Mechanisms of gentamicin-induced dysfunction of renal cortical mitochondria: I. Effects on mitochondrial respiration

Because mitochondrial dysfunction occurs relatively early in the course of nephrotoxicity associated with the aminoglycoside antibiotic, gentamicin, the acute in vitro effects of gentamicin on renal cortical mitochondrial respiration were studied. Gentamicin produced stimulation of State 4 rates and inhibition of State 3 and DNP-uncoupled rates with pyruvate-malate or succinate as substrates. The stimulation of State 4 respiration was not blocked by oligomycin. Both the stimulation of State 4 and inhibition of State 3 were profoundly dependent on the Na⁺ and K⁺ contents of the incubation medium, were potentiated by the presence of EDTA, and were reversed by Mg²⁺. These results suggested that gentamicin's effects on mitochondrial respiration were due to alterations in the interaction of Na⁺ and K⁺ with the inner mitochondrial membrane at Mg²⁺-sensitive sites.     

Copepoda (cyclopoida,Lichomolgidae) associated with the Alcyonacean Nephthea in the moluccas

In the Moluccas five lichomolgid copepods are associated with soft corals of the genus Nephthea. Paramolgus nephtheanus, n. sp., from Nephthea chabrolii, Nephthea sphaerophora, Nephthea cupressiformis, Nephthea albida, and Nephthea galbuloides, Paramolgus prominulus, n. sp., from N. sphaerophora, N. cupressiformis, and N. albida, and Paramolgus accinctus, n. sp., from N. sphaerophora, N. cupressiformis, N. albida, and N. galbuloides are distinguished from conspecifics by combinations of several characters. These include, among others, the length of the caudal ramus, the form of the female genital segment, and the shape of leg 5 in the female. Mecra ellipsaria, n. gen., n. sp., from N. sphaerophora has only two setae on the fourth segment of the first antenna, the formula II, 2 on the third endopod segment of leg 3, and five aesthetes on the second segment of the first antenna of the male. In Metaxymolgus lumarius, n. sp., from N. galbuloides and N. cupressiformis, the two claws on the second antenna are longer than the fourth second antennal segment and the proximal inner expansion of leg 5 in the female has a thorn-like process. Metaxymolgus aculeatus (Humes & Ho, 1968) occurs on N. chabrolii, N. sphaerophora, N. cupressiformis, N. albida, and N. galbuloides.     

Copepoda associated with the coral Gardineroseris planulata (Dana) on the Great Barrier Reef,northeastern Australia

Three new lichomolgid copepods associated with the scleractinian Gardineroseris planulata (Dana) are described: Sociellus torus, n. gen., n. sp., characterized by a 2-segmented endopod in leg 3 and the lack of an inner seta on the first segment of the endopod in legs 1–3; Odontomolgus pumilus, n. sp., of very small size and having a much elongated free segment in leg 5 of the female; and Paramolgus ampullaceus, n. sp., distinguished by the bottle-shaped genital segment of the female. In addition, the harpacticoid Alteuthellopsis corallina Humes, 1981, is reported from this coral. With the inclusion of 3 species of the poecilostomatoid genus Xarifia already described (Humes, 1985) there are now 7 species of copepods known to be associated with Gardineroseris planulata on the Great Barrier Reef.     

Tissue engineering of a bioartificial kidney

Tissue engineering is a rapidly growing field in biotechnology. The use and packaging of synthetic materials, biologic compounds, and cellular components of specific tissues can be envisioned to replace physiologic function of diseased organs. Long-term ex vivo therapy for kidney failure has been achieved, so that the kidney may be the first solid organ in which tissue engineering concepts can produce an implantable device for long-term in vivo replacement therapy. To replace the kidney's excretory function, an implantable bioartificial kidney requires both a device to replace blood ultrafiltration performed by renal glomeruli and a device to replace transport regulatory function of the renal tubule. The initial concepts for these devices are just beginning to be considered and developed. (c) 1994 John Wiley & Sons, Inc.     

Intestinal phenotype of variable-weight cystic fibrosis knockout mice

Cystic fibrosis (CF) transmembrane conductance regulator (Cftr) knockout mice present the clinical features of low body weight and intestinal disease permitting an assessment of the interrelatedness of these phenotypes in a controlled environment. To identify intestinal alterations that are affected by body weight in CF mice, the histological phenotypes of crypt-villus axis height, goblet cell hyperplasia, mast cell infiltrate, crypt cell proliferation, and apoptosis were measured in a population of 12-wk-old (C57BL/6 x BALB/cJ) F2 Cftr(tm1UNC) and non-CF mice presenting a range of body weight. In addition, cardiac blood samples were assessed, and gene expression profiling of the ileum was completed. Crypt-villus axis height decreased with increasing body weight in CF but not control mice. Intestinal crypts from CF mice had fewer apoptotic cells, per unit length, than did non-CF mice, and normalized cell proliferation was similar to control levels. Goblet cell hyperplasia and mast cell infiltration were increased in the CF intestine and identified to be independent of body weight. Blood triglyceride levels were found to be significantly lower in CF mice than in control mice but were not dependent on CF mouse weight. By expression profiling, genes of DNA replication and lipid metabolism were among those altered in CF mice relative to non-CF controls, and no differences in gene expression were measured between samples from CF mice in the 25th and 75th percentile for weight. In this CF mouse model, crypt elongation, due to an expanded proliferative zone and decreased apoptosis, was identified to be dependent on body weight.     

Replacement of renal function in uremic animals with a tissue-engineered kidney.

Current renal substitution therapy with hemodialysis or hemofiltration has been the only successful long-term ex vivo organ substitution therapy to date. Although this approach is life sustaining, it is still unacceptably suboptimal with poor clinical outcomes of patients with either chronic end-stage renal disease or acute renal failure. This current therapy utilizes synthetic membranes to substitute for the small solute clearance function of the renal glomerulus but does not replace the transport, metabolic, and endocrinologic functions of the tubular cells. The addition of tubule cell replacement therapy in a tissue-engineered bioartificial kidney comprising both biologic and synthetic components will likely optimize renal replacement to improve clinical outcomes. This report demonstrates that the combination of a synthetic hemofiltration device and a renal tubule cell therapy device containing porcine renal tubule cells in an extracorporeal perfusion circuit successfully replaces filtration, transport, metabolic, and endocrinologic functions of the kidney in acutely uremic dogs.     

The effect of gentamicin on calcium uptake by renal mitochondria

The effect of the nephrotoxic aminoglycoside antibiotic, gentamicin, on calcium uptake by renal cortical mitochondria was assessed in vitro. Gentamicin was found to be a competitive inhibitor of mitochondrial Ca⁺⁺ uptake. This effect displayed a dose response with a K_i of 233 μM and occurred at gentamicin concentrations below those that inhibit mitochondrial electron transport. These results further demonstrate the potential for gentamicin to alter membrane function and thereby contribute to toxic cell injury via its interactions with divalent cations.     

Two new species ofCerioxynus (Copepoda: Poecilostomatoida) parasitic in corals (Scleractinia: Faviidae) in the South Pacific

Summary The copepodsCerioxynus oulophylliae n. sp., parasitizing the hard coralOulophyllia crispa (Lamarck) on the Great Barrier Reef, Australia, and at Banda in the Moluccas, andCerioxynus montastreae n. sp., living inMontastrea curta (Dana) on the Great Barrier Reef, are described and illustrated. Both new species are distinguished from their four congeners by having wing-like epimera on the segments bearing leg 2 and leg 3. ac]19850419     

An attempt to isolate Brucellaabortus from uterine flushings of brucellosis-reactor donor cattle

Two experiments were conducted to test for the recovery of brucella organisms from uterine flushings and harvested embryos of sero-positive embryo donor females. In Experiment I, 16 sero-positive cows were superovulated with FSH treatments and artificially inseminated at 12, 24 and 36 hours following the onset of estrus with brucella-free semen. At 48 hours after the onset of estrus, one half the potential donor females were administered an intrauterine inoculation of 3.3 to 4.6 × 10⁴$\text{Brucella}$$\text{abortus}$ (strain 2308) organisms while the remainder received a control inoculation. In Experiment II, the same 16 cows were similarly administered superovulatory treatments and inseminated following estrus. The uterine inoculation was increased to 1.5 to 2.5 × 10⁸ organisms administered 48 hours following estrus. Samples of recovered flushing medium and homogenized embryo residues were placed into a validated $\text{in}$$\text{vitro}$ culture system to detect the presence of brucella bacteria. Uterine flushings and embryos recovered from 31 females exhibiting estrus following FSH treatments were free from either field strain or the inoculated $\text{B.}$$\text{abortus}$ (strain 2308) contamination. The flushings obtained from a single female, which did not respond with estrus following FSH treatment but was inoculated at appointment, did contain $\text{B.}$$\text{abortus}$ which was identified as the inoculated strain 2308 and not field strain organisms. These results indicate that brucella contamination of flushing media and harvested embryos will not likely be incurred when collecting embryos from sero-positive donor females. These findings offer further encouragement for the use of embryo transplantation as a method to produce brucella-free offspring from infected cows.     

Characterization of Ca2+ transport in rat renal brush-border membranes and its modulation by phosphatidic acid.

The Ca2+ transport process by isolated renal brush-border membranes was characterized and the influence of the acidic phospholipid phosphatidic acid (PtdA) on this transport process was assessed. Ca2+ uptake by brush-border membranes exhibited saturation kinetics. It was inhibitable by a variety of multivalent cations, as well as by Ca2+-entry inhibitors, including verapamil, Ruthenium Red and gentamicin. It was selective for Ca2+ compared with Mg2+. This process was also electrophoretic since generation of K+ and anion-diffusion potentials, negative inside the vesicle, increased Ca2+ uptake. Elevations in PtdA content of brush-border membranes by either exogenous addition or endogenous generation of PtdA by incubating brush-border membranes with MgATP2- elevated the rate of Ca2+ uptake. This ATP effect could not be attributed to (Ca2+ + Mg2+)-dependent ATPase or contaminating membrane fragments. PtdA also increased the magnitude and rate of Ca2+ efflux from brush-border membranes preloaded with Ca2+. These modulations in uptake and efflux were not observed with phosphatidylcholine or phosphatidylinositol. In summary, these results are consistent with the presence of an electrophoretic uniport system for Ca2+ in renal brush-border membranes, and demonstrate that PtdA uniquely among phospholipids tested appears to facilitate transmembrane flux of Ca2+ across this membrane preparation.