M. Pescador

A systematic meta-analysis on the efficacy of pre-clinically tested nephroprotectants at preventing aminoglycoside nephrotoxicity

Nephrotoxicity limits the use of aminoglycoside antibiotics. Kidney damage is produced mainly in the renal tubule due to an inflammatory and oxidative process. At preclinical level, many drugs and natural products have been tested as prospective protectors of aminoglycoside nephrotoxicity. The main objective of this work was to make a systematic literature review of preclinical studies about aminoglycoside nephrotoxicity protection and a statistical analysis based on the meta-analysis methodology. Studies published up to January 2016 were identified. After applying inclusion criteria, 54 studies were chosen. The size of the experimental groups, means and standard deviations of data on renal function (i.e. plasma creatinine and blood urea nitrogen [BUN] concentrations) were extracted and registered in a database. The studies were grouped according to the mechanism of nephroprotection and their route of administration. The Mean Difference (95% confidence interval) was calculated for each study and group. 40 of 54 products tested produced an amelioration of aminoglycoside nephrotoxicity based on creatinine results. Also a dose dependent protective effect was observed (both in creatinine and BUN). Products orally administered were more effective than via i.p. Products with attributed antioxidant activity were the most used and those which proved statistically significant nephroprotection as a class effect. Aminoglycoside tubular reuptake inhibitors, excretion inducers and calcium channel blockers also showed a promising and rather homogeneous class tendency towards nephroprotection, although more research is necessary to obtain solid and conclusive results, based on a larger number of studies.

Key role of oxidative stress in animal models of aminoglycoside nephrotoxicity revealed by a systematic analysis of the antioxidant-to-nephroprotective correlation

The clinical utility of aminoglycoside antibiotics is partly limited by their nephrotoxicity. Co-administration of a variety of candidate nephroprotectants has been tested at the preclinical level. According to a recent meta-analytic study, antioxidants are the only family of compounds with enough preclinical documentation to draw solid conclusions on their class nephroprotective capacity in animal models. In this study a systematic analysis of the relation between the level of antioxidation and the level of nephroprotection was performed. A regression model is presented which crosses the y-axis (i.e. the axis representing the level of nephroprotection) very nearly the zero value, meaning that maximal prevention of the oxidative stress induced by aminoglycosides results in almost maximal nephroprotection. This indicates that oxidative stress plays a central role in the hierarchy of pathophysiological mechanisms underlying aminoglycoside nephrotoxicity. In addition, this model may potentially serve: i) as a standard to evaluate the role of the antioxidant effect of candidate nephroprotectants; ii) to reveal additional, antioxidant-independent effects among those compounds providing more nephroprotection than that expected from its antioxidant activity; and thus iii) to discriminate and focus most effective nephroprotectants on clinical usage.

Seasonal and water mass size effects on the abundance and diversity of waterbirds in a Patagonian National Park.

Abstract. Over an 18-month period regular counts were made of the water birds inhabiting lakes and ponds in the Lanín National Park in Argentinean Patagonia. A total of 130 bird surveys were conducted on 21 wetland areas, detecting 6,364 individuals belonging to 27 species from nine families. The most abundant and frequent species were Cloephaga poliocephala, Anas flavirostris, Fulica armillata and Fulica. leucoptera. Species richness was higher in spring and summer than in autumn and winter, involving 31 and 27 expected species, respectively. In contrast, bird abundance did not differ between season. The presence and abundance of bird species with respect to the surface area of the water body highlights the importance of certain lakes in particular. Thus, small water bodies (<100 ha) support higher numbers of birds; an average of 78.4–45.0 individuals as compared with larger lakes with an average of 18.58 birds. However, some species such as Phalacrocorax olivaceus, Podiceps major, Tachyeres patachonicus and Anas specularis were observed more at larger lakes, such differences being statistically significant. In contrast, Anas flavirostris, A. platalea and A. sibilatrix were more common in small and medium-sized lagoons. This information contributes to the development of management guidelines for the conservation of Patagonian wetlands.

Does the Song of the Wren Troglodytes troglodytes Change with Different Environmental Sounds

Abstract. Birds inhabiting urban areas have to deal with high levels of ambient noise. Some species show a certain song flexibility that enables them to reduce noise interferences in their communications. This vocal adjustment usually implies an increase in the minimum frequencies of songs. Since urban noise is mainly made up of low frequencies (about 2.5–3.5 kHz), song of species that sing at higher frequencies could be less susceptible to being masked by anthropogenic noise. This study explores whether such species also show any kind of adjustment to noisy environments. For this purpose, the spectral and temporal parameters (note duration, maximum and minimum frequency and diversity) of the song of the European Wren Troglodytes troglodytes were analysed in three different environments (urban, periurban and rural). To evaluate the impact of noise on the vocalizations, a specific acoustic descriptor of song variability was developed. Song variability increased along the urban noise gradient from rural to urban areas and the duration of notes decreased from rural to urban zones. Urban wrens developed more complex songs with higher frequencies and longer notes than their rural counterparts, whereas peri-urban birds occupied an intermediate position, although closer to urban ones in the length of notes. These changes could be associated with higher background noise levels, although other possible causes, such as the population density, could also explain them. Maximum frequencies were mostly outside the background noise range and differed among habitats, whereas lower frequencies unexpectedly did not differ among habitats. Our results suggest that differences in song parameters among species may lead to different mechanisms of vocal adjustment. Even in wrens, with high frequency vocalisation, interference with urban anthropogenic noise could show certain changes in their vocalizations.

Sub-nephrotoxic cisplatin sensitizes rats to acute renal failure and increases urinary excretion of fumarylacetoacetase.

Nephrotoxicity limits the therapeutic efficacy of the antineoplastic drug cisplatin. Due to dosage adjustment and appropriate monitoring, most therapeutic courses with cisplatin produce no or minimal kidney damage. However, we studied whether even sub-nephrotoxic dosage of cisplatin poses a potential risk for the kidneys by predisposing to acute kidney injury (AKI), specifically by lowering the toxicity threshold for a second nephrotoxin. With this purpose rats were treated with a single sub-nephrotoxic dosage of cisplatin (3mg/kg, i.p.) and after two days, with a sub-nephrotoxic regime of gentamicin (50mg/kg/day, during 6 days, i.p.). Control groups received only one of the drugs or the vehicle. Renal function and renal histology were monitored throughout the experiment. Cisplatin treatment did not cause any relevant functional or histological alterations in the kidneys. Rats treated with cisplatin and gentamicin, but not those under single treatments, developed an overt renal failure characterized by both renal dysfunction and massive tubular necrosis. In addition, the urinary excretion of fumarylacetoacetase was increased in cisplatin-treated animals at subtoxic doses, which might be exploited as a cisplatin-induced predisposition marker. In fact, the urinary level of fumarylacetoacetase prior to the second nephrotoxin correlated with the level of AKI triggered by gentamicin in predisposed animals.