Intravenous Injection Of Saline Research Articles

Endovascular occlusion of right to left arteriovenous shunt associated with persistent left superior vena cava

Left-sided superior vena cava (SVC) as the result of persistence of the left superior cardinal vein in postnatal life is a rare congenital anomaly, is usually associated with other cardiac defects, and can cause symptoms of right to left shunt. We report the case of a 58-year-old Asian man with a history of end-stage renal disease and Ebstein anomaly that was corrected surgically who presented with progressively worsening disabling dyspnea. An echocardiogram with concomitant intravenous saline injection raised the suspicion of right to left shunt, a finding that was confirmed with contrast injection of the left SVC that rapidly filled the left heart chambers and subsequently the aortic arch. To treat this anomaly, we accessed the left basilic vein under ultrasound guidance and inserted a 14F sheath into the left subclavian vein. A covered stent was then prepared at the back table with three Prolene 4-0 sutures that were wrapped around the middle portion of the graft to achieve a controlled area of stenosis after deployment. The stent graft was placed along the proximal innominate vein and the contiguous part of the left SVC. Coil embolization was then performed with coils that were positioned at the stenotic area of the covered stent. An immediate venogram demonstrated residual flow into the left SVC; however, a delayed venogram 2 weeks after the procedure showed occlusion of the left SVC and the development of collaterals to the right innominate vein that was draining to a normal right SVC. The patient remained marginally hypotensive after surgery, but he soon noted a substantial improvement in his symptoms. A repeat echocardiogram with intravenous saline injection confirmed the correction of the right to left shunt. Endovascular repair of persistent left SVC is feasible and safe and can be performed with minimal morbidity.

Glucocorticoid pretreatment suppresses chemokine expression and inflammatory cell infiltration in cholestatic rats receiving biliary intervention

Aim Biliary intervention may augment chemokine expression and inflammatory cell infiltration and aggravates liver injury in cholestatic rats. We tested the efficacy of glucocorticoid pretreatment to prevent the complications. Methods A model of biliary intervention was established in rats without (sham) or with bile duct ligation (BDL). Before biliary intervention, rats were randomly assigned to receiving intravenous injection of dexamethasone (DX group) or normal saline (NS group). Plasma levels of monocyte chemoattractant protein–1 (MCP-1) and macrophage inflammatory protein–2 (MIP-2) were measured with enzyme-linked immunosorbent assay, and liver messenger RNA of these chemokines was quantified with real-time quantitative reverse transcriptase–polymerase chain reaction. Monocytes, Kupffer cells, and neutrophils in the rat liver were characterized with antibodies to ectodermal dysplasia 1 (ED1), ED2, and myeloperoxidase, respectively. Results By 3 hours after biliary intervention, plasma MCP-1 and MIP-2 proteins in BDL-NS rats were significantly higher than in BDL-DX. At 3 hours, liver MCP-1 and MIP-2 messenger RNA levels were significantly upregulated in BDL-NS than in BDL-DX. The amount of ED1-, ED2- and myeloperoxidase-staining cells were significantly greater in BDL-NS than in BDL-DX. Most of the changes returned to baseline levels by 24 hours. Conclusion Glucocorticoid pretreatment suppresses chemokine expression and inflammatory cell infiltration, which may consequently alleviate liver injury in cholestatic rats receiving biliary intervention.

Effects of Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker on Ventricular Defibrillation Threshold

Angiotensin converting enzyme (ACE) inhibitors and Angiotensin II (AII) receptor blockers have previously been shown to be beneficial in treating patients with not only hypertension but also with cardiovascular diseases. Therefore, such drugs may potentially be used in patients with an implantable cardioverter defibrillator (ICD) who show cardiac dysfunctions. This study aimed to determine effects of short-term administration of the ACE inhibitor (CV-3317) and the AII receptor blocker (CV-11974, an active form of candesartan) on internal defibrillation threshold (DFT) in anesthetized canine hearts. DFTs were evaluated using a "hot can" defibrillation lead system in: (a) seven dogs following three intravenous administrations of 20 cc saline; (b) 11 dogs that received intravenous CV-3317 doses of 1 mg/kg, 10 mg/kg, and 50 mg/kg; and in (c) 10 dogs that were intravenously given 0.1 mg/kg, 1 mg/kg, and 10 mg/kg CV-11974. DFTs were determined using a "down-up down-up" protocol. Mean DFT delivered energies at baseline and following three consecutive intravenous saline injections were 16.4 +/- 9.3 J, 15.3 +/- 7.5 J, 15.9 +/- 7.1 J, and 15.5 +/- 5.6 J, respectively. Those at baseline and following 1 mg/kg, 10 mg/kg, and 50 mg/kg intravenous CV-3317 were 12.9 +/- 6.4 J, 12.2 +/- 6.4 J, 11.0 +/- 6.6 J, and 11.9 +/- 6.6 J, respectively. Similarly, those at baseline and after 0.1 mg/kg, 1 mg/kg, and 10 mg/kg CV-11974 were 13 +/- 6.6 J, 12.5 +/- 6 J, 12.9 +/- 5.8 J, and 13.2 +/- 6.6 J, respectively. There were no significant differences between DFT at baseline and the others in each treatment group. Since an ACE inhibitor and an AII receptor blocker did not alter DFT, such drugs may be useful in ICD patients without a decrease in safety margins.

Dopamine Antagonist Alters Serum Cortisol and Prolactin Secretion in Lactating Holstein Cows

The role of dopamine in regulating glucocorticoid and prolactin secretion was investigated in lactating Holstein cows by characterizing serum cortisol and prolactin responses to fluphenazine, a dopamine receptor antagonist. Twelve anovulatory cows received an intravenous bolus injection of either saline (n=6) or 0.3mg of fluphenazine/kg of body weight (n=6) in wk 2 postpartum. Blood samples were collected every 30min for 4h before and 4h after saline or fluphenazine injection. Serum progesterone concentration was 0.13±0.1ng/mL and did not differ between groups. No difference in serum cortisol concentrations was detected between groups before treatments. Fluphenazine increased serum cortisol concentrations within 30min after fluphenazine administration (>30ng/mL) and concentrations remained elevated throughout the sampling period. Cortisol remained unchanged in saline-treated cows (<10ng/mL). Prolactin concentrations also increased after fluphenazine administration (103.1±3.1ng/mL), but were unaffected by saline (18±3.1ng/mL). Prolactin concentrations remained elevated throughout the sampling period in fluphenazine-treated cows. Our results indicated that a dopamine antagonist increased cortisol, suggesting that endogenous dopamine, at least in part, regulates cortisol and prolactin secretion. These effects are regulated through dopamine receptors in anovulatory lactating dairy cows during the early postpartum period.

Endogenous pain inhibitory systems activated by spatial summation are opioid-mediated

We previously developed a spatial summation model and demonstrated that spatial summation of pain involves the activation of both excitatory and inhibitory systems. The aim of this study was to determine whether the endogenous pain inhibitory systems recruited by the spatial summation model are opioid-mediated by verifying if they could be blocked by the opioid antagonist naloxone. Twenty healthy volunteers (10 men, 10 women) participated in a randomized, four-session, cross-over study. Each session consisted of pain perception ratings (visual analog scale) taken during the immersion of different surfaces of the arm in circulating noxious cold water (12 °C). The arm was arbitrarily divided into eight segments from fingertips to shoulder. Two sessions were increasing (from fingertips to shoulder) and two sessions were decreasing (from shoulder to fingertips). All sessions consisted of eight consecutive 2-min immersions separated by 5-min resting periods. Intravenous injections of naloxone hydrochloride (0.14 mg/kg) or saline (NaCl, 0.9%) were administered under double-blind conditions. We found that during the control session (saline injection) there was a significant difference in pain intensity ratings between the increasing and decreasing sessions. The decreasing session resulted in lower pain intensity. As previously demonstrated, this lowering of the perception curve seems to be due to a large recruitment of inhibitory systems at the beginning of the decreasing session as opposed to a gradual recruitment during the increasing session. However, during the opioid inhibition session (naloxone injection) no differences were found between the increasing and decreasing sessions. Naloxone inhibited the endogenous pain inhibitory systems activated by the spatial summation model, suggesting that these systems have an opioid-mediated component, as previously reported for diffuse noxious inhibitory controls.

Magnetic Targeting of Magnetoliposomes to Solid Tumors with MR Imaging Monitoring in Mice: Feasibility

To establish the feasibility of magnetoliposome tumor targeting with an extracorporeal magnet. Animal experiments were performed in compliance with Institut National de la Santé Et de la Recherche Médicale animal protection guidelines and were approved by local government authorities. Magnetophoresis was used to measure the velocity of magnetoliposomes constituted of polyethylene glycol-lipids and anionic maghemite nanocrystals in a calibrated magnetic field in vitro. For in vivo studies, 38 male Swiss nude mice bearing a PC3 human prostate carcinoma tumor in each flank received an intravenous injection of magnetoliposomes (n = 27), saline (n = 9), or nonencapsulated superparamagnetic particles (n = 2) after a small magnet with a magnetic field of 0.3 T and a field gradient of 11 T/m was fixed to the skin above one tumor. The animals were examined at magnetic resonance (MR) imaging with eight different sequences, iron doses (13 mice), and magnet-application durations (12 mice). Their excised tumors were then stained with Perls Prussian blue and hematoxylin-eosin and were examined histologically. With use of the paired Student t test, signal intensity, tumor surface enhancement, and number of stained cells were compared between the control and magnet-exposed tumors to determine significant differences (P </= .01). The mean magnetoliposome velocity ranged from 10 to 40 mum/sec when the magnetic field equaled 0.13 T and the field gradient equaled 25 T/m. At T1-weighted three-dimensional spoiled gradient-echo MR imaging in vivo, the tumor exposed to the magnet showed strong negative enhancement, -52%, compared with the -7% enhancement of the other tumor. Maximal enhancement occurred after 3 hours of magnet application. After 24 hours of magnet application, intracapillary iron particle accumulation was observed in the targeted tumors only. Magnetic targeting of sterically stabilized magnetoliposomes after they are intravenously injected is feasible in vivo.

Oxidized Phospholipids Reduce Vascular Leak and Inflammation in Rat Model of Acute Lung Injury

Acute inflammation and vascular leak are cardinal features of acute lung injury and the acute respiratory distress syndrome. Nonspecific tissue inflammation and injury in response to infectious and noninfectious insults lead to oxidative stress and the generation of lipid oxidation products, which may inhibit the acute inflammatory response to bacterial components. To test the hypothesis that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) may attenuate the acute lung inflammatory response to lipopolysaccharide (LPS) and enhance lung vascular barrier recovery, we used in vivo and in vitro models of LPS-induced lung injury. Rats received intratracheal aerosolized LPS (5 mg/kg) or sterile water with concurrent intravenous injection of OxPAPC (0.5-6.0 mg/kg) or saline alone. Nonoxidized PAPC was used as a control. At 18 h, bronchoalveolar lavage was performed and the lungs were removed for histologic analysis. Measurements of endothelial transmonolayer electrical resistance and immunofluorescent analysis of monolayer integrity were used in an in vitro model of LPS-induced lung vascular barrier dysfunction. In vivo, aerosolized intratracheal LPS induced lung injury with profound increases in bronchoalveolar lavage neutrophils, protein content, and the inflammatory cytokines interleukin 6 and interleukin 1beta, as well as tissue neutrophils. OxPAPC, but not nonoxidized PAPC, markedly attenuated the LPS-induced tissue inflammation, barrier disruption, and cytokine production over a range of doses. In vitro, oxidized phospholipids attenuated LPS-induced endothelial barrier disruption and reversed LPS-induced cytoskeletal remodeling and disruption of monolayer integrity. These studies demonstrate in vivo and in vitro protective effects of oxidized phospholipids on LPS-induced lung dysfunction.

Adrenal responsiveness of reindeer (Rangifer tarandus tarandus) to intravenously administered ACTH

AbstractPlasma cortisol concentrations were determined from the blood of eight mature female reindeer (Rangifer tarandus tarandus) after an intravenous injection of either saline (control) or 100, 250 or 500 μg of synthetic ACTH. Blood samples were collected at 0, 2, 4, 6, 8, 10, 15, 20, 25, 30, 45, 60, 75, 90, 120, 150, and 180 min after the injections. The aims were to determine the appropriate dose of ACTH for adrenal stimulation tests, to define the dose level of ACTH which elicited a maximal cortisol response and to describe the range of blood cortisol concentrations for reference when evaluating the stress responses of reindeer.The mean plasma cortisol concentrations (s.e.) at the zero sample times (t0) of the control and the ACTH treatments varied between 93·4 (11·8) and 132·5 (18·1) nmol/l. The total plasma cortisol response (area under curve, AUC, nmol/l × min) increased with increasing dose of ACTH (P &lt; 0·001). The AUC of the control treatment was significantly smaller than of the ACTH treatments (P &lt; 0·001). The highest dose of ACTH (500 μg) gave a significantly bigger AUC than the lowest dose (100 μg) (P = 0·008). The maximal plasma cortisol concentrations (CMAX) were achieved within 60 min of the ACTH injections. The ranges of individual CMAX were 59·0 to 136·8 nmol/l for the control treatment, and 110·0 to 252·0, 152·0 to 247·5 and 135·1 to 257·1 nmol/l for 100, 250 and 500 μg ACTH, respectively. The difference in CMAX was significant between the control treatment and the ACTH treatments (P &lt; 0·001) but not between the different doses of ACTH. The plasma cortisol concentrations at the end of the observation period at t180 were not significantly affected by the ACTH treatment (P &gt; 0·05).In conclusion, the 100-μg dose of ACTH was sufficient to produce a significant cortisol response compared with the control treatment. Increasing the dose did not increase the maximal response, but tended to elongate the response profile. The blood sampling frequency used in the study was found suitable for detection of the cortisol response in reindeer.

Ferumoxtran-10–Enhanced MRI of the Hypercholesterolemic Rabbit Aorta

Ferumoxtran-10 is an MRI contrast agent, which accumulates in macrophages and induces magnetic susceptibility artifacts (MSAs). We evaluated the ability of ferumoxtran-10-enhanced MRI to quantify focal macrophage infiltration in the aortic wall of hypercholesterolemic rabbits. Six weeks after a double-balloon injury of the infrarenal aorta, 12 hypercholesterolemic rabbits underwent MRI of the aorta before (first MRI) and after (second MRI) intravenous injection of ferumoxtran-10 (n=10) or saline (n=2). A third MRI was performed 5 days later to detect ferumoxtran-10-induced MSA in the aortic wall. Aortas were subsequently processed for histology, immunohistochemistry, and gelatin zymography studies. Injured aortas displayed a macrophage-rich neointima with high-matrix metalloproteinase 2 and 9 activities. Iron stain of injured aortas showed massive accumulation of ferumoxtran-10 in neointimal macrophages. Five days after the injection of ferumoxtran-10, MSAs were detected only in the injured aortas by in vivo MRI and were quantified indirectly using the percentage reduction of luminal area attributable to the extension of these MSAs in the aortic lumen. This parameter correlated with macrophage infiltration on corresponding aortic cross-sections (r=0.82; P<0.05). Ferumoxtran-10-enhanced MRI allows quantitative assessment of macrophage infiltration induced by balloon angioplasty in the aorta of hypercholesterolemic rabbits.

Hepatocyte Growth Factor Facilitates the Repair of Large Colonic Ulcers in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in Rats

Hepatocyte growth factor (HGF) modulates intestinal epithelial cell proliferation and migration, serving as a critical regulator of intestinal wound healing. The aim of this study was to clarify the effects of administration of recombinant human HGF on colonic mucosal damage in vivo. Rats were given 7.5 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS) per rectum on day 0. On day 5, the degree of TNBS-induced colitis was evaluated endoscopically, and rats suffering from large ulcers (occupying more than two thirds of the luminal circumference) were treated with intravenous bolus injections of recombinant human HGF (1.0 mg/kg per day) or phosphate-buffered saline (PBS) for 5 days. Rats with TNBS-induced colitis given human HGF showed a significant reduction in colonic ulcer coverage and large intestinal shortening compared with those treated with PBS. Administration of recombinant human HGF also stimulated the proliferation of epithelial cells and reduced the inflammatory cell infiltrate. Finally, HGF treatment decreased the myeloperoxidase activity and tumor necrosis factor alpha levels in the TNBS-inflamed colon tissues. These results indicate that intravenous injection of HGF accelerates colonic mucosal repair and reduces infiltration of inflammatory cells in rats with TNBS-induced colitis and suggest that HGF has the potential to be a new therapeutic modality to promote intestinal mucosal repair in patients with inflammatory bowel disease.

Effect of sodium channel blocker (mexiletine) on pathological ectopic firing pattern in a rat chronic constriction nerve injury model

We studied the efficacy of mexiletine as a sodium channel blocker for neuropathic pain by investigating the effect of mexiletine on the pathological ectopic firing pattern in a chronic constriction nerve injury (CCI) model. The experiment was conducted with 60 male Wistar rats. The CCI model was created by loosely ligating the sciatic nerve. After breeding 7 days, the frequency and pattern of ectopic firing antidromically recorded from the sural nerve and the amplitude of antidromic sensory nerve-evoked potential were analyzed. The CCI rats were given an intravenous injection of normal saline and mexiletine (5 or 15 mg/kg). Mexiletine significantly suppressed spontaneous firing frequency, an on-off firing pattern that consisted of cyclic bursting spikes and ectopic firing generation under the hypoxic condition. Mexiletine did not influence the amplitude of Α-δ component in the antidromic sensory nerve-evoked potential. Mexiletine suppressed ectopic firing by blocking activity of the abnormal sodium channel at the nerve-injured site and dorsal root ganglion without blocking nerve conduction. This study suggests that mexiletine is useful for treating neuropathic pain in peripheral neuropathy.

NF‐κB inhibitors stabilize the mRNA of high‐affinity type‐2 cationic amino acid transporter in LPS‐stimulated rat liver

Induction of inducible nitric oxide synthase (iNOS) results in nitric oxide (NO) overproduction during endotoxemia. Cellular uptake of L-arginine, modulated by the isozymes of type-2 cationic amino acid transporters (CAT), including CAT-2, CAT-2A and CAT-2B, has been reported to be a crucial factor in the regulation of iNOS activity. We sought to elucidate the expression of CAT-2 isozymes and the role of nuclear factor-kappaB (NF-kappaB) in this expression in lipopolysaccharide (LPS)-treated rat liver. Adult male Sprague-Dawley rats were randomly given intravenous (i.v.) injections of normal saline (N/S), LPS, LPS preceded by an NF-kappaB inhibitor (PDTC, dexamethasone or salicylate) or an NF-kappaB inhibitor alone. After injection, rats were sacrificed at different times and enzyme expression and liver injury were examined. Hepatic and systemic NO production were also measured. CAT-2, CAT-2A and CAT-2B were constitutively expressed in un-stimulated rat liver. LPS stimulation not only significantly increased iNOS mRNA and NO concentrations but also decreased the mRNA concentrations of CAT-2 and CAT-2B, but not CAT-2A, in a time-dependent manner. LPS-induced hepatic and systemic NO overproduction was associated with hepatocellular injury. Pre-treatment with NF-kappaB inhibitors significantly attenuated LPS-induced iNOS induction as well as CAT-2/CAT-2B mRNA destabilization, which was associated with significant inhibition of NO biosynthesis and less liver injury. NF-kappaB inhibitors stabilize CAT-2 and CAT-2B mRNA in LPS-stimulated rat liver. The hepatic CAT-2/CAT-2B pathway may be a constitutive part of cytoprotective mechanisms against sepsis.

Inhibition by Lipopolysaccharide of Naloxone‐Induced Luteinising Hormone Secretion Is Accompanied by Increases in Corticotropin‐Releasing Factor Immunoreactivity in Hypothalamic Paraventricular Neurones in Female Rats

We have recently reported that lipopolysaccharide (LPS), a bacterial endotoxin, inhibits steroid-induced as well as naloxone-induced luteinising hormone (LH) secretion in ovariectomised oestrogen-primed rats. In the present study, we examined whether corticotropin-releasing factor (CRF) may be involved in the LPS-induced inhibition of LH secretion. Unanaesthetised rats were treated with an intravenous (i.v.) injection of LPS (10 microg) or saline, followed by an i.v. injection of naloxone (20 mg/kg). After sequential blood samples were collected for determination of serum LH concentrations, the brains were fixed and CRF-immunoreactivity was examined histochemically. In control rats receiving saline injections, only a small number of CRF-immunoreactive (ir) cells were found in the parvocellular portion of the hypothalamic paraventricular nucleus (PVN), and naloxone significantly increased serum LH concentrations within 10 min. By contrast, in LPS-treated rats, the number of CRF-ir cells was significantly greater than that in control rats, and the effect of naloxone was completely abolished. In a separate experiment, an intracerebroventricular injection of 5 microg CRF inhibited naloxone-induced LH release, mimicking the effect of LPS. These results suggest that LPS stimulates production of CRF in PVN neurones, which in turn inhibits LH secretion without opioidergic mediation.

Pulmonary Arteriovenous Malformations

Pulmonary arteriovenous malformations represent a direct communication between one or more pulmonary arteries and one or more pulmonary veins. Common anatomic forms include single sacs ranging from 1 to >10 cm in diameter, macroscopic tangles, and microscopic telangiectases. The main complications of pulmonary arteriovenous malformations are believed to relate to right-to-left shunting of blood through the pulmonary arteriovenous malformations and include stroke and brain abscess, which together occur in up to one half of patients if untreated. However, the association of pulmonary hypertension is not common. In this case, a young woman with a pulmonary arteriovenous fistula localized to the left lower lobe coexisting with pulmonary hypertension is described. A 42-year-old woman was evaluated for progressively worsening exertional dyspnea. Her past medical history was unremarkable. The electrocardiogram revealed sinus rhythm with right ventricular hypertrophy with strain. Transthoracic echocardiography showed enlarged right atrium and ventricle with elevated right ventricular systolic pressure (tricuspid regurgitant jet velocity 4.8 m/s). There was no evidence of pulmonic stenosis. Chest computed tomography was performed to rule out chronic pulmonary embolism and revealed multiple pulmonary arteriovenous fistulas on the left lung, the largest (17mm) on left lower lobe-posterior basal segment, middle on the left lower lobe-medial basal segment, and the smallest on anterior segment of left upper lobe (Fig. 1). Contrast echocardiography was performed by intravenous injection of hand-agitated saline while visualizing the atria. Contrast appears in the left atrium 3 to 5 seconds after it is seen in the right atrium, suggestive of pulmonary arteriovenous fistula (Fig. 2). On cardiac catheterization, peak systolic and diastolic pressures of main pulmonary artery were 90 and 35 mmHg, respectively. Mean pulmonary artery wedge pressure was 11 mmHg. Angiography revealed a huge pulmonary arteriovenous fistula in the middle and lower lobes of the left lung (Fig. 3). The patient decided to be treated conservatively and discharged.

The Effect of Ondansetron and Metoclopramide on the Prevention of Postoperative Nausea and Vomiting After Using Epidural Morphine-Butorphanol Mixture

Background: Neuroaxial morphine may produce nausea and vomiting due to cephalad migration. Though it improves post- operative pain, it may have serious complication delaying recovery. The aim of this study was to investigate the efficacy of prophylactic antiemetics such as conventional metoclopramide or more expensive ondansetron. Methods: Eighty-seven patients who underwent orthopedic knee arthroscopic surgery under epidural anesthesia were randomly assigned to three groups, which are (a) normal saline intravenous injection control group (Group C), (b) metoclopramide intravenous injection and intranasal spray study group (Group M), (c) ondansetron inravenous injection group (Group O). Before the end of surgery, all patients were given 3 mg of morphine and 2 mg of butorphanol mixture via epidural catheter for postoperative pain control. The anesthesia were all standardized. Post-operative nausea and vomiting were observed and used as outcome variables and postoperative pain, itching, somnolence, dizziness, urinary retention were also observed. Results: The incidence of postoperative nausea was significantly lower in Group M (P = 0.0296) and Group O (P = 0.005) compared with Group C. The incidence of postoperative vomiting was significantly lower in Group O (P = 0.01) compared with Group C. But statistically no difference was noted in vomiting between Group C and Group M (P = 0.0579). Conclusions: The results suggest that ondansetron and metoclopramide are effective in reducing the incidence of post-operative nausea. But ondansetron is more effective in reducing the incidence of post-operative morphine induced vomiting.

Relationship between noradrenaline and nonlinear indexes of blood pressure dynamics in normotensive and spontaneously hypertensive rats

Recent studies in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats show that some nonlinear indexes derived from the recurrence plot method may be better markers of sympathetic activity than the spectral powers of blood pressure (BP). We herein investigated the relationships between nonlinear indexes and plasma noradrenaline concentration in conscious WKY rats and SHRs. Blood pressure was recorded for 30 min after intravenous injection of saline (0.9% NaCl, 100 microL/kg), hexamethonium (20 mg/kg), atropine (0.5 mg/kg), atenolol (1 mg/kg) or prazosin (1 mg/kg). Spectral power in the low-frequency (LF) band and the nonlinear index (L(max)), calculated on diastolic (DBP) and systolic blood pressures (SBP), were used to analyse the BP signal. Noradrenaline concentration was determined by radioenzymatic technique. A robust stepwise regression analysis - using noradrenaline concentration as dependent variable, and LF, L(max) and treatment, as independent variables -shows that treatment is the main variable explaining the variance of noradrenaline level in WKY rats, excluding the use of the pooled data to explore the relationship between noradrenaline concentration and LF or L(max). In contrast, in SHRs, treatment has no effect on the variance of noradrenaline concentration and the pooled data were then used. In this group, no correlation was observed between noradrenaline concentration and LF. In contrast, very high positive correlation was observed between noradrenaline level and L(max)-DBP (r = 0.59; P = 0.0005) or L(max)-SBP (r = 0.53; P < 0.002). The results strengthen our previous suggestion that nonlinear indexes may be better tools than spectral powers to investigate the sympathetic nervous system.

NF-kappaB involvement in the induction of high affinity CAT-2 in lipopolysaccharide-stimulated rat lungs.

Endotoxemia stimulates nitric oxide (NO) biosynthesis through induction of inducible NO synthase (iNOS). Cellular uptake of L-arginine, the sole substrate for iNOS, is an important mechanism regulating NO biosynthesis by iNOS. The isozymes of type-2 cationic amino acid transporters, including CAT-2, CAT-2A, and CAT-2B, constitute the most important pathways responsible for trans-membrane L-arginine transportation. Therefore, regulation of CAT-2 isozymes expression may constitute one of the downstream regulatory pathways that control iNOS activity. We investigated the time course of enzyme induction and the role of nuclear factor-kappaB (NF-kappaB) in CAT-2 isozymes expression in lipopolysaccharide-(LPS) treated rat lungs. Adult male Sprague-Dawley rats were randomly given intravenous injections of normal saline (N/S), LPS, LPS plus NF-kappaB inhibitor pre-treatment (PDTC, dexamethasone, or salicylate), or an NF-kappaB inhibitor alone. The rats were sacrificed at different times after injection and enzyme expression and lung injury were examined. Pulmonary and systemic NO production were also measured. LPS co-induced iNOS, CAT-2, and CAT-2B but not CAT-2A expression in the lungs. Furthermore, NF-kappaB actively participated in LPS-induction of iNOS, CAT-2, and CAT-2B. LPS induced pulmonary and systemic NO overproduction and resulted in lung injuries. Attenuation of LPS-induced iNOS, CAT-2, and CAT-2B induction significantly inhibited NO biosynthesis and lessened lung injury. NF-kappaB actively participates in the induction of CAT-2 and CAT-2B in intact animals. Our data further support the idea that CAT-2 and CAT-2B are crucial in regulating iNOS activity.

Dalbavancin compared with vancomycin for prevention of Staphylococcus aureus colonization of devices in vivo

Objectives. Although active against free-floating bacteria, vancomycin displays a poor activity against organisms embedded within the biofilm surrounding implanted devices. Dalbavancin is a novel glycopeptide antibiotic with strong activity against staphylococci and a long half-life that allows for once-a-week dosing. The objective of this animal study was to examine the ability of dalbavancin and vancomycin to prevent Staphylococcus aureus colonization of devices. Methods. Twelve rabbits were randomized, in three groups of four each, to receive intravenous injections of dalbavancin, vancomycin or normal saline (control). Eight polyurethane catheter segments were subcutaneously implanted in the back of each rabbit, then inoculated with S. aureus. Rabbits were sacrificed a week later and explanted devices were cultured. Results. The rates of device colonization were comparable in the vancomycin (53%) and control (47%) groups, whereas only 28% of devices in the dalbavancin group became colonized. There was a trend (although not statistically significant) toward a lower rate of device colonization following receipt of dalbavancin vs. vancomycin ( P=0.07) or saline ( P=0.20). Conclusions: The demonstrated efficacy of dalbavancin in this animal study suggest that this novel antibiotic may have an important role in the prevention and treatment of device-related infection.

Self-administration of fentanyl, cocaine and ketamine: effects on the pituitary?adrenal axis in rhesus monkeys

Drugs of abuse can affect the functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Acute administration of drugs that serve as reinforcers have been observed to stimulate the rat HPA axis, leading to the suggestion that these stimulatory effects may contribute to the development of drug-maintained behaviors. To determine whether reinforcing drugs that are dissimilar with respect to their mechanisms of action have similar effects on HPA axis activity at doses that are self-administered. Rhesus monkeys were randomly assigned to self-administer the mu-opioid agonist fentanyl, the psychomotor stimulant cocaine, or the NMDA antagonist ketamine. Each monkey was trained to press a lever in order to receive an intravenous injection of drug or saline. Blood samples were obtained before, during, and after the self-administration sessions and assayed for ACTH and cortisol by radioimmunoassay. Fentanyl, cocaine, and ketamine were each self-administered across a range of doses. However, the three drugs differed in their effects on ACTH and cortisol. Cocaine stimulated ACTH and cortisol secretion, a finding that is consistent with previous rat and primate studies. Self-administration of both fentanyl and ketamine inhibited HPA axis activity. HPA inhibition by fentanyl is consistent with other monkey and human studies, and contrasts with the stimulatory effects of mu-opioids in rodents. The inhibitory effect of ketamine on ACTH and cortisol secretion contrasts with findings in the few primate studies that have evaluated NMDA antagonists. Neither fentanyl nor cocaine, at doses that maintained maximum rates of responding, produced significant changes in ACTH and cortisol levels. There appears to be little commonality between different classes of abused drugs and their effects on the HPA axis, which calls into question the necessity for HPA axis stimulation in the reinforcement of drug-maintained behavior.

The effects of a cold-water stimulus on butorphanol effects in males and females

Using a crossover, randomized, double-blind, cumulative-dosing procedure, we examined whether a painful stimulus modulated subjective and psychomotor effects of butorphanol in eight male and eight female volunteers. During each session, volunteers received four intravenous injections of either butorphanol (0, 0.5, 1, and 2 mg/70 kg) or saline (placebo) at hourly intervals. Saline and butorphanol were tested in two conditions, forearm immersion 30 min after each injection into either 2 or 37 °C water. During the 180-s immersion, volunteers completed a visual analog scale (VAS), psychomotor test, and pain ratings. VAS ratings of “Coasting (‘spaced out’)”, “heavy or sluggish feeling,” and “sleepy” were lower in the 2 °C than in the 37 °C condition during butorphanol administration, but only in females. Modulation by a painful stimulus of sleepy ratings was confined to the third immersion (i.e., a dose effect). The cold-water stimulus significantly decreased butorphanol-induced impairment during the third immersion for males, and females showed a similar trend. Overall, pain ratings were higher in females, and although not significant, males reported a greater degree of analgesia. The differences in pain ratings and degree of analgesia between the sexes are discussed as a possible mechanism for the sex differences in modulatory effects.