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Biomedical subjects

I Khan

Publications and source records attributed to I Khan.

At least 145 records · Page 8Linked to original sources
PubMed1989

The influence of estradiol on cholesterol processing by the corpus luteum.

Recent studies from our laboratory have suggested that estradiol or androgen precursor may stimulate steroidogenesis in the luteal cell by modulating intracellular cholesterol metabolism including mobilization of cholesteryl esters, stimulation of lipoprotein receptor activity and induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) activity. To test the functionality of cholesteryl ester turnover per se, we measured the activities of acyl CoA:cholesterol acyltransferase (ACAT) and cholesteryl esterase, the enzymes involved in cholesteryl ester synthesis and hydrolysis, respectively; we also measured de novo synthesis of cholesterol, cholesteryl esters, and steroids. Pregnant rats, hypophysectomized and hysterectomized on Day 12, were treated for 72 h with either estradiol or testosterone, and luteal microsomal and cytosolic fractions were utilized to measure ACAT and cholesteryl esterase activity, respectively. Intact corpora luteal were employed for [14C]acetate incorporation experiments. Basal ACAT activity (expressed as pmol.min-1.CL-1 increased from a mean of 78 +/- 16 in vehicle-treated rats to 119 +/- 18 and 197 +/- 16 in the estradiol- and testosterone-treated rats, respectively. Similarly, total ACAT activity (measured in the presence of exogenous cholesterol) was also increased in estradiol- and testosterone-treated groups. On the other hand, cholesterol esterase activity (expressed either pmol.min-1.CL-1 or pmol.min-1.mg protein-1) was similar in all three groups and comparable to corpora lutea from intact pregnant rats. Hypophysectomy and hysterectomy caused a 50-60% reduction in [14C]acetate incorporation into sterols when compared with intact pregnant rat. Treatment with either estradiol or testosterone not only restored the cholesterol biosynthetic capacity but also enhanced the overall rate of [14C]acetate incorporation into steroids as compared to intact pregnant rats. The major (-80%), newly synthesized steroid was identified as progesterone. In conclusion, the present studies suggest that the major function of luteal estradiol is to induce de novo cholesterol biosynthesis, regulate ACAT activity, and channel available free cholesterol (derived from both endogenous and exogenous sources) for steroidogenesis.

Animals↗
PubMed1989

Estradiol regulation of sterol carrier protein-2 independent of cytochrome P450 side-chain cleavage expression in the rat corpus luteum.

A major action of estradiol in the corpus luteum of the pregnant rat is to increase the supply of cholesterol substrate for progesterone production by stimulating both cholesterol synthesis and uptake. To determine whether this steroid also affects cholesterol metabolism and transport, estradiol's action on the expression of cytochrome P450 side-chain cleavage enzyme (P450scc) and the cholesterol transport protein, sterol carrier protein-2 (SCP2), was examined. Mitochondria isolated from corpora lutea of estradiol-treated rats secreted significantly more progestagen than mitochondria of control corpora lutea. Several findings indicate that estradiol enhances cholesterol transport and availability to the P450scc rather than affects the expression of this enzyme: 1) the difference in mitochondrial progestagen synthesis induced by estradiol was obliterated by the presence of 25-hydroxycholesterol; 2) immunoblotting of P450scc indicated no stimulatory effect of estradiol on the amount of enzyme; and 3) levels of P450scc mRNA were not increased by estradiol. Whereas estradiol had no stimulatory effect on P450scc it caused a mark (3-fold) increase in the mitochondrial content of SCP2. Thus, the increase in luteal progestagen synthesis stimulated by estradiol appears to be associated with an increase in mitochondrial SCP2 and is independent of luteal P450 content or message.

Animals↗
PubMed1989

An international survey of the educational activities of schools of pharmacy on psychoactive drugs.

A survey of the educational activities of schools of pharmacy on psychoactive drugs in 92 countries was carried out. All the schools which replied felt that there was a need for specific education on psychoactive drugs, and the majority felt that the rational use of such drugs should also be taught. Both the amount of teaching given and the methods used varied. This was particularly true for related subjects such as alternatives to psychoactive drug use. Almost a third of schools considered that they did not devote adequate time to psychoactive drugs and their rational use, and many would be grateful for specific educational guidelines in this area.

Curriculum↗
PubMed1988

Perurethral ultrasound-guided ovum pickup.

Either a percutaneous-transvesical, a transvaginal, or a perurethral-transvesical approach can be used for oocyte recovery under ultrasound guidance in an in vitro fertilization and embryo transfer program. After having experienced these three different approaches in our program, we preferentially used the perurethral-transvesical approach as our routine technique for oocyte recovery under ultrasound guidance. We feel that this method is easier to perform and also carries less risk for contamination. From January to December 1986, 186 oocyte retrievals under ultrasound guidance were performed. In 7 cases no oocytes were found despite normal ovarian stimulation. A total of 767 oocytes was collected; the fertilization rate was 71.8%. Forty pregnancies were achieved (21.5% per attempt or 27.7% per embryo replacement). Except for transient hematuria, no complications were observed.

Chorionic Gonadotropin↗
PubMed1988

Success rate in gamete intrafallopian transfer using low and high concentrations of washed spermatozoa.

The effect of a reduced number of spermatozoa on pregnancies and miscarriages was studied retrospectively in 307 consecutive gamete intrafallopian transfer (GIFT) cycles. The number of spermatozoa introduced per GIFT in each group was as follows: 100,000 (group I), 50,000 (group II), 10,000 (group III), 5,000 (group IV), and 2,500 (group V), which gave a pregnancy rate of 20%, 38%, 37%, 30%, and 24%, respectively (differences were not significant). With respect to the pregnancies, no correlation was found between the number of spermatozoa transferred and the cause of infertility. In the male factor group also no significant difference was observed in the pregnancy rate when the sperms were reduced from 100,000 to 2,500. Lowering the number of sperms in GIFT did not reduce the abortion rate, which remained around 33%. It was the patients with unexplained infertility who benefited most from the GIFT procedure. Their pregnancy rate was significantly higher than the pregnancy rate of those who had endometriosis, or andrologic or immunologic disorders.

Adult↗
PubMed1988

Addition of Buserelin to human menopausal gonadotrophins in patients with failed stimulations for IVF or GIFT.

The combined therapy of a gonadotrophin-releasing hormone agonist (GnRHa) D-Ser(TBU)6-EA10-LHRH (Buserelin) and human menopausal gonadotrophins (HMG) for ovarian stimulation for in-vitro fertilization and gamete intra-Fallopian transfer was evaluated during 84 cycles. All women selected for this therapy had previously failed stimulations with clomiphene citrate/HMG. The GnRHa prevented spontaneous luteinizing hormone surges and premature luteinization in all patients. After addition of the agonist to HMG, the cancellation rate dropped from 17 to 7% and improved the results in 72.6% of the cycles. Twenty-six per cent of the started cycles resulted in a pregnancy. Eighteen healthy children were born at term.

Buserelin↗
PubMed1988

Hyperstimulation: the need for cryopreservation of embryos.

Successful application of in-vitro fertilization (IVF), zygote intra-Fallopian transfer (ZIFT) and gamete intra-Fallopian transfer (GIFT) requires ovarian hyperstimulation for the maturation of multiple follicles. To control the risk of multiple pregnancies, the number of gametes (GIFT) or embryos (IVF, ZIFT) replaced is limited to three. For the supernumerary embryos resulting from IVF, ZIFT or GIFT, the strategy is cryopreservation for a later transfer. Cryopreservation was performed using either dimethylsulphoxide or 1,2-propanediol as a cryoprotective agent. Embryos were frozen either in the pronucleate stage with 1,2-propanediol or in the multicellular stage with dimethylsulphoxide or 1,2-propanediol. Survival after thawing was scored for both cryoprotective agents as a function of the developmental stage of the embryo and the embryonic quality. Evaluation of survival after thawing was performed on the basis of morphological intactness of the 1-cell pronucleate embryo or of the blastomeres of multicellular embryos. For pronucleate stage embryos, the use of 1,2-propanediol resulted in a 60% survival after thawing. For 2-cell stage embryos the survival was similar for dimethylsulphoxide and 1,2-propanediol. Later stage embryos survived better when dimethylsulphoxide was the cryoprotectant. For all stages, embryo quality before freezing was a crucial factor in survival after thawing. The pregnancy rate (12.2%) was similar for the two cryopreservation protocols. In conclusion, the choice of an appropriate cryoprotective agent can increase the survival after thawing when embryos are of good quality before freezing.

Cryoprotective Agents↗
PubMed1988

Embryo donation in patients with primary ovarian failure.

Thirty-six infertile patients with primary ovarian failure, who were referred for oocyte (embryo) donation are reported. After substitution therapy with oestradiol valerate (per os) and progesterone (i.m. or per os), endometrial tissue was made receptive for embryonic implantation, although the endometrial biopsies on day 21 demonstrated a certain delay in development (of 1.6-2.4 days). Six patients became pregnant, three of them delivered four healthy babies, one pregnancy is progressing normally and two ended in an early clinical abortion.

Chromosome Aberrations↗
PubMed1988

In-vitro fertilization with husband and donor sperm in patients with previous fertilization failures using husband sperm.

When previous attempts at in-vitro fertilization using semen from the husband failed, a subsequent IVF attempt was performed using husband and donor sperm in order to compare fertilization and embryo formation after insemination with husband and donor sperm of the same oocyte population. Significantly more eggs were fertilized in patients suffering from andrological and idiopathic infertility when donor sperm were used. No differences were seen in patients with tubal infertility. In the andrological group, the embryos fertilized by the husband showed significantly more fragmentation. No pregnancies were established when husband-fertilized oocytes (embryos) were replaced in the andrological and idiopathic infertility group. This study suggested that an IVF trial using husband and donor sperm might be indicated in couples suffering from andrological or idiopathic infertility in whom no fertilization occurred in a previous cycle using sperm from the husband.

Adult↗
PubMed1988

The luteal phase after in-vitro fertilization and related procedures.

To evaluate any beneficial effect of progesterone supplementation during the luteal phase of GIFT or IVF cycles stimulated by clomiphene citrate and HMG, two random prospective studies were performed. In the first study, a group of patients received a luteal phase supplement of 50 mg natural progesterone i.m. daily from the day of oocyte retrieval onwards. Initial results on 168 patients indicated that the pregnancy rate was similar in patients with or without progesterone supplements. No differences were found between the two groups in an analysis of pregnant and failed cycles. In a second study two different protocols of luteal phase supplementation after Buserelin-HMG stimulation were compared: natural progesterone in combination with oestradiol valerate (50 patients) or HCG supplements (41 patients). A 32% pregnancy rate per cycle was encountered in both groups. Endometrial biopsies, taken during the luteal phase from patients who did not undergo embryo replacement, revealed retarded endometrial development in most of the biopsies.

Buserelin↗
PubMed1988

The luteal phase and early pregnancy after combined GnRH-agonist/HMG treatment for superovulation in IVF or GIFT.

Endometrial biopsies showing inadequate development were observed after ovarian stimulation with the GnRH agonist Buserelin and HMG for IVF or GIFT when luteal supplementation was omitted. Ninety-one patients were randomly allocated to two luteal supplementation regimens: in 41 women HCG and in 50 women progesterone and oestradiol valerate. The pregnancy patients treated with a combination of the GnRH agonist and HMG a delay of implantation of 1.3 days was observed compared to pregnancies after clomiphene citrate-HMG stimulation. This delay was not due to slower preimplantation embryo development after GnRH agonist-HMG treatment. Temporarily defective function of the corpus luteum was evidenced by measuring serum progesterone, 17 beta-oestradiol and 17-hydroxyprogesterone in the patients receiving progesterone and oestradiol valerate. This inadequate corpus luteum function could be related to the prolonged blockage of pituitary gonadotrophic function after arrest of the GnRH agonist.

Buserelin↗
PubMed1988

Luteal cell 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity and cholesterol metabolism throughout pregnancy in the rat.

The objective of this study was to investigate changes in luteal cell cholesterol biosynthetic capacity, cholesterol accumulation, lipoprotein receptor activity, and in vivo steroidogenesis during pregnancy. Cholesterol biosynthetic capacity was assessed by measuring both the activity and the content of the rate-limiting enzyme 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase and by monitoring [14C]acetate incorporation into luteal sterols. The results showed that HMG-CoA reductase activity increased steadily during the first few days of pregnancy and reached a peak value on day 10. Subsequently, enzyme activity dropped precipitously and remained low until parturition. A parallel decline in the rate of conversion of 14C-labeled sterols was observed. Such changes in HMG-CoA reductase activity were not related to the phosphorylation/dephosphorylation state of the enzyme, but were due to a reduction in the amount of enzyme protein, as determined by the immunoblotting technique. Despite the highly active HMG-CoA reductase in the first half of pregnancy, very little cholesterol ester was stored, and serum progesterone concentrations were only about 50-75 ng/ml. However, from midpregnancy, the corpus luteum became capable of storing more cholesterol ester and producing more progesterone at a time when its ability to synthesize cholesterol declined. At this stage, luteal cells appear to shut off de novo synthesis and use principally exogenous cholesterol. To find out whether this is due to an increase in the number of high density lipoprotein (HDL) receptors, HDL-binding activity was determined in luteal cells throughout pregnancy. Whereas the Kd and the number of binding sites per mg protein were similar between days 6-18, the total content of HDL receptor increased markedly with the size of the corpus luteum. In summary, the present investigation indicates that pregnancy profoundly influences the ability of the corpus luteum to acquire, synthesize, and process the cholesterol substrate needed for steroidogenesis.

Acetates↗
PubMed1988

L-tryptophan in neuroleptic-induced tardive dyskinesia.

Administration of the serotonin precursor L-tryptophan in a patient with neuroleptic-induced tardive dyskinesia, produced a dramatic reduction in the severity of the abnormal movements within 24 hours. This report supports our hypothesis that alterations in the function of serotoninergic neurotransmission are implicated in the pathophysiology of neuroleptic-induced tardive dyskinesia.

Antipsychotic Agents↗
PubMed1988

An acupuncture programme for the treatment of drug-addicted persons.

Over the past 13 years, Lincoln Hospital, New York City, has used acupuncture as the primary method of treatment for drug-addicted persons. The programme receives, on a daily out-patient basis, 200 drug-addicted persons for detoxification. Acupuncture relieves withdrawal symptoms, prevents the craving for drugs and increases the rate of participation of patients in long-term treatment programmes. The best results have been obtained by treating patients in an open-group setting, using acupuncture points in the external ear with needles without electrical stimulation. The same points are used at each visit, regardless of the type of drug to which the person is addicted. This method is also used for the treatment of persons suffering from stress. The National Acupuncture Detoxification Association (NADA) has conducted successful training programmes for physicians and related staff in using the technique and philosophy of traditional Chinese acupuncture. These training programmes usually include courses in counseling skills, ethical responsibilities and sterilization procedures that are appropriate to local conditions. NADA has begun to operate a pilot programme to treat approximately 1,000 drug abusers and people who are under a high level of stress, which may lead them to the abuse of drugs. It is assumed that acupuncture, in conjunction with other drug-demand reduction programmes, can make a significant impact on the illicit demand for drugs by reaching this entire range of patients.

Acupuncture Therapy↗