Biomedical subjects

Robert F Casper

Publications and source records attributed to Robert F Casper.

43 records · Page 3Linked to original sources

PubMedDate not supplied

Resveratrol, a natural aryl hydrocarbon receptor antagonist, protects lung from DNA damage and apoptosis caused by benzo[a]pyrene.

Benzo[a]pyrene (BaP) is an agonistic ligand for the aryl hydrocarbon receptor (AhR) and a major environmental carcinogen implicated in the aetiology of lung cancer through the induction of benzo[a]pyrene diol epoxidation (BPDE) and BPDE-DNA adducts. Because BaP metabolization requires cytochrome P-450 1A1 (CYP1A1) induction through activation of the AhR, we hypothesized that resveratrol, a natural competitive inhibitor of AhR, could prevent these adverse effects of BaP on the lung. Balb-C mice were injected for 5 weeks with corn oil, BaP (5 mg kg(-1) week(-1)), resveratrol (50 mg kg(-1) week(-1)) or BaP + resveratrol. Immunohistochemistry was performed on lung sections for the determination of CYP1A1 protein, BPDE-DNA adducts and apoptosis. A semi-quantitative immunohistochemistry score (H score) was used for data analysis. Mice exposed to BaP had a significant induction of lung BPDE-DNA adducts when compared with controls (H scores: control, 26, interquartile range 18-33; BaP, 276, interquartile range 269-288; P < 0.01). The BPDE-DNA adduct induction by BaP was abrogated significantly by resveratrol (H score: BaP + resveratrol, 103, interquartile range 96-113). A similar pattern was found by immunohistochemistry for apoptosis (H scores: control, 121, interquartile range 102-137; BaP, 288, interquartile range 282-292, P < 0.05; BaP + resveratrol, 132, interquartile range 121-141, P = NS) and CYP1A1 (H scores: control, 170.3, interquartile range 164-175; BaP, 302.3, interquartile range 291-315, P < 0.05; BaP + resveratrol, 200.7, interquartile range 174-215, P = NS). Western blotting confirmed that resveratrol prevented BaP-induced CYP1A1 expression. This increase in CYP1A1 expression in response to BaP administration most likely causes BaP metabolism, BPDE-DNA adduct formation and subsequent apoptosis. All BaP-induced effects could be prevented by resveratrol, suggesting a possible chemopreventive role for this natural phytoalexin against the development of lung cancer.

Animals↗

PubMedDate not supplied

Stem cells: you can't tell a cell by its cover.

Embryonic stem (ES) cells are capable of unlimited self-renewal and have the ability to give rise to all tissue types in the body. The use of human ES cells for tissue and cell therapeutics has been suggested, but is limited by ethical concerns as these cells are derived from the inner cell mass of human embryos. In addition, the need for HLA matching of ES cell-derived tissues for allogeneic transplantation would require a bank of several thousand ES cell lines to make tissue therapeutics practical. Recently, adult stem cells-of which those in bone marrow are the best studied-have been shown to be capable of multilineage differentiation into cells of various non-blood tissues. Umbilical cord blood (UCB) haematopoietic stem cells have been shown to be equivalent to bone marrow stem cells for reconstitution of the haematopoietic system. Preliminary studies have also demonstrated that UCB haematopoietic stem cells are multipotent and capable of differentiating into non-blood cell types. This observation raises the exciting possibility of replacing human ES cells for tissue and cell therapeutics with UCB blood haematopoietic stem cells that are normally discarded with the placenta after delivery.

Adult↗

PubMedDate not supplied

Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome.

OBJECTIVE: To examine the utility of a low-dose estrogen and pulsed progestogen hormone replacement therapy (HRT) regimen for add-back during long-term gonadotropin-releasing hormone-agonist (GnRH-agonist) therapy. DESIGN: A pilot clinical trial conducted at a tertiary referral, academic, reproductive sciences center. The study included 15 patients with endometriosis and 5 patients with severe premenstrual syndrome (PMS). Patients with endometriosis received leuprolide acetate depot 3.75 mg IM monthly until their symptoms had resolved (2-3 months), at which time HRT was initiated along with the GnRH-agonist. Patients with severe PMS received the same treatment with the addition of HRT after 1 month. The HRT regimen consisted of 1 mg oral micronized estradiol daily and 0.35 mg norethindrone daily for 2 days alternating with 2 days without norethindrone. The main outcome measure included bone density assessment in the lumbar spine and femoral neck by dual-energy x-ray absorptiometry at 6- to 12-month intervals. The mean follow-up duration +/- SD while on GnRH-agonist treatment was 31.2 +/- 17 months (for endometriosis patients) and 37.7 +/- 8.4 months (for patients with severe PMS). RESULTS: Bone mineral density was stable after initiation of HRT for the entire follow-up period. No patient had return of pelvic pain or resumption of mood swings after HRT add-back. After the first 3 months of HRT, all women remained amenorrheic. CONCLUSIONS: Long-term GnRH-agonist down-regulation is safe and effective when combined with HRT add-back. Furthermore, on the basis of this small study, the low-dose pulsed progestogen, continuous estrogen HRT regimen seems to be safe for use as add-back therapy in terms of bone health.

Administration, Oral↗

PubMedDate not supplied

Troglitazone: a possible modulator of ovarian steroidogenesis.

OBJECTIVE: Troglitazone increases insulin sensitivity. When used to treat women with insulin-resistant polycystic ovary syndrome (PCOS), troglitazone lowers androgen concentrations and improves ovulatory, endocrine, and metabolic disturbances. However, it is not known whether these effects are due to increased peripheral insulin sensitivity only or to direct effects on steroidogenesis. To determine whether troglitazone has a direct effect on ovarian steroidogenesis, we studied the effect of troglitazone on androgen production in cultured rat theca interstitial cells (rTICs) and on progesterone production in cultured human granulosa lutein cells (hGLCs). METHODS: Primary cell cultures of rTICs were isolated from the ovaries of hypophysectomized immature Sprague-Dawley rats, and hGLCs was obtained from women who had in vitro fertilization-embryo transfer. Treatments included troglitazone, insulin, LH, hCG, and combinations of these agents. Media were collected and assayed for androsterone and progesterone. RESULTS: Troglitazone decreased both basal and insulin-, LH-, and hCG-stimulated androsterone production by TIC and progesterone production by hGLCs in a dose-dependent manner. CONCLUSION: We found a direct effect of troglitazone on the production of androsterone by rTICs and progesterone by hGLCs. These results suggest that the beneficial effects of troglitazone in PCOS may not be due solely to improvement of peripheral insulin resistance and hyperinsulinemia, but also to a possible direct effect on ovarian steroidogenesis.

Adult↗

PubMedDate not supplied

Gestational carrier is an optimal method for pregnancy in patients with vaginal agenesis (Rokitansky syndrome).

OBJECTIVE: To evaluate the results of successful pregnancy for patients with Mayer-Rokitansky-Kuster-Hauser syndrome using a gestational carrier. METHODS: All gestational carrier patients who attended our infertility clinic between 1995 and 2002 were reviewed for this study. Of the patients, 6 women with MRKH syndrome had 12 ovarian stimulation cycles, which resulted in 12 fresh and 5 frozen embryo transfers into six gestational carriers. RESULTS: The mean number (+/-SD) of embryos obtained per cycle was 4.8 (+/-2.9). Either two (n = 15) or three (n = 2) embryos were transferred to the gestational carrier. Three pregnancies were achieved following fresh embryo transfer, which included one clinical pregnancy that ended in spontaneous abortion, a singleton, and a set of twins. The pregnancy rate for fresh embryo transfer was 25% per retrieval and 50% per patient. No pregnancy was achieved following frozen embryo transfer. CONCLUSION: Gestational carrier is shown to be an effective treatment for patients with Mayer-Rokitansky-Kuster-Hauser syndrome.

Adult↗

PubMedDate not supplied

Complete failed fertilization after intracytoplasmic sperm injection--analysis of 10 years' data.

OBJECTIVE: To investigate incidence and causes of complete failed fertilization after intracytoplasmic sperm injection (ICSI) in a tertiary care facility. METHODS: A total of 1,779 cycles between February 1994 and December 2003 were analyzed. Study parameters were female age, infertility diagnosis, ovarian stimulation protocol, estradiol level on day of hCG administration, number of follicles, number of oocytes retrieved, number of oocytes injected, and semen parameters. RESULTS: Complete failed fertilization occurred in 23 cycles (1.29%) involving a total of 85 oocytes injected. Infertility causes among patients with failed fertilization included unexplained (43.6%), male factor (26%), presence of more than one factor (17.4%), hysterectomy (4.4%), premature ovarian failure (4.3%), and advanced age (4.3%). In 12 cycles (52%), fewer than 5 follicles were present. In three (13%) cycles, no mature (MII) oocyte was available and in 61% (14/23) fewer than 3 MII oocytes were available for ICSI. Immotile sperm was used for ICSI in 5 cycles (21.7%). The source of sperm in 17 (74%) cycles was from ejaculate, in 4 cycles from testicular aspiration (TESA), one from percutaneous epididymal sperm aspiration (PESA) and one from retrograde ejaculation. CONCLUSIONS: Our data indicate that major contributing factors to failed fertilization after intracytoplasmic sperm injection are number of MII oocytes retrieved and availability of viable sperm for injection. Although the incidence of complete failed fertilization is not remarkable, it may increase with increasing patient age and a lower number of follicles.

Adult↗

PubMedDate not supplied

Seminal hyperviscosity is associated with poor outcome of controlled ovarian stimulation and intrauterine insemination: a prospective study.

OBJECTIVE: To determine the relationship between seminal hyperviscosity and pregnancy outcome in patients undergoing ovarian hyperstimulation and intrauterine insemination (IUI). METHODS: Patients were enrolled in the study between October 2002 and December 2003 at the Toronto Centre for Advanced Reproductive Technology. This was a prospective trial that included 37 infertile couples with abnormal seminal viscosity who underwent 57 insemination cycles as treatment for infertility (group I) and 37 couples undergoing 51 IUI cycles during the same time period, with normal semen viscosity, who served as controls (group II). Cycles were stimulated using either gonadotropin (FSH) only or FSH combined with an aromatase inhibitor, and raw semen processed for intrauterine insemination using swim-up or density gradient. Results-The mean number (+/-SD) of IUI cycles was 1.93 +/- 1.42 per patient (range 1 to 7 cycles) in group I and 2.4 +/- 1.05 (range 1 to 4) in group II. The overall pregnancy rate (PR) was 14% (8/57) and 11.8% (6/51) per cycle, and 21.6% (8/37) and 16.2% (6/37) per patient in group I and in group II, respectively. Among patients where the male had seminal hyperviscosity, five (62.5%) pregnancies miscarried in the first trimester; there was no miscarriage in the control group. CONCLUSION: The high miscarriage rate in couples with semen hyperviscosity may be attributed to biophysical alterations or chemical changes of the ejaculate that could impact sperm quality despite normal sperm parameters on semen analysis.

Adult↗