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Hemin binding to serum proteins and the catalysis of interprotein transfer.

The reaction of hemin (Hm) with human hemopexin (Hx) has been studied in a mixed dimethyl sulfoxide (Me2SO)-water solvent system and in aqueous caffeine solutions. In both media, the kinetics could be described by a single, second-order process: (formula - see text) with k = 1.8 X 10(6) M-1 s-1 in 40% Me2SO-water [pH 7.4, mu = 0.2 M (NaCl)] and k = 3.9 X 10(7) M-1 s-1 in water [pH 7.4 mu = 0.2 M (NaCl), [caffeine] = 0.025 M]. The reaction shows an ionic strength dependence consistent with a residual 1+ to 2+ charge in the vicinity of the binding region of the protein. The kinetics of the transfer of hemin from albumin to hemopexin (formula - see text) were studied as a function of concentration, ionic strength, pH, and temperature. In experiments conducted at 3 less than or equal to [Alb]0/[Hx]0 less than or equal to 20 where the transfer kinetics are first order, k' = 5 X 10(-3) S-1 at mu = 0.3 M (NaCl), pH 7.1; the reaction is strongly dependent on ionic strength and choice of electrolyte. The addition of imidazole catalyzes this transfer process via a ligand-mediated pathway with k' = 5 X 10(-3) + 21[Im]T2. At [Alb]0/[Hx]0 = 92, the noncatalyzed transfer reaction is second order. From the kinetic analysis of the reaction under these conditions, an estimate is made of the distribution of hemin between the two proteins at concentration levels which are characteristic of serum. The association of hemin and hemopexin is approximately 30 times faster than that of hemin and albumin, a finding consistent with the recycling function of hemopexin during heme transport to the liver parenchymal cells.

Blood Proteins↗

5-bromodeoxyuridine-induced amplification of prolactin gene in GH cells is an extrachromosomal event.

Treatment of a 5-bromodeoxyuridine-resistant (brdUrdr) and prolactin-nonproducing (Prl-) subclone of GH cells with this drug led to amplification of the prolactin (Prl) gene and induced Prl synthesis. Withdrawal of the drug treatment reversed both of these processes. In normal rats, the increased Prl synthesis observed during late pregnancy and lactation does not seem to be mediated via amplification of the gene. Amplification of the Prl gene and induction of Prl synthesis can also be observed in the Prl-, brdUrd-sensitive (brdUrds) GH cell strain. Prl gene amplification thus does not seem to be associated with the mechanism that confers the brdUrdr phenotype to these cells. brdUrd-induced amplification of the Prl gene can be identified with the low molecular weight, extrachromosomal, supernatant DNA fraction, isolated by Hirt's method. Southern blot analysis of Hirt's supernatant DNA (undigested) from brdUrd-treated cells generated a distinct band following hybridization with [32P]pDNAPrl-insert. The size of this band is greater than 23 kb but smaller than chromosomal DNA. Growth hormone (Gh) and albumin (Alb) gene sequences can be detected in the chromosomal DNA preparation but are absent in the extrachromosomal DNA prepared from Hirt's supernatant. The levels of Gh and Alb sequences are unaffected by brdUrd treatment of these cells. Results presented here suggest that in rat pituitary glands as well as in GH cells, hormonally controlled increased Prl synthesis is not caused by gene amplification. However, the brdUrd-induced expression of the Prl gene seems to be linked to the mechanism of drug-induced amplification of the Prl gene, mediated via an extrachromosomal event.

Animals↗

Lanthanum Nickel Silicides with the General Formula La(()(n)()(+1)()(n)()(+2))Ni(n)()(()(n)()(-)(1)+2)Si(n)()(()(n)()(+1)) and Other Series of Hexagonal Structures with Metal:Metalloid Ratios Close to 2:1.

The closely related crystal structures of the compounds La(6)Ni(2)Si(3) (La(12)Ni(4)Si(6), n = 2) and La(5)Ni(2)Si(3) (La(20)Ni(8)Si(12), n = 3) as well as those of the new compounds La(15)Ni(7)Si(10) (La(30)Ni(14)Si(20), n = 4) and La(21)Ni(11)Si(15) (La(42)Ni(22)Si(30), n = 5) were determined from single-crystal X-ray diffractometer data. In these hexagonal silicides (space group P6(3)/m) almost all atoms are situated on mirror planes, which extend perpendicular to the short c axes. The only exceptions are nickel atoms located on the 6(3) axes, which show some disorder resulting in the exact compositions La(6)Ni(1.54(2))Si(3) [a = 1224.3(1) pm, c = 438.3(1) pm, Z = 2, Ce(6)Ni(2)Si(3) type structure], La(5)Ni(1.75(1))Si(3) [a = 1624.4(3) pm, c = 434.2(2) pm, Z = 4, Ce(5)Ni(2)Si(3) type], La(15)Ni(6.62(2))Si(10) [a = 2021.2(3) pm, c = 435.1(1) pm, Z = 2, Pr(15)Ni(7)Si(10) type], and La(21)Ni(10.49(3))Si(15) [a = 2427.7(3) pm, c = 435.2(1) pm, Z = 2, a new structure type]. All of these structures have building elements which resemble the AlB(2) type structure. In these the lanthanum atoms correspond to the aluminum atoms of AlB(2), while the nickel and silicon atoms occupy the boron positions in an ordered manner. Other series of ternary hexagonal lanthanoid and actinoid transition metal silicides and phosphides, e.g., the series with the general formula R(n)()(()(n)()(-)(1))Ni(()(n)()(+1)()(n)()(+2))P(n)()(()(n)()(+1)+1) (R = Th, U), are briefly reviewed, and the systematics in the space groups and the diffraction patterns of these compounds are pointed out.

Journal Article↗

Structure determination of the 4d metal diborides: a quantum mechanical study.

Metal diborides (MB(2)) often have interesting thermal, mechanical, and superconducting properties. MgB(2) was put into focus some years ago for its high transition temperature (39 K) in combination with its simple AlB(2) structure. The boron structure in MB(2) is assumed to be dependent on the electron transfer from the nearby positioned metal atoms. An electronic and structural comparison has been performed here for various initially planar and puckered transition-metal borides, using quantum mechanical density functional theory (DFT) calculations under periodic boundary conditions. In comparison to MgB(2), the experimentally planar transition-metal diborides (ZrB(2), NbB(2), and MoB(2)) and the experimentally puckered ones (TcB(2), RuB(2), RhB(2), and PdB(2)) have been examined. The results indicate that the energetic stability generally follows the experimentally obtained results. The metals that are less electronegative than boron donate electrons to boron, which in turn induce planar boron structures (graphitic-like). The metals that prefer to be planar donate more than one electron, while the trend for metals which favor puckered B structures is that they donate less than one electron per metal atom. Two donated electrons per metal atom (or very close to) will result in the most stable AlB(2) structure.

Journal Article↗

Polymer-supported bisBINOL ligands for the immobilization of multicomponent asymmetric catalysts.

[reaction: see text] Polymer-supported bisBINOL ligands were successfully utilized for the immobilization of multicomponent asymmetric catalysts. The polymer-supported Al-Li-bis(binaphthoxide) (ALB) catalyst was more effective than the dendrimer-supported ALB in the Michael reaction of 2-cyclohexen-1-one with dibenzyl malonate affording the adduct in 91% yield with 96% ee. The polymer was also effective for the immobilization of a mu-oxodititanium complex that promoted carbonyl-ene reaction of ethyl glyoxalate with alpha-methyl styrene to provide the adduct with up to 98% ee.

Journal Article↗

Cadmium biomonitoring and renal dysfunction among a population environmentally exposed to cadmium from smelting in China (ChinaCad).

Cadmium, an environmental pollutant, can have adverse effects on the human body. The kidney is the critical organ. In order to improve the understanding of the dose-response relationship between cadmium exposure and health effects, and especially renal dysfunction, a study on a general population group in China was performed. This study was therefore concerned with cadmium exposure biomarkers, such as the concentrations in blood (BCd) and urine (UCd), and effect biomarkers of renal dysfunction, such as beta2-microglobulin (beta2m), retinol binding protein (RBP) and albumin (ALB). To improve the evaluation of exposure levels in relation to the adverse health effects of cadmium exposure in the general population, a quality control program was conducted to determine analytical quality in the determination of cadmium in blood and urine and for beta2m, creatinine, ALB and RBP. The measurements showed that analytical quality was adequate. The exposure and effect biomarkers were studied in the population groups living in three areas, namely a control area and two Cd polluted areas. In the highly exposed area, most of the BCd values were higher than 5 microg/l and most of the UCd values were higher than 5 microg/g creatinine. Beta2-microglobulin, retinol binding protein, and albumin in urine were all significantly higher in the population living in the heavily polluted area than in that in the control area. Based on data from all three areas, a marked dose-response relationship between UCd or BCd and the prevalence of renal dysfunction was demonstrated. The number of abnormalities in kidney was related to the level of cadmium exposure. Only one index of renal tubular dysfunction was affected in subjects exposed to low levels of cadmium, but more than two indices of renal function were affected in those exposed to high levels.

Air Pollutants↗

Evaluation of some cereals, plants and tubers through protein composition.

Wild and cultivated maize, sorghum, rice, amaranth, soybean, and cassava were screened for variability in seed storage proteins. Total seed proteins, albumin (Alb-1 and Alb-2), globulin, alcohol-soluble (A1 and A2), and glutelin (G1 and G2) fractions were investigated by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The comparison was done by the obtained protein patterns and their relative amounts. Using quantitative analysis of the protein composition and the electrophoretic patterns, the relationships between total proteins and amount of individual proteins were determined. Electrophoretic patterns of extracted proteins from investigated samples showed that the main protein subunits were concentrated between 10 and 45 kDa. Variation was found in major fractions and minor bands. Electrophoretic patterns of the protein fractions are directly related to the genetic background of the protein and can be identified and used to certify the genetic makeup of wild, cultivated, or newly derived cereals and plants.

Edible Grain↗

Environmental epidemiological study and estimation of benchmark dose for renal dysfunction in a cadmium-polluted area in China.

We have performed a study aimed at investigating the critical concentration of urinary cadmium (UCd) required for the development of renal dysfunction. We studied population groups (totally 790 persons) living in two cadmium exposed areas and one control area in China. UCd, was determined as an indicator of cadmium exposure and accumulation, while the concentrations of N-acetyl-beta-D-glucosaminidase (NAG), its iso-form B (NAG-B), beta2-microglobulin (B2M), retinol binding protein (RBP), and albumin (ALB) in urine were measured as indicators of the renal effects caused by cadmium. There was a significantly increased prevalence of hyperNAGuria, hyperNAG-Buria, hyperB2Muria, hyperRBPuria and hyperALBuria with increasing levels of Cd excretion in urine. We used the benchmark dose (BMD) procedure to estimate the critical concentration of urinary cadmium in this general population. The lower confidence limit of the BMD (LBMD-05) of urinary cadmium for a 5% level of risk above the background level was estimated for each of the renal effect indicators. The BMD-05/LBMD-05 were estimated to be 4.46/3.99, 6.70/5.87, 8.36/7.31, 7.98/6.98 and 15.06/12.18 microg/g creatinine for urinary NAG-B, NAG, B2M, RBP and ALB, respectively. Our findings suggest, based on the present study, that the Lower Confidence Limit of the Population Critical Concentration of UCd (LPCCUCd-05) of tubular dysfunction for 5% excess risk level above the background may be ca. 3-4 microg/g creatinine, and that cadmium concentration in urine should be kept below this level to prevent renal tubular damage. This report is the first to use the BMD method in this field and to define the concept of critical concentration in urine.

Acetylglucosaminidase↗

Hepatitis C virus replication in mice with chimeric human livers.

Lack of a small animal model of the human hepatitis C virus (HCV) has impeded development of antiviral therapies against this epidemic infection. By transplanting normal human hepatocytes into SCID mice carrying a plasminogen activator transgene (Alb-uPA), we generated mice with chimeric human livers. Homozygosity of Alb-uPA was associated with significantly higher levels of human hepatocyte engraftment, and these mice developed prolonged HCV infections with high viral titers after inoculation with infected human serum. Initial increases in total viral load were up to 1950-fold, with replication confirmed by detection of negative-strand viral RNA in transplanted livers. HCV viral proteins were localized to human hepatocyte nodules, and infection was serially passaged through three generations of mice confirming both synthesis and release of infectious viral particles. These chimeric mice represent the first murine model suitable for studying the human hepatitis C virus in vivo.

Animals↗

Prostaglandin-mediated loss of proteins during peritonitis in continuous ambulatory peritoneal dialysis.

The loss of proteins into the dialysate and the peritoneal generation of the immunoreactive prostanoids PGE2, 6-keto-PGF1 alpha, PGF2 alpha, and TXB2 were studied in 12 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) during 16 episodes of peritonitis and in inflammation-free periods. Protein permeability, defined as the ratio of dialysate/plasma protein (D/P), decreased with increasing molecular weight, independent of the condition of the peritoneum. With peritonitis a general rise of permeability was noticed for total protein (TP) and the individual proteins beta 2-microglobulin (beta MG), albumin (Alb), immunoglobulin G (IgG), and alpha 2-macroglobulin (alpha MG) (P less than 0.001). Simultaneously, an increase of dialysate prostanoids occurred with predominance of the vasodilative acting prostaglandins PGI2, determined as its metabolite 6-keto-PGF1 alpha, and PGE2 by factors of 8.4 and 9.7, respectively (P less than 0.001), in comparison to peritonitis-free control. In the early phase of peritonitis (0 to 12 hr after the onset of therapy) the augumented peritoneal prostaglandin synthesis correlated positively with the increased permeability of TP (r greater than or equal to 0.7446, P less than 0.01) and the individual proteins beta MG, Alb, IgG, and alpha MG (r greater than or equal to 0.5970, P less than 0.05). Inhibition of cyclo-oxigenase activity by local administration of indomethacin inhibited both the generation of 6-keto-PGF1 alpha and PGE2 by 39 and 42%, respectively (P less than 0.05), and the peritoneal loss of TP by 34% (P less than 0.05). In the absence of peritonitis indomethacin only diminished the synthesis of PGE2 whereas the generation of the other prostanoids remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Effect of the cytoskeletal fixation agent phalloidin on transcapillary albumin transport and interstitial fluid pressure in anaphylaxis in the wistar rat.

OBJECTIVE: Interstitial fluid pressure (P(if)) plays an important role in controlling interstitial fluid volume. In the early phase of rapid edema formation, such as in dextran-induced anaphylaxis in the Wistar rat, P(if) falls from -0.5 mm Hg to a value between -5 and -10 mm Hg. It is believed that P(if) is controlled by the interaction between connective tissue cells and the extracellular matrix. This hypothesis was tested by studying dextran-induced edema formation and the subsequent changes in P(if) in response to a pretreatment with phalloidin, a reagent that fixes the actin filaments within the cell. METHODS: P(if) was measured in anesthetized female Wistar rats by using a micropuncture technique. The rats were pretreated with phalloidin followed by dextran. Albumin extavasation (E(alb)) was measured as the extravascular space of (125)I-labeled human serum albumin (HSA) after 25 minutes. Total tissue water (TTW) was calculated as the difference between wet weight and dry weight divided by dry weight. Localization of phalloidin was determined histologically by using rhodamine-labeled phalloidin. RESULTS: Control P(if) values of -0.3 +/- 0.6 mm Hg dropped to -3.1 +/- 0.8 mm Hg after dextran treatment (p < 0.05). Pretreatment with phalloidin completely abolished this decrease in P(if), giving values of -0.6 +/- 0.2 mm Hg (p < 0.05, compared to dextran). The E(alb) in control rats of 0.02 +/- 0.02 mL/g DW increased to 1.35 +/- 0.43 mL/g DW after dextran treatment. Pretreatment with phalloidin before dextran treatment lowered the dextran value to 0.59 +/- 0.32 mL/g DW. CONCLUSION: This study shows that pretreatment with phalloidin, before the administration of dextran, abolishes the lowering of P(if) and edema formation, which is detected after i.v. injection of dextran alone.

Anaphylaxis↗

Linked markers exclude KIT as the gene responsible for appaloosa coat colour spotting patterns in horses.

The appaloosa coat colour pattern of the horse is similar to that caused by the rump-white (Rw) gene in the mouse. In the mouse Rw colour pattern is the result of an inversion involving the proto-oncogene c-kit (KIT). Therefore, we investigated KIT as a candidate gene that encodes the appaloosa coat colour gene (Lp) in horses. KIT plays a critical role in haematopoiesis, gametogenesis, and melanogenesis and encodes a transmembrane tyrosine kinase receptor that belongs to the PDGF/CSF-1/c-KIT receptor subfamily. Half-sib families segregating for Lp were uninformative for a reported polymorphism in KIT. However, KIT is located on horse chromosome 3 close to albumin (ALB), serum carboxylesterase (ES), vitamin D-binding protein (GC) and microsatellite markers ASB23, LEX007, LEX57, and UCDEQ437. Indeed, KIT and ASB23 were localized to ECA3q21-22.1 and 3q22.1-22.3, respectively, by fluorescent in situ hybridization. Family studies were conducted to investigate linkage of Lp to these markers using eight half-sib families in which Appaloosa stallions were mated to solid coloured mares. Linkage of Lp to the chromosome region containing ES, ALB, GC, ASB23, UCDEQ437, LEX57, and LEX007 was investigated by a multipoint linkage analysis using the computer program GENEHUNTER. LOD scores over the interval under investigation ranged from -4.28 to -12.48, with a score of -12.48 at the location for ASB23. Therefore, it was concluded that appaloosa (Lp) is not linked to any of the tested markers on ECA3, and thus Lp is unlikely to be the product of KIT.

Animals↗

Efficacy of co-administration of albendazole and diethylcarbamazine against geohelminthiases: a study from South India.

The efficacy of single-dose combination drug therapy with diethylcarbamazine (DEC) plus albendazole (ALB), and single-drug therapy with DEC alone against geohelminths was compared as part of a mass drug administration (MDA) for elimination of filariasis. This study was conducted in two blocks of Villupuram District of Tamil Nadu State, India, covering a population of 321 000 including about 100 000 children 1-15 years of age. Prevalence and intensity of geohelminth infection were determined by the Kato-Katz technique immediately before and 3 weeks after the MDA. A pre-treatment cross-sectional survey was undertaken in 18 statistically selected villages out of 204 villages, including 646 school children. About 60% were infected with one or more geohelminths. The overall prevalence rates were 53.9%, 12.4% and 5.7% for Ascaris lumbricoides, hookworms and Trichuris trichiura, respectively. Combination therapy (DEC + ALB) produced a cure rate of 74.3% and an egg reduction rate of 97.3% for geohelminths, which were higher than the corresponding rates (30.4% and 79.0%) observed in the single drug therapy arm with DEC alone. The odds of cure with combination therapy were significantly higher for roundworm (5.3 times) and hookworms (3.5 times), then odds of cure with DEC alone. Both therapies were equally effective against trichuriasis, recording cure rates >77% and egg reduction rates >83%. In combination therapy, 53.5% of the children noticed expulsion of worms after MDA, while in single drug therapy only 20.9% did. Our study indicated that MDA of combination therapy was operationally feasible at the community level, and it may secure higher community compliance because of its perceived benefits and enhanced efficacy against geohelminths than single-drug therapy.

Adolescent↗

Anti-Vel reactivity diminished by adsorption with rabbit RBC stroma.

BACKGROUND: An anti-Vel, nearly missed in antibody identification studies, and the effect of a commercially available rabbit RBC stroma (RESt, Immucor) adsorptions on eight anti-Vel sera are reported. Anti-Vel is an antibody to an antigen of high prevalence. CASE REPORT: A 48-year-old woman with chronic vaginal bleeding presented with a Hct of 14.7 percent. The transfusion service was not informed of her history of anti-Vel when she was transferred from another institution. Studies performed on an emergency request for transfusion were interpreted as a cold autoantibody as adsorption with a commercial source of RESt eliminated the reactivity. Stored anti-Vel sera were tested by titration studies before and after adsorption with commercial RESt. RESULTS: Serum from the index case did not react after adsorption with RESt at the transfusion service. Studies with the stored anti-Vel indicated antibody adsorption with four of four samples at immediate spin (IS) and room temperature (RT) phases, four of eight samples at 37 degrees C in albumin (ALB) phase, and four of eight samples at ALB-IgG-AGT phase. Variations in antibody reactivity were observed in the samples tested, but RESt adsorption diminished antibody reactivity in most samples. All eight stored sera demonstrated some reactivity in at least one phase after adsorption with RESt. CONCLUSION: Anti-Vel was completely or partially adsorbed by RESt. Caution should be used when interpreting cold agglutinins with this method. The manufacturer warns that uncommon alloantibodies may be adsorbed.

ABO Blood-Group System↗

Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients.

Hyperhomocysteinemia, a well-recognized cardiovascular risk factor, is frequent in hemodialysis (HD) patients. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C-->T substitution at nucleotide 677, is associated with homocysteine (Hcy) level elevation. We examined whether three factors involved in the methionine cycle could influence plasma Hcy concentrations in HD patients: MTHFR polymorphism; vitamin B12, an essential cofactor; and folate, the substrate. In a cross-sectional study, serum vitamin B12, folate, and plasma Hcy were measured and MTHFR genotyping was performed in 534 HD patients. Effects of MTHFR genotypes, vitamin B12, and folate on plasma Hcy levels were examined in 450 HD patients not administered vitamin B12 or folate. To examine the effect of vitamin B12 on plasma Hcy concentrations, we compared plasma Hcy concentrations in HD patients with and without vitamin B12 supplementation. To examine whether functional vitamin B12 deficiency exists even in HD patients with normal vitamin B12 concentrations, 15 HD patients (serum vitamin B12 concentrations, 250 to 2,100 pg/mL) were treated with vitamin B12 (mecobalamin, 1.5 mg/d) for 8 weeks. Serum concentrations of methylmalonic acid (MMA) and vitamin B12 were measured. Hcy levels were higher and folate levels were lower in patients with the TT and CT genotypes compared with patients with the CC genotype. Analysis of covariance to determine independent predictors of high Hcy levels identified low serum vitamin B12 and folate levels and high albumin (Alb) levels in CC-genotype patients, low folate levels and high Alb levels in CT-genotype patients, and low folate levels in TT-genotype patients. Plasma Hcy levels were lower in CC- and CT-genotype patients with vitamin B12 supplementation than in those without supplementation. Vitamin B12 supplementation for 8 weeks significantly reduced MMA concentrations in HD patients with normal serum vitamin B12 concentrations. These results indicate that MTHFR genotype influences the correlation of Hcy level with vitamin B12 and folate levels in HD patients. Functional vitamin B12 deficiency may exist, even in HD patients with normal vitamin B12 concentrations. The efficacy of vitamin B12 and folate supplementation on plasma Hcy levels may depend on MTHFR genotype.

Cross-Sectional Studies↗

Muscular mass assessed by ultrasonography after administration of low-dose corticosteroids and muscle relaxants in critically ill hemiplegic patients.

BACKGROUND AIMS: The present study investigates the influence of low-dose and short- term administration of corticosteroids and muscle relaxants on the muscular mass (MM) in hemiplegic ICU patients, with the aid of ultrasonography (U/S). METHODS: Thirty-seven patients hospitalised in the ICU for 18.6+/-3.6 days, were included in the study. Sixteen patients did not receive either drug (group A), five patients received dexamethasone (24 mg/day) for 4 days (group B), eight patients received dexamethasone (24 mg/day) for 4 days and atracurium (0.3-0.6 mg/kg/h) for 2.8+/-0.4 days (group C), whereas eight other non-hemiplegic ICU patients comprised the control group. MM was measured in cm by U/S and serum Albumin (ALB, g/l) at the first and the tenth ICU hospitalisation day. The corresponding differences (DeltaMM, DeltaALB) were compared between the four groups of patients. RESULTS: MM and ALB decreased significantly in all groups. DeltaMM was significantly higher in group C in comparison to all other groups, while DeltaMM was also higher in group B, when compared to the control and A groups. DeltaALB did not show significant inter-group differences. DeltaMM was significantly related to patients' age (r=0.41,P =0.001). CONCLUSIONS: Muscular atrophy of the ICU hemiplegic patients is significantly influenced by the synchronous treatment with muscle relaxants and corticosteroids at low doses and for short term. This myopathy should be taken into account for the better prognosis and the safer outcome of the patient and U/S is suitable for accurate and non-invasive monitoring of MM.

APACHE↗

[Effects of a regional intervention to promote asthma guidelines implementation].

AIM: Despite of asthma guidelines existing for years, secondary data analysis shows insufficient medical care of asthmatics in Germany. The aim of the present study was to improve asthma guideline adherence by promoting guidelines implementation. METHOD: We analyzed prospectively pre- and post-interventional medical care of a sample of 127 asthmatics who were recruited by physicians working in ambulatory care and in hospitals of the Region Neckar-Alb, Germany. Data came primarily from patient interviews by phone. Our intervention to promote guidelines implementation consisted of following methods: 1. analyzing regional asthma care followed by a feedback performance report to physicians; 2. delivering asthma patient diaries and peak flow meters to study patients; 3. developing and adapting regionally asthma guidelines for adult asthmatics in the Region of Neckar-Alb; 4. promoting guidelines utilization by publishing the adapted guidelines in a scientific journal, direct mailing of a short version to the practitioners, and boosting the guidelines at regional CE meetings; 5. reanalyzing asthma care of the study cohort and the implementation of the guidelines 13 months after the beginning of the intervention. We studied the effect of the intervention using a qualitative model comprising 18 quality indicators measuring the proportion of patients who were treated in accordance to the guidelines. To compare pre- and post-interventional proportions we used the McNemar test for statistical analysis. RESULTS: The proportion of asthmatics treated in accordance to the guidelines improved significantly from 48 % to 57 %. The increase was mainly due to an improvement of guidelines adherence within the field of promoting asthma self-management and continuous monitoring of patients (42 % pre- and 57 % post-intervention), whereas guidelines adherence in pharmacotherapy improved only from 53 % to 56 %. CONCLUSION: The proportion of asthmatics treated in accordance to guidelines can be improved by using a multifaceted regional approach to promote guidelines implementation.

Adult↗

Alterations in antioxidant status during neonatal sepsis.

Septicaemia is a major threat to survival during the early stages of life. There are several reports that suggest that reactive oxygen species (ROs) play a role in a wide variety of diseases. We estimated the activity of xanthine oxidase (XO), malondialdehyde (MDA) content, creatine phosphokinase (CPK) activity, activities of key enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and peroxidase (PO), and non-enzymatic antioxidants, viz. uric acid (UA) and albumin (ALB), in 30 neonates with sepsis and 20 age-matched controls. The babies were categorized as preterm/term, early onset/late onset, and shock/without shock, as per clinical and laboratory investigations. The study was carried out to evaluate the status of antioxidant enzymes and non-enzymatic antioxidants with a view to suggesting the introduction of antioxidant therapy in neonatal sepsis. The activities of serum XO, CPK, SOD and GPx, and the content of MDA were found to be significantly elevated in the neonates with sepsis when compared with controls. Conversely, the activity of PO and the levels of UA and ALB were decreased. The septic, full-term neonates registered significantly higher CPK activity (70%) than the preterm septic neonates. However, infants with late-onset and shock sepsis had a significant decrease in CPK activity (p < 0.05) compared with their corresponding sub-groups. Likewise, UA levels were found to be 28% depressed (p < 0.05) in the babies with late-onset sepsis and 51% increased (p < 0.001) in babies with shock compared with their respective sub-groups. Neonates with septic shock also registered a significant elevation in GPx activity (28%) compared with those without shock. This study suggests increased production of ROs in neonates with sepsis, as evidenced by the positive regulation of XO, SOD and GPx activity. The elevation of antioxidant enzymes, however, was not so effective as to protect from cellular damage and thereby result in higher MDA production. It is evident that antioxidant therapy might be useful in the management of neonates with sepsis but further detailed clinico-biochemical investigations are required to define effective antioxidant therapy.

Antioxidants↗