PubMed Health⌕ Search

Biomedical subjects

M S Ansari

Publications and source records attributed to M S Ansari.

87 records · Page 5Linked to original sources
PubMed1993

Evaluation of 5-[18F]fluoropropylepidepride as a potential PET radioligand for imaging dopamine D2 receptors.

This study evaluated the utility of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2,3 - dimethoxybenzamide ([18F]fluorpropylepidepride), [18F]5-FPrEpid, as a ligand for PET studies of cerebral dopamine D2 receptors. The in vitro affinity for the rat striatal dopamine D2 receptor, KD 138 pM, was determined by Scatchard analysis of in vitro binding to rat striatal homogenate. The apparent lipophilicity, log kw 1.6, was measured with reverse phase HPLC at pH 7.5. The receptor specificity was determined by competitive displacement of [18F]5-FPrEpid by a variety of neurotransmitter ligands. Only dopamine D2 ligands displaced [18F]5-FPrEpid with high affinity. Positron tomographic imaging studies in primates of [18F]5-FPrEpid demonstrated a stable striatal uptake of 0.02% injected dose/ml for up to 5 h after injection. The striatal: cerebellar ratio increased from 2 at 15 min, to 7 at 200 min, and to 10 at 300 min. Striatal uptake was displaceable by haloperidol (1 mg/kg) or raclopride (2.5 mg/kg) to cerebellar levels with a t1/2 of washout of 9 or 15 min. Striatal uptake was mildly susceptible to displacement by d-amphetamine (1-2 mg/kg) released endogenous dopamine; d-amphetamine administration produced a 10% h increase in the rate of striatal washout. Although uptake in the striatum is reversible, an equilibrium between receptor bound [18F]5-FPrEpid in striatum and [18F]5-FPrEpid in plasma is not reached within 5 h postinjection.

Animals↗
PubMed1993

High affinity dopamine D2 receptor radioligands. 3. [123I] and [125I]epidepride: in vivo studies in rhesus monkey brain and comparison with in vitro pharmacokinetics in rat brain.

Studies of [123I]epidepride uptake in rhesus monkey brain were performed using single photon tomography. Striatal uptake peaked at 0.85% of administered dose/g at 107 min post-injection, then declined slowly to 0.70% of administered dose/g at 6 h. Striatal:posterior brain ratios rose from 2 at 25 min to 6.8 at 105 min, to 15 at 4 h and to 58 at 6.4 h. [123I]Epidepride was displaced by haloperidol (0.1 and 1 mg/kg) with a half-life of washout of 55 min. Little displacement of [123I]epidepride was observed following administration of 1 or 2 mg/kg d-amphetamine, respectively, indicating [123I]epidepride is not easily displaced by endogenous dopamine. In vitro equilibrium binding studies using rat striatum revealed a KD of 46 pM and Bmax of 33 pmol/g tissue at 37 degrees C, while at 25 degrees C the KD was 25 pM and the Bmax 32 pmol/g tissue. In vitro kinetic analysis of association and dissociation curves revealed a half-life for receptor dissociation at 37 degrees C of 15 min and 79-90 min at 25 degrees C. Allowing for the temperature difference, there is good correspondence between in vivo and in vitro dissociation kinetics at 25 degrees C. Increasing in vitro incubation temperature from 25 to 37 degrees C caused a 6-fold increase in the dissociation rate, suggesting that there is a change in binding kinetics at the dopamine D2 receptor at 37 degrees C compared to in vivo binding. The results of this study indicate that [123I]epidepride is an excellent radioligand for SPECT studies of the dopamine D2 receptor in man.

Amphetamine↗
PubMed1992

Visualization of extrastriatal dopamine D2 receptors in the human brain.

[123I]Epidepride, a potent and selective dopamine D2 radioligand, was administered to a 27 year old normal male volunteer. Single photon tomography revealed that peak striatal uptake occurred at 4 h after injection with a striatal:cerebellar ratio of 7.8 rising to over 100 at 18 h post injection. Uptake above the levels seen in cerebellum was also noted in the thalamus, pituitary, hypothalamus and temporal lobe, particularly medially. Single photon tomography with [123I]epidepride allows visualization of extrastriatal dopamine D2 receptors in man.

Adult↗
PubMed1992

Noninvasive detection of heart transplant rejection with positron emission scintigraphy.

Positron emission tomography has recently been used to evaluate ischemic heart disease through changes in myocardial blood flow and carbohydrate metabolism. Positron-emitting tracers were evaluated for their ability to detect acute allograft rejection after heterotopic cardiac transplantation in the rat. Sham-operated controls, nonrejecting isografts, and rejecting allografts were evaluated. Decay-corrected uptake of 13NH3 and 18F 2-fluoro 2-deoxyglucose (FDG) reflects blood flow and glucose flux, respectively. Histologic examination of rejecting allografts documented mild rejection at 4 days and severe acute rejection by 8 days. All isografts were free from rejection. Uptake of FDG is greater in rejecting allografts than in nonrejecting isografts during both severe rejection (2.4% +/- 0.8% versus 0.7% +/- 0.4%; p less than 0.02) and mild rejection (2.1% +/- 0.6% versus 0.4% +/- 0.1%; p less than 0.02). Uptake of NH3 in severely rejected grafts is reduced compared with nonrejecting grafts (0.6% +/- 0.3% versus 1.7% +/- 1.1%; p less than 0.02). There is no difference in NH3 uptake during mild rejection (1.8% +/- 0.7% versus 1.3% +/- 0.3%; p greater than 0.05). Uptake of FDG and NH3 in native hearts of animals from all experimental groups is not significantly different from that in sham-operated controls. Glucose may be a preferred metabolic substrate during rejection. Our data support a humoral mechanism for substrate preference during transplant rejection and a potential diagnostic role for positron emission tomography.

Ammonia↗
PubMed1991

High affinity dopamine D2 receptor radioligands. 2. [125I]epidepride, a potent and specific radioligand for the characterization of striatal and extrastriatal dopamine D2 receptors.

Epidepride, (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenzamide+ ++, the iodine analogue of isoremoxipride (FLB 457), was found to be a very potent dopamine D2 receptor antagonist. Optimal in vitro binding required incubation at 25 degrees C for 4 h at pH 7.4 in a buffer containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl2 and 1 mM MgCl2. Scatchard analysis of in vitro binding to striatal, medial frontal cortical, hippocampal and cerebellar membranes revealed a KD of 24 pM in all regions, with Bmax's of 36.7, 1.04, 0.85, and 0.37 pmol/g tissue, respectively. The Hill coefficients ranged from 0.91-1.00 in all four regions. The IC50's for inhibition of [125I]epidepride binding to striatal, medial frontal cortical, and hippocampal membranes for SCH 23390, SKF 83566, serotonin, ketanserin, mianserin, naloxone, QNB, prasozin, clonidine, alprenolol, and norepinephrine ranged from 1 microM to greater than 10 microM. Partial displacement of [125I]epidepride by nanomolar concentrations of clonidine was noted in the frontal cortex and hippocampus, but not in the striatum. Scatchard analysis of epidepride binding to alpha 2 noradrenergic receptors in the frontal cortex and hippocampus revealed an apparent KD of 9 nM. At an epidepride concentration equal to the KD for the D2 receptor, i.e. 25 pM, no striatal alpha 2 binding was seen and only 7% of the specific epidepride binding in the cortex or hippocampus was due to binding at the alpha 2 site. Correlation of inhibition of [3H]spiperone and [125I]epidepride binding to striatal membranes by a variety of D2 ligands revealed a correlation coefficient of 0.99, indicating that epidepride labels a D2 site. In vitro autoradiography revealed high densities of receptor binding in layers V and VI of prefrontal and cingulate cortices as well as in striatum. In vivo rat brain uptake revealed a hippocampal:cerebellar and frontal cortical:cerebellar ratio of 2.2:1 which fell to 1.1:1 following haloperidol pretreatment. These properties suggest that [125I]epidepride is a superior radioligand for the in vitro and in vivo study of striatal and extrastriatal dopamine D2 receptors.

Animals↗
PubMed1991

High affinity dopamine D2 receptor radioligands. 1. Regional rat brain distribution of iodinated benzamides.

Five 125I-labeled substituted benzamides, which are close structural analogues of (S)-sulpiride, eticlopride, and isoremoxipride, were evaluated for their selective in vivo uptake into dopamine D2 receptor rich tissue of the rat brain. "Iodopride" (KD 0.88 nM), an iodine substituted benzamide structurally related to sulpiride, displayed a maximal striatum: cerebellar uptake ratio of 7.6. Demonstration of saturation of the receptor with [125I]iodopride in striatum required uptake in frontal cortex to be used, rather than cerebellar uptake, to define nonspecific binding. Two other ligands structurally related to eticlopride, "iclopride" (KD 0.23 nM) and "itopride" (KD 0.16 nM), displayed maximal striatal: cerebellar uptake ratios of 9.8 and 3.3, respectively. The most potent ligands, "epidepride" (KD 0.057 nM) and "ioxipride" (KD 0.070 nM) showed striatal:cerebellar uptake ratios of 234 and 65, respectively. The observed uptake ratios correlated poorly with the affinity constants for the dopamine D2 receptor alone, but were highly correlated (r = 0.92) with the product of the receptor dissociation constant (KD) and the apparent lipophilicity (kw), as determined by reverse-phase HPLC at pH 7.5. Total striatal uptake also appeared dependent on lipophilicity, with maximal uptake occurring for ligands having log kw 2.4-2.8.

Animals↗
PubMed1976

Zinc metabolism and homeostasis in rats fed a wide range of high dietary zinc levels.

Zinc metabolism and homeostasis were studied in young growing rats fed a 38 ppm zinc diet with added zinc levels ranging from 0 to 8400 ppm for 21 days. High dietary zinc did not cause toxicity symptoms. Stable zinc in feces increased linearly with dietary zinc intake but fecal 65Zn, from a single oral dose, did not increase above the 1200 ppm dietary level. Stable zinc in liver, kidney, and tibia increased two to three times with 2400 ppm added zinc, but was not further elevated until 8400 ppm was fed. Stable zinc in muscle and heart was not affected appreciably by dietary zinc level. In all tissues, 65Zn retention was drastically reduced with 1200 ppm added dietary zinc. Additional dietary zinc reduced 65Zn in muscle and heart but had little effect on liver and kidney 65Zn. The data indicate that rats have fairly effective homeostatic control mechanisms for tissue zinc below about 7200 ppm dietary zinc. Whereas, with dietary zinc up to about 1200 ppm, decreasing absorption is the main route of homeostatic control, above this level, more rapid zinc turnover rates and increasing endogenous zinc excretion appear to have major importance.

Animals↗
PubMed1975

Effects of high but nontoxic dietary zinc on zinc metabolism and adaptations in rats.

The effects of feeding a high but nontoxic zinc level to young rats for varied time periods on zinc metabolism and adaptations were investigated. Adding 600 ppm supplemental zinc to a "corn-soy" diet for periods from 7 to 42 days did not materially affect stable zinc level in any tissue studied. However, in every tissue, 65Zn retention from a single oral dose declined sharply with duration of added zinc feeding to 21 days, indicating a continuing adaptation in zinc metabolism for at least this period of time. Likewise, fecal 65Zn excretion increased with length of feeding time on high zinc, indicating a continuing reduction in net absorption for most of the 42-day period. When the data are compared with similar previous cattle studies, it is evident that there are major qualitative differences in zinc metabolism and homeostatic control between rats and cattle.

Animals↗
PubMedDate not supplied

Lycopene: a novel drug therapy in hormone refractory metastatic prostate cancer.

OBJECTIVE: In a prospective study we evaluated the efficacy of lycopene for the treatment of patients with metastatic hormone refractory prostate cancer. MATERIAL AND METHODS: Between January 2001 and December 2002, 20 consecutive patients (median age 72; range 56-90) with metastatic HRPC were enrolled in the study. Lycopene in the dose of 10 mg/day was administered for a period of 3 months. Inclusion criteria were patients previously treated with hormonal therapy now with clinical and biochemical evidence of disease progression. A complete response (CR) was defined as a normalization of PSA (<4 ng/mL) and the disappearance of any sign of disease for at least 8 weeks. A partial response was defined as a >50% decrease in PSA level for at least 8 weeks associated with improvement (or no worsening) in ECOG PS and relief of bone pain if present. Stable disease (SD) was defined as a <50% decrease or <25% increase in the PSA level associated with no worsening of ECOG PS and/or bone pain for at least 8 weeks. RESULTS: One patient (5%) had complete response. Partial response was achieved in 6 (30%), disease remained stable in 10 (50%) and progressed in three (15%) patients. ECOG PS was Grade 0 in five, Grade I in 10 and Grade II in five of the 20 patients. It improved from Grade I to 0 in seven and Grade II to I in three patients. It deteriorated in three and remained unchanged in the rest seven patients. Bone pain was present in 16 (Grade 1 in six and Grade 2 in 10) of the 20 patients. Grade 1 changed to Grade 0 in five and Grade II changed to Grade 1 in five patients. Bone pain remained unchanged in 5 (31%) and worsened in 1 (6%). Ten (62%) patients managed to cut down the dose of analgesics on daily basis. Eighteen patients had associated LUTS, which improved (Q max > or = 12 mL/sec) in 11 (61%) patients. The median duration of response was 25 weeks (range 12-72 weeks). No drug intolerance or toxicity was encountered in any patient. CONCLUSIONS: Lycopene therapy appears to be effective and safe in the treatment of HRPC. It not only takes care of the rising PSA but also improves the ECOG performance status, bone pain and LUTS. Because of its relative innocuousness it should be tried before the use of more toxic substances.

Administration, Oral↗
PubMedDate not supplied

Transrectal ultrasound guided biopsy for detecting early prostate cancer: An Indian experience.

BACKGROUND: With the advent of prostate specific antigen the number of patients undergoing prostate biopsy has dramatically increased. The sextant biopsy technique has been conventionally used for the diagnosis of prostate cancer. Recently, concern has arisen that the original sextant method may not include an adequate sample of the prostate, hence it may result in high false negative rates. We conducted a prospective study to determine whether the 5-region prostate biopsy technique significantly increases the chance of prostate cancer detection as compared to the sextant biopsy technique. AIMS: To evaluate the efficacy of TRUS guided sextant and 5-region biopsy techniques in detecting carcinoma prostate in patients with PSA between 4 and 10 ng/ml and normal digital rectal examination. METHODS AND MATERIAL: Between December 2001 and August 2003 one forty-two men, aged 49-82 years, who presented with LUTS, normal digital rectal examination (DRE) and PSA between 4 and 10 ng/ml underwent TRUS guided sextant prostate biopsy. Serum PSA was reassessed after 3 months in patients whose biopsies were negative for cancer. If PSA was still raised, the patients underwent extensive 5-region biopsy. RESULTS: Mean patient age was 64 years and median PSA was 6.9 ng/ml. TRUS guided sextant biopsy revealed adenocarcinoma prostate in 34 men (24%). Median Gleason score was 7. Seven men (4.9%) had cellular atypia and 3(2.1%) had prostatic intraepithelial neoplasia (high grade). On repeat PSA estimation after 3 months, 48 patients showed stagnant or rising trend for which they underwent TRUS guided 13-core biopsy. Five (10.4%) patients were detected to have adenocarcinoma on repeat biopsy. Biopsy negative patients are on regular follow up with yearly PSA estimation. Complications included transient mild haematuria in14 patients (9.82%) and haematospermia in 4 (2.8%). Urinary retention developed in one patient and required an indwelling catheter for 4 days. CONCLUSION: Transrectal ultrasound guided sextant biopsy has shown a false negative rate of approximately 11%. A repeat 5- region (13-core) biopsy strategy can decrease the false negative rate of conventional sextant biopsy in patients with previously negative biopsies but persistently high PSA levels, high grade PIN or cellular atypia.

Aged↗
PubMedDate not supplied

Massive pleural effusion without bony involvement: an unusual presentation of advanced carcinoma prostate.

As noted under the natural history, the bone of axial skeleton and the ileopelvic lymphnodes specially the obturator groups are the commonest sites of metastasis spread of cancer prostate. Visceral metastasis in the absence of the above is extremely rare. We present a 50-year-male patient of cancer prostate with pleural metastases, pleural effusion and lung collapse on right side. Bone scan was essentially normal. Bilateral orchiectomy was done. Pleural effusion subsided and PSA dropped to 1.4 ng/ml from the initial 120 ng/ml at three months. Patient is on regular follow-up at three monthly intervals and last PSA done at 9 months was 2.1 ng/ml.

Humans↗