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Intravenous Injection (intravenous + injection)
Kinds of Intravenous Injection Selected AbstractsEnhanced Left Ventricular Endocardial Border Delineation with an Intravenous Injection of SonoVue, a New Echocardiography Contrast Agent:ECHOCARDIOGRAPHY, Issue 8 2000A European Multicenter Study The safety and efficacy of SonoVue (also referred to as BR1), a new contrast agent for delineating endocardial border of the left ventricle after intravenous administration, was assessed. Two hundred and eighteen patients with suspected coronary artery disease undergoing fundamental echocardiography for the assessment of left ventricle were enrolled in a prospective multicenter, single blind, cross-over study with random sequence allocation of four different doses of SonoVue. Endocardial border definition in the apical and parasternal views was scored as O = not visible, 1 = barely visible, and 2 = well visualized before and after contrast enhancement. Analysis was performed by two pairs of off-site observers. Safety of SonoVue was also assessed. Results of our study indicated that the mean improvements in the endocardial border visualization score were as follows: 3.1 ± 7.8 (95% CI, 2.5 and 3.7) for 0.5 ml, 3.4 ± 8.0 (95% CI, 2.8 and 4.0) for 1 ml, 3.4 ± 7.9 (95% CI, 2.8 and 4.0) for 2 ml, and 3.7 ± 8.0 (95% CI, 3.1 and 4.3) for 4 ml (P < 0.05 for all doses from baseline). Changes from baseline in endocardial visualization scores were also seen in the apical views (P < 0.05) and they were dose-dependent (P < 0.001). Similar enhancements of endocardial visualization scores were observed in the apical views in patients with suboptimal baseline echocardiographic images. Diagnostic confidence for assigning a score and image quality also were significantly better following contrast enhancement. No significant changes in the laboratory parameters and vital signs were noted following contrast enhancement, and the side effects were minimal. It was concluded that SonoVue is safe and effective in delineating endocardial border, including in patients with suboptimal baseline images. [source] B2 kinin receptors mediate the Indian red scorpion venom-induced augmentation of visceral reflexes via the nitric oxide cyclic guanosine monophosphate pathwayACTA PHYSIOLOGICA, Issue 4 2009S. Kanoo Abstract Aim:, This study was performed to delineate the kinin (receptor)-dependent pathways in the Indian red scorpion (Mesobuthus tamulus; MBT) venom-induced pulmonary oedema as well as the augmentation of cardio-pulmonary reflexes evoked by phenyldiguanide (PDG). Methods:, In urethane-anaesthetized adult rats, the effect of venom on the PDG reflex responses (blood pressure, heart rate and respiration rate) and the pulmonary water content was ascertained using various antagonists(des- Arg, B1 receptor antagonist; Hoe 140, B2 receptor antagonist; N, -nitro- l -arginine methyl ester (l -NAME), nitric oxide (NO) synthase inhibitor; methylene blue, soluble guanylate cyclase inhibitor; and glibenclamide, K+ATP channel blocker). The effect of phosphodiesterase V inhibitor (sildenafil citrate) on the reflex response and the pulmonary water content was also examined and compared with venom-induced responses. Results:, Intravenous injection of PDG (10 ,g kg,1) evoked apnoea, bradycardia and hypotension lasting >60 s. Exposure to MBT venom (100 ,g kg,1) for 30 min augmented the PDG reflex responses by two times and increased the pulmonary water content, significantly. Hoe 140 blocked the venom-induced responses (augmentation of PDG reflex and increased pulmonary water content) whereas des-Arg did not. l -NAME, methylene blue or glibenclamide also blocked the venom-induced responses. Furthermore, sildenafil citrate (that increases cGMP levels) produced augmentation of PDG reflex response and increased the pulmonary water content as seen with venom. Conclusion:, The results indicate that venom-induced responses involve B2 kinin receptors via the NO-dependent guanylate cyclase-cGMP pathway involving K+ATP channels. [source] Route of Administration Differentially Affects Fevers Induced by Gram-Negative and Gram-Positive Pyrogens in RabbitsEXPERIMENTAL PHYSIOLOGY, Issue 3 2002T. Cartmell We have investigated the febrile responses of New Zealand White rabbits to a Gram-negative pyrogen (bacterial lipopolysaccharide (LPS) from Salmonella typhosa), commonly associated with systemic infection, and a Gram-positive pyrogen (Staphylococcus aureus), more frequently associated with superficial soft tissue infection, each administered via one of four different routes (intravenous, intramuscular, subcutaneous or intraperitoneal) at each of three different doses (LPS: 0.1, 1 and 10 ,g kg,1; S. aureus: 1.5 × 107, 1.5 × 108 and 1.5 × 109 cell walls kg,1). Intravenous administration of LPS evoked rapid, dose-dependent biphasic fever. Injection of LPS by the other routes also evoked dose-dependent fever. However, these fevers were monophasic, had increased latency of onset, and were of lower amplitude. It is important to note that a dose of approximately 10 and 100 times that of the standard intravenous dose was required to produce a similar peak rise in temperature when administered subcutaneously and intraperitoneally, respectively. Intravenous injection of the highest dose of S. aureus evoked dose-dependent biphasic fever, with short latency of onset, which was very similar to that induced by intravenous LPS. At lower doses, intravenous S. aureus induced monophasic fever. No fever occurred when the same doses of S. aureus were administered by any other route. We conclude that any of the four routes may be used for the study of LPS-induced fever, provided that the doses are adjusted. However, studies of S. aureus -induced fever, and detection of contamination with either pyrogen, requires intravenous injection. [source] Brain metabolism of exogenous pyruvateJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Susana Villa Gonzalez Abstract Pyruvate given in large doses may be neuroprotective in stroke, but it is not known to what degree the brain metabolizes pyruvate. Intravenous injection of [3- 13C]pyruvate led to dose-dependent labelling of cerebral metabolites so that at 5 min after injection of 18 mmoles [3- 13C]pyruvate/kg (2 g sodium pyruvate/kg), approximately 20% of brain glutamate and GABA were labelled, as could be detected by 13C nuclear magnetic resonance spectrometry ex vivo. Pyruvate, 9 mmoles/kg, was equivalent to glucose, 9 mmoles/kg, as a substrate for cerebral tricarboxylic acid (TCA) cycle activity. Inhibition of the glial TCA cycle with fluoroacetate did not affect formation of [4- 13C]glutamate or [2- 13C]GABA from [3- 13C]pyruvate, but reduced formation of [4- 13C]glutamine by 50%, indicating predominantly neuronal metabolism of exogenous pyruvate. Extensive formation of [3- 13C]lactate from [2- 13C]pyruvate demonstrated reversible carboxylation of pyruvate to malate and equilibration with fumarate, presumably in neurones, but anaplerotic formation of TCA cycle intermediates from exogenous pyruvate could not be detected. Too rapid injection of large amounts of pyruvate led to seizure activity, respiratory arrest and death. We conclude that exogenous pyruvate is an excellent energy substrate for neurones in vivo, but that care must be taken to avoid the seizure-inducing effect of pyruvate given in large doses. [source] Selective ,1 -adrenoreceptor blocking activity of newly synthesized acyl amino-substituted aryloxypropanolamine derivatives, DPJ 955 and DPJ 890, in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2005K. Nandakumar The in-vivo ,-adrenoreceptor antagonistic activity of test compounds DPJ 955 and DPJ 890 was assessed against ,-adrenoreceptor agonist (isoprenaline) induced tachycardia in anaesthetized rats. The selectivity to block isoprenaline responses on different ,-adrenoreceptor subtypes (,1, ,2 and ,3) of the test compounds was carried out on isolated rat right atria, isolated rat uterus and isolated rat colon preparations, respectively. Intravenous injection of isoprenaline alone in anaesthetized rats caused hypotension and tachycardia. DPJ 955 or DPJ 890 alone produced a fall in mean arterial pressure and bradycardia in a dose-dependent manner. Administration of isoprenaline to anaesthetized rats pre-treated with test compounds significantly blocked both the tachycardial and hypotensive responses induced by isoprenaline. The test compounds shifted the concentration response curves of isoprenaline towards the right for isolated rat right atrial preparations, rat uterus and rat colon, indicating ,1, ,2 and ,3 adrenoreceptor blockade, respectively. The selectivity ratio for ,1/,-adrenoreceptors to DPJ 955 and DPJ 890 was 64.6 and 83.2, respectively. DPJ 890 was more potent in blocking ,1 -adrenoreceptors and was more selective towards ,1 receptors than to other ,-adrenoreceptor subtypes. In conclusion, DPJ 955 and DPJ890 have ,-adrenoreceptor blocking activity with high selectivity for the ,1 -adrenoreceptor subtype. [source] Characterization of Histamine Release Induced by Fluoroquinolone Antibacterial Agents In-vivo and In-vitroJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2000KAZUHIKO MORI Characterization of histamine release induced by fluoroquinolone antibacterial agents, levofloxacin and ciprofloxacin, was investigated in-vivo and in-vitro. Intravenous injection of levofloxacin and ciprofloxacin at 1,10 mg kg,1 produced dose-related elevations in plasma histamine level in anaesthetized dogs. In contrast, levofloxacin was devoid of plasma histamine increment in anaesthetized rats at 100 mg kg,1, whereas ciprofloxacin at the same dose caused endogenous histamine release. Levofloxacin and ciprofloxacin induced non-cytotoxic secretion of histamine from all mast cells tested in a concentration-dependent manner, whereas rat skin and peritoneal mast cells were thirty- to one-hundred-times less sensitive to the effect of fluoroquinolones as compared with the canine skin mast cells. These results suggest that the functional heterogeneity of mast cells from different species in histamine releasing activity of fluoroquinolones may exist, and that mast cells from the dog appear to be particularly sensitive to the effect of the fluoroquinolones. [source] Plasma Clearance of Exogenous Creatinine, Exo-Iohexol, and Endo-Iohexol in Hyperthyroid Cats before and after Treatment with RadioiodineJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2008I. Van Hoek Background: Glomerular filtration rate (GFR) can be measured by clearance methods of different markers showing discrepancies and different reproducibility in healthy cats. Studies comparing different methods of GFR measurement in hyperthyroid cats have not yet been performed. Hypothesis: Plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT), and endo-iohexol (PenICT) could lead to differences in GFR measurement and the need to use the same clearance method when comparing GFR before and after radioiodine treatment in hyperthyroid cats. Animals: Fifteen client-owned hyperthyroid cats. Methods: GFR was measured 1 day before and 1, 4, 12, and 24 weeks after treatment. Intravenous injection of iohexol was followed immediately by IV injection of creatinine. Plasma creatinine was measured by an enzymatic method. Plasma endo- and exo-iohexol were measured by high-performance liquid chromatography coupled to ultraviolet detection. Results: Globally, the 3 GFR methods resulted in significantly different (P < .001) GFR results. GFR results among the different methods were the same (P= .999) at all time points. All 3 techniques indicated decreasing GFR after 131I treatment. For each GFR technique, a significant decrease in GFR was observed between time point 0 and all other time points. This decrease stabilized 4 weeks after treatment, with very little decline afterward. Conclusion and Clinical Importance: It is mandatory to use the same GFR technique in follow-up studies. GFR testing at 4 weeks posttreatment could allow assessment of the final renal functional loss after treatment in hyperthyroid cats. [source] Kinetics of Protoporphyrin IX Formation in Rat Oral Mucosa and Skin After Application of 5-Aminolevulinic Acid and its Methylester,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2005Stefan Kristiansson ABSTRACT The kinetics of accumulation of protoporphyrin IX (PpIX) after topical application of 5-aminolevulinic acid (ALA) and its methylester (5-aminolevulinic acid methylester [ALA-Me]) was studied on rat oral mucosa. The accumulation of PpIX in mucosa and skin after intravenous injection of ALA and ALA-Me was also studied. The elimination rate of PpIX was dependent on drug and dose as well as on administration route. Application of ALA on rat oral mucosa and skin caused a systemic effect with PpIX building up in remote skin sites not exposed to the drugs. No such systemic effect was seen after application of ALA-Me either in mucosa or on skin. Intravenous injection of the drugs (0.2 g/kg) leads to more fluorescence in the skin than topical application of the drug (20%). For mucosa, the opposite is true. Maximal PpIX fluorescence appeared later after application of high concentrations of the drugs (around 8 h for 5% and 20% wt/wt) than after application of low concentrations (around 3,5 h for 1% and 2% wt/wt). [source] Effect of quercetin on tachykinin-induced plasma extravasation in rat urinary bladderPHYTOTHERAPY RESEARCH, Issue 5 2001Paulo R. Wille Abstract The effect of quercetin on substance P-induced plasma extravasation in rat urinary bladder and its modulation by endogenous peptidases in conscious rats was studied. Plasma protein extravasation (PE) was assayed by measurement of extravasated Evans blue dye (,g/g dry tissue). Intravenous injection of substance P (SP, 10 nmol/kg) significantly increased PE in the urinary bladder. PE evoked by SP was increased significantly by quercetin (20,mg/kg, p.o.) pretreatment in the urinary bladder (73.5 ± 4.9 to 152.2,±,9.9). Pretreatment with captopril, an angiotensin-converting enzyme (ACE) inhibitor (10 nmol/kg, i.v.), or with phosphoramidon, a neutral endopeptidase (NEP) inhibitor (2.5,,mol/kg, i.v.) also potentiated the SP-induced PE in urinary bladder, 286.2,±,20.4 and 323.3,±,34.0, respectively. Quercetin did not show any effect on neurokinin-A (NKA, 10 nmol/kg, i.v.) -induced plasma extravasation. The present study demonstrates that quercetin potentiates the PE induced by substance P in the urinary bladder. These effects suggest that this flavonoid might cause inhibition of NEP and/or ACE. Copyright © 2001 John Wiley & Sons, Ltd. [source] A New Quinoline Derivative MS-209 Reverses Multidrug Resistance and Inhibits Multiorgan Metastases by P-glycoprotein-expressing Human Small Cell Lung Cancer CellsCANCER SCIENCE, Issue 7 2001Hiroshi Nokihara Development of distant metastases and acquired multidrug resistance (MDR) are major problems in therapy for human small cell lung cancer (SCLC). MS-209 is a novel quinoline compound, which reverses P-glycoprotein (P-gp)-mediated MDR. We previously reported that MS-209 reversed in vitro MDR of human SCLC (SBC-3/ADM and H69/VP) cells expressing P-gp. In the present study, we determined the therapeutic effect of MS-209 in combination with chemotherapy against multiorgan metastases of MDR SCLC cells. SBC-3/ADM cells expressing P-gp were highly resistant to etoposide (VP-16), adriamycin (ADM), and vincristine (VCR) in vitro, compared with parental SBC-3 cells lacking P-gp expression. MS-209 restored chemosensitivity of SBC-3/ADM cells to VP-16, ADM, and VCR in a dose-dependent manner in vitro. Intravenous injection with SBC-3 or SBC-3/ADM cells produced metastatic colonies in the liver, kidneys and lymph nodes in natural killer (NK) cell-depleted severe combined immunodeficiency (SCID) mice, though SBC-3/ ADM cells more rapidly produced metastases than did SBC-3 cells. Treatment with VP-16 and ADM reduced metastasis formation by SBC-3 cells, whereas the same treatment did not affect metastasis by SBC-3/ADM cells. Although MS-209 alone had no effect on metastasis by SBC-3 or SBC-3/ADM cells, combined use of MS-209 with VP-16 or ADM resulted in marked inhibition of metastasis formation by SBC-3/ADM cells to multiple organs. These findings suggest that MS-209 reversed the MDR of SBC-3/ADM cells, but not SBC-3 cells, growing in the various organs, and inhibited metastasis formation in vivo. Therefore, this chemosensitizing agent, MS-209, may be useful for treatment of refractory SCLC patients with multiorgan metastases. [source] 3122: Regulation of retinal tissue oxygenationACTA OPHTHALMOLOGICA, Issue 2010CJ POURNARAS Purpose To evaluate the changes in the retinal oxygen partial pressure (PO2) following physiological stimuli. Methods Evaluation of either the preretinal and intraretina partial pressure of oxygen (PO2) distribution, using oxygen sensitive microelectrodes, in various animal models. Measurements were obtained during changes of the perfusion pressure, systemic hyperoxia, hypoxia, hypercapnia, carbogen breathing and following carbonic anydrase inhibitors use. Results The oxygen tension (PO2) in the inner half of the retina remains largely unaffected by moderate changes in perfusion pressure. The increase of the systemic PaO2 through breathing of 100% O2 (hyperoxia) induces endothelin (ET) mediated marked vasoconstriction of the inner retinal arterioles in both anesthetized animals and normal human subjects. The regulatory vasoconstriction maintains the PO2 in retinal tissue constant. A decrease in PaO2 (hypoxia) induces a vasodilation of the retinal arterioles through endothelium-derived NO release. As a result, trans-retinal PO2 profiles made during steps of systemic hypoxia have shown that the values measured in the inner retina up to half of its thickness, remain rather stable. By contrast, the PO2 values, measured close to the choroid and in the outer retina, decrease in a linear manner with the decrease of the PaO2. An increase in the PaCO2 (hypercapnia) of arteriolar blood, produces an increase in retinal blood flow and retinal tissue PO2. Intravenous injection of acetazolamide (carbonic anhydrase inhibitor) produces an increase in preretinal PO2 due to dilation of the retinal vessels Conclusion Thanks to the autoregulatory capability of the retinal circulation, the oxygen tension (PO2) in the inner half of the retina, remains largely unaffected during physiological stimuli. [source] Evaluation of tumor affinity of mono-[123I]iodohypericin and mono-[123I]iodoprotohypericin in a mouse model with a RIF-1 tumorCONTRAST MEDIA & MOLECULAR IMAGING, Issue 3 2007Humphrey Fonge Abstract In this study we have compared the tumour-seeking properties of mono-[123I]iodoprotohypericin and mono-[123I]iodohypericin in C3H mice with a subcutaneous radiation-induced fibrosarcoma-1 tumor. After intravenous injection, both tracers were rapidly cleared from all organs and were retained by the tumors. There was no significant difference in tumor uptake of the two tracers at all studied time points (p,>,0.05). To study the plausible mechanism of hypericin and mono-iodohypericin uptake in tumor, their plasma binding profile was investigated. Both agents show high affinity for low-density lipoproteins and to a lesser extent high-density lipoproteins and other heavy proteins. Mono-[123I]iodohypericin appears to be more promising as a tumor diagnostic agent, given its faster clearance from all organs. Copyright © 2007 John Wiley & Sons, Ltd. [source] Platelet activating factor (PAF) increases plasma protein extravasation and induces lowering of interstitial fluid pressure (Pif) in rat skinACTA PHYSIOLOGICA, Issue 1 2005V. V. Iversen Abstract Aim:, To investigate the ability of the microdialysis technique to measure capillary selectivity of different sized plasma proteins induced by local administration of platelet activating factor (PAF). Methods:, We used hollow plasmapheresis fibres with 3 cm membrane (cut off 3000 kDa) placed on the back of anaesthetized rats. Results:, Platelet activating factor (50 ,g mL,1) administered locally via the fibre, increased extravasation of radiolabelled 125I-HSA from plasma to the microdialysis fibre by approximately 900% compared both to baseline and the control fibre within 70 min (n = 6, P < 0.05). The extravasation in the control fibre did not change over time. HPLC measurement of plasma proteins in the microdialysis perfusate also demonstrated decreased capillary selectivity for proteins in the diameter range of 73 Å, 56 Å and 39 Å after local administration of PAF (n = 6, P < 0.05). PAF also significantly lowered interstitial fluid (Pif) pressure after subcutaneous administration (50 ,g mL,1). Mean arterial pressure (MAP) after intravenous injection of PAF (0.4 ,g kg,1) fell instantly by about 50 mmHg, and stabilized at 50 mmHg after 15 min (n = 6). MAP was unaltered when PAF was given through the microdialysis fibre (n = 4). Both total tissue water (TTW) and extravasation of albumin, measured as the plasma-to-tissue clearance (E-alb) showed a significant increase after PAF (n = 7, P < 0.05). Conclusions:, The present study demonstrates that PAF induces plasma protein extravasation and decrease capillary selectivity of different sized plasma proteins. It also increases transcapillary fluid flux, and lowers Pif, indicating a role for PAF in the interstitium for generation of transcapillary transport of water and large molecules followed by formation of oedema. [source] Effects of aminoguanidine and tolrestat on the development of ocular and renal structural changes in experimental diabetic ratsDIABETES OBESITY & METABOLISM, Issue 1 2002Ö. Azal Studies that researched the role of aminoguanidine and tolestat in the prevention of diabetic retinopathy and nephropathy resulted in conflicting data. We investigated the effects of these agents in the prevention of ocular and renal changes in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intravenous injection of STZ in 30 rats. Ten rats that were not given STZ served as non-diabetic control (Group 1). Ten STZ-diabetic rats that were not given any treatment served as diabetic control (Group 2). Groups 3 and 4 were composed of STZ-induced diabetic rats (10 each) that were given tolrestat and aminoguanidine respectively. Eyes and kidneys were examined at the 24th week under electronmicroscopy. Cataract was observed in all six of the surviving rats in Groups 2 and 4, and in one of 6 surviving rats in group 3. Cataract development was lower in Group 3 than Groups 2 and 4. All retinal samples obtained from group 2 demonstrated a number of structural abnormalities, whereas there were no significant ultrastructural changes in groups 3 and 4. Groups 2 and 3 demonstrated mesangial proliferation and expansion, diffuse glomerular basement membrane (GBM) thickening, and focal GBM thickening in the bulb form. Group 4 demonstrated a normally appearing mesangial space, minimal diffuse but no focal GBM thickening. The urinary albumin excretion (UAE) was lower in Group 4 than the other groups. In conclusion, our results suggest that aminoguanidine may be an important agent for the prevention of renal changes, whereas tolrestat may be effective for the prevention of ocular changes in diabetes mellitus. [source] Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2009Yumiko Yoshida Abstract Background Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. We investigated here whether and how PEDF could prevent the development of diabetic retinopathy. Methods Streptozotocin-induced diabetic rats were treated with or without intravenous injection of PEDF for 4 weeks. Early neuronal derangements were evaluated by electroretinogram (ERG) and immunofluorescent staining of glial fibrillary acidic protein (GFAP). Expression of PEDF and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress, was localized by immunofluorescence. Vascular endothelial growth factor (VEGF) and p22phox expression were evaluated with western blots. Breakdown of blood retinal barrier (BRB) was quantified with fluorescein isothiocynate (FITC)-conjugated dextran. NADPH oxidase activity was measured with lucigenin luminescence. Results Retinal PEDF levels were reduced, and amplitudes of a- and b-wave in the ERG were decreased in diabetic rats, which were in parallel with GFAP overexpression in the Müller cells. Further, retinal 8-OHdG, p22phox and VEGF levels and NADPH oxidase activity were increased, and BRB was broken in diabetic rats. Administration of PEDF ameliorated all of the characteristic changes in early diabetic retinopathy. Conclusions Results suggest that PEDF could prevent neuronal derangements and vascular hyperpermeability in early diabetic retinopathy via inhibition of NADPH oxidase-driven oxidative stress generation. Substitution of PEDF may offer a promising strategy for halting the development of diabetic retinopathy. Copyright © 2009 John Wiley & Sons, Ltd. [source] Aminoguanidine prevents arterial stiffening in a new rat model of type 2 diabetesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2006K.-C. Chang Abstract Background, Formation of advanced glycation end-products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in rats. Materials and methods, The NIDDM was induced in male Wistar rats, which were administered intraperitoneally with 180 mg kg,1 nicotinamide (NA) 30 min before an intravenous injection of 50 mg kg,1 streptozotocin (STZ). After induction of diabetes mellitus type 2, animals receiving daily peritoneal injections with 50 mg kg,1 AG for 8 weeks were compared with the age-matched, untreated, diabetic controls. Results, After exposure to AG, the STZ-NA diabetic rats had improved aortic distensibility, as evidenced by 18·8% reduction of aortic characteristic impedance (P < 0·05). Treatment of the experimental syndrome with AG also resulted in a significant increase in wave transit time (+23·7%, P < 0·05) and a decrease in wave reflection factor (,26·6%, P < 0·05), suggesting that AG may prevent the NIDDM-induced augmentation in systolic load of the left ventricle. Also, the glycation-derived modification on aortic collagen was found to be retarded by AG. The diminished ratio of left ventricular weight to body weight suggested that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening. Conclusions, Long-term administration of AG to the STZ-NA diabetic rats imparts significant protection against the NIDDM-derived impairment in vascular dynamics, at least partly through inhibition of the AGE accumulation on collagen in the arterial wall. [source] Arterial stiffening and cardiac hypertrophy in a new rat model of type 2 diabetesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2006K.-C. Chang Abstract Background, We determined the effects of NIDDM on haemodynamic parameters describing arterial wall elasticity and cardiac hypertrophy in rats administered streptozotocin (STZ) and nicotinamide (NA), using the aortic impedance analysis. Methods, Male Wistar rats at 2 months were administered intraperitoneally 180 mg kg,1 of NA, 30 min before an intravenous injection of 50 mg kg,1 STZ, to induce type 2 diabetes. The STZ-NA rats were divided into two groups, 4 weeks and 8 weeks after induction of diabetes, and compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured by a high-fidelity pressure sensor and electromagnetic flow probe, respectively, and were then subjected to Fourier transformation for the analysis of aortic input impedance. Results, In each diabetic group, the experimental syndrome was characterized by a moderate and stable hyperglycaemia and a relative deficiency of insulin secretion. However, the 8-week but not the 4-week STZ-NA diabetic rats showed a decrease in cardiac output in the absence of any significant changes in mean aortic pressure, having increased total peripheral resistance. The diabetic syndrome at 8 weeks also contributed to an increase in aortic characteristic impedance, from 1·49 ± 0·33 (mean ± SD) to 1·95 ± 0·28 mmHg s mL,1 (P < 0·05), suggesting a detriment to the aortic distensibility in NIDDM. Meanwhile, the STZ-NA diabetic animals after 8 weeks had an increased wave reflection factor (0·46 ± 0·09 vs. 0·61 ± 0·13, P < 0·05) and decreased wave transit time (25·8 ± 3·8 vs. 20·6 ± 2·8 ms, P < 0·05). Ratio of the left ventricular weight to body weight was also enhanced in the 8-week STZ-NA diabetic rats. Conclusion, The heavy intensity with early return of the pulse wave reflection may augment systolic load of the left ventricle coupled to the arterial system, leading to cardiac hypertrophy in the rats at 8 weeks after following STZ and NA administration. [source] Changes in murine bone marrow macrophages and erythroid burst-forming cells following the intravenous injection of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP)EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2001A. L. Giuliani Abstract: In order to explore the effect on bone marrow macrophages of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP), mice were injected intravenously with a preparation of such liposomes at a dose known to deplete spleen and liver macrophages. Two days later, the macrophages in the marrow of the femoral bones were quantified by flow cytometry using a macrophage-specific monoclonal antibody (F4/80), and their ultrastructure and phagocytic activity towards zymosan particles was assessed. To determine the effect on erythropoiesis of liposome-encapsulated Cl2MDP-induced changes in bone marrow macrophages, red blood cell parameters and the formation of erythroid burst-forming unit (BFU-E)-derived colonies in vitro were evaluated. In mice injected with liposome-encapsulated Cl2MDP, there was a 54% and 67% decrease in the total number of bone marrow macrophages as compared to uninjected controls and mice treated with empty liposomes, respectively. Moreover, residual macrophages showed an abnormal ultrastructure, with reduced numbers of crystalloid inclusions and increased numbers of large myelin figures. However, the phagocytic activity of these cells was unimpaired or slightly enhanced. In mice injected with liposome-encapsulated Cl2MDP there was an approximately 60% decrease in the percentage and total number of circulating reticulocytes and a 54% reduction in the BFU-E number, demonstrating deregulation of erythropoiesis under conditions of macrophage loss and impairment. The results suggest that mice treated with liposome-encapsulated Cl2MDP are a model for studying the role of macrophages in erythropoiesis. [source] Infusion of anti-nerve growth factor into the cisternum magnum of chick embryo leads to decrease cell production in the cerebral cortical germinal epitheliumEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2007F. Mashayekhi There has been considerable recent progress in understanding the processes involved in cerebral cortical development. Several mitogenic and trophic factors have been implicated in the processes of cortical cell proliferation and differentiation. Anti-nerve growth factor (NGF) antibody was administered to 15 days chick foetuses through the cisternum magnum. Control group received phosphate buffered saline (PBS). To identify cells born in the cerebral cortex at the time of antibody or PBS injection, 5,-bromo-2,- deoxyuridine was administered to the foetuses by intravenous injection into an outlying vein using micromanipulation. After injection, the foetuses were re-incubated for another 3 days. All the foetuses were collected on day 18, the brains fixed in paraformaldehyde, cut with a microtome and stained with methyl green pyronin and anti-NGF antibody. Quantitative measurements showed that the thickness of the germinal epithelium (GE) and cerebral cortex in the anti-NGF antibody injected foetuses was decreased when compared with normal control embryos. The number of cells produced in the GE of antibody injected foetuses was decreased when compared with normal control embryos. The results from this study using neutralizing antibody suggests that NGF is an important factor in cerebral cortical development, stimulating neuronal precursor proliferation. [source] Corticospinal control of antagonistic muscles in the catEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Christian Ethier Abstract We recently suggested that movement-related inter-joint muscle synergies are recruited by selected excitation and selected release from inhibition of cortical points. Here we asked whether a similar cortical mechanism operates in the functional linking of antagonistic muscles. To this end experiments were done on ketamine-anesthetized cats. Intracortical microstimulation (ICMS) and intramuscular electromyographic recordings were used to find and characterize wrist, elbow and shoulder antagonistic motor cortical points. Simultaneous ICMS applied at two cortical points, each evoking activity in one of a pair of antagonistic muscles, produced co-contraction of antagonistic muscle pairs. However, we found an obvious asymmetry in the strength of reciprocal inhibition; it was always significantly stronger on physiological extensors than flexors. Following intravenous injection of a single bolus of strychnine, a cortical point at which only a physiological flexor was previously activated also elicited simultaneous activation of its antagonist. This demonstrates that antagonistic corticospinal neurons are closely grouped, or intermingled. To test whether releasing a cortical point from inhibition allows it to be functionally linked with an antagonistic cortical point, one of three GABAA receptor antagonists, bicuculline, gabazine or picrotoxin, was injected iontophoretically at one cortical point while stimulation was applied to an antagonistic cortical point. This coupling always resulted in co-contraction of the represented antagonistic muscles. Thus, antagonistic motor cortical points are linked by excitatory intracortical connections held in check by local GABAergic inhibition, with reciprocal inhibition occurring at the spinal level. Importantly, the asymmetry of cortically mediated reciprocal inhibition would appear significantly to bias muscle maps obtained by ICMS in favor of physiological flexors. [source] Sex hormone-dependent desensitization of 5-HT1A autoreceptors in knockout mice deficient in the 5-HT transporterEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2003Saoussen Bouali Abstract The serotonin transporter (5-HTT) is the target of most antidepressant drugs, whose therapeutic action is related to their facilitatory influence on 5-HT neurotransmission. In this study, we investigated the functional adaptive properties of 5-HT1A autoreceptors, which regulate serotonergic neuronal firing, in knockout mice deficient in 5-HTT. Neurons of the dorsal raphe nucleus (DRN) were recorded extracellularly under chloral hydrate anaesthesia in male and female knockout 5-HTT mice and their wild-type counterparts. The inhibitory response of DRN neurons to intravenous injection of the 5-HT1A agonist 8-OH-DPAT was dramatically reduced in knockout 5-HTT compared with wild-type mice, especially in females. Changes in 8-OH-DPAT-induced hypothermia and autoradiographic labelling of 5-HT1A sites in the DRN confirmed a greater level of desensitization/down-regulation of 5-HT1A autoreceptors in female than in male knockout 5-HTT mice. After gonadectomy, the functional status of 5-HT1A autoreceptors was unchanged in wild-type mice, whereas in knockout 5-HTT, castrated males exhibited a down-regulation, and ovariectomized females an up-regulation of these receptors, as shown by electrophysiological recording and autoradiographic labelling in the DRN, as well as by changes in 8-OH-DPAT-induced hypothermia. Finally, in gonadectomized knockout 5-HTT mice, treatment with testosterone or estradiol restored the DRN neuronal firing sensitivity to 8-OH-DPAT back to sham control level in males or females, respectively. These data indicate that sexual hormones participate in the mechanisms responsible for the desensitization of 5-HT1A autoreceptors in knockout 5-HTT mice. The differential effects of testosterone and estradiol on 5-HT1A -mediated control of 5-HT neurotransmission might be related to the well-established gender differences in the vulnerability to depression. [source] Route of Administration Differentially Affects Fevers Induced by Gram-Negative and Gram-Positive Pyrogens in RabbitsEXPERIMENTAL PHYSIOLOGY, Issue 3 2002T. Cartmell We have investigated the febrile responses of New Zealand White rabbits to a Gram-negative pyrogen (bacterial lipopolysaccharide (LPS) from Salmonella typhosa), commonly associated with systemic infection, and a Gram-positive pyrogen (Staphylococcus aureus), more frequently associated with superficial soft tissue infection, each administered via one of four different routes (intravenous, intramuscular, subcutaneous or intraperitoneal) at each of three different doses (LPS: 0.1, 1 and 10 ,g kg,1; S. aureus: 1.5 × 107, 1.5 × 108 and 1.5 × 109 cell walls kg,1). Intravenous administration of LPS evoked rapid, dose-dependent biphasic fever. Injection of LPS by the other routes also evoked dose-dependent fever. However, these fevers were monophasic, had increased latency of onset, and were of lower amplitude. It is important to note that a dose of approximately 10 and 100 times that of the standard intravenous dose was required to produce a similar peak rise in temperature when administered subcutaneously and intraperitoneally, respectively. Intravenous injection of the highest dose of S. aureus evoked dose-dependent biphasic fever, with short latency of onset, which was very similar to that induced by intravenous LPS. At lower doses, intravenous S. aureus induced monophasic fever. No fever occurred when the same doses of S. aureus were administered by any other route. We conclude that any of the four routes may be used for the study of LPS-induced fever, provided that the doses are adjusted. However, studies of S. aureus -induced fever, and detection of contamination with either pyrogen, requires intravenous injection. [source] Fas and TNFR1, but not cytolytic granule-dependent mechanisms, mediate clearance of murine liver adenoviral infection,HEPATOLOGY, Issue 1 2005Marwan S. Abougergi After intravenous injection of replication-deficient adenovirus, hepatocytes are transduced and express high levels of adenovirus-encoded genes. However, adenovirally encoded gene expression is ablated rapidly by CD8+ T-cell,dependent mechanisms. Thus, this model is suitable for examining intrahepatic cytotoxic T lymphocyte (CTL) effector mechanisms. In the present studies, recombinant adenoviruses encoding secreted (human apolipoprotein A-I) or intracellular (,-galactosidase) gene products were infused into mice with genetic deficiencies affecting the granule exocytosis-, Fas-, or tumor necrosis factor receptor 1 (TNFR1)-mediated pathways of CTL and natural killer cell effector function; the rates of clearance of adenovirus-encoded gene products were assessed. Clearance of secreted or intracellular adenoviral gene products was not delayed in perforin-deficient mice or dipeptidyl peptidase I-deficient mice, which fail to process and activate granzyme A or granzyme B. TNFR1-deficient mice also exhibited no delay in clearance of adenoviral gene products. However, adenoviral clearance from Fas-deficient mice was delayed, and such delays were much greater in mice deficient in both TNFR1 and Fas. In contrast, chimeric mice lacking both hepatic Fas and lymphocyte perforin function exhibited no greater delay in adenoviral clearance than chimeras deficient only in hepatic Fas expression. In conclusion, Fas-dependent mechanisms are required for efficient clearance of virally infected hepatocytes and, in Fas-deficient animals, TNFR1-dependent mechanisms provide an alternative mechanism for hepatic adenovirus clearance. In contrast, perforin- and granule protease,dependent cytotoxicity mechanisms play no apparent role in clearance of adenovirus from the liver. (HEPATOLOGY 2005;41:97,105.) [source] Serum bFGF and VEGF correlate respectively with bowel wall thickness and intramural blood flow in Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 5 2004Dr. Antonio Di Sabatino MD Abstract Serum levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF),two factors known to promote tissue repair, fibroblast proliferation, and angiogenesis,were measured in Crohn's disease patients and correlated with bowel wall thickness (BWT), measured by conventional grey scale ultrasonography, and with the ileal intramural vessel flow, measured by contrast-enhanced color Doppler imaging. Serum samples were obtained from 25 patients with active Crohn's disease and 22 healthy volunteers, all sex- and age-matched. Serum bFGF and VEGF levels were measured by ELISA assay. All the patients were examined with conventional transabdominal bowel sonography. Color Doppler of the intramural enteric vessels was then performed after the intravenous injection of Levovist, a galactose-based sonographic contrast agent. In Crohn's disease patients, serum bFGF and VEGF were significantly higher compared with healthy volunteers. A positive correlation between serum bFGF and BWT and between serum VEGF and color Doppler signal intensity was found. The raised serum bFGF levels in Crohn's disease patients with intestinal strictures compared with patients with other phenotypes (fistulizing, inflammatory), together with the correlation observed between serum bFGF and BWT, suggests a possible involvement of bFGF in the process of transmural fibrogenesis in Crohn's disease. The higher levels of VEGF in those patients with increased intramural blood flow suggests that VEGF may be considered a marker of angiogenesis in this condition. [source] Selective occlusion of tumor blood vessels by targeted delivery of an antibody-photosensitizer conjugateINTERNATIONAL JOURNAL OF CANCER, Issue 7 2006Monica Fabbrini Abstract The irregular vasculature and high interstitial pressure of solid tumors hinder the delivery of cytotoxic agents to cancer cells. As a consequence, the doses of chemotherapy necessary to achieve complete tumor eradication are associated with unacceptably high toxicities. The selective thrombosis of tumor blood vessels has been postulated as an alternative avenue for combating cancer, depriving tumors of nutrients and oxygen and causing an avalanche of tumor cell deaths. The human antibody L19, specific to the EDB domain of fibronectin, a marker of angiogenesis, is capable of selective in vivo localization around tumor blood vessels and is thus a suitable agent for delivering toxic payloads to the tumor neovasculature. Here we show that a chemical conjugate of the L19 antibody with the photosensitizer bis(triethanolamine)Sn(IV) chlorin e6, after intravenous injection and irradiation with red light, caused an arrest of tumor growth in mice with subcutaneous tumors. By contrast, a photosensitizer conjugate obtained with an antibody of identical pharmacokinetic properties but irrelevant specificity did not exhibit a significant therapeutic effect. These results confirm that vascular targeting strategies, aimed at the selective occlusion/disruption of tumor blood vessels, have a significant anticancer therapeutic potential and encourage the use of antibody-photosensitizer conjugates for the therapy of superficial tumors and possibly other angiogenesis-related pathologies. © 2005 Wiley-Liss, Inc. [source] Acute febrile neutrophilic dermatosis (Sweet's syndrome) with nodular episcleritis and polyneuropathyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2002Taizo Kato MD A 56-year-old Japanese housewife presented with multiple erythematous lesions in association with ocular hyperemia and pain in the right upper and lower extremities, including the hands and feet. These symptoms were preceded by a sore throat with persistent fever higher than 38.5 °C for about 1 week. Dermatologic examination showed tender, dull-red, erythematous lesions, measuring 1,2 cm in diameter, located predominantly on the forehead, cheeks, auricular region, neck, forearm, hands, and feet. A biopsy specimen obtained from an erythematous lesion on the right forearm revealed prominent edema in the papillary dermis and remarkable inflammatory cell infiltration throughout the entire dermis (Fig. 1). The infiltrate predominantly consisted of neutrophils and nuclear dust without signs of vasculitis. In routine examination, the leukocyte count was 15,000/mL (normal range, 4000,8000/mL) with severe neutrophilia (80%). The C-reactive protein (CRP) level was 17.65 mg/dL (normal range, < 0.5 mg/dL) and the anti-streptolysin (ASLO) level was 611 IU/mL (normal range, < 166 IU/mL). In human leukocyte antigen (HLA) testing, HLA-A2, -B39, -B35, -Cw2, and -Cw7 were positive, and HLA-B51, -B54, and -Cw1 were negative. Figure Figure 1 . Histologic picture showing a dermal infiltrate of neutrophils Ocular hyperemia was caused by episcleritis forming a nodule and surrounding congestion of the superficial episcleritic vessels at the central portion of the sclera (Fig. 2). The patient suffered from pain once an hour, continuing for about 3 min, at the lateral portion of the right upper and lower extremities, as well as the right small finger. Neurologic examination demonstrated moderate or slight muscle weakness in the extremities. Hand grasping powers were 9 and 7 kg on the right and left, respectively. The patient was right-handed. Dysesthesia and paresthesia were also observed on the hands and feet. The deep tendon reflexes were preserved, however, even in the distal portion of the upper and lower limbs. In addition, essential tremor localized to the neck was recognized. Magnetic resonance imaging did not show any episodes of transient abnormal signal intensity in the central nervous system. Figure 2. Nodular episcleritis (right eye). Telangiectasia of winding vessels with nodular elevation was observed at the upper portion of the sclera The patient was treated with prednisolone (initial dose of 30 mg/day) and intravenous injection of cefazolin sodium (2 g/day for 5 days). Almost complete regression of the ocular and neurologic manifestations, as well as the skin lesions, was achieved in 2 weeks. Prednisolone was reduced gradually and suspended after 4 weeks. Leukocyte and neutrophil counts, CRP, and ASO returned to normal on suspension of therapy. Slight paresthesia remained in the right small finger even after stopping steroid. There was no recurrence at follow-up 6 months later. [source] Erythema induratum with pulmonary tuberculosis: histopathologic features resembling true vasculitisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2001Yong Suk Lee MD A 22-year-old South Korean woman presented with a 4-month history of several nodules on both legs. She looked healthy, but suffered from tenderness and swelling of the legs. Physical examination showed multiple, nonulcerating, erythematous nodules occurring on the calves, knee joints, and thighs (Fig. 1). A biopsy specimen of the skin revealed necrotizing vasculitis of medium-sized arteries with fibrinoid necrosis at the border between the dermis and the subcutis. Dense cellular infiltrates, including numerous neutrophils and lymphocytes, presented within and around the vessel walls as in polyarteritis nodosa, with some eosinophils (Fig. 2A,B). There were no other generalized symptoms. She was diagnosed with cutaneous polyarteritis nodosa and was initially treated with systemic steroids. She was given an intravenous injection of Solu-Cortef, 60 mg/6 h for 7 days. This was replaced with oral prednisolone for 2 weeks. The skin lesions and symptoms improved. Figure 1. Small, nut-sized, erythematous, brown-colored nodules and patches on the lower extremities, even above the knee joints Figure 2. (A) Dense infiltration within and around artery (× 40). (B) Slightly expanded lobular panniculitis with vasculitis (× 100) Six months later, she complained of general weakness and recurrent skin lesions. Purified protein derivative (PPD) test gave a moderate positive reaction and chest X-ray examination showed the features of pulmonary tuberculosis: radio-opaque infiltrations in the right lower lung field. A repeated biopsy revealed mild vasculitis with more diffuse lobular infiltrations of the subcutaneous tissue compared with the former specimen. Polymerase chain reaction (PCR) and tissue culture for Mycobacterium tuberculosis were performed from a biopsy specimen. DNA was extracted from skin tissue with an AplisystemTM DNA/RNA detection kit using the resin-mediated boiling method (Stargene, Seoul, South Korea). The primers were designed on the basis of the M. tuberculosis gene IS6110 target (sense primer, 5,-CCA GAT GCA CCG TCG AAC GGC TGA T-3, antisense primer, 5,-CGC TCG CTG AAC CGG ATC GAT GTG T-3,). The amplification was performed with uracil- N -glycosylase (UNG), to prevent carry-over contamination, and internal control primers, to correct for false-negative reaction (Kox LF, Rhienthong D, Miranda AM et al. A more reliable PCR for detection of Mycobacterium tuberculosis in clinical samples. J Clin Microbiol 1994; 32: 672,678; Longo MC, Berninger MS, Hartley JL. Use of uracil DNA glycosylase to control carry-over contamination in polymerase chain reactions. Gene 1990; 93: 125,128). According to the manufacturer's instructions, amplification was carried out for 40 cycles with denaturation at 94 °C for 40 s, annealing at 70 °C for 1 min, and extension at 72 °C for 1 min in a thermal cycler (Perkin,Elmer Cetus, Norwalk, CT, USA). The results of PCR and tissue culture for M. tuberculosis using the biopsy specimen were all negative (Fig. 3). Figure 3. Negative result in PCR for M. tuberculosis (negative control is not shown; M, marker; P, positive control; I, internal control; S, specimen) The patient was finally diagnosed with erythema induratum with pulmonary tuberculosis and was started on antituberculosis medication (isoniazid 400 mg, rifampicin 600 mg, ethambutol 800 mg, and pyrazinamide 1500 mg daily). She showed prompt improvement after 2 weeks of medication. After 9 months of antituberculosis therapy, her skin lesions and chest X-ray had cleared. She was followed up for 4 months with no recurrence of skin and pulmonary lesions. [source] Single dose intravenous thioacetamide administration as a model of acute liver damage in ratsINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2008Tse-Min Chen Summary Thioacetamide (TAA) has been used extensively in the development of animal models of acute liver injury. Frequently, TAA is administered intraperitoneally to induce liver damage under anaesthesia. However, it is rarely administered by intravenous injection in conscious rats. The experiments in this study were designed to induce acute liver damage by single intravenous injection of TAA (0, 70 and 280 mg/kg) in unrestrained rats. Biochemical parameters and cytokines measured during the 60-h period following TAA administration, included white blood cells (WBC), haemoglobulin (Hb), platelet, aspartate transferase (GOT), alanine transferase (GPT), total bilirubin (TBIL), direct bilirubin (DBI), albumin, ammonia (NH3), r-glutamyl transpeptidase (r-GT), tumour necrosis factor-, (TNF-,) and interleukin-6 (IL-6). Rats were sacrificed by decapitation 60 h after TAA administration and livers were removed immediately for pathology and immunohistochemical (IHC) examination. Another group of rats were sacrificed by decapitation 1, 6 and 24 h after TAA administration and livers were removed immediately for time course change of pathology and IHC examination. TAA significantly increased blood WBC, GOT, GPT, TBIL, DBIL, NH3, r-GT, TNF-, and IL-6 levels but decreased the blood Hb, platelet and albumin level. The levels of histopathological damage in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 60 h after TAA administration. The levels of inducible nitric oxide synthase (iNOS) and nuclear factor-,B (NF-,B) detected by IHC in the liver after intravenous TAA administration were also increased with a dose-dependent trend and more increased at 1 h after TAA administration. Single intravenous TAA administration without anaesthesia is a restorable animal model which may be used to investigate acute liver damage. [source] Cerebral emboli and paradoxical embolisation in dementia: a pilot studyINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 1 2005Nitin Purandare Abstract Background The causes of the common dementias remain unknown. Paradoxical embolisation of the cerebral circulation by venous thrombi passing through venous to arterial shunts (v-aCS) in the heart or pulmonary circulation is known to occur in cryptogenic stroke and post-operative confusion following hip replacement. Objectives To explore the role of paradoxical embolisation in dementia by investigating for cerebral emboli, venous to arterial circulation shunt (v-aCS) and carotid artery disease. Methods Forty-one patients with dementia (24 Alzheimer's AD and 17 vascular VaD) diagnosed using DSM-IV criteria and 16 controls underwent transcranial Doppler (TCD) detection of spontaneous cerebral emboli in both middle cerebral arteries. A v-aCS was detected by intravenous injection of an air/saline ultrasound contrast at rest and after provocation by coughing and Valsalva's manoeuvre. Carotid artery disease was assessed by duplex imaging. Results Cerebral emboli were detected in 11 (27.5%) dementia patients compared with one (7%) control (p,=,0.15) with emboli being most frequent in VaD (41%) compared to controls [OR (95% CI): 10.5 (1.1, 98.9), p,=,0.04]. A v-aCS was detected in 25 (61%) patients and seven (44%) controls (p,=,0.24). In dementia patients with cerebral emboli; v-aCS was detected in seven (64%) and moderate to severe carotid stenosis was present in three (30%). Conclusion Cerebral emboli and v-aCS may be more frequent in patients with both VaD and AD than in controls, which suggest paradoxical embolisation as a potential mechanism for cerebral damage. This pilot study justifies a definitive case-control study. Copyright © 2004 John Wiley & Sons, Ltd. [source] Sedation with midazolam versus local anaesthesia with lignocaine for transrectal prostate biopsiesINTERNATIONAL JOURNAL OF UROLOGICAL NURSING, Issue 2 2008Ilana Golan Abstract Transrectal ultrasound-guided needle biopsy of the prostate is the only method for diagnosing prostate cancer. Although tolerated by most patients, 65,90% of patients complain of pain during the procedure. Most urologists utilize ultrasound-guided transrectal injection of lignocaine. Intravenous sedation with short-acting medications such as midazolam has been successfully used during many invasive ambulatory procedures, reducing discomfort and anxiety. The aim of this study was to compare the efficacy of pain and anxiety reduction using intravenous sedation with midazolam versus local anaesthesia with lignocaine during transrectal biopsies of the prostate in a cross-sectional study. Ninety consecutive candidates for transrectal prostate biopsy were divided into 2 groups. Group A received periprostatic block with 2% lignocaine and group B received sedation with intravenous injection of 4 mg midazolam prior to insertion of the probe. Side-effects and patient satisfaction were documented by questionnaires, which included a pain visual analogue scale (VAS). Significant differences were found between the two groups with respect to the patient's perceived intensity of pain. Pain level expressed by a VAS was 4·2 in group A and 1·9 in group B (P < 0·001). Eighty-seven per cent of the patients in group B stated that they would be willing to repeat the procedure if necessary compared with 55% in group A (P = 0·002). There were no complications or side-effects as a result of midazolam sedation. Midazolam is more effective in relieving pain and anxiety during transrectal prostate biopsies and as safe as a local injection of lignocaine. [source] | |||||||||||||||||||||||||||||||||||||||||||