Effects of angiotensin II type 1 receptor antagonist on pressor responses to pulsatile compression of the rostral ventrolateral medulla in rats.

The rostral ventrolateral medulla (RVLM) is known to be a major center regulating sympathetic and cardiovascular activities. A possible association between neurovascular compression of the RVLM and essential hypertension has been indicated. The present study was performed to determine the role of angiotensin II (AngII) in the pressor and sympathetic responses to pulsatile compression of the RVLM. To determine the role of glutamate and AngII in the RVLM, L-glutamate (Glu) 2 nmol or AngII 100 pmol was injected into the RVLM with or without RVLM pretreatment of kynurenate (Glu receptor antagonist) 3nmol, candesartan (AngII type 1 (AT1) receptor antagonist) 2 nmol, or PD123319 (AngII type 2 (AT2) receptor antagonist) 1 nmol in anesthetized Wistar rats. In addition, to determine the role of glutamate and AngII in the pressor and sympathetic effects to the RVLM compression, kynurenate, candesartan, or PD123319 was locally injected before pulsatile compression of the RVLM. Finally, to determine the effects of peripherally administered AngII antagonists in these pressor and sympathetic excitatory responses, candesartan 0.25 micromol or PD123319 0.05 micromol was intravenously injected before pulsatile compression of the RVLM. Glu injected into the RVLM significantly increased mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SNA), and these effects were reduced by RVLM pretreatment with kynurenate, but were unaffected by candesartan or PD123319. AngII injected into the RVLM and pulsatile compression of the RVLM also increased MAP and SNA. However, in contrast with Glu injections, these effects were reduced by RVLM pretreatment with candesartan or kynurenate, but were unaffected by PD123319. Pressor and sympathetic excitatory responses to RVLM compression were reduced by intravenous pretreatment with candesartan but not with PD123319. These results indicate that, upon pulsatile compression of the RVLM, AngII may activate RVLM neurons via AT1 receptors and stimulate Glu release to thereby elicit sympathetic activation and pressor effects. Candesartan may exert its hypotensive effect at least in part by affecting the RVLM neurons to reduce sympathetic outflow induced by pulsatile compression of the RVLM.     

Ophthalmic Preservatives as Absorption Promoters for Ocular Drug Delivery

The effects of ophthalmic preservatives on the drug permeability through isolated ocular membranes of albino rabbits were investigated using a two-chamber glass diffusion cell. Tilisolol and fluorescein isothiocyanate (FITC)-dextrans (average molecular weights 4400 and 9400 Da; FD-4 and FD-10, respectively) were used as model penetrants of ophthalmic β-blockers and peptide drugs. Preservatives significantly enhanced the corneal penetration of not only tilisolol but also FITC-dextrans. Especially, benzalkonium chloride increased the corneal permeability of FD-4 and FD-10 by 28·8 and 37·1 times, respectively. These results indicate the usefulness of ophthalmic preservatives as absorption promoters for the ocular delivery of β-blockers and hydrophilic macromolecules. Preservatives also enhanced the conjunctival permeability of tilisolol, FD-4 and FD-10. The promoting effect of preservatives on the conjunctival drug penetration was smaller than that on the corneal one. Preservative increased the ratio of corneal to conjunctival permeability of tilisolol, FD-4 and FD-10. The different responses of corneal and conjunctival drug penetrations to ophthalmic preservatives may be useful to control the extent and pathway for the ocular and systemic absorptions of instilled drugs.     

Dorsal dislocation of the D.I.P. joint with fracture of the volar base of the distal phalanx

Between 1978 and 1985, we treated 12 cases of dorsally displaced fracture-dislocation of the I.P. joint of the thumb or of the D.I.P. joint of the finger, with a volar bony fragment. All were treated surgically, active exercise being started three to five weeks later. At the last follow-up, averaging 6.4 years (range 4.3-10 years) after operation, none of the joints was painful but the range of motion was somewhat limited.     

Growth Hormone-Releasing Hormone (GHRH)-GH-Somatic Growth and Luteinizing Hormone (LH)RH-LH-Ovarian Axes in Adult Female Transgenic Mice Expressing Human GH Gene

We have examined alterations in the hypothalamo-pituitary GH-somatic growth axis and the hypothalamo-pituitary LH-ovarian axis in a line of transgenic ICR mice expressing human GH (hGH) under the influence of the whey acid protein promoter. Transgenic female mice weighed twice as much as control females and were infertile. The size of the anterior pituitary (AP) was that of the controls. In transgenic mice, acinar cells in the mammary and mandibular glands displayed hGH-immunoreactivity, and plasma hGH was detected by radioimmunoassay. In the medial basal hypothalamus (MBH) of transgenic females, the immunoreactive-GHRH level was decreased (P<0.01). There was a corresponding reduction in the number of GHRH-immunoreactive neurons in the arcuate nucleus (ARC) and in the immunostaining of GHRH nerve terminals in the median eminence. The level of somatostatin (SRIH) in the MBH was increased (P<0.05), and SRIH-immunoreactive neurons in the periventricular nucleus (PeV) were increased in size and number in transgenic mice. The MBH level of LHRH in transgenic animals was greater (P<0.01) than in controls, although there was no apparent difference in the number of LHRH-immunoreactive neurons or in LHRH level in the preoptic area. There are fewer SRIH- and LHRH-immunoreactive neurons in the ARC in transgenic mice. Cells in the AP for GH, PRL, and LH were fewer in transgenic mice. The ovary suffered disturbance of follicular development and of corpora lutea formation.     

Effects of peripheral axotomy of the inferior alveolar nerve on the levels of neuropeptide Y in rat trigeminal primary afferent neurons

The effects of peripheral axotomy of the inferior alveolar nerve (IAN) on the presence and distribution of neuropeptide Y (NPY)-like immunoreactivity (IR) in the trigeminal sensory nuclear complex (TSNC) and trigeminal ganglion were investigated in the rat by immunohistochemistry. In the normal trigeminal ganglion, there were no NPY-IR cells, and some perivascular nerve fibres exhibited NPY-IR. In normal TSNC, many NPY-IR axons and nerve terminals were observed in the superficial layers of the subnucleus caudalis (SpVc) and paratrigeminal nucleus (paraV), but were sparse in the other subnuclei of the TSNC. Fourteen days following peripheral axotomy of the IAN, many large- and medium-sized cells in the trigeminal ganglion displayed NPY-IR, and marked increases in the numbers and staining densities of NPY-IR were observed in deeper laminae (laminae III-V) of the dorso-medial region of the SpVc and other nuclei, in addition to the dorso-medial region of the spinal trigeminal tract. Degrees of alterations of the levels of NPY were most marked in the SpVc. The present results indicate that peripheral axotomy of the IAN evokes the appearance of NPY-IR in the trigeminal ganglion and alterations of NPY-IR in the entire IAN projection areas of the TSNC.     

Two cases of non-rotation in adults: Its anatomical analysis

Two adult cases of non-rotation were anatomically analysed. The small intestine occupied the right flank and the colon the left. The ileum crossed the midline to enter the cecum from the right. The appendix vermiformis rested on the front of the cecum and extended upwards. The cecum was located in the lesser pelvis. They had no Ladd's bands, but in the first case fibrous bands from the posterior abdominal wall caused kinking. The colon of the first case had an intricate twist under the left kidney. The second case was also complicated with three loops, the third loop posed between the first and the second, accompanied by a rare vascular anomaly, a double inferior mesenteric artery. © 1993 Wiley-Liss, Inc.