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Marked Rise (marked + rise)
Selected AbstractsCETP inhibition in cardiovascular risk management: a critical appraisalEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2007R. P. F. Dullaart Abstract In view of the cardioprotective effect of high-density lipoproteins (HDL) and the limited effects of statin and fibrate therapy on HDL cholesterol, it is clinically relevant to test whether pharmacological treatment aimed at raising HDL lowers cardiovascular risk. Cholesteryl ester transfer protein (CETP) is a new therapeutic target, because the cholesteryl ester transfer process lowers HDL cholesterol and contributes to an atherogenic lipoprotein profile, particularly when plasma triglycerides are high. Clinical evidence suggests that coronary artery calcification as well as intima media thickness is positively related to plasma cholesteryl ester transfer, and that high plasma CETP concentration is associated with increased cardiovascular risk in hypertriglyceridaemia. However, CETP could also have anti-atherogenic potential, since it provides a potentially beneficial route for delivery of HDL-derived cholesteryl esters to the liver. In addition, CETP could also favourably stimulate peripheral cell cholesterol removal and enhance hepatic cholesterol uptake. Recent evidence suggests that a high CETP level may confer lower cardiovascular risk in the context of low triglycerides. At maximal doses, the CETP inhibitors JTT-705 and torcetrapib elicit a marked rise in HDL cholesterol of up to 34% and 91,106%, respectively. The effectiveness of these drugs on (intermediate) clinical outcome measures is currently being tested in large-scale phase III clinical trials, with torcetrapib being only evaluated in combination therapy with atorvastatin. When and how to use CETP inhibitors, e.g. in combination with a statin or a fibrate, is a major challenge. We propose that low HDL cholesterol in the context of high triglycerides, such as found in type 2 diabetes mellitus, could become an important indication area for this new class of drugs. [source] Nitrogen Rates and Water Stress Effects on Production, Lipid Peroxidation and Antioxidative Enzyme Activities in Two Maize (Zea mays L.) GenotypesJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 6 2007L.-X. Zhang Abstract Effects of nitrogen rates and water stress (WS) on production, lipid peroxidation and antioxidative enzyme activities in two maize (Zea mays L.) genotypes were assessed at different stages under two levels of water supply conditions. WS caused a significant decline in dry matter, grain yield and activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) whereas a marked rise in malondialdehyde (MDA) concentration was observed in leaves for the two genotypes. However, the responses of the two varieties to WS were different: significantly higher dry matter, grain yield and antioxidative enzyme activities and lower MDA content were observed for Shaandan 9 than Shaandan 911, therefore the former could be treated as a drought tolerance variety comparatively. A better correlation was obtained amongst dry matter, grain yield and physiological traits. The addition of nitrogen increased dry matter and grain yield as well as activities of SOD, POD and CAT to different levels and significantly decreased MDA content under WS. These effects were higher for Shaandan 911 than for Shaandan 9. Furthermore, a significant effect was found for Shaandan 911 between N rates for all traits unlike Shaandan 9. Hence, we suggest that nitrogen should be applied to a water-sensitive variety to bring out its potential fully under drought. [source] Changes in Bone Density During Childhood and Adolescence: An Approach Based on Bone's Biological OrganizationJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2001Frank Rauch Abstract Bone densitometry has great potential to improve our understanding of bone development. However, densitometric data in children rarely are interpreted in light of the biological processes they reflect. To strengthen the link between bone densitometry and the physiology of bone development, we review the literature on physiological mechanisms and structural changes determining bone mineral density (BMD). BMD (defined as mass of mineral per unit volume) is analyzed in three levels: in bone material (BMDmaterial), in a bone's trabecular and cortical tissue compartments (BMDcompartment), and in the entire bone (BMDtotal). BMDmaterial of the femoral midshaft cortex decreases after birth to a nadir in the first year of life and thereafter increases. In iliac trabecular bone, BMDmaterial also increases from infancy to adulthood, reflecting the decrease in bone turnover. BMDmaterial cannot be determined with current noninvasive techniques because of insufficient spatial resolution. BMDcompartment of the femoral midshaft cortex decreases in the first months after birth followed by a rapid increase during the next 2 years and slower changes thereafter, reflecting changes in both relative bone volume and BMDmaterial. Trabecular BMDcompartment increases in vertebral bodies but not at the distal radius. Quantitative computed tomography (QCT) allows for the determination of both trabecular and cortical BMDcompartment, whereas projectional techniques such as dual-energy X-ray absorptiometry (DXA) can be used only to assess cortical BMDcompartment of long bone diaphyses. BMDtotal of long bones decreases by about 30% in the first months after birth, reflecting a redistribution of bone tissue from the endocortical to the periosteal surface. In children of school age and in adolescents, changes in BMDtotal are site-specific. There is a marked rise in BMDtotal at locations where relative cortical area increases (metacarpal bones, phalanges, and forearm), but little change at the femoral neck and midshaft. BMDtotal can be measured by QCT at any site of the skeleton, regardless of bone shape. DXA allows the estimation of BMDtotal at skeletal sites, which have an approximately circular cross-section. The system presented here may help to interpret densitometric results in growing subjects on a physiological basis. [source] Monochloramine impairs mucosal blood flow response and healing of gastric lesions in rats: Relation to capsaicin-sensitive sensory neuronsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2001Koji Takeuchi Abstract Aims: We examined the effects of monochloramine (NH2Cl) on the gastric mucosal blood flow (GMBF) response and the healing of ethanol-induced gastric lesions in rats. Methods: Rats fasted for 18 h were given the 99% ethanol p.o. for induction of gastric lesions, and were fed normally from 1 h later onwards. Monochloramine, at non-ulcerogenic doses (5~20 mmol/L), was given p.o. twice daily for 7 days, starting 2 h after ethanol treatment. Results: Gastric lesions caused by ethanol healed almost completely within 7 days with re-epithelialization. The repeated administration of NH2Cl significantly delayed the healing of ethanol-induced gastric lesions in a dose-dependent manner. The damaged mucosa showed a marked rise in H+ permeability, resulting in luminal acid loss, but this process was accompanied by an increase of mucosal blood flow. Monochloramine did not affect the increased mucosal H+ permeability observed in the stomach after damage by ethanol, but significantly inhibited the mucosal hyperemic response associated with luminal acid loss. Prior exposure of the mucosa to NH2Cl (20 mmol/L) did not affect the gastric hyperemic response caused by mucosal application of misoprostol (a prostaglandin E1 derivative) or NOR-3 (a nitric oxide donor), but totally attenuated the increase of GMBF in response to intragastric capsaicin. Impaired healing and GMBF responses were also observed in rats following chemical ablation of capsaicin-sensitive sensory neurons. Conclusions: These results suggest that NH2Cl impaired the healing of acute gastric mucosal lesions at low concentrations, and this action may be attributable, at least partly, to the impairment of gastric hyperemic response caused by the dysfunction of capsaicin-sensitive sensory neurons. [source] Glutamate-mediated influx of extracellular Ca2+ is coupled with reactive oxygen species generation in cultured hippocampal neurons but not in astrocytesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1-2 2005Stefan Kahlert Abstract Generation of reactive oxygen species (ROS) in brain tissue leads to neurodegeneration. The major source of ROS is the mitochondrial respiratory chain. We studied regulation of Ca2+ level, mitochondrial potential, and ROS generation in defined mixed hippocampal cell cultures exposed to glutamate (100 ,M). Recordings were made from individually identified astrocytes and neurons to compare the physiologic responses in both cell types. Neurons identified by synaptotagmin immunoreactivity were characterized functionally by the fast Ca2+ increase with K+ (50 mM) stimulation, and the astrocytes identified by glial fibrillary acidic protein (GFAP) staining had the functional characteristic of a transient Ca2+ peak in response to ATP (10 ,M) stimulation. We found that the glutamate-mediated Ca2+ response in neurons is due largely to influx of extracellular Ca2+. This is consistent with our finding that in cultured hippocampal neurons, stores depending on the activity of the sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) pump had a low Ca2+ content, regardless of whether the neurons were challenged or not with K+ before applying the SERCA inhibitor cyclopiazonic acid (CPA). Astrocytes displayed a large CPA-mediated Ca2+ response, indicating a high level of Ca2+ load in the stores in astrocytes. Importantly, the rise in ROS generation due to glutamate application was cell-type specific. In neurons, glutamate induced a marked rise in generation of ROS, but not in astrocytes. In both astrocytes and neurons, the mitochondrial potential was increased in response to glutamate challenge. We conclude that in neurons, Ca2+ influx accounts for the increased ROS generation in response to glutamate. This might explain the high vulnerability of neurons to glutamate challenge compared to the vulnerability of astrocytes. The high resistance of astrocytes is accompanied by an efficient downregulation of cytosolic Ca2+, which is not found in neurons. © 2004 Wiley-Liss, Inc. [source] Role of melatonin in mucosal gastroprotection against aspirin-induced gastric lesions in humansJOURNAL OF PINEAL RESEARCH, Issue 4 2010P. C. Konturek Abstract:, Melatonin and its precursor, l -tryptophan, have been shown to exert gastroprotective effects in animals, but their influence on the gastric damage by aspirin (ASA) in humans has been sparingly investigated. In this study, we designed to determine the effects of melatonin and l -tryptophan on ASA-induced gastric mucosal damage, gastric microbleeding, mucosal generation of prostaglandin E2, and plasma melatonin, and gastrin levels. Three groups of healthy male volunteers (n = 30) with intact gastric mucosa received daily for 11 days either ASA alone or that combined with melatonin or tryptophan. Gastric blood loss and mucosal damage were evaluated at 3rd, 7th, and 11th days of ASA administration by endoscopy using Lanza score. ASA alone caused a marked rise of gastric damage and gastric blood loss, mainly at day 3rd and 7th, but they were significantly reduced at 11th day. Pretreatment with melatonin or tryptophan remarkably reduced ASA-induced gastric lesions and microbleeding. Gastric mucosal generation of PGE2 was suppressed by about 90% in all subjects treated with ASA alone without or with addition of melatonin or tryptophan. Plasma melatonin was markedly increased after treatment with melatonin or tryptophan plus ASA, but it was also raised significantly after application of ASA alone. Plasma gastrin levels were raised in subjects given melatonin or tryptophan plus ASA, but not in those with ASA alone. We conclude that melatonin and its precursor tryptophan given orally significantly reduce gastric lesions induced by ASA possibly due to (a) direct gastroprotective action of exogenous melatonin or that generated from tryptophan and (b) gastrin released from the gastric mucosa by melatonin or tryptophan. [source] A profile of invasive cutaneous malignant melanoma in Malta: 1993,2002JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 8 2006S Aquilina Abstract Background, The incidence of malignant melanoma of the skin has risen in every part of the world where reliable cancer registration data are found. Objective, Our study aims to describe the changing incidence of and survival from invasive cutaneous malignant melanoma in Malta, by analysing the data from the 211 cases that were registered at the Malta National Cancer Registry between 1993 and 2002. Results, The age standardized incidence rates for invasive cutaneous malignant melanoma rose from 3.7 per 100 000 population per year for males and 5.1 for females in the first 5-year period, to 8.0 per 100 000 population per year for males and 5.9 for females in the second 5-year period. In both sexes, numbers of thin (, 1.0 mm) invasive melanomas increased significantly between 1993 and 2002; males also registered a significant increase in intermediate-thickness (1.01,4.0 mm) melanomas. The increase in numbers of thin and intermediate-thickness melanomas between the two 5-year periods was greatest in patients aged 60 years and over. The overall absolute 5-year survival rate for the first period was 74% and for the second period 92%. Conclusion, Numbers of reported cases of invasive cutaneous malignant melanoma in Malta have more than doubled during the 10-year study period. This is mostly due to a marked rise in the diagnosis of thin melanomas in both sexes, occurring mainly in patients aged 60 years and over. As thin melanomas are of low metastasizing potential, this has resulted in an increase in survival between the two 5-year study periods. [source] Ranula: another HIV/AIDS associated oral lesion in Zimbabwe?ORAL DISEASES, Issue 4 2004MM Chidzonga Aim:, To show that sublingual ranula is associated with HIV/AIDS and as such should be considered an HIV/AIDS associated oral lesion in Zimbabwe. Objectives:, To retrospectively study the prevalence, age and gender distribution, the HIV serostatus of ranula patients and the trend in prevalence of ranula and Kaposi's sarcoma (KS) in patients at the two largest referral Oral and Maxillofacial Surgery specialist centres in Harare, Zimbabwe. To use this information to infer an association between ranula and HIV/AIDS in Zimbabwe. Design:, Descriptive study with a retrospective and prospective component. Setting:, Oral and Maxillofacial Surgical clinics at specialist referral hospitals, Harare Central Hospital and Parirenyatwa Government Hospital, Harare, Zimbabwe. Subjects:, Eighty-three cases of ranula were studied: 45 cases retrospectively and 38 consecutively. A total of 231 cases of KS were studied retrospectively. Methods:, Histopathologic records of patients who presented with ranula and KS during the period January 1981 to September 2003 were studied. Gender and age were recorded for each case. Thirty-eight ranula patients studied consecutively during the period June 1999 to September 2003 were consented for HIV testing. Results:, There were 83 cases of ranula; 43.4% male and 56.6% female. There were 231 cases of KS, 61.2% male and 38.8% female. Male to female ratio was 1:1.3 for ranula and for KS was 1:0.6. Ranula was predominant in the 0,10 year age group (73.5%) while KS was most common in the 21,40 year age group (76.4%). Ranula and KS both had a marked rise in prevalence from 1992 to 2003. A total of 88.5% of the ranula cases tested HIV positive with 95% in the 0,10 year age group. Conclusion:, There was a rising prevalence of ranula which mirrors that of KS (an HIV/AIDS associated oral lesion) and that 88.5% of ranula patients were HIV positive with 95% of them in the 0,10 year age group. Sublingual ranula should thus be considered another HIV/AIDS associated lesion in Zimbabwe, especially in children. [source] Epidemiological study of oesophageal and gastric cancer in south-east England,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 9 2001Mr H. M. Kocher Background: This epidemiological study was carried out to establish the magnitude of the changing incidence of gastric and oesophageal cancer. Methods: Time-trend analyses of subsite-specific cancers of the oesophagus and stomach were performed using data from the Thames Cancer Registry database (1960,1996) for the South Thames Region. The changes in sex ratio and peak age of incidence are reported. Results: In the upper two-thirds of the oesophagus there was no significant change in the incidence rate, but the lower third of the oesophagus showed a marked rise for both sexes (average annual change +0·05 for men, +0·009 for women). For the gastric cardia, the incidence in males increased (average annual change +0·025), while in females it remained unchanged. Cancers of the oesophagogastric junction showed a clear increase for both sexes (average annual change +0·07 for men, +0·009 for women). There were changes in the sex ratio and peak age of incidence for all subsite cancers for both sexes. Conclusion: Over a 37-year period the incidence of cancer of the oesophagogastric junction increased threefold, while the incidence of cancers of the other subsites of the stomach decreased. Further studies are needed to investigate the aetiology of these changes. © 2001 British Journal of Surgery Society Ltd [source] | |||||||||||||