The role of central muscarinic and nicotinic receptors in the regulation of sodium and potassium renal excretion

The effect of intraseptal injection of carbachol and nicotine on urinary output of Na+ and K+ in untreated rats as well as in animals pretreated with locally injected atropine, hexamethonium, dibenamine and propranolol was studied in order to evaluate the relative role played by central muscarinic and nicotinic receptors in the regulation of salt and water renal excretion. The injection of 30-250 nmol of nicotine into the medial septal area caused a dose-dependent increase in Na+ and K+ urinary output whereas urine volume was little affected. The effect of 30 nmol of nicotine was blocked by pretreatment with 100 nmol of hexamethonium. In addition, pretreatment with 5 nmol of either hexamethonium or atropine partially antagonized the natriuretic and kaliuretic effect of 1 nmol of carbachol. Also the alpha-blocking agent, dibenamine (150 nmol) antagonized, while the beta-blocker, propranolol (100 nmol) significantly enhanced the effect of carbachol. Propranolol (100 nmol) alone caused a small, but significant increase in Na+ and K+ renal excretion. These results indicate that stimulation of both muscarinic and nicotinic receptors in the septal area, as caused by carbachol, elicits increased disposition of Na+ and K+ by the kidneys. Also, part of the effects of carbachol appear to be mediated by the release of endogenous catecholamines, acting on central alpha receptors to increase Na+ and K+ urinary excretion. On the other hand, simultaneous activation of beta-receptors by the released amines would partially inhibit this effect.     

Quantitative bone histology in children with chronic renal failure

Quantitative bone histology (on undecalcified sections following double tetracycline labeling), radiographs, and biochemistry were studied in 47 children, ages 1 to 17 years, with glomerular filtration rates (GFR) below 80 ml/min/1.73m2. The earliest histologic change was an increased osteoid surface accompanied by increased osteoblast and tetracycline surfaces. However, significant bone disease (increased osteoclastic surface, fibrosis, increased osteoid area, increased mineralization lag time, and reduced tetracycline uptake at osteoid surfaces) occurred only at GFR below 30 ml/min/1.73m2. Radiographs and alkaline phosphatase were normal in 25% of children with significant bone disease; parathyroid hormone was increased in 48% of children without bone disease. Thus, these noninvasive investigations were poor predictors of disease presence. GFR was the most sensitive indicator because bone disease occurred only at GFR below 30 ml/min/1.73m2 and was present in all children with GFR below 20 ml/min/1.73m2. It was concluded that bone histology is required for early detection of bone disease and is an essential tool in experimental studies of renal osteodystrophy. However, because the level of GFR will indicate the presence or absence of bone disease in most children, bone biopsy can be avoided generally in clinical practice.     

Intrapericardial Blalock-Taussig shunt

The standard Blalock-Taussig (B-T) shunt is preferred over other shunts in the treatment of infants with cyanotic heart disease and reduced pulmonary blood flow. The B-T shunt is not, however, without problems such as phrenic nerve injury and excessive bleeding. It is a time-consuming procedure owing to the degree of lateral mediastinal dissection required (the latter is especially important in critically hypoxic infants). An alternative procedure is described in which an intrapericardial approach is used. This approach requires minimal dissection of the subclavian artery and the anastomosis is performed to the pulmonary artery, medial to the superior vena cava (SVC) and lateral to the aorta. The procedure was performed on 17 infants from 1 day to 2 years of age (average age of 9.4 months, with seven of the 17 infants being less than 6 months of age). Follow-up ranged from 1 to 44 months (average of 17 months). In 94%, the shunt was functioning well. The potential advantages of this approach include: elimination of phrenic nerve injury, easy dissection with reduced operating time, reduced intraoperative hemorrhage, and perhaps a larger anastomosis with improved patency rate.     

Clinical comparison of resorbable and non-resorbable barriers for guided periodontal tissue regeneration

The purpose of this study was to compare the clinical results of guided periodontal tissue regeneration (GPTR) using a resorbable barrier manufactured from a copolymer of polylactic and polyglycolic acids (Resolut Regenerative Material) with those of non-resorbable e-PTFE barrier (Gore-Tex Periodontal Material). 12 subjects participated, 6 with similarly paired class II furcations and 6 with 2 similar 2, 3-wall periodontal lesions. The resorbable and non-resorbable barriers were randomly assigned to 1 defect in each subject. Non-resorbable barriers were removed in six weeks. Plaque index (PlI), gingival index (GI), probing depth (PD), clinical attachment level (CAL) and gingival recession (R) were recorded at baseline, (i.e., immediately prior to surgery) and at 12 months postsurgically. The clinical healing was similar and uneventful in both groups. Intrabony pockets depicted significant changes from baseline (p < 0.05) for probing depth reduction and gain in clinical attachment levels. No differences were found between treatments. Class II furcations showed significant improvements from baseline (p < or = 0.05) for probing depth reduction and clinical attachment gain. No differences were detected between treatments. It is concluded that the resorbable barrier tested is as effective as the nonresorbable e-PTFE barrier for the treatment of class II furcations and intrabony defects.     

Amelanotic malignant melanoma

The purpose of this study was to investigate whether extracellular matrix proteins which influence human keratinocyte behaviour are capable of altering intracellular signalling systems in these cells. The effects of extracellular matrix proteins on two major signal transduction pathways, intracellular calcium and cyclic adenosine monophosphate (cyclic AMP), were investigated. The extracellular matrix proteins examined were the basement membrane preparation matrigel, collagens type I and IV, vitronectin and its active tripeptide component Arg-Gly-Asp (RGD). Acute additions of matrigel, vitronectin and RGD caused rapid transient increases in intracellular calcium and, together with collagen type I, also caused sustained elevations in basal calcium when cells were grown on these substrates. Cyclic AMP production was unaffected by acute exposure to these extracellular matrix proteins. Culture of cells on matrigel, collagen type I or IV, however, significantly reduced basal cyclic AMP accumulation and increased the response of the cells to the receptor-independent agonist forskolin. It is concluded that in vitro some extracellular matrix proteins can initiate both acute and sustained changes in intracellular signalling in human keratinocytes.     

Aging alters zonation in the adrenal cortex of men

Whereas aging has been shown to be associated with striking reductions in circulating levels of adrenal androgens in humans, the alteration in adrenal function that occurs in aging has not been identified. We sought to determine if there are changes in the zonation of the adrenal in aging men by performing histomorphologic analyses of adrenal specimens that had been obtained at autopsy following sudden death due to trauma. We evaluated adrenals from 21 young men (20-29 yrs) and 12 older men (54-90 yrs); inclusion criteria required the presence of medullary tissue in the specimen and fixation within the first 24 hrs postmortem. Sections stained with H/E were examined microscopically and areas of the cortex that included adjacent medullary tissue were chosen for quantitative evaluation by use of a computerized image analysis system. The average width (arbitrary units, pixels) of the zona reticularis and that of the combined zonae fasciculata/glomerulosa were determined from sections stained for reticulum fibers. The zona reticularis represented 37.1 +/- 1.9% of the total cortical width in the young men, which was significantly greater than that of the older men (27.1 +/- 3.3%, P = 0.0082). The zona fasciculata/glomerulosa to zona reticularis ratio in the young men (1.84 +/- 0.15) was significantly less that that of the older men (3.29 +/- 0.47, P = 0.0011). There was no significant difference in the total width of the cortex in young compared to older men. These data suggest that aging results in alterations within the cortex of the adrenals in men such that there is a reduction in the size of the zona reticularis and a relative increase in the outer cortical zones. A reduced mass of the zona reticularis could be responsible for the diminished production of dehydroepiandrosterone and dehydroepiandrosterone sulfate that occurs during aging.     

Development of AIDS in a chimpanzee infected with human immunodeficiency virus type 1

The condition of a chimpanzee (C499) infected with three different isolates of human immunodeficiency virus type 1 (HIV-1) for over 10 years progressed to AIDS. Disease development in this animal was characterized by (i) a decline in CD4+ cells over the last 3 years; (ii) an increase in viral loads in plasma; (iii) the presence of a virus, termed HIV-1JC, which is cytopathic for chimpanzee peripheral blood mononuclear cells; and (iv) the presence of an opportunistic infection and blood dyscrasias. Genetic analysis of the V1-V2 region of the envelope gene of HIV-1JC showed that the virus present in C499 was significantly divergent from all inoculating viruses (> or = 16% divergent at the amino acid level) and was suggestive of a large quasispecies. Blood from C499 transfused into an uninfected chimpanzee (C455) induced a rapid and sustained CD4+-cell decline in the latter animal, concomitant with high plasma viral loads. These results show that HIV-1 can induce AIDS in chimpanzees and suggest that long-term passage of HIV-1 in chimpanzees can result in the development of a more pathogenic virus.     

Sensitive and reliable detection of genomic imbalances in human neuroblastomas using comparative genomic hybridisation analysis

Deletions of the short arm of chromosome 1, extra copies of chromosome 17q and MYCN amplification are the most frequently encountered genetic changes in neuroblastomas. Standard techniques for detection of one or more of these genetic changes are karyotyping, FISH analysis and LOH analysis by Southern blot or PCR. Each of these techniques has its own particular limitations. More recently, comparative genomic hybridisation (CGH) was introduced for detection of genomic imbalances including deletions, duplications and gene amplification. We evaluated the sensitivity and reliability of CGH for detection of the most frequently encountered genetic changes in neuroblastoma. For this purpose a panel of well-characterised neuroblastoma cell lines as well as a series of 11 primary neuroblastomas was analysed. Our results show that CGH is a valuable tool for the genetic characterisation of neuroblastomas, both for the detection of frequently occurring genomic imbalances and for the identification of previously unnoticed genetic changes.     

The immunomodulatory compound 2-acetyl-4-tetrahydroxybutyl imidazole causes sequestration of lymphocytes in non-lymphoid tissues

Variceal bleeding is the second cause of death in cirrhosis. To achieve haemostasis, sclerotherapy (or banding) is the first line treatment but vasoactive drugs (terlipressin or somatostatin) are an alternative and even a complement. Porto-systemic shunt is to be rapidly considered if a second endoscopic treatment has failed. Primary prevention lies on beta-blockers (propranolol or nadolol). Organic nitrates are an alternative and even a complement. Secondary prevention lies on banding or sclerotherapy; beta-blockers are an alternative and even a complement.