The Pharmacology of the Blood Vessels of the Human Umbilical Cord and Placenta Second Communication; On the Effect of the Nerve-muscle Poisons and Muscle Poisons

In a previous paper published in this journal, the author reported the results of investigations made for the purpose of finding the innervation of the blood vessels of the human umbilical cord and placenta, and the effects of the autonomic nerve poisons such as adrenalin, pilocarpin, acetyl-cholin, physostigmin and atropin on those vessels were also described. Further researches have been made with some of the nerve-muscle poisons and muscle poisons, in order to study the action of those drugs upon these embryonic blood vessels. The results obtained are as follows: 1. Pituitrin, in low concentration, shows vasoconstrictor action on the arteries of the cord and placenta, by acting on the sympathetic nerve as well as on the muscles of the vessels. In high concentration, it causes those arteries to dilate, chiefly by affecting their muscles. The veins of those organs are dilated by this drug, regardless of the degree of concentration, through the effect produced on the vascular muscles. 2. Tyramin shows vasoconstrictor action on the arteries of the cord and placenta, by affecting on the sympathetic nerves of those vessels, in low concentration, while in a higher concentration, it acts on the muscles. Tyramin, in very high concentration, dilates those arteries, but complete paralysis of the muscles is not likely to occur readily. 3. The effect of nicotin on the blood vessels of the umbilical cord and placenta is to dilate them, and the point where it acts is the muscles of the vessels. 4. Calcium affects the muscles of the blood vessels of the cord and placenta, and the dilatation of the vessels results. 5. Secacornin and Bombelon show vasoconstrictor action on the vessels of the cord and placenta. They seem to act mainly on the muscles, and to some extent on the sympathetic nerve as well. As far as the action on the sympathetic nerve is concerned, secacornin is superior to Bombelou and it manifests constrictor action in all cases. Bombelon, in low or moderate concentration, causes vasoconstriction, while dilatation is effected in high concentration. The effect of Bombelon on the muscles, especially its paralyzing action is stronger than that of secacornin. 6. Ergotinin makes the arteries of the cord and placenta dilate, by affecting the muscles of the vessels. 7. Quinine shows vasodilating action on the blood vessels of the cord and placenta by acting on their muscles. In high cocentration, quinine causes complete paralysis of the muscles. 8. Barium acts on the muscles of the vessels of the cord and placenta, thus causing constriction of those vessels. 9. The action of papaverin on the blood vessels of the cord and placenta is to dilate them by affecting the muscles. Paralysis of the muscles is very easily brought about by this drug. 10. The reaction of the drugs on the blood vessels of the umbilical cord and placenta is generally not very evident. The blood vessels of the cord, and those of the placenta, manifest nearly the same reaction to the drugs above mentioned, but considerable variation in the reactions in the arteries and veins is observed

The Pharmacological Studies on the Human Uterus Second Communication; On the Effects of Uterine Stimulants, Muscle-Poisons and certain other Drugs

In a previous communication the automatism and innervation of the human uterus, together with the effects of the autonomic poisons on the uterus were dealt with. The following results have been obtained in the present research. 1. Pituitrin, in low or moderate concentration, manifests stimulative action on the human uterus, while a highly concentrated, solution causes its depression. Stimulative action in low concentration is due to the stimulation of the motor-sympathetic apparatus, but the same in moderate concentration is to be attributed to the stimulation of not only sympathetic nerve but also of the muscle. Depressive effect from highly concentrated solution is the result of the paralysis of the muscle. But this paralyzing action on the muscle is probably due to the effect of chloretone, which is added to pituitrin. 2. A small quantity of bombelon causes contraction of the uterus by stimulating the muscle, and a moderate quantity leads to depression by affecing the sympathetic depressor, while a large quantity of this drug shows depressive effect by paralyzing the muscle itself. 3. A small quantity of secacornin exhibits depressive action on the uterus by stimulating the sympathetic depressor. The depression caused by a moderate quantity of secacornin is followed by contraction, which is due to the stimulation of the muscle. A large quantity of this drug causes the paralysis of the muscle. 4. Hydrastinin produces a stimulative effect on the uterus regardless of the degree of concentration. This effect is due chiefly to the stimulation of the muscle, but to some extent to the stimulation of the sympathetic nerve as well. 5. Veratrin, in low concentration, manifests stimulative action on the uterus, while in high concentration it leads to depression, by affecting the muscle. 6. The effect of barium on the uterus is to cause its contraction, and the point of attack is the muscle itself. 7. Papaverin, in any degree of concentration within the limit of an efficient quantity, exerts depressive action on the uterus by affecting the muscle. 8. A small quantity of nicotin produces depressive effect on the uterus by stimulating the sympathetic depressor, and a moderate quantity shows stimulative action by affecting the motor-sympathetic, while a large quantity of this drug leads to the depression which may be attributed to the paralysis of the muscle. 9. Caffein produces depressive effect on the uterus regardless of the degree of concentration. Any solution from low up to moderately concentrated, affects the sympathetic depressor, while a highly concentrated solution attacks the muscle. 10. A small quantity of cocain exerts stimulative action on the uterus by affecting the motor-sympathetic, while a moderate quantity produces the same, affecting both the motor-sympathetic and the muscle. The contraction caused by a moderate quantity of cocain is, in some case, followed by relaxation. A large quantity of this drug produces a depressive effect by paralyzing the muscle. 11. Morphin, in low or moderate concentration, manifests stimulative effect on the uterus, while in high concentration it leads to depression. The former is due to the stimulation of the motor-sympathetic, the latter to the paralysis of the muscle. 12. Digitalin acts as a stimulant on the uterus by affecting the muscle. 13. A small quantity of calcium produces stimulative effect on the uterus by affecting its muscle, while a moderate quantity causes depression, owing to the sympathetic depressor. A large quantity of calcium causes depressive action by paralyzing the muscle. 14. As it has been stated in preceding chapters, the human uterus and the uterus of various animals show nearly or quite the same reactions to certain kinds of drugs. while quite different reactions result from the use of certain other drugs

The Pharmacology of the Blood Vessels of the Human Umbilical Cord and Placenta First Communication; On the Effect of the Autonomic Nerve Poisons

This paper deals with pharmacological studies of the blood vessels of the human umbilical cord and placenta, for the purpose of investigating the innervation of those vessels and their pharmacological reactions, a matter which is as yet not established. In the research on this subject, the following results were obtained: 1. Adrenalin manifests vasoconstrictor action on the arteries of the umbilical cord and placenta, as well as on the vein of the cord. Also this action may be depressed or reversed by the use of atropin or ergotamine. Adrenalin in high concentration causes all of these vessels to dilate, while the vein of the placenta is dilated by adrenalin in any degree of concentration, within the limits of an efficient dose. The constrictor and dilator action of this drug on the blood vessels is understood to be due to the stimulation of the motor and inhibitory fibres of the sympathetic nerve respectively. 2. Acethyl-cholin acts as vasoconstrictor on the arteries of the cord and placenta. This action may be attributed to the stimulation of the parasympathetic nerve, as it is antagonized by a small dose of atropin. This suggests that the arteries of the cord and placenta are innervated by the vasoconstrictor fibres of the parasympathetic nerve. Despite these facts, it was not possible to recognize the vasoconstrictor action of acethylcholin on the veins of the cord. and placenta. Acethyl-cholin in high concentration dilates both kinds of the blood vessels of the cord and placenta. This dilating action is due not to the paralysis of the muscles of the vessels, but probably to the stimulation of the vasodilator fibres of the sympathetic nerve. 3. The action of pilocarpin on the blood vessels of the umbilical cord and placenta is to dilate them, and its point of attack seems to be the vasodilator of the sympathetic nerve. The effect of this drug on the parasympathetic nerve in these vessels was not observed in this experiment. 4. Physostigmin shows itself to be a vasoconstrictor on the vessels of the cord and placenta. It affects the muscles chiefly and the parasympathetic nerve of the vessels to some extent. 5. Atropin by itself does not have any definite action on the vessels of the cord and placenta, but it can depress the effect of acethyl-cholin by a very small dose, and it can also depress or reverse the effect of adranalin by a larger dose. So, it is clearly seen that the parasympathetic nerve and the motor fibre of the sympathetic nerve are paralyzed by a certain concentration of atropin, but the inhibitory fibre of the latter is not influenced by this drug. Atropin in very high concentration dilates these vessels, owing to the paralysis of the muscle. 6. From the facts learned in this research regarding the pharmacological reactions, it may be concluded that the arteries of both umbilical cord and placenta are innervated by the vasoconstrictor fibre of the sympathetic and parasympathetic nerves, and the dilatation of these vessels is controlled by the dilator fibre of the sympathetic nerve. The existence of the constrictor fibre of the parasympathetic nerve in the vein of the cord could not be proved. The sympathetic constrictor in the vein is inferior in its developement to the same in the artery. In the vein of the placenta, it was not possible to confirm the innervation of the vasoconstrictor of either the parasympathetic or the sympathetic nerve. 7. The arteries of the umbilical cord and placenta show similar pharmacological reaction to the drugs. Therefore it may be concluded that they are under the same innervation. The vein of the placenta reacts to the drugs in a somewhat different way from what the arteries do. The action of the drugs on the vein of the cord coincides partly with the action observed on the arteries, and partly with that on the placental vein. 8. These embryonic blood vessels manifest nearly the same pharmacological reactions as in the general blood vessels of the body, though there is more or less difference between them

Novel Charge Ordering in the Trimer Iridium Oxide BaIrO3

We have prepared polycrystalline samples of the trimer Ir oxide BaIrO3 with face-shared Ir3O12 trimers, and have investigated the origin of the phase transition at 182 K by measuring resistivity, thermopower, magnetization and synchrotron x-ray diffraction. We propose a possible electronic model and transition mechanism, starting from a localized electron picture on the basis of the Rietveld refinement. Within this model, BaIrO3 can be basically regarded as a Mott insulator, when the Ir3O12 trimer is identified to one pseudo-atom or one lattice site. The transition can be viewed as a transition from the Mott insulator phase to a kind of charge ordered insulator phase.Comment: 8 pages 5 figures, Crystals (in press

Isolation and sequencing of swine carbonic anhydrase VI, an enzyme expressed in the swine kidney

BACKGROUND: Carbonic anhydrase VI (CA-VI) is produced by the salivary gland and is secreted into the saliva. Although CA-VI is found in the epithelial cells of distal straight tubule of swine kidneys, the exact function of CA-VI in the kidneys remains unclear. RESULTS: CA-VI was located in the epithelial cells of distal straight tubule of swine kidneys. A full-length cDNA clone of CA-VI was generated from the swine parotid gland by reverse transcription polymerase chain reaction, using degenerate primers designed based on conserved regions of the same locus in human and bovine tissues. The cDNA sequence was 1348 base pairs long and was predicted to encode a 317 amino acid polypeptide with a putative signal peptide of 17 amino acids. The deduced amino acid sequence of mature CA-VI was most similar (77.4%) to that of human CA-VI. CA-VI expression was confirmed in both normal and nephritic kidneys, as well as parotid. As the primers used in this study spanned two exons, the influence of genomic DNA was not detected. The expression of CA-VI was demonstrated in both normal and nephritic kidneys, and mRNA of CA-VI in the normal kidneys which was the normalised to an endogenous β–actin was 0.098 ± 0.047, while it was significantly lower in the diseased kidneys (0.012 ± 0.007). The level of CA-VI mRNA in normal kidneys was 19-fold lower than that of the parotid gland (1.887). CONCLUSIONS: The localisation of CA-VI indicates that it may play a specialised role in the kidney

Cleavage of Toll-Like Receptor 9 Ectodomain Is Required for In Vivo Responses to Single Strand DNA

Mouse toll-like receptor 9 (TLR9) is an endosomal sensor for single-stranded DNA. TLR9 is transported from the endoplasmic reticulum to endolysosomes by a multiple transmembrane protein Unc93 homolog B1, and proteolytically cleaved at its ectodomain. The structure of TLR9 and its biochemical analyses have shown that the proteolytic cleavage of TLR9 ectodomain enables TLR9-dimerization and TLR9 activation. However, the requirement of TLR9 cleavage in vivo has not been studied. We here show that the 13 amino acids deletion at the cleavage site made TLR9 resistant to proteolytic cleavage. The deletion mutation in the Tlr9 gene impaired TLR9-dependent cytokine production in conventional dendritic cells from the mutant mice. Not only in vitro, in vivo production of inflammatory cytokines (TNF-α and IL-12p40), chemokine (CCR5/RANTES), and type I interferon (IFN-α) induced by administration of TLR9 ligand was also impaired. These results demonstrate that the TLR9 cleavage is required for TLR9 responses in vivo