bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboplatin Sustained Delivery System Using Injectable Microspheres
Authors: Manunta M. L. , Gavini E. , Chessa G. , Passino E. S. , Careddu G. M. , Giua S. , Mollica A. , Demontis M. P. , Leoni A. , Muzzetto P. 
Published: September 2005

SummaryA controlled carboplatin delivery system using biodegradable polymer has been used in this study. The purpose was to evaluate the local and systemic effects of injectable, biodegradable microspheres containing carboplatin when injected as aqueous suspension subcutaneously in rats. Biocompatibility and toxicity of empty microspheres and microspheres loaded with carboplatin were evaluated by clinical and histological examination. The diffusion of carboplatin in tissues and time of drug release were evaluated by platinum determination in plasma and tissues over the time. The results of the study suggest that microspheres provide a sustained slow release of carboplatin and that multiple inoculations of microspheres containing drug and no evidence of local or systemic toxicity is found. This device may be useful in the treatment of solid tumours.
Renal (Uremic) Encephalopathy in a Goat
Authors: Radi Z. A. , Thomsen B. V. , Summers B. A. 
Published: September 2005

SummaryRenal encephalopathy was diagnosed in a 2‐year‐old male boar goat with a history of chronic weight loss and ataxia. Histopathological examination of the brain revealed a striking myelin vacuolation distributed mainly in two patterns: (i) along the junction of the neocortex and corona radiata, and (ii) in the bundles of the internal capsule as it dissects through the basal nuclei. The kidneys had diffuse severe tubular and glomerular necrosis and degeneration. The neural lesions are consistent with renal (uremic) encephalopathy. To the authors’ knowledge, this is the first report of renal encephalopathy in a goat.
Prevalence of Osseous Fragments in Distal and Proximal Interphalangeal, Metacarpo‐ and Metatarsophalangeal and Tarsocrural Joints of Hanoverian Warmblood Horses
Authors: Stock K. F. , Hamann H. , Distl O. 
Published: September 2005

SummaryThe prevalence of osseous fragments in different limb joints was analysed in 3749 young Warmblood riding horses, which were pre‐selected for sale at auction from 1991 to 1998 by the Association of Hanoverian Warmblood Breeders (Verband hannoverscher Warmblutzüchter e.V.) in Verden (Aller), Germany. The evaluation of these horses was based on a standardized radiological examination, including the distal interphalangeal (DIJ), the proximal interphalangeal (PIJ), the metacarpo‐ and metatarsophalangeal (MC/MTJ) and the tarsocrural joints (TCJ). In 32% of all horses at least one osseous fragment was found on these radiographs. TCJ were affected in 9.6% of the horses and MC/MTJ in 20.7%. The percentage of horses affected in the MTJ was significantly higher (13.7%) than that of horses affected in the MCJ (9.5%). The prevalences of osseous fragments were considerably lower in DIJ (4.5%) and PIJ (0.9%). Osseous fragments only occurred either in DIJ or PIJ or MC/MTJ or TCJ in 87% of the affected horses. Depending on the joint type, osseous fragments were found in analogous joints in the front and the hind limbs in up to 26% of the affected horses, whilst bilateral affection occurred in between 10% and 46% of the horses. Distribution of osseous fragments in the limb joints investigated here did not differ significantly between male and female horses. There was a significant increase in the percentage of horses with osseous fragments in MC/MTJ during the study period. The results of this study indicate the need to act against the high prevalences of osseous fragments in the limb joints of young Warmblood riding horses.
Characterization of the Cytokine Pattern of Porcine Bone Marrow‐Derived Cells Treated with 1α,25(OH)2D3
Authors: Sipos W. , Duvigneau J. C. , Schmoll F. , Exel B. , Hofbauer G. , Baravalle G. , Hartl R. T. , Dobretsberger M. , Pietschmann P. 
Published: September 2005

SummaryThe biologically active form of vitamine D3 [1α,25(OH)2D3] has recently been described not only to influence bone metabolism but also to exert immunomodulating activities, which may have an impact on bone formation/resorption as well. In this study, we analysed the effects of 1α,25(OH)2D3 on the cytokine pattern of porcine bone marrow‐derived cells from piglets aged 1–3 weeks. After culture for 1 week, the number of osteoclasts was determined, with tartrate‐resistant acid phosphatase (TRAP)‐positive, multinucleated cells being considered osteoclasts. Cultured bone marrow cell‐derived mRNA was subjected to semiquantitative RT‐PCR specific for a panel of porcine cytokines (IL‐1α, IL‐6, IL‐8, IL‐10, and TNF‐α). In addition, an immunofluorescence analysis using anti‐porcine mAbs specific for IL‐1β, IL‐2, IL‐4, IL‐6, IL‐12, TNF‐α, and IFN‐γ was performed. In order to prove the existence of a porcine homologue of the receptor activator of NF‐κB ligand (RANKL) bone marrow cell‐ as well as porcine white blood cell‐derived mRNA was investigated by RT‐PCR using primer pairs specific for murine RANKL. Cell culture supernatant was analysed for soluble RANKL by means of an ELISA designed for quantification of human RANKL. By means of RT‐PCR, expression of IL‐1α, IL‐6, IL‐8, IL‐10 and TNF‐α mRNA could be found in cells cultured with and without 1α,25(OH)2D3. Immunofluorescence analysis revealed that IL‐1, IL‐6, and TNF‐α were produced by both stromal cells and osteoclasts. Besides its known osteoclastogenic effects, 1α,25(OH)2D3 tended to downregulate the respective cytokines, but significantly upregulated RANKL expression. The homology between the porcine RANKL‐specific sequence and the corresponding human RANKL sequence was 79%. The data found support the idea that porcine bone marrow cell cultures may provide a suitable alternative to murine systems in human osteological research.
Daily Rhythms of Blood Pressure, Heart Rate, and Body Temperature in Fed and Fasted Male Dogs
Authors: Piccione G. , Caola G. , Refinetti R. 
Published: September 2005

SummaryDaily or circadian rhythmicity in physiological processes has been described in a large number of species of birds and mammals. However, in dogs, most studies have either failed to detect rhythmicity or have found that rhythmicity reflects merely an acute exogenous effect of feeding rather than an autonomous rhythmic process. In the present study, we investigated the rhythmicity of body temperature, blood pressure, and heart rate in dogs fed daily as well as in dogs deprived of food for 60 h. Our results document clear rhythmicity in all three parameters and demonstrate that the rhythmicity is independent of the feeding schedule. The failure of various previous investigations to document daily rhythmicity in dogs is probably due to lack of experimental rigour rather than to weakness of daily rhythmicity in dogs.
Current models of human prostate contractility
Authors: Haynes John M , Ventura Sabatino 
Published: September 2005

SUMMARY1. The human prostate is a compact gland contributing to seminal fluid. With increasing age, most humans will develop benign prostatic hyperplasia, a condition of prostatic enlargement and contractility that leads to occlusion of the urethra. Over many years, investigators have used a variety of animal and cell culture models to elucidate some of the contractile and proliferative mechanisms that may be associated with the development of this condition.2. This review briefly assesses the current state of knowledge of the mechanisms underlying human prostatic contractility and compares it with that of animal and cell culture models. It is not intended as a comprehensive methodological review, nor is it intended to indicate our preferences for either model. Our aim is to correlate findings from animal and cell culture models with the current understanding of human prostate contractility.3. We hope that the present review will increase awareness of the suitability of the current models in developing our understanding of benign prostatic hyperplasia.
The anti‐diabetic drug miglitol is protective against anginal ischaemia through a mechanism independent of regional myocardial blood flow in the dog
Authors: Uno Yoshihiro , Minatoguchi Shinya , Arai Masazumi , Wang Ningyuan , Chen Xue‐Hai , Hashimoto Kazuaki , Lu Cuanjiang , Takemura Genzou , Fujiwara Hisayoshi 
Published: September 2005

SUMMARY1. In the present study, we attempted to clarify whether the antidiabetic drug miglitol, an α‐glucosidase inhibitor, has a protective effect against anginal ischaemia. We had reported previously that miglitol reduces myocardial infarct size through inhibition of glycogenolysis during ischaemia in rabbits. However, the effect of miglitol on anginal ischaemia remains unknown.2. In open‐chest beagle dogs with a severely stenosed left anterior descending coronary artery, an epicardial electrode was attached to the surface of the risk area of the left ventricle and a microdialysis probe was implanted into the myocardium to measure ST segment changes and interstitial lactate accumulation. The first episode of anginal ischaemia was induced by atrial pacing and phenylephrine infusion (50–100 µg/min) for 10 min. The second episode of anginal ischaemia was induced 210 min after the first episode. Miglitol (10 mg/kg, i.v.) was administered to the miglitol group (n = 10) 30 min before the second episode of anginal ischaemia, whereas saline was administered to the control group (n = 10). Regional myocardial blood flow was measured using coloured microspheres.3. There was no significant difference in regional myocardial blood flow in the risk and non‐risk areas between the first and second episodes of anginal ischaemia and between the miglitol and control groups. During the first and second episodes of anginal ischaemia, the ST segment was decreased to a similar extent in the control group. Although ST segment depression during the first episode of anginal ischaemia was similar in both groups, ST segment depression during the second episode of anginal ischaemia was significantly attenuated in the miglitol‐treated group compared with the control group (1.3 ± 0.4 vs 2.2 ± 0.4 mV, respectively). Miglitol significantly attenuated myocardial interstitial lactate accumulation in the risk area.4. In conclusion, in the present study miglitol improved ST segment depression and attenuated the accumulation of myocardial interstitial lactate during anginal ischaemia without altering regional myocardial blood flow. Miglitol has an anti‐anginal ischaemia effect via a mechanism that is independent of regional myocardial blood flow.
Antiviral activities of extracts and selected pure constituents of Ocimum basilicum
Authors: Chiang Lien‐Chai , Ng Lean‐Teik , Cheng Pei‐Win , Chiang Win , Lin Chun‐Ching 
Published: September 2005

SUMMARY1. Ocimum basilicum (OB), also known as sweet basil, is a well known medicinal herb in traditional Chinese medicine preparations. In the present study, extracts and purified components of OB were used to identify possible antiviral activities against DNA viruses (herpes viruses (HSV), adenoviruses (ADV) and hepatitis B virus) and RNA viruses (coxsackievirus B1 (CVB1) and enterovirus 71 (EV71)).2. The results show that crude aqueous and ethanolic extracts of OB and selected purified components, namely apigenin, linalool and ursolic acid, exhibit a broad spectrum of antiviral activity. Of these compounds, ursolic acid showed the strongest activity against HSV‐1 (EC50 = 6.6 mg/L; selectivity index (SI) = 15.2), ADV‐8 (EC50 = 4.2 mg/L; SI = 23.8), CVB1 (EC50 = 0.4 mg/L; SI = 251.3) and EV71 (EC50 = 0.5 mg/L; SI = 201), whereas apigenin showed the highest activity against HSV‐2 (EC50 = 9.7 mg/L; SI = 6.2), ADV‐3 (EC50 = 11.1 mg/L; SI = 5.4), hepatitis B surface antigen (EC50 = 7.1 mg/L; SI = 2.3) and hepatitis B e antigen (EC50 = 12.8 mg/L; SI = 1.3) and linalool showed strongest activity against AVD‐II (EC50 = 16.9 mg/L; SI = 10.5).3. No activity was noted for carvone, cineole, β‐caryophyllene, farnesol, fenchone, geraniol, β‐myrcene and α‐thujone.4. The action of ursolic acid against CVB1 and EV71 was found to occur during the infection process and the replication phase.5. With SI values greater than 200, the potential use of ursolic acid for treating infection with CVB1 and EV71 merits further investigation.
Expression and functional role of the RhoA/Rho‐kinase pathway in rat coeliac artery
Authors: Teixeira Cleber E , Jin Liming , Ying Zhekang , Palmer Trenis , Priviero Fernanda BM , Webb R Clinton 
Published: September 2005

SUMMARY1. Rho‐kinase (ROK) stimulation represents a key step in the maintenance of agonist‐induced contraction, an effect counteracted by nitric oxide (NO) released from the endothelium. The aim of the present study was to characterize the involvement of ROK in smooth muscle contraction of the rat coeliac artery using functional and expression studies.2. Rings of rat coeliac artery were mounted in 5 mL myographs containing warmed and oxygenated Krebs' solution. Rings were connected to isometric transducers and data were recorded in a PowerLab system (ADInstruments, Colorado Springs, CO, USA). After a 60 min equilibration period, preparations were precontracted with phenylephrine (1 µmol/L). Endothelial integrity was assessed by treating the vessels with acetylcholine (1 µmol/L). Expression of ROKα, ROKβ and RhoA was analysed using western blot, whereas Rho guanine nucleotide exchange factors (RhoGEF) were measured at the mRNA level.3. The addition of Y‐27632 (0.01–30 µmol/L) caused sustained relaxation of rings contracted with phenylephrine (PE; 1 µmol/L), with intact or denuded endothelium (pEC50 = 6.38 ± 0.03 and 5.65 ± 0.02, respectively). NG‐Nitro‐l‐arginine methyl ester (100 µmol/L) or 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (10 µmol/L), but not indomethacin (10 µmol/L), caused marked rightward shifts of the concentration–response curves to Y‐27632. The contractile response to KCl (80 mmol/L) was significantly reduced by Y‐27632, with a maximal inhibition of 57 ± 6%. Nifedipine (0.1–100 nmol/L) fully blocked KCl‐evoked contractions, but only marginally affected those in response to PE (27 ± 2% maximal inhibition). At 1 µmol/L, Y‐27632 also significantly enhanced relaxations to sodium nitroprusside (SNP; 0.0001–1 µmol/L).4. At 1 µmol/L, SNP (but not 1 µmol/L Y‐27632) significantly elevated the cGMP content above basal levels. Coincubation with SNP and Y‐27632 increased cGMP levels, but the results were not significantly different from those in the presence of SNP alone.5. Western blot analysis revealed the protein expression of RhoA, ROKα and ROKβ. The PDZ‐RhoGEF, p115RhoGEF and leukaemia‐associated RhoGEF (LARG) mRNA expression in coeliac artery was visualized by electrophoresis on agarose gels.6. The results clearly demonstrate a role for the RhoA/ROK signalling pathway in the regulation of rat coeliac artery smooth muscle contraction. The findings of the present study suggest that endogenous nitric oxide‐induced relaxation is mediated, in part, by inhibition of RhoA/ROK signalling in this tissue.
HIGH‐FAT DIET PREVENTS CARDIAC HYPERTROPHY AND IMPROVES CONTRACTILE FUNCTION IN THE HYPERTENSIVE DAHL SALT‐SENSITIVE RAT
Authors: Okere Isidore C , Chess David J , McElfresh Tracy A , Johnson Janean , Rennison Julie , Ernsberger Paul , Hoit Brian D , Chandler Margaret P , Stanley William C 
Published: September 2005

SUMMARY1. The role that dietary lipid and plasma fatty acid concentration play in the development of cardiac hypertrophy in response to hypertension is not clear.2. In the present study, we treated Dahl salt‐sensitive rats with either normal chow (NC), normal chow with salt added (NC + salt) or a diet high in long‐chain saturated fatty acids with added salt (HFD + salt). Cardiac function was assessed by echocardiography and left ventricular (LV) catheterization.3. The HFD + salt group had significantly higher plasma free fatty acid concentrations and myocardial triglyceride content compared with the NC + salt group, but did not upregulate the activity of the fatty acid oxidation enzyme medium chain acyl‐coenzyme A dehydrogenase. Systolic blood pressure was elevated to a similar extent in the NC + salt and HFD + salt groups compared with the NC group. Although LV mass was increased in the NC + salt group compared with the NC group, LV mass in the HFD + salt group did not differ from that of the NC group and was significantly lower than that in the NC + salt group.4. There was no evidence of cardiac dysfunction in the NC + salt group compared with the NC group; however, high fat feeding significantly increased LV contractile performance (e.g. increased cardiac output and peak dP/dt).5. In conclusion, the HFD + salt diet prevented the hypertrophic response to hypertension and improved the contractile performance of the heart. It remains to be determined whether preventing cardiac hypertrophic adaptations would be deleterious to the heart if the hypertensive stress is maintained long term.
Cooling‐induced contraction of the rat gastric fundus: Mediation via transient receptor potential (TRP) cation channel TRPM8 receptor and Rho‐kinase activation
Authors: Mustafa S , Oriowo MA 
Published: September 2005

SUMMARY1. Cooling has been shown to induce contractions of several smooth muscles in vitro. However, the mechanism involved in the response is not yet known. In the present study, we investigated the possible involvement of transient receptor potential (TRP) cation channel TRPM8 receptors and the Rho‐kinase pathway in cooling‐induced contraction of the rat fundus.2. Cooling‐induced contractions were inversely proportional to temperature. Contractions were significantly reduced (by 65.6 ± 2.4%; P < 0.05) in a Ca2+‐free (1 mmol/L EGTA) medium, but were not significantly inhibited by nifedipine (10−6 mol/L).3. Capsazepine (3 × 10−6 and 3 × 10−5 mol/L), a TRPM8 receptor antagonist, inhibited cooling‐induced contraction of the rat gastric fundus.4. The Rho‐kinase inhibitor Y‐27632 concentration‐dependently inhibited cooling‐induced contraction of the gastric fundus, producing approximately 90% inhibition at a concentration of 10−5 mol/L. Contractions were also inhibited by genistein (3 × 10−5 mol/L), a tyrosine kinase inhibitor, but not by GF 109203X (10−7 mol/L), a protein kinase C inhibitor.5. Using reverse transcription–polymerase chain reaction techniques, it was observed that the mRNA for the TRPM8 receptor and Rho‐kinase were expressed in the rat gastric fundus.6. These results would suggest that cooling‐induced contraction of the rat fundus is mediated by activation of TRPM8 receptors via a mechanism involving activation of Rho‐kinase.
Pathophysiological levels of the obesity related peptides resistin and ghrelin increase adhesion molecule expression on human vascular endothelial cells
Authors: Skilton Michael R , Nakhla Shirley , Sieveking Daniel P , Caterson Ian D , Celermajer David S 
Published: September 2005

SUMMARY1. In the present study, we sought to determine whether physiological or pathophysiological concentrations of obesity related peptides influence the key early atherogenic events of monocyte adhesion to endothelial cells and adhesion molecule expression using primary human cells.2. Human umbilical vein endothelial cells were grown to confluence and human monocytes were obtained by elutriation. Adhesion was assessed by automated cell counting and cell adhesion molecule expression (E‐selectin, intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1)) was assayed by ELISA.3. Experimental conditions included untreated control, ghrelin (100, 150, 450 and 1350 pmol/L), resistin (15, 40 and 100 ng/mL) and combined leptin and insulin (combinations of 30 and 120 pmol/L insulin and 5, 50 and 500 ng/mL leptin).4. Both resistin and ghrelin produced modest but significant increases in VCAM‐1 expression (110 ± 4 and 117 ± 13% compared with controls, respectively; both P ≤ 0.01). Ghrelin also increased ICAM‐1 expression (119 ± 17% of control; P ≤ 0.01).5. However, despite these increases in adhesion molecule expression, neither ghrelin nor resistin altered monocyte adhesion values.6. Neither leptin nor insulin altered monocyte adhesion to endothelial cells or cell adhesion molecule expression.7. Pathophysiologically relevant concentrations of ghrelin and resistin, within the range of concentrations exhibited by patients with anorexia nervosa or the Prader–Willi syndrome and type 2 diabetes, respectively, increase endothelial cell adhesion molecule expression, possibly contributing to increased atherosclerosis risk in such subjects.
Tetramethylpyrazine downregulates angiotensin II‐induced endothelin‐1 gene expression in vascular endothelial cells
Authors: Lee Wen‐Sen , Yang Hung‐Yu , Kao Pai‐Feng , Liu Ju‐Chi , Chen Cheng‐Hsien , Cheng Tzu‐Hurng , Chan Paul 
Published: September 2005

SUMMARY1. Tetramethylpyrazine (TMP) is one of the active ingredients of the Chinese herb Ligusticum wallichii Franchat. It is well documented that TMP exerts a cardiovascular protective effect. The aims of the present study were to examine whether TMP alters angiotenisn (Ang) II‐induced endothelin (ET)‐1 gene expression and to identify the putative underlying signalling pathways in vascular endothelial cells.2. Cultured vascular endothelial cells were pre‐incubated with TMP, stimulated with AngII and ET‐1 gene expression was then examined. The effects of TMP pretreatment on AngII‐induced extracellular signal‐regulated kinase (ERK) phosphorylation were investigated to elucidate the intracellular mechanism responsible for the effects of TMP on ET‐1 gene expression.3. Tetramethylpyrazine inhibited AngII‐induced ET‐1 gene expression, as revealed by nothern blotting and a promoter activity assay. Tetramethylpyrazine also inhibited the AngII‐induced increase in intracellular reactive oxygen species (ROS), as measured by the redox sensitive fluorescent dye 2′ 7′‐dichlorofluorescin diacetate and ERK phosphorylation.4. In summary, we have demonstrated, for the first time, that TMP inhibits AngII‐induced ROS generation, ERK phosphorylation and ET‐1 gene expression in vascular endothelial cells. Thus, the present study delivers important new insights into the molecular pathways that may contribute to the proposed beneficial effects of TMP in the cardiovascular system.