Role of unstirred layer in intestinal absorption of phenylalanine in vivo

The appearance rate of l- and d-phenylalanine in the venous blood of rat jejunal loops in vivo is increased up to 60% if the intraluminal solution is mixed more efficiently by the simultaneous perfusion of air. The effect decreases as the luminal concentration is increased to 100 mmol/1. Thus, the apparent Michaelis constants are by 50% lower in the case of the reduced unstirred layer (26 to 17 for l- and 9 to 6 mmol/1 for d-phenylalanine).The enhancement of the absorption and the reduction of the Michaelis constants can be attributed to the reduction of the effective unstirred layer thickness by about 400–500 μm.     

Release of substance P-like immunoreactive material from the stomach of the rainbow trout

Summary The release of substance P-like immunoreactive material (SPLI) from the vascularly perfused stomach of the rainbow trout, Oncorhynchus mykiss, was studied. In most cases, SPLI was detected in the collected vascular perfusate during experimental resting conditions. Distensions of the stomach, accomplished by a water-filled intragastric balloon, produced an initial rapid relaxation of the stomach, followed by a slow further relaxation and a stimulation of contractile activity. The amount of SPLI in the vascular perfusate was significantly elevated during the distension period. Tetrodotoxin had no effect on the response to distension or on the release of SPLI during distension, indicating release from tetrodotoxin-insensitive neurons or endocrine cells. The results suggest that a substance P-like peptide may be involved in the contractile response and/or in the maintenance of muscular tone during gastric distensions in the rainbow trout. Infusion of capsaicin had no effect on the release of SPLI. However, capsaicin caused an increase in vascular flow, an effect that could be repeated on a second infusion of capsaicin, indicating that the action may not be specific to sensory neurons.Abbreviations 5-HT 5-Hydroxytryptamine - RIA radioimmunoassay - SP substance P - SPLI substance P-like immunoreactive material - TTX tetrodotoxin     

Chronopharmacokinetics and Cardiovascular Effects of Nifedipine

Orcadian phase dependency in pharmacokinetics and hemodynamic effects on blood pressure and heart rate of different galenic formulations of nifedipine (immediate-release, sustained-release, and i.v. solution) were studied in healthy subjects or in hypertensive patients. Pharmacokinetics of immediate-release but not sustained-release and i.v. nifedipine were dependent on time of day: immediate-release nifedipine had higher C_max (peak concentration) and shorter t_max (time-to-peak concentration) after morning than evening application, and bioavailibility in the evening was reduced by about 40%. Orcadian rhythm in estimated hepatic blood flow as determined by indocyanine green kinetics may contribute to these chronokinetics. A circadian time dependency was also found in nifedipine-induced effects on blood pressure and heart rate as monitored by 24-h ambulatory blood pressure measurements. In conclusion, the dose response relationship of oral nifedipine is influenced by the circadian organization of the cardiovascular system as well as by the galenic drug formulation.     

Identification of Strychnine Binding Sites in the Rat Retina

Abstract: [³H]Strychnine specifically binds to membrane fractions isolated from rat retinae. The binding is saturable, with an apparent dissociation constant, K _D, of 14.3 × 10⁻⁹ M and 205 fmol bound/mg protein. Specific binding is time-dependent and proportional to protein concentration. Glycine and taurine are equally potent inhibitors of [³H]strychnine binding ( K _i= 4 × 10⁻⁵ M); no other amino acids endogenously present in the retina inhibited [³H]strychnine binding.     

Relative position of trypsin banded homologous chromosomes in human (female) metaphase figures.

"Generalized distances" between centromeres were statistically analyzed (chi2 test) on 50 normal female trypsin-banded metaphase figures. This study revealed that the homologous chromosomes of the pairs 13, 17, 14, and 21 lie closer together than would be expected by a reference distribution, and this in a statistically significant way. The same relative position was demonstrated for the chromosome groups 13-14, 13-21, 14-21, 15-22, and 14-22. Evidences were collected that also showed that homologous chromosomes of the pairs 1, 19, and 20 and the chromosome groups 15-21, 13-15, and 18-20 tend to lie closer together. Giving a functional interpretation to the phenomenon of non-random distribution of chromosomes in metaphase figures, it may be suggested that the chromosomes 13, 14, and 21 are involved in the organization of the human nucleolar organizers, more frequently than the other D- and G-group chromosomes.     

Optogenetic manipulation of cyclic guanosine monophosphate to probe phosphodiesterase activities in megakaryocytes

Cyclic guanosine monophosphate (cGMP) signalling plays a fundamental role in many cell types, including platelets. cGMP has been implicated in platelet formation, but mechanistic detail about its spatio-temporal regulation in megakaryocytes (MKs) is lacking. Optogenetics is a technique which allows spatio-temporal manipulation of molecular events in living cells or organisms. We took advantage of this method and expressed a photo-activated guanylyl cyclase, Blastocladiella emersonii Cyclase opsin (BeCyclop), after viral-mediated gene transfer in bone marrow (BM)-derived MKs to precisely light-modulate cGMP levels. BeCyclop-MKs showed a significantly increased cGMP concentration after illumination, which was strongly dependent on phosphodiesterase (PDE) 5 activity. This finding was corroborated by real-time imaging of cGMP signals which revealed that pharmacological PDE5 inhibition also potentiated nitric oxide-triggered cGMP generation in BM MKs. In summary, we established for the first-time optogenetics in primary MKs and show that PDE5 is the predominant PDE regulating cGMP levels in MKs. These findings also demonstrate that optogenetics allows for the precise manipulation of MK biology.