Mild gentamicin nephrotoxicity reduces the progression of chronic adriamycin nephrosis

SUMMARY: The effect of mild acute tubular injury on the progression of tubulointerstitial fibrosis was studied in pair-fed uninephrectomized male Wistar rats with established adriamycin nephrosis ( n = 34). Rats were stratified into three groups according to endogenous creatinine clearance (CrCl), proteinuria (Upr) and body weight (BW): (i) group 1 (Fe, n = 12) received a single intraperitoneal injection of ferric nitrilotriacetate (5 mg Fe/kg BW); (ii) group 2 (G, n = 10) three daily subcutaneous injections of gentamicin (60 mg/kg BW) and; (iii) group 3 (C, n = 12) saline injections. Serial CrCl (day 2, day 5, weeks 2, 4, 6 and 8) and renal histology (week 8) were examined following administration of nephrotoxin. CrCl was reduced on d2 (Fe: 0.78 ± 0.23 mL/min; mean ± SD) and day 5 (G: 0.91 ± 0.36 mL/min) as compared with C (1.22 ± 0.12 mL/min; P <0.05). There was no change in the serum creatinine and functional recovery occurred by d5 (Fe) and week 2 (G). Upr decreased transiently in G at week 2 (G: 482 ± 208 mg/day vs C: 716 ± 233; P = 0.05) despite similar food intake, baseline Upr and CrCl. At week 8, CrCl in Fe (0.84 ± 0.40 mL/min) was similar to C (0.84 ± 0.58 mL/min), whereas in G it remained stable (1.27 ± 0.39 mL/min; P <0.05). By morphometric analysis, mean relative interstitial volume (RIV) and glomerulosclerosis (GS) in Fe (RIV: 28.5 ± 13.4%; GS: 10.3 ± 12.3%) was no different to C (RIV: 24.5 ± 12.5%; GS: 20.9 ± 20.0%), whereas both parameters were reduced in G (RIV: 14.1 ± 8.1%; GS: 4.0 ± 4.8%; P <0.05). Mild gentamicin nephrotoxicity therefore reduced the progression of adriamycin nephrosis. the mechanism of this finding is unclear, but it may relate to altered glomerular and tubular cell handling of protein.     

Reelin expression is upregulated following ocular tissue injury

Purpose Reelin is important in the guidance of neuronal stem cells in the central nervous system during normal development. We wished to determine whether reelin is expressed in the retina and cornea after injury. Methods Mice underwent laceration of their retina as well as corneal epithelial debridement. The mice were sacrificed at 3 days, and eyes were fixed and stained for reelin expression and reelin messenger ribonucleic acid (mRNA). Results In normal eyes, reelin was expressed only at very low levels in the ganglion cell layer of the retina and the endothelial cell layer of the cornea. In injured eyes, there was marked expression in reelin immunoreactivity in the retina and cornea. Reelin gene expression was seen in the retina and cornea. Conclusions Reelin is expressed during normal retinogenesis. This study shows that reelin is also upregulated following injury to the retina and cornea. The expression of reelin following injury suggests that reelin may play an important role in regulating stem cell trafficking in neuronal and nonneuronal tissues following injury similar to its role in normal organogenesis. For consideration of publication in Graefe’s Archive for Clinical and Experimental Ophthalmology.     

无环鸟苷亲脂性前体药物脂质体的制备及体外抗病毒活性(英文)

本文通过将无环鸟苷(acyclovir,简称ACV)2’位羟基分别与月桂酰氯或棕榈酰氯进行酯化反应,制得亲脂性前体药物无环鸟苷月桂酸酯和无环鸟苷棕榈酸酯(分别简称为C₁₂-ACV和C₁₆-ACV),使脂质体包封率从ACV的29.9%提高到C₁₂-ACV的95.6%和C₁₆-ACV的97.1%;漏泄实验表明在4℃透析60h后,一半以上的ACV从脂质体中漏泄,而C₁₂-ACV和C₁₆-ACV的滞留率分别为70%和80%;体外抗疱疹病毒的试验中,在最低试验浓度0.044μmol/L时,ACV不显示抗病毒活性,而C₁₆-ACV脂质体抑制细胞病变率达75%,说明前体药物通过与脂质体脂膜的结合增加了药物的进入细胞能力,从而提高了ACV的抗病毒能力。     

Aluminum-citrate interaction in end-stage renal disease.

The influence of a sodium citrate/citric acid mixture on the gastrointestinal (GI) absorption of aluminum (Al) from an Al(OH)3 preparation was evaluated in six stable maintenance hemodialysis patients. Plasma Al concentrations were determined serially after each of the following treatment sequences (I) Al(OH)3; (II) Al(OH)3 + sodium citrate/citric acid; (III) sodium citrate/citric acid; (IV) Al(OH)3 + NaHCO3. AUC0-8 for plasma Al from 0 to 8 hours was significantly greater (p less than 0.05) for Al(OH)3 + sodium citrate/citric acid (73 +/- 23 micrograms.hr/l; mean +/- SEM) than Al(OH)3 (16 +/- 30 micrograms.hr/l); sodium citrate/citric acid (-27 +/- 14 micrograms.hr/l); or Al(OH)3 + NaHCO3 (6 +/- 22 micrograms.hr/l). The 24 hour Al level remained above baseline (p less than 0.03) following Al(OH)3 + sodium citrate/citric acid (31 +/- 12 (pre) vs 54 +/- 14 micrograms/l (post), in contradistinction to study limb: l (34 +/- 14 vs 30 +/- 12 micrograms/l); III (79 +/- 40 vs 65 +/- 35 micrograms/l); and IV (71 +/- 37 vs 66 +/- 42 micrograms/l). We conclude that the GI absorption of Al from Al(OH)3 is enhanced by citrate in patients undergoing hemodialysis and that elevations of plasma Al persist longer. The concomitant administration of citrate and Al-containing phosphate (PO4) binders should be avoided in patients with end-stage renal disease (ESRD). NaHCO3 may serve as an alternative therapy for metabolic acidosis with less risk of enhancing Al absorption.     

Relationship of prediagnostic serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing premenopausal breast cancer.

Dehydroepiandrosterone and dehydroepiandrosterone sulfate are steroids which may be associated with the development of breast cancer. To examine the association between serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate and the risk of developing premenopausal breast cancer, we measured hormone levels in 15 women who donated blood to a community-based serum bank in 1974 and who subsequently developed premenopausal breast cancer and in 29 matched controls from the same group of volunteers. The mean serum level of dehydroepiandrosterone among cases was 10% lower than among controls. The risk of developing breast cancer for women in the highest tertile compared with the lowest tertile of serum dehydroepiandrosterone was 0.40 with a suggestion of a dose-response trend with increasing levels. No consistent association between dehydroepiandrosterone sulfate and the risk of premenopausal breast cancer was evident. In contrast to postmenopausal breast cancer, a protective effect of dehydroepiandrosterone against premenopausal breast cancer is suggested, but because of the small sample size, the results of this study need to be replicated by others.     

Management of bacterial peritonitis and exit‐site infections in continuous ambulatory peritoneal dialysis*

SUMMARY: Peritonitis and exit‐site infections remain the most important limitations to the delivery of continuous ambulatory peritoneal dialysis (CAPD). Contamination of the peritoneum, from endogenous or exogenous sources, is responsible for most peritonitis episodes. Patients usually present with a cloudy bag, although other causes should be distinguished. Clinical suspicion of peritonitis should be followed rapidly by microbiological examination and empirical treatment. Microbiological confirmation allows for subsequent treatment based on sensitivities. Other interventions such as catheter removal may be appropriate in some patients. Exit‐site infections should also be identified and treated early. Peritonitis may be further prevented by adequate exit‐site care, hygienic methods, and techniques to minimise early contamination of the exit site. Mupirocin may also have a role in preventing infections caused by Staphylococcus aureus.     

Traumatic or septic aortic regurgitation: diagnosis by oesophageal echocardiography

Severe aortic regurgitation was discovered in a young man 21 days after blunt chest trauma and after a prolonged febrile state with positive blood cultures. Using transoesophageal echocardiography (TEE), it was possible to make the differential diagnosis between traumatic rupture and endocarditis as the cause of valvular insufficiency. The use of TEE in the initial evaluation of severe thoracic trauma with an unclear clinical picture is recommended. This method is easy to use at the bedside and gives precise information on the aortic valve and the ascending aorta.