Enantioselective Pharmacokinetics of Homochlorcyclizine: Disposition of (+)- and (–)-Homochlorcyclizine after Intravenous and Oral Administration of Racemic Homochlorcyclizine to Rats

Abstract— Concentrations of homochlorcyclizine enantiomers in blood, urine, and tissues of the liver, lung, kidney, brain, heart, spleen, intestine and stomach of rats after drug administration were determined by high-performance liquid chromatography on a chiral stationary phase. After intravenous administration (10 mg kg^?1), homochlorcyclizine was rapidly distributed in many tissues, with the highest concentration in lung. No differences were found between enantiomers in blood concentrations. After oral administration (50 mg kg^?1), the concentrations of the (+)-isomer in nearly all tissues were higher than those of the (–)-isomer. The AUC_0-x values of the (+)- and (–)-isomers differed significantly. The absorption of racemic homochlorcyclizine from rat small intestine was not enantioselective. These results suggested that the different concentrations between enantiomers after oral administration were not caused by enantioselective absorption or distribution but rather by preferential first-pass metabolism of the (–)-isomer in the liver. The enantioselectivity of metabolism was also demonstrated by in-vitro experiments.     

Health-related quality of life after radical prostatectomy in Japanese men with localized prostate cancer

PURPOSE: We evaluated retrospectively health-related quality of life (HRQOL) after radical prostatectomy (RP) in Japanese men with localized prostate cancer. METHODS: The study was based on self-reported HRQOL of 280 patients. Patients were divided into seven groups: time 0 (T0), baseline before operation; T1, 1-3 months after RP; T2, 4-6 months after RP; T3, 7-12 months after RP; T4, 13-24 months after RP; T5, 25-36 months after RP; and T6, more than 36 months after RP. We measured the general and disease-specific HRQOL using the RAND 36-item Health Survey 1.0 (SF-36) and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI). RESULTS: The general HRQOL of the postoperative groups was assessed by SF-36. The postoperative groups showed almost the same or higher scores than those of the baseline group. Urinary function scores decreased substantially after surgery. In contrast, there was no difference in urinary bother between the baseline and postoperative groups. Sexual function deteriorated substantially in all postoperative groups. Similarly, the sexual bother score significantly deteriorated after RP. The sexual bother score of men aged 65-years or younger was significantly worse than that of their counterparts in the T1-2 groups. CONCLUSION: Despite reports of problems with sexual activity and urinary continence, general HRQOL was mostly unaffected by RP. Although there was a substantial decrease in urinary function, recovery from urinary bother was rapid. Since the deterioration of sexual function was marked through the postoperative period, careful attention should be paid to this issue during preoperative counseling, especially for younger patients.     

Long-term sequential changes of antibody to p40tax in HTLV-I carrier mothers and children

Antibody to p40^tax (anti-p40^tax) in serum specimens obtained sequentially from a human T cell lymphotropic virus type I carrier population of mothers and children were assayed. The prevalences of anti-p40^tax at the initial sampling were 88% (7/8) in children and 55% (16/29) in mothers. Two of the seven positive children lost their anti-p40^tax during the investigation period, resulting in a final prevalence of 63% (5/8) in children. However, anti-p40^tax status was constant in all the 22 mothers with multiple serum samples (15 remained positive and seven remained negative). A decline in the absorbance value of EIA for anti-p40^tax was observed in seven of the 15 anti-p40^tax positive mothers. This decline may result in the disappearance of anti-p40^tax in some of them.     

Accidental transmission of HCV and treatment with interferon

Accidental transmission of contagious pathogens, especially hepatitis C virus (HCV), by needlestick or other means as an occupational hazard for medical staff is of concern. We retrospectively analysed cases of work-related accidental injury with pathogens such as hepatitis B virus (HBV), HCV, syphilis and human immunode?ciency virus (HIV) reported to the centres for disease control at 15 hospitals (total 5776 beds) in the Gunma prefecture, Japan, from December 1990 to August 1993 (24.7 months). There were 416 such cases (16.8 cases/month), with an incidence of 0.2–3.5 accidents per month per hospital. Such accidents occurred in 297 (71.2%) nurses, 98 (23.5%) medical doctors, 13 (3%) laboratory technicians, four (1.0%) hospital maintenance workers, one (0.2%) assistant nurse, one secretary and two others. There were 323 (77.6%) injuries caused by needlestick, 42 (10.1%) from suture needles or surgical knife cuts, 17 (4.1%) from blood splatters from patients into the eyes or mouth, 10 (2.4%) from contact with injured skin and 24 (5.8%) simple skin contacts. Of the pathogens, 60.3% were HCV, 22.6% HBV, 5.8% syphilis, 0.7% HIV and 10.6% were of unknown origin. Four cases (1.6%) of HCV infection were found and treated with one or two courses of interferon therapy, and HCV was subsequently cleared. All four patients were cured with interferon therapy. None of the HBV-injured cases resulted in infection, possibly because of prophylaxis with HB immunoglobulin and HB vaccine. No HIV or syphilis infection was contracted. In summary, chronic HCV infection acquired as an occupational hazard can be cured by appropriate treatment, such as with interferon, after early detection of the infection.     

Uptake Mechanism of Trientine by Rat Intestinal Brush-border Membrane Vesicles

The uptake characteristics of trientine by rat intestinal brush-border membrane vesicles were studied. The uptake characteristics of trientine were similar to those of the physiological polyamines with respect to the excessive accumulation in vesicles, the pH dependency, the temperature dependency and the ineffectiveness of K⁺ diffusion potential (inside negative). The initial uptake of trientine was saturable with a K_m value of 1.13 mM, which was larger than that of spermine and spermidine. Furthermore, the uptake rate of trientine was dose-dependently inhibited by spermine and spermidine. Spermine competitively inhibited the uptake of trientine with a K_i value of 18.6 μM, and it was close to the K_m value for spermine (30.4 μM). These data suggested that the uptake of trientine was similar to that of spermine and spermidine in rat small intestinal brush-border membrane vesicles, and these polyamines seem to inhibit the absorption of trientine from the gastrointestinal tract.     

Splenogonadal fusion: Case report and review of published works

Splenogonadal fusion is a rare congenital anomaly. We report herein a case of splenogonadal fusion associated with contra lateral testicular aplasia, and review the etiology, pathogenesis and management of this rare disease. As far as we know, this is the first reported case of splenogonadal fusion associated with testicular aplasia.     

Biochemical modulation of 5-fluorouracil with interferon α/β and γ on murine renal cell carcinoma

BACKGROUND: Conventional therapy for renal cell carcinoma (RCC) using interferon (IFN) has shown limited antitumor action. The purpose of the present study was to investigate the synergistic antitumor effects of IFN and 5-fluorouracil (5-FU) and to elucidate the mechanism underlying antitumor effects. METHODS: The antitumor effects and biochemical modulation of murine IFN and 5-FU were determined using murine renal cell carcinoma (RENCA). The activity of thymidylate synthase, thymidine kinase and the concentration of 5-FU incorporated into RNA was measured using cytosolic extracts of tumors. RESULTS: Triple combination therapy (5-FU, IFN alpha/beta and IFN gamma) showed a synergistic antitumor effect on RENCA tumors, because triple combination therapy suppressed growth significantly compared to combination therapy (IFN alpha/beta and IFN gamma, P = 0.0258) and 5-FU (P < 0.0001). Total thymidylate synthase was decreased by triple combination therapy (5-FU, IFN alpha/beta and IFN gamma, P = 0.0019) and combination therapy (5-FU and IFN gamma, P = 0.0018) compared to 5-FU alone. Thymidine kinase activity was decreased by triple combination therapy (5-FU, IFN alpha/beta and IFN gamma, P < 0.0001) and combination therapy (5-FU and IFN alpha/beta, P < 0.0001) compared to 5-FU alone. The concentration of 5-FU incorporated into RENCA tumors was increased by triple combination therapy (P = 0.0132) and combination therapy (5-FU and IFN alpha/beta, P = 0.0124) compared to 5-FU alone. CONCLUSIONS: Interferons alpha/beta and gamma showed different biochemical modulation for 5-FU. Therefore, combination therapy using 5-FU and IFN showed synergistic antitumor effects on murine RCC.     

Changes in work performances in obstructive sleep apnea patients after dental appliance therapy

Abstract The effects of dental appliances on work performances of obstructive sleep apnea syndrome (OSAS) is not well examined. This study evaluated the polysomnographic and psychological findings before and after therapy. Nine patients were diagnosed OSAS by nocturnal polysomnography. The psychological battery was performed from 13:00 to 14:00, which consisted of Uchida-Kraepelin psychodiagnostic test (U-K's test) and Bourdon's cancellation test (Bourdon's test). Approximately 3 months after the treatment, the examinations were performed. Apnea and desaturation index decreased significantly after the therapy. In addition, sleep architecture improved after the therapy compared with that before the therapy. Dysfunction of task performances, such as mean level of work amounts in U-K's test, mean error, mean performance time and mean deviation in Bourdon's test improved after therapy. We conclude that dental appliances therapy is effective not only to apnea but also to work performance in OSAS.     

Inhibiting microbial adhesion to denture base acrylic resin by titanium dioxide coating

Summary Mechanical cleaning of dentures is effective in preventing infections such as aspiration pneumonia and denture stomatitis. For denture wearers with a physical handicap and the elderly, however, mechanical cleaning can present problems. The aim of this study was to investigate the effect of coating denture base acrylic resin with titanium dioxide (TiO₂) in the inhibition of oral microbial adhesion. We prepared uniformly sized acrylic resin plates (10 mm × 10 mm × 0·5 mm), which were divided into two groups (a non‐coated group and a TiO₂‐coated group). The plates were immersed in cultured Streptococcus sanguinis or Candida albicans and incubated for 24 h. After incubation, each plate was washed to remove loosely adherent microorganisms, and then incubated for a further 24 h. Adenosine triphosphate (ATP) content of the microorganisms was evaluated using a reagent containing benzalkonium, which extracts intra‐cellular ATP. In addition, to determine biofilm formation, we also observed each plate by scanning electron microscopy (SEM). We found that the ATP content of both S. sanguinis and C. albicans was reduced by the TiO₂ coating (P = 0·000). Observation by SEM confirmed that the TiO₂ coating inhibited biofilm formation. The results indicate that a TiO₂ coating on a denture base acrylic resin inhibits adhesion of S. sanguinis and C. albicans.     

Comparison of 2-Year Weight Loss Trends in Behavioral Treatments of Obesity: Diet, Exercise, and Combination Interventions

Objective The effects of three cognitive-behavioral weight control interventions for adults were compared: diet only, exercise only, and a combination of diet and exercise. This article reports 2-year follow-up data.Design The three interventions were compared in a randomized, experimental design.Subjects A total of 127 men and women who were at least 14 kg overweight (according to height-weight tables) were recruited from an urban community and assigned randomly to the experimental conditions.Intervention The dietary intervention was a low-energy eating plan adjusted to produce a 1 kg/week loss of weight. The exercise component involved training in walking and a home-based program of up to five exercise periods per week. There were 12 weekly instructional sessions, followed by 3 biweekly and 8 monthly meetings. All sessions were led by registered dietitians.Outcome measures Changes in body weight.Statistical analyses Analysis of variance for weight changes and repeated measures analysis of variance for weight change trends.Results At 1 year, no significant differences were noted among the three groups. The diet-only group lost 6.8 kg, the exercise-only group lost 2.9 kg, and the combination group lost 8.9 kg (P=.09). During the second year, the diet-only group regained weight — reaching 0.9 kg above baseline; the combination group regained to 2.2 kg below baseline; and the exercise-only group regained slightly to 2.7 kg below baseline (P=.36). Repeated measures analysis of variance showed a group-by-time interaction (P=.001); data for the dieting groups best fit a U-shaped regain curve (P=.001).Applications The results suggest that dieting is associated with weight loss followed by regain after treatment ends, whereas exercise alone produced smaller weight losses but better maintenance. The large outcome variability and unequal difficulty of the regimens across groups limit the generalizability of the findings. J Am Diet Assoc. 1996; 96:342-346.