Mannitol Solution Research Articles

A Precision Ultrasonic Phase Velocity Measurement Technique for Liquids

Present paper reports the design and developmental aspects of a new technique for ultrasonic phase velocity measurement in liquids, which is based on the studies carried out on frequency dependence of ultrasonic velocity in pure, binary and ternary liquids/mixtures. The design and developmental aspects of the experimental set up are reported along with optimisation of data acquisition software developed in LabVIEW. Finally, the developed technique is used to measure phase velocity in water (W), aqueous solution of mannitol (M), binary mixture of tertiary butyl alcohol (TBA) in water and a tertiary mixture of TBA + W + M. The results are reported within frequency bandwidth from 3 to 7 MHz. The main reason for selecting these liquids was to identify some of the liquids which can be used as reference liquids for metrological applications. Although, reporting the systematic studies to find out the reference liquid is beyond the scope of the present paper due to obvious reasons, and will be dealt separately, but the studies certainly demonstrate that the technique can successfully be used for phase velocity measurement as a function of frequency and temperature.

Role of Central and Peripheral Chemoreceptors in Vasopressin Secretion Control

In this review, we analyzed the role played by central and peripheral chemoreceptors (CHRs) in vasopressin (AVP) secretion control. Central neural pathways subserving osmotic and non-osmotic control of AVP secretion are strictly correlated to brain areas participating in chemoreception mechanisms. Among the different brain areas involved in central chemoreception, the most important site has been localized in the retrotrapezoid nucleus of the rostral ventrolateral medulla. These central CHRs are able to detect very small pH/CO2 fluctuations, participating in brain blood flow regulation, acid-base balance and blood pressure control. Decreases in arterial pH and increases in arterial pCO2 stimulate AVP release by the Supraoptic and Paraventricular Nuclei. Carotid CHRs transduce low arterial O2 tension into increased action potential activity, leading to bradycardia and coronary vasodilatation via vagal stimulation, and systemic vasoconstriction via catecholaminergic stimulation. Stimulation of carotid CHRs by hypoxia increases neurohypophyseal blood flow and AVP release, an effect inhibited by CHRs denervation. Two renal CHRs have been identified: Type R1 CHRs do not have a resting discharge but are activated by renal ischemia and hypotension; Type R2 CHRs have a resting discharge and respond to backflow of urine into the renal pelvis. Signals arising from renal CHRs modulate the activity of hypothalamic AVPergic neurons: activation of R1 and R2 CHRs, following increased intrapelvic pressure with solutions of mannitol, NaCl and KCl, produces a significant increase of AVP secretion and the same effect has been obtained by the intrarenal infusion of bradykinin, which excites afferent renal nerves, as well as by the electrical stimulation of these nerves.

Phytotoxicity induced by Phragmites australis: an assessment of phenotypic and physiological parameters involved in germination process and growth of receptor plant

This study investigated the possible phytotoxicity induced by Phargmites australis on phenotypic and physiological parameters of recipient plants with identification of major inhibitors in the donor plant. This was achieved using aqueous extracts of different organs and root exudates of P. australis in laboratory and greenhouse experiments with Lactuca sativa as the model test plant. The observed reduced liquid imbibition and altered resource mobilization in seeds of L. sativa, in particular an insufficient carbohydrate supply, demonstrated that the onset of germination might be negatively affected by phytotoxicity. Dose-response studies pointed out that oxidative stress through reactive oxygen species production could potentially cause the observed germination and seedling growth reductions. The osmotic effects by mannitol solution on germination as well as growth and physiology at a level of −0.57 and −0.45 bar, respectively, demonstrated that the results from aqueous plant extracts were partially induced by the osmotic potential on and above those levels. Overall, the relative strength of inhibition on measured parameters was the highest in leaf extract, followed by rhizome, root, stem, and inflorescence. Root exudates of P. australis also had negative impacts by reducing germination and growth of plant. High-performance liquid chromatography (HPLC) analysis revealed gallic acid, a potent phytotoxin, as a major compound with an order of leaf >inflorescence>rhizome>root>stem.

Breaking of Plant Stomatal One-Cell-Spacing Rule by Sugar Solution Immersion

The spatial distribution of plant stomata is a model system to study epidermal cell pattern formation. Molecular genetic approaches have identified several key genes required for stomatal distribution patterning, but environmental conditions that perturb the stomatal spacing distribution have not yet been identified. We found that immersing hydroponic cultures in 1–5% sucrose solution induced abnormally clustered stomata in the cotyledons of Arabidopsis seedlings. Clustered stomata were also induced by treatment with glucose or fructose solution but not by mannitol solution, suggesting that osmotic stress was not a cause of the disturbed stomatal patterns. Stomatal lineage cell-specific enhancer trap lines revealed that the sugar solution treatment led to ectopic expression of stomatal lineage cell-specific genes in non-stomatal lineage cells. Aniline blue staining also showed that there was reduced deposition of callose, a plant cell wall component, in new cell walls during formation of stomatal precursor cells (meristemoids). These results suggested that the immersion treatment with sugar solution permitted ectopic guard cell differentiation through dysfunction of the cell wall dividing stomatal- and non-stomatal lineage cells. Our simple induction system for clustered stomata provides a suitable tool for further studies to investigate the one-cell-spacing rule during plant stomatal development.

BiOX (X = Cl, Br, I) nanostructures: Mannitol-mediated microwave synthesis, visible light photocatalytic performance, and Cr(VI) removal capacity

A facile microwave irradiation method has been successfully developed for the controllable fabrication of BiOX (X=Cl, Br, I) nanostructures in mannitol solution. The morphology and size of BiOX nanostructures could be readily tailored by adjusting the amount of halide, reaction precursor, and mannitol concentration. Mannitol molecule acts as both a capping agent and a cohesive agent in the formation of BiOX nanostructures. A possible two-stage formation mechanism was discussed based on the morphology evolution of BiOI nanostructures obtained in mannitol solution with different concentrations. The as-synthesized BiOX nanostructures exhibit much higher photocatalytic activities than that of commercial TiO2. In particular, flower-like BiOX hierarchical nanostructures display the best photocatalytic performance, which is mainly ascribed to their unique hierarchical structure, high BET surface area, and large band gap. Moreover, BiOX nanostructures also demonstrate superior Cr(VI) removal capacity. The Cr(VI) adsorption behavior was also analyzed by the Langmuir and Freundlich adsorption isotherms.

Aerosol Delivery of Nanoparticles in Uniform Mannitol Carriers Formulated by Ultrasonic Spray Freeze Drying

While most examples of nanoparticle therapeutics have involved parenteral or IV administration, pulmonary delivery is an attractive alternative, especially to target and treat local infections and diseases of the lungs. We describe a successful dry powder formulation which is capable of delivering nanoparticles to the lungs with good aerosolization properties, high loadings of nanoparticles, and limited irreversible aggregation. Aerosolizable mannitol carrier particles that encapsulate nanoparticles with dense PEG coatings were prepared by a combination of ultrasonic atomization and spray freeze drying. This process was contrasted to particle formation by conventional spray drying. Spray freeze drying a solution of nanoparticles and mannitol (2wt% solids) resulted in particles with an average diameter of 21 ± 1.7μm, regardless of the fraction of nanoparticles loaded (0-50% of total solids). Spray freeze dried (SFD) powders with a 50% nanoparticle loading had a fine particle fraction (FPF) of 60%. After formulation in a mannitol matrix, nanoparticles redispersed in water to < 1μm with hand agitation and to < 250nm with the aid of sonication. Powder production by spray drying was less successful, with low powder yields and extensive, irreversible aggregation of nanoparticles evident upon rehydration. This study reveals the unique advantages of processing by ultrasonic spray freeze drying to produce aerosol dry powders with controlled properties for the delivery of therapeutic nanoparticles to the lungs.

Influence of Non-Water-Soluble Placebo Pellets of Different Sizes on the Characteristics of Orally Disintegrating Tablets Manufactured by Freeze-Drying

The present study describes the development of an orally disintegrating tablet containing a non-water-soluble drug delivery system. A model system was applied to evaluate the effect of different-sized particles on tablet characteristics. Cellets were incorporated into tablets prepared by freeze-drying from a 100 mg/mL mannitol or sucrose solution. Particle size distributions were 200-355 µm for Cellets 200 (C200) and 500-710 µm for Cellets 500 (C500). An examination of the tablets revealed that the particles could not be sufficiently embedded in mannitol because of its crystalline nature. The tablet hardness was also inadequate. In contrast, the hardness of sucrose tablets was increased by the addition of Cellets 500. Therefore, the sucrose-based formulation was studied further. Binders [hydroxyethylstarch, sodium alginate, methylcellulose (MC), and gelatin] were added in different concentrations, and tablets were made either with or without placebo pellets. A positive effect of the Cellets on the hardness of tablets was identified. Furthermore, disintegration time could be clearly reduced by Cellets for tablets made from 100 mg/mL sucrose with addition of 10 mg/mL MC, 20 or 40 mg/mL gelatin. The freeze-dried tablet index revealed that the formulations of sucrose with 50 mg/mL hydroxyethylstarch or 20 mg/mL gelatin were particularly advantageous.

Development of a New Method for Bioassay of Allelopathy Using Protoplasts of a Leguminous Plant Mucuna pruriens With a High Content of the Allelochemical L-DOPA

To study allelopathy at the cellular level, we established a new bioassay method using protoplasts from etiolated leaves of a leguminous plant, Mucuna pruriens, which contains a large amount of L-3,4-dihydroxyphenylalanine (L-DOPA) and protoplasts prepared from cotyledons, leaves or roots of Lactuca sativa (lettuce) grown in an axenic condition. The bioassay was performed using 96 multi-well culture plates and required only a small volume of medium, 50 ?L, per well. For the mixed culture of Mucuna and recipient lettuce protoplast, the optimum condition was Murashige and Skoog’s basal medium, containing 1 ?M of 2,4-dichlorophenoxyacetic acid, 5 ?M of benzyladenine and 0.4 M mannitol solution. The inhibitory effect of M. pruriens protoplasts was found to vary with the density of the recipient L. sativa protoplasts. The M. pruriens protoplasts had no effect on the division of protoplasts from suspension cells of Oryza sativa. These results were in agreement with those obtained by the conventional plant box method. Our study offered a novel in vitro assay method, which will be widely applicable to study allelopathy of various plants on lettuce and also for quantitative studies between plant species under different culture conditions in order to simulate the possible future environmental risk.

Multi-institutional outbreak of Burkholderia cepacia complex associated with contaminated mannitol solution prepared in compounding pharmacy

Burkholderia cepacia complex (BCC) has been described as a cause of nosocomial outbreaks. We describe an outbreak of and identify risk factors for nosocomial BCC infections associated with intrinsically contaminated mannitol 3% solution. Urinary and bloodstream infection caused by BCC were identified in hospitalized patients who underwent urologic surgery and received intraoperative irrigation of 3% mannitol solution in February 2009. The investigation included retrospective chart review, case control study, procedural review, and culture of mannitol solution. Seven BCC infections were identified. BCC isolates were recovered from blood and/or urine from patients and lots of mannitol in use during the outbreak period. Mannitol solution was produced by a compounding pharmacy. Receipt of larger volumes of contaminated solution was identified as a significant risk factor for infection (odds ratio, 1.5; P value < .05). BCC was also cultured in lots of mannitol in use in other hospitals. Manipulated mannitol solution is a potential source of infection. Contamination with paraben-degrading organisms can occur at the time of manufacture. Our findings suggest that contamination of mannitol at a compounding pharmacy occurred. Prompt communication to other hospitals and implementation of infection control measures were effective in avoiding further cases of infection.

Controlling the physical form of mannitol in freeze-dried systems

A potential drawback with the use of mannitol as a bulking agent is its existence as mannitol hemihydrate (MHH; C6H14O6·0.5H2O) in the lyophile. Once formed during freeze-drying, MHH dehydration may require secondary drying under aggressive conditions which can be detrimental to the stability of thermolabile components. If MHH is retained in the lyophile, the water released by MHH dehydration during storage has the potential to cause product instability. We systematically identified the conditions under which anhydrous mannitol and MHH crystallized in frozen systems with the goal of preventing MHH formation during freeze-drying. When mannitol solutions were cooled, the temperature of solute crystallization was the determinant of the physical form of mannitol. Based on low temperature X-ray diffractometry (using both laboratory and synchrotron sources), MHH formation was observed when solute crystallization occurred at temperatures⩽−20°C, while anhydrous mannitol crystallized at temperatures⩾−10°C. The transition temperature (anhydrate – MHH) appears to be ∼−15°C. The use of a freeze-dryer with controlled ice nucleation technology enabled anhydrous mannitol crystallization at ∼−5°C. Thus, ice crystallization followed by annealing at temperatures⩾−10°C can be an effective strategy to prevent MHH formation.

Comparison of Equivolume, Equiosmolar Solutions of Mannitol and Hypertonic Saline with or without Furosemide on Brain Water Content in Normal Rats

Mannitol and hypertonic saline (HS) are used by clinicians to reduce brain water and intracranial pressure and have been evaluated in a variety of experimental and clinical protocols. Administering equivolume, equiosmolar solutions in healthy animals could help produce fundamental data on water translocation in uninjured tissue. Furthermore, the role of furosemide as an adjunct to osmotherapy remains unclear. Two hundred twenty isoflurane-anesthetized rats were assigned randomly to receive equivolume normal saline, 4.2% HS (1,368 mOsm/L 25% mannitol (1,375 mOsm/L), normal saline plus furosemide (8 mg/kg), or 4.2% HS plus furosemide (8 mg/kg) over 45 min. Rats were killed at 1, 2, 3, and 5 h after completion of the primary infusion. Outcome measurements included body weight; urinary output; serum and urinary osmolarity and electrolytes; and brain, lung, skeletal muscle, and small bowel water content. In the mannitol group, the mean water content of brain tissue during the experiment was 78.0% (99.3% CI, 77.9-78.2%), compared to results from the normal saline (79.3% [99.3% CI, 79.1-79.5%]) and HS (78.8% [99.3% CI, 78.6-78.9%]) groups (P < 0.001), whereas HS plus furosemide yielded 78.0% (99.3% CI, 77.8-78.2%) (P = 0.917). After reaching a nadir at 1 h, brain water content increased at similar rates for mannitol (0.27%/h [99.3% CI, 0.14-0.40%/h]) and HS (0.27%/h [99.3% CI, 0.17-0.37%/h]) groups (P = 0.968). When compared to equivolume, equiosmolar administration of HS, mannitol reduced brain water content to a greater extent over the entire course of the 5-h experiment. When furosemide was added to HS, the brain-dehydrating effect could not be distinguished from that of mannitol.

Induction of water deficit tolerance by cold shock and salicylic acid during germination in the common bean

The application of short-term stresses or elicitors in seedlings or embryos with high metabolic activity might increase multi-adversity tolerance. Beans seeds cv. IAC-Carioca were exposed to cold shock temperatures (S - 7°C 24h -1 ) and salicylic acid (SA - 0.01 mM 48h -1 ) during imbibition to study physiological responses to osmotic stress physiological responses. The seeds were soaked in paper towel imbibed in water or salicylic acid at 25°C for 24h. The seed were subsequently submitted to temperatures of 7oC and 25oC for another 24h in water or salicylic acid. Following each treatment, the seeds were transferred to mannitol solutions (0, -0.3, -0.6, and -1.2 MPa) and evaluated after seven days for germination, vigour, shoot and root length, dry mass, proline accumulation and protein electrophoretic profile. Treatments with salicylic acid and cold shock did not affect germination, but germination was reduced through the mannitol-induced progression of water deficit. However, both salicylic acid and cold shock treatments affected seed vigour. The application of salicylic acid increased root and total seedling length and dry weight, especially at intermediate water stress levels. Both salicylic acid and cold shock treatments changed the protein pattern of the treated seeds, but only SA showed promise as a technology for seed treatment.

Effect of polymers for aerolization properties of mannitol-based microcomposites containing meloxicam

The aim of this study was to develop respirable microcomposites of meloxicam and adjuvants (different polymers and amino acid) for inhalation as drug delivery systems for local lung therapy. Meloxicam was transformed into microcomposites, i.e. crystals of drug embedded in mannitol and other adjuvants. We focused on the influence of polymers concentration on the physico-chemical properties of the microparticles. The objective was to optimize the aerodynamic parameters of the particles and to achieve the fast release of meloxicam.The size of the meloxicam particles suspended in aqueous mannitol solution containing different additives was reduced by high-pressure homogenization. Dry powders were produced from the microsuspensions by a co-spray-drying technique. Morphological, structural and in vitro dissolution studies were presented. The in vitro aerosol performance was tested by using the multistage Next Generation Impactor.It was found that polyvinyl alcohol and polyvinylpyrrolidone, promoted the presence of individual microcomposites by decreasing the aggregation tendency. L-leucine improved the fine particle fraction content of the samples. The co-spray-dried mannitol-based formulations containing the additives released 90% of the meloxicam by dissolution in 5min. Aerodynamic assessment showed the fine particle fraction was >53% and the mass median aerodynamic diameter was <3.52μm. This study indicated that meloxicam microcomposites prepared according to the described procedure are suitable for pulmonary local anti-inflammatory and antifibrotic therapy.

Pharmacokinetic evaluation in mice of amorphous itraconazole-based dry powder formulations for inhalation with high bioavailability and extended lung retention

Three Itraconazole (ITZ) dry powders for inhalation (DPI) were prepared by spray-drying a mannitol solution in which the ITZ was in suspension (F1) or was in solution without (F2) or with phospholipid (PL) (F3). These powders were endotracheally insufflated in vivo at a single dose of 0.5mg/kg for pharmacokinetic profile (lung and plasma concentration) determination in ICR CD-1 mice. ITZ was crystalline in F1 and assumed to be amorphous in the F2 and F3 formulations. F2 and F3 formulations allowed the in vitro formation of an ITZ supersaturated solution with a maximum solubility of 450±124ng/ml (F2) and 498±44ng/ml (F3), in contrast to formulation F1 (<10ng/ml). As a result of these higher solubilities, absorption into the systemic compartment after endotracheal administration was faster for formulations F2 and F3 (shorter tmax) and in larger quantities compared to the F1 formulation (plasmatic AUC0–24h of 182ngh/ml, 491.5ngh/ml and 376.8ngh/ml, and tmax of 60min, 30min and 5min for F1, F2 and F3, respectively). PL increased the systemic bioavailability of ITZ (determined by the AUCplasma to AUClung ratio) as a consequence of their wetting and absorption enhancement effect. ITZ lung concentrations after pulmonary administration remained higher than the targeted dose, based on the minimal inhibitory concentrations for Aspergillus fumigatus (2μg/glung), 24h post-administration for both F1 and F2 formulations. However, this was not the case for formulation F3, which exhibited a faster elimination rate from the lung, with an elimination half-life of 4.1h vs. 6.5h and 14.7h for F1 and F2, respectively.

Treating mannitol in a saturated solution of mannitol: A novel approach to modify mannitol crystals for improved drug delivery to the lungs

The aim of this study was to evaluate the influence of treatment of a promising dry powder aerosol carrier (mannitol) on the aerosolization performance of salbutamol sulphate (SS) using a novel approach: treating excess commercial carrier particles in a saturated solution of the same carrier. Commercial mannitol (CM) particles were treated with aqueous mannitol supersaturated solutions (20% and 25% w/v), under stirring, (300 rpm) for either 24h or 48 h. The results showed that particle treatment did not alter the polymorphic form of mannitol (β-mannitol); however, all treated mannitol particles demonstrated smoother surface topography and improved aerosolization performance compared to CM in dry powder inhalations. Unlike the concentration of mannitol solution used during treatment, the time of treatment to collect mannitol crystals was an essential key to modify the physical properties of mannitol and its effect on the aerosolization performance. In comparison to mannitol particles treated for 48 h, mannitol particles treated for 24h demonstrated larger size, more elongated-less regular shape, and smoother surfaces. No apparent relationship was obtained between in vitro aerosolisation behavior of SS with either mannitol particle size or shape descriptors. However, despite their larger size and more irregular-less uniformed shape, treated mannitol particles with smoother surfaces generated drug particles with smaller aerodynamic size and are expected to deliver higher amounts of drug to lower airways. The results demonstrated the potential of treating mannitol particles in aqueous solutions of the same material under controlled conditions to produce mannitol particles promising for dry powder inhaler systems. The results suggested that mannitol particle surface texture properties dominate over both particle size and particle shape of mannitol in terms of determining the aerosolization performance of mannitol.

Mannitol, a compatible solute synthesized by Acinetobacter baylyi in a two‐step pathway including a salt‐induced and salt‐dependent mannitol‐1‐phosphate dehydrogenase

The nutritionally versatile and naturally competent soil bacterium Acinetobacter baylyi copes with salt stress by the accumulation of compatible solutes. NMR analyses revealed that cells amassed glutamate and the rather unusual sugar alcohol mannitol upon an increase of the external NaCl concentration. To unravel the path of mannitol biosynthesis, the genome was inspected for genes potentially involved in its biosynthesis. A gene encoding a potential mannitol-1-phosphate dehydrogenase (mtlD) was identified in the genome of A. baylyi. Expression of mtlD was highly induced at high salinity. mtlD was overexpressed and the purified protein indeed produced mannitol-1-phosphate from fructose-6-phosphate. The enzyme preferred NADPH over NADH and the specific activity of fructose-6-phosphate reduction with NADPH was 130 U mg(-1) . Enzymatic activity was strictly salt-dependent. Deletion of mtlD resulted in a complete loss of salt-dependent mannitol biosynthesis. We provide clear evidence that osmo-induced synthesis of the compatible solute mannitol is by a two-step pathway and that the mannitol-1-phosphate dehydrogenase mediating the first step of this pathway is regulated by salinity on the transcriptional as well as on the activity level.

The morphology of spray dried mannitol particles — The vital importance of droplet size

Abstract As the morphology of spray dried aqueous mannitol solutions is strongly influenced by the scale of the used spray dryer or more correctly by the droplet size generated in the spray dryer the purpose of this work is to carefully study and compare the morphologies and underlying particle formation mechanisms on lab and pilot scale. Therefore drying experiments of 15% [w/w] aqueous mannitol solutions were performed on a lab and pilot scale spray dryer at different outlet temperatures. The obtained spray dried products are intended to be used as carrier particles for pulmonary drug delivery. In order to show that the morphology is highly dependent on the initial droplet size, irrespective of the size of the used spray dryer, droplets of different size were dried in the pilot scale spray dryer at different air outlet temperatures. Additionally the influence of feed temperature on particle morphology was studied. For small droplets crystallization from a highly viscous liquid or even water-free melt is observed, leading to rough particles at high outlet temperatures and smooth particles at low temperatures. When drying larger droplets, however crystallization obviously starts from a more diluted solution leading to rougher surfaces, containing larger single crystals at lower outlet temperatures than at higher ones. For large droplets an increase in the mannitol solution feed temperature leads to particles of comparably rougher surface. No influence of feed temperature was observed for smaller droplets.

Improved pharmaceutical stability of a boronphenylalanine mannitol formulation for boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a radiotherapy based cancer treatment requiring the availability of a low energy thermal neutron beam and a boron containing drug. These requirements limit BNCT availability with the latter pharmaceutical issue related to the extremely short shelf-life and clinical acceptability of the current fructose based L-boronphenylalanine (BPA) formulation. Resolution of the formulation issues would remove this factor and therefore the stability of an alternative mannitol BPA formulation has been investigated. A mannitol BPA solution formulation was prepared and either lyophilised or stored as a solution at varying temperatures. After suitable periods the formulation was analysed by HPLC for BPA and degradation products. Lyophilised and solution mannitol BPA formulations exhibited a temperature and time dependent loss of BPA with concomitant increases in degradation products. Autoclaving the solution induced and accelerated degradation. A solution or lyophilised mannitol BPA formulation has a shelf-life of between 1 and 4years respectively, a marked improvement over the current fructose formulation. Due to temperature dependent degradation the formulation cannot be terminally sterilised by autoclaving. The enhanced stability of the mannitol formulation removes the requirement for extemporaneous aseptic preparation of BPA just prior to treatment and eliminates one of the issues complicating the delivery of BNCT.

Influence of compound aescine gel on ultrastructure of vein infused mannitol and its mechanism

Purpose: When hypertonic solution 20% mannitol solution was injected into vein, inflammatory mediators and Mitogen-activated protein kinases activated by mannitol can directly induce the fading of vascular endothelial cell, which leads to phlebitis. The study aims to observe the influences of reparil-gel N coated at the proximal parts of the puncture point and basing on this along with infusing heated mannitol to veins to the injure and ultrastructure of veins which were infused the 20% mannitol solution by indwelling needle in vein. Methodology: There are 15 adult New Zealand rabbits. We randomly divided 24 ear veins of 12 adult New Zealand rabbits into Control group, Gelatum group, Gel heated group and injected 20% mannitol solution by vein detained needle in three groups. In Gelatum group, we coated the proximal end of the puncture point with a thin layer of compound aescine gel. Based on Gelatum group, we heated 20% mannitol solution to 35oC-37oC in Gel heated group. Then we observed the intravenous parts and took the veins of each group out to observe their morphology and ultrastructural after the second day of transfusion. 6 ear veins of the rest 3 rabbits as Health group weren’t given any interventions, the veins were taken out to observe their morphology. Results: Comparison between Gelatum group and Gelatum heated group on vascular dilatation, Infiltration of inflammatory cell and Formation of thrombus had no significance, P> 0.05, while the case was different for the comparison on injury of vascular wall, perivascular edema and perivascular hemorrhage, P< 0.05). The statistical significance exists between control group and Gelatum group and Gel heated group, P< 0.05. It was observed under the electron microscope that, in control group, the membrane of endothelial cell peeled off and the mitochondria swelled and vacuolized. In Gelatum group, the membrane of endothelial cell was defective, the parts of the mitochondria were fuzzy, intercellular substance was slightly edematous. In Gel heated group, the mitochondria were clear and intercellular substance slightly swelled. It could be found that the function of phagocyte was complete. Conclusions: Compound aescine gel can prevent phlebitis or reduce the incidence of phlebitis. The combined intervention of coating with a thin layer of compound aescine gel and heating mannitol solution can produce better effect.

Effect of Acute Hyperglycemia on Cardiac Conduction

Diabetes is associated with a relatively high prevalence of sudden cardiac death but the underlying mechanism is not well understood. In experimental diabetes, cardiac expression of connexin43 is reduced. Downregulation of connexin43 is linked to a slowing of cardiac conduction which increases the risk of cardiac arrhythmias and thereby sudden cardiac death. It is known that hyperglycemia causes downregulation of connexin43 but it is unknown to which extend this occurs in whole hearts. Here, we test the hypothesis that acute hyperglycemia leads to slowing of cardiac conduction through downregulation of connexin43 in whole hearts. We measured ventricular conduction velocity in Langendorff perfused guinea pig hearts using a multi-electrode array under normo- and hyperglycemic conditions (5.5 and 30mM glucose respectively) for up to 4 hrs. In addition, one group of hearts was perfused with a mannitol solution as a control for changes in osmolarity. Expression of connexin43 was quantified by western blotting. In the control group, longitudinal conduction velocity remained stable over 4 hrs (63 cm/s) while transverse conduction decreased slightly (from 27 to 25 cm/s). Similar results were obtained from both the hyperglycemia and mannitol groups suggesting that conduction was unaffected by changes in glucose concentration and osmolarity. Accordingly, no differences were observed in the protein levels of connexin43 between the groups supporting the functional results. In conclusion, acute exposure to hyperglycemia does not appear to have any significant effects on cardiac conduction and does not modulate the expression of connexin43 in guinea pig hearts.