Search PubMed⌕ Search

Biomedical subjects

S Z Lin

Publications and source records attributed to S Z Lin.

At least 55 records · Page 3Linked to original sources
PubMed1995

Regional skin blood flow in deep burn wounds: a preliminary report.

Local skin blood flow (LSBF) using the Walker's deep burn rat model was studied on the first three postburn days using the carbon-14 iodoantipyrine ([14C]IAP) perfusion method. The radioactive [14C]IAP (12.5 microCi) was infused through the femoral vein over a period of 30 seconds and the blood samples were collected by a free flow from the femoral artery at 5-s intervals to evaluate the concentration of the isotope, in the blood. At the conclusion of the infusion, the rats were guillotined and biopsies were obtained from the burned skin, unburned skin from burned rats and skin from sham control rats to assay the isotope in the skin. The LSBF was calculated from the skin tissue and plasma radioactivity data using Jay's equation. The results showed significant decreases of the skin blood flow in the deep burn wound with 4.05 +/- 1.16, 5.31 +/- 1.32 and 4.77 +/- 2.48 ml/100 g/min as compared to the LSBF of unburned skin 10.27 +/- 1.49, 12.39 +/- 2.05, 14.79 +/- 1.85 ml/100 g/min on postburn days 1, 2 and 3 (P < 0.05). The blood flow of the control group skin was 11.5 +/- 1.97 ml/100 g/min (P < 0.05). There were also significant differences of LSBF among burn wounds on postburn days 1, 2 and 3 (P < 0.05). Pathological study of the deep burn wound showed that more of the blood flow was in the subcutaneous adjacent areolar tissue, than in the deep reticular dermis, and only a little occurred in the upper reticular dermis occasionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Characterization of the excitoprotective actions of N-methyl-D-aspartate in cultured cerebellar granule neurons.

Exposure of cultured cerebellar granule neurons to subtoxic concentrations of N-methyl-D-aspartate (NMDA) has been shown previously to result in a neuroprotective state, as measured by subsequent exposure to toxic concentrations of glutamate. In the present study, we have further characterized the excitoprotective actions of NMDA in these neurons. NMDA-induced excitoprotection was concentration dependent (EC50 approximately 30 microM) and time dependent, with maximal protection observed following 16 h of preexposure to NMDA. NMDA-induced excitoprotection did not require continuous exposure to NMDA, as a 4-h preincubation was sufficient to induce full excitoprotection when measured 8 h later. Maximal protection was manifest as a "right shift" in the concentration-response relationship for glutamate toxicity of approximately three orders of magnitude (EC50 approximately 30 microM in untreated neurons compared with > or = 50 mM in NMDA-treated neurons). After removal of NMDA, complete reversal of the excitoprotective state was observed by 48 h (t1/2 approximately 24 h). The ability of NMDA to induce excitoprotection was observed in neurons maintained for up to 14 days in vitro (DIV) [postnatal day (PND) 22], but was absent at 21 and 32 DIV (PND 29-40), despite little to no difference in the toxicity of glutamate at any DIV examined. Preexposure of cerebellar granule neurons to a maximally excitoprotective concentration of NMDA (50 microM) failed to alter the density of NMDA receptors measured by the specific binding of [3H]MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Activation of G proteins bidirectionally affects apoptosis of cultured cerebellar granule neurons.

Cultured cerebellar granule neurons maintained in depolarizing concentrations of K+ (25 mM) and then switched to physiological concentrations of K+ (5 mM) undergo apoptosis. We now report that activation of specific G proteins robustly and bidirectionally affects apotosis of cultured rat cerebellar granule neurons. Stimulation of Gs with cholera toxin completely blocks apoptosis induced by nondepolarizing concentrations of K+, whereas stimulation of Go/Gi with the wasp venom peptide mastoparan induces apoptosis of cerebellar granule neurons even in high (depolarizing) concentrations of K+. Moreover, pretreatment of cerebellar granule neurons with cholera toxin attenuates neuronal death induced by mastoparan. By contrast, pertussis toxin, cell-permeable analogues of cyclic AMP, and activators of protein kinase A do not affect apoptosis of cultured cerebellar granule neurons. These data suggest that G proteins may function as key switches for controlling the programmed death of mammalian neurons, especially in the developing CNS.

Animals↗
PubMed1995

Hemodilution accelerates the passage of plasma (not red cells) through cerebral microvessels in rats.

BACKGROUND AND PURPOSE: Hemodilution lowers the total circulatory red cell mass and blood viscosity and thereby may alter the time of passage of red cells and plasma through cerebral microvessels. This study was designed to clarify this question. METHODS: Adult Wistar-Kyoto rats, aged approximately 32 weeks, were divided into hemodilution and control groups. Local cerebral blood flow and microvascular red cell and plasma volumes in 14 brain structures were measured with the use of [14C]iodoantipyrine, 55Fe-labeled red cells, and [14C]inulin, respectively. RESULTS: In the control group, the hematocrit in cerebral microvessels ranged from 0.29 to 0.45 with a mean of 0.36, which was 71% of the systemic hematocrit (0.51). The mean transit times of blood, red cells, and plasma through microvessels were 0.62 to 1.77 seconds (mean, 0.92 second), 0.44 to 1.15 seconds (mean, 0.65 second), and 0.78 to 2.5 seconds (mean, 1.25 seconds), respectively. In the hemodilution group, the mean hematocrit in microvessels was 0.28, which was 89% of the systemic hematocrit (0.32). Local cerebral blood flow was approximately 59% higher (P < .01) than that of the control animals. The rate of oxygen delivered to the brain was slightly increased (9%) after hemodilution. Blood volume in cerebral microvessels was similar to that of the control group. Mean transit time of blood was 0.62 second (68% of the control), transit time of red cells was 0.53 second (85% of the control), and transit time of plasma was 0.67 second (54% of the control). CONCLUSIONS: These findings indicate that isovolemic hemodilution accelerates the plasma (not red cell) flow velocity in cerebral microvessels.

Animals↗
PubMed1995

Diphenylhydantoin induces apoptotic cell death of cultured rat cerebellar granule neurons.

Apoptosis is one form of physiological or programmed cell death responsible for the selective elimination of various cell types during development. We have observed and characterized a delayed-type of neurotoxicity induced in cultured cerebellar granule neurons by diphenylhydantoin. Diphenylhydantoin toxicity of cerebellar granule neurons is time and concentration dependent. Morphological studies using Nomarski optics and staining with the fluorescent dye Hoechst 33258 demonstrate that diphenylhydantoin-induced neurotoxicity of cerebellar granule neurons is associated with cytoplasmic blebbing, heterochromatic clumping and condensation of chromatin that precede cell death. Unlike glutamate toxicity (excitotoxicity) diphenylhydantoin-induced neurotoxicity of cerebellar granule neurons is attenuated by actinomycin D and cycloheximide, and is associated with nucleosomal size DNA fragmentation. Since we have previously reported that depolarization of cultured cerebellar granule neurons with high concentrations of K+ promotes the survival of these neurons by blocking apoptosis, we examined the effects of diphenylhydantoin on the K(+)-evoked increase in intracellular calcium. Using microfluorimetry and fura-2 to measure intracellular calcium we found that neurotoxic concentrations of diphenylhydantoin markedly reduce the increase in intracellular calcium associated with elevated extracellular potassium. Taken together, these data demonstrate that exposure of cultured cerebellar granule neurons to pharmacologically relevant concentrations of diphenylhydantoin results in a delayed type of neurotoxicity characterized by the biochemical and morphological features of apoptosis.

Animals↗
PubMed1995

Activation of muscarinic cholinergic receptors blocks apoptosis of cultured cerebellar granule neurons.

We have recently reported that the majority of cultured rat cerebellar granule neurons undergo apoptosis when maintained in the presence of physiological concentrations of K+ (nondepolarizing conditions). We now report that exposure of cultured cerebellar granule neurons, maintained under nondepolarizing conditions, to the muscarinic cholinergic receptor (mAchR) agonists carbachol and muscarine results in a concentration- and time-dependent inhibition of apoptosis. The nicotinic cholinergic receptor agonist (-)-nicotine fails to mimic, and the nicotinic cholinergic receptor antagonist dihydro-beta-erythroidine fails to antagonize, the survival-promoting effects of carbachol. In contrast, relatively low concentrations of atropine completely prevent the effects of carbachol in blocking apoptotic death of cultured granule neurons. Although the m1- and m2-preferring mAchR antagonists pirenzepine and gallamine, respectively, fail to reverse the effects of carbachol, the m3-preferring antagonist 4-diphenylacetoxyl-N- methylpiperidine methiodide completely blocks the survival-promoting effects of carbachol. These data demonstrate that activation of the mAchR (possibly of the m3 subtype) blocks apoptosis of cultured cerebellar granule neurons. The antiapoptotic effects of mAchR agonists are not indirectly mediated via glutamate release from granule neurons, because antagonists of either N-methyl-D-aspartate or non-N-methyl-D-aspartate glutamate receptors fail to affect the antiapoptotic effects of carbachol or muscarine. Moreover, exposure of cultured cerebellar granule neurons to antiapoptotic concentrations of carbachol, in contrast to high concentrations of K+ or glutamate receptor agonists, results in only a small and transient elevation of the intracellular Ca2+ concentration, as measured by fura-2 microfluorimetry. Slow neurotransmitters such as acetylcholine, acting via their cognate G protein-coupled receptors, may prevent neuronal apoptosis in the developing (and perhaps adult) central nervous system.

Animals↗
PubMed1995

Mitochondrial alterations of skeletal muscle in a heat stress rat model.

The morphological and ultrastructural alterations of skeletal muscle in experimental rats with heat stress were investigated. Fifteen male Sprague-Dawley rats were exposed in a 42 degrees C constant temperature oven, resulting in a heat stress state; ten rats were used as controls. All treated rats had weakness of the 4 limbs associated with increased serum creatine kinase levels (p < 0.01). Soleus muscles were submitted to histological, histochemical, ultrastructural and quantitative-morphometric analysis. The group receiving heat stress showed many ragged-red fibers in Gomori trichrome stain and appeared hyper-reactive in succinate dehydrogenase and cytochrome C oxidase stains. The ultrastructure of ragged-red fibers showed increased mitochondrial aggregation as multiple small nests, which were particularly located in the subsarcolemmal space. The mitochondrial area was significantly increased in heat stress rats (p < 0.001). The consistently increased mitochondrial area and histochemical alterations of mitochondria are early pathological abnormalities in muscles with heat stress and indicate fundamental impairment of energy metabolism.

Animals↗
PubMed1994

A simple method for diagnosing traumatic occlusion of the vertebral artery at the craniovertebral junction.

STUDY DESIGN: A simple method, thin-slice contrast-enhanced computed tomographic (CT) scan, was evaluated as a first-line rapid screening procedure for diagnosing traumatic occlusion of the vertebral artery at the craniovertebral junction. OBJECTIVES: This procedure was performed in patients suffering from injuries of the high cervical spine or the craniovertebral junction. Vertebral angiography was undertaken after this procedure to confirm the diagnosis. SUMMARY OF BACKGROUND DATA: Well-enhanced vertebral arteries can be demonstrated clearly in normal subjects by using this method. Occlusion of the vertebral artery produces delayed contrast enhancement of the proximal artery and abrupt interruption of its course. METHODS: Thin-slice CT scan was performed from the atlas to the occipital condyles after an intravenous injection of angiograffin. The plane of the CT scan was aligned in a parallel manner to the upper margin of the atlas. The CT scanning was repeated until the contrast enhancement of the vertebral arteries became faint. RESULTS: Occlusion of the unilateral vertebral artery was successfully diagnosed in a patient with Jefferson's fracture by using the present technique. A subsequent vertebral angiography confirmed the diagnosis. CONCLUSIONS: The present technique should be performed as a routine screening procedure in patients suffering from injuries to the craniovertebral junction.

Atlanto-Axial Joint↗
PubMed1994

Combined treatment with nicardipine, phenobarbital, and methylprednisolone ameliorates vasogenic brain edema.

Free radicals formed around the edematous areas of the brain can cause lipoperoxidation of the cellular membrane, followed by calcium influx into the cell through calcium channels. These secondary insults may aggravate vasogenic brain edema. Since phenobarbital is a free radical scavenger, methylprednisolone has an antilipoperoxidation effect; and nicardipine is a calcium channel blocker, we hypothesized that combined treatment with phenobarbital, methylprednisolone, and nicardipine would be beneficial in vasogenic brain edema. This hypothesis was tested in Sprague-Dawley rats with a transdural cold-injury on the right parietal cortex. The animals were randomly divided into two groups. Animals in the treatment group were injected intraperitoneally with phenobarbital (4 mg/kg), methylprednisolone (50 mg/kg), and nicardipine (10 micrograms/kg) at 5 min and 8 hours after the cold-injury. The control animals were injected with saline. These animals were sacrificed 24 hours after the injury. The extent of brain edema was assessed by measuring the water content, the inulin distribution volume, and the distribution area of Evans blue in the brain. Our results showed that the water content of the edematous hemisphere was similar in the control and the treatment groups. However, Evans blue distribution area and inulin distribution volume of the treatment group were less than those of the control group by 12% and 31%, respectively. In conclusion, the combined treatment with phenobarbital, methylprednisolone and nicardipine is beneficial in vasogenic brain edema.

Animals↗
PubMed1994

Restoration of dopamine overflow and clearance from the 6-hydroxydopamine lesioned rat striatum reinnervated by fetal mesencephalic grafts.

The purpose of these experiments was to investigate the electrochemical indices of mesencephalic dopaminergic grafts as they function in the rat striatum. Sprague-Dawley rats were injected unilaterally with 6-hydroxydopamine into the medial forebrain bundle, and the effectiveness of these lesions was tested by measuring apomorphine-induced rotation. The unilaterally lesioned rats were later transplanted with fetal ventral mesencephalon. Only animals receiving ventral mesencephalon transplants showed significant decreases in rotation after grafting. High-speed chronoamperometric recording techniques using Nation-coated carbon fiber electrodes were used to evaluate dopamine (DA) overflow in the striatum of urethane-anesthetized rats. We found that 6-hydroxydopamine lesions resulted in a loss of KCl-induced DA overflow and clearance. Ventral mesencephalon grafts restored neurochemical indices. The zone of normalized DA clearance was considerably larger than that of normalized release. Furthermore, histochemical studies using tyrosine hydroxylase immunoreactivity confirmed graft survival and neurite outgrowth from the graft into the lesioned striatum. In conclusion, these findings suggest that the behavioral improvements by grafts of fetal mesencephalic tissue are accompanied by morphological and electrochemical evidence of reinnervation and the restoration of DA input. Measurement of DA clearance may reveal a wider area of reinnervation than that indicated by more traditional immunocytochemical methods.

Animals↗
PubMed1994

Steroid potentiation and inhibition of N-methyl-D-aspartate receptor-mediated intracellular Ca++ responses: structure-activity studies.

Pregnenolone sulfate and 15 related steroids were investigated for their effects on N-methyl-D-aspartate (NMDA)-induced elevations in intracellular Ca++ ([Ca++]i) in cultured rat hippocampal neurons by microspectrofluorimetry with the Ca(++)-sensitive indicator fura-2. Several pregn-5-ene steroids markedly potentiated NMDA-mediated [Ca++]i responses. Pregnenolone sulfate and its 21-acetoxy derivative and pregnenolone hemisuccinate were the most active. At a concentration of 50 microM, each produced approximately 300% potentiation of 5 microM NMDA responses. In addition, several steroids were identified that inhibited NMDA-induced elevations in [Ca++]i, the most potent of which was 3 alpha-hydroxy-5 beta-pregnan-20-one sulfate (IC50, 37 microM). Concentration-response curves for NMDA in the presence of active steroids revealed noncompetitive interaction(s) of these steroids with the NMDA receptor. Although the mechanism(s) responsible for either steroid-induced augmentation or inhibition of NMDA-receptor responses is unknown, these data suggest the presence of one or more steroid recognition sites with a high degree of structural specificity associated with NMDA receptors. These results further raise the possibility that pregn-5-ene 3-sulfates and pregnane 3-sulfates could be endogenous modulators of NMDA receptor-mediated synaptic events.

Animals↗
PubMed1994

N-methyl-D-aspartate induces a rapid, reversible, and calcium-dependent intracellular acidosis in cultured fetal rat hippocampal neurons.

The ability of NMDA to alter intracellular pH (pHi) was studied in fetal rat hippocampal neurons and glia using the pH-sensitive fluorescent indicator 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF). Brief exposure (60 sec) of hippocampal neurons to NMDA (2.5-250 microM) results in a rapid, and in most cells reversible, reduction in pHi, with full recovery to baseline pHi values taking several minutes following removal of NMDA. In contrast, little or no change in pHi was observed in glial cells exposed to these same concentrations of NMDA. The NMDA-induced acidification of neurons was concentration and time dependent, with an EC50 of 39 microM and Emax (delta pH) of -0.53. More prolonged exposure to NMDA (> or = 10 min) resulted in a more prolonged reduction in pHi values over the ensuing 20 min observation period. The intracellular acidification resulting from NMDA exposure of hippocampal neurons was blocked by the NMDA receptor antagonist 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). Moreover, removal of extracellular Ca2+ eliminated both the selective NMDA-induced elevation in [Ca2+]i and the reduction in pHi, indicating that Ca2+ influx may be required for the decrease in pHi induced by NMDA receptor activation. Finally, the NMDA-induced reduction in pHi was not significantly attenuated when extracellular [H+] was decreased by increasing extracellular pH to 8.0. The latter suggests that an intracellular source of H+ is responsible for the NMDA-induced reduction in neuronal pHi. The reduction in neuronal pHi induced by NMDA receptor activation may mediate some of the physiological and (or) pathophysiological actions of glutamate.

Acidosis↗
PubMed1992

Cerebral ischemia is the main cause for the onset of heat stroke syndrome in rabbits.

During the onset of heat stroke, rabbits displayed hyperthermia (42.8 degrees C), and decreased cerebral perfusion pressure and decreased cerebral blood flow (as reflected by a prolonged cerebral circulation time) compared to those of normothermic rabbits. On the other hand febrile rabbits, during the fever plateau did not show the above responses, although they had a similar level of hyperthermia (42.4 degrees C). The data support the concept that cerebral ischemia is the main cause for the onset of the heat stroke syndrome.

Animals↗
PubMed1992

Differences and similarities in albumin and red blood cell flows through cerebral microvessels.

The hypothesis that microvessels in brain parenchyma are continuously perfused by plasma but intermittently perfused by red blood cells (RBCs) was tested in awake Sprague-Dawley rats. The microvascular distribution volumes of radioiodinated serum albumin (RISA) and 51Cr- and 55Fe-labeled RBCs were measured for periods from 15 s to 30 min. Local cerebral blood flow (LCBF) was assessed by the iodoantipyrine technique. The RISA and RBC distribution volumes were constant in the 12 areas studied from 15 s onward. These data fit a model of continuous plasma flow with intermittent RBC flow (and thus support the hypothesis), but they are also consistent with other models, e.g., continuous flow of both plasma and RBCs through all perfused microvessels. In parallel with LCBF, microvascular blood volume varied greater than 10-fold among brain areas. Relative to arterial hematocrit, microvascular hematocrits were low, which indicates that the passage of RBCs through parenchymal microvessels is more rapid than that of RISA. This could be the result of both the Fahraeus effect and intermittent RBC flow.

Animals↗
PubMed1992

Cerebral glucose utilization and blood flow in adult spontaneously hypertensive rats.

Not only blood pressure but also behavioral activity, brain morphology, and cerebral ventricular size differ between young spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. This suggests that cerebral blood flow and cerebral metabolism may vary between these two rat strains. To test this hypothesis, we measured local cerebral glucose utilization in 31 brain areas of 26-30-week-old rats. Local cerebral blood flow was also assessed in these same areas. Cerebral glucose utilization was measured by the 2-deoxyglucose method; cerebral blood flow was determined by the iodoantipyrene method. In virtually all gray matter structures, the apparent rate of glucose utilization was lower in SHR than in normotensive WKY rats; the interstrain differences varied significantly among structures and were statistically significant (uncorrected t tests) in 14 of 28 gray matter areas. Local cerebral blood flow was fairly similar in the two rat strains. The coupling of blood flow to glucose utilization varied significantly among brain areas in normotensive WKY rats as well as in SHR. In a number of gray matter structures, the coupling of flow to metabolism differed between hypertensive and normotensive animals. These data suggest that for many brain areas, either glucose utilization or glucose partitioning differs between WKY rats and SHR.

Analysis of Variance↗
PubMed1992

[Effects of caffeine on shuttle, operating behaviors, and brain metabolism in rats].

Effects of caffeine (30, 60, and 120 mg.kg-1, ip) on shuttling and operating behaviors in 80 rats were studied. Effects of caffeine (60, 120 mg.kg-1, ip) on contents of dinucleotides and pterins in 6 brain areas of 18 rats were investigated by HPLC with fluorescent detector. The results showed that the dose of caffeine that induced augment of shuttle behavior was lower than that induced operating behavior. Caffeine 120 mg.kg-1 inhibited both shuttling and operating behavior, decreased FAD content in caudate nucleus; caffeine 60 mg.kg-1 increased FAD in cerebellum and brain stem. Caffeine 60, 120 mg.kg-1 increased brain NADH contents, decreased pterin contents, and increased biopterin contents in some brain areas.

Animals↗
PubMed1991

Functional variations in parenchymal microvascular systems within the brain.

Variations in microvascular system functions were observed among a number of brain areas. The rates of local blood flow varied 18-fold among areas and were extremely high in neuroendocrine structures. Marked differences in blood flow were also found within some brain structures. The volume of radiolabeled blood in perfused parenchymal microvessels ranged from 5 to 70 microliters/g and correlated closely with local cerebral blood flow. The hematocrits within parenchymal microvessels were 45-75% of the arterial hematocrit, which indicates that red cells more rapidly traverse brain microvessels than do plasma proteins. The mean transit times of blood through parenchymal microvessels were extremely short and ranged from 0.3 to 0.6 s.

Animals↗