Regional analysis of 5-HT1A and 5-HT2 receptors in the fawn-hooded rat.

The Fawn-Hooded strain of rats exhibits a hemorrhagic disorder, known as platelet storage pool deficiency. In addition to the platelet dysfunction, there is an altered response to certain serotonin drugs. To assess the characteristics of the binding to 5-HT1A and 5-HT2 receptors in this strain, regions of the brain from Fawn-Hooded, Sprague-Dawley and Wistar male rats were examined. The drug [3H]8-OH-DPAT was used to label 5-HT1A receptors and the Kd values for frontal cortex, hippocampus, striatum, hypothalamus and brainstem were similar in all three strains of rat. As with the 5-HT1A receptors, no differences were observed in the Kd values for 5-HT2 receptors, in any of the regions examined, among the three strains. However, the Bmax for the binding of [3H]8-OH-DPAT in the striatum and brainstem of Fawn-Hooded rats was less than in the Sprague-Dawley and Wistar animals. Furthermore, 5-HT2 receptors displayed a greater Bmax value in the striatum and in the frontal cortex of Fawn-Hooded animals, compared to Sprague-Dawley and Wistar rats. These differences in receptors are consistent with previous studies in which Fawn-Hooded rats were found to have altered serotonergic function, relative to Wistar and Sprague-Dawley animals.     

Statistical MUNE: A comparison of two methods of setting recording windows in healthy subjects and ALS patients

OBJECTIVE: To address the issue as to how best to perform statistical MUNE, we applied two different approaches and compared results in healthy subjects and ALS patients. METHODS: Twelve normal subjects (women 8, mean age 52years) and 11 ALS patients (women 4, mean age 54years) underwent two consecutive MUNE studies, which differed in terms of setting and modifying the recording window. These are referred to as the 'expansion' and 'narrowing' methods, respectively. Size-weighted average (Av) SMUP and MUNE values were obtained using the two methods, and compared in control and patient groups. RESULTS: Expansion method-derived Av SMUP sizes and MUNE values differed only slightly from those obtained using the narrowing method in healthy subjects, whereas the narrowing method resulted in significantly larger Av SMUP sizes and smaller MUNE values than the expansion method in ALS patients (Wilcoxon signed ranks test, p=0.003). The sizes of tested areas (mean+/-SD) were significantly larger for the narrowing method than the expansion method in both subject groups with much greater difference in ALS patients; 9.6+/-3.1% vs. 7.9+/-1.7% in healthy subjects and 16.1+/-5.1% vs. 11.2+/-3.0% in ALS patients (Student t-test, p<0.01). CONCLUSIONS: The present study shows, unlike that found in normal subjects, that the results of statistical MUNE in ALS patients are heavily dependent on the approach used to set and modify recording windows. SIGNIFICANCE: The expansion method using a 10%-sized window is likely to suffer from systemic errors due to the ceiling effect and the sampling of artifactually small motor units in ALS patients. The authors recommend that the narrowing method be considered as an alternative that avoids these problems.     

Effect of dietary protein on renal tubular clearance of drugs in humans

Diet is one of many factors that influence the pharmacokinetics of drugs. The level of protein intake has been found to significantly influence drug metabolism and glomerular filtration, both of which play an important role in the clearance of drugs. Recently, a marked change, resulting from restricted dietary protein intake, has been reported in the handling of several drugs which are reabsorbed and/or secreted by the renal tubules. In studies of healthy volunteers on protein-restricted diets the renal clearance and fractional excretion of model compounds have been altered, falling to 30% of values obtained on normal diets in the case of the weak acids oxipurinol and uric acid; the fractional excretion of the weak base cimetidine has been increased by 30%. These studies have also found that the change in the renal clearance of both acids is sustained with prolonged dietary protein-calorie restriction, and that, for oxipurinol, the magnitude of the change is directly related to the quantity of protein in the diet, the change is related specifically to the protein content in the diet (and not the total calories), the onset of change is rapid, and on a low-protein diet the renal clearance undergoes marked diurnal variation. The mechanism for the alteration in tubular function is not clear, but may be related to renal haemodynamic changes or competition for transport associated with protein intake. Regardless of the mechanism, these results have important implications for pharmacokinetic research and clinical practice.     

Clinical evaluation of a prostate-specific antigen as a serum marker of prostatic cancer

Combined measurement of serum prostate-specific antigen (PA) and prostatic acid phosphatase (PAP) was performed in 235 patients with various urologic diseases including 55 patients with prostatic cancer. A PA level of over 24.7 ng/ml and a PAP level of over 3.1 ng/ml were considered to be positive. The positive rate of PA was 57% in the patients with untreated prostatic cancer and 3% in the patients without prostatic cancer. The positive rate of PAP was 52% in the patients with untreated prostatic cancer and 1% in the patients without prostatic cancer. PA and PAP were considered to be equally sensitive and specific serum markers of prostatic cancer. However, the positive rate increased to 65% without increasing the false positive rate when the PA and PAP were both measured simultaneously. The combined assay of PA and PAP is recommended for screening prostatic cancer. The cross-over titer of PA and gamma-Sm using standard samples in each kit revealed linearity, which suggested that PA and gamma-Sm possess the same antigenicity.     

Posterior chamber intraocular lenses in a series of 75 autopsy eyes. Part I: Loop location

Over a period of 27 months, November 1983 to February 1986, 75 eyes obtained postmortem with posterior chamber intraocular lenses (IOLs) were examined at the Center for Intraocular Lens Research, University of Utah Health Sciences Center. These IOLs were studied by histopathological techniques to determine the location of the loops. The most common combination, found in 47% of the specimens, was one loop in the lens capsular sac (bag) and one loop in the ciliary sulcus. In 32% of the specimens, both loops were in the capsular sac; in 17%, both loops were in the ciliary sulcus. Compared to results observed in other autopsy studies, in which capsular fixation was documented in less than 3% of cases, these findings reflect a trend toward capsular sac (in-the-bag) implantation of open-looped posterior chamber IOLs.     

Monoclonal antibodies directed characterization of epidermal and hepatic cytochrome P-450 isozymes induced by skin application of therapeutic crude coal tar

A single application of crude coal tar (CCT) solution (USP) to the skin of neonatal rats was shown to induce epidermal and hepatic cytochrome P-450(P-450)-dependent monooxygenase activities. To further characterize the induction response, in this study we have utilized highly specific monoclonal antibodies (MoAb) 1-7-1, 2-66-3, and 1-98-1 directed against highly purified rat liver P-450s induced by 3-methyl-cholanthrene, phenobarbital and ethanol, respectively. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of hepatic microsomes prepared from CCT-treated animals showed a significant increase in the coomassie blue stainable proteins in the P-450 region; however, this was not evident in epidermal microsomes. Immunoblot analysis of epidermal and hepatic microsomes with MoAb 1-7-1 revealed strong immunoprecipitin bands in both tissues. MoAb 2-66-3 showed significant immunoreactivity only with hepatic microsomes. Interestingly, CCT treatment resulted in suppression of immunoreactivity with MoAb 1-98-1 in hepatic microsomes. MoAb 1-7-1 and 2-66-3 exhibited concentration-dependent inhibitory effects in aryl hydrocarbon hydroxylase and 7-ethoxycoumarin-O-deethylase activities induced by CCT application. MoAb 1-7-1 was substantially more effective in this respect. Epidermal and hepatic microsomes prepared from CCT-treated rats showed significantly greater metabolism of benzo(a)pyrene (BP). MoAb 1-7-1 and MoAb 2-66-3 inhibited BP metabolism in both the tissues. However, MoAb 1-7-1 was more inhibitory in this regard as compared to MoAb 2-66-3. These studies indicate that topical application of therapeutic CCT to the skin of neonatal rats results in induction of P-450 isozyme c in epidermis and isozymes b and c in liver, and that this induction is associated with the suppression of P-450 isozyme j in liver.     

Molecular and mechanical property changes during aging of bone cement in vitro and in vivo

The changes in mechanical properties and free radical concentration of curing Simplex P Radiopaque Bone Cement in vivo and in vitro conditions were studied. Samples were prepared so that each in vivo sample that cured and aged in the canine femoral intramedullary cavities had an in vitro counterpart that was cured and aged in a constant-temperature saline bath at 37 degrees C. An electron paramagnetic resonance (EPR) spectrometer was used to measure the growth and decay (curing) of polymerization radicals. The results of EPR measurements showed that the curing (disappearance of free radicals) of in vivo samples takes a much longer time (more than 4 weeks) than in vitro curing (less than 2 weeks). The mechanical tests indicate that, whether aged in vivo or in vitro, the strength increased rapidly for the first 1-2 weeks and then slight increases were seen for up to 6 months.     

Retained intrahepatic stones: treatment with piezoelectric lithotripsy combined with stone extraction

Extracorporeal shock wave lithotripsy (ESWL) was performed in 11 patients with oriental cholangiohepatitis and intrahepatic stones associated with segmented strictures of intrahepatic ducts. All patients had previously undergone biliary surgery and basket extraction via a T-tube tract at the time of lithotripsy. The indication for ESWL was failure of, or anticipated difficulty with, basket extraction of the stones via a T-tube tract. A piezoelectric lithotriptor was used in all procedures. The average total number of shock waves administered was 29,756 (range, 10,000-61,395). The average number of treatment sessions was 3.1 (range, 1-6); the number of shock waves used in a single session ranged from 10,000 to 15,000 with a frequency of five shots per second and 30%-50% power. In six patients, the stones were successfully fragmented and completely removed; in three of the others of the stones were fragmented and removed. The overall success rate, including complete (54%) and incomplete (27%) success, was 82%. Difficulty in targeting stones, and severe strictures and deformities of intrahepatic ducts, were the factors responsible for failure. No significant complications were observed.     

Poly(L-lysine)-g-poly(D,L-lactic-co-glycolic acid) micelles for low cytotoxic biodegradable gene delivery carriers.

Poly(lactic-co-glycolic acid) (PLGA)-grafted poly(L-lysine) (PLL) (PLL-g-PLGA) was synthesized to demonstrate its micelle-forming property in an aqueous solution. The micelles were used as a gene delivery carrier. The hydrodynamic diameter of PLL-g-PLGA micelles in an aqueous solution was ca. 149 nm with a narrow size distribution. Critical micelle concentration (cmc) was 9.6 mg/l. The PLL-g-PLGA micelles could be used to produce compact nanoparticulate complexes with plasmid DNA, which could efficiently protect the complexed DNA from enzymatic degradation by DNase I. The micelle/DNA complexes had highly compacted structure sized between 200-300 nm with a positive surface charge value. The PLL-g-PLGA micelles exhibited much higher transfection efficiency with lower cytotoxicity than PLL. Here, we demonstrated that biodegradable and cationic PLL-g-PLGA micelles could be used as an effective DNA condensation carrier for gene delivery system.