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Biomedical subjects

J H Li

Publications and source records attributed to J H Li.

At least 109 records · Page 6Linked to original sources
PubMed1995

Zeneca ZD6169 and its analogs from a novel series of anilide tertiary carbinols: in vitro KATP channel opening activity in bladder detrusor.

The potassium (K+) channel opening activity of Zeneca ZD6169 and one of its pyridylsulfonyl analogs from the anilide tertiary carbinol series was ascertained. Their mechanoinhibitory effects on the myogenic activity of the guinea pig bladder detrusor muscle were measured in a set of functional assays. Elevating the K+ concentration in the tissue bath from 15 to 80 mmol/l increased the IC50 value of ZD6169 from 1.61 +/- 0.22 223 +/- 37 mumol/l. This result suggests that ZD6169 may act as a K+ channel opener. Similar to the prototypic ATP-sensitive K+ (KATP) channel opener cromakalim, the K+ channel openers from the anilide tertiary carbinol series displayed stereoselective mechanoinhibitory activity only in the test protocol in which the detrusor was stimulated with 15 mmol/l KCl. Being the active enantiomer, ZD6169 has an activity more than 30-fold higher than the less active enantiomer. ZD6169 at 10 mumol/l hyperpolarized the guinea pig detrusor membrane potential by 6.1 +/- 1.2 mV and increased the whole cell KATP current in isolated guinea pig smooth muscle cells by 34.9 +/- 7.9 pA. This is comparable to the increase of 26.8 +/- 5.0 pA obtained with 10 mumol/l of lemakalim, the active enantiomer of cromakalim. The K+ channel opening activity of ZD6169 and the pyridylsulfonyl analog was competitively antagonized by the KATP channel blocker glibenclamide in the guinea pig detrusor with a pA2 value of 7.2. This activity, however, was unaffected by blockers of small and large conductance Ca-dependent K+ channels, such as apamin and charybdotoxin, respectively. The present study showed that Zeneca ZD6169 and its analog from the anilide tertiary carbinol series are K+ channel openers that activate KATP channels in vitro to relax bladder detrusors.

Adenosine Triphosphate↗
PubMed1995

Mechanoinhibitory effect of estradiol in guinea pig urinary bladder smooth muscles.

The mechanoinhibitory effect of estradiol on the myogenic activity of guinea pig urinary bladder detrusor muscles was studied. In detrusor muscles tonically contracted with 80 mmol/lKCl, 17 beta-estradiol and the nonestrogenic isomer 17 alpha-estradiol at 30 mumol/l reduced the contraction by 64 +/- 3 and 59 +/- 1%, respectively. In detrusor muscles maintained in Ca(2+)-free media and depolarized with 80 mmol/lKCl, the contractile response of muscles to the reintroduction of Ca2+ was inhibited in a dose-dependent manner by 17 beta-estradiol, suggesting that 17 beta-estradiol blocked entry of extracellular Ca2+ into bladder smooth muscle cells and reduced the rise of intracellular Ca2+ required for contraction. In detrusor muscles mildly depolarized with 15 mmol/lKCl, 17 beta-estradiol reduced the myogenic activity with an IC50 of 6.8 +/- 1.3 mumol/l. The higher activity of 17 beta-estradiol in this latter test indicated that estradiol could also possess some K+ channel opening activity. Glibenclamide at 1 mumol/l did not affect the relaxant activity of 17 beta-estradiol in detrusor muscles stimulated with 15 mmol/l; however, this activity was diminished in a dose-dependent manner by iberiotoxin. Collectively, these results have demonstrated that in addition to the Ca2+ antagonist activity, 17 beta-estradiol possesses K+ channel opening activity in guinea pig urinary bladder smooth muscles, activating probably not the adenosine triphosphate sensitive, but the Ca(2+)-dependent large-conductance K+ channels.

Adenosine Triphosphate↗
PubMed1995

Dementia and physical disability as competing risks for mortality in a community-based sample of the elderly Japanese.

To examine whether an excess mortality due to dementia is independent of coexisting physical disability, a probability-sample of the non-institutionalized elderly (n = 3,308) living in Sendai City, Japan was followed between 1988 and 1991. Of those, 128 were diagnosed as dementia in 1988 by psychiatrists, using Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised as a diagnostic standard. Information on the ability to perform activities of daily living (ADL) was collected by self-report of the study subjects in 1988 baseline survey. The survival status was investigated three years later. The risks of dementia and co-existing ADL disability for mortality was examined by Cox proportional hazard models. The results indicated that the relation between dementia and mortality was two-fold, depending upon the physical functions. Dementia increased the risk for mortality among those without ADL disability, but it did not so among those with ADL disability, rather ADL function was a stronger predictor for mortality among the latter individuals. Prevention and treatment of physical disability would be important for improving the survival of the demented people.

Aged↗
PubMed1995

The secular trend in the incidence of subarachnoid hemorrhage in Miyagi, Japan: 1979-1990.

Since 1978, a stroke registry has been carried out in Miyagi Prefecture (2.2 million in population), Japan. Approximately 2,000 cases of stroke were annually registered through 16 hospitals which have cerebrovascular disease units. The incidence of subarachnoid hemorrhage was 17.4 per 100,000 population in 1990. The incidence increased gradually during early 1980's and reached plateau during late 1980's. Further, the trend in the incidence of subarachnoid hemorrhage is compared with those in other communities in other countries as well as Japan.

Adolescent↗
PubMed1995

A 28-year-old woman with swelling of the thumb.

The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopedic surgeon. The initial history, physical findings, and roentgenographic examinations are found on this page. The clinical and roentgenographic diagnoses are presented on the following pages.

Adult↗
PubMed1995

K-channel opening activity of dihydropyridine ZM244085: effect on 86Rb efflux and 3H-P1075 binding in urinary bladder smooth muscle.

Zeneca ZM244085, 9-(3 cyanophenyl)hexahydro-1,8 acridinedione, is a novel dihydropyridine (DHP) which relaxes KCl precontracted urinary bladder smooth muscle in vitro. The effect of ZM244085 on low and high KCl induced contractions, 86Rb efflux and [3H]-P1075 binding in guinea pig bladder strips was investigated to characterize the K-channel opening properties of this compound. Since ZM244085 is a dihydropyridine its effect on DHP binding sites on Ca2+ channels was also investigated. ZM244085 was found to be more potent in relaxing detrusor strips precontracted with 15 mM KCl than strips precontracted with 80 mM KCl (Li et al., 1995). This functional profile of ZM244085 is similar to that exhibited by typical K-channel openers (PCO). In addition, inhibition of ZM244085 induced relaxation of detrusor strips by glibenclamide suggests that ZM244085 opens ATP sensitive K-channel (KATP) in urinary bladder (Li et al., 1995). Since the glibenclamide sensitive smooth muscle relaxation activity of ZM244085 could still be an indirect effect of this compound on KATP channels we carried out 86Rb efflux studies and [3H]-P1075 binding studies to further confirm these findings. The 86Rb efflux assay is a direct method for monitoring the movement of K+ ions across the cell membranes. Displacement of [3H]-P1075 binding to bladder membranes supports a direct action of the compound on the KATP channel. The present study demonstrates that ZM244085 in a concentration dependent manner increases the rate of 86Rb efflux from guinea pig bladder strips. This effect was inhibited by glibenclamide (30 microM), a known KATP channel blocker. In addition, interaction of ZM244085 with KATP channels was also confirmed in human bladder smooth muscle cells using a 42K efflux assay. Furthermore, we were able to demonstrate that ZM244085, structurally distinct PCO, inhibited the binding of 3H-P1075 to urinary bladder strips in a manner similar to other KATP openers such as cromakalim and pinacidil. Inhibition of 3H-P1075 binding by ZM244085 and other PCO's correlates well with increases in 86Rb efflux and bladder muscle relaxation studies. Finally, ZM244085 did not exhibit any significant affect on VSCC as evidenced by very weak inhibition of [3H]-PN200,110 binding to bladder membranes by ZM244085. It is concluded that Zeneca ZM244085 is a PCO which activates KATP channels in urinary bladder.

Acridines↗
PubMed1995

Determination of free digoxin in sera of 8 patients with chronic cardiac insufficiency.

AIM: To establish a method for the determination of free digoxin in serum for clinical use and to study the relationship between the free and total digoxin concentrations in chronic cardiac insufficiency patients receiving digoxin with different renal function. METHODS: The ultrafiltration with fluorescence polarization immunoassay was used to determine the concentration of free digoxin. RESULTS: The concentrations of digoxin standards in serum were 0.96, 1.92, and 3.84 nmol.L-1. The relative standard deviation was < 7% for intra-day and < 6% for inter-day determinations. The average recovery was 99.95 +/- 2.18%. The ratio of free/total digoxin in chronic cardiac insufficiency patients with renal dysfunction was lower than that in patients with normal kidneys (63.5 +/- 4.7% vs 75.1 +/- 3.9%, P < 0.01). CONCLUSION: The present method is simple and reliable. In these patients there is an over-measurement for total digoxin concentration, suggesting the presence of elevated endogenous digoxin-like immunoreactive substances.

Aged↗
PubMed1995

Clinics in diagnostic imaging (4). Renal angiomyolipoma with spontaneous perinephric haemorrhage.

A 69-year-old Chinese woman presented with acute right-sided abdominal pain. Intravenous urogram and ultrasound demonstrated a fatty lower renal pole mass with a perinephric collection. The diagnosis of renal angiomyolipoma was confirmed by computerised tomography. The perinephric haemorrhage resolved with conservative treatment. The classification, clinical features and management of this entity is discussed. The role of imaging in diagnosis and follow-up of renal angiomyolipoma is emphasised.

Abdominal Pain↗
PubMed1995

[Effects of lesion or stimulation of pituitary gland and hypothalamic arcuate nucleus on pain modulation in rats].

Relationship between pituitary gland and hypothalamic arcuate nucleus (ARC) in the modulation of pain threshold was investigated in Wistar rats with method of focal lesion and stimulation of pituitary gland. Experimental results indicated that electrolytic lesion of the pituitary intermediate and anterior lobes resulted in a decrease of pain threshold and disappearance of the analgesia immediately produced by ARC stimulation. Stimulation of the same area of pituitary gland could induce a delayed analgesia, which could be blocked by ARC lesion.

Animals↗
PubMed1994

Maxillary osteonecrosis after radiotherapy for nasopharyngeal carcinoma.

A case of extensive osteoradionecrosis of the posterior maxillae, pterygoid plates and floor of the sphenoid sinuses is reported. The patient received more than one full course of radical radiotherapy for nasopharyngeal carcinoma. Although there was complete remission of the tumour, she suffered from repeated episodes of gum bleeding which was found to be due to oroantral fistulas and severe dental decay. The large fraction dose and total dose, severe dental caries and xerostomia are the most likely contributory causes to this unusual complication in our patient.

Adult↗
PubMed1994

Diuretic and antihypertensive activity of ZENECA ZM224,832: a novel eukalemic diuretic with calcium channel blocking activity.

ZENECA ZM224,832 is a novel eukalemic diuretic from the aminomethylphenol pyrazine series which demonstrated a profile of calcium channel blockers. It produced diuretic and saluretic effects in animals but had only minimal alterations in kaliuresis after oral administration. In contrast to standard diuretics, the plasma K+ concentration was not altered in conscious dogs treated for 14 days with ZENECA ZM224,832 and the concurrent plasma renin activity was also minimally elevated. The isolated rat aorta evaluation indicated that ZENECA ZM224,832, like tiapamil and nifedipine, inhibited vascular smooth muscle tone by inhibiting voltage-dependent calcium channels. ZENECA ZM224,832 produced a dose-dependent decrease of blood pressure in spontaneously hypertensive rats (SHR) in which the antihypertensive activity was not noted with HCTZ. In addition, ZENECA ZM224,832, similar to diltiazem, produced an acute blood pressure lowering effect in nephrectomized SHR which was independent of its diuretic activity. It is concluded that ZENECA ZM224,832 is a potent eukalemic diuretic with calcium channel blocking properties.

Animals↗
PubMed1994

Characterization of ATP-sensitive potassium channel-blocking activity of ZENECA ZM181,037, a eukalemic diuretic.

ZENECA ZM181,037 is a novel eukalemic diuretic from a series of 1,1-diarylcarbin-1-01-2 amines. In contrast to the standard diuretic hydrochlorothiazide, the blood pressure-lowering effect was not observed with ZENECA ZM181,037 in spontaneously hypertensive rats. ZENECA ZM181,037 demonstrated a K+ channel-blocker profile. In the isolated rat aorta stimulated with 20 mmol/l KCl, both the d- and l-enantiomer of ZENECA ZM181,037 antagonized the relaxation of cromakalim with mean pKB values of 6.4 and 6.7, respectively. In the isolated guinea-pig portal vein and urinary detrusor muscle, both enantiomers enhanced the spontaneous myogenic activity at concentrations of 1 mumol/l and higher, in addition to antagonizing the effect of cromakalim. ZENECA ZM 181,037, similar to glibenclamide, prevented a significant increase in 86Rb+ by cromakalim in both portal vein and detrusor muscle strips; however, ZENECA ZM181,037, dissimilar to glibenclamide and tolbutamide, did not increase plasma glucose when given orally to dogs. Thus, ZENECA ZM181,037 is a blocker of the ATP-sensitive K+ channel (KATP) in vascular and nonvascular tissues. In view of the profound saluresis produced by ZENECA ZM181,037, the lack of antihypertensive effect appears to result from its blocking activity on KATP in vascular tissues.

Acetamides↗
PubMed1994

[Research on corneal thickness at multi-points in normal and myopic eyes].

The corneal thickness of the center and other 24 points were measured in 31 normal eyes and 246 myopic eyes. The results show that the mean central corneal thickness of the normal eye is 541 +/- 45.29 microns and that of the myopic eye, 544 +/- 35.01 microns. There are no significant differences in the central corneal thickness in comparisons between the left and right eye, between the male and female, among various age groups, and among various degrees of refractive error. However, with the increase of age and increase of myopic refractive error, the central corneal thickness gradually becomes thinner. There are differences in thickness among various directions, the superior direction being the thickest and the temporal inferior, the thinnest. From the center to the limbus, the thickness of the cornea gradually increases, but the values of the increase of the thickness are various in various directions, that should be paid attention to in radial keratotomy.

Adolescent↗
PubMed1994

[Determination of yuanhuacine in Daphne genkwa Sieb. et Zucc. by HPLC].

Separated on phenox RP18 column with a mobile phase of methyl alcohol-water (82:18) and detected at wavelength 232nm, yuanhuacine has shown a good linearity in the range from 7.6 x 10(-3) to 0.76 microgram. The recovery is 99.56% with RSD 3.61% (n = 9). The content of yuanhuacine in Daphne genkwa is 0.00848%.

Chromatography, High Pressure Liquid↗
PubMed1994

[The analgesia effect and plasma corticosterone reaction during stress in adult rats treated neonatally with monosodium glutamate].

In the present investigation, it was found that the number of beta-endorphin (beta-END)-immunoreactive neurons of hypothalamic arcuate nucleus (ARC) in MSG-treated rats decreased by 60.7%. No significant differences in the baseline pain threshold and the baseline corticosterone (CS) level were observed between the MSG-treated group and the control group. After electrical foot shock for 30 min, the analgesia effect was decreased significantly (P < 0.001) in MSG-treated rats, while the CS levels of both MSG-treated rats and control rats were increased remarked (P < 0.01). The results suggest that the beta-END neurons of ARC were involved in analgesia, but not in CS reaction during stress.

Animals↗
PubMed1993

Stereoselective blockade of amphibian epithelial sodium channels by amiloride analogs.

The blockade of amphibian epithelial sodium channels by amiloride has been shown to not be a simple diffusion-limited encounter but rather a selective binding process with the rate of approach of the molecule for the channel site determined by the side chain at position 2 of the pyrazine ring and the stability of the blocking complex provided largely by the bond of the ligand at position 6. The presence of such a putative channel-associated receptor suggests that the sodium channel might have chiral recognition for its blockers. Using the short-circuit technique to measure the amiloride-sensitive sodium current through the apical membrane of the toad urinary bladder and frog skins, we evaluated the sodium channel-blocking potency of three enantiomeric pairs of amiloride analogs with chiral centers on the side chain. We demonstrated the stereoselectivity in sodium channel blockade of those analogs and confirmed the existence of a second attachment site on the channel for interacting with the lipophilic ligand on the side chain of the analog molecule to enhance its blocking activity. Depending on the separation between the chiral carbon and the pyrazine ring and the chemical groups on the chiral carbon, the eudismic ratio for the 50% inhibition constant of the enantiomers, i.e., the ratio of the sodium channel-blocking potency of the more active enantiomer to that of the less active enantiomer, was found to range from slightly more than 1 to more than 100.

Amiloride↗
PubMed1992

Beta-adrenoceptor subtypes in the detrusor of guinea-pig urinary bladder.

beta-Adrenoceptors have been demonstrated in the urinary bladders of many animals including the guinea pig. However, there is little information on the subtypes involved in the antispasmodic activity of beta-adrenoceptor activation in the guinea-pig detrusor. The present study uses the non-selective beta-agonist isoproterenol, the antagonist nadolol, the beta 2-selective agonists salbutamol and terbutaline, the antagonist ICI 118551, and the beta 1-selective antagonist metoprolol, to demonstrate functionally the subtypes existing in the guinea-pig detrusor. Isoproterenol dose-dependently reduces the myogenic activity in the guinea-pig detrusor induced by mild depolarization with 20 mM potassium in the tissue bath. At the supramaximal concentration of 30 microM, isoproterenol achieves 73 +/- 2% of the reference maximal response. This activity of isoproterenol is reduced to 9 +/- 5, 24 +/- 6 and 54 +/- 1% in the total blockade of beta, beta 1 and beta 2 with nadolol, metoprolol and ICI 118551, respectively. Consistently, salbutamol and terbutaline at the same concentration produce only 35 +/- 1 and 38 +/- 4% of the response, respectively. Thus, both beta 1- and beta 2-adrenoceptors are present in the detrusor of the guinea-pig urinary bladder. Although activation of either subtype results in antispasmodic action, the larger portion of the antispasmodic activity appears to be associated with the activation of the beta 1-subtype.

Adrenergic beta-Agonists↗