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Biomedical subjects

H F Huang

Publications and source records attributed to H F Huang.

At least 19 recordsLinked to original sources

Purging of murine erythroblastic leukemia by ZnPcS2P2-based-photodynamic therapy.

A key point for successful transplantation of autologous hematopoietic stem cells in the treatment of leukemia is the purging technique, of which photodynamic therapy (PDT) proved effective and promising. The aim of this study was to evaluate the purging effect of a novel amphipathic photosensitizer, di-sulfo-di-phthalimidomethyl phthalolcyanine zinc (ZnPcS2P2)-based PDT (ZnPcS2P2-PDT) on murine erythroblastic leukemic EL9611 cells. Bone marrow cells (BMC), harvested from normal BALB/c mice, were contaminated with variable EL9611 cells. Cell suspensions were incubated with 4 microg/ml ZnPcS2P2 for 5 h and then exposed to 2.1 J/cm2 irradiation by a semiconductor laser 670 nm. Lethally irradiated recipient BALB/c mice (7 Gy) received syngeneic bone marrow transplantation with purged or nonpurged cell mixtures of 10(7) BMC contaminated with variable numbers (10(2)-10(5)) of EL9611 cells. All of the irradiated controls died due to sepsis. All of the mice injected with nonpurged cell mixtures developed leukemia and died, whereas the mice transplanted with ZnPcS2P2-PDT-treated mixtures had a longer survival time, and the fewer leukemic cells there were in the cell mixtures, the higher the leukemia-free survival rate. We conclude that ZnPcS2P2-PDT could purge leukemic cells from bone marrow autografts but could retain sufficient progenitor cells for the hematopoietic activity.

Animals↗

Incidence of Haemophilus influenzae type b and other invasive diseases in South Korean children.

To determine incidence of invasive Haemophilus influenzae type b (Hib) disease in a defined population of Jeonbuk Province, Korea, children <5 years were evaluated in prospective, population-based surveillance of invasive bacterial diseases using standardized methods for patient referral, clinical evaluation and laboratory testing (optimized culture, latex agglutination, polymerase chain reaction). Vaccine utilization was assessed with vaccination histories of patients in surveillance, monthly data on Hib vaccine distribution and a coverage survey of clinic patients in study population. From September 1999 to December 2001, 2176 children were evaluated for possible meningitis, 1541 had no cerebrospinal fluid (CSF) findings of meningitis, 605 had CSF abnormalities (suspected bacterial meningitis) but no pathogen identified; six patients had probable Hib meningitis and eight had confirmed Hib meningitis. The annual suspected bacterial meningitis incidence was 258.4/100,000 <5 years and the probable/confirmed Hib meningitis incidence was 6.0/100,000 <5 years. Pneumococcal meningitis incidence was 2.1/100,000 <5 years and Group B streptococcal meningitis incidence was 0.17/1000 live births. A total of 69,589 Hib vaccine doses were distributed during the study. Hib vaccine coverage was negligible initially but increased to 16% (complete Hib immunization) and 27% (partial immunization) in final months of study. Suspected bacterial meningitis incidence was high but proven invasive Hib meningitis incidence was low. Hib was leading cause of bacterial meningitis yet bacterial pathogens were identified in only 4% of abnormal CSF. These findings may reflect truly low incidence, presumptive antibiotic treatment, partial Hib immunization, or incomplete clinical evaluations. Given the apparent Hib meningitis burden in Jeonbuk Province, additional studies to describe other invasive Hib syndromes, Hib-associated mortality and disability, and economic impact of Hib disease will be useful to guide public health decisions regarding routine Hib vaccine introduction.

Adolescent↗

IL-6 signaling by STAT3 participates in the change from hyperplasia to neoplasia in NRP-152 and NRP-154 rat prostatic epithelial cells.

BACKGROUND: STAT3 phosphorylation is associated with the neoplastic state in many types of cancer, including prostate cancer. We investigated the role of IL-6 signaling and phosphorylation of STAT3 in 2 rat prostatic epithelial lines. NRP-152 and NRP-154 cells were derived from the same rat prostate, yet the NRP-152 cells are not tumorigenic while the NRP-154 cells are tumorigenic. These lines are believed to represent 2 of the stages in the development of prostate cancer, hyperplasia and neoplasia. Differences in signaling pathways should play a role in the 2 phenotypes, hyperplastic and neoplastic. METHODS: We looked at the phosphorylation state of STAT3 by intracellular flow cytometry, using phospho-specific antibodies to STAT3. We used the same method to examine IL-6 production by the cell lines. We also measured apoptosis by binding of fluorescent annexin V to the cells. RESULTS: Although both cells lines made IL-6 constitutively, phosphorylated-STAT3 was present in untreated NRP-154 cells, but not in NRP-152 cells. Treatment with dexamethasone inhibited the IL-6 production of NRP-152 cells, but enhanced that of NRP-154 cells. Treatment with the JAK2 inhibitor AG490 induced apoptosis in NRP-152, but not NRP-154 cells. CONCLUSIONS: We conclude from these experiments that STAT3 activity plays a role in the phenotype of NRP-154 cell, but not NRP-152 cells. The significance of alternative IL-6 signaling pathways in the different phenotypes of the 2 cell lines is discussed.

Animals↗

Alteration of follicle-stimulating hormone and testosterone regulation of messenger ribonucleic acid for Sertoli cell proteins in the rat during the acute phase of spinal cord injury.

The detrimental effects of spinal cord injury (SCI) on spermatogenesis in the rat can be attenuated by exogenous testosterone (T) but enhanced by exogenous follicle-stimulating hormone (FSH). These results suggest that T-dependent cellular events may be involved in testicular injury after SCI and that such events may be associated with modification of FSH effects on Sertoli cell function. The current study compared the responses of Sertoli cells to exogenous T and FSH after SCI or sham surgery using steady-state levels of Sertoli cell protein mRNA transcripts as markers of responsiveness. Rats underwent sham surgery or SCI and then were treated for 7 or 14 days with T-filled silastic capsules (2 x 5 cm) and/or daily injections of 0.1 units of porcine FSH. Vehicle-treated control rats received 5-cm empty capsules and daily injections of saline vehicle. Two weeks after sham surgery, levels of mRNA for the androgen receptor (AR), FSH receptor (FSHR), androgen-binding protein (ABP), or sulfated glycoprotein (SGP)-2 in the testis were unaffected by T or FSH alone. Testosterone alone, however, significantly decreased transferrin (Trf) mRNA levels in the testis (P: < 0.01). The combination of T and FSH treatments resulted in significant decreases in levels of the above transcripts (P: < 0.05; P: < 0.01). Seven days after SCI, the testes of vehicle-treated SCI rats had higher levels of AR and SGP-2 mRNA than did those of sham control rats (P: < 0.01); such effects were transient and disappeared by Day 14 post-SCI. Testosterone treatment of SCI rats for 7 days resulted in decreases in mRNA levels for AR and Trf in the testes (P: < 0.01) but increased testicular levels of mRNAs for FSHR and SGP-2 in SCI rats. Follicle-stimulating hormone treatment for 7 days prevented the increase in AR mRNA that was seen in the testis of untreated SCI rats and increased levels of ABP and SGP-2 mRNAs in SCI rats (P: < 0.01). Follicle-stimulating hormone treatment of SCI rats did not affect FSHR mRNA levels by itself, but it blocked the stimulatory effect of T on FSHR and SGP-2 mRNAs. Fourteen days after SCI, testicular AR mRNA levels were not affected by T alone, but they increased in those rats that received FSH with or without concurrent T treatments (P: < 0.05). In contrast to their effects in sham control rats, T or FSH alone or in combination resulted in significant increases in testicular levels of ABP, SGP-2, and FSHR mRNAs (P: < 0.05). At this time, Trf mRNA in the testis of SCI rats was also suppressed by T (P: < 0.05), as it did in sham control rats, but Trf mRNA was increased by the FSH (P: < 0.01) that had inhibited this transcript in the testes of sham control rats. The effects of FSH on the Sertoli cell transcripts in SCI rats were either attenuated or blocked when T was given concurrently. In addition, testicular and serum T levels in those SCI rats that received FSH (alone or in combination with T) for 14 days were significantly increased, an effect that was not seen after sham surgery. These findings demonstrate that hormonal regulation of both Sertoli and Leydig cells was altered during the acute phase of SCI. Such changes may modify the functions of both cell types, thereby affecting the endocrine and/or paracrine microenvironment within the seminiferous epithelium. These effects could impair the functional capacity of Sertoli cells and contribute to impairment of spermatogenesis after SCI.

Androgen-Binding Protein↗

The effects of testicular denervation on spermatogenesis in the Sprague-Dawley rat.

In the rat, regression of spermatogenesis during the chronic stages of spinal cord injury (SCI) occurs in the presence of normal function of the pituitary-testis hormone axis, thus suggesting that nonendocrine mechanisms might be involved. The current study examined whether disruption of neural input to the testis contributes to the cascade that leads to the regression of spermatogenesis. Four weeks after denervation of the superior spermatic nerve (SSN), testis weight was 25% lower (p < 0.01) than that of the contralateral sham-operated testis. Defects in spermatogenesis including phagocytosis of mature spermatids, vacuolization of spermatid nuclei, delayed spermiation and incomplete cellular associations were observed in >60% of the tubules. In the remaining 30-40% of tubules, the seminiferous epithelium was severely regressed. While cutting the inferior spermatic nerve (ISN) alone did not affect spermatogenesis significantly, it enhanced the effect of SSN denervation on both spermatogenesis and testis weight (p < 0.01). Spermatogenesis was totally regressed in the SSN/ISN-denervated testes. At this time, quantitatively normal spermatogonial proliferation was maintained in SSN- or ISN-denervated testes. Twelve weeks after surgery, regression of the seminiferous epithelium characterized by absence of proliferating spermatogonia, while undifferentiating spermatogonia were present, was observed in all SSN-denervated testes. At this time, regression of the seminiferous epithelia also occurred in >30% of the tubules in ISN-denervated testes. At both times, serum follicle-stimulating hormone, luteinizing hormone and testosterone levels were normal and >60% of normal testicular testosterone concentrations were maintained in the denervated testes. These results indicate that disruption of neural input to the testis is not a cause for the decrease in spermatogonial proliferation during the acute phase of SCI, but may contribute to the chronic effects of SCI on spermatogenesis.

Animals↗

Risk factors for renal allograft survival in patients receiving cyclosporine immunosuppression.

BACKGROUND AND PURPOSE: Although cyclosporine (CsA) has been widely used in renal transplantation for more than 10 years, no large series of renal transplant patients has been studied in southern Taiwan. The purpose of this retrospective cohort study was to investigate the risk factors for graft survival in renal transplant recipients. METHODS: From August 1987 to January 1998, 101 primary cadaveric renal transplantations were performed. The minimum follow-up period was 1 year. CsA and prednisolone were initially used as immunosuppressive agents in all patients. Use of lower doses of CsA to reduce CsA trough level (50-99 ng/mL) in hepatitis B surface antigen (HBsAg)-positive recipients was attempted at 6 months after transplantation. RESULTS: Graft actuarial survival rates at 1, 5, and 10 years posttransplantation were 89%, 75%, and 57%, respectively. Acute rejection and increased recipient age were found to be significant risk factors (p < 0.05) affecting graft survival, with hazard ratios of 5.20 and 1.74, respectively, by multivariate analysis using a Cox proportional hazards model. Hepatitis B and/or hepatitis C infection had no influence on graft survival. CONCLUSIONS: In this series of cadaveric renal allograft patients, the risk factors affecting allograft survival were acute rejection and recipient age.

Adolescent↗

Retinoid and androgen regulation of cell growth, epidermal growth factor and retinoic acid receptors in normal and carcinoma rat prostate cells.

Recent in vivo and in vitro studies suggest that retinoic acid receptor (RAR)-mediated processes may be involved in androgen regulation of prostate cells in a manner that may be altered during prostatic carcinogenesis. We tested this hypothesis in the newly established carcinoma and non-carcinoma rat prostate epithelial cell lines, NRP-154 and NRP-152, respectively. In DMEM/F-12 medium supplemented with 10% charcoal stripped fetal calf serum (cFCS), the number of both NRP-152 and NRP-154 cells were stimulated by testosterone (T), with a 4-fold greater effect in NRP-152 than in NRP-154 cells. Retinoic acid (RA) alone also stimulated the growth of NRP-152 cells, but failed to induce cell growth of NRP-154 cells. Importantly, the level of RAR alpha mRNA was elevated whereas the levels of RAR gamma and androgen receptor (AR) mRNA were lower in NRP-154 cells compared to those in NRP-152 cells. Treatment of NRP-152 cells with increasing doses of T resulted in a dose-dependent decrease and rebound of the level of RAR alpha and gamma mRNA in NRP-152 cells; these effects were not apparent, if not reversed, in NRP-154 cells. Both ligand binding and Western blot analyses revealed that epidermal growth factor receptor (EGF-R) was stimulated by 20 nM T but was suppressed by 0.1 microM RA, which also attenuated the stimulating effects of T on EGF-R in NRP-152 and to a lesser extent in NRP-154 cells. The differences in the level and androgen regulation of RAR mRNAs and reciprocal regulation of EGF-R expression by T and RA between NRP-154 and NRP-152 cells suggest that variations in the EGF-R and RAR signal events may contribute to differences in growth rate between these two cell lines.

Animals↗

Epididymal sperm transport in normal and recent spinal cord injured Sprague Dawley rats.

Causes of poor semen quality following spinal cord injury (SCI) are not known. One possible reason, based upon studies that reported improved semen quality in SCI men after several induced ejaculations, is delayed epididymal sperm transport. Our study was designed to establish baseline epididymal sperm transport values in the Sprague Dawley rat and evaluate effects of SCI on this process. Spermatozoa protamine was labeled with tritiated arginine, and the rats were sacrificed various times after injection. Each epididymis was divided into six equal sections from proximal to distal. Sperm tails were dissolved with 8 molar (M) urea in the presence of 2 mM dithiothreitol (DTT); sperm heads were collected by centrifugation (3,000 rpms, 10 min.). The radioactivity in sperm heads from each section was counted and expressed as counts per million sperm heads. To account for different rates of labeled arginine incorporation, the percentage of counts per million sperm heads in each section was calculated relative to the total number of counts in all six sections. Our results showed there was an orderly progression of sperm through the epididymis. It took 8 days for labeled sperm to enter the epididymis and 28 days to peak in the caudal (tail) section in non-SCI rats. Stasis was present 10 days after T-9 SCI in rats compared with transport in sham controls. This was evidenced by a significant increase in the percentage of labeled sperm in proximal sections of the epididymis (sections 1, 2, and 4) in T-9 transected animals (p < 0.01). If similar stasis occurs in SCI men, it could obviously contribute to poor semen quality. However, it remains to be determined how long this stasis persists after SCI in rats.

Animals↗

Effects of spinal cord injury on spermatogenesis and the expression of messenger ribonucleic acid for Sertoli cell proteins in rat Sertoli cell-enriched testes.

The study was an examination of the effects of spinal cord injury (SCI) on spermatogenesis and Sertoli cell functions in adult rats with Sertoli cell-enriched (SCE) testes. The effects of SCI on the seminiferous epithelium were characterized by abnormalities in the remaining spermatogenic cells during the first month after SCI. Three days after SCI, serum testosterone levels were 80% lower, while serum FSH and LH levels were 25% and 50% higher, respectively, than those of sham control SCE rats. At this time, the levels of mRNA for androgen receptor (AR), FSH receptor (FSH-R), and androgen-binding protein (ABP) were normal whereas those for transferrin (Trf) had decreased by 40%. Thereafter, serum testosterone levels increased, but they remained lower than those of the sham control rats 28 days after SCI; and serum FSH and LH levels returned to normal. The levels of mRNA for AR, ABP, and Trf exhibited a biphasic increase 7 days after SCI and remained elevated 28 days after SCI. FSH-R mRNA levels were also elevated 90 days after SCI. Unexpectedly, active spermatogenesis, including qualitatively complete spermatogenesis, persisted in > 40% of the tubules 90 days after SCI. These results suggest that the stem cells and/or undifferentiated spermatogonia in SCE testes are less susceptible to the deleterious effects of SCI than the normal testes and that they were able to proliferate and differentiate after SCI. The presence of elevated levels of mRNA for Sertoli cell FSH-R and AR, as well as of that for the Sertoli cell proteins, in the SCE testes during the chronic stage of SCI suggests a modification of Sertoli cell physiology. Such changes in Sertoli cell functions may provide a beneficial environment for the proliferation of the stem cells and differentiation of postmeiotic cells, thus resulting in the persistence of spermatogenesis in these testes.

Androgen-Binding Protein↗

The detrimental effects of spinal cord injury on spermatogenesis in the rat is partially reversed by testosterone, but enhanced by follicle-stimulating hormone.

Our previous studies have demonstrated that impaired spermatogenesis during the acute phase of spinal cord injury (SCI) is preceded by a transient (but significant) suppression of serum FSH, LH, and testosterone (T) concentrations. It is hypothesized that hormonal deprivation may impair Sertoli cell function, leading to the loss of spermatogonia, degeneration of spermatogenic cells, and eventual regression of the seminiferous epithelium. The current study examined the efficacy of exogenous T and FSH in the maintenance of spermatogenesis and Sertoli cell functions in SCI rats. Implantation of T capsules (TC, 2 x 5 cm) attenuated some of the spermatogenic lesions and maintained qualitatively complete spermatogenesis in all SCI rats 4 weeks after the surgery. In contrast, daily injections of 0.1 U of FSH alone, or in combination with TC implants, paradoxically enhanced the regression of spermatogenesis in SCI rats. At this time, the numbers of Aal, A1, and B spermatogonia and preleptotene spermatocytes in SCI rats have decreased by 25-30%. Though not prevented by TC implants, the decrease in Aal and A1 spermatogonia was attenuated by FSH alone but was further enhanced when FSH-treated rats also received TC implants. The intratesticular T concentration in untreated and FSH-treated SCI rats was not different from that of sham control rats, but it decreased by more than 95% in those SCI rats given TC implants alone. These results demonstrate that impairment of spermatogenesis during the acute phase of SCI is not related to the availability of FSH and/or T. Northern blot analysis revealed an increase in androgen receptor messenger RNA (mRNA) in the testis of SCI rats; this increase was prevented by TC implants but persisted when FSH was also given. In contrast, the levels of FSH-receptor, androgen binding protein, and transferrin mRNA were not affected by SCI but were significantly higher in those SCI rats given FSH alone or in combination with TC. TC implants alone suppressed mRNA levels of transferrin in testes of SCI rats, without concomitant change in those for FSH-receptor and ABP. The changes in Sertoli cell responses to FSH and T, and perhaps other hormones, may alter signal events elicited by these hormones, thus contributing to abnormal epithelial environments and regression of spermatogenesis. Maintenance of spermatogenesis in SCI rats by exogenous T suggests the feasibility of using exogenous hormones to impede the detrimental effects of SCI on spermatogenesis. This approach may have clinical applicability for the preservation of spermatogenic functions in SCI men.

Animals↗

Subcutaneous tumors of mice treated with rhodamine-123 and laser irradiation.

BACKGROUND: Treatment involving photosensitizers and laser irradiation (LIR) in cancer therapy is known as photodynamic therapy (PDT). The purpose of our study was to assess the therapeutic effect of PDT using rhodamine-123 (Rh123) and LIR on subcutaneous tumors (ST) in mice. METHODS: Sarcoma-180 cells (1 x 10(7)) were implanted subcutaneously into the breast area of strain Cr1:CD-1-ICR (BR) female mice. Mice bearing ST were treated with Rh123 or LIR alone, or a combination of both, once a day for 3 successive days. RESULTS: The best therapeutic effect was observed in the group treated with 7.5 mg Rh123 per kilogram of body weight, combined with 75 J/cm2 laser irradiation energy. The group's mortality rate, tumor control rate, mean survival time, and increase in lifespan within 120 days after treatment were 16.7%, 83.3%, 109.4 days, and 135.8%, respectively. The most inhibitory effect on tumor cells was found in the group treated with 15 mg/kg Rh123 and 90 J/cm2 laser irradiation. The biosyntheses of DNA, RNA, and protein in tumor cells of this group was obviously inhibited. CONCLUSION: PDT with the photosensitizer Rh123 and laser irradiation was therapeutically effective in treating subcutaneous tumors of mice. The tumor cells and the syntheses of DNA, RNA, and protein of the tumor cells in these PDT treated mice were obviously inhibited.

Animals↗

Effects of glycyrrhizae and glycyrrhizic acid on cellular immunocompetence in low-dose gamma-ray irradiated mice.

BACKGROUND: For both animals and human beings, it is important to prevent damage from ionizing radiation and to restore immunocompetence following irradiation. The present study was conducted to investigate the effects of glycyrrhizae (GL) and glycyrrhetinic acid (GA) on cellular immunocompetence in low dose gamma-ray-irradiated mice. METHODS: Six- to 8-week-old ICR strain' Crl:CD-1-ICR (BR) strain male mice, bred in the Institute of Cancer Research, U.S.A., were chosen and divided into four groups. Group A was the normal control. Group B, the experimental control, received 1 Gy of whole body gamma-ray irradiation. Groups C and D, the experimental groups, were treated with 500 mg/kg of GL (orally) and 5 mg/kg body weight of GA (i.p.), respectively, once a day, 5 days a week for 2 weeks after gamma-irradiation. The tested mice were killed, at 6 different intervals to measure their leukocyte and differential counts. Cellular immunocompetence was measured by the 3H-thymidine uptake in each group. RESULTS: One gray of gamma-ray irradiation had evident inhibition on the leukocyte and differential counts and the cellular immunity of mice. GL and GA could help to restore the decreased leukocyte counts and the cellular immunocompetence in low dose gamma-irradiated mice. CONCLUSION: GL and GA could help to restore decreased leukocyte counts and the cellular immunocompetence in low-dose gamma-ray-irradiated mice.

Animals↗

The use of Chinese herbal medicine on experimental fracture healing.

The purpose of this study was to examine the effect of Ru-Yih-Jin-Huang-Saan (RYJHS) and Jie-Guu-Saan (JGS) on experimental fracture healing in rats. Seventy-five rats were fractured in the middle of the left tibia and fibula. They were randomly divided into experimental and control groups and injected with Ringer's solution and applied with Ru-Yih-jin-Huang-Saan externally or fed with Jie-Guu-Saan respectively. The animals were sacrificed at 4, 8 and 12 days after fracture. The contents of hydroxyproline and the synthesis of DNA, RNA and protein were observed. The results demonstrate that groups treated with herbal medicine were more rapidly and thoroughly healed than the control group in respect to collagen formation and bone cell metabolism.

Administration, Oral↗

Androgen modulation of the messenger ribonucleic acid of retinoic acid receptors in the prostate, seminal vesicles, and kidney in the rat.

Previously, we reported that the steady state level of messenger RNA (mRNA) transcripts of retinoic acid receptors (RAR) alpha and gamma in the testes of 20-day-old rats can be modulated by exogenous testosterone. These results suggest that androgen regulation of Sertoli cell functions may involve biochemical events mediated by RAR genes. In this study, we examined the effects of castration and testosterone replacement on the steady state level of mRNA transcripts for RAR alpha and gamma in the prostate, seminal vesicles, and kidney of the rat. Northern blot analysis revealed that in intact adult rats, the relative steady state levels of the 3.4- and 2.7-kilobase (kb) mRNA transcripts for RAR alpha and the 3.4-kb transcript for RAR gamma in the prostate were at least 20-fold higher than those in the seminal vesicles and kidney. The relatively high abundance of RAR mRNA transcripts in the prostate suggests the physiological importance of RAR-mediated processes in this organ. Castration resulted in an increase in the level of RAR mRNA transcripts in the prostate and seminal vesicles, reaching a maximum of 2- to 4-fold in the prostate and 15- to 23-fold in the seminal vesicles within 6 days. On the other hand, the levels of mRNA transcripts of RAR alpha and -gamma in the kidney were reduced by 40-50% 1 day after castration. The effects of castration on RAR mRNA levels in all three organs were prevented by implantation of 3-cm testosterone capsules at the time of castration, a regimen that provides physiological levels of serum testosterone. In a subsequent experiment, adult male rats were given a single sc injection of 2 mg testosterone 3 days after castration. This treatment resulted in an acute suppression of the level of RAR mRNA transcripts in all three organs within 30 min. Thereafter, the levels of RAR alpha and -gamma mRNA transcripts in the prostate continued to decrease, whereas those in the seminal vesicles returned to the castrated levels within 6 h. On the other hand, RAR mRNA levels in the kidney rebounded by 1 h and remained at the level found in the untreated castrated rats. These results demonstrate that the steady state level of mRNA transcripts for RAR alpha and -gamma in the prostate, seminal vesicles, and kidney can be modulated by testosterone in organ-specific manners, thus suggesting that the RAR-mediated processes may be involved in the effects of androgen in these organs. Furthermore, the relatively low increment in prostatic RAR mRNA levels after castration compared to that in the seminal vesicles demonstrates a difference in androgen responses between these two organs. This difference could dictate the efficacy of the effects of androgen on cellular function and may contribute to the disparate vulnerabilities to androgen-related uncontrolled cell proliferation and/or malignancy in the prostate and seminal vesicles.

Animals↗

Lack of pharmacokinetic interaction between buspirone and haloperidol in patients with schizophrenia.

The pharmacokinetic interaction between buspirone and haloperidol was evaluated in schizophrenic patients in two different groups. In both groups, haloperidol doses (10-40 mg/day) remained constant for 6 weeks before the addition of buspirone 10 mg three times daily. Serial blood samples were obtained from the 11 patients in group I at baseline (before addition of buspirone) and after administration for 24 hours. The pharmacokinetic parameters of haloperidol were determined alone and with coadministration of buspirone. In group II, buspirone 10 mg three times daily was added to treatment with haloperidol in 27 patients. Blood samples were obtained before addition of buspirone and at weeks 2 and 6 of treatment with buspirone. Samples were obtained 10 to 12 hours after administration of the evening dose and before the morning dose. Haloperidol and its metabolite, reduced haloperidol (RH), were assayed by means of high-performance liquid chromatography with electrochemical detection. Significant changes in the pharmacokinetic parameters of haloperidol were not found in group I; a mean increase in the half-life (t1/2) of haloperidol from 21.5 to 28.1 hours was observed, but this finding was not statistically significant. Under steady-state conditions, plasma levels of haloperidol in the patients in group II did not change significantly from baseline to week 6. Plasma concentrations of RH remained unaltered in both groups. The results indicate that coadministration of buspirone does not markedly affect the pharmacokinetics or plasma concentrations of haloperidol.

Adult↗