Injection Of Distilled Water Research Articles

Injection péridurale accidentelle d’eau pour préparation injectable : analyse systémique d’un cas

Four milliliters of distilled water was accidentally injected during labor epidural analgesia in a 32-year-old woman. This epidural injection resulted in severe and instantaneous thoracolumbar pain, which disappeared after epidural administration of NaCl 0.9% 5mL followed by 20ml of an analgesic mixture (ropivacaïne 0.1%+sufentanil 0.25μg/ml). There was no evidence of any neurologic deficit or residual pain until discharge 10 days later. Although no other cases of accidental epidural injection of distilled water have been described up to now, a literature survey showed that it had been used previously as an old method to find the epidural space. However, few experimental data suggest that distilled water can be neurotoxic, which strictly contraindicates its use by epidural route. We used the Reason's systemic analysis model to identify each step that contributed to this error. Corrective measures were then implemented to avoid the recurrence of this error.

Surgical Adhesive/Soft Tissue Adhesion Measured by Pressurized Blister Test

AbstractThe practical adhesion of equine pericardium membranes bonded with surgical glue has been measured by the bulge-and-blister technique under injection of pressurized distilled water. The value of the interfacial crack propagation energy can be estimated from the critical debonding pressure. The measured practical adhesion energies are weak with regards to those of engineering structural adhesives, but they are reliable enough to allow a comparison between different surgical glues and a study of the influence of the bonding experimental conditions.

Comparison of Hemostatic Efficacy for Argon Plasma Coagulation and Distilled Water Injection in Treating High-risk Bleeding Ulcers

Endoscopic treatment is recommended for initial hemostasis in nonvariceal upper gastrointestinal bleeding. Many endoscopic devices have been demonstrated to be effective in the hemostasis of bleeding ulcers. However, the hemostatic efficacy of argon plasma coagulation (APC) has not been widely investigated. From February 2007 to February 2008, 271 consecutive patients with high-risk bleeding ulcers, characterized by active bleeding, nonbleeding visible vessels and adherent clots, were admitted to our hospital. Among these patients, 135 nonrandomly underwent either APC therapy or distilled water injection. Pantoprazole infusion was conducted during the fasting period after endoscopy and orally for 8 weeks to encourage ulcer healing. Episodes of rebleeding were retreated with endoscopic combination therapy. Patients who did not benefit from retreatment underwent emergency surgery. In all,135 patients were enrolled, among whom 6 with gastric malignancy, acute severe illness or multiple bleeding sites were excluded. Finally, hemostatic efficacy in 59 patients treated with APC was prospectively compared with 70 patients treated with distilled water injection. The two treatment groups were similar with respect to all baseline characteristics. Initial hemostasis was accomplished in 57 patients treated with APC, and 64 patients with distilled water injection therapy (97% vs. 91%, P=0.29). Bleeding recurred in 6 patients treated with APC, and in 17 patients treated with distilled water injection (11% vs. 27%, P=0.03). No significant differences were observed between the 2 groups in hospital stay, transfusion requirements, surgery and mortality. Endoscopic therapy with APC is more effective than distilled water injection for preventing rebleeding in the treatment of high-risk bleeding ulcers.

Should Pharmacists have a Role in Harm Reduction Services for IDUs? A Qualitative Study in Tallinn, Estonia

Despite the high number of injecting drug users (IDUs) in Estonia, little is known about involving pharmacies into human immunodeficiency virus (HIV) prevention activities and potential barriers. Similarly, in other Eastern European countries, there is a need for additional sources for clean syringes besides syringe exchange programmes (SEPs), but data on current practices relating to pharmacists' role in harm reduction strategies is scant. Involving pharmacies is especially important for several reasons: they have extended hours of operation and convenient locations compared to SEPs, may provide access for IDUs who have avoided SEPs, and are a trusted health resource in the community. We conducted a series of focus groups with pharmacists and IDUs in Tallinn, Estonia, to explore their attitudes toward the role of pharmacists in HIV prevention activities for IDUs. Many, but not all, pharmacists reported a readiness to sell syringes to IDUs to help prevent HIV transmission. However, negative attitudes toward IDUs in general and syringe sales to them specifically were identified as important factors restricting such sales. The idea of free distribution of clean syringes or other injecting equipment and disposal of used syringes in pharmacies elicited strong resistance. IDUs stated that pharmacies were convenient for acquiring syringes due to their extended opening hours and local distribution. IDUs were positive toward pharmacies, although they were aware of stigma from pharmacists and other customers. They also emphasized the need for distilled water and other injection paraphernalia. In conclusion, there are no formal or legislative obstacles for providing HIV prevention services for IDUs at pharmacies. Addressing negative attitudes through educational courses and involving pharmacists willing to be public health educators in high drug use areas would improve access for HIV prevention services for IDUs.

The Effects of Low-Level Laser Therapy on Bone in Diabetic and Nondiabetic Rats

The aim of the present study was to examine the effects of low-level laser therapy (LLLT) on the tibia of streptozotocin-induced diabetic (STZ-D) rats. LLLT has been found to accelerate fracture healing in animals. Diabetes mellitus decreases bone volume and its biomechanical parameters. Twenty rats were divided randomly into four groups. Rats in the first two groups were administrated a single injection of STZ to induce diabetes, while animals in groups 3 and 4 were given a sham injection of distilled water. The right tibia in groups 1 and 2 was treated with a He-Ne laser (632.8 nm, 10 mW) of 28.6 and 382.2 J/cm(2), respectively. LLLT was performed daily for 14 consecutive days. The right tibia of rats in group 3 was treated with LLLT the same as group 2. The right tibia of rats in group 4 was used for based line studies. After 14 d, right tibiae and left tibiae (control bone) were extracted and subjected to the three-point bending test and histological study. Maximum force (N) was significantly greater in laser-treated bones of groups 2 and 3 compared with their relevant control groups (paired Student t test, p = 0.05 and p = 0.007, respectively). Density of the bone lamella meshwork of compact bone in group 2 was significantly greater in comparison with its control group (paired Student t test, p = 0.005). LLLT on tibia of STZ-D rats increased the bone lamella meshwork density of compact bone and also increased its strength.

Postnatal Repeated Mild Stress and DEγE Treatment Induce a Reduction of S of DBA/2J in Mice

The present paper evaluates the effect of DEγE on the epileptiform EEG activity in a mouse model of epilepsy, i.e., the DBA/2J epileptiform pattern and the DBA/2J audiogenic seizures. Repeated neonatal mild stress, such as manipulation of pups and a brief isolation from the dam performed daily for a few weeks, induces brain, behavioural and hormonal alterations which may perdure up to adult and senescent ages. Since DEγE (a well known β-endorphin fragment) was able to modulate the epileptiform activity in animal models, we started an investigation to verify whether DEγE could modulate epileptiform EEG activity in DBA/2J mice. Litters of DBA/2J mice born in our laboratories were used. Pups of the litter W once per day were separated from mam for ten minutes, weighed and injected with distilled water sc or DEγE (50 and 100 mg/kg), from day 2 to day 21 (weaning). At the age of 60-90 days, mice under general (ketamine-xylazine) plus local (xylocaine) anaesthesia were implanted with 4 stainless electrodes in the anterior and posterior sensorimotor cortex bilaterally. At least 6 days later, they were placed in a sound-proof room, and EEG and motor activity were recorded for 60 min. Two parameters were evaluated: sleep-wakefulness cycle and epileptiform activity. The latter parameter consisted of four different data: spikes, polispikes, series of spike-and-waves, and series of polispike-and-waves. Our results show that a chronic mild stress in neonatal period, as daily injection of distilled water sc., in adult age induced a significant reduction of mean number of series of polispike-and-wave versus control; this effect in mice, chronically treated with DEγE at both doses 50 ng/μL and 100 ng/μL, was also observed. Chronic neonatal mild stress also induced alterations in response to visual evoked potentials. Flash evoked potentials of mice injected with distilled water appeared with a significant delay of latency at the frequency of 1 Hz and at the lower intensity of luminous stimulation versus control; we observed the same trend in chronically treated with DEγE 50 and 100 ng/μL/mice. The results of our experiments indicate that adult mice which had received DEγE showed a consistent reduction in mean number of series of polispike-and-wave versus controls. Other epileptiform parameters in stressed mice did not show consistent alteration, neither sleep-wakefulness cycle did. Also audiogenic seizures did not show consistent differences between groups. We conclude that some, but not all epileptiform parameters in a genetic model of epilepsy in mice are sensitive to DEγE. Keywords: Mild stress, Epilepsy, DBA/2J mice, DEγE

Retrospective analysis of clinical characteristics of toxic anterior segment syndrome

To investigate the etiology, clinical features, treatment and prognosis of toxic anterior segment syndrome (TASS). It was a retrospective series case study. The clinical data of eight definite diagnosed TASS cases were retrospectively analyzed. Among eight TASS cases, seven were post cataract surgery cases and one was post cornea penetrating injury. Three cases were caused by residual povidone iodine on instruments, 2 cases resulted from the misuse of distilled water as intraocular irrigating liquid during cataract surgery, 2 cases were produced by the countercurrent of antibiotic solution via the cornea-scleral incision into anterior chamber during subconjunctival injection at the end of the surgery, and 1 case was induced by the injection of the distilled water into the anterior chamber at the end of the surgery. Three TASS cases occurred during operation and 5 cases occurred at 1 day after operation. All eight cases suffered from the painless blurred vision. Three cases occurred during operation presented with decrease of corneal transparency and depigmentation of iris. On the first day after operation, all cases had diffuse corneal stroma edema and severe anterior uveitis. Dexamethasone 0.1% or prednisolone acetate 1% eye drops, three times per day or one time per hour was used in all cases. Carteolol 2% eye drop, two times per day, was used for the cases with ocular hypertension. The cornea was clear in 6 cases, but corneal endothelial decompensation in 2 cases after therapy. Various toxic agents injected into anterior chamber by misuse can result in TASS. All these misuse can be avoided. Early diagnosis and proper management may be important to improve the prognosis of TASS.

Pentoxifylline suppresses the expression of tumor necrosis factor-α and interleukin-1β in ulcerative colitis in rats

AIM: To investigate the effects of pentoxifylline (PTX) on the expression of tumor necrosis factoralpha (TNF-α) and interleukin-1β (IL-1β) in trinitrobenzene sulfonic acid (TNBS) -induced ulcerative colitis (UC) in rats. METHODS: UC was induced in rats with TNBS and ethanol. The rats were randomly divided into three groups: normal group (C), TNBS group (T), and PTX group (D). Three days after UC was induced, the rats in the PTX group received a PTX injection every 12 hours for five consecutive days, while the remaining two groups received an injection of distilled water. The disease activity index (DAI) was evaluated daily. The expression of TNF-α and IL-1β mRNAs was measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with the normal group and the PTX group, the expression of TNF-α and IL-1β mRNAs and DAI in the TNBS group were markedly higher (6.85 ± 2.78 vs 0.45 ± 0.11 and 1.85 ± 2.01; 1.02 ± 0.16 vs 0.61 ± 0.08 and 0.74 ± 0.16;and 0.95 ± 0.17 vs 0.57 ± 0.07 and 0.64 ± 0.13, respectively; all P＜0.05). No significant differences were noted in the expression levels of TNF-α and IL-1β mRNAs and DAI between the normal group and the PTX group (all P ＞ 0.05). CONCLUSION: The expression of proinflammatory factors TNF-α and IL-1β mRNAs increases in rat ulcerative colitis. PTX exerts protective effects against UC possibly by downregulating the expression of TNF-α and IL-1β mRNAs.

Open elevated plus maze-induced antinociception in rats: A non-opioid type of pain inhibition?

CORNÉLIO, A. M. AND NUNES-DE-SOUZA, R. L. Open elevated plus maze-induced antinociception in rats: A non-opioid type of pain inhibition? PHYSIOL BEHAV 00 (0) 000–000, 2008. This study investigated whether antinociception induced by exposure to an open elevated plus-maze (oEPM: four open arms) (i) shows cross-tolerance to morphine (Exp. 1 and 2), (ii) is attenuated by repeated exposure to the oEPM (Exp. 3), (iii) is blocked by systemic treatment with naltrexone (Exp. 4), and (iv) is affected by adrenalectomy (Exp. 5) in rats. Animals were daily treated with morphine (M, 5 mg/kg, i.p.) or distilled water (DW) for 5 consecutive days (antinociceptive tolerance assessed by tail-flick test). Then, rats received formalin 2.5% injection (50 μl) into the right hind paw followed by M or DW injection and 25 min later, time spent licking the injected paw was recorded for 10 min (Exp. 1). Similar procedure was followed in Experiment 2, except that licking response was recorded during exposure to an oEPM or enclosed EPM (eEPM: four enclosed arms) in undrugged rats. Experiment 3 evaluated nociception in rats submitted to 1, 2, 3, 4 or 6 exposures to either eEPM or oEPM (formalin was injected only during the last exposure). Experiment 4 investigated the effects of naltrexone (2.5 mg/kg; s.c.) on nociception during eEPM or oEPM exposure. Nociception was also assessed during eEPM or oEPM exposure in sham and adrenalectomized rats (Exp. 5). The results shown that oEPM-induced antinociception (i) did not display cross-tolerance to morphine, (ii) was unchanged by at least 6 maze re-exposures, (iii) failed to be reversed by naltrexone, and (iv) was not prevented by adrenalectomy.

Ototoxicity in Guinea Pigs: NO Levels in Cochlear Fluids

Problem Ototoxicity continues to be the most common side effect of gentamicin, and its physiopathology is still unclear. Currently the main accepted theory relates the ototoxicity with over production of free radicals, like nitric oxide (NO). Objective: To analyze the NO levels in the cochlear fluids of guinea pigs exposes to gentamicin and its relation with ototoxicity and propose an experimental model to study ototoxicity and drugs that may prevent it. Methods Six guinea pigs were used, divided in two groups: a) Study – submitted to intraperitoneal injections of gentamicin, (135mg/kg/day) for 14days; b) Control - submitted to intraperitoneal injections of distilled water, daily, for 14days; the hearing loss was evaluated with Preyer's reflex. On 14 day the guinea pigs were sacrificed and the cochlear fluids were collected for dosage of the nitric oxide through the chemiluminescence method (NOA-TM 280). Results The Preyer's reflex was absent at the end of the experiment in the Study group, what did not happen in the control group. The average of the nitric oxide levels of the guinea pigs of the study group was 26.2μ and the Control group 11.26μM. Conclusion It was possible to measure nitric oxide levels in guinea pigs cochlear fluids. The results reinforce the role of nitric oxide in ototoxicity induced by gentamicin. Significance Experimental study (Level 2).

Chronic Indomethacin Treatment Enhances the Portal-systemic Collateral Vascular Response to Vasopressin in Bile-duct Ligated Rats

Liver cirrhosis is often accompanied by portal-systemic collateral formation with hemorrhage and encephalopathy. Prostacyclin participates in hyperdynamic circulation and vascular hyporeactiveness to vasoconstrictors in cirrhosis. It has been shown that arginine vasopressin (AVP) induces direct collateral vasoconstriction in portal hypertensive rats, which is potentiated by indomethacin preincubation. However, the influence of chronic indomethacin administration in cirrhosis remains unexplored. This study was performed on male Sprague-Dawley rats with liver cirrhosis induced by common bile duct ligation. They received subcutaneous indomethacin (5 mg/kg/day) or distilled water (control) injection from the 36th to 42nd day after operation. On the 43rd day, systemic and portal hemodynamics were evaluated and the following experiments were performed with an in situ collateral perfusion model: in the first series, concentration-response curves to AVP (10(-10) to 10(-7) M) were obtained; in the second series, flow-pressure curves were plotted (Krebs solution, 6-18 mL/min), where the slope represents an index of collateral vascular resistance (the higher the resistance, the smaller the amount of shunting vessels, that is, the lower the degree of shunting). The mean arterial pressure and portal pressure were similar between indomethacin and control groups (p > 0.05). Indomethacin elevated the collateral perfusion pressure to AVP (3 x 10(-9), 10(-8) M, p < 0.05) but did not influence the slope of the flow-pressure curve (p > 0.05). In bile duct-ligated cirrhotic rats, indomethacin improves the portal-systemic collateral vascular responsiveness to AVP without alleviating the severity of shunting.

Bevacizumab inhibits corneal neovascularization in an alkali burn induced model of corneal angiogenesis

New and uncontrolled blood vessel development in the cornea is a pivotal process in the pathogenesis of several corneal diseases. These corneal diseases may finally cause blindness and managing them therapeutically is problematic. The data supporting a causal role for vascular endothelial growth factor in corneal neovascularization are extensive. This study aimed to evaluate the effect of subconjunctival bevacizumab (Avastin) on experimental corneal neovascularization in rabbits. Chemical cauterization of the cornea was performed by touching central cornea with a 5-mm-diameter NaOH-soaked cotton applicator for 10 s in 20 eyes of 20 White New Zealand rabbits. The rabbits were then divided randomly into two equal groups. Bevacizumab (2.5 mg) was administered to 10 eyes (group 1) by a subconjunctival injection immediately after chemical cauterization of corneal surface. As a control, 10 eyes (group 2) received an injection of distilled water. Rabbits were examined daily for detection of the first signs of neovascularization. Three weeks later, the extent of corneal neovascularization was evaluated by direct examination and photograph analyses. Total corneal neovascularization area, degree of circumference involved and longest neovascular pedicle length were assessed. Bevacizumab significantly decreased the total neovascularization area (P < 0.009), the circumference involved (P < 0.011) and the longest neovascular pedicle length (P < 0.023). Local injection of bevacizumab has a significant effect on inhibition of alkali burn-induced corneal neovascularization. This shows the potential value of bevacizumab in the treatment of corneal neovascularization.

Lack of detrimental or therapeutic effects of cyclooxygenase inhibition in bile duct‐ligated rats with hepatic encephalopathy

The pathogenetic mechanisms of hepatic encephalopathy (HE) are not fully understood. Cerebral blood flow regulated by cyclooxygenase (COX) may be involved in the development of HE. There are no comprehensive data concerning the effects of COX inhibition on HE in chronic liver disease. Male Sprague-Dawley rats weighing 240-270 g at the time of surgery were selected for experiments. Secondary biliary cirrhosis was induced by bile duct ligation (BDL). Those rats were then divided into two groups to receive i.p. injection of indomethacin (5 mg/kg per day) or distilled water for 7 days from day 36 to day 42 after BDL. The control group consisted of rats receiving a sham operation. Severity of encephalopathy was assessed by counts of motor activity. Plasma levels of tumor necrosis factor (TNF)-alpha and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), and liver biochemistry tests were determined after treatment. The motor activity in both groups of BDL rats were significantly lower than that of the control group (P < 0.001). As compared with the BDL rats treated with distilled water, BDL rats treated with indomethacin had significant lower levels of 6-keto-PGF(1alpha), but the motor activity, TNF-alpha levels and serum biochemistry tests were not significantly different between both BDL groups. Chronic indomethacin administration did not have significantly detrimental or therapeutic effects on the severity of encephalopathy in BDL rats.

Retinal Thickness and Subnormal Retinal Oxygenation Response in Experimental Diabetic Retinopathy

To test the hypothesis that subnormal retinal oxygenation response (DeltaPo2) found at 3 months of experimental diabetes is associated with cellular swelling and increased retinal thickness. Two groups of animals were studied: control rats injected intraperitoneally with either 15% body weight of saline or distilled water (cellular swelling model) or with intravitreal N-methyl-D-aspartate (NMDA) and 3-month-old diabetic and age-matched control rats. Intraocular pressure and retinal thickness was assessed using an applanation tonometer or high-resolution MRI (23.4 microm2 in-plane). In separate studies, functional MRI was used to measure blood-retinal barrier (BRB) integrity after Gd-DTPA injection intravenously and retinal DeltaPo2 during carbogen provocation. Inner and total retinal thickness were lower (P < 0.05) after NMDA injection, not different (P > 0.05) between control, before and after saline injection and before distilled water injection, and supernormal (P < 0.05) after distilled water injection. In diabetic rats, thickness was normal (P > 0.05) at most distances from the optic nerve but was subnormal (P < 0.05) in superior retina (0.5 mm from the optic nerve). Intraocular pressure was not different (P > 0.05) between groups. BRB was intact (P > 0.05) after saline and distilled water injection. DeltaPo2 was normal (P > 0.05) after saline injection and over inferior hemiretina of the diabetic group but was subnormal (P < 0.05) after distilled water injection and over superior hemiretina of diabetic rats. The lack of increased thickness in 3-month-old diabetic rats in vivo raises the possibility that intracellular swelling is unlikely to underlie subnormal DeltaPo2 in experimental diabetes. In diabetic rats, the spatial disconnect between subnormal DeltaPo2 pansuperiorly and retinal thinning only superiorly to the optic nerve suggests that neurovascular coupling is perturbed.

Transdifferentiation in Holothurian Gut Regeneration

It has recently been shown that the whole spectrum of cell types constituting a multicellular organism can be generated from stem cells. Our study provides an example of an alternative mechanism of tissue repair. Injection of distilled water into the coelomic cavity of the holothurian Eupentacta fraudatrix results in the loss of the whole digestive tract, except the cloaca. The new gut reforms from two separate rudiments. One rudiment appears at the anterior end of the body and extends posteriorly. The second rudiment grows anteriorly from the cloaca. In the anterior rudiment, the luminal epithelium (normally derived from endoderm) develops de novo through direct transdifferentiation of the coelomic epithelial cells (mesodermal in origin). In the posterior rudiment, the luminal epithelium originates from the lining epithelium of the cloaca. After 27 days, the two rudiments come into contact and fuse to form a continuous digestive tube lined with a fully differentiated luminal epithelium. Thus in this species, the luminal epithelia of the anterior and posterior gut rudiments develop from two different cell sources-i.e., from the mesodermally derived mesothelium and the endodermally derived epithelium of the cloacal lining, respectively. Our data suggest that differentiated cells of echinoderms are capable of transdifferentiation into other cell types.

Inhibitory effect of triamcinolone acetonide on corneal neovascularization

Corneal neovascularization (NV) plays an important role in the pathogenesis of corneal disorders. Recently, triamcinolone acetonide (TA) has been reported as a potential treatment for ocular angiogenesis. However, there are no reports on the inhibitory effect of TA on the corneal NV. Triamcinolone acetonide (2 mg) was administered to four rabbits' eyes by a subconjunctival injection immediately after a basic fibroblast growth factor (bFGF)-pellet was placed into the cornea. As a control, four eyes received an injection of distilled water. Four weeks later, the inhibition of corneal NV was evaluated as the percentage ratio of the vessel invasion area to the area that was sandwiched between the pellet and the limbus cornea. To identify the characteristic appearance of new corneal vessels, the control cornea was examined by using the antibody of vascular endothelial growth factor (VEGF). To confirm TA concentration in TA-treated corneas, the TA level was measured using high-performance liquid chromatography. Neovascularization from the limbus to the pellet was detected in control eyes 4 weeks after the bFGF pellet implantation. TA-treated eyes demonstrated the inhibition of the neovascular response to the pellet. The severity of NV as compared between control and TA-treated eyes was statistically significant (P<0.05). Morphologically, new vessel growth was shown in the control cornea, and endothelial cells of new vessels were positively stained with the antibody of VEGF. TA concentration in TA-treated corneas at 2 weeks showed 63.5+/-42.8 microg/g (n=4, mean +/- SD), while TA was not detected in control and TA-treated corneas at 4 weeks. The level of TA was effectively maintained for at least 2 weeks after the subconjunctival injection. We have demonstrated that subconjunctival TA administration inhibited rabbit corneal NV. This agent may prove useful in the treatment of corneal angiogenic disorders.

Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice

The present study was conducted to evaluate the effects of central administration of melanotan II (MTII), a melanocortin-3/4 receptor agonist, on hepatic and whole-body insulin sensitivity, independent of food intake and body weight. Over a period of 24 h, 225 ng of MTII was injected in three aliquots into the left lateral ventricle of male C57Bl/6 mice. The animals had no access to food. The control group received three injections of distilled water. Whole-body and hepatic insulin sensitivity were measured by hyperinsulinaemic-euglycaemic clamp in combination with [(3)H]glucose infusion. Glut4 mRNA expression was measured in skeletal muscle. Plasma glucose and insulin concentrations under basal and hyperinsulinaemic conditions were similar in MTII- and placebo-treated mice. Endogenous glucose production (EGP) and glucose disposal in the basal state were significantly higher in MTII-treated mice than in the control group (71+/-22 vs 43+/-12 micromol.min(-1).kg(-1), p<0.01). During hyperinsulinaemia, glucose disposal was significantly higher in MTII-treated mice (151+/-20 vs 108+/-20 micromol.min(-1).kg(-1), p<0.01). In contrast, the inhibitory effect of insulin on EGP was not affected by MTII (relative decrease in EGP: 45+/-27 vs 50+/-20%). Glut4 mRNA expression in skeletal muscle was significantly increased in MTII-treated mice (307+/-94 vs 100+/-56%, p<0.01). Intracerebroventricular administration of MTII acutely increases insulin-mediated glucose disposal but does not affect the capacity of insulin to suppress EGP in C57Bl/6 mice. These data indicate that central stimulation of melanocortin-3/4 receptors modulates insulin sensitivity in a tissue-specific manner, independent of its well-known impact on feeding and body weight.

Aquaporin-4 Gene Disruption in Mice Reduces Brain Swelling and Mortality in Pneumococcal Meningitis

The astroglial water channel aquaporin-4 (AQP4) facilitates water movement into and out of brain parenchyma. To investigate the role of AQP4 in meningitis-induced brain edema, Streptococcus pneumoniae was injected into cerebrospinal fluid (CSF) in wild type and AQP4 null mice. AQP4-deficient mice had remarkably lower intracranial pressure (9 +/- 1 versus 25 +/- 5 cm H2O) and brain water accumulation (2 +/- 1 versus 9 +/- 1 microl) at 30 h, and improved survival (80 versus 0% survival) at 60 h, through comparable CSF bacterial and white cell counts. Meningitis produced marked astrocyte foot process swelling in wild type but not AQP4 null mice, and slowed diffusion of an inert macromolecule in brain extracellular space. AQP4 protein was strongly up-regulated in meningitis, resulting in a approximately 5-fold higher water permeability (P(f)) across the blood-brain barrier compared with non-infected wild type mice. Mathematical modeling using measured P(f) and CSF dynamics accurately simulated the elevated lower intracranial pressure and brain water produced by meningitis and predicted a beneficial effect of prevention of AQP4 upregulation. Our findings provide a novel molecular mechanism for the pathogenesis of brain edema in acute bacterial meningitis, and suggest that inhibition of AQP4 function or up-regulation may dramatically improve clinical outcome.

On-line monitoring and control of substrate concentrations in biological processes by flow injection analysis systems

Concentrations of substrates, glucose, and ammionia in biological processes have been on-line monitored by using glucose-flow injection (FIA) and ammonia-FIA systems. Based on the on-line monitored data the concentrations of substrates have been controlled by an on-off controller, a PID controller, and a neural network (NN) based controller. A simulation program has been developed to test the control quality of each controller and to estimate the control parameters. The on-off controller often produced high oscillations at the set point due to its low robustness. The control quality of a PID controller could have been improved by a high analysis frequency and by a short residence time of sample in a FIA system. A NN-based controller with 3 layers has been developed, and a 3(input)-2(hidden)-1(output) network structure has been found to be optimal for the NN-based controller. The performance of the three controllers has been tested in a simulated process as well as in a cultivation process ofSaccharomyces cerevisiae, and the performance has also been compared to simulation results. The NN-based controller with the 3-2-1 network structure was robust and stable against some disturbances, such as a sudden injection of distilled water into a biological process.

Seismic wave monitoring of CO2 migration in water-saturated porous sandstone

We have carried out laboratory measurements of P-wave velocity and deformation strain during CO2 injection into a porous sandstone sample, in dry and water-saturated conditions. The rock sample was cylindrical, with the axis normal to the bedding plane, and fluid injection was performed from one end.Using a piezoelectric transducer array system, we mapped fluid movement during injection of distilled water into dry sandstone, and of gaseous, liquid, and supercritical CO2 into a water-saturated sample. The velocity changes caused by water injection ranged from 5.61 to 7.52%. The velocity changes caused by CO2 injection are typically about -6%, and about -10% for injection of supercritical CO2. Such changes in velocity show that the seismic method may be useful in mapping CO2 movement in the subsurface.Strain normal to the bedding plane was greater than strain parallel to the bedding plane during CO2 injection; injection of supercritical CO2 showed a particularly strong effect. Strain changes suggest the possibility of monitoring rock mass deformation by using borehole tiltmeters at geological sequestration sites. We also found differences associated with CO2 phases in velocity and strain changes during injection.