19.1 The terminal phase

Author(s):  
Mike Harlos
Keyword(s):  
1990 ◽  
Vol 122 (2) ◽  
pp. 191-200 ◽  
Author(s):  
C. G. J. Sweep ◽  
Margreet D. Boomkamp ◽  
István Barna ◽  
A. Willeke Logtenberg ◽  
Victor M. Wiegant

Abstract The effect of intracerebroventricular (lateral ventricle) administration of arginine8-vasopressin (AVP) on the concentration of β-endorphin immunoreactivity in the cerebrospinal fluid obtained from the cisterna magna was studied in rats. A decrease was observed 5 min following injection of 0.9 fmol AVP. No statistically significant changes were found 5 min after intracerebroventricular treatment of rats with 0.09 or 9 fmol. The decrease induced by 0.9 fmol AVP was of short duration and was found 5 min after treatment but not 10 and 20 min. Desglycinamide9-AVP (0.97 fmol), [pGlu4, Cyt6]-AVP-(4–9) (1.44 fmol), Nα-acetyl-AVP (0.88 fmol), lysine8-vasopressin (0.94 fmol) and oxytocin (1 fmol) when intracerebroventricularly injected did not affect the levels of β-endorphin immunoreactivity in the cerebrospinal fluid 5 min later. This suggests that the intact AVP-(1–9) molecule is required for this effect. Intracerebroventricular pretreatment of rats with the vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP (8.63 fmol) completely blocked the effect of AVP (0.9 fmol). In order to investigate further the underlying mechanism, the effect of AVP on the disappearance from the cerebrospinal fluid of exogenously applied β-endorphin was determined. Following intracerebroventricular injection of 1.46 pmol camel β-endorphin-(1–31), the β-endorphin immunoreactivity levels in the cisternal cerebrospinal fluid increased rapidly, and reached peak values at 10 min. The disappearance of β-endorphin immunoreactivity from the cerebrospinal fluid then followed a biphasic pattern with calculated half-lifes of 28 and 131 min for the initial and the terminal phase, respectively. Treatment of rats with AVP (0.9 fmol; icv) during either phase (10, 30, 55 min following intracerebroventricular administration of 1.46 pmol β-endorphin-(1–31)) significantly enhanced the disappearance of β-endorphin immunoreactivity from the cerebrospinal fluid. The data suggest that vasopressin plays a role in the regulation of β-endorphin levels in the cerebrospinal fluid by modulating clearance mechanisms via V1-receptors in the brain.


Proceedings ◽  
2020 ◽  
Vol 78 (1) ◽  
pp. 11
Author(s):  
Alexander Parra-Coca ◽  
Antonio Boix-Montañés ◽  
Ana C. Calpena ◽  
Helena Colom

Osteoarthritis is frequently treated in veterinary settings with non-steroidal anti-inflammatory drugs (NSAID) such as carprofen (CP). Its action over the articular cartilage can be enhanced by increasing drug uptake into the cartilage, alongside its site of action, and anticipating its rapid distribution towards the bloodstream. A pharmacokinetic study to evaluate carprofen nanoparticles (NP) after intraarticular administration (IA) in rabbits was performed through a modeling allometric approach. The pharmacokinetic analysis of plasma profiles showed a rapid CP distribution outwards the synovial chamber but mainly remaining in plasma (Vc = 0.14 L/5 Kg), according to its high protein-binding. The absorption data modeling showed the occurrence of two different release–absorption rate processes after nanoparticle administration in the synovial space, i.e., a fast rate process causing a burst effect and involving the 59.5% of the total CP absorbed amount and a slow rate process, involving 40.5%. Interestingly, the CP burst effect inside the joint space enhances its diffusion towards cartilage resulting in CP accumulation in about three times higher concentrations than in plasma. In line with these results, the normalized-by-dose area under the concentration vs. time curve (AUC) values after IA were 80% lower than those observed after the intravenous. Moreover, the slower slope of the concentration–time terminal phase after IA administration vs. intravenous (IV) suggested a flip-flop phenomenon (0.35 h-1 vs. 0.19 h-1). Notably, CP clearances are predictive of the pharmacokinetic (PK) profile of CP in healthy humans (0.14 L/h/5 kg vs. 2.92 L/h/70 kg) although an over-estimation has been detected for cats or dogs (10 times and 4 times, respectively). This fact could probably be attributed to inter-species metabolic differences. In summary, despite the limited number of animals used, this study shows that the rabbit model could be suitable for a predictive evaluation of the release enhancement of CP-NP towards the biophase in arthritic diseases not due to sterical retention of the formulation.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Minoru Moriyama ◽  
Kouji Yasuyama ◽  
Hideharu Numata

AbstractInsect eggshells must meet various demands of developing embryos. These demands sometimes conflict with each other; therefore, there are tradeoffs between eggshell properties, such as robustness and permeability. To meet these conflicting demands, particular eggshell structures have evolved in diverse insect species. Here, we report a rare eggshell structure found in the eggshell of a cicada, Cryptotympana facialis. This species has a prolonged egg period with embryonic diapause and a trait of humidity-inducible hatching, which would impose severe demands on the eggshell. We found that in eggs of this species, unlike many other insect eggs, a dedicated cleavage site, known as a hatching line, was formed not in the chorion but in the serosal cuticle. The hatching line was composed of a fine furrow accompanied by ridges on both sides. This furrow-ridge structure formed in the terminal phase of embryogenesis through the partial degradation of an initially thick and nearly flat cuticle layer. We showed that the permeability of the eggshell was low in the diapause stage, when the cuticle was thick, and increased with degradation of the serosal cuticle. We also demonstrated that the force required to cleave the eggshell was reduced after the formation of the hatching line. These results suggest that the establishment of the hatching line on the serosal cuticle enables flexible modification of eggshell properties during embryogenesis, and we predict that it is an adaptation to maximize the protective role of the shell during the long egg period while reducing the barrier to emerging nymphs at the time of hatching.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Qiao Wang ◽  
Wenjin Liu ◽  
Junjun Wang ◽  
Hong Liu ◽  
Yong Chen

Abstract In this study, daidzein long-circulating liposomes (DLCL) were prepared using the ultrasonication and lipid film-hydration method. The optimized preparation conditions by the orthogonal design was as follows: 55 to 40 for the molar ratio of soybean phosphatidylcholine (SPC) to cholesterol, 1 to 10 for the mass ratio of daidzein to total lipid (SPC and cholesterol) (w:w), the indicated concentration of 5% DSPE-mPEG2000 (w:w), 50 °C for the hydration temperature, and 24 min for the ultrasonic time. Under these conditions, the encapsulation efficiency and drug loading of DLCL were 85.3 ± 3.6% and 8.2 ± 1.4%, respectively. The complete release times of DLCL in the medium of pH 1.2 and pH 6.9 increased by four- and twofold of that of free drugs, respectively. After rats were orally administered, a single dose of daidzein (30 mg/kg) and DLCL (containing equal dose of daidzein), respectively, and the MRT0−t (mean residence time, which is the time required for the elimination of 63.2% of drug in the body), t1/2 (the elimination half-life, which is the time required to halve the plasma drug concentration of the terminal phase), and AUC0−t (the area under the plasma drug concentration-time curve, which represents the total absorption after a single dose and reflects the drug absorption degree) of daidzein in DLCL group, increased by 1.6-, 1.8- and 2.5-fold as compared with those in the free group daidzein. Our results indicated that DLCL could not only reduce the first-pass effect of daidzein to promote its oral absorption, but also prolong its mean resident time to achieve the slow-release effect.


2019 ◽  
Vol 81 (4) ◽  
Author(s):  
Hari Prasetijo ◽  
Winasis Winasis ◽  
Priswanto Priswanto ◽  
Dadan Hermawan

This study aims to observe the influence of the changing stator dimension on the air gap magnetic flux density (Bg) in the design of a single-phase radial flux permanent magnet generator (RFPMG). The changes in stator dimension were carried out by using three different wire diameters as stator wire, namely, AWG 14 (d = 1.63 mm), AWG 15 (d = 1.45 mm) and AWG 16 (d = 1.29 mm). The dimension of the width of the stator teeth (Wts) was fixed such that a larger stator wire diameter will require a larger stator outside diameter (Dso). By fixing the dimensions of the rotor, permanent magnet, air gap (lg) and stator inner diameter, the magnitude of the magnetic flux density in the air gap (Bg) can be determined. This flux density was used to calculate the phase back electromotive force (Eph). The terminal phase voltage (V∅) was determined after calculating the stator wire impedance (Z) with a constant current of 3.63 A. The study method was conducted by determining the design parameters, calculating the design variables, designing the generator dimensions using AutoCad and determining the magnetic flux density using FEMM simulation.  The results show that the magnetic flux density in the air gap and the phase back emf Eph slightly decrease with increasing stator dimension because of increasing reluctance. However, the voltage drop is more dominant when the stator coil wire diameter is smaller. Thus, a larger diameter of the stator wire would allow terminal phase voltage (V∅) to become slightly larger. With a stator wire diameter of 1.29, 1.45 and 1.63 mm, the impedance values of the stator wire (Z) were 9.52746, 9.23581 and 9.06421 Ω and the terminal phase voltages (V∅) were 220.73, 221.57 and 222.80 V, respectively. Increasing the power capacity (S) in the RFPMG design by increasing the diameter (d) of the stator wire will cause a significant increase in the percentage of the stator maximum current carrying capacity wire but the decrease in stator wire impedance is not significant. Thus, it will reduce the phase terminal voltage (V∅) from its nominal value.


Copeia ◽  
1980 ◽  
Vol 1980 (4) ◽  
pp. 887 ◽  
Author(s):  
Robin W. Bruce
Keyword(s):  

Author(s):  
P H Whiting ◽  
D J King ◽  
A Ireland ◽  
M A Ratcliffe ◽  
A A Dawson

The activity of the lysosomal hydrolase N-acetyl-β-d-glucosaminidase (NAG) was measured in the urine of patients with leukaemia or myeloma. Elevated pre-treatment enzymuria was noted in all patient groups with acute myeloblastic leukaemias (AML) FAB type M4 or 5 displaying higher activities than AML patients FAB types M1–3, which in turn were higher than those found in patients with myelomatosis and chronic lymphocytic leukaemia. The ratio of the major isoenzymes of NAG, A/B was reduced significantly only in patients with AML. Following treatment, AML patients who entered remission demonstrated NAG levels which approached normal values. In those AML patients who were either in relapse, in the terminal phase of their illness or treated with aminoglycoside antibiotics, NAG enzymuria was similar to pre-treatment values. A reduction in urinary NAG levels and both serum and urine β2 microglobulin concentrations was also observed following treatment in myeloma patients. The use of enzymuria both as a guide to progress towards remission in AML patients and for assessing prognosis and progress in myeloma patients is discussed.


2021 ◽  
pp. 1-18
Author(s):  
Józef Szykulski ◽  
Jakub Wanot

The collapse of the Tiwanaku state around AD 1000 resulted in dramatic changes in the areas of its former colonies such as the Moquegua Valley, which featured the largest Tiwanaku communities outside the Altiplano. The inhabitants of these former colonies were forced to relocate to the areas north of Moquegua, including the Tambo River estuary (Arequipa Department, Province of Islay). This relocation has been confirmed at La Pampilla 1, where a large graveyard featuring funerary contexts of the postcollapse communities of Tiwanaku-Timulaca was found, with a calibrated 14C date between the eleventh and thirteenth centuries AD. In this article we discuss the results of excavations and analyses conducted at the La Pampilla 1 graveyard, the first systematically researched Tiwanaku site in the Tambo Valley: these findings confirm the existence of a relatively large, terminal-phase Tiwanaku population, represented by Tumilaca funerary contexts.


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