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T H Lin

Publications and source records attributed to T H Lin.

At least 145 records · Page 8Linked to original sources
PubMed1987

Inhibition of blood-brain barrier permeability to DL-propranolol by serum from acute renal failure rats.

The effect of uranyl nitrate-induced acute renal failure on the brain uptake of DL-propranolol was investigated in rats with a series of tissue-sampling single-carotid injection techniques. When the buffer solution was used as an injection solution, the brain uptake index (BUI), the extraction ratio (ET), and the blood-brain barrier (BBB) permeability-surface area product (PSapp) and PSu (corrected PSapp for the unbound fraction) in uremic rats were significantly lower than those in control rats. These parameters for DL-propranolol were decreased significantly in both control and uremic rats receiving injection of the uremic serum. The PSu values in both of the control and uremic rats injected with either control or uremic rat serum were significantly higher than those in rats injected with the buffer solution, suggesting the presence of a protein-mediated transport mechanism; that is, the conventional assumption that the fraction of the drug which is available for the uptake in vivo is equal to the unbound fraction as measured in vitro may not hold. In contrast, the brain extraction of D-[14C]glucose, [3H]inulin and [3H]water, which show no binding to serum protein, was not affected by the coinjection of either control or uremic rat serum. On the other hand, using either the ultrafiltrate from serum (control and uremic) or supernatant fraction from heat-treated serum (control and uremic) as the injection solution, no significant difference in the PSu value for DL-propranolol was observed between control and uremic serum. These results suggest that (1) the decrease in the PSu value for DL-propranolol in uremic rats may be attributed mainly to the presence of an endogenous inhibitory substance(s) for the brain uptake or to the decrease in the exchangeable fraction in vivo in the uremic serum; (2) the decrease in the PSu value for DL-propranolol may also be partly attributed to the change in the BBB permeability and/or surface area; (3) the inhibitor for the brain uptake may be characterized as a temperature-sensitive and nonfiltrable substance(s) at physiological pH; and (4) the ability of protein-mediated transport for DL-propranolol into brain was decreased in uremic rats.

Acute Kidney Injury↗
PubMed1987

Interactions between estrogen and EGF in uterine growth and function.

The rat uterus contains specific, high-affinity EGF receptors which possess a tyrosine kinase activity. As demonstrated autoradiographically, these receptors are present in the epithelial, stromal and myometrial cells of the uterus. Estrogen treatment in vivo produces a 2-3-fold increase in EGF receptor levels in the immature rat, the immature mouse and the ovariectomized adult rat; furthermore, EGF receptor levels vary throughout the estrus cycle in concert with levels of occupied nuclear estrogen receptor. This estrogen-induced increase in EGF receptor is preceded by an increase in the level of EGF receptor mRNA as judged by Northern blot analysis. In general, there is a good correlation between estrogen-induced DNA synthesis and EGF receptor levels in the uterus, although in certain situations EGF receptor levels are elevated without a subsequent increase in DNA synthesis. These observations suggest that an increase in tissue EGF receptor levels is important in estrogen-induced uterine growth, but that this increase in receptor levels alone is not sufficient to stimulate DNA synthesis. In addition to its possible role in tissue growth, we have shown very recently that EGF causes contraction of myometrial smooth muscle in a completely in vitro organ bath system. The qualitative nature of this contractile response is distinct from that produced by other classical uterotonic agents. The physiological significance of this uterine response to EGF remains to be elucidated.

Animals↗
PubMed1986

Intranasal nafarelin: an LH-RH analogue treatment of gonadotropin-dependent precocious puberty.

The agonistic analogues of luteinizing hormone releasing hormone decrease biochemical findings and clinical signs of gonadotropin-dependent precocious puberty. We tested a new analogue, nafarelin acetate, in 15 girls with gonadotropin-dependent precocious puberty. The hydrophobic nature and potency of this compound allow it to be administered by intranasal inhalation. Laboratory assessment of vaginal cytology, estradiol and urinary gonadotropin levels, and growth velocity revealed that nafarelin acetate 800 to 1200 micrograms/day diminished these values during a 6-month treatment period. These results suggest gonadotropin-dependent precocious puberty in girls can be treated with intranasal administration of nafarelin acetate.

Administration, Intranasal↗
PubMed1986

Portasystemic shunt fraction quantification with colonic iodine-123 iodoamphetamine.

Portasystemic shunting was quantified in dogs with [123I]iodoamphetamine (IMP) administered transrectally into the colon and monitored externally with a gamma camera. IMP was absorbed rapidly and unchanged from the colon. After direct injection into the portal vein, IMP was almost completely extracted by the liver on the first pass, and the washout half-life was approximately 60 min. Based on these kinetic data, computer simulation of this biologic system was carried out. Errors associated with simplified models are calculated. The simplest model with insignificant error, which assumed that the tracer behaved like microspheres, was used to quantitate portasystemic shunt fraction in animals with surgically created shunts. Results were compared with the standard of 99mTc-labeled macroaggregated albumin infused into a branch of inferior mesenteric vein. For shunt fractions ranging from 0 to 100%, an excellent correlation was seen, indicating that this approach is potentially a simple, noninvasive method of portasystemic shunt fraction quantification.

Amphetamines↗
PubMed1985

Effect of phenobarbitone on the distribution and elimination of imipramine in rats.

The effect of phenobarbitone on the steady state volume of distribution (Vdss) and the total body blood clearance (CLtot, b) of imipramine and the serum concentration of its metabolite, desipramine was examined. The serum disappearance of imipramine after an 8 mg kg-1 i.v. dose followed a biexponential decline in both control and phenobarbitone-treated rats while the concentration of its metabolite increased in the phenobarbitone-treated rats then rapidly declined compared with that in control rats. Since CLtot,b was nearly equal to the hepatic blood flow (QH), QH may be the rate-determining step of imipramine elimination. In the control rats the Vdss of imipramine was large at 19.9 litre kg-1. In the phenobarbitone-treated rats the pharmacokinetic parameters, biological half-life (t1/2) and Vdss significantly decreased to approximately 23-40% while CLtot,b increased to 126% of those in the control rats, although the latter difference was not statistically significant. The blood-to-plasma concentration ratios (RB) of imipramine and desipramine decreased in the phenobarbitone-treated rats. The urinary excretion ratios of imipramine and desipramine, to the dose of imipramine over 8 h, were less than 1.5% in both groups. These ratios were not significantly changed in the phenobarbitone-treated rats. It was concluded that the significant decrease in t1/2 of the phenobarbitone-treated rats may not be attributed to the changes in CLtot,b and/or in the urinary excretion, but mainly to the decrease in Vdss.

Animals↗
PubMed1984

[Electron microscopic study on the angioarchitecture of glomeruli in experimental toxemia of pregnant rabbits].

The present paper reports studies on the change in the angioarchitecture of the glomeruli in induced hypertensive pregnancy in rabbits. Experimental toxemia of pregnancy in late pregnancy in rabbits was induced by constriction of the aorta below the renal arteries, followed by estradiol administration. The results are as follows: 1) Constriction of the aorta in the pregnant rabbits on the 21st day of gestation significantly elevated the blood pressure and resulted in intrauterine growth retardation in 88.9% of the living fetuses. 2) When the pregnant rabbits underwent constriction of the aorta and estradiol treatment, all the fetuses were in a state of intra-uterine death. 3) The transmission electron microscopic findings of the glomeruli revealed swelling of endothelial cells with vacuolization and vacuolated mesangial cells. 4) The angioarchitecture of the glomeruli was observed by scanning electron microscopy. The enlargement of the endothelial cells was found to reduce the size of cavities of vessels.

Animals↗
PubMed1984

The relationship of the eye uptake of N-isopropyl-p-[123I]iodoamphetamine to melanin production.

Eye uptake has been a potential concern with N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP) because it has been observed in certain animal species. We have investigated the cause of the eye uptake and its relationship to melanin synthesis. In a 1-yr-old cynomolgus monkey, high concentration of the tracer was seen in the eyes regardless of the type of anesthesia (pentobarbital or ketamine) or the oral administration of Lugol's solution. The eye uptake at 24 hr after injection of I-123 IMP was equally high in an 8-yr-old rhesus monkey. The ratio of radioactivity in the eye of black compared with white albino mice was 10:1 at 30 min, 18:1 at 2 hr and 36:1 at 24 hr after injection of I- 123 IMP. No eye uptake above soft-tissue background was seen in five patients at 2, 24, and 48 hr after injection. I-123 IMP is avidly incorporated into melanocytes actively producing melanin, but substantially less in melanocytes where production of melanin has ceased as in the human eye.

Amphetamines↗
PubMed1982

Quantifying local cerebral blood flow by N-isopropyl-p-[123I]iodoamphetamine (IMP) tomography.

A model was validated wherein local cerebral blood flow (LCBF) in humans was quantified by single-photon emission computed tomography (SPECT) with intravenously injected N-isopropyl-p-[123I]iodoamphetamine (IMP) combined with a modification of the classic method of arterial input sampling. After intravenous injection of IMP in rat, autoradiograms of the brain showed activity distributions in the pattern of LCBF. IMP was nearly completely removed on first pass through monkey brain after intracarotid injection (CBF=33 ml/100 g/min) and washed out with a half-time of approximately 1 hr. When the modified method of arterial input and tissue-sample counting applied to dog brain, there was good correspondence between LCBF based on IMP and on that by microsphere injection over a wide flow range. In applying the method to human subjects using SPECT, whole-brain CBF measured 47.2 +/- 5.4 ml/100 g/min (mean +/- s.d., N=5), stable gray-white distinction persisted for over 1 hr, and the half-time for brain washout was approximately 1 hr. Perfusion deficits in patients were clearly demonstrated and quantified, comparing well with results now available from positron ECT.

Adolescent↗
PubMed1982

Initial experience with SPECT (single-photon computerized tomography) of the brain using N-isopropyl I-123 p-iodoamphetamine: concise communication.

Forty-six patients were studied with N-isopropyl I-123 p-iodoamphetamine (IMP) and the Harvard Scanning Multidetector Brain System. In nine control patients, good differentiation between the gray and white matter of the cerebral cortex and the basal ganglia was evident. Regional uptake was affected by physiologic maneuvers (visual stimulation). In 24 patients studied for stroke, IMP images demonstrated areas that were involved in acute infarction in eight patients whose initial transmission computerized tomography (TCT) was normal; IMP also showed perfusion abnormalities larger than the TCT abnormality in ten patients. Perfusion abnormalities were present in 23/24 of these patients. Seven patients studied with a history of TIA had normal TCT and IMP images. In three patients studied during seizure activity, regions of hyperperfusion corresponded to the EEG seizure focus. Markedly decreased activity was present in three patients with brain tumor and corresponded to the focal abnormality on the TCT study. Our study demonstrates the feasibility of assessing regional brain perfusion using a radiopharmaceutical that is lipid soluble and has a high extraction fraction in the brain, together with single-photon ECT.

Amphetamines↗
PubMed1978

Relationship of molecular structure to in vivo scintigraphic distribution of carbon-11-labeled compounds. 4. Carbon-11-labeled mandelonitriles, Mandelic acids, and their esters.

11C-Labeled HCN was collected in water containing carrier KCN following bombardment of 99% N2-1% H2 with 22 MeV protons. 11C-Labeled mandelonitrile and p-methoxy-, p-hydroxy-, and 3,4-dihydroxymandelonitrile were synthesized from K11CN and the corresponding benzaldehyde. The initial distribution of 11C activity of these nitriles in dogs was primarily in the region of the heart, liver, and kidneys followed by rapid redistribution to the parotids and stomach with [11C]hydroxymandelonitriles. 11C-Labeled mandelic acid and m-methyl-, o-chloro-, and p-chloromandelic acid were synthesized from the corresponding [11C]mandelonitrile. Serial scintigraphy of 11C activity of these mandelic acids in dogs showed progressive renal excretion with accumulation of activity in the bladder. 11C-Labeled ethyl and benzyl mandelate were synthesized from [11CA]mandelic acid. These esters showed initial accumulation of activity in the lungs with eventual excretion by the kidneys.

Animals↗
PubMed1978

Pregnancy-associated plasma proteins in pregnant and pseudopregnant rats.

As in the human, the rat pregnancy-associated plasma proteins consisted of four distinct entities as revealed by immunological methods. All showed gradual increases during gestation and rapid disappearance postpartum. They could be physicochemically, although not immunologically, tentatively related to the human pregnancy proteins. None of them was detectable in the serum of rats at various stages of pseudopregnancy, nor in nonpregnant rats.

Animals↗
PubMed1976

Relationship of molecular structure to in vivo scintigraphic distribution patterns of carbon-11 labeled compounds. 3. (11C)Hydantoins.

The preparation and gamma-scintigraphic evaluation of the in vivo distribution patterns in dogs of a series of structurally related hydantoins labeled with the positron emitting, 20.4 min half-life radionuclide, carbon-11 are described. Carbon-11 labeled HCN was collected in water or aqueous Me2SO containing carrier KCN following cyclotron bombardment of 99% N2-1% H2 gas mixture with 22 MeV protons for 1 hr at 25-35 muA. Five 11C-labeled 5,5-dialkylhydantoins, three [11C]diarylhydantoins, five [11C]-5-alkyl-5-phenylhydantoins, and five [11C]spirohydantoins were prepared by heating generally under pressure, a mixture of 11C-labeled KCN, which was produced by isotopic exchange with carrier KCN, the corresponding aldehyde or ketone, and excess (NH4)2CO3 in aqueous ethanol or Me2SO solvent. The 11C-labeled hydantoins were dissolved in 1-1.5% aqueous NaOH for intravenous administration to dogs. Total synthesis time was 70-106 min and 1-59 mCi of final product was available for conducting serial in vivo imaging for up to 2 hr or more with the gamma-scintillation camera. Carbon-11 activity from all compounds showed initial blood-pool distribution with variable concentration of activity in the brain, lungs, liver, and kidney. All of the 11C-labeled diarylhydantoins, and most having one phenyl substituent, and one having a hexamethylene moiety showed initial accumulation of 11C activity in brain. Carbon-11 labeled 5,5-diphenylhydantoin (dilantin) showed the greastest qualitative accumulation of activity in the brain. Those 11C-labeled hydantoins having a carboxyl substituent showed prominent renal concentration and urinary excretion of activity. Most 11-c-labeled hydantoins showed a progressive homogenous whole body distribution of activity in all cellular tissues of the body. The relatively uniform distribution of activity in cellular tissues and slow excretion from the body support the thesis that the pharmacologic action of the hydantoins is related to physical effects on biomembranes rather than to specific chemical interactions with cell constituents.

Animals↗