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Extracellular fluid and total body water changes in neonates undergoing extracorporeal membrane oxygenation.

After being placed on extracorporeal life support (ECLS), newborn patients typically weight 5% to 30% more than their birthweight. Recovery and eventual decannulation from ECLS is associated with a return to baseline weight or birthweight values after a pronounced diuresis. It has been assumed that the increases in weight in these patients are due to increases in extracellular fluid (ECF) and total body water (TBW). This study was undertaken to prove or disprove this hypothesis. ECF space was measured using the compound sodium bromide and TBW was determined with the use of deuterium oxide (nonradioactive heavy water). Fluid compartment measurements were made prior to the institution of ECLS, immediately after placement on bypass, approximately every other day while on bypass, and a final measurement was made once the patient was off bypass. Sodium bromide concentration was analyzed by high-pressure liquid chromatography, and deuterium oxide concentration was measured by the falling drop method. Eight newborns with respiratory failure were placed on either venoarterial (4 patients) or venovenous (4 patients) ECLS for an average of 106 hours (range, 71 to 219 hours). Pre-ECLS TBW was high in the neonates (87% of total body weight v the normal of 75% to 80%). Mean values for each fluid compartment were corrected for the additional volume of the bypass circuit when the patient was on bypass. ECF increased immediately after the institution of ECLS; however, both ECF and TBW decreased during the bypass run, and post-ECLS levels of ECF and TBW were similar to those found prior to ECLS.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Water↗

The pharmacological differences and similarities between stress- and ethanol-induced gastric mucosal damage.

Stress- and ethanol-induced gastric mucosal damage are the two commonly used ulcer models in animals. They share some of the similarities but also have differences in the etiology of gastric ulceration. This article reviews the influences of various protective drugs on these two types of gastric damage in rats. Verapamil (a calcium antagonist) or N-ethylmaleimide (a sulfhydryl depletor) prevents cold restraint-, but potentiates ethanol-provoked gastric lesion formation. N-Acetylcysteine (a mucolytic agent) and acetaminophen (an antipyretic analgesic) have the opposite actions. Prostaglandins provide a much better antiulcer effect on ethanol-induced lesions. Cimetidine (a histamine H2-receptor antagonist) prevents only stress-induced mucosal damage. These differences in drug actions indicate that stress and ethanol may have dissimilar ulcerogenic mechanisms in rats. On the other hand, carbenoxolone (a mucus inducer), histamine H1-receptor antagonists, leukotriene inhibitors (FPL 55712 and nordihydroguaiaretic acid) and mast cell stabilizers (like zinc compounds, sodium cromoglycate, FPL 52694 and ketotifen), all protect against gastric mucosal damage by stress or ethanol in rats. However, the role of gastric sulfhydryls in both types of gastric lesions is still controversial. These findings imply that the two types of lesion formation share some of the ulcerogenic mechanisms. This communication attempts to analyze the various findings and to relate them to the etiology of stress and ethanol-induced gastric lesions. It also summarizes the uses, and the antiulcer mechanisms, of the drugs that have been studied utilizing these two animal ulcer models, and suggests their possible implications in man.

Acetaminophen↗

Inhibition of rat heart mitochondrial respiration by cadmium chloride.

Mitochondria were isolated from hearts obtained from adult male Sprague-Dawley rats by two-part differential centrifugation of heart homogenates. Time-dependent (0-120 sec) and concentration-dependent (0-10 microM CdCl2) effects of cadmium on pyruvate-malate-supported state 3 and state 4 respiration were measured in a constant temperature reaction chamber at 37 degrees C, according to established procedures. The ID50 for cadmium chloride on state 3 respiration was determined to be 4.2 microM. The inhibition produced by cadmium chloride in heart mitochondria was compared, using identical procedures, to the effects induced by two compounds, sodium atractyloside and potassium cyanide, which are known to alter mitochondrial respiration at specific sites. The calculated ID50 values for these agents in heart mitochondria were 1.8 and 16 microM, respectively. The concentration-dependent inhibition of mitochondrial respiration induced by either cadmium chloride or potassium cyanide was maintained in the presence of 50 microM carbonyl cyanide m-chlorophenylhydrazone (CCCP), a known uncoupling agent. In contrast, sodium atractyloside did not block the uncoupling effect of 50 microM CCCP. In addition cadmium chloride was also shown to inhibit CCCP-uncoupled mitochondrial respiration. The cadmium-induced inhibition of mitochondrial respiration was reversed partially by cysteine and completely by 2,3-dimercaptopropanol. The results of the present study indicate that, at all concentrations, cadmium chloride acted solely as an inhibitor of rat heart pyruvate-malate-supported mitochondrial respiration. These findings suggest a possible mechanism for the reported disturbances in myocardial metabolism and function that occur in conjunction with acute and chronic cadmium exposure in humans and experimental animals.

Animals↗

Nitric oxide modulation of the growth and differentiation of freshly isolated acute non-lymphocytic leukemia cells.

Freshly isolated acute non-lymphocytic leukemia (ANLL) cells were treated with the nitric oxide (NO)-liberating compounds sodium nitroprusside or S-nitrosoacetyl penicillamine and analyzed for viability, growth, and differentiation at 3-5 days. NO decreased the viability and the growth of freshly isolated ANLL cells in vitro. NO treatment significantly increased expression of CD14 in blast cells from patients with M5 ANLL, and increased at least one differentiation parameter in M4 or M5 cells. It had little or no effect on parameters of differentiation in other ANLL cells. We conclude that in vitro culture with NO decreases the growth and viability of most freshly isolated ANLL cells. NO also induces the differentiation of ANLL cells with a monocytic phenotype.

Cell Differentiation↗

Nitric oxide modulates gamma-interferon-induced MHC class II antigen expression on rat astrocytes.

Brain astroglial cells can be brought in vivo and in vitro to express an immunocompetent cell-like phenotype. We investigated the effect of the NO. releasing compound sodium nitroprusside (SNP) on Ia expression in rat astrocyte cultures. SNP down-regulates, in a concentration-dependent manner, the gamma-interferon-induced Ia expression. Inhibition of the NO. synthesis attenuates the glutamate mediated down-regulation of class II expression. Our results show that NO. is implicated in the immunomodulatory reactions in the brain parenchyma.

Animals↗

Involvement of nitric oxide in spinally mediated hyperalgesia in the mouse.

Intrathecal injection of N-methyl-D-aspartate (NMDA) induces a short duration hyperalgesia in mice. An inhibitor of nitric oxide synthase (NOS), N omega-nitro-L-arginine methyl ester (L-NAME), administered either systemically or intrathecally, blocked the NMDA-induced hyperalgesia. This effect was partially reversed by the NOS substrate, L-arginine. Intrathecal hemoglobin mimicked the effects of L-NAME. Intrathecal injection of the NO-donating compounds, sodium nitroprusside (SNP) and hydroxylamine, resulted in a hyperalgesia that lasted 3 h and was reduced by coadministration of hemoglobin. Thus, nitric oxide production appears to mediate NMDA-induced hypersensitivity and may contribute to other forms of centrally induced hyperalgesia.

Amino Acid Oxidoreductases↗

Relationship between cardiovascular neurones and descending antinociceptive pathways in the rostral ventrolateral medulla of the cat.

It has been previously reported that injection of neuroexcitatory compounds into the rostral ventrolateral medulla (RVLM) can produce an inhibition of nociceptive reflexes, often associated with a rise in arterial blood pressure. The aim of this study was to determine whether the subretrofacial (SRF) nucleus, which is a highly circumscribed group of cells within the RVLM known to play a major role in cardiovascular regulation also has an antinociceptive function. In barbiturate-anaesthetised and paralysed cats, unilateral microinjections of the neuroexcitatory compound sodium glutamate (8-20 nl of 0.5 M solution) into the SRF nucleus produced large increases in mean arterial pressure but had only small and inconsistent effects on the simultaneously measured ventral root responses to stimulation of primary afferent C-fibres. On the other hand, glutamate microinjections into RVLM sites closely adjacent to the SRF nucleus, or into the nucleus raphe magnus, produced powerful inhibition of the C-fibre evoked response in the ventral root which was accompanied by no or only small changes in arterial pressure. It is concluded that the SRF pressor cells do not exert any control over nociceptive spinal reflexes, but that such a function may be served by cells in closely adjacent parts of the RVLM. Moreover, the method of recording C-fibre evoked responses in ventral roots as a measure of the magnitude of nociceptive spinal reflexes, combined with the glutamate microinjection procedure, was shown to have a sufficient resolution to allow an accurate mapping of the location of antinociceptive cell groups within the ventrolateral medulla.

Action Potentials↗

Effects of ions on partitioning of serum albumin and lysozyme in aqueous two-phase systems containing ethylene oxide/propylene oxide co-polymers.

Aqueous two-phase systems composed of ethylene oxide/propylene oxide random co-polymers, EO30/PO70 or Ucon (EO50/PO50), in the top phase and dextran T500 in the bottom phase, have been studied. The cloud point diagram for EO30/PO70 in water solution was determined. EO30/PO70 has a cloud point of 32 degrees C at a concentration of 10% (w/w). The phase diagram for the system EO30/PO70-dextran T500-water was determined. Salt effects have been studied on the partitioning of two model proteins, bovine serum albumin and hen egg white lysozyme, in EO30/PO70-dextran and Ucon-dextran systems. Ions with different hydrophobicity, i.e., with different position in the Hofmeister or lyotropic series, were investigated with reference to their effect on protein partition. The counterion hydrophobicity was shown to have a strong influence on the partitioning of BSA and lysozyme. Most extreme partitioning was obtained with hydrophobic (chaotropic) ions like CIO4- and I-. A comparison of protein partitioning between PEG-dextran and EO30/PO70-dextran has been done. A more extreme protein partitioning was obtained in the EO30/PO70-dextran containing system. Temperature-induced phase separation was studied with EO30/PO70 at 45 degrees C. Both BSA and lysozyme were completely partitioned to the water phase formed above the cloud point of EO30/PO70. Model calculations, based on Flory-Huggins theory of polymer solutions, have been done which could reproduce the salt effect on the protein partitioning in aqueous-two phase system.

Bromides↗

Ketorolac penetration into the cerebrospinal fluid of humans.

STUDY OBJECTIVE: To determine the cerebrospinal fluid (CSF): total plasma concentration ratio of ketorolac tromethamine following a single intramuscular (IM) dose. DESIGN: Open, single-dose, IM-administration study. SETTING: General operating theaters of a medical school hospital. PATIENTS: 29 ASA physical status I and II patients scheduled to undergo elective surgery with spinal anesthesia. INTERVENTIONS: Patients were premedicated with ketorolac 90 mg IM formulated as 3 ml of a 3% solution. Between 1 and 4 1/2 hours later, an intravenous infusion of 500 ml of compound sodium lactate was begun. Lumbar puncture was then performed, and 2 ml of CSF was collected prior to administration of the spinal anesthetic. In addition, a 5 ml sample of venous blood was taken within 5 minutes of the CSF sample. MEASUREMENTS AND MAIN RESULTS: Simultaneous plasma and CSF concentrations of ketorolac were measured between 62 and 277 minutes following IM administration in 29 patients undergoing spinal anesthesia. The CSF concentrations were on the order of 1,000 times less than the total plasma concentrations; free concentrations of ketorolac in plasma were estimated to be about 10 times more than those in CSF. There appeared to be no constant time factor relating the appearance of ketorolac in the CSF to its plasma concentration following IM administration. CONCLUSION: Although the sensitivity of central prostaglandin synthetase systems to inhibition is unknown, it is unlikely from this pharmacokinetic data that there is a major central mechanism of analgesia for ketorolac.

Adult↗

The effects of IgG and immune complexes on the endotoxin-induced cytokine response.

Cytokine induction following stimulation by endotoxin (LPS) was investigated in human peripheral whole blood. Blood cells were suspended in autologous plasma diluted in basal medium (BM-plasma) or Compound Sodium Lactate Solution (CSL-plasma), or in autologous serum diluted in CSL. Induction of interleukin 1 beta, interleukin 6 and tumour necrosis factor alpha (IL-1 beta, IL-6 and TNF-alpha, respectively) was investigated following incubation of blood cells with LPS, IgG (Sandoglobulin) alone, or preformed LPS/IgG immune complexes. All three cytokines were induced by LPS alone. With 30 mg/ml Sandoglobulin alone, IL-1 beta production changed little from control, whilst IL-6 production increased markedly in CSL-serum only. TNF-alpha production increased slightly in BM-plasma and CSL-plasma, but not in CSL-serum. Lower concentrations of Sandoglobulin did not affect cytokine production. Upon stimulation with LPS/Sandoglobulin immune complexes, a trend in cytokine production was seen compared with the response to LPS alone: IL-1 beta and IL-6 production increased, whilst TNF-alpha production decreased. This only occurred in CSL-plasma and CSL-serum. Complement activation was present only in CSL-plasma and CSL-serum. Thus in the presence of complement activation and/or serum, Sandoglobulin can induce IL-6 production whilst suppressing the small TNF-alpha response it otherwise stimulates. In addition, when LPS is presented in the form of IgG immune complexes, dissociation of IL-1 beta and IL-6 production from TNF-alpha production is seen but only in the presence of complement activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Antibody Complex↗

Formation of hydroxyapatite onto glasses of the CaO-MgO-SiO2 system with B2O3, Na2O, CaF2 and P2O5 additives.

New bioactive glasses with compositions based on the CaO-MgO-SiO(2) system and additives of B(2)O(3), P(2)O(5), Na(2)O, and CaF(2) were prepared. The in vitro mineralization behaviour was tested by immersion of powders or bulk glasses in simulated body fluid (SBF). Monitoring of ionic concentrations in SBF and scanning electron microscopy (SEM) observations at the surface of the glasses were conducted over immersion time. Raman and infrared (IR) spectroscopy shed light on the structural evolution occurring at the surface of the glasses that leads to formation of hydroxyapatite.

Biocompatible Materials↗

Effects of individual and combined exposure to sodium arsenite and sodium fluoride on tissue oxidative stress, arsenic and fluoride levels in male mice.

Arsenic and fluoride are potent toxicants, widely distributed through drinking water and food and often result in adverse health effects. The present study examined the effects of sodium meta-arsenite (100 mg/l in drinking water) and sodium fluoride (5 mg/kg, oral, once daily), administered either alone or in combination for 8 weeks, on various biochemical variables indicative of tissue oxidative stress and cell injury in Swiss albino male mice. A separate group was first exposed to arsenic for 4 weeks followed by 4 weeks of fluoride exposure. Exposure to arsenic or fluoride led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity and glutathione (GSH) level. These changes were accompanied by increased level of blood and tissues reactive oxygen species (ROS) level. An increase in the level of liver and kidney thiobarbituric acid reactive substance (TBARS) along with a concomitant decrease in the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) and reduced GSH content were observed in both arsenic and fluoride administered mice. The changes were significantly more pronounced in arsenic exposed animals than in fluoride. It was interesting to observe that during combined exposure the toxic effects were less pronounced compared to the effects of arsenic or fluoride alone. In some cases antagonistic effects were noted following co-exposure to arsenic and fluoride. Arsenic and fluoride concentration increased significantly on exposure. Interestingly, their concentration decreased significantly on concomitant exposure for 8 weeks. However, the group which was administered arsenic for 4 weeks followed by 4 weeks of fluoride administration showed no such protection suggesting that the antagonistic effect of fluoride on arsenic or vice versa is possible only during interaction at the gastro intestinal sites. These results are new and interesting and require further exploration.

Alanine Transaminase↗

Soil quality and vulnerability in a Mediterranean natural ecosystem of Central Italy.

Wet and dry atmospheric depositions and soil chemical and microbiological properties were determined in a Mediterranean natural ecosystem of Central Italy near Rome (Castelporziano Estate). The monitoring of depositions permitted us to quantify the exceedances of S and N compounds (expressed as eqH(+)ha(-1)year(-1)) over the critical loads of acidity. Critical loads, i.e. the quantity of a substance which a part of the environment can tolerate without adverse effects occurring, were determined adopting the level 0 methodology following the UN/ECE Convention on Long-range Transboundary Air Pollution. Deposition data were available for the period 1992-1997, and acidity exceedances were referred to the main vegetation types present in the area. Results showed that most part of the Estate has a medium degree of vulnerability to acidification, and the corresponding risk of acidification deriving from the exceedances of atmospheric deposition was rather low. The study of soil chemical and microbiological properties included mainly total soil organic carbon (SOC), microbial biomass-C, biomass-C/SOC, soil respiration, and metabolic quotient (qCO2). Soil organic C metabolism has been discussed on the basis of the results from eight sampling sites.

Air Pollutants↗

A chromatographic estimate of the degree of surface heterogeneity of reversed-phase liquid chromatography packing materials. II-Endcapped monomeric C18-bonded stationary phase.

In a previous report, the heterogeneity of a non-endcapped C30-bonded stationary phase was investigated, based on the results of the measurements of the adsorption isotherms of two neutral compounds (phenol and caffeine) and two ionizable compounds (sodium naphthalene sulfonate and propranololium chloride) by frontal analysis (FA). The same method is applied here for the characterization of the surface heterogeneity of two new brands of endcapped C18-bonded stationary phases (Gemini and Sunfire). The adsorption isotherms of the same four chemicals were measured by FA and the results confirmed by the independent calculation of the adsorption energy distribution (AED), using the expectation-maximization (EM) method. The effect of the length of the bonded alkyl chain was investigated. Shorter alkyl-bonded-chains (C18 versus C30) and the end-capping of the silica surface contribute to decrease the surface heterogeneity under the same experimental conditions (30% methanol, 25 mM NaCl). The AEDs of phenol and caffeine are bimodal with the C18-bonded columns while they are trimodal and quadrimodal, respectively, with a non-endcapped C30-bonded column. The "supersites" (adsorption energy > 20 kJ/mol) found on the C30-Prontosil column and attributed to a cation exchange mechanism completely disappear on the C18-Gemini and C18-Sunfire, probably because the end-capping of the silica surface eliminates most if not all the ionic interactions.

Adsorption↗

Effects of selective oxidation of chitosan on physical and biological properties.

Chitosan was selectively oxidized at C-6 primary alcohol groups by TEMPO in the presence of sodium hypochlorite (NaOCl) and sodium bromide (NaBr), and also non-specifically oxidized only by NaOCl. Sequentially oxidized chitosan samples from 25 to 100% were produced by 25% increment, from both oxidation processes. By introducing carbonyl groups in chitosan structure with either oxidizing process, the water solubility was shown to be enhancing from all the oxidized sample groups. At the 25% of non-specific oxidation, 0.56% of solubility was detected but there was no proportional increase in solubility as the oxidation level increased. Moreover, the decreases in solubility were observed at 50%-oxidized (0.43%) and 100%-oxidized (0.45%) chitosan samples. During the specific oxidation process, 25%-oxidized 6-oxychitosan had the highest solubility, and the solubility decreased substantially from 0.72 to 0.15% as the degree of oxidation increased from 25 to 100%. Possibly, excessive incorporation of negative charges on chitosan resulted in the aggregation among 6-oxychitosan molecules by charge-charge interactions. The strongest cholic acid-retardation index (CRI, %) of highly soluble 25%-oxidized 6-oxychitosan was consistently observed until 24h of dialysis, which means the CRI is closely related to the water solubility of 6-oxychitosan. Therefore, the solubility improvement should be considered for enhancing the biological activity such as bile acid-binding capacity. Also, it was suggested that negative charge increase in chitosan structure above a certain level led to adverse effect on the binding capacity.

Alcohols↗

Surface complexation of condensed phosphate to aluminum hydroxide: an ATR-FTIR spectroscopic investigation.

Two model compounds, sodium pyrophosphate (pyro-P) and sodium tripolyphosphate (tripoly-P), were employed to elucidate the binding mechanisms of condensed phosphate on aluminum hydroxide by utilizing attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Peak assignments for the condensed phosphates in the solution phase and those adsorbed on the surface of aluminum hydroxide were made. Electron delocalization and polarization were employed to explain the peak shifts and the complexation of condensed phosphate with aluminum hydroxide. The tripoly-P and pyro-P were adsorbed on aluminum hydroxide by forming inner-sphere complexes. The adsorbed condensed phosphates were deprotonated in the pH range from 4 to 10. Monodentate, bidentate, and binuclear complexes were formed when pyro-P was adsorbed on aluminum hydroxide, while monodentate and binuclear complexes were formed when tripoly-P was adsorbed. Based on the FTIR data, we proposed that when either bidentate or binuclear complexes were formed, the two oxygen atoms participating in the complexation with aluminum hydroxide could not be originated from the same terminal phosphate moiety. The AlO bond formed in the complexation of pyro-P or tripoly-P with aluminum hydroxide (AlPO(-3)) was not as strong as the HO bond in terminal HPO(-3). The bridging PO(-2) of tripoly-P did not coordinate with aluminum hydroxide. The real-time ATR-FTIR study on condensed phosphate adsorption revealed that a long contact time between condensed phosphates and aluminum hydroxide particles can result in a transformation of an initially formed species into a thermodynamically more stable phase.

Adsorption↗

Influence of carrageenan on the rheology and skin permeation of microemulsion formulations.

Three different microemulsions (A-C) and one semisolid preparation D were investigated in terms of viscoelastic properties and skin permeation of the model compound sodium fluorescein. The influence of the polysaccharide carrageenan on these parameters was investigated. Carrageenan is frequently used as food additive and has very interesting properties like good adhesiveness on skin which can be a benefit for topical application. The viscoelastic properties of the preparations (A-D) and of mixtures with carrageenan (A'-D') were characterized by oscillatory measurements. It was possible to adjust the rheologic properties of the formulations and to increase the sodium fluorescein permeation through porcine skin by mixing them with carrageenan gels. Therefore, the presented formulations as well as mixtures with carrageenan might be promising alternative drug carrier systems for topical pharmaceutical as well as cosmetics.

Animals↗

Cytotoxic effects of activated bromine on human fetal osteoblasts in vitro.

Although sodium hypochlorite is routinely used as an irrigant, the scope and limitation of another hypohalide sodium hypobromite has not been adequately studied. The objective of this study was to compare the cytotoxic effects of sodium hypobromite and sodium hypochlorite on human osteoblasts by evaluating cell proliferation. One day after plating and every other day after that, cells were treated with a combination of sodium hypochlorite and sodium bromide, resulting into three molar ratios of activated sodium hypobromite. Positive control cells were not treated with hypohalides, while negative controls were separately treated with hypochlorite or bromide alone. Photomicrographic analysis of the cultures was done on days 1 and 6 of treatment. Trypsinized cells were counted to determine cell proliferation. Our results show that sodium bromide is more cytotoxic compared to sodium hypochlorite or activated sodium hypobromite. In activated sodium hypobromite, 4:1 molar ratio was less cytotoxic compared to other molar ratios.

Analysis of Variance↗