bluuebunny/crossref_metadata_2025 huggingface dataset:
Exogenous hepatocyte growth factor inhibits myoblast differentiation by inducing myf5 expression and suppressing myoD expression in an organ culture system of embryonic mouse tongue
Authors: Yamane Akira , Amano Osamu , Urushiyama Toki , Nagata Junji , Akutsu Satonari , Fukui Tadayoshi , Diekwisch Thomas G. H.
Published: March 2004

We examined the effects of exogenous hepatocyte growth factor (HGF) on the differentiation and proliferation of tongue myoblasts by using an organ culture system of tongue obtained from mouse embryos at embryonic day (E) 13. Exogenous HGF induced reductions in the quantities of muscle creatine kinase and myogenin mRNAs and in the number of fast myosin heavy chain‐positive myoblasts and myotubes, suggesting that HGF suppressed the differentiation of myoblasts in the cultured E13 tongues. Exogenous HGF induced no significant changes in the percentage of proliferating cell nuclear antigen (PCNA)‐positive cell nuclei to total cell nuclei (labeling index) in the muscle portion of the cultured E13 tongue, suggesting that HGF did not affect the proliferation of myoblasts. Exogenous HGF induced the expression of myf5 mRNA but inhibited the expression of myoD mRNA. Since mouse tongue myoblasts are reported to complete proliferation by E13, it appears that exogenous HGF arrests myoblasts in the cell cycle and does not allow them to enter the differentiation process. This is achieved by controlling the expression of myf5 and myoD mRNAs, thus inhibiting the differentiation of tongue myoblasts.
Primary and secondary cartilages of the neonatal rat: the femoral head and the mandibular condyle
Authors: Delatte Myriam , Von den Hoff Johannes W. , Van Rheden René E. M. , Kuijpers‐Jagtman Anne M.
Published: March 2004

Primary and secondary cartilages differ in embryonic origin and in histological organization, and are generally considered to have a different mode of growth. However, few studies have directly compared the two types of cartilage of the same animal at the same age. Therefore, we analysed several histological and biochemical differences between secondary cartilage of the mandibular condyle and primary cartilage of the femoral head of 4‐d‐old rats. We evaluated the tissue organization, the level of DNA and glycosaminoglycan (GAG) synthesis, and the GAG and collagen content. The expression of collagen types I, II and III and of receptors for insulin‐like growth factor (IGF)‐I, fibroblast growth factor (FGF), and transforming growth factor (TGF)‐β were investigated by immunohistochemistry. The ex vivo DNA and GAG synthesis as well as the GAG content of femoral heads were much higher than that of mandibular condyles. Mandibular condyles expressed both collagen types I and II, while femoral heads expressed only type II collagen. In the mandibular condyles, receptors for IGF‐I, FGF, and TGF‐β were observed mainly in the superficial layers, whereas they were found throughout the entire femoral head. In conclusion, major differences were found between both types of cartilage, which might be related to their specific functional demands.
Detection of dentin sialoprotein in rat periodontium
Authors: Baba Otto , Qin Chunlin , Brunn Jan C. , Jones Jarrod E. , Wygant James N. , McIntyre Bradley W. , Butler William T.
Published: March 2004

Cloning and sequencing of the cDNA indicates that dentin sialophosphoprotein (DSPP) is a precursor of both dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Dentin sialophosphoprotein must be proteolytically processed to form these two extracellular matrix (ECM) proteins. Numerous studies led us to conclude that DSP (and DSPP) are exclusively expressed by odontoblasts and preameloblasts. However, recent observations suggest a wider distribution. To test this hypothesis, we conducted systematic studies on rat first molar during root formation with immunohistochemical techniques using specific anti‐DSP polyclonal and monoclonal antibodies. We also performed in situ hybridization, using high‐stringency RNA probes to detect DSP transcripts. Immunohistochemical studies demonstrated that DSP is not only localized in odontoblasts, dentin ECM and preameloblasts, but also in alveolar bone, cellular cementum, osteocytes, cementocytes, and their matrices. The results of in situ hybridization were consistent with those from immunohistochemistry, showing the expression of DSP transcripts in osteoblasts of alveolar bone, fibroblasts in periodontal ligament and cementoblasts in cellular cementum. Together, these observations suggest that DSP is involved in formation of the periodontium as well as tooth structures.
Advances in the conservation of British mammals, 1954–2004: 50 years of progress with The Mammal Society
Authors: FLOWERDEW John R.
Published: March 2004

1. The Mammal Society was established in 1954 to link amateurs and professionals in promoting the study of mammals. It now directly assists British conservation science, and has fostered The British Deer Society, the National Federation of Badger Groups, The Bat Conservation Trust, the Ungulate Research Group and Sea Watch Foundation. The Society also has strong links with the Zoological Society of London, the Vincent Wildlife Trust and the People's Trust for Endangered Species/Mammals Trust UK, as well as with many other non‐governmental organizations (NGOs) and statutory bodies.

2. The Mammal Society provides fora for discussion, scientific symposia, mammal publications, and practical studies. It has also instigated major advances in the presentation of scientific knowledge through three editions ofThe Handbook of British Mammalsunder three successive editors: H.N. Southern, G.B. Corbet and S. Harris.

3. From the 1970s the Society has highlighted conservation concerns (e.g. the decline of otters and persecution and management of badgers), informed legislation, supported many surveys, including harvest mice, pine marten, polecat, small rodents, hares, yellow‐necked mice and foxes, and published authoritative species’ accounts, guides to methodology,Mammal Review,Notes/Communications from The Mammal Society, the annualCurrent Projects on British Mammalsand other scientific and educational material.

4. Country‐wide mammal recording and training (Look Out for Mammals) developed in the 1990s alongside the Endangered British Mammals Fund. The ‘ground breaking’A Red Data Book for British Mammals, andA Review of British Mammals, both drew on Mammal Society expertise, helping to meet the UK Government's conservation responsibilities and emphasizing the growing influence of The Society. Co‐operative monitoring has been developed with the British Trust for Ornithology through the Winter Mammal Monitoring scheme and is further projected with more than 20 NGOs and statutory bodies forming the ‘Tracking Mammals Partnership’.

5. The Mammal Society now advises on UK Biodiversity Action Plans and plays a lead role in UK mammal conservation, highlighting problems and promoting solutions. However, many British mammals are still declining, many are neither legally protected nor subject to national conservation initiatives, and data are still lacking on the status of many terrestrial and most marine species. Much has been done, but there is still much to do.
Could we live with reintroduced large carnivores in the UK?
Authors: WILSON CHARLES J.
Published: March 2004

1. Literature on the wolf Canis lupus, brown bear Ursus arctos and lynx Lynx lynx is reviewed to determine if sufficient semi‐natural habitat exists in the UK for a viable population of any of these species and to assess the potential risks to human safety, livestock and economically valuable wildlife. Public attitudes to the recovery and reintroduction of some other mammals are also briefly reviewed.

2. The large home range sizes and low population densities of large carnivores mean that the Scottish Highlands is the only UK region with the potential to support a viable population. Human population density is also lower in the Highlands and the density of wild ungulate prey higher than in many parts of Europe where large carnivores survive.

3. Attacks on people have been recorded in Europe for healthy bears and for rabid bears and wolves but there are no reports of attacks by lynx. Bears are more carnivorous in the north of their range than in the south and although wild mammals seldom appear to be important prey serious predation of livestock can occur. Livestock predation is also reported for the wolf and the lynx but they appear to prefer wild prey if available. However, mass kills of up to 100 or more sheep are occasionally recorded for wolves.

4. Attitudes to reintroductions and carnivores generally tend to be favourable amongst the general public, but negative amongst those most likely to be adversely affected. Fears for human safety and significant livestock predation with bears and wolves, respectively, suggest that reintroduction of these species is unlikely to be acceptable in the foreseeable future. Reintroduction of the lynx may be feasible but habitat suitability and potential impact on vulnerable native wildlife need to be assessed. Socio‐economic and legal issues also need to be addressed before such a reintroduction is considered.
The potential interplay of posture, digestive anatomy, density of ingesta and gravity in mammalian herbivores: why sloths do not rest upside down
Authors: CLAUSS MARCUS
Published: March 2004

1. The interaction between the density of ingesta and gravity observed in the digestive systems of ruminant herbivores should receive attention in other non‐ruminant herbivorous mammals. The resting postures adopted by non‐ruminants are of particular interest.

2. A new interpretation of established findings regarding the digestive tract of sloths illustrates that the interplay of posture, anatomy, the density of ingesta and gravity can provide a novel explanation of behavioural and morphological adaptations in herbivores, as the average particle size and dry‐matter content increases within their forestomach from its caudal towards its cranial portion. In sloths, this could be indicative of a stratification of ingesta occurring in the upright sitting posture adopted while resting, as opposed to their characteristic upside down posture when moving.

3. The sitting resting posture of sloths could therefore be an adaptation to exploit the tendency of the forestomach contents to stratify in order to pass larger, more difficult‐to‐digest particles faster from the fermentation chamber.
Distribution and population density of badgers Meles meles in Luxembourg
Authors: SCHLEY L. , SCHAUL M. , ROPER T. J.
Published: March 2004

1. The distribution and density of Eurasian badgers Meles meles in Luxembourg was estimated by gathering information about the location of badger setts with a questionnaire survey, by visiting 708 setts in order to classify them as ‘main setts’ or ‘outliers’, and by estimating social group size by directly counting emerging badgers.

2. Badgers were found to be widely distributed in Luxembourg, with a minimum main sett density of 0.17 setts/km2. Setts were sited preferentially in forest habitat. The mean minimum group size was 4.6 badgers.

3. The Luxembourg badger population was conservatively estimated to contain at least 2010 adult and young badgers (95% CI 1674–2347) in spring 2002, equivalent to a density of 0.78 adult and young badgers/km2 (95% CI 0.65–0.91). This is moderate compared to most of continental Europe.
Cyclosporin induces renal proto‐oncogene RNA message and increased transforming growth factor‐β prior to renal fibrosis: Modification by calcium channel blockade in the salt replete rat
Authors: SAGGI SUBODH J , ANDOH TAKESHI F , SAFIRSTEIN ROBERT , BENNETT WILLIAM M
Published: March 2004

Background:  Chronic cyclosporin (CsA) administration has been shown to result in the replacement of epithelial cells in the kidney with fibrous tissue. These changes are kidney‐specific, as they do not occur in any other organ.

Results:  Cyclosporin exposure increases c‐fos and c‐jun mRNA in the rat kidney but not in the liver. Furthermore, chronic CsA exposure causes a further increase in c‐fos and c‐jun mRNA and increases the renal expression of transforming growth factor‐β (TGF‐β) mRNA. These changes precede the development of fibrosis. The combined insult of ischaemia and CsA resulted in synergistic increases in c‐fos, suggesting that CsA recruited a pathway for c‐fos activation different from ischaemia. The calcium channel blocker, verapamil, blocked CsA‐induced expression of c‐fos and c‐jun mRNA, and reduced the amount of TGF‐β expression.

Conclusion:  These data are consistent with the notion that CsA induces protooncogenes, which may be, at least partially, responsible for long‐term CsA nephrotoxicity.
Effects of long‐term passive smoking on the diameter of glomeruli in rats: Histopathological evaluation
Authors: DÜNDAR MEHMET , KOCAK IZZET , CULHACI NIL
Published: March 2004

Background and Aims:  Long‐term smoking increases the risk of renal diseases and it also causes the progression of the diseases. The aim of this study was to evaluate the effects of smoking on glomeruli in healthy rats exposed to long‐term passive smoking for a short period of time after birth.

Methods:  Sixty‐five rats were randomly assigned into four groups. Groups 1 (18 males) and 2 (18 females) were exposed to smoke, whereas groups 3 (15 males) and 4 (14 females) were not exposed to smoke. Overall, 130 renal units were evaluated, and diameters of 10 different glomeruli were measured. The renal and bodyweights of the rats were measured.

Results:  The diameter of the glomeruli was 95.51 ± 9.25 and 100.91 ± 4.06 µm in groups 1 and 3, respectively (P < 0.05). It was 97.32 ± 4.06 and 98.86 ± 6.25 µm in groups 2 and 4, respectively (P > 0.05). Irrespective of the sex, the diameter of the glomeruli was 96.42 ± 7.15 µm in smokers and 99.92 ± 5.56 µm in non‐smokers (P < 0.05). The renal weights of the male rats affected by smoke were significantly lower than that of those that were not affected by smoke (P < 0.05). Bodyweights of male rats affected by smoke were significantly lower that of those not affected (P < 0.05). There was a weak correlation between the diameter of the glomeruli and the bodyweights of male rats affected by smoke (r = 0.474, P < 0.05).

Conclusion:  We conclude that passive smoking might have a negative affect on renal morphometry and body growth.
Acute renal failure associated with Legionella pneumonia and acute cholecystitis
Authors: FUNG ANNIE SC , LEIKIS MURRAY J , McMAHON LAWRENCE P
Published: March 2004

Background and Aims:  Acute cholecystitis in critically ill patients has a high morbidity and mortality. We observed a number of patients presenting with Legionella pneumonia and acute renal failure who subsequently developed acute cholecystitis. There has previously been no reported association between Legionella pneumonia, renal failure and cholecystitis, prompting this examination of the cases and review of the available literature.

Methods:  The Western Hospital patient record discharge codes (DRG) from 1993 to 2001 were searched retrospectively for all cases of Legionella pneumonia or acute renal failure requiring dialysis (ARF) at presentation or during their period of hospitalization. Acute cholecystitis was then included as a cross‐search and results analysed.

Results:  Twenty‐six cases of isolated Legionella pneumonia and 112 of ARF were identified with a further 10 having both conditions simultaneously. Of these 10 cases, three were identified as also having acute cholecystitis. The combination of Legionella pneumonia and ARF was associated with an increased risk of acute cholecystitis (P = 0.002) whereas neither condition in isolation demonstrated this association.

Conclusions:  Patients with Legionella pneumonia can become critically ill with multiple complications including acute renal failure requiring dialysis. In this setting, they may have an increased risk of developing acute cholecystitis, which clinically can be difficult to ascertain. Diagnosis requires a high index of suspicion and vigilance.
Incidence and outcome of antiglomerular basement membrane disease in Chinese
Authors: LI FU KEUNG , TSE KAI CHUNG , LAM MAN FAI , YIP TERENCE PS , LUI SING LEUNG , CHAN GAVIN SW , CHAN KWOK WAH , CHAN ERIC YT , CHOY BO YING , LO WAI KEI , CHAN TAK MAO , LAI KAR NENG
Published: March 2004

Background:  Antiglomerular basement membrane (anti‐GBM) disease is an uncommon disease, especially among Asian population. Many reports and studies on this condition in the Caucasian population are available, but little information exists on anti‐GBM disease in Asians. To study the incidence and clinical characteristics of anti‐GBM disease among Chinese patients, we reviewed our experience of anti‐GBM disease in our hospital (Queen Mary Hospital, Hong Kong) from 1992 to 2003.

Methods:  All patients who were admitted for acute renal impairment, which was caused by crescentic glomerulonephritis associated with linear immunoglobulin G (IgG) staining on immunofluorescence, were included in the analysis. Serum anti‐GBM antibodies were detected by either enzyme‐linked immunofluorescence or indirect immunofluorescence. Ten patients were treated for anti‐GBM disease during this 11‐year period, yielding an incidence of approximately 0.6 cases per million population per year.

Results:  In this cohort, anti‐GBM disease predominantly affected older patients (mean age: 58.6 ± 21.7 years). Eight patients were aged between 60 and 80 years and there was a female preponderance (M:F =  2:8). The 1‐year renal and patient survival was 15% (95% CI 0–40%) and 70% (95% CI 42–98%), respectively. Most patients presented with non‐specific symptoms as well as impaired renal function. Detection of anti‐GBM antibody provided a good screening test for the disease. Antiglomerular basement membrane antibodies were not detected in two patients. All but two patients received steroid, cyclophosphamide and intensive plasmapheresis therapy. Haemoptysis occurred in four patients (40%), and usually lagged behind the renal presentation and commencement of treatment. Six patients required long‐term dialysis after the acute disease. Three patients died from the disease, two died from pulmonary complications and one died suddenly after a partial recovery of renal function.

Conclusion:  Antiglomerular basement membrane disease is uncommon among the Chinese population. It predominantly affects older patients, and prognosis is poor. Long‐term preservation of renal function after the initial attack is unusual.
Cardiac troponins and renal disease
Authors: DE ZOYSA JANAK R
Published: March 2004

SUMMARY:  Cardiovascular disease is the most common cause of death in patients with renal failure. Patients with renal failure are at greater risk of atypical presentations of myocardial ischaemia. Traditional markers of myocardial damage are often increased in renal failure in the absence of clinically suspect myocardial ischaemia. The cardiac troponins are specific markers of myocardial injury. Large‐scale trials, excluding patients with renal disease, have shown the importance of the cardiac troponins in predicting adverse outcome and in guiding both therapy and intervention in acute coronary syndromes. Cardiac Troponin T and cardiac Troponin I are increased in patients with renal failure and this is likely to represent multifactorial pathology including cardiac dysfunction, left ventricular hypertrophy and cardiac microinfarctions. Increases in serum troponin from baseline, in patients with renal disease with acute coronary syndromes, may represent a poor prognosis. Small studies of patients with renal failure have suggested that elevation of the cardiac troponins is associated with an increased risk of cardiac death.
Formaldehyde scavenging from peritoneal dialysis solutions using reduced aminothiol compounds
Authors: BIRD STEPHEN D , LEGGE MICHAEL , WALKER ROBERT J
Published: March 2004

Background:  Aldehydes were identified in clinical solutions, including peritoneal dialysis (PD) and cryoprotection solutions, which were used to freeze cells, tissues and embryos. Aldehydes are associated with increased cellular injury and may contribute to peritoneal membrane damage that occurs in patients on peritoneal dialysis. Recently, it was demonstrated that aldehydes could be ‘scavenged’ from these solutions by using aminothiol compounds. Although aldehydes were removed during the scavenging process, the kinetics of scavenging and the products formed were not characterized.

Methods:  Proton nuclear magnetic resonance (NMR) spectroscopy was used to investigate formaldehyde scavenging from an artificial PD solution supplemented with aminothiol compounds, cysteamine or l‐cysteine. Artificial PD solutions were formulated on the basis of commercial PD solutions and consisted of 132 mmol/L NaCl, 0.25 mmol/L MgCl2, 1.25 mmol/L CaCl2, and buffered with lactate (4.0 mmol/L) and lacked d‐glucose. Formaldehyde scavenging was a two‐step process involving an intermediate step followed by the formation of stable thiazolidine compounds. These included the derivatives of cysteamine and l‐cysteine; thiazolidine and thiazolidine‐4‐carboxylic acid, respectively.

Conclusion:  Scavenging with aminothiol compounds masked the destructive carbonyl group (C = O) of formaldehyde and formed a compound that has antioxidant properties. The addition of aminothiol compounds may improve the biocompatibility of commercial PD solutions.
Intracranial calcification and tumoural calcinosis during vitamin D therapy
Authors: SEYAHI NURHAN , APAYDIN SUHEYLA , SARIYAR MUZAFFER , SERDENGEÇTI KAMIL , EREK EKREM
Published: March 2004

SUMMARY:  Extraskeletal calcifications are frequently observed in patients with chronic renal failure. However, clinically, they usually remain silent. In this report, we describe two patients with massive extraskeletal calcifications that caused significant morbidity. The first patient had tumoural calcification located on the shoulder and the second patient had severe neurological symptoms caused by intracranial calcifications. High calcium phosphorus product and severe secondary hyperparathyroidism were present in both patients. Furthermore, they both received inappropriately high doses of active vitamin D, even though they failed to respond to this therapy. We suggest to monitor closely the calcium, phosphorus and parathyroid hormone levels during calcitriol therapy and to perform parathyroidectomy, without delay, in patients who were resistant to calcitriol.
Involvement of apoptosis in patients with diabetic nephropathy: A study on plasma soluble Fas levels and pathological findings
Authors: BABA KAORI , MINATOGUCHI SHINYA , SANO HIROTAKE , KAGAWA TOMOYO , MURATA ICHIJIRO , TAKEMURA GENZOU , HIRANO TAKAHIRO , OHASHI HIROSHIGE , TAKEMURA MASAO , FUJIWARA TAKAKO , FUJIWARA HISAYOSHI
Published: March 2004

Aims:  We investigated the relationship between levels of plasma soluble Fas (sFas) and stages of diabetic nephropathy, with special reference to apoptosis and clinical features of diabetic nephropathy in 168 patients with diabetic nephropathy.

Results:  There was a positive correlation between plasma sFas and creatinine levels, between sFas levels and urinary protein levels, and between sFas levels and urinary albumin. There was a negative correlation between plasma sFas levels and creatinine clearance. Plasma sFas levels in the early stage (stages 1, 2, 3A) and advanced stage (stages 3B and 4) were 2.6 ± 0.1 and 5.4 ± 0.5 ng/mL, respectively. Plasma sFas level of the advanced stage was significantly higher than that of the early stage. The number of proliferating cell nuclear antigen (PCNA) positive cells was significantly lower in the advanced stage than in the early stage. The number of in situ nick‐end labelling (TUNEL) positive cells was also significantly lower in the advanced stage than in the early stage, suggesting the suppression of apoptosis.

Conclusion:  These data suggest that apoptosis is involved in the advancement of diabetic nephropathy, and that plasma sFas level might be a predicting factor for prognosis.
Prevalence of Helicobacter pylori antibodies in long‐term dialysis patients
Authors: NAKAJIMA FUMITAKA , SAKAGUCHI MASAHIRO , OKA HIROSHI , KAWASE YOSHIO , SHIBAHARA NOBUHISA , INOUE TORU , UEDA HARUHIKO , KATSUOKA YOJI
Published: March 2004

Background:  Helicobacter pylori has been reported to play an important role in the development of gastritis and gastric ulcer.

Methods:  This study included 168 patients with end‐stage renal disease (ESRD; 30 non‐dialysis patients, 138 patients receiving dialysis; mean duration of dialysis: 57.3 ± 61.7 months) and 138 control volunteers. We investigated the prevalence of H. pylori infection by measuring H. pylori antibody (IgG) levels.

Results:  The prevalence of H. pylori infection was 62.3% in the control group, 53.3% in the non‐dialysis patients, and 36.9% in the dialysis patients. The percentage decreased with a reduction of renal function. In addition, the proportion of H. pylori‐positive patients decreased with the duration of dialysis, and the antibody titre was also significantly decreased. There was no association between long‐term oral administration of H2RA (H2 receptor antagonist) and the incidence of H. pylori infection.

Conclusion:  Among dialysis patients, the proportion of H. pylori‐positive patients was low. An aetiological factor other than H2RA agents was suggested. Renal failure or dialysis treatment may influence H. pylori infection.
Changes in serum markers of oxidative stress with varying periods of haemodialysis
Authors: KÖKEN TÜLAY , SERTESER MUSTAFA , KAHRAMAN AHMET , GÖKÇE ÇIGDEM , DEMIR SERAP
Published: March 2004

Background and Aims:  Oxidative stress possibly helps promote the progression and complications of chronic renal failure (CRF). Haemodialysis (HD) may aggravate oxidative stress. This controlled, cross‐sectional clinical study with blind outcome assessment evaluated the effect of prolonged HD treatment on oxidative stress.

Methods and Results:  Seventy patients (M/F =  33/37) with CRF and who were on HD were divided into six groups with differing treatment periods of HD; from 3 to 12 months to 85–120 months. Twelve healthy subjects acted as controls. The serum levels of thiobarbituric acid reactive substances (TBARS), total sulfhydryl (SH) groups and protein carbonyls (PCs) were determined. Compared with controls, PCs were increased in patients, and this positively correlated with the duration of HD. Treatment for more than 24 months caused the most striking increases in PCs, with relevant differences as compared to those on HD for a maximum of 12 months. Increasing periods of HD were associated with increases in TBARS and similar decreases in SH as compared with controls; the differences between the SH levels of those on HD for more than 84 months and those on HD for up to 24 months were significant.

Conclusion:  Our results indicate that HD continued for more than 2 years aggravates the latter. Decreased potential for oxygen‐radical‐scavenger activity becomes pronounced after 7 years of HD treatment.
Role and regulation of intestinal epithelial heat shock proteins in health and disease
Authors: Petrof Elaine O , Ciancio Mae J , Chang Eugene B
Published: April 2004

Mucosal injury and inflammation are cardinal manifestations of inflammatory bowel diseases (IBD), arising when the effects of cytotoxic factors and conditions overwhelm the cell's capacity for defense (i.e. cytoprotection) or repair. To date, most research in this area has focused primarily on agents and processes involved in producing tissue injury, with less consideration given to inherent mechanisms of cytoprotection and cellular repair. Therapeutic approaches to IBD reflect this bias, being largely directed towards down‐regulating the inflammatory process by inhibiting the production of immune and inflammatory mediators. This review will focus on the cell's inherent ability to defend itself against cellular stress and injury through the production of evolutionarily conserved stress proteins called heat shock proteins (HSP). The physiological role of these proteins in maintaining intestinal epithelial cell structure and function will be reviewed, with emphasis on studies that examine the role of HSP in IBD. A clearer understanding of the innate cytoprotective mechanisms inherent in intestinal epithelial cells will foster the development of new insights into basic epithelial cell biology, which ultimately can be used to establish target‐specific therapies directed at reducing or alleviating mucosal injury, thereby promoting tissue healing and repair.
Genetic polymorphism analysis of cytochrome P4502C19 in Chinese Uigur and Han populations
Authors: Niu Chun Yan , Luo Jin Yan , Hao Zhi Ming
Published: April 2004

OBJECTIVE:  To assess the genotype patterns of cytochrome P4502C19 in the Chinese Uigur and Han populations and compare them with other populations.

METHODS:  Ninety‐six Uigur and 104 Han healthy, unrelated subjects (Uigur: 51 males, 45 females, aged from 23 to 30 years; Han: 53 males, 51 females, aged from 21 to 26 years) were genotyped for CYP2C19 by the PCR‐RFLP technique to identify the wild‐type (wt) gene and two mutations, CYP2C19m1 in exon5 and CYP2C19m2 in exon 4.

RESULTS:  In the Uigur, the incidence of the poor metabolizer phenotype was 4.17% (4 of 96 subjects with m1/m1 genotype) and that of the extensive metabolizer was 95.83% (92 of 96 subjects), consisting of 6 (6.25%) homozygous for CYP2C19wt (wt/wt) in both exon 4 and exon 5, 83 (86.46%) heterozygous for CYP2C19wt and CYP2C19m1 and 3 (3.13%) heterozygous for both wt/m1 and wt/m2. None of the Uigur subjects was homozygous for CYP2C19m2 (m2/m2) or heterozygous for wt/m2 or m1/m2. Thus in the Uigur, the frequency of the CYP2C19m1 allele was 0.4818, the CYP2C19m2 allele was 0.0078, and that of the CYP2C19wt was 0.5104. In the Han, the frequency of the CYP2C19m1 allele was 0.3333, the CYP2C19m2 allele was 0.0686, and the frequency of the CYP2C19wt was 0.6058. CYP2C19m1 was the majority of the two mutations found in the Uigur, which was consistent with the situation in the Han population, and the frequency of the CYP2C19m1 allele was approximately 60‐fold that of the mutant allele CYP2C19m2. On the other hand, there were significant interethnic differences when the Uigur population was compared with other minorities with regard to the CYP2C19 genotype.

CONCLUSIONS:  The results indicate that the distribution frequency of the poor and the extensive metabolizers in the Uigur population is significantly lower and higher, respectively (P < 0.025), than in the Han population. There are significant differences between the Uigur and Han populations regarding the CYP2C19 allele frequency, which is consistent with results for the Caucasian population. On the other hand, there are significant interethnic differences when the Uigur population is compared with the Miao and Dai populations.
Effects of a natural extract of (–)‐hydroxycitric acid (HCA‐SX) and a combination of HCA‐SX plus niacin‐bound chromium and Gymnema sylvestre extract on weight loss
Authors: Preuss H. G. , Bagchi D. , Bagchi M. , Rao C. V. S. , Dey D. K. , Satyanarayana S.
Published: March 2004

Aim:  The efficacy of optimal doses of highly bioavailable (–)‐hydroxycitric acid (HCA‐SX) alone and in combination with niacin‐bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA‐SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels.

Methods:  A randomized, double‐blind, placebo‐controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21–50, BMI >26 kg/m2). Subjects were randomly divided into three groups. Group A was administered HCA‐SX 4667 mg, group B was administered a combination of HCA‐SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30–60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking.

Results:  At the end of 8 weeks, body weight and BMI decreased by 5–6% in both groups A and B. Food intake, total cholesterol, low‐density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high‐density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non‐significant effect was observed in all parameters in group C.

Conclusion:  The present study shows that optimal doses of HCA‐SX and, to a greater degree, the combination of HCA‐SX, NBC and GSE can serve as an effective and safe weight‐loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.
Smoking cessation and glycaemic control in type 2 diabetic patients
Authors: Iino K. , Iwase M. , Tsutsu N. , Iida M.
Published: March 2004

Aim:  To elucidate the relationship between glycaemic control, blood pressure and body‐weight change after smoking cessation in type 2 diabetic patients.

Methods:  We examined HbA1c, blood pressure and body weight in 15 type 2 diabetic patients before, 6 and 12 months after quitting smoking. Sixteen type 2 diabetic patients who did not quit smoking served as control.

Results:  Body weight slightly increased after quitting smoking. Although HbA1c levels showed no change in the control group, those in patients who quit smoking significantly increased (6.8 ± 0.3% before quitting smoking; 7.4 ± 0.3% 6 months after quitting smoking, p < 0.05; 7.8 ± 0.4% 12 months after quitting smoking, p < 0.001). Fasting blood glucose also increased in patients who quit smoking. The increase in body weight after quitting smoking did not correlate with the deterioration of glycaemic control. Diastolic blood pressure showed no change in control, whereas that in patients who quit smoking increased at month 12 (69 ± 3 vs. 76 ± 3 mmHg, p < 0.01). The increase in HbA1c at month 12 after quitting smoking correlated with body mass index before quitting smoking (r = 0.72, p < 0.005) and serum triglyceride before quitting smoking (r = 0.68, p < 0.01).

Conclusions:  Glycaemic control and diastolic blood pressure deteriorated in type 2 diabetic patients after quitting smoking. Type 2 diabetic patients who want to stop smoking need a caution to prevent deterioration of glycaemic control and blood pressure after quitting smoking.
Strong family history predicts a younger age of onset for subjects diagnosed with type 2 diabetes
Authors: Molyneaux L. , Constantino M. , Yue D.
Published: March 2004

Aims:  Age of onset of type 2 diabetes is becoming earlier and with it there is an increase in the development of chronic complications. This study examined the relationship between the strength of family history of diabetes on (i) age of diabetes onset and (ii) prevalence of diabetic complications.

Research design and methods:  Data on family history of diabetes and age of diabetes onset were prospectively collected on 5193 subjects. Family members were deemed to include grandparents, parents, siblings, aunts/uncles and children. To adjust for family size and to assess effects of pathway to diagnosis, we also contacted a subset of 180 patients selected on the basis of the strength of family histories of diabetes. A full assessment for diabetic complications including retinopathy, neuropathy and renal and macrovascular status was performed for the total cohort.

Results:  The more cases of diabetes found in a family, the younger the age of onset of type 2 diabetes. This phenomenon does not appear to be due to patients with strong family history of diabetes being more concerned about the possibility of having diabetes. The effect of strong family history is also evident in many ethnic groups when examined individually, although they differ from each other in their characteristic age of onset of diabetes. Once adjusted for duration of diabetes, strength of family history does not appear to affect metabolic profiles or prevalence of chronic complications.

Conclusions:  There is a strong relationship between the number of affected family members with diabetes and age of developing diabetes. The genetic and environmental factors underlying this phenomenon remain to be elucidated. However, it may be one of the reasons explaining why type 2 diabetes is affecting younger people worldwide.
The effect of valsartan on regression of left ventricular hypertrophy in type 2 diabetic patients
Authors: Suzuki K. , Kato K. , Soda S. , Kamimura T. , Aizawa Y.
Published: March 2004

Aim:  The aim of the present study was to examine the effects of an angiotensin II receptor antagonist, valsartan, on echocardiographically proven left ventricular hypertrophy (LVH) in patients with type 2 diabetes.

Methods:  Outpatients with type 2 diabetes mellitus were recruited at Niigata University Hospital. The left ventricular mass index (LVMI) was calculated by echocardiography. LVH was considered to be present if the LVMI was > 131 g/m2 in males and > 100 g/m2 in females. Patients with LVH received a low dose (40 mg/day) of valsartan for 12 months. This low dose had no clinical effect on blood pressure.

Results:  Of the 38 patients who entered the study, 14 (36.8%) had LVH. After only 6 months of valsartan therapy, the mean LVMI decreased significantly, from 126.5 ± 27.8 to 119.0 ± 23.5 g/m2 (p < 0.01 vs. baseline). Also, a significant decrease was observed after 12 months (116.5 ± 30.9 g/m2, p < 0.05 vs. baseline). Compared to baseline, there were no significant differences after treatment in body mass index, glycosylated haemoglobin (HbA1c), systolic blood pressure and diastolic blood pressure.

Conclusions:  In type 2 diabetic patients with LVH, treatment with a low dose of valsartan, an angiotensin II receptor antagonist, for 12 months, reduced LVMI, with no reduction in systemic blood pressure. This drug may be safely administered to type 2 diabetic patients with LVH. The long‐term risk‐reduction effects will have to be evaluated in further trials.
Influence of α‐lipoic acid on lipid peroxidation and antioxidant defence system in blood of insulin‐resistant rats
Authors: Thirunavukkarasu V. , Anuradha C. V.
Published: March 2004

Background:  High fructose feeding induces insulin resistance and hyperinsulinaemia in rats. A role for oxidative stress in the occurrence of insulin resistance has been suggested by several workers.

Aim:  The aim of this study was to investigate the effect of α‐lipoic acid (LA) on oxidant–antioxidant balance in rats fed on a high‐fructose diet that showed characteristic features of insulin resistance.

Methods:  Male Wistar rats weighing 150–170 g were divided into seven groups. The control group received the control diet containing starch. The fructose group was given a high‐fructose diet (>60% of total calories). The third and fourth groups were given fructose diet and were administered two different doses of LA at a low dose (35 mg/kg body weight) and high dose (70 mg/kg body weight) using olive oil as vehicle. The fifth group received fructose diet and olive oil. The sixth group received control diet and was administered LA (70 mg/kg body weight). And, the seventh group received the control diet and olive oil. Products of lipid peroxidation and activities of enzymic antioxidants, namely superoxide dismutase, catalase, glutathione peroxidase, glutathione‐S‐transferase and glutathione reductase, in red blood cells were assayed. Levels of non‐enzymic antioxidants α‐tocopherol, ascorbic acid and reduced glutathione were determined in plasma.

Results:  The levels of lipid peroxides, diene conjugates and thiobarbituric acid‐reactive substances were significantly higher in fructose‐fed rats. Inadequate antioxidant system was observed in high‐fructose‐fed rats. Treatment of fructose rats mitigated the imbalance between peroxidation and antioxidant defence system at both the doses tested. Increases in glucose, triglycerides, free fatty acids, insulin and insulin resistance were observed in fructose‐fed rats. LA administration prevented these alterations and improved insulin sensitivity. Significant positive correlations were obtained between insulin resistance and lipid peroxidation indices.

Conclusions:  Increased lipid peroxidation and deficient antioxidant system are observed in high‐fructose‐fed rats. LA administration preserves the antioxidant system and lowers lipid peroxidation. The findings suggest an interrelationship between lipid peroxidation and insulin resistance.
Lower plasma adiponectin concentration predicts the efficacy of pioglitazone in diabetic patients
Authors: Hiramatsu S. , Tajiri Y. , Karashima T.
Published: March 2004

Aim:  To investigate clinical efficacy of pioglitazone in association with plasma adiponectin concentration in type 2 diabetic patients.

Methods:  Ten diabetic patients were treated with 15 or 30 mg of pioglitazone for 8 weeks, and association between plasma adiponectin concentration before treatment and decrease in glycated albumin levels was examined.

Results:  Treatment with pioglitazone for 8 weeks lowered glycated albumin level (27.1 ± 1.2 to 23.8 ± 1.4%, p < 0.05), and inverse relationship between changes in glycated albumin and plasma adiponectin concentration before treatment was revealed (r = −0.66, p < 0.05). Plasma adiponectin concentrations of patients whose glycated albumin level reduced by more than 10% of the levels before treatment were significantly lower than those of patients whose glycaemic control was affected less (5.2 ± 0.6 vs. 8.0 ± 1.0 µg/ml, p < 0.05).

Conclusion:  Lower plasma adiponectin concentration predicts the clinical efficacy of pioglitazone.
Changes in sex hormone‐binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome
Authors: Niskanen L. , Laaksonen D. E. , Punnonen K. , Mustajoki P. , Kaukua J. , Rissanen A.
Published: March 2004

Background:  Mild hypoandrogenism in men, usually defined by low levels of testosterone, is a peculiar feature of abdominal obesity that independently predicts the development of insulin resistance and diabetes mellitus. Little is known about the short‐ and long‐term effects of weight loss on sex steroids in abdominally obese men, however.

Objectives:  We assessed the effect of rapid weight loss and sustained weight maintenance on the plasma concentrations of testosterone and other sex hormones in 58 abdominally obese men (age, 46.3 ± 7.5 years; body mass index, 36.1 ± 3.8 kg/m2; waist girth, 121 ± 10 cm) with the metabolic syndrome.

Results:  The men lost on average 16.3 ± 4.5 kg during a 9‐week very low‐calorie diet (VLCD) and maintained 14.3 ± 9.1 kg weight loss after a 12‐month maintenance period (vs. baseline, p < 0.001). Sex hormone‐binding globulin (SHBG) increased from 27.6 ± 11.9 to 48.1 ± 23.5 nmol/l during the VLCD but decreased to 32.6 ± 12.9 nmol/l during weight maintenance, which was still higher than at baseline (p < 0.001). Free testosterone (fT) increased from 185 ± 66 to 208 ± 70 pmol/l (p = 0.002) during the VLCD and remained high after 1 year of weight maintenance (212 ± 84 pmol/l, p = 0.002). Total testosterone levels followed a pattern intermediate between fT and SHBG. Plasma estradiol and dehydroepiandrosterone sulphate concentrations changed only transiently or not at all.

Conclusions:  Rapid weight loss with successful weight maintenance in abdominally obese men with the metabolic syndrome brings about a sustained increase in fT levels. The dramatic increase in SHBG attenuated initially during weight maintenance but remained elevated. These findings may be important with regard to prevention of progressive metabolic decompensation and cardiovascular disease associated with obesity and the metabolic syndrome.
Ophthalmoscopic and morphogenetic changes in rat lens induced by galactose: attenuation by pyruvate
Authors: Kalakonda S. , Hegde K. R. , Varma S. D.
Published: March 2004

Background: Investigations have been conducted on the potential of pyruvate, a normal tissue metabolite, in the prevention of cataract formation.

Methods: Cataract was induced by maintaining young rats on a diet containing 30% galactose. The progress of cataract was monitored by visual inspection and ophthalmoscopic and slit‐lamp examinations. The protective effect of pyruvate was assessed by incorporating it in the galactose diet and drinking water. The progress of cataract was substantially thwarted by this dietary regimen.

Results: Substantial morphogenetic changes in the lenses of the galactosaemic animals, which by themselves can offer obstruction to light penetration through the lens and scattering, were significantly attenuated. These changes were ascertained by histological detection of errors in cellular differentiation and their migration in unwanted areas.

Conclusions: As per previous studies, the pyruvate effect is attributed to its direct effect on the biochemistry of lens related to the inhibition of oxidative stress, as well as to its effect on tissue physiology related to the lifelong process of organogenesis, characteristic of this tissue.
Effects of gender, Helicobacter pylori and hepatitis B virus serology status on cardiovascular and renal complications in Chinese type 2 diabetic patients with overt nephropathy
Authors: Lo M. K. W. , Lee K.‐F. , Chan N. N. , Leung W. Y. S. , Ko G. T. C. , Chan W.‐B. , So W.‐Y. , Ng M. C. Y. , Ho C.‐S. , Tam J. S. L. , Lam C. W. K. , Tong P. C. Y. , Chan J. C. N.
Published: March 2004

Background:  The aim of this study was to investigate whether chronic infections with Helicobacter pylori and hepatitis B virus (HBV) might affect clinical outcomes in Chinese type 2 diabetic patients with advanced nephropathy.

Methods:  A prospective study of 97 type 2 diabetic patients with clinical proteinuria and renal insufficiency (median serum creatinine 200 µmol/l).

Results:  During a median follow‐up period of 2 years, 34 developed end‐stage renal disease (ESRD), 28 had cardiovascular endpoints and 11 patients had died (seven men and four women), and 52.7% developed a combined endpoint. Female patients had longer disease duration, higher blood pressure, lower body weight but higher serum creatinine and spot urine albumin : creatinine ratio as well as lower haemoglobin than male patients. On logistic regression analysis, female gender (hazard ratio: 5.91, p = 0.02), negative H. pylori serology (8.39, p = 0.004), baseline serum creatinine (1.04, p = 0.001) and haemoglobin (1.86, p = 0.01) were independent predictors for ESRD. Systolic blood pressure (1.04, p = 0.003), prior treatment with angiotensin‐converting enzyme inhibitors or angiotensin II receptor antagonists (3.41, p = 0.04) and positive hepatitis B surface antigen (4.88, p = 0.025) were independent predictors for cardiovascular endpoints. Female gender (7.89, p = 0.002) and baseline serum creatinine (1.05, p < 0.001) were independent predictors for combined death and cardio‐renal endpoints.

Conclusions:  In Chinese type 2 diabetic patients with clinical proteinuria renal insufficiency, there were high rates of death and cardio‐renal outcomes. Female gender, low haemoglobin and negative H. pylori serology were important predictors for ESRD, whereas chronic HBV infection was associated with increased cardiovascular risks.