Pharmacokinetics and Biodistribution of Oligonucleotide Adsorbed onto Poly(isobutylcyanoacrylate) Nanoparticles After Intravenous Administration in Mice

Purpose. The goal of this study was to evaluate the ability of nanoparticles to be used as a targeted delivery system for oligonucleotides. Methods. Pharmacokinetic and tissue distribution were carried out in mice by measuring the radioactivity associated to the model oligothymidylate ³³P-pdT₁₆ loaded to poly(isobutylcyanoacryrate) (PIBCA) nanoparticles. In addition, we have used a TLC linear analyzer to measure quantitatively on a polyacrylamide gel electrophoresis, the amount of non degraded pdT₁₆ Results. Organ distribution study has shown that nanoparticles deliver ³³P-pdT₁₆ specifically to the liver reducing its distribution in the kidney and in the bone marrow. Nanoparticles could partially protect pdT₁₆ against degradation in the plasma and in the liver 5 min after administration, whereas free oligonucleotide was totally degraded at the same time. Conclusions. Nanoparticles protect oligonucleotides in vivo against degradation and deliver them to the liver.     

Rebound alkalosis and persistent lactate: multinuclear (1H, 13C, 31P) NMR spectroscopic studies in rats

Intracellular pH levels of infarcted brain determined by phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy disclosed a notable phenomenon. The acidotic brain pH seen in the acute stage of infarction was observed to rebound into the alkalotic range in the subacute phase before returning to the normal range in the chronic phase. This "rebound alkalosis" which was usually observed between the 24th and the 48th hour after experimental induction of infarction in rats was accompanied by significant lactate levels as detected by proton NMR spectroscopy. Analysis of the satellite methyl resonance of 13C-lactate using high-resolution proton NMR spectroscopy after 13C-glucose infusion indicated that no lactate was produced in the subacute phase of infarction and that the lactate detected during this phase must have been generated prior to this phase of infarction.     

Area density of smooth muscle cells and response to endothelin 1 in human hyperplastic prostate

BACKGROUND: alpha-Agonists and endothelins (ETs) are the only agents that have been proved to induce significant contraction of the prostate. Although the response to phenylephrine (PE) is dependent on the quality of smooth muscle (SM) within the prostate, it is not clear whether the response to ET-1 is also influenced by SM density. We evaluate the relationship between contractile responsiveness to ET-1 and the area density of SM of the human prostate. MATERIALS AND METHODS: Specimens were obtained from 17 patients with prostatic hyperplasia that underwent transurethral resection of the prostate. Specimens were used for isometric tension study (PE, KCl and ET) and also for quantitative morphometric analysis. RESULTS: PE and ET-1 induced dose-dependent contractile responses. There were no significant differences in the average maximum response (E(max)) to these two agents. E(max) to KCl and PE showed direct positive correlations with the area density of SM. E(max) to ET-1 also showed a positive correlation with the SM density, although this relationship was weaker than those for the other two agents. Moreover, there was a strong positive relationship between E(max) to PE, KCl and that to ET-1. CONCLUSIONS: The area density of SM appeared to significantly influence the contractile response to ET-1 as well as the response to PE and KCl.     

Detection of chromosome 15 deletion in Prader-Willi syndrome using fluorescence in situ hybridization

Deletion of chromosome 15 was investigated in 6 patients with Prader-Willi syndrome (PWS) using chromosome and fluorescence in situ hybridization (FISH) analysis. Although chromosome analysis using G-banding methods revealed the deletion of 15q11-q13 in only 3 cases, staining by FISH using D15S11 and/or small nuclear ribonucleoprotein polypeptide N (SNRPN) probes detected chromosome 15 deletion in all cases. It would appear that FISH analysis is an effective diagnostic test for the detection of chromosome 15 deletion in patients with PWS.     

Determination of stone composition by noncontrast spiral computed tomography in the clinical setting

OBJECTIVES: Several investigators have evaluated noncontrast computed tomography (NCCT) in predicting stone composition in vitro. We assessed NCCT in predicting stone composition in patients presenting to our emergency room with flank pain and stone disease. METHODS: One hundred twenty-nine patients presenting to our university hospital with flank pain underwent renal colic protocol NCCT scans at the request of the emergency room physicians. A General Electric, high-speed advantage CT scanner was used at 120 kV, 200 mA, and 1.4:1 pitch, with collimation varying between 3 and 5 mm. Ninety-nine patients with predominantly (greater than 50%) calcium oxalate or uric acid composition after either stone passage or stone removal were identified. Each scan was analyzed by one of two radiologists, who determined the predominant attenuation for each stone. Stones once passed or retrieved were analyzed by Urocor Laboratories. The attenuation and attenuation/size ratio (peak attenuation/size in millimeters) were compared with the results of the stone analysis. RESULTS: Eighty-two calculi predominantly composed of calcium oxalate and 17 calculi predominantly composed of uric acid were identified in 99 patients. The calculi ranged in size from 1 to 28 mm. A significant difference (P = 0.017, unpaired t test) was found between the Hounsfield measurement of uric acid calculi (mean 344 +/- 152 HU) and the Hounsfield measurement of calcium oxalate calculi (mean 652 +/- 490 HU). If only the Hounsfield units from stones 4 mm or larger were compared, the data were even more compelling (P = 0.002). However, using an attenuation/size ratio cutoff of greater than 80, the negative predictive value was 99% that a stone would be predominantly calcium oxalate. CONCLUSIONS: Using peak attenuation measurements and the attenuation/size ratio of urinary calculi from NCCT, we were able to differentiate between uric acid and calcium oxalate stones.     

Influence of sex hormones on prostate volume in men on hemodialysis

The relationship between sex hormones and prostate volume in 90 men on hemodialysis and 91 healthy men was investigated. In men on hemodialysis, serum levels of total and free testosterone were significantly reduced compared with the controls (P < .001), whereas the serum estradiol level was significantly elevated in men on hemodialysis (P < .001). However, prostate volumes were not different between the 2 groups. Serum estradiol level correlated with the prostate volume in controls (P < .001), whereas total and free testosterone levels did not correlate with the prostate volume. In men on hemodialysis, serum levels of total and free testosterone and estradiol did not correlate with the prostate volume. The present study suggests that sex hormones do not play important roles in the prostate growth in men on hemodialysis.     

A case of intra-articular fracture of the knee joint with three layers within lipohemarthrosis by ultrasonography and computed tomography

We report a case of intra-articular fracture of the knee joint showing three layers within lipohemarthrosis. Sagittal ultrasonography showed three layers (double fluid-fluid level): a superior hyperechoic layer of fat, an intermediate anechoic layer of serum, and an inferior hypoechoic layer of red blood cells. Horizontal computed tomography imaging demonstrated the same three layers. This is the first case of lipohemarthrosis in which three layers of joint effusion were confirmed by both ultrasonography and computed tomography.     

Bone fracture receiving LH-RH agonists for prostatic cancer

BACKGROUND: Luteinizing hormone-releasing hormone (LHRH) agonists are popularly used drugs in the treatment of prostatic cancer. However, it has been reported that continuation of a low testosterone level following a longterm administration of these drugs reduces the bone mineral density and makes for osteoporosis, which is accountable for fracture, we measured the bone mineral density and bone metabolic markers in the cases who suffered fracture receiving LHRH agonists for prostatic cancer. PATIENTS AND METHODS: Between 1994 and 1998, 196 patients (mean age 78.1 years) were treated with LHRH agonists for prostatic cancer. Of these patients, 13(7%) who had bone fracture during treated with LHRH agonists were divided into fracture group, and 70 patients who had not bone fracture divided into non-fracture group. Fracture by traffic accident was excluded. The bone density in the third lumbar vertebra was measured using quantitative computed tomography (QCT). Osteocalcin, 1, 25- (OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone (PTH) and calcitonin were measured as bone metabolic markers. RESULTS: The mean age of fractured cases was 78 years. The period from the start of treatment to fracture was 11 to 45 months (mean 27 months). No case of fracture at the site of metastasis of prostatic cancer was found. The bone density was significantly low in the fracture group compared with that of non-fracture group. Of the bone metabolic markers, NTx showed high values in the fracture group. CONCLUSION: There is a need to measure bone mineral density and bone metabolic markers periodically and to evaluate secondary osteoporosis in the patients receiving LHRH agonists for prostatic cancer.