that IRAK-4 KD cells displayed reduced JNK and p38 signaling, while NF-,B was activated to a normal level but with delayed kinetics compared to wild-type cells. TLR4-mediated IRF3 activation was intact in these cells. Comprehensive analysis of expression of LPS-inducible genes by microarray demonstrated that IRAK-4 KD cells were severely impaired in the expression of many pro-inflammatory genes, suggesting their dependence on IRAK-4 kinase activity. In contrast, the expression of a subset of LPS-induced genes of anti-viral response was not affected by IRAK-4 kinase deficiency. Additionally, we demonstrate that LPS-activated early expression and production of some cytokines, e.g., TNF-,, is partially induced in the absence of IRAK-4 kinase activity. This suggests that the partially unaffected TLR4-mediated signaling could still drive expression of these genes in early phases and that IRAK-4 kinase activity is important for a more sustained anti-bacterial response. See accompanying commentary http://dx.doi.org/10.1002/eji.200838161 [source] Impaired formation of the inner retina in an AChE knockout mouse results in degeneration of all photoreceptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2004Afrim H. Bytyqi Abstract Blinding diseases can be assigned predominantly to genetic defects of the photoreceptor/pigmented epithelium complex. As an alternative, we show here for an acetylcholinesterase (AChE) knockout mouse that photoreceptor degeneration follows an impaired development of the inner retina. During the first 15 postnatal days of the AChE,/, retina, three major calretinin sublaminae of the inner plexiform layer (IPL) are disturbed. Thereby, processes of amacrine and ganglion cells diffusely criss-cross throughout the IPL. In contrast, parvalbumin cells present a nonlaminar IPL pattern in the wild-type, but in the AChE,/, mouse their processes become structured within two ,novel' sublaminae. During this early period, photoreceptors become arranged regularly and at a normal rate in the AChE,/, retina. However, during the following 75 days, first their outer segments, and then the entire photoreceptor layer completely degenerate by apoptosis. Eventually, cells of the inner retina also undergo apoptosis. As butyrylcholinesterase (BChE) is present at a normal level in the AChE,/, mouse, the observed effects must be solely due to the missing AChE. These are the first in vivo findings to show a decisive role for AChE in the formation of the inner retinal network, which, when absent, ultimately results in photoreceptor degeneration. [source] Azidothymidine causes functional and structural destruction of mitochondria, glutathione deficiency and HIV-1 promoter sensitizationFEBS JOURNAL, Issue 11 2002Tokio Yamaguchi Mitochondrial functional and structural impairment and generation of oxidative stress have been implicated in aging, various diseases and chemotherapies. This study analyzed azidothymidine (AZT)-caused failures in mitochondrial functions, in redox regulation and activation of the HIV-1 gene expression. We monitored intracellular concentrations of ATP and glutathione (GSH) as the indicators of energy production and redox conditions, respectively, during the time-course experiments with U937 and MOLT4 human lymphoid cells in the presence of AZT (0.05 mg·mL,1) or H2O2 (0.01 mm) for 15,25 days. Mitochondrial DNA integrity and NF-,B-driven HIV-1 promoter activity were also assessed. ATP concentration began to decrease within several days after exposure to AZT or H2O2, and the decrease continued to reach 30,40% of the normal level. However, decline of GSH was detectable after a retention period for at least 5,6 days, and progressed likewise. PCR analyses found that mitochondrial DNA destruction occurred when the ATP and GSH depletion had progressed, detecting a difference in the deletion pattern between AZT and H2O2 -treated cells. The GSH decrease coincided with HIV-1 promoter sensitization detected by enhanced DNA binding ability of NF-,B and induction of the gene expression upon H2O2 -rechallenge. Our results suggest that, in the process of AIDS myopathy development, AZT or oxidative agents directly impair the energy-producing system of mitochondria, causing dysfunction of cellular redox control, which eventually leads to loss of the mitochondrial DNA integrity. The mechanism of cellular redox condition-mediated NF-,B activation is discussed. [source] Glucose-Responsive Bioinorganic Nanohybrid Membrane for Self-Regulated Insulin ReleaseADVANCED FUNCTIONAL MATERIALS, Issue 9 2010Claudia R. Gordijo Abstract A bioinorganic nanohybrid glucose-responsive membrane is developed for self-regulated insulin delivery analogous to a healthy human pancreas. The application of MnO2 nanoparticles as a multifunctional component in a glucose-responsive, protein-based membrane with embedded pH-responsive hydrogel nanoparticles is proposed. The bio-nanohybrid membrane is prepared by crosslinking bovine serum albumin (BSA),MnO2 nanoparticle conjugates with glucose oxidase and catalase in the presence of poly(N -isopropyl acrylamide- co -methacrylic acid) nanoparticles. The preparation and performance of this new nanocomposite material for a glucose-responsive insulin release system is presented. The activity and stability of immobilized glucose oxidase and the morphology and mechanical properties of the membrane are investigated. The enzymatic activity is well preserved in the membranes. The use of MnO2 nanoparticles not only reinforces the mechanical strength and the porous structure of the BSA-based membrane, but enhances the long-term stability of the enzymes. The in vitro release of insulin across the membrane is modulated by changes in glucose concentration mimicking possible fluctuations of blood-glucose level in diabetic patients. A four-fold increase in insulin permeation is observed when the glucose concentration is increased from normal to hyperglycemic levels, which returns to the baseline level when the glucose concentration is reduced to a normal level. [source] The lowering effect of high copper intake on selenium retention in weanling rats depends on the selenium concentration of the dietJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2001S. Yu The question addressed was whether the influence of dietary copper concentration on selenium metabolism depends on the amount of selenium in the diet. Weanling, male rats were fed purified diets containing either 1 (low), 4 (normal) or 42 (high) mg Cu/kg diet and either 0.03 (low), 0.05 (normal) or 1.0 (high) mg Se/kg diet in a 32 factorial design. Extra copper was added to the diets in the form of CuSO4,·,5H2O and selenium as Na2SeO3,·,5H2O. In rats fed either the low or normal amounts of selenium, higher intakes of copper decreased the apparent intestinal selenium absorption and increased urinary selenium excretion. The effects of copper on selenium absorption, excretion and retention were not seen in rats fed the high-selenium diets. An increase in dietary copper concentrations elevated selenium concentrations in the liver and kidneys, but slightly lowered those in the spleen of rats that were fed the diets with the normal level of selenium. In rats that were fed the diets with either low or high selenium concentration, copper intake had no effect on organ selenium concentrations. Glutathione peroxidase activity in erythrocytes was raised by feeding the diets which contained either normal or high copper content instead of those that were low in copper. It is concluded that the amount of selenium in the diet determines whether or not an increase in dietary copper concentration affects selenium metabolism. [source] Effects of estrogen and progesterone treatment on rat hippocampal NMDA receptors: Relationship to Morris water maze performanceJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2004Nahid K. El-Bakri Abstract Estrogen modulates NMDA receptors function in the brain. It increases both dendritic spine density and synapse number in the hippocampus, an effect that can be blocked by NMDA antagonist. In this study, we investigated the effect of 17,-estradiol and progesterone treatment on NMDA receptors in ovariectomized rats. Two different doses were used for 10 weeks. Receptor autoradiography was done on brain sections using [3H] MK-801 as a ligand. Our results showed a significant increase in [3H] MK-801 binding in the dentate gyrus, CA3 and CA4 areas of the hippocampus of ovariectomized compared to sham operated rats. In addition, we observed similar changes in CA1. 17,-estradiol treatment in both doses reduced the binding back to the normal level while progesterone treatment did not show any effect. Spatial reference memory was tested on Morris water maze task. Ovariectomy severely impaired spatial reference memory. Estradiol but not progesterone treatment significantly improved the memory performance of the ovariectomized rats. Low dose treatment showed better learning than high dose estrogen treatment. The decrease in the antagonist sites by estradiol treatment could result in an increase in the sensitivity of the hippocampus to the excitatory stimulation by glutamate system and hence the effect of estradiol on learning and memory. The changes of NMDA receptors in the hippocampus support the concept that estrogen-enhancing effect on spatial reference memory could be through the enhancing of NMDA function. [source] Are mice calorically restricted in nature?AGING CELL, Issue 4 2003Steven N. Austad Summary An important question about traditional caloric restriction (CR) experiments on laboratory mice is how food intake in the laboratory compares with that of wild mice in nature. Such knowledge would allow us to distinguish between two opposing views of the anti-aging effect of CR , whether CR represents, in laboratory animals, a return to a more normal level of food intake, compared with excess food consumption typical of laboratory conditions or whether CR represents restriction below that of animals living in nature, i.e. the conditions under which house mice evolved. To address this issue, we compared energy use of three mouse genotypes: (1) laboratory-selected mouse strains (= laboratory mice), (2) house mice that were four generations or fewer removed from the wild (= wild-derived mice) and (3) mice living in nature (= wild mice). We found, after correcting for body mass, that ad libitum fed laboratory mice eat no more than wild mice. In fact, under demanding natural conditions, wild mice eat even more than ad libitum fed laboratory mice. Laboratory mice do, however, eat more than wild-derived mice housed in similar captive conditions. Therefore, laboratory mice have been selected during the course of domestication for increased food intake compared with captive wild mice, but they are not particularly gluttonous compared with wild mice in nature. We conclude that CR experiments do in fact restrict energy consumption beyond that typically experienced by mice in nature. Therefore, the retarded aging observed with CR is not due to eliminating the detrimental effects of overeating. [source] Palliation in cancer of the oesophagus , what passes down an oesophageal stent?JOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 5 2003A. Holdoway Introduction: Self-expanding metal stents are becoming an increasingly popular method of palliation of dysphagia in advanced oesophageal carcinoma. Approximately 10% require intervention post-placement because of blockage (Angorn, 1981). This could be prevented by effective dietary advice. We set out to write evidence-based dietary guidelines for patients undergoing oesophageal stent insertion. A comprehensive literature search failed to identify evidence to support the present guidelines used by manufacturers and dietitians on foods allowed or to avoid and the use of fizzy drinks to ,clean' the stent. Only reference on the ability to consume a semi-solid or solid diet was made (Nedin, 2002). We therefore tested the ability of 50 foods to pass through a stent and the efficacy of fizzy water in unblocking an occluded stent. Method: Normal mouthfuls of raw and cooked, peeled/unpeeled fruit and vegetables, casseroles, griddle or grilled plain meat, poultry or fish, eggs, nuts, dried fruit and bread in various forms were tested. An adult female chewed a ,normal' mouthful of each test food and at the point of swallowing the bolus of food was passed into an expanded Ultraflex metal covered stent (internal diameter 18 mm). If occlusion occurred, water was dribbled through the stent, simulating swallowing fluid, in an attempt to unblock the stent. If the occlusion remained, the stent was agitated to mimic advice given about moving around to unblock a stent in a patient. If it remained occluded, a smaller amount of food, approximately half a mouthful, was chewed for twice as long and re-tested. To test the efficacy of fizzy water to clear an occlusion, we compared the ability of water, warm water and fizzy water to unblock a stent artificially occluded with a bolus of bread. Results: Foods that occluded the stent but passed through if eaten in half mouthfuls and chewed for twice normal chewing time included sandwiches, dry toast, apple, tinned pineapple, fresh orange segments with pith removed, up to six sultanas, chopped dried apricot, boiled egg, muesli, meat and poultry. Dry meat, fruit with pith, skins of capsicum peppers and tomatoes, more than seven sultanas and dried apricots caused occlusion. Nuts and vegetables such as lettuce, which are cited in many diet sheets as items to avoid (Nedin, 2002), passed through the stent when chewed to a normal level. The volumes of fluid required to unblock a stent occluded with bread were 5 l of fizzy water, 3.5 l of cold water or 1 l of warm water. Conclusion: If a patient has good dentition and can chew well and take small mouthfuls and prepare and cook food appropriately, it is likely that they can enjoy a wide variety of solid foods. The use of fizzy drinks to maintain the patency of the stent in patients prone to reflux is questionable, warm fluids may be more efficacious. Based on these initial findings we are updating our dietary guidelines for patients undergoing oesophageal stent insertion and hope to audit stent occlusion following implementation. [source] Favorable efficacy of long-term lamivudine therapy in patients with chronic hepatitis B: An 8-year follow-up studyJOURNAL OF MEDICAL VIROLOGY, Issue 4 2005Norio Akuta Abstract The long-term efficacy of lamivudine therapy in patients with hepatitis B virus (HBV) infection is still not clear. In this study, 20 non-cirrhotic Japanese patients infected with HBV received lamivudine therapy for more than 1 year and were followed for a median period of 8.5 years (range, 6.7,8.7 years). The rates of HBe antigen (HbeAg) negative, HBV-DNA undetectable, and alanine aminotransferase (ALT) normal level at the start of lamivudine were 55%, 25%, and 20% and 85%, 80%, and were 80%, respectively, at the last visit, including patients who received additional treatment. The values at the last visit tended to and were significantly higher than those at the start. The values improved at the last visit regardless of the emergence of YMDD motif mutant and continuation of lamivudine. YMDD mutant and biochemical relapse with mutant virus (breakthrough hepatitis) appeared in 65% and 45% during follow-up, respectively, but severe breakthrough hepatitis occurred in only 5%. Furthermore, 80% of patients who received additional treatment for breakthrough hepatitis, regardless of continuation of lamivudine, were ALT normal level at the last visit, in contrast to 25% untreated. HBsAg clearance occurred in two patients of the discontinuous lamivudine group with non-vertical transmission, who were relatively young. One was infected with HBV genotype C with breakthrough hepatitis and the other had no YMDD mutant and was infected with genotype D, a rare type in Japan. None developed cirrhosis or hepatocellular carcinoma (HCC) during follow-up. Our results suggest that long-term lamivudine therapy improves long-term prognosis, especially when additional treatment for breakthrough hepatitis is used. J. Med. Virol. 75:491,498, 2005. © 2005 Wiley-Liss, Inc. [source] Regulation of glutamate carboxypeptidase II hydrolysis of N -acetylaspartylglutamate (NAAG) in crayfish nervous tissue is mediated by glial glutamate and acetylcholine receptorsJOURNAL OF NEUROCHEMISTRY, Issue 3 2005Albert K. Urazaev Abstract Glutamate carboxypeptidase II (GCPII), a glial ectoenzyme, is responsible for N -acetylaspartylglutamate (NAAG) hydrolysis. Its regulation in crayfish nervous tissue was investigated by examining uptake of [3H]glutamate derived from N -acetylaspartyl-[3H]glutamate ([3H]NAAG) to measure GCPII activity. Electrical stimulation (100 Hz, 10 min) during 30 min incubation with [3H]NAAG increased tissue [3H]glutamate tenfold. This was prevented by 2-(phosphonomethyl)-pentanedioic acid (2-PMPA), a GCPII inhibitor, suggesting that stimulation increased the hydrolysis of [3H]NAAG and metabolic recycling of [3H]glutamate. Antagonists of glial group II metabotropic glutamate receptors (mGLURII), NMDA receptors and acetylcholine (ACh) receptors that mediate axon,glia signaling in crayfish nerve fibers decreased the effect of stimulation by 58,83%, suggesting that glial receptor activation leads to stimulation of GCPII activity. In combination, they reduced [3H]NAAG hydrolysis during stimulation to unstimulated control levels. Agonist stimulation of mGLURII mimicked the effect of electrical stimulation, and was prevented by antagonists of GCPII or mGLURII. Raising extracellular K+ to three times the normal level stimulated [3H]NAAG release and GCPII activity. These effects were also blocked by antagonists of GCPII and mGLURII. No receptor antagonist or agonist tested or 2-PMPA affected uptake of [3H]glutamate. We conclude that NAAG released from stimulated nerve fibers activates its own hydrolysis via stimulation of GCPII activity mediated through glial mGLURII, NMDA and ACh receptors. [source] Triplet pregnancy with partial hydatidiform mole coexisting with two fetuses: A case reportJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4pt2 2008Cheol Hong Kim Abstract Hydatidiform mole with a coexistent fetus is rare, but this condition has recently shown an increased incidence because of assisted reproduction technology. Herein, we report on a case of triplet pregnancy with a partial hydatidiform mole coexisting with two fetuses. It was diagnosed by p57kip2 immunohistochemical staining which is helpful in determining histologically equivocal cases. After termination of pregnancy, the patient was diagnosed with persistent gestational trophoblastic disease. Six courses of methotrexate chemotherapy were performed. Her ,-human chorionic gonadotrophin titers then fell to a normal level. [source] The importance of brain PGE2 inhibition versus paw PGE2 inhibition as a mechanism for the separation of analgesic and antipyretic effects of lornoxicam in rats with paw inflammationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2009Dr Nobuko Futaki Abstract Objectives Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits strong analgesic and anti-inflammatory effects but a weak antipyretic effect in rat models. Our aim was to investigate the mechanism of separation of potencies or analgesic and antipyretic effecls of lornoxicam in relatioin to its effect on prostaglandin E2 (PGE2) production in the inflammatory paw and the brain. Methods A model of acute or chronic paw inflammation was induced by Freund's complete adjuvant injection into the rat paw. Lornoxicam (0.01,1 mg/kg), celecoxib (0.3,30 mg/kg) or loxoprofen (0.3,30 mg/kg) was administered orally to the rats and the analgesic and antipyretic effects were compared. The paw hyperalgesia was assessed using the Randall,Selitto test or the flexion test. Dorsal subcutaneous body temperature was measured as indicator of pyresis. After the measurement of activities, the rats were sacrificed and the PGE2 content in the paw exudate, cerebrospinal fluid or brain hypothalamus was measured by enzme-immunoassay. Key findings In a chronic model of arthritis, lornoxicam, celecoxib and loxoprofen reduced hyperalgesia with an effective dose that provides 50% inhibition (ED50) of 0.083, 3.9 and 4.3 mg/kg respectively, whereas the effective dose of these drugs in pyresis was 0.58, 0.31 and 0.71 mg/kg respectively. These drugs significantly reduced the PGE2 level in paw exudate and the cerebrospinal fluid. In acute oedematous rats, lornoxicam 0.16 mg/kg, celecoxib 4 mg/kg and loxoprofen 2.4 mg/kg significantly reduced hyperalgesia to a similar extent. On the other hand, lornnoxicam did not affect the elevated body temperature, whereas celecoxib and loxoprofen siginificantly reduced the pyrexia to almost the normal level. These drugs significantly reduced the PGE2 level in inflamed paw exudate lo almost the normal level. On the other hand, lornoxicam did not change PGE2 level in the brain hypothalamus, whereas celecoxib and loxoprofen strongly decreased it. Conclusions Lornoxicam exhibits strong analgesic but weak antipyretic effects in rats with paw inflammation. Such a separation of effects is related to its efficacy in the reduction of PGE2 levels in the paw and brain hypothalamus. [source] Anemia and its impact on function in nursing home residents: What do we know?JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 1 2010CRNP Assistant Professor, Valerie K. Sabol PhD Purpose: To provide the advanced practice nurse (APN) information on the prevalence and causes of anemia in elderly nursing home (NH) residents, in order to affect diagnostic and management strategies that may help improve physical function and mobility outcomes. Data Sources: Literature review of current peer-reviewed research articles. Conclusions: In the United States, the prevalence of anemia increases with advancing age, and are reported to be much higher among older NH residents than among community-dwelling older adults. Causes of anemia among the elderly are often multifactorial. Older individuals with anemia, including mild anemia and even low normal level, have demonstrated lower muscle strength, physical function, mobility, and increased morbidity and mortality outcomes. Implications for Practice: Given the potentially significant relationship between anemia and physical performance outcomes among NH residents, gaining a better understanding will help guide future evidence-based care by allowing the APN an opportunity to tailor both medical and restorative care interventions. Because anemia is a potentially modifiable condition, intervention may preserve, limit, or reverse functional impairment and/or disablement, and allow for maximal functional independence. [source] Open-label pilot study of folic acid in patients with nonalcoholic steatohepatitisLIVER INTERNATIONAL, Issue 2 2007Phunchai Charatcharoenwitthaya Abstract: Background/Aims: Folate deficiency disturbs hepatic methionine metabolism and promotes the development of steatohepatitis in animal models. Our aims were (1) to determine the safety and efficacy of folic acid treatment in patients with nonalcoholic steatohepatitis (NASH) on changes in liver biochemistries, and (2) to investigate the presence of subclinical folate deficiency in this population. Methods: Patients with biopsy-proven NASH were treated with folic acid 1 mg/day for 6 months. Liver enzymes and adverse events were monitored every 3 months until completion. Results: Ten patients (one male and nine females) with a median age of 54 years were enrolled in this study. At baseline, the median steatosis grade was 2 (range 1,3), the median necroinflammatory grade was 1 (1,3), and the median fibrosis stage was 2 (0,4). The median level of red cell folate was 526 ng/ml (range 99,708); the normal level was 268,616 ng/ml. One compensated cirrhotic patient had folate deficiency. No serious adverse events occurred. After 6 months of therapy, no significant reductions in serum aspartate and alanine aminotransferase levels (60±25 vs. 54±29, P=0.5 and 86±29 vs. 83±42, P=0.6, respectively), were observed. Serum levels of bilirubin, alkaline phosphatase, albumin, and prothrombin time remained in the normal range during treatment in all patients. Conclusion: Six months of therapy with folic acid at a dose of 1 mg/day, although safe and well tolerated, does not lead to a significant biochemical improvement in patients with NASH. In a small number of patients, folate deficiency was present in only a cirrhotic patient. [source] Serum, liver, and kidney proteomic analysis for the alloxan-induced type I diabetic mice after insulin gene transfer of naked plasmid through electroporationPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 21 2006Wei-Fei Diao Abstract Gene therapy has been reported to be effective in treating diabetes mellitus (DM), while little has been found out about the functional protein changes since. The liver and kidney play important roles in glucose absorption, metabolism, and excretion. Changes in the two organs may reflect pathologic alterations during DM, while the serum has a direct connection with most organs and pathological changes. We used alloxan to induce diabetic mice, electrotranferred the insulin gene into their sural muscles, and discovered that their blood glucose decreased to normal level. Consequently, proteomic approaches were applied to evaluate protein changes in the liver, kidney, and serum of normal, diabetic, and gene transferred mice. Forty-three proteins were found either up-regulated or down-reglulated in the liver, kidney, and serum of the alloxan-induced type I diabetic mice. Only five proteins in the liver, five proteins in the kidney, and seven proteins in the serum of diabetic mice were found to be back-regulated to normal levels after gene transfer. These back-regulated proteins are involved in lipid and glucose metabolism, associated with phosphorylation, signal transduction, oxidation, and immune inflammation. Our findings might promote a better understanding for the mechanism of DM, and provide novel targets for estimating the effects of gene therapy. [source] Safety and efficacy of adeno-associated viral vector-mediated insulin gene transfer via portal vein to the livers of streptozotocin-induced diabetic Sprague-Dawley ratsTHE JOURNAL OF GENE MEDICINE, Issue 5 2005Young Mi Park Abstract Background Previous studies demonstrating the efficacy of insulin gene therapy have mostly involved use of adenoviral vectors or naked DNA to deliver the insulin gene. However, this procedure may not guarantee long-term insulin production. To improve the performance, we prepared recombinant adeno-associated viral vectors (rAAV) harboring the gene encoding a furin-modified human insulin under the cytomegalovirus (CMV) promoter [rAAV-hPPI(F12)]. Methods Streptozotocin (STZ)-induced diabetic Sprague-Dawley rats were used as a diabetic animal model. The levels of blood glucose, insulin, and HbA1c were measured to test the effect. An intraperitoneal glucose tolerance test was performed to test the capability of blood glucose disposal. Immunohistochemical staining and Northern blot analyses were performed to survey the expression pattern of the therapeutic insulin gene. Results STZ-induced diabetic Sprague-Dawley rats infused via the portal vein with rAAV-hPPI(F12) produced human insulin and after a 6-h fast were normoglycemic for over 90 days post-treatment, whereas diabetic rats treated with recombinant adenoviral vector harboring the hPPI(F12) gene [rAV-hPPI(F12)] were normoglycemic only for days 3 to 13 post-treatment. Insulin mRNA was detected mainly in the liver of the rAAV-hPPI(F12)-treated diabetic rats. The glucose tolerance capability of the rAAV-hPPI(F12)-treated diabetic rats was comparable to that of non-diabetic rats, even without injection of recombinant insulin. Furthermore, blood HbA1c concentrations in rAAV-hPPI(F12)-treated diabetic rats were reduced to almost the normal level. Importantly, studies of rAV or rAAV vector-dependent side effects on the targeted liver strongly suggested that only rAAV treatment caused no side effects. Conclusions These results demonstrate that our rAAV-mediated in vivo insulin gene therapy provides safer maintenance of the insulin gene expression required for long-term and thus more effective blood glycemic control. Copyright © 2005 John Wiley & Sons, Ltd. [source] Economic Integration of Yunnan with the Greater Mekong Subregion,ASIAN ECONOMIC JOURNAL, Issue 3 2006Sandra Poncet F14; F15 This paper examines the process of economic integration between the Chinese province of Yunnan and its riparian areas of the Mekong region. The gravity model of trade is used to investigate the evolution of Yunnan's international trade integration between 1988 and 1999. Although Greater Mekong Subregion cooperation efforts have had a positive effect on trade, trade has progressively decreased from an above-standard level to a normal level, according to the gravity model of trade. During this process, Yunnan's trade has increased with other countries such as Singapore, Indonesia and Malaysia. This evolution is in line with Yunnan's development and indicates a progressive re-orientation of its trade toward more developed partners. The results suggest that the Mekong cooperation project has to broaden its perspective, taking into consideration Yunnan's expanding trade relations with countries outside the Greater Mekong Subregion. [source] Competition between Australian native and introduced grasses along a nutrient gradientAUSTRAL ECOLOGY, Issue 5 2003R. H. GROVES Abstract Seven grass species were grown in monocultures and in multispecies mixtures along a gradient of total nutrient levels that ranged from 1/64 to 16× the normal level of nutrient solution. The seven grasses represented three ecological groups: (i) three perennial species native to Australia (Themeda triandra, Poa labillardieri and Danthonia carphoides); (ii) two introduced annuals (Vulpia bromoides and Hordeum leporinum); and (iii) two introduced perennials (Lolium perenne and Dactylis glomerata). We hypothesized that the native grasses would prove less competitive when grown at increased nutrient levels than those introduced from Europe. Results supported the hypothesis. The native species were unable to compete in mixtures even at the lowest nutrient level, where T. triandra was the most productive species in monoculture. Lolium perenne and Dactylis glomerata dominated mixtures at intermediate nutrient levels. The responses of the annual introduced grasses differed in that Vulpia bromoides showed an optimum at intermediate nutrient levels in both monoculture and in mixtures, whereas Hordeum leporinum dominated at the highest nutrient levels in mixture but was suppressed by V. bromoides, L. perenne and D. glomerata at intermediate levels. The results are discussed in terms of predicting species responses in mixtures from their performance in monocultures as well as in terms of previous observations on the sequential changes in botanical composition of south-eastern Australian grasslands after 150 years of continuous grazing by sheep. [source] Long-term results of gastrectomy for ,-fetoprotein-producing gastric cancer,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2010M. Inoue Background: ,-Fetoprotein (AFP)-producing gastric cancer is a rare tumour. It is said to have a high incidence of liver metastasis and poor prognosis. This study sought to evaluate long-term outcomes in such patients. Methods: Records of consecutive patients with gastric carcinoma who underwent preoperative measurement of serum AFP levels and gastrectomy were reviewed to identify those who satisfied the following criteria: preoperative AFP level exceeding 40 ng/ml with a decrease after gastrectomy, or raised preoperative AFP level (10,39 ng/ml) and resected tumour showing histologically characteristic features or immunohistochemically positive AFP production. Results: Of 3374 patients with gastric cancer, 53 (1·6 per cent) met the selection criteria. Tumours were characterized by a high incidence of nodal (79 per cent) or liver (53 per cent) metastasis. Preoperative serum AFP levels showed no correlation with tumour size, depth of invasion, disease stage or survival. The 5-year survival rate was 34 per cent. Five patients survived after recurrence following multimodal treatment. A rising AFP level during follow-up always led to tumour recurrence, but the level remained normal in 11 of 31 patients with recurrence. Conclusion: AFP-producing tumours represent a small subgroup of gastric cancer with high metastatic potential. Postoperative serum AFP level can help predict recurrence but a normal level does not mean absence of recurrence. Prognosis is not as poor as previously thought, and multimodal treatment may be worthwhile even in patients with recurrent tumour. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Cardiac troponin-I as a screening tool for myocarditis in children hospitalized for viral infectionACTA PAEDIATRICA, Issue 2 2010M Renko Abstract Aim:, The incidence of myocarditis in children is uncertain because patients with minor symptoms can remain undiagnosed. We hypothesized that screening all children who are hospitalized for an acute infection with troponin-I (TnI) would reveal myocarditis cases and performed a prospective screening study. Methods:, Between October 2005 and July 2008, a blood sample for TnI measurement was taken every time a sample for C-reactive protein measurement was drawn. If TnI value was above the screening limit (0.06 ,g/L), electrocardiogram (ECG) and cardiac ultrasound were performed. TnI measurements were repeated until at normal level. Results:, Altogether, 1009 children were screened during the 33 months. TnI was above the screening limit (0.06 ,g/L) in six children. None of them had any signs of myocarditis in ECG or cardiac ultrasound. Five of those six children were younger than 30 days. All had a respiratory infection as a cause for hospitalization, three of which was caused by RSV. In four children, all younger than 30 days, TnI levels remained high (>0.37 ,g/L) for two months, but decreased after that to normal levels. Conclusion:, The incidence of myocarditis during viral infections is low and a routine TnI screening for asymptomatic myocarditis is not useful. [source] Self-esteem in a clinical sample of morbidly obese children and adolescentsACTA PAEDIATRICA, Issue 1 2009P Nowicka Abstract Aim: To study self-esteem in clinical sample of obese children and adolescents. Methods: Obese children and adolescents aged 8,19 years (n = 107, mean age 13.2 years, mean BMI 32.5 [range 22.3,50.6], mean BMI z-score 3.22 [range 2.19,4.79]; 50 boys and 57 girls) were referred for treatment of primary obesity. Self-esteem was measured with a validated psychological test with five subscales: physical characteristics, talents and skills, psychological well-being, relations with the family and relations with others. A linear mixed effect model used the factors gender and adolescence group, and the continuous covariates: BMI z-scores, and BMI for the parents as fixed effects and subjects as random effects. Results: Age and gender, but neither the child's BMI z-score nor the BMI of the parents were significant covariates. Self-esteem decreased (p < 0.01) with age on the global scale as well as on the subscales, and was below the normal level in higher ages in both genders. Girls had significantly lower self-esteem on the global scale (p = 0.04) and on the two subscales physical characteristics (p < 0.01) and psychological well-being (p < 0.01). Conclusion: Self-esteem is lower in girls and decreases with age. In treatment settings special attention should be paid to adolescent girls. [source] 2B4 expression on natural killer cells increases in HIV-1 infected patients followed prospectively during highly active antiretroviral therapyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005S. R. Ostrowski Summary Human immunodeficiency virus (HIV)-1 infection influences natural killer (NK) cell expression of inhibitory NK receptors and activating natural cytotoxicity receptors. It is unknown whether expression of the co-stimulatory NK cell receptor 2B4 (CD244) on NK cells and CD3+ CD8+ cells are affected by highly active antiretroviral therapy (HAART), low-level viraemia, proviral-DNA or immune activation in HIV-1 infected patients. A total of 101 HAART-treated HIV-1 infected patients with ,,200 HIV-RNA copies/ml were followed prospectively for 24 months. HIV-RNA was investigated 3-monthly and 2B4 expression on CD3, CD16+ NK cells and CD3+ CD8+ cells, proviral-DNA and plasma soluble tumour necrosis factor receptor (sTNFr)-II were investigated 6-monthly. For comparison, 2B4 expression was investigated in 20 healthy individuals. The concentration of 2B4+ NK cells was initially reduced in HIV-1 infected patients (P < 0·001) but increased to a normal level during the 24 months' follow-up. The concentration of CD3+ CD8+ 2B4+ cells in HIV-1 infected patients was normal and did not change during follow-up. The relative fluorescence intensity (RFI) of 2B4 increased on both NK cells and CD3+ CD8+ cells during follow-up (both P < 0·001). Higher levels of proviral-DNA carrying cells and plasma sTNFrII were associated with reductions in the concentration of 2B4+ NK cells (all P < 0·05). HIV-RNA had no effect on 2B4 expression on NK cells or CD3+ CD8+ cells. These findings demonstrate that the concentration of 2B4+ NK cells normalizes during long-term HAART in HIV-1 infected patients. The finding that proviral-DNA and sTNFrII were associated negatively with the concentration of 2B4+ NK cells suggests that immune activation in HIV-1 infected patients receiving HAART influences the target cell recognition by NK cells. [source] Variation in GH and IGF-I assays limits the applicability of international consensus criteria to local practiceCLINICAL ENDOCRINOLOGY, Issue 1 2007A. Pokrajac Summary Background, There is increasing reliance on consensus criteria for decision making. Recent criteria state that acromegaly is excluded by a nadir GH during an oral glucose tolerance test (OGTT) of < 1 µg/l and a normal level of IGF-I. Objective, To study GH and IGF-I assay performance close to cut-off values for active acromegaly. Design and methods, Two serum samples known to give borderline results were sent to all centres participating in the UK National External Quality Assessment Service (NEQAS). Sample A was assigned to be a nadir during an OGTT and sent for GH assessment to 104 centres. Sample B, with a clinical scenario, was sent to 23 centres that measure IGF-I, and these centres were asked to measure IGF-I, interpret the result and provide the source of their reference ranges (RRs). Results, For sample A, the median GH was 2·6 mU/l (range 1·04,3·5 mU/l). Applying a conversion factor (CF) of 2·0 (1 µg/l = 2 mU/l), the most negatively biased method classified 10% of the values consistent with acromegaly, while the most positively biased method classified all values as consistent with the diagnosis. Applying a CF of 3·0 (1 µg/l = 3 mU/l), only 11% of results were consistent with acromegaly. For sample B, the median IGF-I was 50·8 nmol/l (range 24·3,60·9 nmol/l). All centres used age-related RRs. There was a 50% variation in the upper limit of the RRs between centres. Overall, 30% of the IGF-I results were against the diagnosis. There was little agreement in the RRs quoted by centres using the same method. Conclusion, Variability in assay performance, coupled with use of inappropriate CFs and RRs, undermines the applicability of international consensus criteria to local practice. [source] No relationship between enzyme activity and structure of nucleotide binding site in sarcoplasmic reticulum Ca2+ -ATPase from short-term stimulated rat muscleACTA PHYSIOLOGICA, Issue 4 2009T. Mishima Abstract Aim:, We examined whether structural alterations to the adenine nucleotide binding site (ANBS) within sarcoplasmic (endo) reticulum Ca2+ -ATPase (SERCA) would account for contraction-induced changes in the catalytic activity of the enzyme as assessed in vitro. Methods:, Repetitive contractions were induced in rat gastrocnemius by electrical nerve stimulation. Measurements of sarcoplasmic reticulum properties were performed on control and stimulated muscles immediately after or at 30 min after the cessation of 5-min stimulation. In order to examine the properties at the ANBS, the binding capacity of SERCA to fluorescence isothiocyanate (FITC), a competitive inhibitor at the ANBS, was analysed in microsomes. Results:, Short-term electrical stimulation evoked a 23.9% and 32.6% decrease (P < 0.05) in SERCA activity and in the FITC binding capacity, respectively, in the superficial region of the muscle. Whereas SERCA activity reverted to normal levels during 30-min recovery, a restoration of the FITC binding capacity did not occur. Conclusion:, The discordant changes between the enzyme activity and the FITC binding suggest that, at least during recovery after exercise, changes in SERCA activity may not correlate closely with structural alterations to the ANBS within the enzyme. [source] Diagnosing PNH with FLAER and multiparameter flow cytometryCYTOMETRY, Issue 3 2007D. Robert Sutherland Abstract Background: PNH is an acquired hematopoietic stem cell disorder leading to a partial or absolute deficiency of all glycophosphatidyl-inositol (GPI)-linked proteins. The classical approach to diagnosis of PNH by cytometry involves the loss of at least two GPI-linked antigens on RBCs and neutrophils. While flow assays are more sensitive and specific than complement-mediated lysis or the Hams test, they suffer from several drawbacks. Bacterial aerolysin binds to the GPI moiety of cell surface GPI-linked molecules and causes lysis of normal but not GPI-deficient PNH cells. FLAER is an Alexa488-labeled inactive variant of aerolysin that does not cause lysis of cells. Our goals were to develop a FLAER-based assay to diagnose and monitor patients with PNH and to improve detection of minor populations of PNH clones in other hematologic disorders. Methods: In a single tube assay, we combined FLAER with CD45, CD33, and CD14 allowing the simultaneous analysis of FLAER and the GPI-linked CD14 structure on neutrophil and monocyte lineages. Results: Comparison to standard CD55 and CD59 analysis showed excellent agreement. Because of the higher signal to noise ratio, the method shows increased sensitivity in our hands over single (CD55 or CD59) parameter analysis. Using this assay, we were able to detect as few as 1% PNH monocytes and neutrophils in aplastic anemia, that were otherwise undetectable using CD55 and CD59 on RBC's. We also observed abnormal FLAER staining of blast populations in acute leukemia. In these cases, the neutrophils stained normally with FLAER, while the gated CD33bright cells failed to express normal levels of CD14 and additionally showed aberrant CD45 staining and bound lower levels of FLAER. Conclusion: FLAER combined with multiparameter flow cytometry offers an improved assay for diagnosis and monitoring of PNH clones and may have utility in detection of unsuspected myeloproliferative disorders. © 2007 Clinical Cytometry Society [source] The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticityDEVELOPMENTAL NEUROBIOLOGY, Issue 5 2010Eero Castrén Abstract Recent evidence suggests that neuronal plasticity plays an important role in the recovery from depression. Antidepressant drugs and electroconvulsive shock treatment increase the expression of several molecules, which are associated with neuronal plasticity, in particular the neurotrophin BDNF and its receptor TrkB. Furthermore, these treatments increase neurogenesis and synaptic numbers in several brain areas. Conversely, depression, at least in its severe form, is associated with reduced volumes of the hippocampus and prefrontal cortex and in at least some cases these neurodegenerative signs can be attenuated by successful treatment. Such observations suggest a central role for neuronal plasticity in depression and the antidepressant effect, and also implicate BDNF signaling as a mediator of this plasticity. The antidepressant fluoxetine can reactivate developmental-like neuronal plasticity in the adult visual cortex, which, under appropriate environmental guidance, leads to the rewiring of a developmentally dysfunctional neural network. These observations suggest that the simple form of the neurotrophic hypothesis of depression, namely, that deficient levels of neurotrophic support underlies mood disorders and increases in these neurotrophic factors to normal levels brings about mood recovery, may not sufficiently explain the complex process of recovery from depression. This review discusses recent data on the role of BDNF and its receptors in depression and the antidepressant response and suggests a model whereby the effects of antidepressant treatments could be explained by a reactivation of activity-dependent and BDNF-mediated cortical plasticity, which in turn leads to the adjustment of neuronal networks to better adapt to environmental challenges. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 2010 [source] | ||||||||||||||||||||||||||||||||||||||||