bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Type-2 Diabetes and Troglitazone on the Expression Patterns of Small Intestinal Sugar Transporters and PPAR-Gamma in the Zucker Diabetic Fatty Rat
Authors: Corpe Christopher , Sreenan Seamus , Burant Charles
Published: April 2003

Background/Aims: We have used the Zucker diabetic fatty (ZDF) rat to study the effects of type-2 diabetes and troglitazone on the small intestinal mucosal mass, sugar transporters and the peroxisomal proliferator-activated receptor, PPAR-γ. Methods: Age-matched ZDF and lean control (ZLC) rats were fed a standard chow or a troglitazone-enriched diet for 6 weeks. The mucosa of the small intestines were then extracted, weighed, and SGLT1, GLUT2, GLUT5 and PPAR-γ mRNA expression levels assessed by Northern blotting. In the same animal groups, Western blotting and immunohistochemistry were used to study SGLT1, GLUT2 and GLUT5 protein expression levels and targeting. Results: The ZDF rat small intestinal mucosal mass was 60% greater than the ZLC rat. However, the expression levels of SGLT1, GLUT2, GLUT5 mRNA and protein, and PPAR-γ mRNA in the ZDF and ZLC rats were the same. In addition, the targeting of brush-border GLUT5 and basolateral GLUT2 protein in the ZDF and ZLC rats were the same. Troglitazone treatment reduced SGLT1 mRNA and protein expression levels by 50% in ZDF and ZLC rats, but had no effect on mucosal mass or the expression levels of GLUT2 mRNA and protein, GLUT5 mRNA, and PPAR-γ mRNA. The expression levels of GLUT5 protein in troglitazone-treated ZLC rats were unchanged when compared to untreated ZLC rats. However, GLUT5 protein expression levels in the troglitazone-treated ZDF rats were 50% below the untreated ZDF rats. Conclusions: Hyperphagia and insulin are the chronic regulators of small intestinal mucosal mass and sugar transporter expression patterns, respectively. Furthermore, troglitazone suppresses SGLT1 expression at the transcriptional level and GLUT5 at the post-translational level, independent of changes in glycemia or PPAR-γ gene expression.
Delayed Healing of Gastric Ulcers in Adjuvant Arthritis Rats: Role of Acid Secretion and Basic Fibroblast Growth Factor
Authors: Kato Shinichi , Ogawa Yoshihiro , Tanaka Akiko , Kunikata Tomonori , Takeuchi Koji
Published: April 2003

Background/Aim: We examined the healing process of chronic gastric ulcers in adjuvant-induced arthritic rats and investigated the mechanism for delayed ulcer healing in arthritic rats, in relation to acid secretion and basic fibroblast growth factor (bFGF). Methods: Arthritis was induced in male dark Agouti rats by a single injection of Freund’s complete adjuvant (FCA), while gastric ulcers were induced by thermal cauterization (70°C for 30 s) 7 days after FCA injection. Results: Injection of FCA induced severe arthritis in all animals with a marked acid hypersecretion. The healing of gastric ulcers was significantly delayed in arthritic rats as compared with normal rats. Daily administration of indomethacin delayed ulcer healing in both normal and arthritic rats, but this effect was more pronounced in the latter. In contrast, the healing of gastric ulcers was significantly promoted in both normal and arthritic rats by omeprazole at a dose that inhibited acid secretion completely. The delayed healing of gastric ulcers was not influenced by twice daily administration of NG-nitro-L-arginine methyl ester, aminoguanidine or FR167653 (IL-1/TNF-α synthesis inhibitor), but was significantly accelerated by CS-23 (recombinant human bFGF) in a dose-dependent manner, without effect on the acid secretion. The expression of bFGF was markedly increased after ulceration, but this response was decreased in arthritic rats. Conclusion: The healing of gastric ulcers was delayed in arthritic rats, and this mechanism may be partly attributable to both acid hypersecretion and less expression of bFGF.
Beneficial Effects of a Novel IH636 Grape Seed Proanthocyanidin Extract in the Treatment of Chronic Pancreatitis
Authors: Banerjee Bhaskar , Bagchi Debasis
Published: April 2003

Oxygen-derived free radicals mediate tissue damage in acute and chronic pancreatitis. Low levels of natural antioxidants in pancreatitis indicate their increased utilization as scavengers of free radicals. Combination therapy with selenium, β-carotene, methionine, and vitamins C and E are known to improve symptoms of chronic and recurrent pancreatitis. This, however, requires many tablets to be taken daily, which is impractical and may reduce compliance. Three patients with chronic pancreatitis (two with a history of alcohol excess and one idiopathic) are reported. Treatment with narcotic analgesics and pancreatic enzyme supplements had failed to control their symptoms. The addition of a commercially available IH636 grape seed proanthocyanidin extract (commercially known as ActiVin) to their treatment regimen led to a reduction in the frequency and intensity of abdominal pain as well as resolution of vomiting in 1 patient.
The Immuno-Inflammatory Mechanism for Tissue Injury in Inflammatory Bowel Disease and Helicobacter pylori-Infected Chronic Active Gastritis
Authors: Nagura Hiroshi , Ohtani Haruo , Sasano Hironobu , Matsumoto Takayuki
Published: April 2003

The gastrointestinal mucosa is exposed to myriads of infectious and food antigens, and a unique barrier mechanism handles them on the mucosal surface, and specific immune responses to these antigens call on the mucosal immune system in the mucosal tissues to maintain homeostasis of gastrointestinal functions and structure. Abrogation of these mucosal defense mechanisms may lead to alter immunologic homeostasis in the gastrointestinal tract and to induce pathological features of inflammatory bowel disease (IBD) and Helicobacter pylori-infected chronic active gastritis, including chronic active inflammation, mucosal atrophy and tissue injuries. Regardless of the initiating cause of these long-standing chronic active mucosal inflammations, characteristic immuno-inflammatory mechanisms are involved in their pathogenesis, that is, similar and/or different specific prolonged impaired and excessive immuno-inflammatory responses following the abrogation of the mucosal barrier system are present in the diseased mucosa with IBD and H. pylori infection, respectively.
Increased Secretion of Granulocyte-Macrophage Colony-Stimulating Factor in Mucosal Lesions of Inflammatory Bowel Disease
Authors: Noguchi Mitsunori , Hiwatashi Nobuo , Liu Zhang-xu , Toyota Takayoshi
Published: April 2003

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 transmit a same signal needed for growth and activation in granulocytes and macrophages, because these receptors utilize a common beta chain. Little is known about growth factors for intestinal myeloid cells in lesions of inflammatory bowel disease (IBD). Aim: To find out whether GM-CSF is produced by the intestinal cells in IBD patients and controls. Methods: We measured levels of GM-CSF, tumor necrosis factor (TNF), and IL-3 in the media of organ culture and lamina propria mononuclear cells (LPMCs) culture of colonic mucosa from the patients with IBD. Next, we have investigated GM-CSF production of colonic epithelial cell lines. Results: Spontaneous secretion of GM-CSF was increased in inflamed mucosa, while secretion of IL-3 was not detected. Release of GM-CSF was enhanced in LPMCs from inflamed mucosa. Mucosal GM-CSF production was correlated to TNF-α production. Colonic epithelial cell line and T cell produced GM-CSF with superantigen stimulation. Conclusion: We revealed pivotal production of GM-CSF but not IL-3 in intestinal lesion of IBD. Increased secretion of GM-CSF might lead to chronic gut inflammation.
Role of Granuloma in the Immunopathogenesis of Crohn’s Disease
Authors: Matsumoto Takayuki , Nakamura Shiro , Jin-no Yoshio , Sawa Yoshinori , Hara Jun-ichi , Oshitani Nobuhide , Arakawa Tetsuo , Otani Haruo , Nagura Hiroshi
Published: April 2003

Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) are chronic long-lasting inflammatory diseases with yet unknown etiology. Recent advancement revealed that both diseases are associated with genetic predisposition and environmental factors such as luminal microorganisms and antigens. Crohn’s disease is associated with histopathologic features such as granuloma formation and longitudinal ulceration. In this article we describe the role of granuloma in the immunopathogenesis of Crohn’s disease. Granuloma of Crohn’s disease may play crucial roles as antigen-presenting cites to memory type T cells, which leads to activation and proliferation of T cells. Antigens presented at granuloma may be closely related to the disease.
The Pathogenesis of Crohn’s Disease
Authors: Okabe Nobuo
Published: April 2003

Although much progress has been made in understanding the pathogenesis of Crohn’s disease, the precise etiology of Crohn’s disease still remains unknown. In our serial studies on Crohn’s disease, we found a decrease in NK and ADCC activities as well as a decrease in the phagocytic activity by monocytes, whereas an increased superoxide production activity by monocytes was evident. On the other hand, the characterization of lymphocyte subsets has demonstrated no abnormalities. According to these findings, I would like to propose a new tentative hypothesis for the pathogenesis of Crohn’s disease. It has been suggested that impaired killing system activities, such as phagocytic as well as NK and ADCC activities, are primarily responsible for the promotion and perpetuation of chronic inflammation and ulceration. When our attention is directed to the common target substances of these protective mechanisms, viral antigens appear as the most likely causative organism. Therefore, a lot of attention must be focused on viral infection as a causative factor. Furthermore, effects of psychological and physical stress on the disease onset or the recurrence of inflammatory bowel disease are also discussed.
Intravital Demonstration of Modulation of T Lymphocyte Migration by CINC/gro in Rat Peyer’s Patches
Authors: Fujimori Hitoshi , Miura Soichiro , Koseki Seiichiro , Hokari Ryota , Tsuzuki Yoshikazu , Komoto Shunsuke , Hara Yuriko , Suzuki Hidekazu , Serizawa Hiroshi , Ishii Hiromasa
Published: April 2003

Background/Aims: Cytokine-induced neutrophil chemoattractant (CINC/gro), a member of interleukin-8 family, was found as a potent chemotactic factor for rat neutrophils. Although several chemokines have been shown to be potent regulators of T cell chemotaxis in vitro, the potential role of chemokines in T-cell migration in gut-associated lymphoid tissues has not been investigated in vivo. In the present study, the effects of CINC/gro on T-lymphocyte migration were examined in rat Peyer’s patches. Methods: T lymphocytes collected from intestinal lymph of rats were fluorescence-labeled and injected into the jugular vein. Peyer’s patches of the recipient rats were observed with intravital fluorescence microscopy and the effects of CINC/gro infusion was investigated. Lymphocyte flux in mesenteric collecting lymphatics was also observed. Results: In vivo infusion of CINC/gro significantly attenuated the initial lymphocyte interaction with postcapillary venules of Peyer’s patches. However, once these lymphocytes adhered to venules, CINC/gro treatment significantly accelerated the transendothelial migration of T lymphocytes and they also significantly increased their subsequent flux in collecting lymphatics. Conclusion: There is a possibility that CINC/gro could modulate the characteristics of T lymphocyte homing in the inflammatory sites of gut.
Effect of the Central Nervous System on Mucosal Growth and Apoptosis in the Small Intestine
Authors: Fujimoto Kazuma , Iwakiri Ryuichi , Utsumi Hiroyoshi , Kojima Masataka , Ishibashi Sadatoshi , Wu Bin , Sakata Hiroyuki , Noda Takahiro
Published: April 2003

Recently our studies have demonstrated that the central nervous system regulates in part mucosal cell growth and apoptosis in the rat small intestine. Ornithine decarboxylase (ODC) activity is a key enzyme for polyamine synthesis which plays an important role for the intestinal mucosal growth. We have demonstrated that the increase of ODC activity in the duodenum just before the dark period is abolished by truncal vagotomy and that the infusion of 2-deoxy-D-glucose into the third cerebroventricle activates ODC activity in the small intestine. Epithelial homeostasis is balanced by regulation of cell proliferation and cell death. Our preliminary data showed that intestinal mucosal apoptosis decreased in the ventromedial-hypothalamus-lesioned rat. These results indicate that the central nervous system, in addition to local factors, is related to regulation of mucosal homeostasis in the intestinal mucosa.
Lack of Therapeutic Effect of a Specially Designed Yogurt for the Eradication of Helicobacter pylori Infection
Authors: Wendakoon Chitra N. , Thomson Alan B.R. , Ozimek Lech
Published: April 2003

Background: Current antibiotic treatment for Helicobacter pylori infection is often associated with frequent adverse effects and resistance to antibiotics. Alternative treatment methods to control H. pylori infection are needed. Some specific strains of lactic acid bacteria (probiotics) in dairy products are known to inhibit the growth of H. pylori in vitro. A clinical trial was conducted to see the efficacy of a specially designed yogurt product containing specific probiotics on the eradication of H.pylori. Method: The yogurt was prepared using three Lactobacillus spp. (L. acidophilus and L. casei) and one commercial starter culture (L. acidophilus, L. bulgaricus and Streptococcus thermophilus). All these cultures were previously evaluated, and found to have strong in vitro inhibitory effects on the growth of H. pylori. Twenty-seven asymptomatic women positive for H. pylori on gastric biopsy and 13C urea breath test were recruited, and administered 175 ml of the yogurt three times a day for 30 days. The 13C urea breath test was administered again, one month after stopping the yogurt treatment to detect the presence of H. pylori.Results: In 26 of 27 subjects, the urea breath test values remained positive, indicating that the consumption of the yogurt had no effect on the eradication of H. pylori. Conclusion: Although the designed fermented milk containing lactobacilli is very effective in the inhibition of H. pylori growth in vitro, eradication of this infection in humans is difficult to achieve by consuming this product.
Pheochromocytoma Presenting as an Abdominal Emergency: Association with Perforation of the Colon
Authors: Mazaki Takero , Hara Junko , Watanabe Yoshihiro , Suzuki Shigeru , Kohno Tomohisa , Eguchi Teruo , Iwai Shigetomi
Published: April 2003

A pheochromocytoma is a rare tumor derived from the adrenal medulla (or from chromaffin cells of sympathetic ganglia). Its symptoms derive mostly from the excessive release of catecholamines (adrenaline and noradrenaline). Hypertension is the most recognized feature of this disease, but gastrointestinal manifestations can on rare occasions be just as serious and life threatening. This report describes a rare case of a 70-year-old woman with pheochromocytoma who developed an acute abdominal emergency with shock and panperitonitis as a result of perforation of the descending colon which was effectively treated by surgical removal of the tumor and the perforated colon. There have been 2 such cases in the English literature in whom a pheochromocytoma was associated with perforation of the colon. Successful surgical removal of such a pheochromocytoma has been not reported previously. Our case demonstrates the importance of recognizing that a pheochromocytoma presents with a wide spectrum of manifestations, and rapid treatment brings improvement to the patient.
Compulsory Substance Abuse Treatment: An Overview of Recent Findings and Issues
Authors: Wild T. Cameron , Roberts Amanda B. , Cooper Erin L.
Published: April 2003

An overview of research trends and issues in the area of compulsory substance abuse treatment is presented, using a sample of 170 English-language articles obtained from a search of 4 databases (Medline, PubMed, Embase, PsychINFO, supplemented by a manual search). About half (51%) of these articles were non-empirical (i.e. literature reviews, policy proposals, legal and ethical commentaries on compulsory treatment). A subsample of empirical studies published since 1988 (n = 71) was coded to summarize research trends in relation to 3 key issues: (1) how compulsory treatment was studied (country of origin; type of compulsory treatment; treatment population), (2) the evidence base for judging effectiveness of compulsory treatment (research design; sampling; type, timing and results of outcome measures), and (3) the relationship between compulsory treatment and coercion (measurement strategies). Directions for future research are discussed.
‘Getting Checked and Having the Test’: Drug Injectors’ Perceptions of HIV Testing – Findings from Qualitative Research Conducted in England
Authors: Hughes Rhidian
Published: April 2003

If HIV and AIDS policy initiatives are to be successful in tackling the spread of infection it is important to understand more about the ways in which people perceive HIV and AIDS. HIV testing is a policy initiative that will work when people take the test and make appropriate changes to their behaviour as a result. This paper is based on a study that used in-depth interviews and a vignette with drug injectors to explore drug injectors’ perceptions of HIV risk outside and inside prison. HIV testing was an integral part of drug injectors’ perceptions of risk. Three main themes emerged from the analysis of these data: first, reasons for not taking a test; second, reasons for taking a test; and third, the impact of testing upon subsequent behaviour. The paper ends with a summary and conclusions highlighting implications for future research and policy development.
Acute Cerebrovascular Disease in Women
Authors: Arboix Adrià , Oliveres Montserrat , García-Eroles Luis , Maragall Clara , Massons Juan , Targa Cecilia
Published: April 2003

In 2,000 consecutive stroke patients collected in a prospective hospital-based stroke registry over a 10-year period, we assessed whether stroke in men and women was different in respect to vascular risk factors, clinical features and natural history. The frequency of the different variable in men and women was analyzed by means of univariate analysis and logistic regression models. Women accounted for 48% of the study population (n = 967) and were older than men (mean age 75 vs. 69 years, p < 0.001). In the age group of 85 years or older, stroke was more frequent in women than in men (69.8 vs. 30.2%, p < 0.001). Women showed a higher frequency of cardioembolic infarction and a lower occurrence of lacunar infarction and stroke of undetermined cause than men. In-hospital mortality (17.4 vs. 13.3%) and length of hospital stay (19.6 vs. 16.7 days) was significantly higher (p < 0.001) in women than in men. In the model based on demographic variables and cardiovascular risk factors, obesity, heart failure, atrial fibrillation and age were significant predictors of stroke in women, while intermittent claudication, ischemic heart disease, chronic obstructive pulmonary disease, cigarette smoking and alcohol abuse were predictors in male sex. Hypertension and limb weakness were predictors for stroke in women, and absence of neurological deficit at hospital discharge, lacunar syndrome and ataxia were predictors in men in the models based on all variables. Women differ from men in the distribution of risk factors and stroke subtype, stroke severity and outcome. Differences in stroke pathology and/or differences in functional anatomy or plasticity of the brain between sexes may account for these findings.
Effect of Renin-Angiotensin System Blockade on the Expression of the Angiotensinogen Gene and Induction of Hypertrophy in Rat Kidney Proximal Tubular Cells
Authors: Zhang Shao-Ling , To Catherine , Chen Xing , Filep Janos G. , Tang Shiow-Shih , Ingelfinger Julie R. , Carrière Serge , Chan John S.D.
Published: April 2003

Studies have shown that high levels of glucose and angiotensin II (Ang II) stimulate hypertrophy and the expression of matrix protein genes in mouse proximal tubular cells in vitro. The present study tested the hypothesis that blockade of the renin-angiotensin system (RAS) inhibits the stimulatory effect of high levels of glucose on the expression of the renal angiotensinogen (ANG) gene and the formation of Ang II and subsequently attenuates the induction of hypertrophy in kidney proximal tubular cells. Immortalized rat proximal tubular cells (IRPTC) were cultured in monolayer. The levels of expression of rat ANG and ANG mRNA in the IRPTC were quantified by specific radioimmunoassays for rat ANG (RIA-rANG) and by a reverse-transcription polymerase chain reaction (RT-PCR) assay, respectively. Hypertrophy of IRPTC was analyzed by flow cytometry (FACScan) and cellular protein assay. Our studies showed that losartan (an Ang II (AT1)-receptor blocker), perindopril and captopril (inhibitors of angiotensin-converting enzyme) blocked the stimulatory effect of a high level of glucose (i.e. 25 mM) on the expression of the rat ANG gene and hypertrophy in IRPTC but not by the Ang II (AT2)-receptor blocker. Our studies indicate that the blockade of RAS is effective in inhibiting the stimulatory effect of hyperglycemia on the expression of the ANG gene and hypertrophy in IRPTC, supporting the notion that the local formation of intrarenal Ang II may play a role in the development of renal hypertrophy during early diabetes.
Angiotensin II Administration Causes Enhanced Expression of Glomerulosclerosis-Related Markers and Decreased Renal Antioxidant Enzyme Activities in Rats
Authors: De Craemer Dirk , Lobe Emmanuel , Pauwels Marina , Verbeelen Dierik , van den Branden Christiane
Published: April 2003

Angiotensin II administration to rats during 6 weeks causes decreased activity of catalase and glutathione peroxidase in renal cortex. Rats show mild hypertension, subclinical signs of renal injury, increased glomerular expression of desmin, glomerular and interstitial expression of α-smooth muscle actin and an increased number of ED-1-positive cells in glomeruli. An inverse correlation exists between catalase activity and glomerular α-smooth muscle actin expression and between glutathione peroxidase activity and glomerular desmin expression. The decrease of antioxidant enzyme activity, early after angiotensin II administration, might be an important initiating factor in the complex process leading eventually to renal sclerosis by reduction of reactive oxygen intermediate breakdown. The significant relationship between markers of sclerosis and some antioxidant enzyme activities suggests either a causative link or a common triggering factor.
Interleukin-2-Dependent Mechanisms Are Involved in the Development of Glomerulosclerosis after Partial Renal Ablation in Rats
Authors: Hamar Péter , Peti-Peterdi János , Szabó Attila , Becker Gerold , Flach Regina , Rosivall László , Heemann Uwe
Published: April 2003

Background: Glomerulosclerosis is a common feature of many end-stage renal diseases. The contribution of cellular immune mechanisms has been implicated in the development of glomerulosclerosis. We investigated whether the inhibition of lymphocyte activation influences this process in an established rat model of renal hyperfiltration. Methods: After removal of two-thirds of their respective kidney mass, rats were treated with either tacrolimus (0.08 mg/kg/day) or vehicle until the end of the study (n = 10/group). The rats were pair-fed and proteinuria was assessed regularly. Twenty weeks after nephrectomy, creatinine clearance and systemic blood pressure were determined, and kidneys were harvested for morphological, immunohistological and PCR analysis. Results: In control animals, renal function started to decline from week 12, as indicated by an elevated proteinuria. Interleukin (IL)-2 and IL-2 receptor synthesis was upregulated in control animals and inhibited by tacrolimus treatment. Transforming growth factor-β (TGF-β1), platelet-derived growth factor-AA (PDGF-AA) and macrophage chemoattractant protein-1 (MCP-1) mRNA levels were upregulated in control animals, but were significantly lower in immunosuppressed hosts. Additionally, tacrolimus treatment resulted in a significant reduction of proteinuria. Morphological analysis supported these functional results; glomerular sclerosis, tubular atrophy and intimal proliferation were more pronounced in controls than in the tacrolimus group. These morphological parameters were accompanied by reduced infiltration of CD5+ (rat T-cell marker) T cells, ED1+ (rat macrophage marker) macrophages, and less intense staining for laminin and fibronectin. Conclusion: A continuous treatment with tacrolimus – an inhibitor of lymphocyte proliferation – reduced the pace of glomerulosclerosis in the remnant kidney.
Long-Term Ammonium Chloride or Sodium Bicarbonate Treatment in Two Models of Polycystic Kidney Disease
Authors: Torres Vicente E. , Cowley Jr. Benjamin D. , Branden Michael G. , Yoshida Izumi , Gattone Vincent H.
Published: April 2003

Administration of ammonium chloride aggravates, while short-term administration of sodium or potassium bicarbonate lessens the development of polycystic kidney disease in Han:SPRD rats. We have conducted studies to determine whether the protection afforded by the administration of sodium bicarbonate is sustained and prevents development of uremia during chronic administration and whether the effects of the administration of ammonium chloride and sodium bicarbonate are also observed in a different model of polycystic kidney disease, the CD1-pcy/pcy mouse. We found that chronic administration of 200 mM sodium bicarbonate to Han:SPRD rats inhibited cystic enlargement and prevented the subsequent development of interstitial inflammation, chronic fibrosis, and uremia. We also found that, while the administration of ammonium chloride has similar effects in Han:SPRD rats and CD1-pcy/pcy mice, the administration of sodium bicarbonate is only protective in the Han:SPRD rats. This probably reflects differences in these models (predominately involvement of proximal tubules in Han:SPRD rats and of collecting ducts and distal tubules in pcy/pcy mice) and the different location and nature of the renal metabolic responses to the administration of acid or alkaline load.
High Glucose Decreases Matrix Metalloproteinase-2 Activity in Rat Mesangial Cells via Transforming Growth Factor-β1
Authors: Singh Rekha , Song Ruo Hua , Alavi Nahid , Pegoraro Alfredo A. , Singh Ashok K. , Leehey David J.
Published: April 2003

Diabetic nephropathy is characterized by accumulation of mesangial matrix. Glucose-induced inhibition of matrix-degrading enzymes such as collagenases is believed to contribute to matrix accumulation. We have previously demonstrated that 72 kDa type IV collagenase activity is decreased in the rat mesangial cells cultured in high glucose media [Diabetes 1995;44:929–935]. The present studies were designed to investigate if the cytokine transforming growth factor-β1 (TGF-β1) mediates this effect of glucose. Type IV collagenases degrade type IV collagen as well as gelatin (denatured collagen) and are thus also called gelatinases. They belong to the family of matrix metalloproteinases (MMPs); MMP activity is controlled by tissue inhibitors of metalloproteinases (TIMPs). The activity of 72 kDa type IV collagenase, also known as matrix metalloproteinase-2 (MMP-2), was assessed using three methods: (1) fluoresceinated gelatin degradation assay to detect free enzyme activity (activity which is present in excess of TIMP-inhibited activity); (2) zymography to measure total (free + TIMP-bound) enzyme activity; (3) ELISA using specific antibodies to measure MMP-2 levels. TGF-β1 and TIMP-2 levels were also determined by ELISA. Incubation of primary cultures of rat mesangial cells for 5 days in 30 vs. 5 mM glucose resulted in a 3-fold increase in production of total TGF-β1, a significant decrease in MMP-2 activity and immunoreactive MMP-2 levels, and an increase in TIMP-2 levels. Addition of exogenous TGF-β1 to mesangial cells incubated in 5 mM glucose replicated the high glucose effect by producing a significant decrease in MMP-2 levels with a concurrent increase in TIMP-2 levels. Furthermore, glucose-induced inhibition of MMP-2 activity was completely blocked by neutralization of TGF-β1 with anti-TGF-β1 antibody. We conclude that the decrease in MMP-2 activity induced by glucose loading is mediated via TGF-β1.
Preconditioning with Sodium Arsenite Inhibits Apoptotic Cell Death in Rat Kidney with Ischemia/Reperfusion or Cyclosporine-Induced Injuries
Authors: Yang Chul Woo , Kim Byung Soo , Kim Jin , Ahn Hee Jong , Park Joo Hyun , Jin Dong Chan , Kim Yong Soo , Bang Byung Kee
Published: April 2003

This study was performed to evaluate the effect of heat-shock protein (HSP)70 induction with sodium arsenite (SA) on ischemia/reperfusion (I/R) or cyclosporin A (CsA)-induced injuries in rat kidney. Rats were classified into five groups (sham, I/R, SA+I/R, I/R+CsA and SA+I/R+CsA groups) according to both the status of SA pretreatment and treatment with CsA. SA (6 mg/kg, i.v.) pretreatment was accomplished 12 h before I/R injury, and CsA (20 mg/kg, s.c.) was given subsequent to I/R injury. The effect of SA pretreatment on I/R injury was evaluated using measurements of renal function, the histopathology score, and assays for apoptosis (DNA fragmentation analysis, TUNEL staining, mRNA expressions of the pro-apoptotic genes and caspase activities). In addition, mitochondrial morphology was examined by electron microscopy. Induction of HSP70 with SA improved both renal function and the histopathology score as compared to the group without HSP70 induction. The assays for apoptosis revealed that SA pretreatment decreased the DNA laddering pattern, TUNEL-positive cells, mRNAs expression of pro-apoptotic genes and caspase activities as compared with the group without SA pretreatment. In addition, the mitochondrial morphology was well preserved in the groups with SA pretreatment. In conclusion, SA pretreatment prevents subsequent I/R or CsA-induced injuries in the rat kidney, and this renoprotective effect appears to be mediated by induction of HSP70.
Apoptosis and Angiotensin II: Yet Another Renal Regulatory System?
Authors: Bonnet Fabrice , Cao Zemin , Cooper Mark E.
Published: April 2003

Apoptosis plays a key role in the regulation of normal renal structure and kidney remodeling in various renal diseases. Angiotensin II plays a prominent role in renal injury through its receptor subtypes, the type 1 (AT1) receptor and the type 2 (AT2) receptor, which involve different molecular mechanisms. In addition to its haemodynamic actions, angiotensin II induces apoptosis. Angiotensin II also increases proliferation in the kidney. A close correlation between renal cell proliferation and apoptosis has been shown in renal diseases as well as in the angiotensin II infusion model. Angiotensin induces upregulation of p53 and other pro-apoptotic proteins. Recent studies suggest that both AT1 and AT2 receptors influence the apoptotic process in the kidney. These apoptotic effects of angiotensin II should be considered as representing another regulatory mechanism that may modulate the balance between cell growth and proliferation within the kidney.
High Glucose Concentrations Stimulate Renal Papillary Phosphatidylcholine Biosynthesis
Authors: Setton-Avruj Clara P. , Speziale Emir H.S. , Sterin-Speziale Norma B.
Published: April 2003

The effects of a high glucose concentration (HGC) on renal phosphatidylcholine (PtdCho) biosynthesis were studied. In control rats, HGC increased papillary PtdCho biosynthesis. In chronic diabetic rats, an increase above that induced by diabetes was observed. Such glucose-responsive phospholipid pools were shown to be transient in adult control rats, while in acute diabetic and aged control and chronic diabetic rats they seem to be of slow breakdown or permanent. Deoxyglucose evokes the HGC effect only in the presence of 5 mM glucose. Neomycin, which blocks phospholipase C action, corrected the HGC effect in control and chronic diabetic rats, but not the increase due to diabetes. CDP-choline: 1,2-diacylglycerol cholinephosphotransferase activity was increased by both in vivo and simulated diabetes. Therefore, transient high extracellular glucose levels promote a reversible increase in papillary 32P-PtdCho, while diabetes causes an irreversible increase resulting in PtdCho accumulation, possibly related to papillary necrosis.
Genetic Susceptibility to Renal Injury in Hypertension
Authors: Bidani Anil K. , Griffin Karen A. , Churchill Paul C. , Churchill Monique C. , Lezin Elizabeth St. , Kurtz Theodore W.
Published: April 2003

Substantial evidence indicates that hypertension plays a predominant role in the progression of most chronic renal diseases including diabetic nephropathy. Nevertheless, significant differences are observed in the susceptibility to develop hypertension-associated renal damage between individuals, racial groups and animal strains despite comparable hypertension. Recent studies employing a variety of genetic methods both in humans and in experimental models, have provided strong support for the potential importance of genetic factors and have suggested that genes influencing susceptibility to renal damage may be inherited separately from genes that influence blood pressure. However, due to the genetic complexity involved in a multifactorial trait such as the susceptibility to hypertensive renal damage, very limited progress has been achieved thus far in attempts to link such susceptibility to specific genetic mechanisms, chromosome regions and/or candidate genes. It is anticipated that the rapid recent advances in molecular genetic techniques and the simultaneous use of multiple complementary strategies, as is currently under way, will greatly facilitate this search and provide fundamental new insights into the pathogenesis of hypertensive renal damage.
Comparison of Cross-Language Generalisation Following Speech Therapy
Authors: Holm Alison , Dodd Barbara
Published: April 2003

Little is known about the phonological development of children who acquire two languages sequentially in the preschool years. Some of these children will be referred for assessment of speech disorder. Distinguishing between delayed development due to the language learning environment and disorder is problematic in the absence of normative data on the typical phonological development of bilingual children. Another major issue concerns whether both languages require intervention, or only one because of generalisation to the other language. Treatment efficacy studies of 2 bilingual children are reported. The data indicate that different patterns of cross-language generalisation occur depending upon the deficit in the speech processing chain underlying the speech disorder.
Evidence of the Significance of Secondary Excitations of the Vocal Tract for Vocal Intensity
Authors: Alku Paavo , Vintturi Juha , Vilkman Erkki
Published: April 2003

In the production of voiced speech the main excitation of the vocal tract occurs during the glottal closing phase when the rate of change of the flow reaches its absolute maximum. The level of this maximum, the negative peak amplitude of the differentiated glottal flow, correlates strongly with sound pressure level. This study presents a straightforward method that yields a numerical value to characterize the effect of the main excitation on vocal intensity. The method, energy ratio by modified excitation (ERME), utilizes the glottal flow and the vocal tract transfer function estimated by inverse filtering and it synthesizes two signals based on the linear source-filter theory. The first sound is produced using the glottal flow given by inverse filtering per se. The second signal is synthesized by removing the main excitation from the differentiated flow. ERME is defined as the ratio between the energy of the first synthesized signal and the energy of the second one. It is shown that when the loudness of speech increases, the value of ERME first rises but in the case of very loud voices it starts to decrease. Hence, ERME shows that effects of secondary excitations of the vocal tract that occur during glottal opening become important in the production of very loud voices.
Body Mass in Wild Microcebus murinus over the Dry Season
Authors: Fietz Joanna
Published: April 2003

The main aim of this field study was to compare adult male and female grey mouse lemurs (Microcebus murinus) with respect to body size, seasonal changes in body mass, onset of reproductive activity and sex ratio of captured animals. M. murinus was studied in the dry deciduous forest of western Madagascar. The lemurs were trapped in capture/recapture sessions during the dry season of 1993 (August, September, October). In order to verify results of studies in captivity concerning body mass and rank order among males, distribution patterns and body mass of males and females were examined. The results of this study indicate that rank in males is related to body mass and testes size, rather than determined by body size. Heavier males occurred closer to females, possibly facilitating access to breeding opportunities. There was no sexual dimorphism in body size. Differences between the sexes in seasonal changes in body mass, and in numbers of each sex caught, indicate that males and females have different activity patterns during the dry period, when food availability is restricted.
Social Influence on Induced Food Preference in Common Marmosets (Callithrix jacchus)
Authors: Queyras Armelle , Scolavino Manuela , Puopolo Maria , Vitale Augusto
Published: April 2003

In this paper, we investigate the role of sociality in changing an induced food preference in captive common marmosets (Callithrix jacchus), in the particular case of interactions between animals with contrasting information. After modifying a food preference by making a preferred food unpalatable for pairs of individuals (labelled as conditioned individuals) we recorded food choice under three experimental conditions: pairs interacting (one conditioned pair with one non-conditioned pair); pairs separated (conditioned and non-conditioned pairs by themselves the day after the social condition); control (conditioned and non-conditioned pairs alone). The main results was that only the conditioned individuals modified their food choice, consuming significantly more of the spontaneously preferred food during the pairs interacting and pairs separated conditions, but not during the control condition.
Seasonal Home Range Changes of the Sichuan Snub-Nosed Monkey (Rhinopithecus roxellana) in the Qinling Mountains of China
Authors: Li Baoguo , Chen Chao , Ji Weihong , Ren Baoping
Published: April 2003

The seasonal changes in home range and habitat use of the Sichuan snub-nosed monkey, Rhinopithecus roxellana, have been studied by radio tracking and direct observation in the Qinling Mountains of China. The home range size was 14.1 km2 in spring, 9.5 km2 in summer, 12.1 km2 in autumn and 12.3 km2 in winter; the total area used was 22.5 km2. The area of the home range is closely correlated with the distribution and abundance of food resources. Seasonal change in the home range area is correlated with the phenology of the vegetation. An unusually large home range is a unique characteristic of this monkey.
Prognostic Impact of Plasma Brain Natriuretic Peptide for Cardiac Events in Elderly Patients with Congestive Heart Failure
Authors: Tamura Koji , Takahashi Nobuyuki , Nakatani Yuko , Onishi Satoshi , Iwasaka Toshiji
Published: April 2003

Background: Plasma brain natriuretic peptide (BNP) has been reported to be useful in determining the prognosis of patients with ischemic heart disease and cardiomyopathy. However, aging increases the level of plasma BNP; therefore, the prognostic impact of plasma BNP in elderly patients with congestive heart failure has not been fully established. Objective: We sought to determine whether plasma BNP could predict recurrent cardiac events in elderly patients with congestive heart failure. Methods: Forty-eight consecutive elderly patients (>65 years old) were enrolled in the present study. All patients were admitted with their first episode of congestive heart failure. Clinical characteristics, plasma BNP, left ventricular ejection fraction, and left ventricular mass index were compared between patients with and those without recurrent cardiac events. Results: During the follow-up period, twelve cardiac events were observed. The New York Heart Association functional class was signi- ficantly higher in patients with cardiac events than in those without (p < 0.05). The plasma BNP level in pa- tients with cardiac events was significantly higher than in those without (521.0 ± 156.0 vs. 126.8 ± 20.1 pg/ml, p < 0.001), despite more frequent treatment with angiotensin-converting enzyme inhibitors (75 vs. 28%, p < 0.05). The left ventricular ejection fraction was significantly lower and the left ventricular mass index higher in patients with cardiac events as compared with those without (38.1 ± 5.0 vs. 49.2 ± 2.4%, p < 0.05; 193.8 ± 14.3 vs. 132.6 ± 7.8 g/m2, p < 0.001, respectively). The plasma BNP was selected as an independent factor associated with cardiac events besides New York Heart Association functional class, left ventricular ejection fraction, and left ventricular mass index using multivariate Cox proportional-hazards regression analysis (hazard ratio = 2.656, p < 0.05). The cardiac event rate was significantly higher in patients with a plasma BNP concentration >132 pg/ml using Kaplan-Meier analysis (p < 0.001). Moreover, the plasma BNP level correlated inversely with the length of time from hospital discharge to a cardiac event (r = –0.575, p < 0.05). Conclusion: Measuring the plasma BNP level before hospital discharge in elderly patients with congestive heart failure was more useful than other conventional examinations for predicting the recurrence of cardiac events.
Superficial Siderosis of the Central Nervous System: A 70-Year-Old Man with Ataxia, Depression and Visual Deficits
Authors: Polidori Maria Cristina , Pelliccioli Giampiero , Catani Marco , Finali Giancarlo , Senin Umberto , Mecocci Patrizia
Published: April 2003

Background: Superficial siderosis of the central nervous system (SSNS) is caused by cerebral, cerebellar and spinal cord tissue deposition of hemosiderin, often related to repeated episodes of subarachnoid hemorrhage. Typical symptoms include ataxia, sensorineural deafness and dementia. Methods and Results: An elderly patient with SSNS presenting with ataxia, depression and severe visual impairment was admitted to the Unit of Geriatrics of the University Hospital of Perugia, Italy. Late diagnosis and the association of symptoms with SSNS prevented the possible surgical treatment of the disease. Conclusions: Recognition of uncommon clinical variants may facilitate early diagnosis of SSNS and improve therapeutic results.
Institutionalized Older Adults in a Health District in the United Arab Emirates: Health Status and Utilization Rate
Authors: Margolis Stephen A. , Reed Richard L.
Published: April 2003

Background: Little is known about the rate of institutionalization and health status of nursing home (NH) type patients living in the Middle East. This study was set in the Al-Ain Medical District, a geographically discrete region of the United Arab Emirates, a country with a developing economy located on the shores of the Arabian Gulf. NH-type patients were defined as people aged 60 years and older who were admitted to a hospital or a long-term institutionalized setting for at least 6 weeks and with no evidence of an expectation of discharge at the time of the evaluation. Objective: To determine the clinical, functional, cognitive, and nutritional status of NH-type patients living in a defined community within a developing country. Method: Cross-sectional survey. Results: All NH-type patients were identified, and all were included in this study (n = 47, 100% participation rate). All were located within three public institutions, none of which was a dedicated NH facility. The rate of institutionalization was 7.0–14.0 per 1,000 people aged 65 or older. The age distribution was 30% (60–74 years), 49% (75–84 years), and 21% (85+ years). The length of stay was 3.8 years. The female:male ratio was 1.6. All except 1 had a neurological disorder, and 89% had dementia. The cognitive deficits were severe with only 61% alert, 41% able to speak, 17% orientated in place, and 15% orientated in time. The functional status was also poor: 98% received assistance with all instrumental activities of daily living, 85% received assistance with five activities of daily living, and 94% were bed bound. The nutritional status was also impaired with a mean body weight of 45 ± 14 kg and a mean albumin level of 3.1 ± 0.6 g/dl. When compared with the USA data from the National Center for Health Statistics, the study population was younger, had a longer length of stay, a lower female:male ratio, a higher rate of neurological diseases and dementia, and were far more dependent and disorientated. The rate of institutionalization was one sixth to one third of that in the USA. Conclusion: From these data we concluded that this region has a distinctly different population of institutionalized older people who demonstrate greater impairments in all domains of health status.
Neuroendocrinology of Aging: The Potential of Gene Therapy as an Interventive Strategy
Authors: Goya Rodolfo G. , Bolognani Federico , Hereñú Claudia B. , Rimoldi Omar J.
Published: April 2003

Objective: This paper reviews the current status of gene therapy in the neuroendocrine system and discusses the interventive potential of this methodology for neuroendocrine pathologies associated with aging. Background and Results: A brief description is first presented of the viral-vector-based gene delivery systems being currently used in the neuroendocrine system, namely the adenoviral and herpetic (HSV1) vector systems. Next, an account of the neuroendocrine pathologies for which gene therapy approaches in animal models are being implemented is provided. This includes the treatment of experimental pituitary tumors by adenoviral-vector-mediated transfer of the suicide gene for the HSV-1 thymidine kinase. At the hypothalamic level, an adenovirus harboring the cDNA for arginine vasopressin has been used in Brattleboro rats to correct their diabetes insipidus. Next, the interventive potential of gene therapy for correcting age-associated neurodegenerative processes at neuroendocrine level is outlined. Finally, the role that emerging technologies may play in the development of future genetic therapies for aging is considered. Conclusion: Although effective implementation of gene therapy strategies still faces significant technical obstacles, these are likely to be progressively overcome as gene delivery systems are refined.