The extracellular matrix of stratum corneum: role of lipids in normal and pathological function

The mammalian stratum corneum, formerly treated as a homogeneous film, is now more properly viewed as a two-compartment system. The cornified cell is protein-enriched and lipid-depleted, lying embedded in an expanded extracellular matrix of highly nonpolar lipids. Because of its strategic location between the cornified layer, this lipid matrix is responsible for many phenomena related to the permeability barrier, as well as cohesion and desquamation. Thus, manipulation of this compartment could lead to enhanced drug delivery and improved lubrication, as well.     

Melatonin Receptors on Ovine Pars Tuberalis: Characterization and Autoradiographicai Localization

The functional significance of the pars tuberalis (PT) of the mammalian adenohypophysis has remained an enigma (1, 2). One view of its function is that it acts as an auxiliary gland to support the endocrine role of the pars distalis (PD) (2), as it has been shown to contain immunocytochemically identifiable thyrotrophs and gonadotrophs (1). Many of the cells of the PT are, however, ultrastructurally unique suggesting an independent function for this tissue. Our recent demonstration that the PT of the rat is a major binding site for the ligand iodomelatonin lends further support to this idea (3). We have utilized the highly specific ligand [¹²⁵l]melatonin, and have demonstrated that it binds exclusively, with very high affinity, to the PT but not the PD of the adult sheep adenohypophysis. These findings support the conclusion that the PT has a distinct role in relation to melatonin action and seasonal reproduction.     

Pharmacology of the internal anal sphincter and its relevance to faecal incontinence

1 The internal anal sphincter (IAS) has a spontaneous tone and is the main contributor to the maintenance of faecal continence. The spontaneous resting tone exhibited by the sphincter can be modified by neurotransmitters from the autonomic and enteric nervous systems. 2 In this review, the influence of the sympathetic and parasympathetic nervous systems on IAS tone are discussed and the putative roles of nitric oxide, carbon monoxide, vasoactive intestinal peptide and adenosine triphosphate in non‐adrenergic non‐cholinergic transmission are considered. 3 Faecal incontinence is a common condition that places a heavy financial burden on the health service and severely affects patients’ quality of life. Resting anal pressure is reduced in patients with faecal incontinence and agents that increase sphincter tone tend to relieve symptoms. The results of clinical studies of the use of phenylephrine to treat faecal incontinence are reviewed. 4 It is concluded that the IAS is a potential target for drug development for the treatment of faecal incontinence.     

Histopathological characterisation of effects of the mouse Pax6 missense mutation on eye development

Mutations in PAX6/Pax6 lead to a variety of ocular anomalies in humans and mice. The aim of the study was to characterise the ocular abnormalities caused by the missense Pax6^Leca4 mutation and compare them to published observations on Pax6 alleles that are functionally equivalent to Pax6⁻ null alleles (such as Pax6^Sey and Pax6^Sey-Neu) and human inherited eye diseases. Ocular features of homozygous Pax6^Leca4/Leca4 and heterozygous Pax6^Leca4/+ embryos at E12.5-E18.5, heterozygous Pax6^Leca4/+ young mice at P18 and heterozygous Pax6^Leca4/+ adults at 12 weeks were analysed histologically with their wild-type Pax6^+/+ littermates. Homozygous Pax6^Leca4/Leca4 fetuses died perinatally with no eyes although an optic cup rudiment with pigmented cells developed. Pax6^Leca4/+ mice were microphthalmic and a range of other severe ocular phenotypes affected both the anterior and the posterior segments. In contrast to Pax6^+/−, the Pax6^Leca4/+ eyes had no goblet cells in the corneal epithelium, the iris was not hypoplastic and there was no lens-corneal epithelial plug. However, microphthalmia was more severe, corneal vascularisation occurred earlier (during fetal stages), pigmented cells were present in the vitreous and corneal stroma and the ciliary body was malformed or abnormal. These results show that, although Pax6^Leca4/+ lacked some eye abnormalities commonly seen in Pax6^Sey/+ and Pax6^Sey-Neu/+ eyes, in most respects their eyes were more severely affected. These differences probably reflect both differences between the Pax6^Leca4 and the Pax6^Sey-Neu mutations and differences in modifier gene expression in different genetic backgrounds. The presence of pigmented cells in the cornea is a novel observation. Some Pax6^Leca4/+ ocular abnormalities were similar to those present in human Peters' anomaly and persistent hyperplastic primary vitreous (PHPV) so Pax6^Leca4/+ mice provide a useful model for some inherited eye diseases.     

Computed tomography (CT) analysis of the effects of chemonucleolysis

Computed tomography (CT) was performed on 30 patients with herniated lumbar discs before chemonucleolysis and at three and 12 months postinjection. At three months the compression produced by the herniated disc was reduced in 20 of the 30 patients; at 12 months there was complete relief of compression in all but four patients. Twenty-four patients developed diffuse bulging of the annulus. There was good correlation between the clinical results at three months and the reduction in compression as shown by the CT scan. At 12 months, no correlation was found between the remaining focal abnormalities and the clinical result. None of the patients developed epidural fibrosis. Chemonucleolysis has thus been shown to be an effective treatment of herniated lumbar discs, but it is definitely not indicated in cases where compression of the nerve root or dural sac is due to a bulging annulus.     

Physiologic and pathologic evaluation of chronic extra-aortic counterpulsation with latissimus dorsi flap. Preliminary results

This study attempted to evaluate the efficacy of chronic extra-aortic counterpulsation with a latissimus dorsi neuro vascular flap. Five dogs had a preliminary procedure consisting of the creation of a latissimus dorsi flap and a thoracotomy in which the flap was wrapped around the descending aorta just distal to the left subclavian artery. An epicardial lead was placed on the left ventricle and a nerve stimulating lead placed around the thoraco-dorsal nerve. Three weeks later, both leads were connected to a cardiomyostimulator programmed to function in a counterpulsation mode with a 1:2 assist frequency. Hemodynamic measurements were made at 6 and 8 and 10 and 12 weeks and the dogs were sacrificed. Three dogs had all sets of hemodynamic measurements made. Two of the three dogs demonstrated diastolic augmentation at 6 and 8 and 10 and 12 weeks average 20 to 25 mmHg. The third dog failed to demonstrate any change. All dogs were sacrificed at 12 weeks and specimens were submitted for histologic evaluation. The muscle flap was preserved in all animals. The aorta subjacent to the flap showed, (1) normal intima with no evidence of disruption or thrombus in all animals, (2) in the animals in whom counterpulsation was observed, there appeared to be thinning of the media in the aorta subjacent to the muscle flap, and (3) no evidence of distal emboli. This study demonstrated that chronic counterpulsation can be obtained with a latissimus dorsi flap. The actual hemodynamic benefits are not determined from this study. The medial thinning in the aortic wall may limit the long-term benefit of this procedure.