Intestinal water and solute absorption studies: comparison of in situ perfusion with chronic isolated loops in rats

The effects of lumenal glucose on jejunal water transport and the influence of glucose-induced water absorption on solute uptake from single-pass perfusions are compared in anesthetized rats in situ and isolated chronic loops in unanesthetized rats in vivo. While the magnitudes of solute membrane permeabilities are consistently higher in the chronic loop system, the effects on water transport and its promotion of jejunal solute uptake are comparable between the two experimental systems. The effect of glucose-induced water absorption on the enhanced/baseline jejunal uptake ratio of the hydrophilic drug, acetaminophen, is greater than that for the lipophilic drug, phenytoin, in both experimental systems. The fact that chronic loop effective solute permeabilities were equivalent to solute membrane permeabilities in situ is consistent with greater lumenal fluid mixing in vivo. In addition, in situ body temperature affects the uptake of phenytoin but not acetaminophen, water, or glucose. This suggests that active and paracellular solute transport is not compromised in situ, while membrane partitioning and diffusion of lipophilic species are more sensitive to experimental conditions.     

Molecular mechanism for the relative binding affinity to the intestinal peptide carrier. Comparison of three ACE-inhibitors: enalapril, enalaprilat, and lisinopril

Three-dimensional magnetic resonance angiography (MRA) is a noninvasive technique that images the intracranial arterial vasculature without contrast agents. The suitability of MRA was evaluated for routine use and all children were prospectively studied with conventional MR imaging and time off flight MRA (FISP3D). All MR studies were performed on a 1.5 T-MRA system using a circularly polarized head coil. The study comprised 140 children, ages 3 weeks to 18 years, with different neuropediatric diseases. Major cervical and intracranial arteries were visualized in all age groups. Smaller branches of the supratentorial arteries were identified inconstantly and the number of arteries visualized increased up to the age of 6 years. Sixty-seven children (47%) had normal intracranial vasculature. MRA demonstrated anatomic variations in 21 patients (15%). Twenty-two of 32 children with congenital malformations demonstrated abnormalities of the intracranial vasculature. The diagnostic value of MRA was confirmed in 11 of 12 patients after neonatal stroke and in 3 of 10 children after stroke at older ages. Seven of 18 children with acute hemorrhage demonstrated arteriovenous malformations or an aneurysm on MRA. The correlation with digital subtraction angiographic findings was established in 13 patients. In 9 of 13 children with brain tumor, MRA proved to be diagnostically valuable. MRA proved to be of particular value in the evaluation of the carotid artery following extracorporeal membrane oxygenation therapy. MRA can be used in children of all age groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Selectivity of action of 8-alkylamino analogues of N6-cyclopentyladenosine in vivo: haemodynamic versus anti-lipolytic responses in rats

1. A1 adenosine receptor agonists with reduced intrinsic activity may be therapeutically useful as result of an increased selectivity of action. In this study the tissue selectivity of three 8-alkylamino substituted analogues of N6-cyclopentyladenosine (CPA) was investigated for haemodynamic and anti-lipolytic effects using an integrated pharmacokinetic-pharmacodynamic approach. 2. Chronically instrumented male Wistar rats received intravenous infusions of 4.0 mg kg(-1) 8-methylaminoCPA (8MCPA), 12.0 mg kg(-1) 8-ethylaminoCPA (8ECPA), 20.0 mg kg(-1) 8-butylaminoCPA (8BCPA) or vehicle during 15 min. During experimentation, serial arterial blood samples were drawn for the determination of agonist concentrations and plasma non-esterified fatty acid (NEFA) levels. Blood pressure and heart rate were monitored continuously. In addition to the CPA analogues, each rat received a rapid bolus infusion of CPA to determine the maximal effects of the full agonist. 3. The concentration-time profiles of the CPA analogues could be described by a bi-exponential function. Values for clearance, volume of distribution at steady state and elimination half-life were 44+/-5, 48+/-6 and 39+/-2 ml min(-1) kg(-1), 0.97+/-0.09, 0.84+/-0.10 and 1.05+/-0.07 1 kg(-1) and 25+/-2, 28+/-2 and 40+/-2 min for 8MCPA, 8ECPA and 8BCPA, respectively (mean+/-s.e.mean, n=6-8). 4. Different models were used to derive the concentration-effect relationships for heart rate and NEFA, yielding estimates of potency (EC50) and intrinsic activity (Emax) for both effects of the compounds in vivo. On heart rate the compounds acted as partial agonists, with Emax values of -173+/-14, -131+/-11 and -71+/-6 beats min(-1) for 8MCPA, 8ECPA and 8BCPA, respectively. These Emax values were significantly lower than the maximal effect of CPA (-208+/-8 beats min(-1)). With regard to the anti-lipolytic effect all three compounds were full agonists and lowered NEFA levels to the same extent as CPA (69%). The estimated Emax values were 63+/-5, 63+/-4 and 68+/-2%, respectively. 5. Furthermore, the compounds were more potent in causing anti-lipolytic than cardiovascular effects. The EC50 values for the NEFA and heart rate lowering effects were 37+/-15, 68+/-22 and 659+/-108 ng ml(-1) and 164+/-22, 341+/-76 and 975+/-190 ng ml(-1) for 8MCPA, 8ECPA and 8BCPA, respectively (mean+/-s.e.mean, n=6-8). 6. This study demonstrates that partial agonists for the A1 adenosine receptor have increased selectivity of action in vivo. The 8-alkylamino analogues of CPA may be useful anti-lipolytics with less pronounced haemodynamic side effects.     

An inverse method for the design of TIR collimators to achieve a uniform color light beam

Color-over-angle (CoA) variation in the light output of white LEDs is a common and unsolved problem. In this article we introduce a new method to reduce CoA variation using a special collimator. The method is based on analytical inverse design methods. We present a numerical algorithm to solve the differential equations arising from this method and verify the results using Monte Carlo raytracing.     

Economic and environmental impact of electric vehicles production in Indonesia

The use of fossil fuel-based vehicles may gradually be replaced by electric vehicles in the future. The trend indicates that the number of users of electric vehicles, especially electric cars, continues to increase. Indonesia is well-positioned to take advantage of this opportunity as it has the world’s largest nickel reserves, an essential raw material for making electric vehicle batteries (EVB). The study examines the economic and environmental implications if Indonesia were to successfully set up electric vehicle (EV) production rather than exporting such raw materials overseas. We use an input–output model to estimate electric vehicle production’s economic and environmental impacts in Indonesia. This study assumes that nickel, which is usually exported, is absorbed by domestic economic activities, including being used in manufacturing batteries and electric vehicles in Indonesia. Our estimates include direct and indirect output, value-added, and employment changes. The same model is also used to estimate changes in emissions’ environmental costs. It is evident from the results that batteries and EV production are economically beneficial. Additional value-added is Rp. 100.57 trillion, 1.5% of GDP in 2010. At the same time, 538,658 additional jobs were created, which is about a 0.5% increase. Lastly, EV production will have extra external costs of emissions, around Rp. 2.23 trillion, or an increase of about 0.6%. Based on these findings, it is concluded that electric vehicle production increases productivity, gross value-added, and job creation with a relatively small impact on the environment. A limitation of this study is that we assumed EVs were produced for export only, and we did not assume a reduction in economic activities in the supply chain of conventional vehicles.

Graphical Abstract

Economic and Environmental Impact of Electric Vehicles Production in Indonesia.