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PubMed1987

Lysosomal cystine transport in cystinosis variants and their parents.

Children with nephropathic cystinosis store 50 to 100 times normal amounts of free cystine in many cells and display negligible lysosomal cystine transport in their leucocytes and cultured fibroblasts. A patient with intermediate (adolescent) cystinosis exhibited a similar deficiency of egress out of fibroblast lysosome-rich granular fractions. Another individual with benign (adult) cystinosis accumulated only 2.85 nmol 1/2 cystine/mg leucocyte protein, or 20-50% of the amount stored in nephropathic cystinosis leucocytes. His leucocyte granular fractions also displayed substantial residual cystine-carrying capacity, as determined by measurement of lysosomal cystine counter-transport. We conclude that the variant forms of cystinosis represent a continuum of lysosomal cystine storage, with the varied clinical presentation depending on the amount of residual cystine-carrying capacity, genetic predispositions, and differential tissue susceptibilities.

Adult↗

PubMed2001

Work profile and functional capacity of formwork carpenters at construction sites.

PURPOSE: This study established a work profile and functional capacity for formwork carpenters (FCs) working at construction sites. METHOD: Thirty male FCs aged 19-45 were recruited by convenient sampling from the construction training centres. All FCs participated in an interview/questionnaire and a standardized functional capacity evaluation (FCE) using the Baltimore Therapeutic Equipment Primus (BTE Primus) and Valpar Component Work Sample (VALPAR19). Thirty male adults (office workers) aged 19-45 participated in the exact FCE for comparison. RESULTS: The results of the questionnaire indicated that the job demands of formwork carpenters were frequent lifting (46.7%), carrying (50.0%) and handling (60.0%). Significantly higher lifting and carrying capacities were revealed among the FCs, but not in their isometric strengths and the endurance of the upper limbs (chi2 = 6.48, df = 2, p < 0.05). CONCLUSIONS: The dynamic and repetitive sub-maximal nature of the work of formwork carpentry induced an elevation of job-specific lifting and carrying capacities among the FCs. The job and functional capacity profiles would be useful for formulating guidelines for the rehabilitation of injured workers and the training of new workers in the trade.

Adult↗

PubMed1983

Hypoxia and the radiation response of tumors.

The effect of hypoxia on the in vivo radiation response of tumors is demonstrated both for the measurement of cell survival and growth delay following treatment. Results using these endpoints for the KHT Sarcoma are then presented to demonstrate the effect of various parameters which are expected to control tumor oxygenation: blood flow, blood pO2, blood oxygen carrying capacity and tissue consumption of oxygen. Intrinsic blood flow does not correlate with the level of hypoxia in the tumor, but acute reductions in blood flow do result in decreases in tumor oxygenation. Changing the blood PaO2 or the oxygen carrying capacity change the level of hypoxia as predicted, but only certain aspects have been studied. The intricate feedback mechanism which controls normal tissue oxygenation and compensates for any deficiencies cannot be assumed to work effectively in tumors.

Animals↗

PubMed1994

Hemodilution and blood substitutes.

The primary consequence of the substitution or replacement of blood with a surrogate is the dilution of the original constituents. This hemodilution produces systemic and microvascular phenomena that underlie all forms of blood replacement and provides a physiological reference for comparison for blood substitutes. The basic features of hemodilution become evident when the procedure is carried out in isovolemic and isoocotic conditions where blood viscosity and oxygen carrying capacity are changed. Blood viscosity is decreased, which redistributes macro and microcirculatory blood pressure increasing the arterio/venular pressure difference and central venous pressure, which improves cardiac filling and cardiac output and therefore blood flow velocity. These effects coupled to the oxygen carried by the diluted blood maintains the rate of oxygen delivery to the microcirculation up to hematocrit reductions of one third. The increased flow velocity counteracts the diffusive losses of oxygen from the microvessels. The increased flow velocity increases shear stress at the vessel wall lowering the tendency of activated leukocytes to adhere. Hemodilution with dextran 70 also maintains functional capillary density to hematocrit decreases of one half. Hemodilution with alpha alpha-hemoglobin presents all the features found with non-oxygen carrying colloids, however the increased oxygen carrying capacity is not fully exploited because systemic and microvascular effects due to colloids do not develop to the same extent.

Biological Transport↗

PubMed2004

Convergence of a structured metapopulation model to Levins's model.

We consider a structured metapopulation model describing the dynamics of a single species, whose members are located in separate patches that are linked through migration according to a mean field rule. Our main aim is to find conditions under which its equilibrium distribution is reasonably approximated by that of the unstructured model of Levins (1969). We do this by showing that the (positive) equilibrium distribution converges, as the carrying capacity of each population goes to infinity together with appropriate scalings on the other parameters, to a bimodal distribution, consisting of a point mass at 0, together with a positive part which is closely approximated by a shifted Poisson centred near the carrying capacity. Under this limiting regime, we also give simpler approximate formulae for the equilibrium distribution. We conclude by showing how to compute persistence regions in parameter space for the exact model, and then illustrate all our results with numerical examples. Our proofs are based on Stein's method.

Animals↗

PubMed2003

Parasite-mediated selection in experimental Daphnia magna populations.

It has been suggested that parasites are a strong selecting force for their hosts and therefore may alter the outcome of competition among host genotypes. We tested the extent to which parasite-mediated selection by different parasite species influenced competition among clones of the cyclic parthenogen Daphnia magna. We monitored clone frequency changes in laboratory microcosm populations consisting of 21 D. magna clones. Parasite treatments (two microsporidians, Glugoides intestinalis and Ordospora colligata) and a parasite-free control treatment were followed over a nine-month period. A further treatment with the bacterium Pasteuria ramosa failed. We found significant differences in clonal success among the treatments: the two parasite treatments differed from the control treatment and from each other. Additionally, we measured the clone-specific population carrying capacity, competitive ability against tester clones, and reproductive success of infected and uninfected females to test whether they correlate with clonal success in the microcosms. The clone-specific competitive ability was a good predictor of clonal success in the microcosms, but clonal carrying capacity and host reproductive success were not. Our study shows that parasite-mediated selection can strongly alter the outcome of clonal competition. The results suggest that parasites may influence microevolution in Daphnia populations during periods of asexual reproduction.

Animals↗

PubMed1986

The effect of water content on the stiffness of seating foams.

The chairbound, disabled person requires a supportive cushion to distribute pressure in order to reduce the risk of pressure sores and any alteration to the load carrying capacity of the cushion may have a deleterious effect on its ability to provide adequate support. The National Health Service supplies two basic grades of polyurethane foam for wheelchair cushions and this study investigated the effect of water content on their compressive load carrying capacity. Both foams became less stiff and exhibited greater than 20% increase in deformation when containing 20% water by volume at loads encountered in seating. This decrease in stiffness may result in a dramatic change in the pressure distribution under a patient particularly if only a small section of the cushion becomes wet. This result emphasizes the need to fit waterproof coverings to these foam cushions and to maintain the integrity of the covering.

Humans↗

PubMed1990

Mechanism of intestinal fatty acid uptake in the rat: the role of an acidic microclimate.

1. Micellar solubilization of lipolytic products is an important step in lipid absorption. However, micelles are not absorbed intact; dissociation of lipolytic products from bile salt micelles must occur. The dissociation of micelles has been postulated to occur in an acidic microclimate. 2. The effect of an acidic microclimate on the uptake of micellar fatty acid was examined in the rat intestine. We reported that the presence of a lower pH microclimate is associated with a higher fatty acid uptake, suggesting that a lower pH enhances fatty acid uptakes from the micelles. 3. Fatty acid uptake from solutions containing a constant amount of bile salt (10 mM) and varying amounts of fatty acid (3.3-26.4 mM) revealed a saturation phenomenon which reflects the fatty acid carrying capacity of a 10 mM-taurocholate solution. 4. There was a linear relationship between fatty acid uptake and fatty acid concentration when the micellar solutions contained a constant ratio of fatty acid and taurocholate (1.32). 5. Our results indicate that the fatty acid carrying capacity of the micelle and the number of micelles in the solution are both important determinants for the amount of fatty acids delivered to the microclimate. The amount of fatty acids derived from the dissociation of micelles within the microclimate determines fatty acid uptake by the intestine.

Animals↗

PubMed2001

A novel method for controlled and reversible long term compression of the umbilical cord in fetal sheep.

1. In fetal sheep during late gestation the aims of the present study were to (1) develop a technique for inducing prolonged but reversible periods of controlled compression of the umbilical cord and (2) characterise the cardiovascular, endocrine and metabolic responses to this challenge. 2. Under 1-2 % halothane anaesthesia, 16 Welsh Mountain sheep fetuses were chronically instrumented at 118 +/- 2 days of gestation (term is ca 145 days) with an inflatable occluder cuff around the umbilical cord, amniotic and femoral vascular catheters and with transit-time flow probes around the contra-lateral femoral artery and an umbilical artery. At 125 days, umbilical blood flow was reduced by 30 % from a pre-determined 24 h baseline for 3 days by automated servo-controlled inflation of the occluder cuff (n = 8). The occluder was then deflated allowing return of umbilical blood flow to baseline. The remaining eight fetuses were used as sham-operated controls in which the occluder was not inflated throughout the protocol. Fetal cardiovascular variables were recorded at 8 s intervals and arterial blood samples taken for measurement of blood gases, glucose and lactate and plasma adrenaline, noradrenaline and vasopressin concentration throughout the study. 3. Automated servo-controlled inflation of the occluder cuff, programmed to reduce umbilical blood flow by 30 % from baseline, reduced umbilical blood flow by 30.2 +/- 1.7 %, with a coefficient of variation during compression of 6.5 +/- 1.1 %. Sustained partial compression of the umbilical cord produced falls in fetal arterial pH, P(a,O2), percentage O(2) saturation of haemoglobin, and hindlimb oxygen delivery, and increases in P(a,CO2), haemoglobin concentration, arterial blood oxygen carrying capacity and in blood glucose and lactate concentrations. While the reductions in P(a,O2), percentage saturation of haemoglobin and hindlimb oxygen delivery and the increase in P(a,CO2) were sustained throughout compression, the reduction in arterial pH and the increase in arterial oxygen carrying capacity had returned towards baseline values by 48 h compression. Fetal blood lactate concentrations reached a peak at 8 h of compression and, thereafter, were maintained at an elevated level relative to baseline. 4. Partial compression of the umbilical cord produced fetal hypertension, a reduction in femoral blood flow and, consequently, an increase in calculated fetal femoral vascular resistance for the duration of the challenge. In addition, the fall in heart rate measured in sham control fetuses by the end of the study, did not occur in cord-compressed fetuses. Cosinor analysis on 24 h rhythms of cardiovascular data indicated a significant increase in the amplitude of the 24 h rhythm in heart rate in cord-compressed fetuses relative to sham controls during the period of compression or sham-compression. Furthermore, cord compression led to an increase in fetal plasma noradrenaline, but not adrenaline and vasopressin concentrations relative to sham control fetuses. 5. In conclusion, a novel reversible method for controlled, long-term compression of the umbilical cord in sheep has been developed. The data show that sustained, partial compression of the umbilical cord produced moderate but sustained asphyxia, which resolved after the end of the compression period, and induced changes in fetal cardiovascular, endocrine and metabolic functions.

Animals↗

PubMed1977

[In vitro and in vivo study of a hemoglobin solution used as a blood substitute].

In vitro studies of a stroma free haemoglobin solution of human origin (Wx B 8326, Warner-Lambert) in comparison with fresh and stored low DPG whole human blood, was undertaken with regard to the fixation. of oxygen. Such an hemoglobin solution was shown to exhibit a high affinity for oxygen and a low Bohr effect (assessed from the delta log Po2/delta pH ratio). The specific effect of Co2 (assessed from the delta log Po2/delta log. Pco2 ratio) appeared to be increased as compared to fresh whole blood. This hemoglobin solution was tested as a blood substitute in two in vivo experimental situations: exsanguino transfusion on rabbits (n = 6) and closed-chest extracorporeal circulation on dogs (n = 6). In order to evaluate the part taken by the tested Hb solution in arterial O2 carrying capacity and in O2 delivery, two ratios were calculated: arterial plasmatic O2 content/arterial circulating blood O2 content and arterio-venous plasmatic O2 difference/arterio-venous circulating blood O2 difference. These two ratios amounted 28,2 +/- 2,5% (rabbits) and 47,0 +/- 6% (dogs) for the arterial O2 carrying capacity and 13,8 +/- 3,0% (rabbits) and 25,8 +/- 5,0% (dogs) for the tissular O2 delivery. Among the properties of the tested stroma free hemoglobin solution its low contribution to the tissular O2 delivery, its high affinity for oxygen, its low Bohr effect and its short half-life as compared to whole blood are not favouring its use in clinical practice.

Acid-Base Equilibrium↗

PubMed2000

The influences of training on rowers of different age.

We measured 14 rowers and divided them into two groups according to age and years of training. Our goal has been to establish the influence of several years of programmed training on the structure of the body, oxygen carrying capacity and oxidation capacity of muscle cells, the chemical composition of blood and characteristics of pulse and lactate curves in rowers. As to the structure of the body, the two groups did not differ if we equalised them according to body height. Differences existed in the determinants of oxygen carrying capacity and oxidation capacity of muscle cells. Older rowers had lower pulse at rest, higher step test index, lower pulse immediately after the step test and in the last minute of the test on a bicycle ergometer and higher maximal oxygen pulse. While at rest, no significant differences between the groups were observed in most of the analysed substances in the blood serum. With the increase of age and training period an increase of the concentration of creatinin and activity of creatine kinase and lessening of the activity of alkaline phosphatase was noted. Length of training period lowers the levels of cholesterol and free fatty acids and increases the level of triglycerides in blood serum. An increase of the activity of creatine kinase and lactate dehydrogenase and the formation of a specific pattern of isoenzymes was observed. The pulse and lactate curve flattened and moved to the right.

Adolescent↗

PubMed2002

The unusual properties of effective blood substitutes.

Blood substitutes or oxygen carrying plasma expanders were originally formulated to simulate the transport properties of blood, particularly oxygen carrying capacity, viscosity, p50, and colloid osmotic pressure, under the hypothesis that blood is the most desirable fluid in volume restitution. However, changes introduced into the organism during hemorrhage adversely affect microvascular function due to reflex vasoconstriction which causes the fall of functional capillary density, and lowers tissue oxygenation, conditions that are not universally reversed with retransfusion of blood. The restoration of microvascular function is seldom complete upon retransfusion of blood. New formulations of hemoglobin molecules in solutions whose oncotic pressure is in the range of 60-100 mmHg, p50 is about 5 mmHg, viscosity 3-4 cP, and oxygen carrying capacity in the range of 4-7 g/dl equivalent hemoglobin deliver better microvascular function after resuscitation when compared to whole blood and oxygen carrying plasma expanders with transport properties similar to those of blood. The improved performance is in part due to the increased plasma viscosity which increases capillary transmural pressure which reverses capillary collapse induced during low perfusion pressures. High oncotic pressure reinforces this effect, since it brings more fluid into the circulation. Microvascular transport studies of the effects of resuscitation in shock show that functional capillary density is the primary determinant of survival, thus maintenance of an open and fully perfused microcirculation is more critical than insuring oxygen supply, since closed capillaries lead to the accumulation of slowly diffusing byproducts of metabolism which ultimately become toxic. The required combination of properties can be achieved by conjugating hemoglobin and polyethylene glycol. Resuscitation fluids based on hemoglobin containing vesicles may provide the next level of functional improvement in the formulation of volume restitution fluids since their biophysical properties can be specifically controlled through the inclusion of specialized compounds into the vesicles, and the formulation of the suspending medium.

Blood Circulation↗

PubMed2006

Catalyst-induced growth with limited catalyst lifespan and competition.

Spatially extended catalyst-induced growth processes are studied. This type of processes exists in all domains of biology, ranging from ecology (nutrients and growth), through immunology (antigens and lymphocytes) to molecular biology (signaling molecules initiating signaling cascades). The extinction-proliferation transition is considered for a system containing discrete catalysts (A) that induces the proliferation of a discrete reactant (B). The realization of this model on an infinite capacity d-dimensional discrete lattice for immortal catalysts has been previously considered (the AB model). It was shown that the adaptation of the reactants to the diffusive noise induced by stochastic fluctuations of catalyst density yields proliferation even if the average environmental conditions lead to extinction. This model is extended here to include more realistic situations, like finite lifespan of the catalysts and finite carrying capacity of the reactants. By using a combination of Monte Carlo simulation, percolation-theory-based estimations and an analytic perturbative analysis, the asymptotic behavior of these systems is studied. In both cases studied, it turns out that the overall survival of the reactant population at the long run is based on the size and shape of a typical single colony, related to the localized proliferation around spatio-temporal catalyst density fluctuations. If the density of these colonies (based on the lifetime of the spatial fluctuation and the carrying capacity of the medium) is large enough, i.e. above the percolation threshold, the reactant population survives even in (on average) hostile environment. This model provides a new insight on the population dynamics in chemical, biological and ecological systems.

Animals↗

PubMed1987

Effects of chemical stress on the population dynamics of Daphnia magna: a comparison of two test procedures.

Ten substances were tested to compare two methods that can be used in chronic toxicity studies with the Cladoceran Daphnia magna. In semistatic experiments with cohorts (life-table studies) survival appeared to be a dominant factor in exponential population growth. Specific inhibition of reproduction as a result of toxic stress was observed only in tests with bromide and 2,4-dichloroaniline. For some substances (cadmium, bichromate, metavanadate, and bromide) individual growth (carapace length) was found to be a sensitive parameter. In intermittent-flow experiments with small expanding populations the yield (carrying capacity) proved to be a highly sensitive parameter, probably owing to the fact that in these tests populations grow logistically, i.e., become additionally stressed by food limitation. Chemically induced reductions in food ingestion and conversion efficiency may thus become very predominant. In view of the place of these crustaceans in the food web such reductions in the carrying capacity would seem to be of great ecotoxicological importance.

Aniline Compounds↗

PubMed1985

On the stability of polymorphic host-pathogen populations.

The stability of populations of hosts and micro-parasites is investigated where each consists of n varieties that are equal in every respect except that each strain of parasites can infect only one specific strain of hosts and none of the others. Collectively the host strains are limited by a carrying capacity and through this limitation the host populations interact with each other. Hosts are assumed to reproduce asexually or such that different strains do not mate or are not fertile if they do. When the excess death rate caused by the pathogenic parasites is sufficiently large, then the host population is regulated to an equilibrium below the carrying capacity of the environment. This polymorphic equilibrium is shown to be locally asymptotically stable. When one of the parasite strains is absent, then all the other strains die out asymptotically. However, if host resistance to all infectious strains of parasites is achieved at the cost of a lower birthrate of the resistant host strain, then, if a certain condition for the various parameters is satisfied, stable coexistence between infected and resistant hosts is possible. There are many examples where susceptibility and resistance of hosts depends upon the conformation of specific proteins that are involved in host-parasite interactions and hence upon alleles at genetic loci that code for these proteins. We propose that polymorphism in wildtype populations which has been the subject of much theorizing in mathematical genetics may be due to host-pathogen interactions. Our model suggests how a polymorphic population, once established, can remain polymorphic indefinitely.

Animals↗

PubMed2000

Estimating the time to extinction in an island population of song sparrows.

We estimated and modelled how uncertainties in stochastic population dynamics and biases in parameter estimates affect the accuracy of the projections of a small island population of song sparrows which was enumerated every spring for 24 years. The estimate of the density regulation in a theta-logistic model (theta = 1.09 suggests that the dynamics are nearly logistic, with specific growth rate r1 = 0.99 and carrying capacity K = 41.54. The song sparrow population was strongly influenced by demographic (ŝigma2(d) = 0.66) and environmental (ŝigma2(d) = 0.41) stochasticity. Bootstrap replicates of the different parameters revealed that the uncertainties in the estimates of the specific growth rate r1 and the density regulation theta were larger than the uncertainties in the environmental variance sigma2(e) and the carrying capacity K. We introduce the concept of the population prediction interval (PPI), which is a stochastic interval which includes the unknown population size with probability (1 - alpha). The width of the PPI increased rapidly with time because of uncertainties in the estimates of density regulation as well as demographic and environmental variance in the stochastic population dynamics. Accepting a 10% probability of extinction within 100 years, neglecting uncertainties in the parameters will lead to a 33% overestimation of the time it takes for the extinction barrier (population size X = 1) to be included into the PPI. This study shows that ignoring uncertainties in population dynamics produces a substantial underestimation of the extinction risk.

Animals↗

PubMed1998

Initial stability of femoral neck osteosynthesis with absorbable self-reinforced poly-L-lactide (SR-PLLA) and metallic screws: a comparative study on 21 cadavers.

The initial stability of femoral neck osteosynthesis provided by three self-reinforced poly-L-lactide (SR-PLLA) or three metallic cannulated screws was compared. A standard transverse subcapital osteotomy was created with a hand saw in 19 pairs of human cadaver femora. Two fixation methods were randomly used in each pair. Fixations were exposed to a progressive cyclic loading test to determine the deflection curves, the ultimate load-carrying capacity, and the total amount of load absorbed. One pair served as a pilot and two nonoperated pairs served as controls. The positioning of the three fixation screws, whether one screw proximally and two screws distally or vice versa, provided equal stability. Metallic fixation proved to be more stable than SR-PLLA fixation as the average maximum load-carrying capacity was 3400N for the metallic and 2600N for the SR-PLLA fixation. However, SR-PLLA screws showed sufficient fixation properties for considering clinical trials in Garden I-II femoral neck fractures in well cooperative patients.

Absorption↗

PubMed1997

Optimal killing for obligate killers: the evolution of life histories and virulence of semelparous parasites.

Many viral, bacterial and protozoan parasites of invertebrates first propagate inside their host without releasing any transmission stages and then kill their host to release all transmission stages at once. Life history and the evolution of virulence of these obligately killing parasites are modelled, assuming that within-host growth is density dependent. We find that the parasite should kill the host when its per capita growth rate falls to the level of the host mortality rate. The parasite should kill its host later when the carrying capacity, K, is higher, but should kill it earlier when the parasite-independent host mortality increases or when the parasite has a higher birth rate. When K(t), for parasite growth, is not constant over the duration of an infection, but increases with time, the parasite should kill the host around the stage when the growth rate of the carrying capacity decelerates strongly. In case that K(t) relates to host body size, this deceleration in growth is around host maturation.

Animals↗