Future emergence of new ecosystems caused by glacial retreat.

Glacier shrinkage and the development of post-glacial ecosystems related to anthropogenic climate change are some of the fastest ongoing ecosystem shifts, with marked ecological and societal cascading consequences1-6. Yet, no complete spatial analysis exists, to our knowledge, to quantify or anticipate this important changeover7,8. Here we show that by 2100, the decline of all glaciers outside the Antarctic and Greenland ice sheets may produce new terrestrial, marine and freshwater ecosystems over an area ranging from the size of Nepal (149,000 ± 55,000 km2) to that of Finland (339,000 ± 99,000 km2). Our analysis shows that the loss of glacier area will range from 22 ± 8% to 51 ± 15%, depending on the climate scenario. In deglaciated areas, the emerging ecosystems will be characterized by extreme to mild ecological conditions, offering refuge for cold-adapted species or favouring primary productivity and generalist species. Exploring the future of glacierized areas highlights the importance of glaciers and emerging post-glacial ecosystems in the face of climate change, biodiversity loss and freshwater scarcity. We find that less than half of glacial areas are located in protected areas. Echoing the recent United Nations resolution declaring 2025 as the International Year of Glaciers' Preservation9 and the Global Biodiversity Framework10, we emphasize the need to urgently and simultaneously enhance climate-change mitigation and the in situ protection of these ecosystems to secure their existence, functioning and values.

Quantitative evaluation of renal function in healthy Beagle puppies and mature dogs.

Daily urinary collection and assessment of glomerular filtration rate (GFR) and effective renal plasma flow were performed in ten 2-month-old Beagle puppies and ten 6-9 year-old Beagle dogs to identify age-associated differences in renal function. The most striking differences in puppies compared to mature dogs were a higher daily urinary volume (+65%), GFR (+87%), free water reabsorption (+159%), a lower daily protein excretion (-88%), and fractional excretion of phosphorus (-35%). Renal function in Beagle puppies, but not mature dogs, was also quite different compared to data published in younger adult dogs.

APOE: a potential marker of disease progression in ALS.

Although documented in AD, the role of APOE remains unclear in ALS. APOE phenotype and plasma levels were measured in 403 patients with ALS and were correlated with clinical parameters and survival time. No correlations were observed between the APOE phenotype and these variables. In contrast, APOE plasma levels were correlated with both rate of deterioration and survival time and appeared to be an important risk factor for decreased survival time with a relative risk of 0.647 (95% CI: 0.465 to 0.901; p = 0.01).

Measurement of glomerular filtration rate and effective renal plasma flow in the conscious beagle dog by single intravenous bolus of iohexol and p-aminohippuric acid.

The objective of this study was to validate a kinetic approach for the simultaneous measurement of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in the dog. Six healthy male Beagle dogs were randomly assigned in a three-period cross-over study of intravenous bolus administration of iohexol (64.7 mg/kg), PAH (10 mg/kg), and an iohexol/PAH mixture. PAH and iohexol were determined simultaneously by a validated high-performance liquid chromatographic method. The iohexol and PAH data obtained after intravenous administration were analyzed using noncompartmental and bicompartmental approaches. A simplified iohexol plasma clearance was also calculated from the terminal elimination phase of the plasma iohexol concentrations versus time profile. The total plasma clearance values for PAH and exo-iohexol were 13+/-2.3 mL/kg/min and 2.9+/-0.3 mL/kg/min, respectively. No significant (or biologically relevant) effect of coadministration of PAH and iohexol was observed on the pharmacokinetic parameters of either drug. The calculation of simplified plasma clearance led to an overestimation of the true plasma clearance. In conclusion, GFR and ERPF can easily and rapidly be measured in the dog by this approach which is relatively noninvasive.

Effect of experimental renal impairment on disposition of marbofloxacin and its metabolites in the dog.

The pharmacokinetics of marbofloxacin was studied in eight healthy female Beagle dogs before and after moderate renal impairment was induced experimentally. A single intravenous (i.v.) administration and repeated administration for 8 days (2 mg/kg, once-a-day) of marbofloxacin were studied. Renal impairment was induced by a right kidney nephrectomy and electrocoagulation of the left kidney. An increase (P < 0.001) in the plasma concentrations of urea (from 3.8+/-0.7 to 9.8+/-2.1 mmol/L) and creatinine (from 78.8+/-3.4 to 145.8+/-22.3 micromol/L), and a significant decrease (2.9+/-0.3 vs 1.5+/-0.2 mL/kg/min) (P < 0.001) in glomerular filtration rate were observed in the renal-impaired dogs. The clearance of marbofloxacin was slightly decreased after the induction of renal failure (1.6+/-0.2 to 1.4+/-0.1 mL/kg/min) (P < 0.05), but no significant variation of volume of distribution at steady state (Vss) and mean residence time (MRT) was observed after intravenous administration of marbofloxacin (P > 0.05). Following oral administration of marbofloxacin, an increase in total area under the concentration time curve (AUC) was observed after renal failure (from 10372+/-1710 to 11459+/-1119 mg x min/L) (P < 0.05), but indices of accumulation were not modified. An increase (P < 0.01) in the AUC of N-oxide-marbofloxacin was observed after surgery. In conclusion, renal impairment has no biologically relevant influence on marbofloxacin disposition and there is no need for dosage adjustment of marbofloxacin in dogs with mild renal impairment.

A non-invasive and quantitative method for the study of tissue injury caused by intramuscular injection of drugs in horses.

The present study was undertaken to measure the weight of muscle destroyed by an intramuscular injection of phenylbutazone (PBZ) in horses. In six horses, CK disposition parameters were evaluated after intravenous (i.v.) and intramuscular (i.m.) administration of a CK horse preparation. The same horses received PBZ, a potentially irritating agent, by i.v. and i.m. (neck and hindquarter) routes. Data were analysed using compartmental approaches and instantaneous CK flux was calculated using a discrete deconvolution method. For a 150 U/kg CK dose, the steady-state volume of distribution was 0.050 +/- 0.0115 L/kg and the plasma half-life was 112 +/- 18 min. After CK i.m. administration, the half-life of the terminal phase was 11.8 +/- 5.3 h indicating a flip-flop process and the mean bioavailability of CK was close to 100%. After PBZ i.m. administration, the CK activity was significantly increased with peak values of 508 +/- 109 U/L after the neck administration and 873 +/- 365 U/L after the gluteal administration. By measuring the total amount of CK released from injured muscle, it was calculated that an equivalent of 0.044 +/- 0.029 g/kg of muscle was destroyed after PBZ administration in the neck. The corresponding figure was 0.118 +/- 0.048 g/kg after intragluteal PBZ administration. By deconvoluting plasma CK activity, it was shown that the CK entry rate was maximum for the first 30-60 min following PBZ administration, which then decreased slowly to return to the control value after a delay of 24-48 h after PBZ administration. It was concluded that the CK release pattern following a controlled muscular damage was a non-invasive approach useful for quantifying the amount of damaged muscle, and that the calculation of CK input rate by deconvolution was of potential interest in describing events at the muscle cell level.

[A treatise on medieval toxicology: the "Liber de venenis" by Pietro d'Abano (French translation from the early 15th century)]. / Un traité de toxicologie médiévale: le Liber de venenis de Pietro d'Abano (traduction française du début du XVe siècle.

Presentation of the manuscript Paris, B.N.F., Fr. 14820 (French translation of the Liber de venenis by Pietro d'Abano completed in 1402) and description of the treatise from the 14th century, which is a sum of the knowledge on poisons as of that time. The critical study of the manuscript, now in the process of publication, sets forth evidence of significant variations between the original text and the translation.

Migrating motor complex of the intestine and absorption of a biliary excreted drug in the dog.

The role of the migrating motor complex (MMC) of the small intestine in the absorption of an enterally administered marker (tolfenamic acid, TA) used to investigate enterohepatic recycling was studied in the fasted dog. TA was rapidly and extensively absorbed in the duodenum as well as in the ileum. In contrast, the conjugated form of TA (CTA) was not absorbed in the duodenum but only in the ileum, i.e., after bacterial hydrolysis. By administering CTA in the duodenum at different phases (I and II) of the MMC, it was shown that CTA had to be propelled from the duodenum to the ileum by the motor activity of the MMC. Under these conditions, the peak plasma TA concentration was only observed when phase II of the MMC present in the duodenum at the time of CTA administration arrived in the ileum. The estimated mean transit time of CTA from the duodenum to ileum was 45 min and the mean hydrolysis time of CTA to TA was about 75 min. It was concluded that 1) in the fasted dog, a relatively long delay must exist between bile excretion of a conjugate and the reabsorption of its free moiety in the ileum and 2) a realistic physiological model of enterohepatic recycling must take into account the MMC pattern of the intestine when drugs are administered to animals in the fasted state.