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PubMed2004

Feasibility of quantitative ultrasound measurements on the humerus of newborn infants for the assessment of the skeletal status.

Quantitative ultrasound (QUS), although widely used in adults has, so far, been scarcely employed in newborn infants and children. This study aimed to evaluate the feasibility of the use of QUS in newborn children and the factors influencing QUS parameters. In 140 consecutive healthy full-term newborn babies (76 male and 64 female; gestational age: 39.5 +/- 1.5 weeks) QUS parameters were assessed within 3 days of the child's birth at the distal diaphysis of the humerus by use of Bone Profiler, after an appropriate modification of caliper and software. In all subjects we evaluated the amplitude-dependent speed of sound (AD-SoS) (meters per second), the characterizing graphic trace parameters [signal dynamic (SDy), fast wave amplitude (FWA) and bone transmission time (BTT)], SoS (meters per second), that is, the speed of sound calculated on the first peak, and hBTT, that is, the interval time between the first peak of the ultrasound and when this reaches the speed of 1,570 m/s, which is the velocity of ultrasound in the soft tissue. This latter parameter allows one to measure bone tissue independently of soft tissue. QUS measurements were also performed at the phalanges on all mothers (age range 24-38 years), who also completed a self-report questionnaire on their obstetric history, smoking and dietary habits and family history of osteoporosis. In 73 mothers and their children QUS was repeated after 12 months. All QUS parameters were slightly higher in male than in female newborn infants but the difference was not significant. BTT and hBTT of neonates showed a significant relationship with birth weight (r = 0.20; P < 0.05 and r = 0.37; P < 0.01, respectively) and with cranial circumference (r = 0.22; P < 0.05 and r = 0.36; P < 0.01, respectively). In newborn infants none of the QUS parameters was significantly influenced by maternal QUS or by maternal smoking and calcium intake. In a model of multiple regression analysis the cranial circumference was the only parameter entered into the model, explaining approximately 15% of hBTT value. At month 12 AD-SoS and SoS were slightly lower than at birth (-11% and -0.1%, respectively), whereas both BTT and hBTT showed a significant (P < 0001) increase. The present study demonstrated the feasibility of the use of QUS, as assessed by a new measurement approach at the humerus, in the evaluation of skeletal status in neonates. BTT and, above all, hBTT, appears to be the best parameter for both evaluation of skeletal status at birth and monitoring of bone growth in the first year of life.

Adult↗

PubMed2002

Constitutive activity of G-protein-coupled receptors: cause of disease and common property of wild-type receptors.

The aim of this review is to provide a systematic overview on constitutively active G-protein-coupled receptors (GPCRs), a rapidly evolving area in signal transduction research. We will discuss mechanisms, pharmacological tools and methodological approaches to analyze constitutive activity. The two-state model defines constitutive activity as the ability of a GPCR to undergo agonist-independent isomerization from an inactive (R) state to an active (R*) state. While the two-state model explains basic concepts of constitutive GPCR activity and inverse agonism, there is increasing evidence for multiple active GPCR conformations with distinct biological activities. As a result of constitutive GPCR activity, basal G-protein activity increases. Until now, constitutive activity has been observed for more than 60 wild-type GPCRs from the families 1-3 and from different species including humans and commonly used laboratory animal species. Additionally, several naturally occurring and disease-causing GPCR mutants with increased constitutive activity relative to wild-type GPCRs have been identified. Alternative splicing, RNA editing, polymorphisms within a given species, species variants and coupling to specific G-proteins all modulate the constitutive activity of GPCRs, providing multiple regulatory switches to fine-tune basal cellular activities. The most important pharmacological tools to analyze constitutive activity are inverse agonists and Na(+) that stabilize the R state, and pertussis toxin that uncouples GPCRs from G(i)/G(o)-proteins. Constitutive activity is observed at low and high GPCR expression levels, in native systems and in recombinant systems, and has been reported for GPCRs coupled to G(s)-, G(i)- and G(q)-proteins. Constitutive activity of neurotransmitter GPCRs may provide a tonic support for basal neuronal activity. For the majority of GPCRs known to be constitutively active, inverse agonists have already been identified. Inverse agonists may be useful in the treatment of neuropsychiatric and cardiovascular diseases and of diseases caused by constitutively active GPCR mutants.

Animals↗

PubMed2005

Association of body composition and physical activity with proximal femur geometry in middle-aged and elderly Afro-Caribbean men: the Tobago bone health study.

Osteoporotic fractures are less prevalent in African Americans than in caucasians, possibly because of differences in bone structural strength. Bone structural adaptation can be attributed to changes in load, crudely measured as lean and fat mass throughout life. The purpose of this analysis was to describe the associations of leg lean mass, total body fat mass, and hours walked per week with femoral bone mineral density (BMD) and bone geometry in a cross-sectional sample of 1,748 men of African descent between the ages of 40 and 79 years. BMD, section modulus (Z), cross-sectional area (CSA), and subperiosteal width were measured from dual energy X-ray absortiometry (DXA) scans using the hip structural analysis (HSA) program. Multiple linear regression models explained 35% to 48% of the variance in bending (Z) and axial (CSA) strength at the femoral neck and shaft. Independent of all covariates including total body fat mass, one standard deviation increase in leg lean mass was significantly associated with a 5% to 8% higher Z, CSA, and BMD (P < 0.010) at the neck and shaft. The number of hours walked per week was not a strong or consistent independent predictor of bone geometry or BMD. We have shown that weight is the strongest independent predictor of femur BMD and geometric strength although the effect appears to be mediated by lean mass since leg lean mass fraction and total body fat mass fraction had significant and opposing effects at the narrow neck and shaft in this group of middle aged and elderly men.

Absorptiometry, Photon↗

PubMed2005

Microbial assemblages in soil microbial succession after glacial retreat in Svalbard (high arctic).

Microbial community composition (cyanobacteria and eukaryotic microalgae abundance and diversity, bacterial abundance, and soil respiration) was studied in subglacial and periglacial habitats on five glaciers near Ny-Alesund, Svalbard (79 degrees N). Soil microbial communities from nonvegetated sites (subglacial, recently deglaciated, and cryoconite sediments) and sites with plant cover (deglaciated some hundreds of years ago) were analyzed. Physicochemical analyses (pH, texture, water content, organic matter, total C and N content) were also performed on the samples. In total, 57 taxa of 23 genera of cyanobacteriaand algae were identified. Algae from the class Chlorophyceae (25 species) and cyanobacteria (23 species) were richest in biodiversity. The numbers of identified species in single habitat types were 23 in subglacial, 39 inbarren, 22 in cryoconite, and 24 in vegetated soils. The highest cyanobacterial and algal biovolume and cell numbers, respectively, were present in cryoconite (13x10(4) microm3 mg-1 soil and 508 cells per mg of soil), followed by barren (5.7x10(4) and 188), vegetated (2.6x10(4) and 120), and subglacial (0.1x10(4) and 5) soils. Cyanobacteria prevailed in all soil samples. Algae (mainly green algae) were present only as accessory organisms. The density of bacteria showed a slightly different trend to that of the cyanobacterial and algal assemblages. The highest number of bacteria was present in vegetated (mean: 13,722x10(8) cells per mg of soil dry wt.), followed by cryoconite (3802x10(8)), barren (654x10(8)), and subglacial (78x10(8)) soils. Response of cyanobacteria and algae to physical parameters showed that soil texture and water content are important for biomass development. In addition, it is shown that nitrogen and water content are the main factors affecting bacterial abundance and overall soil respiration. Redundancy analysis (RDA) with forward selection was used to create a model explaining variability in cyanobacterial, algal, and bacterial abundance. Cryoconites accounted for most of the variation in cyanobacteria and algae biovolume, followed by barren soils. Oscillatoriales, desmids, and green coccoid algae preferred cryoconites, whereas Nostocales and Chroococcales occurred mostly in barren soils. From the data obtained, it is evident that of the studied habitats cryoconite sediments are the most suitable ones for the development of microbial assemblages. Although subglacial sediments do not provide as good conditions as cryoconites, they support the survival of microbial communities. Both mentioned habitats are potential sources for the microbial recolonization of freshly deglaciated soil after the glacier retreat.

Arctic Regions↗

PubMed2006

The bovine seminal plasma protein PDC-109 extracts phosphorylcholine-containing lipids from the outer membrane leaflet.

The bovine seminal plasma protein PDC-109 modulates the maturation of bull sperm cells by removing lipids, mainly phosphatidylcholine and cholesterol, from their cellular membrane. Here, we have characterized the process of extraction of endogenous phospholipids and of their respective analogues. By measuring the PDC-109-mediated release of fluorescent phospholipid analogues from lipid vesicles and from biological membranes (human erythrocytes, bovine epididymal sperm cells), we showed that PDC-109 extracts phospholipids with a phosphorylcholine headgroup mainly from the outer leaflet of these membranes. The ability of PDC-109 to extract endogenous phospholipids from epididymal sperm cells was followed by mass spectrometry, which allowed us to characterize the fatty acid pattern of the released lipids. From these cells, PDC-109 extracted phosphatidylcholine and sphingomyelin that contained an enrichment of mono- and di-unsaturated fatty acids as well as short-chain and lyso-phosphatidylcholine species. Based on the results, a model explaining the phospholipid specificity of PDC-109-mediated lipid release is presented.

Animals↗

PubMed2005

Gene activation and deactivation related changes in the three-dimensional structure of chromatin.

Chromatin in the interphase nucleus is dynamic, decondensing where genes are activated and condensing where they are silenced. Local chromatin remodelling to a more open structure during gene activation is followed by changes in nucleosome distribution through the action of the transcriptional machinery. This leads to chromatin expansion and looping out of whole genomic regions. Such chromatin loops can extend beyond the chromosome territory. As several studies point to the location of transcription sites inside chromosome territories as well as at their periphery, extraterritorial loops cannot simply be a mechanism for making transcribed genes accessible to the transcriptional machinery and must occur for other reasons. The level of decondensation within an activated region varies greatly and probably depends on the density of activated genes and the number of engaged RNA polymerases. Genes that are silenced during development form a more closed chromatin structure. Specific histone modifications are correlated with gene activation and silencing, and silenced genes may become associated with heterochromatin protein 1 homologues or with polycomb group complexes. Several levels of chromatin packaging are found in the nucleus relating to the different functions of and performed by active genes; euchromatic and heterochromatic regions and the models explaining higher-order chromatin structure are still disputed.

Animals↗

PubMed2005

Health-related and work-related aspects associated with sick leave: a comparison of chronically ill and non-chronically ill workers.

OBJECTIVES: Our aims were to study to what extent chronically ill workers (CIWs) take more sick leave than non-chronically ill workers (NCIWs) and to explore which health-related and work-related aspects are associated with the sick leave patterns of the two groups. METHODS: A questionnaire on work, health and sick leave was sent to all employees of a university in The Netherlands (response: 49.1%). Analyses were conducted for 444 CIWs and 1,347 NCIWs. Odds ratios (ORs) were calculated to quantify the contribution of being chronically ill to sick leave in general, frequent sick leave, prolonged sick leave, and present sick leave. The contributions of health-related and work-related aspects to sick leave were investigated by multiple logistic regression analyses for both CIWs and NCIWs separately. RESULTS: CIWs showed significantly increased ORs for general, frequent, prolonged and present sick leave when compared with NCIWs. Fatigue, emotional exhaustion and perceived health complaints showed stronger associations with sick leave for both CIWs and NCIWs than various work-related aspects. Workers of 46 years of age and older showed less sick leave than workers under the age of 36. Male respondents and scientific personnel showed less frequent sick leave than the other respondents, and so did respondents working more than 40 h a week, compared with part-timers. The final regression models explained 8%-16% of the variance in sick leave. CONCLUSIONS: CIWs take two to three times more and longer sick leave than NCIWs. Health-related aspects are more strongly associated with sick leave than work-related aspects for both CIWs and NCIWs. Sick leave patterns were, nevertheless, only partly explained by health-related and work-related aspects. In any case, future studies of sick leave should certainly take the presence of chronic disease into account as an important determinant of sick leave.

Adult↗

PubMed2004

Role of cytokinin in the regulation of root gravitropism.

The models explaining root gravitropism propose that the growth response of plants to gravity is regulated by asymmetric distribution of auxin (indole-3-acetic acid, IAA). Since cytokinin has a negative regulatory role in root growth, we suspected that it might function as an inhibitor of tropic root elongation during gravity response. Therefore, we examined the free-bioactive-cytokinin-dependent ARR5::GUS expression pattern in root tips of transformants of Arabidopsis thaliana (L.) Heynh., visualized high cytokinin concentrations in the root cap with specific monoclonal antibodies, and complemented the analyses by external application of cytokinin. Our findings show that mainly the statocytes of the cap produce cytokinin, which may contribute to the regulation of root gravitropism. The homogenous symmetric expression of the cytokinin-responsive promoter in vertical root caps rapidly changed within less than 30 min of gravistimulation into an asymmetrical activation pattern, visualized as a lateral, distinctly stained, concentrated spot on the new lower root side of the cap cells. This asymmetric cytokinin distribution obviously caused initiation of a downward curvature near the root apex during the early rapid phase of gravity response, by inhibiting elongation at the lower side and promoting growth at the upper side of the distal elongation zone closely behind the root cap. Exogenous cytokinin applied to vertical roots induced root bending towards the application site, confirming the suspected inhibitory effect of cytokinin in root gravitropism. Our results suggest that the early root graviresponse is controlled by cytokinin. We conclude that both cytokinin and auxin are key hormones that regulate root gravitropism.

Arabidopsis↗

PubMed2005

Characterization of candidate class A, B and E floral homeotic genes from the perianthless basal angiosperm Chloranthus spicatus (Chloranthaceae).

The classic ABC model explains the activities of each class of floral homeotic genes in specifying the identity of floral organs. Thus, changes in these genes may underlay the origin of floral diversity during evolution. In this study, three MADS-box genes were isolated from the perianthless basal angiosperm Chloranthus spicatus. Sequence and phylogenetic analyses revealed that they are AP1-like, AP3-like and SEP3-like genes, and hence these genes were termed CsAP1, CsAP3 and CsSEP3, respectively. Due to these assignments, they represent candidate class A, class B and class E genes, respectively. Expression patterns suggest that the CsAP1, CsAP3 and CsSEP3 genes function during flower development of C. spicatus. CsAP1 is expressed broadly in the flower, which may reflect the ancestral function of SQUA-like genes in the specification of inflorescence and floral meristems rather than in patterning of the flower. CsAP3 is exclusively expressed in male floral organs, providing the evidence that AP3-like genes have ancestral function in differentiation between male and female reproductive organs. CsSEP3 expression is not detectable in spike meristems, but its mRNA accumulates throughout the flower, supporting the view that SEP-like genes have conserved expression pattern and function throughout angiosperm. Studies of synonymous vs nonsynonymous nucleotide substitutions indicate that these genes have not evolved under changes in evolutionary forces. All the data above suggest that the genes may have maintained at least some ancestral functions despite the lack of perianth in the flowers of C. spicatus.

Amino Acid Sequence↗

PubMed2005

Sapling growth as a function of light and landscape-level variation in soil water and foliar nitrogen in Northern Michigan.

Interspecific differences in sapling growth responses to soil resources could influence species distributions across soil resource gradients. I calibrated models of radial growth as a function of light intensity and landscape-level variation in soil water and foliar N for saplings of four canopy tree species, which differ in adult distributions across soil resource gradients. Model formulations, characterizing different resource effects and modes of influencing growth, were compared based on relative empirical support using Akaike's Information Criterion. Contrary to expectation, the radial growth of species associated with lower fertility (Acer rubrum and Quercus rubra) was more sensitive to variation in soil resources than the high fertility species Acer saccharum. Moreover, there was no species tradeoff between growth under high foliar N versus growth under low foliar N, which would be expected if growth responses to foliar N mediated distributions. In general, there was functional consistency among species in growth responses to light, foliar N, and soil water availability, respectively. Foliar N influenced primarily high-light growth in F. grandifolia, A. rubrum, and Q. rubra (but was not significant for A. saccharum). In A. saccharum and A. rubrum, for which soil water availability was a significant predictor, soil water and light availability simultaneously limited growth (i.e., either higher light or water increased growth). Simple resource-based models explained 0.74-0.90 of growth variance, indicating a high degree of determinism. Results suggest that nitrogen effects on forest dynamics would be strongest in high-light early successional communities but that water availability influences growth in both early successional and understory environments.

Ecosystem↗

PubMed2006

Magnetization influence on the performance of ferrosoferric oxide: polyacrylonitrile membranes in ultrafiltration of pig blood solution.

Three kinds of membranes were prepared from suspensions containing polyacrylonitrile, dimethyl sulfoxide, polyethylene glycol and different amount of Fe3O4 by the phase inversion process. The rejection rate and the flux of membrane were investigated in the filtration of pig blood solution. SEM also studied the morphologies of fouled membranes. The permeate flux and the rejection rate decline fast in the initial several minutes and then change slowly. The magnetized membrane has a higher flux and a relative flux than the corresponding non-magnetized membrane. And the magnetized membrane containing about 3 wt% Fe3O4 has a prominent anti-fouling performance with above 52% relative flux. The results indicate that the magnetized ferrosoferric oxide-polyacrylonitrile membranes are promising in the recovery of blood proteins in the slaughterhouse effluents. In addition, the hydraulic resistance model explained results and the fouling mechanism was also given.

Acrylic Resins↗

PubMed2005

Prevalence and associated factors for temporomandibular disorders in a group of Mexican adolescents and youth adults.

The objective of the study was to determine the prevalence and associated factors for temporomandibular disorders (TMD) in a university sample of Campeche, Mexico. A cross-sectional study was carried out in 506 subjects aged 14-25 years. The subjects were requested to answer questionnaires concerning sociodemographic variables, history of stress, lifestyle, and anxiety. The Research Diagnostic Criteria for TMD (RDC/TMD) was used as TMD diagnostic system by four examiners capacitated and standardized. Data were analyzed using binary logistic regression in STATA. The results showed that 46.1% of the subjects exhibited some grade of TMD. Logistic regression analysis with TMD as the dependent variable identified sex (women odds ratio [OR]=1.7), bruxism (OR=1.5), anxiety (OR=1.6), unilateral chewing (OR=1.5), and an interaction between number of tooth loss and stress as the most significant associated variables, thus (1) the effect of having high levels of stress in the group of subjects without tooth loss (OR=1.2; 95% confidence interval [CI]=0.7-1.8) and (2) the effect of having high levels of stress in the group of subjects with at least one tooth lost (OR=2.4; 95% CI=1.01-5.9). The variables associated with diagnosis of pain were principally psychosocial (stress and anxiety), whereas for the non-pain diagnosis group, the variables were clinical, such as bruxism, chewing site preference, and restorations in mouth. We found associations among variables that were similar to findings in other studies, such as bruxism, tooth loss, stress, and anxiety. The final model explains that the effect of stress on TMD depends of the tooth loss, controlling for sex, bruxism, unilateral chewing, and anxiety. Finally, it can be concluded that the variables associated with pain and non-pain diagnosis were of distinct nature.

Adolescent↗

PubMed2006

Effects of methylmalonyl-CoA mutase gene knockouts on erythromycin production in carbohydrate-based and oil-based fermentations of Saccharopolyspora erythraea.

In carbohydrate-based fermentations of Saccharopolyspora erythraea, a polar knockout of the methylmalonyl-CoA mutase (MCM) gene, mutB, improved erythromycin production an average of 126% (within the range of 102-153% for a 0.95 confidence interval). In oil-based fermentations, where erythromycin production by the wild-type strain averages 184% higher (141-236%, 0.95 CI) than in carbohydrate-based fermentations, the same polar knockout in mutB surprisingly reduced erythromycin production by 66% (53-76%, 0.95 CI). A metabolic model is proposed where in carbohydrate-based fermentations MCM acts as a drain on the methylmalonyl-CoA metabolite pool, and in oil-based fermentations, MCM acts in the reverse direction to fill the methylmalonyl-CoA pool. Therefore, the model explains, in part, how the well-known oil-based process improvement for erythromycin production operates at the biochemical level; furthermore, it illustrates how the mutB erythromycin strain improvement mutation operates at the genetic level in carbohydrate-based fermentations.

Bacterial Proteins↗

PubMed2006

I can use a condom, i just don't: the importance of motivation to prevent HIV in adolescent seeking psychiatric care.

Youth continue to show high HIV infection rates, and adolescents with mental health problems are especially at risk. We used longitudinal data to test a cognitive-behavioral model of risky sexual behavior among 175, ethnically diverse urban adolescents seeking mental health services. Path analyses of the cross-sectional data revealed that Motivation was a strong predictor of Behavioral Skills and Sexual Risk Taking. The model explained 42% of the variance in Sexual Risk Taking with age included-29% without age. In the longitudinal path analyses, Motivation had a significant negative effect on levels of Sexual Risk Taking 6 months later, controlling for Information, Behavioral Skills, age, and baseline levels of Sexual Risk Taking. These longitudinal effects explained 60% of the variance in Sexual Risk Taking. These results underscore the need to address motivational factors in HIV prevention programs designed for adolescents with mental health problems.

Adolescent↗

PubMed2006

Evaluation of resistance pattern to fenpyroximate and pyridaben in Tetranychus urticae collected from greenhouses and apple orchards using lethal concentration-slope relationship.

This study aimed to monitor the present and future developments of the resistance of Tetranychus urticae Koch to fenpyroximate and pyridaben, using the relationship of the LC(50) and slope of the concentration-mortality line in a probit model, for the provision of reliable resistance management tactics. Tetranychus urticae populations were collected from 16 commercial greenhouses, where various crops were cultivated, as well as from 10 apple orchards throughout Korea. The resistance to fenpyroximate and pyridaben of each population was estimated by calculating the median lethal concentration (LC(50)), resistance ratio (RR) and slope of the concentration-mortality regression. Most of the greenhouse populations exhibited moderate levels of resistance, whereas the apple orchard populations showed only low levels, indicating that T. urticae populations in greenhouses were more strongly selected than those in apple orchards. Four population groups were established based on either the habitats (greenhouse and apple orchard) or acaricides (fenpyroximate and pyridaben). To test the hypothesis, "the slope is greatest at low and high levels of resistance," the slopes were regressed as a function of the LC(50), and fitted to a polynomial regression. The polynomial regression model explained this relationship well for the four population groups (p < 0.05), indicating that the development of resistance toward fenpyroximate or pyridaben was consistent with the gradient. A laboratory selection study agreed with the results from both acaricide field populations. These results suggest that the gradient was a good indicator of the susceptibility of T. urticae to genetic variations, which was related to the LC(50). The application of these findings is also discussed in relation to the resistance management of T. urticae.

Animals↗

PubMed2006

Distribution and statistical analysis of leachable and total heavy metals in the sediments of the Suez Gulf.

The concentrations of nine heavy metals (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pd and Zn) in the labile and total fractions of muddy and sandy sediment samples collected from twelve sites in Suez Gulf during April 1999 were studied to evaluate the pollution status of the Suez Gulf. The enrichment factors (EF) for each element were calculated. There are extremely high concentrations of Cd, Ni, Pb and slightly concentration of Cr and Cu in both muddy and sandy sediments. The concentration of Zn was moderately high and can be considered as seriously contaminate Metal pollution index (MPI) shows high values ranged between 46 to 156 and 40 to 232 for both sandy and muddy sediments, respectively. Concentrations of heavy metals were normalized against iron for total fraction in both of sandy and muddy sediments. Principal component analysis (PCA) was studied on the data matrix obtained and represented three-factor model explaining 92.22% for labile and 88.82% for total fractions of muddy sediment. The main source of contamination is the offshore oil fields and industrial wastes. This is largely a result of ineffective and inefficient operation equipment, illegal discharge of dirty ballast water from tankers and lack of supervision and prosecution of offenders.

Environmental Monitoring↗

PubMed2005

Pharmacokinetics of ricobendazole after its intravenous, intraruminal and subcutaneous administration in sheep.

Ricobendazole (RBZ) was administered in sheep at the dose rate of 5 mg/kg by intravenous (i.v.) route as a 10% experimental solution, by the intraruminal (i.r.) route as a 10% experimental suspension, and by the subcutaneous (s.c.) route as a 10% commercial formulation available in Argentina. Blood samples were drawn during a 60 h period. Plasma concentrations of RBZ and its inactive metabolite albendazole sulphone (ABZSO2) were determined by high-performance liquid chromatography. The pharmacokinetic parameters were determined by compartmental analysis. The fitting of the data was done by weighted least-squares non-linear regression analysis. The pharmacokinetic parameters were estimated for every animal by simultaneous fitting of the plasma concentrations profiles of RBZ obtained after its administration by the three routes. The kinetic analysis of ABZSO2 was performed by a statistical moment approach. Ricobendazole bioavailability was poor after i.r. administration, whereas high and sustained plasma concentrations and higher bioavailability were obtained after s.c. administration. A simple two-compartment open model explains in a mechanical sense the pharmacokinetic behaviour of RBZ in sheep and allows us to estimate the real first-order constant rate of absorption and the loss of drug from the absorption site after its administration by s.c. and i.r. routes.

Albendazole↗

PubMed1978

Membrane-bound cooperative enzymes. Stokes' radii, Hill plots and membrane fluidity in the regulation of adenosinetriphosphatase from Escherichia coli.

The soluble Ca2+-ATPase from Escherichia coli had a distinctive behavior with respect to inhibition by Na+ measured at 36 degrees C and 19 degrees C. At the first temperature the Hill plots are linear and show a slope of 1.1 while at 19 degrees C the plots are biphasic, with slopes of 1.8 and 0.8 before and after the break, respectively. The break occurs at about 50 nM NaCl. Gel chromatography was performed in jacketed Sepharose 4B columns kept at 2 temperatures in the presence of different concentrations of NaCl. It was found that the Stokes' radius of the enzyme was dependent on the temperature and on the salt concentration. Equilibrium sucrose gradients run at 19 degrees C showed that the sedimentation constant of the enzyme remained constant irrespective of the NaCl concentration used. It is concluded that a "folding" of the enzyme takes place in the presence of NaCl, the process being complete at about 50 mM NaCl at 19 degrees C and at about 20 mM at 36 degrees C. The results are in excellent agreement with the kinetic data: the "folded" or "compact" configuration would show no cooperative response towards Na+ while the "expanded" conformer would present strong cooperativity. This is also in agreement with the results obtained with the enzyme embedded in the membrane: when the membrane is fluid a high n value (Hill coefficient) is found; when the membrane is more rigid the value of n falls. A model explaining all our results is proposed and discussed.

Adenosine Triphosphatases↗