The effects of mesenchymal stem cell mitochondrial transplantation on doxorubicin‐mediated nephrotoxicity in rats

The effect of dysfunctional mitochondria in several cell pathologies has been reported in renal diseases, including diabetic nephropathy and acute kidney injury. Previous studies have reported that mitochondrial transplantation provided surprising results in myocardial and liver ischemia, as well as in Parkinson's disease. We aimed to investigate the beneficial effects of isolated mitochondria transplantation from mesenchymal stem cells (MSCs) in vivo, to mitigate renal damage that arises from doxorubicin‐mediated nephrotoxicity and its action mechanism. In this study, a kidney model of doxorubicin‐mediated nephrotoxicity was used and isolated mitochondria from MSCs were transferred to the renal cortex of rats. The findings showed that the rate of isolated mitochondria from MSCs maintains sufficient membrane integrity, and was associated with a beneficial renal therapeutic effect. Following doxorubicin‐mediated renal injury, isolated mitochondria or vehicle infused into the renal cortex and rats were monitored for five days. This study found that mitochondrial transplantation decreased cellular oxidative stress and promoted regeneration of tubular cells after renal injury (P < .001, P = .009). Moreover, mitochondrial transplantation reduced protein accumulation of tubular cells and reversed renal deficits (P = .01, P < .001). Mitochondrial transplantation increased Bcl‐2 levels, and caspase‐3 levels decreased in injured renal cells (P < .015, P < .001). Our results provide a direct link between mitochondria dysfunction and doxorubicin‐mediated nephrotoxicity and suggest a therapeutic effect of transferring isolated mitochondria obtained from MSCs against renal injury. To our knowledge, this study is the first study in the literature that showed good therapeutic effects of mitochondrial transplantation in a nephrotoxicity model, which is under‐researched.     

Preparation and <Emphasis Type="Italic">In Vitro</Emphasis>/<Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Microparticle Formulations Containing Meloxicam

In this study, we have formulated chitosan-coated sodium alginate microparticles containing meloxicam (MLX) and aimed to investigate the correlation between in vitro release and in vivo absorbed percentages of meloxicam. The microparticle formulations were prepared by orifice ionic gelation method with two different sodium alginate concentrations, as 1% and 2% (w/v), in order to provide different release rates. Additionally, an oral solution containing 15 mg of meloxicam was administered as the reference solution for evaluation of in vitro/in vivo correlation (ivivc). Following in vitro characterization, plasma levels of MLX and pharmacokinetic parameters [elimination half-life (t _1/2), maximum plasma concentration (C _max), time for C _max (t _max)] after oral administration to New Zealand rabbits were determined. Area under plasma concentration–time curve (AUC_0–∞) was calculated by using trapezoidal method. A linear regression was investigated between released% (in vitro) and absorbed% (in vivo) with a model-independent deconvolution approach. As a result, increase in sodium alginate content lengthened in vitro release time and in vivo t _max value. In addition, for ivivc, linear regression equations with r ² values of 0.8563 and 0.9402 were obtained for microparticles containing 1% and 2% (w/v) sodium alginate, respectively. Lower prediction error for 2% sodium alginate formulations (7.419 ± 4.068) compared to 1% sodium alginate formulations (9.458 ± 5.106) indicated a more precise ivivc for 2% sodium alginate formulation.     

Decay and termite resistance,water absorption and swelling of thermally compressed wood panels

This study evaluated decay and termite resistance of thermally compressed pine wood panels under pressure at either 5 or 7 MPa and either 120 or 150 °C for 1 h. Wood specimens from the panels were exposed to laboratory decay resistance tests by using the wood degrading fungi, Gloeophyllum trabeum and Trametes versicolor. The thermal compression process caused increases in density and decreases in thickness of the panels; however, laboratory decay resistance tests revealed that thermally compressed wood was not resistant against the wood degrading fungi tested. More interesting results were found in laboratory termite resistance tests by using the Eastern subterranean termites, Reticulitermes flavipes. As pressure and temperature applied to the specimens increased to 7 MPa and 120 °C, mass losses in the specimens gradually decreased in comparison with control specimens. However, the specimens compressed at 7 MPa and 150 °C showed higher mass losses when compared to the specimens compressed at 7 MPa and 120 °C. The lowest water absorption and swelling rates were seen in the specimens exposed to a pressure of 7 MPa at 120 °C. The thermal compression process at 7 MPa and 150 °C resulted in the highest water absorption and swelling in the specimens.     

Donor heart preservation with iloprost supplemented St. Thomas Hospital cardioplegic solution in isolated rat hearts

This study was designed to assess the influence of St. Thomas Hospital cardioplegic solution (St. Th.) on heart preservation in rat hearts subjected to 6h ischemia when supplemented with iloprost. In the control group (n=8), nothing was added to St. Th., whereas 10 or 1000 nmol L(-1) iloprost was added in the second (n=7) and third (n=8) groups, respectively. Mechanical contraction parameters, cardiac tissue damage and oxidative stress markers were evaluated. The 10 nmol/L iloprost group peak systolic pressure (71.0+/-30.9 versus 41.0+/-9.4 mm Hg) and -dp/dtmax (1103.8+/-94.3 versus 678.6+/-156.8 mm Hg s(-1)) were significantly higher than control group at 30 min of reperfusion (p<0.05). Iloprost supplemented groups had higher GSH and catalase levels of coronary perfusate at reperfusion, in comparison with initial values (p<0.05). AST, CK, CK-MB values increased at 0 min of reperfusion and cTnI values at 45 min of reperfusion (p<0.05) in all groups with no difference between groups. According to our results, iloprost supplementation had mild but significant improvement in postischemic values in mechanical and oxidative stress parameters, resulting in better heart preservation.     

Effect of zinc ion on cadmium-induced auditory changes

Cadmium, which has adverse effects on many physiological systems, is an important environmental pollutant. Our previous experimental study showed that cadmium also has a dose-dependent deleterious effect on the auditory system in rats. Because zinc reverses cadmium cytotoxicity in many systems, we investigated the possible preventive effect of a zincenriched diet given isochronally on cadmium-induced hearing loss in rats. Fifty-four male rats were divided into three equal groups. Control rats were fed normal rat food and tap water, whereas the cadmium group was subjected to 15 ppm cadmium-containing water as CdCl₂. The third group received 15 ppm CdCl₂ and food enriched with 200 ppm zinc as ZnSO₄ for 30 d. On d 30, eight animals from each group were used for the measurement of kidney functions. In the remaining animals, hearing functions were measured by auditory brainstem response and distortion product otoacoustic emission. Blood cadmium increased from 1.87±1.69 to 6.08±2.62 μg/dL and elevated cadmium contents of ear ossicles and kidney cortex were associated with a decreased glomerular filtration rate in rats subjected to high cadmium. A zinc-enriched diet obviously reduced cadmium accumulation in the kidney and prevented the nephrotoxicity. Our data indicated that cadmium-induced ototoxicity seems to be partially zinc preventable and zinc addition to diet without altering cadmium content in ear ossicles may help to prevent cadmium-induced hearing loss.     

Estimation of the true growth yield and maintenance coefficient for yoghurt cultures

Point and 95% confidence interval estimates of the true growth yield and maintenance coefficient are reported for four pure cultures andtwo mixed cultures of Lactobacillus bulgaricus and Streptococcus thermophilus grown anaerobically on 3% nonfat dry milk using batch followed by fed batch culture. An improved method of data analysis, which includes separate analysis of the exponential growth region and a new method of selecting smoothing spline functions, is utilized. The parameter estimation results are compared with the theoretical maximum yields for one and two moles of ATP produced per mole of glucose and to the growth yield estimated from the exponential growth region analysis.     

Authorized Generic Drugs: an Overview

In the United States (U.S.), an authorized generic (AG) drug is essentially the approved brand-name drug (i.e., innovator drug), but marketed with a different name. Like independent generics, authorized generics (AGs) generally tend to cost less than their brand name counterpart, even though AGs are essentially identical to the brand. Most patients and health professionals are unaware of the availability of AGs even though they are commonplace. The launch of an AG has a financial impact on patients and on the competitive landscape of the pharmaceutical industry. Information regarding AGs is limited. The purpose of this study is to familiarize the reader with AGs. A review of the government documents and literature was conducted. The marketing of AGs has resulted, but not always, in benefits to the patient. AGs have been used as a tool in agreements between brand and generic companies. Countries have differing allowance and approval policies for AGs. AGs have played an important role in the healthcare system.     

Estimation of true growth and product yields in aerobic cultures

In the microbial production of useful products, it is important to understand the allocation of substrate energy for maintanance, growth, and product formation. Methods are presented to obtain point and 95% confidence interval estimates for the true growth yield parameter, true product yield parameter, and the maintenance parameter. Methods are presented which allow all data to be used simultaneously for those cases where more than the minimum number of measurements are made at each specific growth rate (or dilution rate). Three estimation methods and two forms of the energy allocation equations are investigated. Point estimates are similar for the three methods, but interval estimates are considerably larger for one of the three methods. The results depend on the form of the equations.