Isotonic Glucose Solution Research Articles

Optimization of transfection into cultured cells with siRNA lipoplexes prepared using a modified ethanol injection method

To simplify the preparation of cationic liposome/small interfering RNA (siRNA) complexes (siRNA lipoplexes), we previously developed a modified ethanol injection (MEI) method, in which siRNA-containing phosphate-buffered saline was rapidly poured into a small volume of a lipid-ethanol (EtOH) solution. In this study, to optimize the lipid composition and solvents for dissolving lipids and siRNA in the transfection of siRNA lipoplexes prepared using the MEI method, we selected five types of cationic lipids, three types of neutral lipids, and five types of polyethylene glycol (PEG)-lipids and prepared siRNA lipoplexes via the MEI method using a lipid-EtOH solution of cationic lipids, neutral lipids, and PEG-lipids. Regardless of the cationic lipid type, siRNA lipoplexes composed of cationic lipids, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, and poly(ethylene glycol) cholesteryl ether showed high gene knockdown efficiency in human breast tumor MCF-7 cells. Regardless of the PEG-lipid type, the size of the siRNA lipoplexes decreased with increasing amounts of PEG-lipid in the lipid-EtOH solution. However, the gene knockdown activity of the siRNA lipoplexes was not abolished via PEGylation when siRNA lipoplexes were PEGylated with PEG-lipids having short lipid anchors. Furthermore, the preparation of siRNA lipoplexes by mixing a lipid-dimethyl sulfoxide solution with a phosphate-buffered saline solution of siRNA increased the size of the siRNA lipoplexes compared with that using a lipid-EtOH solution. However, these lipoplexes showed high gene knockdown efficiency in cells. When prepared by mixing a lipid-EtOH solution with an isotonic glucose or sucrose solution of siRNA, the siRNA lipoplexes tended to reduce gene knockdown efficiency in the cells. These results indicate that the lipid composition and solvents used for dissolving the lipids and siRNA affect the transfection efficiency and size of the siRNA lipoplexes. This study provides information on the optimal preparation of siRNA lipoplexes using the MEI method.

Effect of Fluid Intake on Acute Changes in Plasma Volume: A Randomized Controlled Crossover Pilot Trial.

Plasma volume (PV) undergoes constant and dynamic changes, leading to a large intra-day variability in healthy individuals. Hydration is known to induce PV changes; however, the response to the intake of osmotically different fluids is still not fully understood. In a randomized controlled crossover trial, 18 healthy individuals (10 females) orally received an individual amount of an isotonic sodium-chloride (ISO), Ringer (RIN), or glucose (GLU) solution. Hemoglobin mass (Hbmass) was determined with the optimized carbon monoxide re-breathing method. Fluid-induced changes in PV were subsequently calculated based on capillary hemoglobin concentration ([Hb]) and hematocrit (Hct) before and then every 10 minutes until 120 min (t0-120) after the fluid intake and compared to a control trial arm (CON), where no fluid was administered. Within GLU and CON trial arms, no statistically significant differences from baseline until t120 were found (p > 0.05). In the ISO trial arm, PV was significantly increased at t70 (+138 mL, p = 0.01), t80 (+191 mL, p < 0.01), and t110 (+182 mL, p = 0.01) when compared to t0. Moreover, PV in the ISO trial arm was significantly higher at t70 (p = 0.02), t110 (p = 0.04), and t120 (p = 0.01) when compared to the same time points in the CON trial arm. Within the RIN trial arm, PV was significantly higher between t70 and t90 (+183 mL, p = 0.01) and between t110 (+194 mL, p = 0.03) and t120 (+186 mL, p < 0.01) when compared to t0. These results demonstrated that fluids with a higher content of osmotically active particles lead to acute hemodilution, which is associated with a decrease in [Hb] and Hct. These findings underpin the importance of the hydration state on PV and especially on PV constituent levels in healthy individuals.

Inverted Scanning Microwave Microscopy of a Vital Mitochondrion in Liquid

The inverted scanning microwave microscope (iSMM) is a recently developed variety of scanning microprobe microscopes. Similar to a scanning microwave microscope (SMM), the iSMM is sensitive to not only surface structure, but also electromagnetic properties below the surface. Different from the SMM, the iSMM can be converted from any scanning probe microscope, such as an atomic force microscope (AFM) and a scanning tunneling microscope, with a simple metal probe to outperform the SMM in terms of ruggedness, bandwidth, sensitivity, and dynamic range. This letter reports the first iSMM images of a vital mitochondrion in an isotonic glucose solution. Compared to the AFM and SMM, the iSMM offers more insights into the mitochondrion. This shows the potential of iSMM for noninvasive and label-free imaging and characterization of subcellular structures.

Osmolarity and spectrophotometric property of brilliant blue green define the degree of toxicity on retinal pigment epithelial cells exposed to surgical endoilluminator.

ObjectiveTo evaluate the effect of varying concentrations of brilliant blue green (BBG) and their different biochemical characteristics on retinal pigment epithelial (RPE) cells under xenon light source illumination at varying distances to identify safe parameters for intraoperative use.MethodsHuman retinal RPE cells (ARPE-19) were exposed to two concentrations (0.25 and 0.50 mg/mL) of BBG and illuminated with a xenon surgical illuminator at varying distances (10 and 25 mm), intensity levels, and time intervals (1, 5, and 15 minutes). Additionally, the effect of osmolarity was examined by diluting BBG in different concentrations of glucose. Cytotoxicity of BBG and osmolarity effects on cell viability were evaluated using a WST-1 assay. Light absorption and emission characteristic of BBG in different solvents were measured using a plate reader at different wavelengths. Lastly, the activity of caspase-3 was also studied.ResultsCell viability of ARPE-19 cells was 77.4%±12.7%, 78.7%±17.0%, and 65.0%±19.7% at 1, 5, and 15 minutes to exposure of high illumination xenon light at 10 mm (P<0.05) compared to controls. At both distances of illumination (10 and 25 mm), similar cell viabilities were seen between 1 and 5 minutes of exposure. However, there was a decline in viability when the illumination was carried out to 15 minutes in all groups (P<0.05). There was no significant reduction in cell viability in presence or absence of xenon light in different osmolar solutions concentrations of glucose (P>0.05). Maximal light absorption of BBG was noted between 540 and 680 nm. Activated caspase-3 level was not significant in both the concentrations of BBG (P>0.05).ConclusionOur findings suggest that BBG at 0.25 mg/mL during vitreoretinal surgery is safe and not toxic to RPE cells up to 5 minutes under focal high illumination (10 mm) and up to 15 minutes under medium diffuse illumination (25 mm). BBG was safe to be mixed with isotonic glucose solution at the concentration range of 2.5%–10%, regardless of the illumination status.

Use of vacuum impregnation for the production of high quality fresh-like apple products

The application of vacuum impregnation (VI) for the production of high quality fresh like apple products has been investigated. Preliminary tests were carried out to select the optimal VI treatment conditions (P: 857–50 mbar; VI time: 10–1000 s). The use of isotonic sorbitol, glucose, fructose, sucrose, trehalose and maltose solutions was then studied to keep quality and improve stability of the VI treated apples. VI at 738 mbar for 10 s allowed the penetration of the impregnation agent (water) with minimal effects on fruit composition and quality. VI isotonic solutions determined a limited solute increase while affected mechanical properties positively; firmness of apples processed with sorbitol solution was higher than that of the fresh fruit. Moreover, they contributed to preserve apples from browning. After 7 days, h° values significantly higher than the untreated samples were obtained with trehalose > sorbitol > glucose > sucrose > maltose. Sensory analysis confirmed the positive effect of isotonic VI solution on apples quality.

A New Method to Determine the Half-Life for Penicillin Using Microcalorimeter

The dissolution process of penicillin in normal saline and isotonic glucose solution was reported using a microcalorimeter. Both the integral and differential heats of solution were measured. The quantitative relationships between the amount of heat released and the quantity of dissolved penicillin were established. Meanwhile, the kinetics and the half-life of the dissolution processes as well as the enthalpy of solution, the entropy of dissolution, and the free energy of dissolution were determined. The results showed that a change of the solvent from normal saline to isotonic glucose solution had little effect on the half-life of penicillin in the dissolution process, and there was no significant difference between the stabilities of penicillin in isotonic glucose solution and normal saline. Moreover, the dissolution process of penicillin in isotonic glucose solution followed the first-order kinetics. These results could provide a theoretical basis for the clinical applications of penicillin.

Effect of Eye Drops Containing Disulfiram and Low-Substituted Methylcellulose in Reducing Intraocular Pressure in Rabbit Models

Purpose: We attempted to develop anti-glaucoma eye drops using 0.5% disulfiram (DSF), 5% 2-hydroxypropyl-β-cyclodextrin, 0.1% hydroxypropylmethylcellulose, and 2% methylcellulose (MC) (DSF eye drops with MC), and tested the ability of a DSF eye drops with MC to reduce intraocular pressure (IOP) in rabbit models.Methods: Elevated IOP was induced by the rapid infusion of 5% glucose solution (15 ml/kg of body weight) through the marginal ear vein or by keeping rabbits in the dark for 5 h. IOP and the nitric oxide (NO) level in the aqueous humor were measured with an electronic tonometer and by a microdialysis method, respectively. ΔIOP and ΔNO values were analyzed as the differences in IOP and NO in rabbits instilled with saline or eye drops, respectively.Results: Increased IOP in rabbit models was reduced by the instillation of DSF eye drops with or without MC, and a close relationship was observed between IOP and NO levels in rabbit receiving a rapid infusion of isotonic glucose. We present kinetic parameters [secondary AUC (prolonged drug effect) and secondary MRT (prolonged effective time)] analyzed as the area under the curve (AUC) of ΔIOP or ΔNO versus time using rabbits instilled with eye drops 10, 50, or 90 min prior to the infusion of the isotonic glucose solution. The elevations in IOP and NO level were reduced by the instillation of DSF eye drops with or without MC; the addition of MC increased the secondary AUC and MRT of DSF eye drops.Conclusions: The present study demonstrates that 0.5% DSF eye drops suppress increased IOP in rabbit models, probably by inhibiting the elevation in NO levels. In addition, we propose a kinetic analysis method to predict drug effects and effective time. These findings suggest that a low-substituted MC-based drug delivery system promotes drug effectiveness and effective time.

Evaluation of the stability and pharmacokinetics of cabazitaxel‐loaded intravenous lipid microspheres: Beneficial effect of cholesterol

AbstractIn this work, we describe the evaluation of the stability and pharmacokinetics of cabazitaxel‐loaded lipid microspheres (CTX‐LM) prepared by high‐pressure homogenization. Investigation of the physicochemical stability under different homogenization cycles and diverse sterilization times confirmed that 8 cycles at 800 bar and 121°C for 8 min were the optimal technological parameters. The beneficial effect of cholesterol on the physical stability of CTX‐LM was confirmed and its mechanism of action was identified. The stability of CTX‐LM using an aqueous isotonic glucose solution as a diluting agent was greater compared with using 0.9% NaCl solution as a result of an electric charge effect. CTX‐LM are stable under freeze‐thaw conditions and should not be exposed to high temperatures and protected from light during storage. Furthermore, all the changes in parameters were within an acceptable range at 4°C within 9 months, which supported the good long‐term stability of CTX‐LM. Finally, to compare the pharmacokinetics of CTX‐LM with cabazitaxel‐solution in vivo, a rapid, accurate UPLC‐MS/MS method was developed and used to determine cabazitaxel in rat plasma after a single intravenous administration of 4 mg/kg. An obviously larger area under the curve (AUC) of CTX‐LM was observed than that of CTX‐solution, which will improve the antitumor efficacy of cabazitaxel.Practical applications: As a novel semisynthetic taxane, cabazitaxel has shown antitumour activity in a broad range of cell‐lines and tumor models and has been approved in combination with prednisone for the treatment of patients with castration‐resistant metastatic prostate cancer. However, serious undesirable effects in humans, such as anaphylactoid hypersensitivity reactions and peripheral neuropathy were produced by the addition of polysorbate 80 to commercial products. In this paper, CTX‐LM was prepared by high‐pressure homogenization in order to overcome the above drawbacks. The good stability and markedly higher AUC of CTX‐LM may hasten their passage from a pre‐clinical phase to a clinical trial phase and allow their production on a large scale.In this paper, cabazitaxel lipid microspheres exhibited a great stability and had a higher AUC than cabazitaxel solution.

The Stability of Citrate-Capped Silver Nanoparticles in Isotonic Glucose Solution for Intravenous Injection

Citrate-capped silver nanoparticles (AgNP) are widely used in industry, consumer products, and medical appliances. However, information on the environmental toxicity and human health is not comprehensive. Further, the physicochemical properties of AgNP make it difficult to test toxicity, as nanosized particles, due to their size, may increase by aggregation or agglomeration in some administration vehicles. In this study, stability of AgNP was investigated in different types of isotonic solutions, which is important for in vitro testing or toxicokinetic studies using intravenous (iv) injection. Size, morphology, zeta potential, and ion formation were investigated in isotonic solutions for the physicochemical characterization of AgNP. Aggregation and precipitation of AgNP were observed in phosphate-buffered saline or 0.9% NaCl, while AgNP were stable without aggregation or precipitation in 5% glucose in isotonic solution. The average size of AgNP in 5% glucose was approximately 10 nm at different temperatures of 10, 25, or 36°C and at varying concentrations from 10 to 1000 ppm. It is noteworthy that this is almost the same size distribution as that in the water-based suspension of AgNP supplied by the manufacturer. Zeta potential ranged from –40 to –60 mV, suggesting that the repulsion forces of AgNP are not disturbed to a sufficient degree to aggregate while osmolarity is in the isotonic range of 290 ± 10 mOsm/kg in 5% glucose solution. Data suggest that AgNP in a 5% glucose solution may be used in the toxicity test via iv injection without adverse consequences in blood.

Physicochemical characterization and an injection formulation study of water insoluble ZCVI4-2, a novel NO-donor anticancer compound

ZCVI(4)-2 was a novel nitric oxide-releasing glycosyl derivative of oleanolic acid that displayed strong cytotoxicity selectively against human hepatocellular carcinoma in vitro and in vivo. In this study, ZCVI(4)-2 was characterized by FT-IR spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, Raman spectroscopy, hygroscopicity and stability. A high performance liquid chromatography method was also established for the quantitative determination of solubility and additional stability profile of ZCVI(4)-2. ZCVI(4)-2 was found to be an amorphous and stable solid with low solubility of less than 10 μg/mL. Based on the solubilization tests that included methods of cosolvency and micellization, the solution mixture of 5% Solutol HS-15, 5% 1, 2-propylene glycol and 5% anhydrous ethanol was determined to be the system for the preparation of the ZCVI(4)-2 early injection solution. The effect of pH, temperature, light and injectable isotonic glucose or NaCl solution on ZCVI(4)-2 injection was also investigated. Good stability was observed at all testing conditions. Under the conditions studied, the NO-releasing rate and amount of ZCVI(4)-2 from the early injection solution in rat plasma demonstrated a promising therapeutic efficacy while maintaining a good safety profile.

In-vitro evaluation of contrast media for assessment of regional perfusion distribution by Electrical Impedance Tomography (EIT)

Abstract Electrical impedance tomography (EIT) has become an accepted tool for monitoring regional ventilation. Interest is growing to derive additional information on pulmonary perfusion and ventilation/perfusion distribution. Favoured ap-proach is the impedance indicator dilution technique. Until now hyperosmolar sodium chloride solutions (5.8% and 20%NaCl) have been used as indicators in experiments which, however, may be problematic in view of side effects and are not approved for application in patients. Different radiographic contrast media (CM) approved for use in patients and five reference solutions were tested in vitro. Resistivities were measured in blood at 37°C by a conductivity meter (LF39, Meinsberg GmbH, Germany) in the indica-tor content range from 0 to 28 Vol%. Three non-ionic CM: Iodixanol, Iomeprol, Iobitridol and two ionic CM: Ioxaglate and Diatrizoate were examined. As references 0.9%, 5.8% and 20%NaCl as well as isotonic (4.5%) and hypertonic (18.2%) glucose solutions were included. Proportionality Proportionality between test solution concentration and deter-mined resistivity changes was proven by regression/correlation analysis. Non-ionic CM induced linear increases of blood resistivity by 80% (Iodixanol), 75% (Iomeprol) and 66% (Iobitridol) at the highest test concentration of 28Vol%. Ionic CM changed resistivity by 13% (Ioxaglate) and 24% (Diatrizoate). The determined r

Oral Hypertonic Electrolyte-Glucose/Mosapride Complex Solution for Resuscitation of Burn Shock in Dogs

The objective of this study is to investigate the effect of oral feeding of an electrolyte glucose mosapride solution for resuscitation in dogs with shock after a 35% TBSA full-thickness burn and the effect of mosapride on gastric emptying time. Eighteen male Beagle dogs were randomly divided into intravenous isotonic solution group, intragastric hypertonic solution group, and mosapride group after they were subjected to a 35% TBSA full-thickness flame injury. In intravenous isotonic solution group (I group), isotonic electrolyte glucose solution was given through vein with adoption of the Parkland formula. The resuscitation fluid in intragastric hypertonic solution group (H group) and mosapride group (M group) consisted of 1.8% NaCl and 5% glucose, the total fluid volume was one half of that for I group, and it was given in divided amount every 2 hours. Mosapride was added to the resuscitation fluid in mosapride group. Fluid replacement was begun 30 minutes after the injury in all the groups. Mean arterial pressure (MAP), cardiac output index (CI), intrathoracic blood volume index (ITBI), blood volume (BV), serum sodium concentration, intestinal mucosal blood flow (IMBF), gastric emptying, and serum motilin levels were determined at different time points. The urinary output of all animals was measured immediately after burn upto 360 minutes postburn. CI, ITBI, BV, and IMBF were all decreased obviously after burn. In I group and M group, CI, ITBI, BV, and IMBF were increased gradually after resuscitation, and they were significantly higher than that of H group (P < .05). MAP in all three groups was lowered significantly and then gradually recovered, showing no significant difference among groups. The urinary output in M group was similar to that in I group (P > .05), and it was higher than that in H group (P < .05). Serum sodium level in H group and M group increased in varying degrees and were markedly higher compared with the I group (P < .05). Postburn gastric emptying in H group was much more delayed (P < .05), but in M group it was much faster. Motilin level in the latter group also increased gradually postburn and was markedly higher than that of the other two groups (P < .05). At the early stage of 35% TBSA third-degree burns, gavage of 1.8% hypertonic electrolytes glucose ends in slow gastric emptying, resulting in delayed recovery from shock. When a prokinetic drug mosapride was added to the solution, gastric emptying could be accelerated and a resuscitation effect similar to that of intravenous isotonic fluid resuscitation can be achieved, while total fluid volume can be decreased by half.

Glucose-Induced Intestinal Vasodilation Via Adenosine A1 Receptors Requires Nitric Oxide but Not K +ATP Channels

Both nitric oxide (NO) and adenosine A1 receptor activation mediate microvascular vasodilation during intestinal glucose absorption. Our overall hypothesis is that adenosine triphosphate (ATP) utilization during glucose absorption would increase adenosine metabolite release, which acts on adenosine A1 receptors to alter endothelial production of NO and/or activate ATP-dependent potassium channels (K(+)(ATP)) to dilate intestinal microvessels. Intravital videomicroscopy of the rat jejunum was used to record the vascular responses of inflow (termed 1A) arterioles, proximal (p3A), and distal (d3A) premucosal arterioles during exposure to isotonic glucose or mannitol solutions alone or in the presence of the selective nitric oxide synthase (NOS) inhibitor (L-NMMA), an adenosine A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine (DPCPX)), or a K(+)(ATP) channel inhibitor (glibenclamide). As expected, glucose exposure caused rapid dilation of both p3A and d3A arterioles, while mannitol exposure had no effect on microvascular diameters. Adenosine A1 receptor blockade completely prevented glucose-induced dilation of the premucosal arterioles. NOS inhibition significantly blunted the glucose-induced vasodilation of the premucosal arterioles, but had little effect in the mannitol group. Simultaneous application of both the NOS inhibitor and the adenosine A1 receptor antagonist gave the same reduction in glucose-induced dilation of the premucosal arterioles as the adenosine A1 receptor antagonist alone. Blockade of K(+)(ATP) channels with glibenclamide did not attenuate glucose-induced vasodilation of the premucosal arterioles. These data suggest that glucose-induced vasodilation of premucosal jejunal arterioles is mediated through adenosine A1 receptors, and NO at least partially mediates the adenosine A1 receptor-induced vasodilation. In addition, K(+)(ATP) channels are not involved in premucosal arteriolar vasodilation during intestinal glucose exposure.

The curative effect of 1.8% hypertonic electrolyte glucose solution in enteral resuscitation of burn shock

To study the resuscitative effect of hypertonic electrolyte glucose solution (HEGS) in enteral resuscitation of burn shock. Eighteen Beagle dogs with 35% TBSA full-thickness flame injury were used in this study. They were randomized to a control group (no-fluid resuscitation, N group), a HEGS resuscitation group (H group) or an isotonic electrolyte glucose solution (IEGS) resuscitation group (I group). The solution enterally was given for resuscitation from half an hour after burn. The volumes and rates of fluid infusion in the H group were basically in accordance with 2 ml/(kg x 1%TBSA), those in the I group were basically in accordance with parkland formula [4 ml/(kg x 1%TBSA)]. The haemodynamic parameters, global end-diastolic volume index, plasma volume, osmotic pressure of plasma, intestinal absorptive rates of water and Na(+), and intestine mucosa blood flow were continuously assessed. The cardiac output index, global end-diastolic volume index, plasma volume and intestine blood mucosa flow reduced markedly after burn in the three groups, and then gradually returned from 2 h after burn in two resuscitation groups, which were higher than that in the N group (P < 0.05). The activities of diamine oxidase in plasma in the two resuscitation groups were higher than that in N group (P < 0.05). The intestinal absorption rates of water and Na(+) reduced markedly after burn in two resuscitation groups with the lowest levels, and then returned from 6 h after burn. The rates of water in H group were lower than that in I group (P < 0.05); the rates of Na(+) in H group were higher than in I group (P < 0.05). The results indicated that 35%TBSA III degrees burn-injury dogs be resuscitated effectively with 1.8% hypertonic electrolyte-glucose solution by enteral, which 1/2 volume of an isotonic electrolyte glucose solution.

Benzamil prevents brain water accumulation in hyponatraemic rats

It has been recently shown that A6 cells exposed to hyponatraemic stress respond with increased sodium uptake via activation of benzamil-sensitive sodium channels. This study was performed, therefore, to explore the possible involvement of benzamil-sensitive sodium channels and cellular sodium influx in brain oedema formation in hyponatraemic rats. Four groups of male Wistar rats were studied (n = 13 in each group). Animals in group I with normonatraemia received intracerebroventricular (icv) 0.9% NaCl; animals in group II-IV were made hyponatraemic by intraperitoneal administration of isotonic glucose solution in a dose of 20% per body weight. Rats were pretreated with icv 0.9% NaCl (group II), 120 microg arginine vasopressin (AVP) (group III) or 4 microg benzamil-hydrochloride (group IV). Plasma sodium (ion-selective electrode) plasma osmolality (vapour pressure osmometer) and brain sodium and potassium content (flame photometer) as well as brain water content (desiccation method) were measured after a 2-h hydration period. Plasma sodium, osmolality and tissue sodium and potassium contents were markedly depressed in hyponatraemic rats (group II-IV, p < 0.0005 for each group) irrespective of drug pretreatment. Brain water content, however, responded to hyponatraemia with an increase from 77.55 +/- 1.00% to 78.45 +/- 0.94% (p < 0.01), and it was further augmented to 79.35 +/- 0.80% (p < 0.0005) by icv AVP pretreatment. By contrast, benzamil administration prevented the rise of brain water caused by hyponatraemia (77.61 +/- 1.04%). Early in the course of hyponatraemia, brain sodium channels may be activated, and the subsequent cellular sodium uptake may generate osmotic gradient to allow passive water flow into the cells. The simultaneous reduction of osmotic water conductivity of brain-specific aquaporin-4 by hyponatraemia, however, may limit water accumulation.

Fertility and post-thawing characteristics of deep frozen boar spermatozoa.

Eight-nine gilts were inseminated with deep frozen boar spermatozoa thawed in seminal plasma, filtrate of seminal plasma, skimmed milk and isotonic glucose solution. The most favourable fertility results were obtained when seminal plasma was used as thawing diluent. It was shown that a relationship exists between the post thawing acrosome morphology, the post thawing GOT-release and the fertility of frozen spermatozoa.

Effect of suckling isotonic or hypertonic solutions of sodium bicarbonate or glucose on abomasal emptying rate in calves

To determine and compare the abomasal emptying rates in calves suckling milk replacer or an isotonic or hypertonic solution of NaHCO(3) or glucose. 5 male Holstein-Friesian calves that were < 30 days of age. Calves were fed 2 L of milk replacer or isotonic (300 mOsm/L) or hypertonic (600 mOsm/L) solutions of NaHCO(3) or glucose containing acetaminophen (50 mg/kg). Venous blood samples and transabdominal ultrasonographic abomasal dimensions were obtained periodically after feeding, and abomasal luminal pH was continuously monitored by placement of a luminal pH electrode through an abomasal cannula. Abomasal emptying rate was assessed by the time to maximal plasma acetaminophen concentration, ultrasonographic determination of the half-time of abomasal emptying, and the time for luminal pH to return to within 1 pH unit of the preprandial value. Hypertonic NaHCO(3) solution was emptied slower than an isotonic NaHCO(3) solution, isotonic glucose solution was emptied slower than an isotonic NaHCO(3) solution, and hypertonic glucose solution emptied slower than an isotonic glucose solution. An electrolyte solution for oral administration with a high osmolarity and glucose concentration may lead to a slower resuscitation of dehydrated diarrheic calves because such solutions decrease the abomasal emptying rate and therefore the rate of solution delivery to the small intestine. Whether slowing of the abomasal emptying rate in dehydrated diarrheic calves suckling an oral electrolyte solution is clinically important remains to be determined.

A case of acute lead poisoning in a 2‐year‐old child

Lead poisoning still remains a matter of concern, especially in children, in spite of widespread preventive practices [1]. Children are particularly vulnerable through mouthing behaviour [2–4] and high absorption from the gastrointestinal tract as compared with adults. This may adversely affect the developing nervous system, with neurocognitive effects and IQ decline in chronic intoxication [5]. We describe a sporadic case of severe lead poisoning rapidly treated by therapeutic means including surgery, thereby avoiding possible death through encephalopathy. In January 2004 while his parents were looking on, a 2-year-old boy with pica behaviour swallowed toy money made from pure metallic lead. No specific abdominal pain or vomiting was noted by the attending physician. What is more, the child’s behaviour did not change, and he showed no loss of appetite. On the second day (D2), possible elimination of the object in stools was found to be negative, so the child was admitted to a hospital paediatric ward, which ordered blood lead (Pb) measurement, a blood and urine check-up and an X-ray abdominal examination. Blood Pb concentrations were assessed by electrothermal atomic absorption spectrometry with Zeeman background correction. Analytical efficiencies have been monitored by participation in an interlaboratory survey, the Quebec Toxicology Centre Interlaboratory Comparison Programme [6]. The results of 1.51 ± 0.02 µmol l−1 (mean ± SD, in triplicate) already indicated Pb overload in this child, largely exceeding the threshold defined by the 1998 Centers for Disease Control and Prevention [1] (CDC) ( 2.17 µmol l−1, chelation therapy is strongly recommended [1]. On D4, calcium disodium edetate (CaNa2 EDTA) diluted in 5% isotonic glucose solution was infused slowly by intravenous administration (500 mg m−2 day−1) over 5 h for 5 days. No symptoms such as headache, fatigue and nausea were noted. Samples of urine were collected on D3 to D7. High urinary lead excretion from D3 to D5 (1560 µg 24 h−1, 810 µg 24 h−1 and 510 µg 24 h−1, respectively) indicated accelerated elimination of this toxic metal (reference value in urine: <100 µg 24 h−1) [7] and thereby confirmed body lead burden in the child. After the results for D6-D7 in urine (190 µg 24 h−1 and 150 µg 24 h−1, respectively), body pools tended to equilibrate. A decrease of blood lead was observed from D4 to D8 (2.04 ± 0.39 µmol l−1, 1.86 ± 0.02 µmol l−1, 1.54 ± 0.04 µmol l−1, 1.50 ± 0.04 µmol l−1, 1.52 ± 0.04 µmol l−1) vs. D2 (2.95 ± 0.04 µmol l−1). Over the months of February, March, April and May 2004, we noted a relative stability in blood Pb concentrations (1.45 ± 0.01 µmol l−1, 1.25 ± 0.01 µmol l−1, 1.20 ± 0.01 µmol l−1, 1.20 ± 0.01 µmol l−1, respectively), but the concentrations remained high for a child [1]. Figure 1 (A) Child’s anteroposterior abdominal radiography. Toy money is located in the gastric area (black arrow) with minimal colon dilatation. (B) Picture of toy money. Specifications of the toy money: 4 g pure metallic lead, diameter 2 cm Furthermore, in May, an increase of zinc protoporphyrin (ZPP) and a microcytic anaemia (5 µg g−1 Hb; reference value: <1 µg g−1 Hb) was noted. In this acute lead poisoning, clinically speaking, no symptom or loss of appetite was observed, nor was there any intellectual impairment or decline in cognitive function. Lastly, a decrease of blood Pb concentrations appeared over the course of June, July, August and September 2004 (0.85 ± 0.02 µmol l−1, 0.82 ± 0.04 µmol l−1, 0.82 ± 0.04 µmol l−1, 0.75 ± 0.02 µmol l−1, respectively), and was likewise correlated with the ZPP determination in August (1.9 µg g−1 Hb). These concentrations constantly remained above the CDC [1]. It was only during the tenth month (October 2004) that the child’s blood Pb and ZPP concentrations (0.48 ± 0.01 µmol l−1 and 1 µg g−1 Hb, respectively) came within the previously mentioned reference values. It is a well-known fact that the average fractional gastrointestinal absorption of lead is much greater in children than in adults [5] and subsequently, without rapid medical intervention, the extremely high concentrations in this child could have provoked possibly devastating effects on his nervous system [8].

Postoperative amino acid infusions: An appraisal

Amino acid infusions either as a 7 per cent solution or as an isotonic 3.5 per cent solution produce a nitrogen-sparing effect in the postoperative period. The nitrogen-sparing effect is independent of the concentration and rate of infusion of the amino acid solution; or of any changes in plasma substrate and hormone concentrations. These solutions have no advantage over conventional intravenous therapy with isotonic glucose and saline solutions and there is no indication for their routine use in the management of postoperative patients.

Disparity in osmolarity-induced vascular reactivity.

Conventional peritoneal dialysis solutions (PDS) are vasoactive. This study was conducted to identify vasoactive components of PDS and to describe quantitatively such vasoactivity. Anesthetized nonheparinized rats were monitored continuously for hemodynamics while the microvasculature of the jejunum was studied with in vivo intravital microscopy. In separate experiments, vascular reactivity of rat endothelium-intact and -denuded aortic rings (2 mm) was studied ex vivo in a standard tissue bath. In both studies, suffusion of the vessels was performed with filter-sterilized isotonic and hypertonic solutions that contained glucose or mannitol as osmotic agents. PDS served as a control (Delflex 2.25%). Hypertonic glucose and mannitol solutions produced a significant vascular reactivity in aortic rings and instantaneous and sustained vascular relaxation at all levels of the intestinal microvasculature. Similarly, lactate that was dissolved in a low-pH isotonic physiologic salt solution produced significant force generation in aortic rings. Whereas isotonic glucose and mannitol solutions had no vasoactivity in aortic rings, isotonic glucose produced a selective, insidious, and time-dependent vasodilation in the intestinal premucosal arterioles (18 +/- 0.2% of baseline), which was not observed in the larger inflow arterioles (100 mum). This isotonic glucose-mediated vascular relaxation can be attenuated by approximately 50% with combined adenosine A(2a) and A(2b) receptor antagonists and completely abolished by adenosine A(1) receptor inhibition. By using two different experimental techniques, this study demonstrates that hyperosmolality and lactate are the major vasoactive components of clinical peritoneal dialysis solutions. The pattern and the magnitude of such reactivity are dependent on vessel size and on the solutes' metabolic activity. Low pH of conventional PDS is not a vasoactive component by itself but renders lactate vasoactive. Energy-dependent transport of glucose into cells mediates vasodilation of small visceral arterioles by an adenosine receptor-mediated mechanism and constitutes a significant fraction of PDS-mediated vascular reactivity in the visceral microvasculature.