2nd Compartment Research Articles

Modelling of a water filtration pilot by a chemical tracer using the Modflow "Finite Differences"

For the supply of drinking water to the population, we have set up a surface water treatment system: horizontal sand filtration. This process is based on the principle of bank filtration; it is a natural rustic treatment, based on slow biological filtration, which does not require any reagent. The objective of this work is to propose a tool to describe the groundwater flow on a complete water filtration system with the MODFLOW model in order to follow the evolution of the hydrodynamic parameters on the one hand and to determine the transit time of the water in the pilot. The calibration with a chemical tracer, fluorescein, allowing to optimise the defined parameters (hydraulic conductivities, recharge) of the aquifer in order to obtain calculated loads as close as possible to those measured in given observation points, and the reading and saving of the imposed hydraulic loads were carried out with the "results extractor" module. The variation of the slope of the 2nd compartment from 5% to 20% significantly reduces the transit time of the tracer from 6.3 h to 5.2 h in the device. It was also found that the transit time increased as the sand grain size decreased, but this did not indicate a malfunction of the device. The results obtained showed that it is possible to perform a hydrodynamic modelling of the system in order to reproduce the experiments performed on the physical device. The steady-state modelling shows that the curves calculated at each piezometer are close to the experimental curves, except for the variation in sand grain size (piezometer 3), probably due to the preferred path. The differences in concentration between the calculated and experimental values at piezometers 3 and 4 are due to a dilution and/or adsorption effect by the fine sand. The calibration of the model allows an appropriate sizing according to each problem

Apical but not sub-apical hyphal compartments are self-sustaining in growth

It was recently demonstrated that apical compartments of Aspergillus niger hyphae are self-sustaining in growth. This was shown by assessing the growth rate of individual hyphae before and after dissection of the second compartment. Using the same methodology, it is here demonstrated that single apical compartments of the septate fungi Penicillium chrysogenum and Schizophyllum commune as well as the 500-µm-apical region of the non-septate fungus Rhizopus stolonifer are also self-sustaining in growth. In contrast, single 2nd compartments (obtained by dissection of the first and third compartment) of the septate fungi or the region between 500 and 1000 µm from tips of R. stolonifer were severely impacted in their growth rate. In addition, it is shown that existing or newly formed branches originating from the 2nd compartments function as a backup system for hyphal growth when the apical part of the hypha of the three studied fungi is damaged. Together, it is concluded that the apical compartments/zones of the studied fungi are self-sustaining in growth. In contrast, the subapical region is not self-sustaining but functions as a backup once the apical zone is damaged. This back up system is relevant in nature because the apices of hyphae are the first to be exposed to (a)biotic stress conditions when entering an unexplored substrate.

Effect of C/N ratios on nitrogen removal and microbial communities in the anaerobic baffled reactor (ABR) with an anammox-coupling-denitrification process.

Effects of different C/N (NO2 -N) ratios on nitrogen removal and microbial community structure were investigated using an anaerobic baffled reactor (ABR). Results indicated that the C/N ratio exerted an important effect on nitrogen removal in the anammox-coupling-denitrification process associated with the ABR. When the C/N ratio was 1.29, the ABR could achieve the highest total nitrogen (TN) removal efficiency of 99.9%. Most of TN was removed in the 1st and 2nd compartment, accounting for about 81.0-97.6% of total TN removal. The nitrogen removal resulted from the interaction among anammox, heterotrophic denitrificans, and other microbes within the ABR. The contribution of anammox to nitrogen removal varied from 6.8% to 32.4%. High-throughput MiSeq sequencing analyses revealed that the C/N ratio was one of the most important factors regulating the microbial community structure, and the predominant phylum changed from Proteobacteria to Chloroflexi with the elevated C/N ratio. In addition, the Candidatus Brocadia was the major anammox bacterium, and its percentage varied from 1.0-2.9% at day 9 to 2.8-9.1% at day 46.

The pattern of lymph node metastases in microsatellite unstable gastric cancer

BackgroundMicrosatellite instability (MSI) is one of the new groups of molecular divisions of gastric cancer (GC). The aim of this study was to investigate the pattern of lymph node metastasis according to MSI status. MethodsMSI analysis of 361 GC patients with information about lymph node stations was performed using 5 quasimonomorphic mononucleotide repeats. The metastasis rates for each lymphatic station was analyzed, combined with clinicopathologic characteristics. Stations were divided into compartments 1–3 on the basis of Japanese Classification. A median number (interquartile range, IQR) of 33 (18–50) lymph nodes were removed and analyzed. ResultsN0 status was observed in 53.7% MSI patients, and in 29.7% microsatellite stable (MSS) (p < 0.001).The median value of involved nodes was 1 in MSI vs. 5 in MSS (p < 0.001). Furthermore, the number of involved node stations was significantly lower in the MSI group (p < 0.001). MSS tumors showed a higher propensity to spread to second and third compartment nodes. In absence of lymphovascular invasion only 3.2% cases demonstrated positive nodes beyond the first compartment. Skip metastases were seen in 6.1% MSS patients and 0% MSI (p = 0.011). No difference in the 10-year cancer related survival among MSI and MSS patients was found, for both those with 1st compartment (p = 0.223) and with 2nd compartment involvement (p = 0.814). ConclusionsMSI GC shows a high rate of N0 stage, a lower number of lymph node metastases, and a less extensive spread to lymph node stations than MSS tumors. These data indicate that tailored lymphadenectomy may be investigated for these patients.

Functional distinction of hyphal compartments

Hyphae of higher fungi grow at their tips and are compartmentalized by porous septa that enable inter-compartmental cytoplasmic streaming. Woronin bodies discontinue cytoplasmic streaming by plugging the septal pores. Here, it was assessed whether apical compartments of Aspergillus niger sustain their own growth or whether their growth depends on subapical compartments. Hyphae of wildtype and the ΔhexA strain, lacking Woronin bodies, had a similar morphology and growth rate. A total of 58% and 17% of the hyphae continued growing, respectively, after dissecting the 2nd compartment. Extension rate of the apical compartments that continued growing was not affected, even when the carbon or nitrogen source was limiting. Thus, apical compartments are self-sustaining in growth. It was also shown that the first 8 subapical compartments of the wildtype, but not of the ΔhexA strain, function as a backup system for growth by forming new branches when their apical neighbouring compartment has been damaged. This backup system is pivotal in nature because of the life style of fungi to continuously explore their surrounding substrate that may prove hostile.

Abstract 4523: Population pharmacokinetic (PPK) modeling of onapristone in patients (pts) with progesterone receptor (PR)-expressing cancers

Abstract Background: Onapristone is a type I PR antagonist, which prevents PR-induced DNA transcription. Onapristone anti-cancer activity is well documented. An extended-release (ER) tablet formulation of onapristone was designed to address the liver function test (LFT) elevations seen with immediate-release (IR) onapristone. A phase 1 study with onapristone in patients with tumors expressing PR is underway. Objectives included determining the PK profile of ER onapristone using a PPK approach. Materials and methods: This is an ongoing multi-center, open-label, randomized, parallel-group, 2-stage ph1 study. Female pts ≥18 yrs with tumors expressing PR are eligible. The Stage 1 primary endpoint is the recommended ph2 dose of ER onapristone; secondary endpoints include: safety, efficacy, and PK. Pts received onapristone ER 10, 20, 30, 40 or 50 mg BID, or onapristone IR tablets 100 mg QD until progressive disease or intolerability. PK blood samples from 8 time points were collected over 12 h post-dose Day 1 for the ER and 9 blood samples over 24 h post-dose for the IR formulation. Onapristone plasma concentrations were measured using validated UPLC with tandem mass spectrometry detection (range 1-250 ng/mL). Monolix V4.1 was used to calculate absorption constant (Ka); apparent clearance (CL/F); inter-compartmental clearance (Q); apparent distribution volume (V1/F), 2nd compartment distribution volume (V2) and bioavailability (F) of ER vs IR. Results: Stage 1 is complete. 42 pts have validated PK data. A 2-compartment open model adequately described the total onapristone time-concentration curve with linear elimination. Results are in Table 1. Table 1.Estimated PK parameters for onapristone in pts with PR-expressing cancers (n = 42)ParameterValueRelative standard error (%)Ka0.191 h-114CL/F1.51 L/h20Q3.11 L/h25V1/F5.41 L25V241.1 L45F60%20 Conclusions: The PPK modeling described the plasma onapristone time-concentration curves well. A central volume equivalent to the circulating blood volume and a large volume of the deep compartment suggest a large tissue diffusion. PPK/PD modeling to explore safety and efficacy is ongoing, with no overt PK/safety relationship detected. Citation Format: Keyvan Rezai, Paul Cottu, Samuel Huguet, Mario Campone, Antoine Italiano, Andrea Varga, Jacques Bonneterre, Alexandra Leary, Marie-Paule Sablin, Stefan Proniuk, Alice Bexon, Erard Gilles, Joseph Bisaha, Alexander Zukiwski, Francois Lokiec. Population pharmacokinetic (PPK) modeling of onapristone in patients (pts) with progesterone receptor (PR)-expressing cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4523. doi:10.1158/1538-7445.AM2015-4523

Theophylline Pharmacokinetics in Foetal Sheep: Maternal Metabolic Capacity is the Principal Driver.

Understanding theophylline pharmacokinetics (PK) in the foetus is essential to prevent in utero toxicity and optimize prophylactic therapies. Previous studies in pregnancy have been obfuscated by maternal dosing and inadequate sampling in the foetus; both render modelling of foetal PK difficult. Six ewes carrying singleton foetuses received theophylline (60mg) into the foetal jugular vein. Blood samples were drawn from the foetus and ewe over 36hr. Serum concentrations were measured. Maternal and foetal pharmacokinetic parameters were estimated. Foetal non-compartmental pharmacokinetic parameters were as follows: half-life 7.37±1.22hr; volume of distribution 44.62±11.45L; area under the curve 14.82±2.71hr/(μg/mL); and clearance 4.15±0.70L/hr. Rapid theophylline distribution across the placenta was observed. Maternal non-compartmental pharmacokinetic parameters were as follows: half-life 6.54±2.44hr; volume of distribution 32.48±9.99L; area under the curve 16.28±4.53hr/(μg/mL); and clearance 3.69±1.47L/hr. Foetal and ewe serum concentration-time profiles were fit together into a 3-compartment population pharmacokinetic model, and parameters were as follows: central volume 1.38±0.11L; 2nd peripheral compartment volume 3.11±0.29L; 3rd peripheral compartment volume 60.14±6.02L; elimination clearance 9.89±0.90L/hr; distribution clearance between central and 2nd compartment 30.87±2.31L/hr; and distribution clearance between 2nd and 3rd compartments 13.89±1.11L/hr. Cytochrome P4501A expression was robust in maternal liver; negligible activities were observed in placenta, foetal liver and foetal kidney. In vitro protein binding of theophylline was 30% lower in foetal serum compared to maternal serum (29.7±4.4 versus 42.0±3.6%-bound). Free concentrations were lower in the foetus than in the ewe, suggesting active transport across placenta. In summary, foetal clearance of theophylline is attributable to rapid distribution into the maternal circulation across the placenta followed by greater maternal protein binding and metabolic activity.

AB1262 Relative contribution of tenosynovitis and joint synovitis in rheumatoid and psoriatic arthritis revealed by contrast-enhanced, dynamic MRI: Das 28 correlates with the extension of synovitis but not with its severity

BackgroundDynamic, contrast-enhanced MRI (DCE-MRI), the quantification of enhancement within the synovial membrane and bone by extracting curves using fast T1-weighted sequences during intravenous administration of contrast agent, is useful to...

Simultaneous Transport and Separation of Cu(II) and Zn(II) in Cu-Zn-Co Sulfate Solution by Double Strip Dispersion Hybrid Liquid Membrane (SDHLM)

A double strip dispersion hybrid liquid membrane (SDHLM) was successfully used in the simultaneous extraction and separation of Cu(II), Zn(II), and Co(II) from Cu-Zn-Co dilute feed phase. In the double SDHLM system, Acorga M5640-loaded membrane was placed between the 1st and the 2nd compartment, whereas the mono(2-ethylhexyl) 2-ethylhexyl phosphonate [HEH(EHP)]-loaded membrane was placed between the 1st and the 3rd compartment of the transport cell. The feed solution was filled in the central feed compartment(1st compartment) of the transport cell. The effect of the different experimental variables on separation was examined. The optimum separation conditions were summarized. An analysis of mass transfer resistances in the double SDHLM system shows that the mass transfer resistance for the diffusion of Zn(II) ions in the microporous membrane phase is dominant and the mass transfer resistances for the diffusion of copper (II) ions in the aqueous boundary layer and in the microporous membrane phase are dominant in comparison with the overall mass transfer resistance. The experiments verify that the double strip dispersion hybrid liquid membrane (SDHLM) possesses the nonequlibrium mass transfer characteristic.

The performance and phase separated characteristics of an anaerobic baffled reactor treating soybean protein processing wastewater

A laboratory-scale anaerobic baffled reactor (ABR) with four compartments using soybean protein processing wastewater as organic loading rates (OLRs) was investigated for the performance and phase separated characteristics. It was found that the chemical oxygen demand (COD) removal efficiencies were 92–97% at 1.2–6.0 kg COD/m 3 d feeding. The dominated species, propionate and butyrate, were found in the 1st compartment. Acetate was dominated in the 2nd compartment and then decreased in the 3rd and 4th. Meanwhile, 93% volatile fatty acids (VFAs) were removed in the 3rd and 4th compartments. In the 1st compartment, biogas revealed carbon dioxide (CO 2) and hydrogen (H 2). The highest H 2 yield was found in the 2nd compartment, thereafter decreased from the 2nd to 4th which corresponded to the increased of the methane (CH 4) yield. It indicated that the proper anaerobic consortium in each separate compartment was developed along with substrate availability and specific environmental conditions.

Studies on supported liquid membrane for simultaneous separation of Fe (III), Cu (II) and Ni (II) from dilute feed

Supported liquid membranes (SLMs) are used in the extraction and separation of metals from dilute feed. In this paper, we show an innovative application of SLMs in the simultaneous separation of three metal species, employing a two-membrane–three-compartment cell. Two PTFE support membranes loaded with Alamine 336 and LIX 84, respectively, were used in this study. An Alamine 336-loaded membrane was placed between the 1st and the 2nd compartment, whereas the LIX 84-loaded membrane was placed between the 2nd and the 3rd compartment of the transport cell. With this cell, we were able to separate Fe 3+, Cu 2+ and Ni 2+ simultaneously from a feed containing these three species in 1 M NaCl and at pH of 2, into three compartments of the transport cell. Fe 3+ was separated from the feed through the Alamine 336-loaded membrane, whereas Cu 2+ was transported through the LIX 84-loaded membrane. Ni 2+ remained in the central feed compartment (2nd compartment) of the cell. The transport fluxes of Fe 3+ and Cu 2+ through the two membranes were found to be 3.6 and 5.1 μmol/m 2 s, respectively.

Redistribution of renal blood flow in patients with liver cirrhosis: The role of renal PGE 2

Cirrhotic patients frequently show a decrease in renal blood flow and redistribution of the flow from the outer cortex to the juxtamedullary cortex. The cause of the maintenance of juxtamedullary perfusion is not presently known. Prostaglandin E2 (PGE2) has its vasodilating effect on medullary and juxtamedullary vessels where it is synthesized. Therefore, its increased production, frequently shown in cirrhotics, could be responsible for the relative preservation of juxtamedullary blood flow. To verify this hypothesis we examined 13 cirrhotic patients. In these patients we determined mean renal blood flow (MRBF), blood flow in the 1st compartment (ICBF) and in the 2nd compartment (IICBF) with the 133-Xenon washout technique and PGE2 plasma levels in the renal veins (PGE2V). MRBF and ICBF were significantly reduced as compared to control subjects (P less than 0.01); IICBF resulted unaltered. Significant correlation was found between IICBF and PGE2V (P less than 0.01). Our data confirm the decrease in renal blood flow and the redistribution of intrarenal blood flow in cirrhotic patients. The maintenance of IICBF is likely to be a consequence of PGE2 renal production.

Neuronal and extraneuronal uptake and efflux of catecholamines in the isolated rabbit heart.

1. Isolated rabbit hearts were perfused with (−)-noradrenaline, (−)-adrenaline and (±)-isoprenaline for various time periods (1–180 min) and then washed with an amine-free medium. The venous concentration of the amine was estimated fluorimetrically during the infusion and after its end, to study removal and efflux, respectively. 2. In untreated hearts and after pretreatment with reserpine the removal had a constant rate over 20–60 min. After pretreatment with pargyline to block monoamine oxidase (MAO), however, the removal of noradrenaline declined exponentially to zero. Inhibition of the neuronal uptake (desipramine) and chemical sympathectomy (6-hydroxydopamine) abolished the removal of noradrenaline. Isoprenaline was not removed to any significant extent. 3. The efflux of noradrenaline originated in 4 different compartments as indicated by the various efflux components. The half-times in untreated hearts were about 0.1, 0.4 and 7 min, and after block of intraneuronal inactivation (pargyline plus reserpine) 0.1, 0.4 and 43 min. 4. The 1st compartment (t1/2=0.1 min) represents an open compartment including the vascular space. Several results indicate that the 2nd compartment is identical with the extracellular space. Inhibition of amine uptake by desipramine caused a strong increase of the total output resulting from the 2nd phase of efflux which then contributed a fraction of 0.21 to the total initial rate of efflux. Furthermore, endogenous noradrenaline released by sympathetic nerve stimulation and by DMPP was washed out of the heart into the perfusate with nearly the same half-time (t1/2=0.32 min) as that found for the 2nd phase of efflux following noradrenaline infusion (t1/2=0.41 min). The 3rd compartment of untreated hearts (t1/2=7 min) is not identical with that found after block of both MAO and vesicular uptake (t1/2=43 min). The former compartment was smaller and more rapidly equilibrated, and access of catecholamines was not depressed by inhibition of neuronal uptake or by chemical sympathectomy. On the other hand, the compartment occurring after block of intraneuronal inactivation became smaller—or even disappeared—after inhibition of neuronal uptake or after chemical sympathectomy; this latter compartment was not affected by block of vesicular uptake. It is concluded that the 3rd compartment of untreated hearts is located extraneuronally; an intraneuronal compartment could not be detected in these hearts under efflux conditions. The 4th noradrenaline compartment, occuring as 3rd phase of efflux after block of MAO, is located within the adrenergic nerves but outside the vesicles; therefore this compartment is identical with, or is part of, the axoplasm. 5. The efflux of isoprenaline originated in 3 different compartments of which the 1st and 2nd (t1/2=0.1 and 0.3 min) seem to be identical with the corresponding noradrenaline compartments. The 3rd isoprenaline compartment must be extraneuronal since the slow isoprenaline efflux, even after block of MAO, was similar to that of noradrenaline from untreated hearts. In contrast, after block of intraneuronal inactivation the slow adrenaline efflux was identical with the neuronal efflux of noradrenaline. 6. Since the half-time of elimination of noradrenaline from the axoplasmic compartment increased with increasing initial rates of efflux (Yo), it was assumed that a capacity-limited process was involved in the neuronal efflux. This can be exhaustion of intraneuronal binding sites, saturation of efflux or enzymatic degradation.