bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALTEREDl‐ARGININE/NITRIC OXIDE SYNTHASE/NITRIC OXIDE PATHWAY IN THE VASCULAR ADVENTITIA OF RATS WITH SEPSIS
Authors: Jia Yue Xia , Pan Chun Shui , Yang Jing Hui , Liu Xiu Hua , Yuan Wen Jun , Zhao Jing , Tang Chao Shu , Qi Yong Fen 
Published: December 2006

SUMMARYIn recent studies, the vascular adventitia has been established as an important source of inducible nitric oxide synthase (iNOS) and subsequent nitric oxide (NO) production, even more powerful than the media in response to certain inflammatory factors, such as lipopolysaccharide (LPS). The adventitia has an independentl‐arginine (l‐Arg)/NOS/NO pathway and is involved in the regulation of vascular function. In the present study, we explored the changes in and the pathophysiological significance of thel‐Arg/NOS/NO pathway in the adventitia of rats with sepsis.Sepsis was induced by caecal ligation and puncture in order to observe changes inl‐Arg transport, NOS gene expression and activity and NO generation in the vascular adventitia to determine the mechanism of activation of thel‐Arg/NOS/NO pathway.Severe sepsis resulted in severe disturbance of haemodynamic features, with decreased mean arterial blood pressure, brachycardia and inhibited cardiac function (decreased left ventricular ±dP/dtmax). Left ventricular end‐diastolic pressure was elevated threefold (P < 0.01) under anaesthesia. Rats with sepsis showed severe glucopenia and lacticaemia. Plasma levels of the inflammatory factors macrophage chemoattractant protein‐1 and interleukin‐8 were increased five‐ and 29‐fold, respectively (P < 0.01).In the adventitia of the thoracic and abdominal aortas, thel‐Arg/NO pathway was similarly characterized: the uptake of [3H]‐l‐Arg was Na+independent, with the peak occurring at approximately 40 min incubation. Total NOS activity was largely calcium independent (> 90%). The Vmaxofl‐Arg transport in the sepsis group was increased by 83.5% (P < 0.01), but the Kmvalue was not significantly different compared with controls.The mRNA levels of cationic amino acid transporter (CAT)‐1 and CAT‐2B in the sepsis group were increased by 86 and 62%, respectively (bothP < 0.01). Inducible NOS activity was increased 2.8‐fold compared with controls (P < 0.01) and iNOS mRNA levels were elevated approximately sixfold (P < 0.01). The NO levels in the plasma and incubation media (incubation for 40 min) in the sepsis group were increased by 144 and 273%, respectively (bothP < 0.01).The Arg/NOS/NO pathway was activated in the vascular adventitia of rats with sepsis shock. Thel‐Arg/NOS/NO pathway in the aortic adventitia may play an important role in the pathogenesis of sepsis and septic shock.
ROSIGLITAZONE MODULATES FASTING AND POST‐PRANDIAL PARAOXONASE 1 ACTIVITY IN TYPE 2 DIABETIC PATIENTS
Authors: Van Wijk Jeroen , Coll Blai , Cabezas Manuel Castro , Koning Eelco , Camps Jordi , Rabelink Ton , Mackness Bharti , Joven Jorge 
Published: December 2006

SUMMARY

In the present study, we have explored the effect of rosiglitazone on post‐prandial paraoxonase (PON)‐1, an enzyme with potent anti‐oxidant properties that may protect against atherosclerosis because increased post‐prandial lipaemia, although sometimes understated, is part of the diabetic dyslipidaemia.
A randomized, cross‐over, placebo‐controlled, double‐blind clinical trial was performed. Participants (19 type 2 diabetic patients on oral antihyperglycaemic agents) were randomly assigned to receive either placebo or rosiglitazone 4 mg twice daily for 8 weeks. After a 6 week wash‐out, the alternative treatment was implemented. Standardized 6 h oral fat‐loading tests were performed after each treatment period.
Patients assigned to rosiglitazone had increased fasting PON‐1 activity (from 331 ± 29 to 362 ± 32 U/L before treatment vs after treatment, respectively; P = 0.015), although the PON‐1 mass did not change (68.8 ± 21.1 vs 64.2 ± 25.4 mg/L before treatment vs after treatment, respectively). In addition, rosiglitazone significantly decreased fasting plasma peroxides compared with placebo (162 ± 25 vs 214 ± 28 mmol/L, respectively; P = 0.019). The post‐prandial fall in PON‐1 activity, expressed as area under the curve, was attenuated by rosiglitazone (−97 ± 14 vs−161 ± 24 Uh/L for rosiglitazone vs placebo, respectively; P = 0.02) and the increase in PON‐1 activity caused by rosiglitazone correlated with reductions in fasting plasma glucose (r = ‐0.42; P < 0.05), homeostatic model assessment index (r = ‐0.59; P < 0.01) and peroxides (r = ‐0.40; P = 0.07).
The present data indicate that rosiglitazone may convey increased protection against the oxidative modification that represents increased post‐prandial lipaemia.
GREEN TEA EXTRACT IMPEDES DYSLIPIDAEMIA AND DEVELOPMENT OF CARDIAC DYSFUNCTION IN STREPTOZOTOCIN‐DIABETIC RATS
Authors: Anandh Babu PV , Sabitha KE , Shyamaladevi CS 
Published: December 2006

SUMMARY

The efficacy of green tea extract (GTE) on serum and cardiac lipids was investigated in streptozotocin (STZ)‐diabetic rats.
Diabetes was induced in rats by a single intraperitoneal injection of STZ (60 mg/kg bodyweight). Six weeks after the induction of diabetes, GTE was administered orally for 4 weeks (300 mg/kg bodyweight daily). Bodyweight, heart weight, heart weight : bodyweight ratio, blood glucose, serum and cardiac lipids were determined in experimental rats.
In diabetic rats, there was a significant decrease in bodyweight with an increase in heart weight : bodyweight ratio and blood glucose. Diabetic rats had significantly increased serum levels of cholesterol, triglycerides, free fatty acids and low‐density lipoprotein–cholesterol (LDL‐C) and decreased levels of high‐density lipoprotein–cholesterol (HDL‐C). In the hearts of diabetic rats, there was a significant increase in cholesterol, triglycerides and free fatty acids levels, with an increase in lipoprotein lipase activity.
The administration of GTE to diabetic rats resulted in significant recovery in bodyweight, heart weight : bodyweight ratio and blood glucose levels. The administration of GTE reduced cholesterol, triglyceride, free fatty acid and LDL‐C levels, and increased HDL‐C levels, in the serum of diabetic rats. In addition, GTE decreased cholesterol, triglyceride, free fatty acids levels and lipoprotein lipase activity in the myocardium of diabetic rats. These beneficial effects of GTE are ascribed to its antihyperglycaemic and hypolipidaemic activity. In conclusion, green tea can reduce the risk of cardiovascular disease in diabetes with a significant improvement in lipid metabolism.
EXPRESSION OF HUMAN FACTOR IX GENE IN MURINE PLASMA THROUGH LENTIVIRAL VECTOR‐INFECTED HAEMATOPOIETIC STEM CELLS
Authors: Chen Haoming , Yao Hengmei , Huang Lu , Shen Qi , Jia William , Xue Jinglun 
Published: December 2006

SUMMARY

Haematopoietic stem cells (HSC) are an attractive target for gene therapy. Gene transfer to HSC can provide a potential cure for many inherited diseases. Moreover, recombinant lentiviral vectors can transfer genes efficiently to HSC. In the present study, we used the recombinant lentiviruses FUGW (Flip, ubiquitin promoter, GFP and WRE vector) and FUXW (Flip, ubiquitin promoter, F IX and WRE vector), which carry the enhanced green fluorescent protein (EGFP) and human factor IX (hFIX) gene, respectively, to infect HSC.
High titres of recombinant lentivirus were prepared from 293T cells by calcium phosphate‐mediated transient cotransfection. Murine mononuclear cells (MNC) separated from murine bone marrow and HSC separated by magnetic cell sorting were cultured in vitro. Cells they were infected by the recombinant lentiviruses FUGW and FUXW. The expression of EGFP was observed under a fluorescent microscope and was analysed by fluorescence‐activated cell sorting, whereas the expression of hFIX was detected by ELISA.
The results show that the lentiviral vectors can efficiently infect murine HSC in vitro and that transduction was more efficient following cytokine treatment with interleukin (IL)‐3, IL‐6 and stem cell factor.
Haematopoietic stem cells infected with lentivirus FUXW were transplanted into [60Co]‐irradiated non‐obese diabetic/severe combined immunodeficiency (NOD‐SCID) mice. The expression of hFIX in the blood plasma of the transplanted mice reached a peak of 44.9 ± 7.6 ng/mL on Day 7. An assay of transaminase levels and a histological study of the liver showed that there was no significant damage following HSC transplantation to mice.
The results of the present study suggest that transplantation of HSC results in the persistant expression of hFIX in mice, which may be useful in haemophilia B gene therapy.
TIME‐DEPENDENT TRANSITION FROM H2O2–EXTRACELLULAR SIGNAL‐REGULATED KINASE‐ TO O2−–NITRIC OXIDE‐DEPENDENT MECHANISMS IN THE STIMULATORY EFFECT OF LEPTIN ON RENAL Na+/K+‐ATPase IN THE RAT
Authors: Marciniak Andrzej , Borkowska Ewelina , Kȩdra Anna , Rychlik Monika , Beltowski Jerzy 
Published: December 2006

SUMMARYRecent studies suggest that leptin, a peptide hormone secreted by white adipose tissue, is involved in the pathogenesis of arterial hypertension, in part by regulating renal sodium handling. Previously, we have demonstrated that in normal rats leptin has a time‐dependent effect on renal Na+/K+‐ATPase that drives tubular sodium reabsorption. Short‐term leptin infusion results in a transient decrease in Na+/K+‐ATPase activity, whereas prolonged administration stimulates the enzyme.In the present study, we investigated whether these acute effects of leptin are preserved in rats with experimentally induced chronic hyperleptinaemia.Hyperleptinaemia was induced by administration of exogenous leptin (0.25 mg/kg twice daily, s.c., for 7 days). Acute effects of leptin in anaesthetized control (normoleptinaemic) and hyperleptinaemic animals was investigated. Leptin was infused into the abdominal aorta proximally to the renal arteries for 0.5, 1, 2 or 3 h.Leptin (1 µg/min per kg) had a time‐dependent effect on renal Na+/K+‐ATPase in both the control and hyperleptinaemic groups. The inhibitory effect observed after 0.5 h infusion was impaired in the hyperleptinaemic group. However, in both groups this effect was abolished by the Janus kinase inhibitor tyrphostin AG490 (100 nmol/min per kg), as well as by the phosphatidylinositol 3‐kinase inhibitors wortmannin (10 nmol/min per kg) and LY294002 (1 µmol/min per kg).The stimulatory effect of leptin on Na+/K+‐ATPase activity was observed after 3 h of infusion and was of similar magnitude in control and hyperleptinaemic groups. In the control group, the stimulatory effect of leptin was abolished by the NADPH oxidase inhibitor apocynin (1 µmol/min per kg), the H2O2scavenger catalase (1 mg/min per kg) and the extracellular signal‐regulated kinase (ERK) inhibitor PD98059 (100 nmol/min per kg). In contrast, in the hyperleptinaemic group, the stimulatory effect of leptin was abolished by the cGMP analogue 8‐bromo‐cGMP (100 nmol/min per kg) and by the superoxide dismutase mimetic tempol (100 µmol/min per kg) but was not affected by catalase or PD98059.Leptin increased urinary H2O2excretion and ERK phosphorylation in the renal tissue only in the control group.The results suggest that the acute stimulatory effect of leptin on renal Na+/K+‐ATPase is mediated by divergent mechanisms depending on the chronic leptin level (i.e. by H2O2‐dependent stimulation of ERK in normoleptinaemic animals and by superoxide‐dependent impairment of the nitric oxide–cGMP pathway in hyperleptinaemic rats).
PROTECTIVE EFFECTS OF BENDAZAC LYSINE ON DIABETIC PERIPHERAL NEUROPATHY IN STREPTOZOTOCIN‐INDUCED DIABETIC RATS
Authors: Yu Jun‐Xian , Zhang Yin‐Di , Yin Xiao‐Xing , Shen Jian‐Ping , Qiu Jun , Yin Hong‐Lin , Jiang Shao‐Jun 
Published: December 2006

SUMMARY

Diabetic neuropathy is a many faceted complication of both type I and II diabetes. The aim of the present study was to investigate the effects of bendazac lysine (BDL), an anticataract drug, on experimental diabetic peripheral neuropathy (DPN) in rats.
Diabetes was induced in rats by intraperitoneal injection of 75 mg/kg streptozotocin (STZ) dissolved in 0.1 mol/L citrate buffer (pH 4.4). Bendazac lysine was administered to rats at doses of 50, 100 and 200 mg/kg twice a day for 12 weeks.
Diabetic rats without treatment showed hypopraxia, polydipsia, polyuria, slow weight gain, cataract, increased tail‐flick threshold temperature, decreased motor nerve conduction velocity (nd induced pathological morphological changes of myelinated nerve fibres. All these symptoms were ameliorated in diabetic rats treated with BDL. Bendazac lysine ameliorated the blood glucose concentration, glycosylated haemoglobin levels and insulin levels in the plasma of diabetic rats, reduced aldose reductase activity in erythrocytes and advanced glycation end‐products in both nerves and serum and increase the activity of glutathione peroxidase in the nerves and Na+/K+‐ATPase in the nerves and erythrocytes.
Bendazac lysine exerts its protective effects against the progression of diabetic peripheral neuropathy in STZ‐diabetic rats through multiple mechanisms and is a potential drug for the prevention of deterioration in DPN.
COMPARISON BETWEEN GASTRIC SCINTIGRAPHY AND THE [13C]‐ACETATE BREATH TEST WITH WAGNER–NELSON ANALYSIS IN HUMANS
Authors: Sanaka Masaki , Urita Yoshihisa , Sugimoto Motonobu , Yamamoto Takatsugu , Kuyama Yasushi 
Published: December 2006

SUMMARY

The [13C]‐acetate breath test (ABT) quantifies gastric emptying as the half [13CO2]‐excretion time (T1/2b), but T1/2b differs from the scintigraphic half‐emptying time (T1/2s). The aims of the present study were to accurately determine the half‐emptying time by ABT with Wagner–Nelson analysis (T1/2WN), to compare T1/2WN with T1/2s and to validate the Wagner–Nelson strategy in ABT.
For a comparative study, eight volunteers simultaneously underwent ABT and scintigraphy. Anterior images were acquired and breath samples were collected every 15 min for 4.0 h after ingestion of a 200 kcal liquid meal labelled with 37 MBq [99mTc]‐colloidal sulphur and 100 mg [13C]‐acetate. For the validation experiment, another six volunteers underwent ABT, on two randomized occasions, using the 200 kcal liquid meal with 100 mg [13C]‐acetate. On either of the two occasions, a gel‐forming agent was stirred into the meal to intentionally delay gastric emptying by increasing meal viscosity. Breath samples were collected at regular 15 min intervals for 4 h post ingestion.
The Wagner–Nelson equation for ABT is F(t) = (Abreath(t) + C(t)/0.65)/Abreath(∞), where F(t) is a fractional dose of the [13C] label emptied, C(t) is the [13CO2] excretion (% dose/h), Abreath(t) is the area under the C(t) curve (% dose) and Abreath(∞) is the ultimate [13CO2] recovery in breath (% dose). The percentage gastric retention was estimated as 100 × (1 − F(t)). The time plots of scintigraphic activity and 100 × (1 − F(t)) were fitted to y(t) = 100 × e−K×t, K values were estimated mathematically for each plot by regression analysis and T1/2s and T1/2WN were calculated as (ln2)/K. The time versus pulmonary [13CO2] excretion plots were fitted to z(t) = m × k × β × e−kt(1 − e−k×t)β−1, where m, k and β are constants; T1/2b was calculated as –(ln(1 − 2−1/β)]/k.
Values of T1/2WN were closer to T1/2s than T1/2b, although T1/2WN and T1/2b yielded significant under‐ and overestimation of T1/2s, respectively. The high viscosity meal significantly prolonged T1/2WN and T1/2b; T1/2WN could detect the delayed transit of the viscous meal more sensitively than T1/2b.
The Wagner–Nelson method improves the accuracy of the ABT.
Clinical differentiation of atypical pneumonia using Japanese guidelines
Authors: ISHIDA Tadashi , MIYASHITA Naoyuki , NAKAHAMA Chikara 
Published: December 2006

Background and objective:  Atypical pneumonia occupies an important position in community‐acquired pneumonia. The aim of this study was to examine whether making a diagnosis of atypical pneumonia is possible based upon the Japanese Respiratory Society guidelines.Methods:  The data from three prospective studies were reviewed. A total of 285 patients with mycoplasmal pneumonia or chlamydial pneumonia and 515 patients with pneumococcal pneumonia or Haemophilus influenzae pneumonia were assessed to determine whether these pneumonias met the diagnostic criteria for atypical pneumonia used in the Japanese Respiratory Society guidelines. The criteria were: (i) age less than 60 years; (ii) no or only minor underlying diseases; (iii) persistent cough; (iv) limited chest auscultatory findings; (v) no sputum, or no identified aetiological agent by rapid diagnosis; and (vi) a peripheral white blood cell count below 10 000/µL.Results:  All items of the criteria proved to be valid except for ‘age’ in patients with Chlamydophila pneumoniae pneumonia using multiple regression analysis. The sensitivity and specificity for atypical pneumonia were 77.0% and 93.0% based on four or more of the criteria respectively.Conclusion:  Pure atypical pneumonia can be differentiated to some degree by clinical symptoms and laboratory findings. It is important to differentiate and treat bacterial pneumonia and atypical pneumonia in regions such as Japan, where Streptococcus pneumoniae resistance to macrolides is high. Treatment covering the two types of pneumonia should be considered in elderly patients and those with underlying respiratory disease.
Early switch to oral antibiotics and early discharge guidelines in the management of community‐acquired pneumonia
Authors: LEE Richard Wai Wing , LINDSTROM Steven Terence 
Published: December 2006

Background and objective:  The major cost of managing community‐acquired pneumonia (CAP) relates to the duration i.v. antibiotic use and length of hospital stay (LOS). Guidelines on early switch to oral antibiotics and early discharge from hospital may help to achieve a unified approach to managing CAP. The aim of this study was to assess the benefits and safety of these guidelines in an Australian respiratory medicine unit.Methods:  This prospective study included consecutive patients admitted with a diagnosis of CAP over a 6‐month period. Early switch to oral antibiotics and early discharge guidelines were implemented one month prior to the evaluation period. Comparison was made to a retrospective control group admitted before the guidelines were implemented. Data collection included patient demographics, clinical and outcome parameters, duration of i.v. antibiotics and LOS. Thirty‐day outcomes on patient safety and satisfaction were collected from the prospective group.Results:  One hundred and twenty‐five patients in the prospective group were compared to 100 patients in the controls. Baseline characteristics were similar between the comparison groups. Both the mean duration of i.v. antibiotics used (3.38 ± 0.22 vs. 3.99 ± 0.28 days, P = 0.03) and LOS (7.62 ± 0.60 vs. 8.36 ± 0.55 days, P = 0.04) were significantly shorter in the prospective group. Thirty‐day readmission rate was 6% and patient self‐reported overall satisfaction was 93.9% in those who were followed up.Conclusions:  The use of early switch and early discharge guidelines for CAP reduced the duration of i.v. antibiotics and LOS while maintaining high levels of safety and patient satisfaction.
Open‐label, randomized comparison trial of long‐term outcomes of levofloxacin versus standard antibiotic therapy in acute exacerbations of chronic obstructive pulmonary disease
Authors: RUIZ‐GONZÁLEZ Agustin , GIMÉNEZ Antonio , GÓMEZ‐ARBONÉS Xavier , SOLER‐GONZÁLEZ Jorge , SÁNCHEZ Virginia , FALGUERA Miquel , PORCEL Jose M. 
Published: December 2006

Background and objective:  This study investigated whether treating acute exacerbations of COPD (AE‐COPD) with levofloxacin modifies the long‐term outcome of COPD patients in comparison with standard antibiotic regimens.Methods:  A 6‐month open‐label clinical trial of AE‐COPD patients compared the outcomes of treating with levofloxacin versus standard therapy (clarithromycin, cefuroxime, or amoxicillin/clavulanate) at recommended doses for 10 days. Several variables were analysed: pulse oximetry, FEV1, health‐related quality of life, infection‐free interval, number of exacerbations, hospitalizations due to an exacerbation and mortality.Results:  Of the 116 patients initially enrolled, completion or withdrawal information was available for 50 patients in the levofloxacin arm and 52 in the standard therapy arm. At the end of the study, there were no differences in mortality (17.8% vs. 22.9%, P = 0.53), number of exacerbations (33 vs. 41, P = 0.40), pulse oximetry (median 91.71% vs. 92.46%, P = 0.18), FEV1 (median 51.31% vs. 47.14%, P = 0.30), health‐related quality of life (median 8.63 vs. 10.75, P = 0.94) and infection‐free interval (median 112 vs. 101 days, P = 0.72), for the levofloxacin and standard therapy, respectively. However, 12 out of 33 (33.6%) exacerbations treated with levofloxacin required in‐hospital management versus 27 out of 41 (65.8%) treated with standard therapy (P = 0.02).Conclusion:  This preliminary study suggests that 10‐day treatment of AE‐COPD with levofloxacin is associated with a reduction in hospitalizations compared with standard antibiotics despite there being no significant benefit in other outcome variables.
Monoclonal antibody 7F9 recognizes rat protein homologous to human carboxypeptidase‐M in developing and adult rat lung
Authors: FUJIWARA Naoyuki , IKEDA Mitsunobu , HIRABAYASHI Susumu , MORI Hiroki , SHIRASAWA Madoka , KANSAKU Ai , SUNAMORI Makoto , HATA Yutaka 
Published: December 2006

Background and objective:  The purpose of this study was to obtain an antibody that would be useful for investigating the yet unclear molecular mechanism underlying the differentiation of lung alveolar type I and II cells.Methods:  Monoclonal antibodies were raised against membrane proteins from embryonal day 18.5 rat lungs and characterized by immunoblotting on rat lung lysates at various developmental stages to select an appropriate clone. The antigen of the selected antibody was purified by serial column chromatography and immunoprecipitation and identified by mass spectrometry.Results:  7F9 antibody recognizes a 65‐kDa protein that is expressed most prominently from embryonal day 20.5 to postnatal day 1. This protein was identified as a rat protein that is similar to 5730456K23Rik protein. The protein is homologous to human carboxypeptidase‐M. Although human carboxypeptidase‐M is known as a marker of type I cells, the expression of this rat protein was detected in columnar epithelial cells expressing type II cell markers, SP‐C and a lamellar body protein ABCA3, in developing lung. Its expression was detected in alveolar cells lacking T1α, a type I cell marker protein, in adult lung. It was also expressed in RLE‐6TN cells derived from type II cells. The expression in RLE‐6TN cells was down‐regulated by transforming growth factor‐β1 and up‐regulated by Wnt3a.Conclusions:  7F9 antibody detects a protein in rat lung cells expressing type II markers. The antibody is a useful tool for studying signalling triggered by transforming growth factor‐β1 and Wnt3a in rat type II cells.