bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetics of lopinavir in combination with ritonavir in HIV‐1‐infected patients
Authors: Crommentuyn K. M. L. , Kappelhoff B. S. , Mulder J. W. , Mairuhu A. T. A. , Van Gorp E. C. M. , Meenhorst P. L. , Huitema A. D. R. , Beijnen J. H. 
Published: September 2005

AimsTo develop a population pharmacokinetic model for lopinavir in combination with ritonavir, in which the interaction between both drugs was characterized, and in which relationships between patient characteristics and pharmacokinetics were identified.MethodsThe pharmacokinetics of lopinavir in combination with ritonavir were described using NONMEM (version V, level 1.1). First, ritonavir data were fitted to a previously developed model to obtain individual Bayesian estimates of pharmacokinetic parameters. Hereafter, an integrated model for the description of the pharmacokinetics of lopinavir with ritonavir was designed.ResultsFrom 122 outpatients 748 lopinavir and 748 ritonavir plasma concentrations were available for analysis. The interaction between the drugs was described by a time‐independent inverse relationship between the exposure to ritonavir over a dosing‐interval and the apparent clearance (CL/F) of lopinavir. The model parameters volume of distribution and absorption rate constant were 61.6 l (95% prediction interval (PI) 22.4, 83.7) and 0.564 h−1 (95% PI 0.208, 0.947), respectively. The model yielded a theoretical value for the CL/F of lopinavir without ritonavir of 14.8 l h−1 (95%PI 12.1, 20.1), which translates to a value of 5.73 l h−1 in the presence of ritonavir. The only factor with significant effect on the pharmacokinetics was concurrent use of non‐nucleoside reverse transcriptase inhibitors (NNRTI), which increased the CL/F of lopinavir by 39% (P < 0.001).ConclusionsWe have developed a model that has defined a time‐independent inverse relationship between the exposure to ritonavir and the CL/F of lopinavir, and provided an adequate description of the pharmacokinetic parameters for the latter. Concomitant use of the NNRTIs efavirenz and nevirapine increased the CL/F of lopinavir.
Within‐ and between‐ subject variability in methadone pharmacokinetics and pharmacodynamics in methadone maintenance subjects
Authors: Hanna Julia , Foster David J.R. , Salter Amy , Somogyi Andrew A. , White Jason M. , Bochner Felix 
Published: September 2005

AimsTo investigate within‐ and between‐subject variability of the pharmacodynamics and pharmacokinetics of (R)‐ and (S)‐methadone in methadone maintenance subjects at steady‐state.MethodsSix non‐holder subjects were studied on three occasions at 7–16 day intervals; doses (20–170 mg/day) remained unchanged. Blood samples and pharmacodynamic data were collected 10–12 times over a 24‐h inter‐dosing interval. All pharmacodynamic data were expressed as the area under the end‐point versus time curve. Using analyses of variance with mixed effects, best estimates were made of the ratio of between‐ to within‐subject variation, with corresponding 95% confidence intervals (CI) for within‐subject variation at the average value.ResultsSubjects were relatively consistent between occasions, whereas there was much greater between‐subject variability (P < 0.02) for all measures. Estimates of the ratio of between‐ to within‐subject variation ranged from 2.2–12.8 for pharmacodynamic measures, and 1.3–7.9 for pharmacokinetic parameters. For pain, total mood disturbance, withdrawal, pupil size and respiration rate, 95% CI for within‐subject measures ranged ≤ 2‐fold, while this was greater for subjective direct opioid effects (4.2‐fold). For CL/F of the active (R)‐methadone, the variance ratio was 4.9 (P < 0.0003), with 95% CI for within‐subject measures ranging ≤ 2‐fold. (S)‐methadone CL/F demonstrated greater within‐subject variability (3.4‐fold), possibly contributing to a smaller (2.7; P < 0.0003) ratio of between‐ to within‐subject variance.ConclusionsNon‐holder methadone maintenance treatment participants appear to respond consistently with respect to pharmacokinetics and pharmacodynamics over a 1–2 month period. Such knowledge may help prescribers to determine whether alternative dosing regimens or treatments might be more appropriate in this population.
Long‐term incubation with IL‐4 and IL‐10 oppositely modifies procoagulant activity of monocytes and modulates the surface expression of tissue factor and tissue factor pathway inhibitor
Authors: Paysant Jérôme , Soria Claudine , Cornillet‐Lefèbvre Pascale , Nguyen Philippe , Lenormand Bernard , Mishal Zohar , Vannier Jean‐Pierre , Vasse Marc 
Published: September 2005

SummaryMonocytes can be induced to express both tissue factor (TF) and its inhibitor, TF pathway inhibitor‐1 (TFPI‐1). A short incubation (<6 h) with interleukin (IL)‐4 and IL‐10, two potent deactivators of monocyte functions, has been shown to modulate the synthesis and expression of TF by monocytes activated by lipopolysaccharide, but the consequences of longer incubations (up to 96 h) on both TF and TFPI‐1 are unknown. The results of this study showed that adherent monocytes in culture spontaneously expressed TF and TFPI and that prolonged incubation with IL‐10 induced a time‐ and dose‐dependent decrease of monocyte TF synthesis, and an accumulation of TF/TFPI‐1 complexes at the moncyte surface, suggesting a decreased clearance of these complexes. In contrast, IL‐4 induced a time‐ and dose‐dependent increase in TF synthesis, which remained intracytoplasmic, as shown by confocal microscopy. Surprisingly, TF:antigen (Ag) was decreased at the monocyte surface, but the procoagulant activity (PCA) of IL‐4‐treated monocytes was increased, as a result of more pronounced decrease of TFPI‐1:Ag expression than that of TF. In conclusion, prolonged incubation with IL‐4 and IL‐10 oppositely modified PCA of cultured monocytes, and altered TF and TFPI trafficking and clearance. These data explain the respective deleterious or benefit effects of IL‐4 or IL‐10 in atherothrombosis.
Chronic fatigue syndrome is associated with diminished intracellular perforin
Authors: Maher K J , Klimas N G , Fletcher M A 
Published: September 2005

SummaryChronic fatigue syndrome (CFS) is an illness characterized by unexplained and prolonged fatigue that is often accompanied by abnormalities of immune, endocrine and cognitive functions. Diminished natural killer cell cytotoxicity (NKCC) is a frequently reported finding. However, the molecular basis of this defect of in vitro cytotoxicy has not been described. Perforin is a protein found within intracellular granules of NK and cytotoxic T cells and is a key factor in the lytic processes mediated by these cells. Quantitative fluorescence flow cytometry was used to the intracellular perforin content in CFS subjects and healthy controls. A significant reduction in the NK cell associated perforin levels in samples from CFS patients, compared to healthy controls, was observed. There was also an indication of a reduced perforin level within the cytotoxic T cells of CFS subjects, providing the first evidence, to our knowledge, to suggest a T cell associated cytotoxic deficit in CFS. Because perforin is important in immune surveillance and homeostasis of the immune system, its deficiency may prove to be an important factor in the pathogenesis of CFS and its analysis may prove useful as a biomarker in the study of CFS.
Identification of paramyosin T cell epitopes associated with human resistance toSchistosoma mansonireinfection
Authors: Fonseca C T , Cunha-Neto E , Goldberg A C , Kalil J , De Jesus A R , Carvalho E M , Correa-Oliveira R , Hammer J , Sidney J , Sette A , Oliveira S C 
Published: September 2005

SummaryParamyosin, a Schistosoma mansoni myoprotein associated with human resistance to infection and reinfection, is a candidate antigen to compose a subunit vaccine against schistosomiasis. In this study, 11 paramyosin peptides selected by TEPITOPE algorithm as promiscuous epitopes were produced synthetically and tested in proliferation and in vitro human leucocyte antigen (HLA)-DR binding assays. A differential proliferative response was observed in individuals resistant to reinfection compared to individuals susceptible to reinfection in response to Para (210–226) peptide stimulation. In addition, this peptide was able to bind to all HLA-DR molecules tested in HLA-DR binding assays, confirming its promiscuity. Para (6–22) and Para (355–371) were also shown to be promiscuous peptides, because they were able to bind to the six and eight most prevalent HLA-DR alleles used in HLA-DR binding assays, respectively, and were also recognized by T cells of the individuals studied. These results suggest that these paramyosin peptides are promising antigens to compose an anti-schistosomiasis vaccine.
Increased plasma N‐terminal pro‐B‐type natriuretic peptide and markers of inflammation related to atherosclerosis in patients with primary hyperparathyroidism
Authors: Øgard Christina Gerlach , Engelmann Mads D. , Kistorp Caroline , Nielsen Steen Levin , Vestergaard Henrik 
Published: September 2005

SummaryObjective  Increased risk of cardiovascular disease has been reported in patients with primary hyperparathyroidism (PHPT). The aim of this study was to evaluate novel plasma risk markers of cardiovascular disease in patients with PHPT.Design  PHPT patients were evaluated with a control group. Patients who underwent parathyroidectomy were re‐evaluated after 7 and 18 months.Patients  Forty‐five PHPT patients and 40 matched controls participated. Seventeen patients underwent parathyroidectomy.Measurements  Plasma N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), high‐sensitivity C‐reactive protein (CRP), interleukin‐6 (IL‐6) and tumour necrosis factor alpha (TNF‐α), lipids and blood pressure were measured. In 27 patients a bicycle exercise test and radionuclide angiography were performed, and repeated in those who underwent parathyroidectomy.Results  Plasma NT‐proBNP, CRP and TNF‐α, but not IL‐6, were higher in patients with PHPT than in controls (P < 0·01 and P = 0·17, respectively). In patients with PHPT, NT‐proBNP correlated with systolic blood pressure, left ventricular end‐diastolic volume, and peak oxygen uptake (all P < 0·01). Log CRP correlated with systolic and diastolic blood pressure (both P < 0·05) and log IL‐6 (P < 0·01). No significant correlations were observed between PTH or calcium and risk markers of cardiovascular disease. No decrease in NT‐proBNP, markers of inflammation or blood pressure was observed after parathyroidectomy.Conclusions  Our data suggest that hypertension or other factors, rather than plasma calcium or PTH, could explain the increased levels of the inflammatory markers and NT‐proBNP in PHPT. We therefore suggest that aggressive treatment of hypertension should be initiated in patients with PHPT to try to reduce the increased cardiovascular mortality described in PHPT. Further prospective studies are needed to validate the suggestion that increased levels of NT‐proBNP and inflammatory markers also represent strong prognostic markers of cardiovascular disease in patients with PHPT.
Alterations in the oxidant‐antioxidant status in prepubertal children with growth hormone deficiency: effect of growth hormone replacement therapy
Authors: Mohn Angelika , Di Marzio Daniele , Giannini Cosimo , Capanna Rita , Marcovecchio Maria , Chiarelli Francesco 
Published: September 2005

SummaryObjective  Growth hormone deficiency (GHD) in adults is associated with increased oxidative stress determined by the underlying GH–IGF‐1 axis alterations. Despite GHD being a common diagnosis in children with short stature, no data on the oxidant/antioxidant status are available in this age group. This study was designed to detect differences in oxidative stress parameters between prepubertal GH‐deficient children and healthy controls. Furthermore, the effect of 12 months of conventional GH replacement (rGH) on oxidant–antioxidant status was evaluated in the GHD group only.Patients  Ten (nine males and one female) prepubertal children (mean age 9·1 ± 1·3 years) with GHD were recruited and matched for sex and age (9·2 ± 1·9 years) with 20 healthy controls (18 males and two females).Measurements  At study entry, lag phase, an index of susceptibility of low density lipoprotein (LDL) to in vitro oxidation, malondialdehyde (MDA) and vitamin E were measured in all subjects. These parameters were also evaluated in GH‐deficient children after 12 months of rGH treatment.Results  The lag phase was significantly decreased in GH‐deficient children compared to healthy controls (15·50 ± 7·4 vs. 43·00 ± 9·2 min; P = 0·0007), while MDA was significantly increased (1·33 ± 0·38 vs. 0·46 ± 0·10 nmol/mg; P = 0·0006). Vitamin E levels were significantly decreased (22·44 ± 9·57 vs. 35·38 ± 16·49 µmol/l; P = 0·001). IGF‐1 and IGFBP‐3 correlated directly to lag phase (r = 0·48; P = 0·01; r = 0·63, P = 0·002, respectively) and to vitamin E (r = 0·59, P = 0·003; r = 0·58, P = 0·006, respectively). By contrast, IGF‐1 and IGFBP‐3 correlated indirectly to MDA (r = –0·47, P = 0·01; r =−0·65, P = 0·002, respectively). After 1 year of rGH therapy, lag phase (39·32 ± 15·24 min; P = 0·005) and vitamin E (34·9 ± 7·7 µmol/l; P = 0·005) increased significantly, while MDA decreased significantly (0·71 ± 0·42 nmol/mg; P = 0·005), reaching normal levels.Conclusions  These data show that children with GHD have substantially increased oxidative stress parameters compared to healthy controls and demonstrate a normalization of these parameters after 1 year of rGH therapy.
Geographic patterns in the demersal ichthyofauna of the Aleutian Islands
Authors: LOGERWELL E. A. , AYDIN K. , BARBEAUX S. , BROWN E. , CONNERS M. E. , LOWE S. , ORR J. W. , ORTIZ I. , REUTER R. , SPENCER P. 
Published: September 2005

AbstractThe goals of this research were to investigate geographic patterns in the Aleutian Island region's demersal ichthyofauna and to determine whether they reflected the physical and biological oceanographic patterns documented by other authors in this volume. The analyses were structured according to the level of organization: at the community level, patterns in species occurrence and community structure were investigated; at the population level, distribution and abundance were examined; at the individual level, food habits and growth were studied. There were step‐changes in species occurrence, diversity, population distribution and food habits at Samalga Pass and at sites farther west. These longitudinal trends indicated physical and biological variation along the length of the Aleutian Islands chain; however, depth‐related patterns were as common as longitudinal patterns in demersal fish distribution. In addition, high catches of patchily distributed species occurred in areas expected to be biological ‘hot spots’ because of increased productivity and prey availability. These patterns suggest linkages between demersal fish ecology and the biophysical processes described by other authors in this volume and indicate that inter‐disciplinary research is needed to elucidate the underlying mechanisms.
Zooplankton distribution, abundance and biomass relative to water masses in eastern and central Aleutian Island passes
Authors: COYLE KENNETH O. 
Published: September 2005

AbstractConductivity–temperature–depth (CTD), acoustic and net samples were taken through a series of passes in the eastern and central Aleutian Island archipelago to document regional differences in the physical and biological conditions. The water column in central passes had elevated salinity and depressed temperatures, indicating upwelling of deep water through the passes. The zooplankton community included the oceanic genera Neocalanus and Eucalanus, and the euphausiid Euphausia pacifica, all oceanic taxa. Eastern passes had significantly lower salinity and elevated temperature relative to the central passes, suggesting a more neritic environment. Calanus marshallae, Pseudocalanus, Acartia and Thysanoessa inermis, common neritic species, were observed in the eastern passes. Canonical correlation indicated that up to 50% of the observed variance in mean zooplankton abundance in the passes could be explained by salinity and temperature. Elevated sound scattering was observed in fronts and eddies in the passes, particularly at the northern ends of the passes, in association with elevated zooplankton abundance and biomass. The central passes were characterized as an oceanic environment, influenced primarily by Alaskan Stream water with its associated interzonal copepod species, while the eastern passes were influenced by the Alaska Coastal Current, which contains a mixture of oceanic and neritic zooplankton species.
Tidal front affects the size of prey used by a top marine predator, the short‐tailed shearwater (Puffinus tenuirostris)
Authors: VLIETSTRA LUCY S. , COYLE KENNETH O. , KACHEL NANCY B. , HUNT GEORGE L. 
Published: September 2005

AbstractOceanographic features are known to influence the distribution of marine predators by affecting the abundance and distribution of their prey. We tested the hypothesis that oceanographic features also affect predator distribution by enhancing the profitability of small‐sized prey. During July and August 1999, short‐tailed shearwaters feeding in Akutan Pass, Alaska (Aleutian Islands) fed upon small (11.6 ± 0.2 mm) euphausiids present in high density near the sea surface. Conductivity–temperature–depth (CTD) casts, hydroacoustic surveys, and net tows revealed that high densities of small euphausiids were associated with a tidal front on the north side of Akutan Pass. At most sites elsewhere in the Bering Sea, away from tidal fronts, shearwaters selected larger (14.2–20.1 mm) euphausiids, even when small euphausiids were present. This study provides evidence that, by promoting high densities of easily accessible prey, oceanographic features can broaden the range of prey sizes taken by marine predators.
Corals of the Aleutian Islands
Authors: HEIFETZ JONATHAN , WING BRUCE L. , STONE ROBERT P. , MALECHA PATRICK W. , COURTNEY DEAN L. 
Published: September 2005

AbstractA unique feature of the benthic habitat in the Aleutian Islands is the presence of a highly diverse and abundant coral and sponge community. These communities likely provide important habitat for a variety of fish and invertebrate species. Summaries of historical data and recent direct observations with a submersible indicate that the Aleutian Islands may harbour the highest diversity and abundance of coldwater corals in the world. There are 69 documented taxa (species and subspecies) of coral in the Aleutians of which 25 are endemic. Within the Aleutian Islands, there is an increase in diversity of corals west of about longitude 169°W. This shift in diversity is consistent with the hypothesis of an ecological boundary in the vicinity of Samalga Pass. Given the endemism and high diversity and abundance of corals in the Aleutians, there is evidence that this region is the evolutionary centre of origin for some taxa of coldwater corals.
Oceanography and ecology of the Aleutian Archipelago: spatial and temporal variation
Authors: HUNT GEORGE L. , STABENO PHYLLIS J. 
Published: September 2005

AbstractThis compilation of new information and summaries of earlier work emphasizes variability within marine waters of the Aleutian Archipelago. From the Alaska Peninsula to Near Strait, net flow through the passes is northward, with four passes (Amukta, Amchitka, Buldir, and Near Strait) contributing most of the flow. East of Samalga Pass (169°W), waters derived from the Alaska Coastal Current predominate, whereas west of Samalga Pass, waters of the Alaskan Stream predominate. The pattern of storm tracks creates a climatological (interannual and long term) transition zone in weather features (e.g. surface air temperature) near 170°W. The marine ecosystem of the Aleutian Archipelago also has a strong discontinuity at Samalga Pass, where cold‐water corals, zooplankton, fish, marine mammals and foraging seabirds show a step change in species composition. Diets of ground fish, Steller sea lions (Eumetopias jubatus) and some seabirds also change there. Lower growth rates of some fish species and stable isotope data indicate that productivity declines westward along the archipelago. The available data demonstrate considerable ecosystem variability over time scales of decades to millennia. Abrupt changes in composition of fish communities at several of the major passes suggest that Samalga Pass may mark only one of several ecological divisions of Aleutian waters. This spatial and temporal heterogeneity provides an important context within which to view recent declines in populations of Steller sea lions and other species, and has important implications for the management of regional marine resources. We conclude that the marine waters of the Aleutian Archipelago are divided into at least two different ecological regions, with potential for a concomitant separation of some fishery resources.
Immature Steller sea lion (Eumetopias jubatus) dive activity in relation to habitat features of the eastern Aleutian Islands
Authors: FADELY BRIAN S. , ROBSON BRUCE W. , STERLING JEREMY T. , GREIG ANGIE , CALL KATHERINE A. 
Published: September 2005

AbstractCurrent flow and bathymetry in the Aleutian Islands define unique habitats that influence prey distribution and foraging behaviour of top‐level predators. We explored whether oceanographic features and bathymetry influenced the diving activity of 30 immature sea lions (ages 5–21 months) equipped with satellite‐linked depth recorders in the eastern Aleutian Islands (EAI) during 2000–02. Sea surface temperature (SST) and chlorophyll a concentrations were obtained from remote sensing satellite imagery and associated with locations where sea lion diving was recorded. Most locations associated with diving to >4 m were within 10 nautical miles (nm) of shore and associated with onshelf waters <100 m deep. Use of offshore and deeper waters in the Bering Sea increased during May, as did trip durations. General movements at that time were generally northwesterly from the North Pacific Ocean to the Bering Sea. Diving activity varied coincidently with increases in SST and chlorophyll a concentrations, but also with sea lion age. Associations with habitat features did not consistently explain variability in dive count, time at depth, dive focus or focal depth. Nearshore diving tended to be influenced by distance from shore or seafloor depth, whereas increased SST coincided with activity of sea lions diving >30 nm offshore. Immature sea lions developing into independent foragers in the relatively shallow pass areas of the EAI do so at a time of rapid changes in oceanography and prey availability.