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.     

玻璃体内注射庆大霉素致视网膜损伤的实验研究Ⅰ．组织病理学观察

为探讨庆大霉素对视网膜的毒性作用和评估玻璃体内注射庆大霉素的安全剂量，采用眼底镜观察及光镜、电镜技术对注射５种不同剂量庆大霉素的青紫蓝兔视网膜标本进行观察。结果：３０００μｇ庆大霉素注射后眼底表现为视盘水肿，后极部视网膜大片坏死，镜下视网膜组织形态严重破坏；５０～５００μｇ剂量注射引起后极部视网膜色素改变，组织损伤早期局限在视网膜内层，晚期全层受累。提示庆大霉素对视网膜的损伤程度随注入剂量增加而加重，即使５０μｇ的微小剂量仍可产生视网膜损伤。     

Atrial natriuretic peptide and verapamil can prevent gentamicin induced acute renal failure in the rat

Summary: Calcium channel blockers are able to improve renal function in acute renal failure (ARF) and natriuretic peptides can also exert beneficial effects. At present it is unknown whether administration of atrial natriuretic peptide (ANP) and a calcium channel blocker given before a toxic lesion can prevent gentamicin induced ARF. the mechanisms of action of natriuretic peptides and calcium channel blockers are different and, as yet, it has not been clarified if combined administration can augment the effects on renal function. After a basal period we investigated the effects of verapamil (VER, 0.66 mg/kg), ANP, (30 μg/kg) and a combination of both (identical doses as described individually). the drugs were given intravenously for a period of 40 min (infusion period) before gentamicin (15 mg/kg, i.v.) was administered for induction of ARF. Basal values for glomerular filtration rate (GFR, mL/min) were around 1.8 with no differences between the groups. At the end of the infusion period (before application of gentamicin) GFR was significantly elevated with VER + ANP (3.13 ± 0.51), ANP (2.70 ± 0.59) and VER (2.34 ± 0.47) compared to controls (saline, 1.7 ± 0.48). After application of gentamicin GFR significantly dropped in the control group (0.77 ± 0.21, 0.75 ± 0.19, respectively), indicating development of ARF. In contrast with VER + ANP, ANP and VER GFR could be maintained for 30 min (2.47 ± 0.39, 2.28 ± 0.33, 2.22 ± 0.43, respectively) and 130 min (2.11 ± 0.32, 1.86 ± 0.29, 2.11 ± 0.28, respectively) after gentamicin. Moreover ANP and VER revealed natriuretic activity and, due to their vasorelaxing potency, also influenced arterial blood pressure. We conclude that both VER and ANP are able to prevent early gentamicin induced ARF when given before the toxic lesion. Both drugs induce hyperfiltration while infused, in particular when administered in combination.     

爱大霉素和庆大霉素对肾皮质线粒体~(45)Ca~(2+)摄取的影响

目的研究爱大霉素和庆大霉素对大鼠肾皮质线粒体钙摄取的影响。方法应用４５Ｃａ２＋示踪技术。结果两药在１ｍｍｏｌ·Ｌ－１时显著促进线粒体钙摄取（分别由每３０ｍｉｎ（１１３．５±７．５）μｍｏｌ·ｇ－１Ｐｒｏ上升到（１４８．０±２４．０）μｍｏｌ·ｇ－１Ｐｒｏ，（１１１．９±１３．０）μｍｏｌ·ｇ－１Ｐｒｏ上升到（１４０．１±１６．６）μｍｏｌ·ｇ－１Ｐｒｏ，Ｐ＜０．０５）；在１０μｍｏｌ·Ｌ－１时显著抑制线粒体钙摄取（分别由每３０ｍｉｎ（１１３．５±７．５）μｍｏｌ·ｇ－１Ｐｒｏ下降到（９２．３±５．７）μｍｏｌ·ｇ－１Ｐｒｏ，（１１１．９±１３．０）μｍｏｌ·ｇ－１Ｐｒｏ下降到（１４０．０±５．３）μｍｏｌ·ｇ－１Ｐｒｏ，Ｐ＜０．０５或Ｐ＜０．０１）。结论两药对线粒体钙摄取的这种双相变化可能与它们肾毒性有关     

EFFECTS OF ACUTE AND CHRONIC ADMINISTRATION OF TWO ANTIBIOTICS, AZTREONAM AND GENTAMICIN, ALONE OR IN COMBINATION, ON "OPEN-FIELD TEST" IN MICE

A study aimed at investigating the behavioural effects of aztreonam and gentamicin, given separately or in combination, was carried out in mice. Animals were randomly assigned to two test conditions: acute and chronic treatment. Those receiving acute treatment had a single IP injection 60 min before the test. Those receiving chronic treatment had IP injections once daily for 5 successive days prior to the test. Behavioural patterns (ambulation, rearing, grooming and defecation) were assessed using the "open-field" test. The results indicate that, both after single and multiple dosing, aztreonam (10, 40 and 80 mg/kg IP) and/or gentamicin (10 mg/kg IP) do produce changes in the behaviour of animals. A rate increasing effect for certain behaviours (rearing, grooming and defecation) and a reduction in other behaviours (ambulation) seems to occur.     

Atracurium and vecuronium interaction with gentamicin and tobramycin

Drug interactions between the aminoglycosides (tobramycin and gentamicin) and atracurium and vecuronium were studied prospectively in 44 patients. Twenty-two patients had therapeutic serum levels of tobramycin or gentamicin and 22 served as controls. Onset time, clinical duration, and time to spontaneous recovery of T4/T1 ratio of 0.70 after atracurium or vecuronium injection were measured. No statistically significant differences were found in onset time, but clinical duration and time to recovery were significantly longer in patients receiving tobramycin or gentamicin and paralyzed with vecuronium than for controls (P less than 0.01 for clinical duration and P less than 0.0005 for recovery). The neuromuscular block produced by atracurium was not significantly influenced by the presence of therapeutic serum levels of tobramycin or gentamicin. We conclude that for patients treated with these antibiotics, atracurium may present some advantages over vecuronium when a prolonged block is not desired.     

Gentamicin susceptibility in Escherichia coli related to the genetic background: problems with breakpoints

In total, 120 Escherichia coli isolates positive for one of the gentamicin resistance (GEN(R)) genes aac(3)-II, aac(3)-IV or ant(2')-I were tested for gentamicin susceptibility by the agar dilution method. Isolates positive for aac(3)-IV or ant(2')-I had an MIC distribution of 8-64 mg/L, whereas isolates positive for aac(3)-II had MICs of 32 to >512 mg/L, suggesting a relationship between the distribution of MICs and the specific GEN(R) mechanism. The MIC distribution, regardless of the GEN(R) mechanism, was 8 - >512 mg/L, which supports the clinical breakpoint of MIC >4 mg/L suggested by EUCAST and questions the breakpoint recommended by the CLSI (> or =16 mg/L).     

庆大霉素分泌过程的初步研究

应用恒温系统及缓冲液体系,考察了温度及pH值分泌过程的影响,然后在此基础上又讨论了添加葡萄糖、金属离子Fe^2 、K^ 和Mn^2 以及超声波和微波处理的效果,实验发现,pH＝7．4,温度34℃,以及添加5g／LKCl或50mg／LMnSO4都能刺激庆大霉素的分泌。     

Collagen shields and intraocular drug delivery: concentration of gentamicin in the aqueous and vitreous of a rabbit eye after lensectomy and vitrectomy

Five albino New Zealand rabbits underwent bilateral lensectomy and vitrectomy. All left eyes were fitted with a collagen shield that had been soaked for 5 min in 2.0 mL of gentamicin solution (40 mg/mL for IV use). Right eyes were treated with fortified gentamicin drops (13.6 mg/mL) every 30 min for 12 hrs. Aqueous and vitreous specimens were obtained at the following time intervals: 1, 2, 4, 8, 12 and 24 hrs.We found the gentamicin concentrations to be higher in the aqueous of all eyes treated with fortified gentamicin drops. Only those eyes treated with fortified gentamicin drops attained a therapeutic drug level (4g–9g/mL) in the aqueous. Therapeutic drug levels were not attained in the vitreous of either treatment group.