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Biomedical subjects

S L Chang

Publications and source records attributed to S L Chang.

At least 109 records · Page 6Linked to original sources
PubMed1987

Periodic crosslinking of microtubules by cytoplasmic microtubule-associated and microtubule-corset proteins from a trypanosomatid.

The dominant element in the cytoskeleton of Crithidia fasciculata is a peripheral corset of microtubules enclosing the cell body and closely underlying the plasma membrane. A lateral spacing of 50 nm is maintained by crosslinks, and microtubules may also be linked to the plasma membrane. We have characterized groups of polypeptides that associate with microtubules polymerized in vitro from the cytoplasm, or that are associated with the corset complex. They differ except for one of Mr 33,000 present in both groups. The corresponding native corset protein appears to be a dimer of Mr 66,000. These protein(s) copolymerize with brain tubulin, and the resultant polymer consists of pairs or small parallel bundles of microtubules, joined by periodic crosslinks spaced about 8.5 nm apart.

Alkaloids↗
PubMed1987

Effects of standard surgical procedures on the patellar blood flow in monkeys.

The effects of various surgical dissections on the patellar blood flow were studied in ten monkeys by the use of the hydrogen washout technique. The patellar blood flow was decreased to an average of 65% of the control value after an extensive medial parapatellar arthrotomy. When the infrapatellar fat pad was completely removed following extensive medial arthrotomy, the blood flow further decreased to an average of 49% of the control. When a lateral retinacular release with sacrifice of the lateral superior genicular artery was performed following the medial arthrotomy, the blood flow decreased to an average of 53% of the control. When a lateral release was combined with removal of the fat pad following the main medial arthrotomy, the patellar blood flow showed marked decrease to an average of only 17% of the control. The vascular anatomic study demonstrated that many vessels penetrate from the fat pad into the inferior pole of the patella. It is suggested that the lateral superior genicular artery and/or the fat pad should be carefully preserved to avoid ischemia of the patella during extensive procedures such as total knee arthroplasty.

Animals↗
PubMed1986

Characterization of antipyrine autoinduction in the rat utilizing a new microsampling technique for serial blood sample collections.

A new microsampling technique is described and applied to the collection of a large number of blood samples from individual rats receiving a chronic intravenous antipyrine infusion. From these samples, a detailed description of the time-course of antipyrine autoinduction of clearance in the rat was provided. Antipyrine clearance was increased 4-5-fold over 8 d of antipyrine administration, with the increase in clearance following a monoexponential process in all animals. The assumption that the time-course of induction should reflect the degradation rate of induced enzymes was examined by comparing the half-life of antipyrine autoinduction with in vitro estimates for the half-life of induced cytochrome P-450 enzymes. The results of this comparison are discussed with respect to utilizing this kinetic model to quantitate the turnover of drug metabolism enzymes in vivo.

Animals↗
PubMed1986

Brain SPECT imaging with 99Tcm-hexamethylpropyleneamine oxime in the early detection of cerebral infarction: comparison with transmission computed tomography.

A new cerebral blood flow agent, 99Tcm-hexamethylpropyleneamine oxime (HM-PAO), was evaluated for early detection of acute cerebral infarction in conjunction with the transmission computed tomographic (CT) studies. The data from 22 cases were analysed. Results reveal that 99Tcm-HM-PAO enables the early detection of acute cerebral infarction prior to CT with rather proper depiction of the extent of physiological abnormality in the majority of patients. This promising result together with the lack of logistical problems will make 99Tcm-HM-PAO a useful and practical agent worldwide for diagnosing and managing acute cerebral infarction.

Brain↗
PubMed1986

Radioimmunoassay screening for etorphine in racing horses.

A commercially available radioimmunoassay kit was used to screen for the presence of etorphine in post-race urines from horses racing in Kentucky. Most horse urines contained small amounts of materials which reacted positively in this immunoassay. These materials are apparently endogenous to the horse and were called apparent etorphine equivalents. The levels of these apparent etorphine equivalents in post-race urines from 70 horses were estimated. Their modal level averaged 0.1 ng/ml, the population distribution was log normal, and individual horses showed levels of up to 0.8 ng/ml.

Animals↗
PubMed1985

Inhibition of epoxidation of carbamazepine by valproic acid in the isolated perfused rat liver.

The effect of valproic acid on carbamazepine epoxidation in the perfused liver was investigated in two separate studies. In study I, significant decreases were observed both in the intrinsic clearance of carbamazepine and the intrinsic formation clearance of carbamazepine-epoxide in the presence of therapeutic concentrations of valproate. The same inhibitory effect of valproate was also observed in liver preparations from a group of animals pretreated with carbamazepine. Study II focused on the effect of valproate and carbamazepine on the apparent Michaelis-Menten parameters (Vmax,m, Km,m) associated with the intrinsic formation clearance of carbamazepine-epoxide in the perfused liver. Valproate had no statistically significant effect on either the Vmax,m or the Km,m of epoxidation, although the Km,m value was 43% higher in the presence of valproate. However, the ratio of Vmax,m and Km,m (intrinsic formation clearance) was significantly reduced by valproate. The Vmax,m and Km,m values obtained in study II predicted a significant decrease in the intrinsic formation clearance of carbamazepine-epoxide, consistent with the results of study I. Carbamazepine pretreatment was associated with significant increases in apparent Vmax,m and Km,m of epoxide formation.

Animals↗
PubMed1985

Effects of phenobarbital and SKF-525A on in vitro hepatic metabolism of verapamil and nifedipine.

Both verapamil and nifedipine are first-generation calcium-entry antagonist drugs which are eliminated by hepatic metabolism. To evaluate the effects of enzyme induction and suppression on the biotransformation of these compounds, liver homogenate fractions were prepared from male Fisher (F344) rats, which were either untreated, or injected intraperitoneally with phenobarbital or with SKF-525A prior to sacrifice. Known concentrations of verapamil or nifedipine were incubated with the 9,000 g supernatant, and the quantity of unchanged drug remaining after 10 min was measured. SKF-525A pretreatment significantly decreased the elimination (disappearance) rate of both calcium-entry antagonist compounds. Phenobarbital increased the rate of disappearance of verapamil, but had no effect on that of nifedipine. Difference spectra of hepatic microsomes to which verapamil had been added revealed a concentration-dependent, saturable interaction between drug and enzymes with spectral changes characteristic of "type I' substrates for cytochrome P-450 monooxygenase(s). The spectral characteristic of microsomes to which nifedipine was added could not be determined because of drug absorption at 350-500 nm. These data imply that verapamil metabolism is mediated by the cytochrome P-450 monooxygenase(s), and that nifedipine metabolism likely involves hepatic enzyme systems other than those known to be induced by phenobarbital.

Animals↗
PubMed1985

Effect of fixation devices on radiostrontium clearance in the intact canine femur.

Femoral metaphyseal/diaphyseal blood flow was studied by 85Sr clearance in unfractured segments of dog femurs following compression plating and various control procedures (drilling with and without application of screws). The animals were tested as early as seven days and as late as two months after surgery. The only statistically significant change in strontium clearance (SrC) was an increase produced by the application of stainless-steel bone screws, with or without plates. The presence or absence of compression had no consistent effect on changes in the rate of SrC. During the period of study, no changes in bone mineralization, haversian porosity, or cortical bone thickness accompanied the SrC alterations.

Animals↗
PubMed1984

From bone lining cell to osteocyte--an SEM study.

We describe the SEM appearance of the rat endosteal bone lining cell ( BLC ) population, and the sequence of morphological changes of these cells as they self-incorporate into unmineralized bone matrix (osteoid), establish intercellular connections, and construct lacunae. The osteoblast/nascent osteocyte series was progressively unsheathed by gentle digestion of the osteoid with 0.25% collagenase. The osteoblasts which leave the polygonally packed BLC compartment rapidly develop numerous complexly branched processes that contact the processes elaborated by previous generations of maturing and mature osteocytes. As osteoblasts mature and approach the mineralization front, they appear to lose processes. The mature cells begin to form osteocyte lacunae by depositing an asymmetric perimeter of woven collagen fibrils, such that as the cells roof-over, the lacunae appear as pocketlike constructions. The collagen fibrils on the perilacunar matrix are oriented in a tangential or circular pattern, while those in the more distal matrix are arranged in a parallel pattern. With the completion of a lacuna, its wall appears to mineralize quickly, for lacunae could be recognized only when they are forming.

Animals↗
PubMed1984

Heart rate pattern during respiratory pauses in normal infants during sleep.

We examined the pattern of heart rate during respiratory pauses in 10 normal infants at 1, 2, 3 and 4 months of age during sleep. Ventilation was recorded using barometric plethysmography and heart rate was measured using a precision R-R preprocessor. Typically, during a respiratory pause, the R-R interval increases, reaches a maximum and then returns towards baseline within the period of a respiratory pause or shortly after. The R-R interval starts to increase within 1-3s after the onset of the respiratory pause. The magnitude of increase in R-R interval varies considerably and, in some cases, reaches up to 50% of baseline. More than 73% of respiratory pauses are associated with an increase in R-R interval in quiet sleep but only about 50% in rapid-eye-movement sleep. Screening all the R-R data in each study revealed also spontaneous fluctuations in R-R interval without respiratory pauses. These data suggest that in normal infants in the first 4 months of life a respiratory pause is more likely to be associated with an increase in R-R interval in quiet than in rapid-eye-movement sleep; the increase in R-R interval during a respiratory pause is not related to hypoxaemia and respiratory pauses are not the only events that are associated with an increase in R-R interval during sleep.

Heart Rate↗
PubMed1984

Effects of hemodynamic changes on the elimination kinetics of verapamil and nifedipine.

This study used a steady-state approach to evaluate the relationships between the pharmacodynamic and pharmacokinetic characteristics of nifedipine and verapamil. In anesthetized and instrumented dogs, i.v. bolus/infusion dosing regimens were used for each drug to achieve and maintain stable drug concentrations in four different ranges rapidly. For both compounds, increases in doses were associated with disproportionate higher plasma drug concentrations, greater hemodynamic effects and significant reductions in systemic drug clearance. Progressive increases in the dose of nifedipine produced reductions in arterial pressure and reflex augmentation in cardiac output, together with decreases in calculated hepatic plasma flow which closely paralleled the decline in mean aortic pressure. Increasing doses of verapamil also resulted in decreased hepatic plasma flow, which was associated with both systemic hypotension and drug-induced decreases in cardiac output. These data imply that the hemodynamic effects of both nifedipine and verapamil result in changes in hepatic plasma flow which, in turn, result in significant alterations in systemic drug clearance. In this experimental model, the calculated hepatic plasma flow and observed systemic clearance values for nifedipine and verapamil were closely related to concentrations of the respective drugs in plasma.

Animals↗
PubMed1983

Steady-state determination of the contribution of lung metabolism to the total body clearance of drugs: application to carbamazepine.

A steady-state approach is proposed to examine the contribution that the lung makes to the total body elimination of medium- to high-clearance drugs. Carbamazepine, a potential candidate of pulmonary metabolism, was investigated by infusion into the femoral vein in seven unrestrained Sprague-Dawley rats (250-300 g). Blood samples (0.45 ml), taken simultaneously from the jugular vein and carotid artery in each rat during the infusion (2-5 days), were assayed in duplicate for carbamazepine by GLC/CI/MS. Venous blood concentrations were used to calculate the total body clearance of carbamazepine, 440 +/- 38 ml/hr (mean +/- SEM), and the difference between simultaneous venous and arterial blood concentrations were used to calculate the extraction ratio of carbamazepine by the lung. The mean extraction ratio of 0.0058 (n = 28) suggests that the lung only contributes approximately 5% to the total body clearance of carbamazepine. It is proposed that this technique could be useful in examining the importance of the lung in the total body clearance of other drugs, and that it has several advantages over some currently used techniques.

Animals↗
PubMed1983

Respiratory pauses during sleep in near-miss sudden infant death syndrome.

To study transient ventilatory changes in infants with the near-miss sudden infant death syndrome (SIDS), we examined the distribution, frequency, and mean duration of all respiratory pauses defined as expiratory time (Te) greater than 2 s in 12 infants with near-miss SIDS and 10 age-matched normal infants during REM and quiet sleep at 1, 2, 3, and 4 months of age. Using the barometric method, we monitored ventilation and respiratory timing while these infants breathed (1) ambient gas concentrations and (2) 2% CO2. We found that infants with near-miss SIDS did not have more frequent or prolonged respiratory pauses than did normal infants at any age in either REM or quiet sleep breathing ambient gas. With 2% CO2, respiratory pauses decreased in number or were eliminated and their mean duration was shorter in both groups. If these infants have hypoxemia during sleep, these data do not support the hypothesis that hypoxemia is secondary to prolonged and more frequent respiratory pauses.

Carbon Dioxide↗
PubMed1983

The effect of protracted tetracycline treatment on bone growth and maturation.

Mature female rhesus monkeys were used to evaluate the effects of a one-year course of tetracycline (50 mg/kg/day, intramuscularly) on the formation, maturation, and mineralization of mandibular bone. The bones from the treated group contained normal concentrations of calcium (Ca), inorganic phosphorus (Pi), and hydroxyproline (HO-Pr), and the treatment schedule did not alter the distribution (percentage) of total osteons into slightly, moderately, and highly mineralization classes. Tetracycline impairs bone mineralization and the subsequent maturation of the mineral and matrix moieties. The percentage of highly mineralized osteons labeled with tetracycline is subnormal. Density gradient fractionation studies indicate the presence of abnormally high Ca/Pi ratios in the temporally young newly formed bone mineral and somewhat higher ratios in the most mature bone fraction. Protracted tetracycline treatment at high dosages impairs bone growth and maturation in adult rhesus monkeys.

Animals↗
PubMed1983

Healing of canine femoral osteotomies. Effects of compression plates versus Eggers' plates.

The effects of rigid self-compressing plates were compared with the effects of less rigid internal contact splints on the healing characteristics of osteotomized canine femora. Radiographically, the rigid fixation afforded by the compression plate produced accelerated healing as compared with the less rigid fixation obtained with splints at two to four months. At six months there was little or no difference between the two groups. Comparison of the material biomechanical properties of the healing femora suggested that the repair tissue formed early after compression plating was stronger than the callus tissue that surrounded the less rigidly fixed femora. A comparison of the structural biomechanical properties of the bones suggested, conversely, that a stronger whole bone resulted from the less rigid fixation splint. The histomorphometric data showed that some cortical bone was lost under both types of fixation plates. However, the patterns of loss were not comparable. Use of rigid internal fixation led to loss of cortical bone after four to six months, while the less rigid fixation obtained with the Eggers splint produced mild intracortical resorption only. These observations point to the desirability of rigid internal fixation early in the healing process and the possible benefit of decreasing the rigidity of the fixation device as healing proceeds.

Animals↗
PubMed1981

Bioavailability of allopurinol oral and rectal dosage forms.

The bioavailability of allopurinol from orally administered tablets and rectally administered suppositories is reported. Two types of rectal suppositories (cocoa butter and polyethylene glycol) were compounded and contained 300 mg allopurinol (from oral tablets). Five healthy volunteers received 300 mg allopurinol orally from tablets or rectally from suppositories in a randomized, three-way crossover design. Serial blood samples were drawn for 72 hours following administration and were analyzed by high-pressure liquid chromatography for allopurinol and its metabolite, oxipurinol. The interaction between allopurinol and PEG was studied in vitro using a dialysis method. Serum allopurinol levels following oral administration of tablets peaked at 1.5 +/- 0.23 microgram/ml at 5.20 +/- 0.65 hours. Allopurinol was not detectable after administration of cocoa butter/allopurinol suppositories; oxipurinol peaked at 0.34 +/- 0.14 microgram/ml at 13 +/- 11 hours. The bioavailability of allopurinol from the cocoa butter suppository, relative to the tablet, was 5.77 +/- 2.5%. Neither allopurinol nor oxipurinol was detectable (less than 0.1 microgram/ml) in the sera of persons following administration of PEG suppositories. Dialysis studies showed decreased loss of allopurinol from the dialysis sac as PEG concentration increased. The rectal suppositories of allopurinol used in this study did not appear to be an efficient means of administering this drug.

Administration, Oral↗
PubMed1979

Pathogenesis of pathogenic Naegleria amoeba.

In brain sections of the Naegleria-caused cases of primary amoebic meningoencephalitis, extensive demyelinization was found in the white matter, besides the severe histopathological changes and large clusters of trophozoites in the grey matter. The myelinoclasis appeared to be a result of a specific phospholipolytic effect, unlike that in post-viral encephalomyelitis, which has been attributed to vascular blockade or hemorrhages. In monkey kidney cell cultures a very early cytopathic effect was observed and traced to the cytolytic property of the seeding culture fluid. Rat brain slices inoculated with Naegleria culture exhibited amoebic growth and demyelinization in 28-52 hours incubation at 35 degrees C. In a chemically defined medium containing sphingomyelin, casein and glucose, the Naegleria produced a limited growth parallelling the clearance of the lipid turbidity during a 72 hour incubation at 35 degrees C. Chromatographic analysis of the turbidity-cleared cultures revealed decomposition of sphingomyeline with liberation of choline, sphingosine and fatty acids. It is, hence, concluded that the pathogenicity of cytopathic effect of pathogenic Naegleria can be attributed to the latter's capacity to liberate a phospholipolytic enzyme or factor during active growth, which "makes holes" in the lipid-rich cytoplasmic membrane of cells as well as demyelinizes nerve tissue.

Amebiasis↗