Over-expression of NCS-1 in AtT-20 cells affects ACTH secretion and storage.

The effect of over-expressing neuronal calcium sensor 1 (NCS-1) upon stimulated adrenocorticotrophin (ACTH) secretion was studied in AtT-20 cells. Stably-transfected AtT-20 cell lines over-expressing NCS-1 were obtained and compared to wild type AtT-20 cells. Corticotrophin releasing factor (CRF-41)-stimulated ACTH secretion from NCS-1 over-expressing cells was significantly reduced from that obtained in wild type AtT-20 cells. The effects of other stimulants of ACTH secretion from wild type AtT-20 cells were not attenuated in NCS-1 over-expressing cells. Calcium, guanosine 5'-O-(3'-thiotriphosphate) (GTP-gamma-S) and mastoparan stimulated ACTH secretion from permeabilised wild type AtT-20 and NCS-1 over-expressing AtT-20 cells with significantly greater ACTH secretion obtained in NCS-1 over-expressing cells. This study shows that in intact cells over-expression of NCS-1 reduces exocytotic ACTH release, while in permeabilised cells increases ACTH release. NCS-1 has multiple cellular targets and that directly and indirectly via these targets acts to increase the releasable ACTH pool while inhibiting CRF-41 stimulus-secretion coupling.

Pigmented paravenous retinochoroidal atrophy: a literature review supported by a unique case and insight.

Pigmented paravenous retinochoroidal atrophy (PPRCA) is a rare disorder of unknown origin characterised by bone corpuscle pigmentation accumulation along the distribution of the retinal veins. In addition there are peripapillary pigmentary changes as well as areas of chorioretinal atrophy adjacent to the perivenular pigmentary changes. The finding of PPRCA is usually incidental and does not affect vision. The literature regarding this condition is reviewed. Its natural course has been considered controversial. Observation of the initial insult leading to PPRCA has not previously been reported. A case that provides a photographic record over 20 years of the development of this condition from the initial insult, including the gradual development of the characteristic fundus appearance, is described. The initial presentation was with a sudden reduction of vision and gross diffuse macular oedema in one eye, which was rapidly followed by similar involvement of the fellow eye despite treatment. Thus it was possible to examine the patient at the stage of the initial insult, 5 years before the development of the typical and pathognomonic retinal changes of PPRCA. The clinical and electrophysiological findings are discussed, as also is the relevance of this case to the literature reviewed.

Corneal topographic lagoons: a potential new marker for post-traumatic recurrent corneal erosion syndrome.

BACKGROUND: Post-traumatic recurrent corneal erosion syndrome is a common clinical problem in which a definitive diagnosis is not always possible based solely upon biomicroscopic corneal signs. Indeed, in some cases archetypical symptoms or a preceding history of epithelial trauma cannot always be elucidated. METHODS: Four groups of patients underwent corneal analysis using computer videokeratography. Group 1 (n = 11), subjects who presented with simple corneal epithelial trauma approximately three months before the study. Group 2 (n = 11), prospective analysis of subjects presenting with simple corneal epithelial trauma. Group 3 (n = 12), prospective analysis subjects with an established diagnosis of post-traumatic recurrent erosion syndrome. Group 4 (n = 135), prospective analysis of healthy control subjects. RESULTS: Small, well delineated areas (1.0 to 1.5 mm in diameter) of markedly reduced corneal dioptric power (greater than 2 dioptres), which we have termed 'corneal topographic lagoons', were identified more commonly in eyes with recurrent corneal erosion syndrome and in eyes that had recently sustained corneal epithelial trauma; being found in 18.2% of Group 1, 9.1% of Group 2, 58.3% of Group 3 but only 1.5% of Group 4 (control). CONCLUSIONS: The identification of areas of focal abnormality in the corneas of patients with post-traumatic recurrent corneal erosion syndrome remains a significant clinical problem. Corneal topographic analysis has demonstrated a focal abnormality, the 'corneal topographic lagoon', which is much more prevalent in cases of recent corneal trauma and recurrent corneal erosion syndrome than in the 'normal' population. Computerised videokeratography therefore adds a new tool to the armamentarium of the clinician seeking to identify and locate abnormalities in these difficult cases.

Differential effect of impaired renal function on the kinetics of clavulanic acid and amoxicillin.

Amoxicillin and clavulanic acid are prescribed as a fixed drug combination. The purpose of the present study was to assess the influence of various degrees of renal insufficiency (glomerular filtration rate [GFR], less than 5 to greater than 75 ml/min per 1.73 m2) on the pharmacokinetics of amoxicillin and clavulanic acid following oral (500 and 125 mg of amoxicillin and clavulanic acid, respectively) and intravenous (1,000 and 200 mg, respectively) dosing. The volume of distribution and the systemic availability were independent of the renal function, while the total body clearance and the renal and the nonrenal clearance of amoxicillin and clavulanic acid decreased with decreasing renal function. The decrease in the total body clearance was more pronounced for amoxicillin than for clavulanic acid. This explains the increase in the ratio of the area under the plasma concentration versus time curve of amoxicillin to that of clavulanic acid with decreasing glomerular filtration rate after oral dosing; for example for a GFR of 75 ml/min, the ratio of amoxicillin to clavulanic acid was 4.9 +/- 1.2; for a GFR of 35 to 75 ml/min, 5.3 +/- 2.4; for a GFR of 10 to 35 ml/min, 11.9 +/- 5.8; for a GFR of 5 to 10 ml/min, 13.4 +/- 9.1; and for patients on hemodialysis, 14.7 +/- 5.3. Dosage recommendations are suggested which prevent undue accumulations of amoxicillin while maintaining adequate concentrations of clavulanic acid.

A modification of imazalil residue analysis in treated grapefruit.

Residues of imazalil, 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole, a fungicide that prevents decay of citrus, were determined in treated grapefruit. The method consists of a simplified heptance-isoamyl extraction solvent, acid-base clean-up, and direct gas chromatographic analysis with electron-capture detection.