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Biomedical subjects

C W Lin

Publications and source records attributed to C W Lin.

At least 55 records · Page 3Linked to original sources

Serratia marcescens bacteremia: clinical features and antimicrobial susceptibilities of the isolates.

From July 1996 to June 1997, 22 adult patients with Serratia marcescens bacteremia were retrospectively studied at China Medical College Hospital. All patients had severe underlying disease, most commonly diabetes mellitus. Eighteen (82%) patients had nosocomial infection. Clinical syndromes included primary bacteremia (68%), pneumonia (14%), urinary tract infection (9%), suppurative thrombophlebitis (5%) and surgical wound infection (5%). Twelve patients had central venous catheters in place at the onset of bacteremia, but only one case met the definition of catheter-related infection. In 14 (64%) patients, portal of entry of S. marcescens infection was unknown. Five (23%) patients had concurrent polymicrobial bacteremia. The overall mortality rate was 50% (11/22). Seven (32%) of the 22 patients died of S. marcescens bacteremia. All isolates were resistant to ampicillin and cephalothin and susceptible to imipenem. Ninety-five percent of strains were susceptible to moxalactam, 68% to amikacin, 55% to ceftazidime, 45% to aztreonam, 32% to ceftriaxone, 27% to gentamicin, 18% to cefoperazone and cefotaxime, and 9% to piperacillin. MICs of various antibiotics demonstrated that ciprofloxacin and imipenem had good activities against S. marcescens, with MIC90 of 0.19 microg/mL and 1.0 microg/mL, respectively. Due to increasing multidrug resistance, choosing appropriate antimicrobial agents such as moxalactam, imipenem, and ciprofloxacin should be highly recommended for the treatment of S. marcescens infections.

Adolescent↗

Clinical and microbiologic characteristics of Ochrobactrum anthropi bacteremia.

Ochrobactrum anthropi is an oxidase-positive, nonfermenting, gram-negative bacillus that is an emerging pathogen in immunocompromised patients, particularly in those with indwelling central venous catheters. Reports of clinical manifestation of O. anthropi bacteremia are rare. Herein, we report the clinical and microbiologic characteristics of O. anthropi bacteremia in 15 patients. There were eight males and seven females, whose ages ranged from 1 month to 84 years (mean, 34 years). Ten infections were community acquired. All patients had severe underlying disease and manifested primary O. anthropi bacteremia with no obvious focus. Only three patients had central venous catheters in place at the onset of bacteremia, but none of these showed evidence of catheter-related infection. The mean duration of fever was 4 days (range 0-11) and the mean white blood cell count was 13 x 10(9)/L (range 5.5-28 x 10(9)). All O. anthropi isolates tested were resistant to ampicillin, cephalothin, cefonicid, amoxicillin/clavulanic acid, piperacillin, aztreonam, and ceftazidime, and all were susceptible to gentamicin, amikacin, imipenem, ceftriaxone, and cefoperazone. Most were also susceptible to cefotaxime and moxalactam. Monotherapy with an aminoglycoside or an appropriate beta-lactam (such as cefotaxime or ceftriaxone) yielded good clinical response. None of the 15 patients died directly from O. anthropi bacteremia. Our findings indicate that O. anthropi is often community acquired and can be pathogenic in critically ill or immunocompromised patients with or without indwelling catheters. Although O. anthropi can produce clinically significant infections, the organism seems to be of relatively low virulence.

Adolescent↗

Preparation and pharmacological evaluation of physostigmine-loaded polyisobutylcyanoacrylate nanoparticles in rats.

The nanoparticles of physostigmine were prepared by an emulsion polymerization of polyisobutylcyanoacrylate. The drug content, release and particle size distribution of the nanoparticles were characterized. In vitro drug release profiles displayed a retardation by the nanoparticles in comparison to the aqueous solution. Pharmacological evaluation of physostigmine nanoparticles in vivo were carried out with Sprague-Dawley rats. The endogenous acetylcholine was sampled by on-line microdialysis and determined by a sensitive microbore HPLC/ED system in the striatum of rats. The choline oxidase and catalase immobilized enzyme reactors were used as the pre-column to erase choline. Accordingly, this chromatographic flow sequence could be utilized for the quantitative assay of acetylcholine without interference. The results indicate that the increase of acetylcholine (%) in the rats striatum by the nanoparticle was 2.3 times (AUC) higher than that of aqueous solution.

Acetylcholine↗

Incidence and clinical manifestations of Campylobacter enteritis in central Taiwan.

BACKGROUND: Campylobacter species are recognized as a major cause of acute gastroenteritis in humans throughout the world and are increasingly associated with the development of Guillain-Barré syndrome. The age distribution of persons and the seasonal patterns of Campylobacter infection are different in many developed and developing countries. The present study reports the investigation of the clinical and epidemiologic features of Campylobacter infections in central Taiwan. METHODS: From January 1994 to December 1996, stool specimens from patients with diarrhea or gastroenteritis were cultured for the Campylobacter species at the China Medical College Hospital. Data collected and evaluated included the type of Campylobacter species isolated, date of report, age and sex of the person from whom the isolate came, and clinical symptoms. RESULTS: Of 6,540 patients with diarrhea or gastroenteritis, 162 Campylobacter isolates were identified, yielding an isolation rate of 2.5% from the population studied. One hundred and fifty-four patients (95%) with Campylobacter infection were younger than five years old, which was significantly different from the population studied (p < 0.001). The Campylobacter infection was significantly higher in males (62.3%) than females (37.7%) (p = 0.0017). In central Taiwan, the incidence of Campylobacter enteritis is higher during the winter (35.2%) than during the spring (19.1%), summer (24.1%) or fall (21.6%) (35.2 vs 24.1%, p = 0.021). Campylobacter jejuni was found to comprise 81% (132 strains) of 162 Campylobacter isolates, and its isolation rate was significantly higher than Campylobacter lari (10%) and Campylobacter coli (9%) (p < 0.001). From 1994 to 1996, isolation rates of Campylobacter species increased from 1.9 to 2.8% of the population studied (34/1, 754 vs 57/2, 187) and the positive isolation rate ratio of Campylobacter species to Salmonella species also increased from 15.4 to 27.8% (34/221 vs 57/205). However, no significant difference was found between these results (p > 0.05). Watery diarrhea is the most characteristic manifestation of illness, and fever occurs in more than half of the patients. CONCLUSIONS: In central Taiwan, the incidence of Campylobacter enteritis in patients with diarrhea or gastroenteritis is lower than those in China and Tanzania, but the highest prevalence occurs before five years of age in central Taiwan as well as these countries. The Campylobacter infection rate was significantly higher in males than females, and occurred primarily in winter. We conclude that Campylobacter cultures should be performed for fecal specimens of all diarrheal children aged up to five years.

Adolescent↗

Substituted hexahydrobenzo[f]thieno[c]quinolines as dopamine D1-selective agonists: synthesis and biological evaluation in vitro and in vivo.

A series of substituted 9,10-dihydroxyhexahydrobenzo[f]thieno[c]quinolines (TB[f]Q), varying with respect to the position of the thiophene relative to the benzo[f]quinoline core and the nature and position of the substituent on the thiophene, were prepared and evaluated for their affinity and selectivity for the dopamine D1-like receptor. The thieno[3,2-c]B[f]Q regioisomers bearing a small alky1 (C1-C3) substituent at the 2 position were potent (Ki < 20 nM) and selective (D2/D1 > 50) D1 agonists with close to full agonist activity (IA > 85%). The compounds were resolved and found to exhibit a high level of enantiospecificity in their interaction with the D1 receptor. Selected compounds were tested in vivo in the 6-OHDA rodent model of Parkinson's disease and for their liability to produce seizure-like activities in mice. (5aR)-trans-2-Propyl-4,5,5a,6,7, 11b-hexahydro-3-thia-5-azacyclopent-1-ena[c]phenanthrene-9,10-diol (5) emerged as the compound with the best overall in vivo profile in terms of potency (ED50 = 0.04 mumol/kg) and safety.

Adenylyl Cyclases↗

Minor structural differences in Boc-CCK-4 derivatives dictate affinity and selectivity for CCK-A and CCK-B receptors.

We previously reported novel Boc-CCK-4 (Boc-Trp-Met-Asp-Phe-NH2) derivatives possessing the general structure Boc-Trp-Lys[N epsilon-CO-NH-(R-Ph)]-Asp-Phe-NH2 (Shiosaki et al. J. Med. Chem. 1991, 34, 2837-2842). In contrast to Boc-CCK-4, which is 70-fold selective for the CCK-B receptor, the modified lysine-bearing tetrapeptides were highly potent and selective full agonists at the CCK-A receptor. Further investigation of the structure-activity profile following modification of the substituted phenylurea moiety appended off the lysine revealed that moving certain substituents, e.g. nitro or acetyl, from the 2- or 3-position on the phenyl ring to the 4-position, a relatively minor and subtle structural modification within the tetrapeptide, resulted in loss of CCK-A receptor selectivity and development of a trend toward CCK-B selectivity. These tetrapeptides, e.g. Boc-Trp-Lys[N epsilon-CO-NH-(4-NO2-Ph)]-Asp-Phe-NH2 and Boc-Trp-Lys[N epsilon-CO-NH-(4-Ac-Ph)]-Asp-Phe-NH2, were full agonists relative to CCK-8 in stimulating intracellular calcium mobilization in a cell line that expresses the CCK-B receptor.

Cell Line↗

Prevalence and heterogeneity of Helicobacter pylori in gastric biopsies of patients with gastroduodenal diseases.

Helicobacter pylori is a risk factor for development of peptic ulcers and adenocarcinoma of distal stomach. There are several highly specialized virulence factors, such as the production of sialic acid-specific hemagglutinins, cytotoxins and enzymes. This study was designed to study the in vivo prevalence of H. pylori in patients with gastroduodenal diseases, the in vivo correlation between H. pylori infection and blood group O, and the heterogeneity of H. pylori isolates in central Taiwan. We enrolled 776 symptomatic patients residing in the central Taiwan area. The age-specific in vivo prevalence of H. pylori in patients with gastroduodenal diseases increased from 11.1% in those between the ages of 1 to 20, 73.1% in those between the ages of 21 and 30, and to 79.8% in those between the ages of 51 and 60. In conclusion, H. pylori was present in 70% of biopsied specimens of symptomatic patients with gastroduodenal diseases and had the highest incidence (86%) in patients with peptic ulcers. The prevalence of H. pylori cag A expression positive strains in central Taiwan was 92.5%. This study has also demonstrated the high correlation between H. pylori and the blood group O-positive patients with gastroduodenal diseases. The prevalence of H. pylori infection in blood O-positive patients in central Taiwan was 86.4%.

ABO Blood-Group System↗

Evaluation of CLO test and polymerase chain reaction for biopsy-dependent diagnosis of Helicobacter pylori infection.

Helicobacter pylori is now recognized as possibly playing an etiologic role on the development of chronic gastritis, peptic ulcers and adenocarcinoma of the distal stomach. CLO test and polymerase chain reaction (PCR) assay are rapid, biopsy-dependent diagnostic tests for H. pylori identification. In this study, we assessed four diagnostic methods (CLO test, PCR assay, culture and histological examination) for H. pylori detection in biopsy specimens from 78 patients with gastroduodenal diseases and investigating the efficiency of CLO test and PCR assay for the diagnosis of H. pylori infection. H. pylori was identified in 75.6%, 75.6%, 64.1%, 69.2% of patients by CLO test, PCR assay, culture and histological examination, respectively. Compared with the detection of H. pylori by culture and/or histological examination, the sensitivity and specificity of the CLO test were 98.2% and 81.8%, respectively, whereas the sensitivity and specificity of PCR assay were 96.4% and 77.3%, respectively. According to the H. pylori infection state as determined from the results of three concordant tests, the sensitivities of culture, CLO test, histological examination, and PCR assay were 90.9%, 96.4%, 98.2% and 100%, respectively. Whereas, the specificity was 100%, 95%, 95% and 90% for culture, CLO test, histological examination, and PCR assay, respectively. We found that both CLO test and PCR assay were highly sensitive and specific for H. pylori identification; however, PCR assay was more sensitive than other methods for detecting the specimens after patients received treatment. The results of this study suggest that CLO test is a rapid and sensitive method of screening for H. pylori infection and that PCR assay could provide an accurate indication of the state of infection both during treatment for eradication of H. pylori and at follow-up.

Biopsy↗

Agrobacterium radiobacter bacteremia in a patient with chronic obstructive pulmonary disease.

Agrobacterium radiobacter is a gram-negative bacillus, which is recognized as an emerging opportunistic human pathogen. To our knowledge, there have been only 25 cases of A. radiobacter bacteremia reported. In most of these, A. radiobacter was associated with long-term indwelling plastic central venous catheters. We describe a 78-year-old man who had a history of chronic obstructive pulmonary disease with long-term use of a corticosteroid. He was admitted to the China Medical College Hospital with pneumonia caused by Serratia marcescens. His general condition gradually improved after initiation of appropriate treatment. Unfortunately, he developed A. radiobacter bacteremia while hospitalized in the medical intensive care unit. With the onset of this infection, the patient had a high fever, leukocytosis, raised C-reactive protein level, and positive blood cultures for A. radiobacter. A central venous catheter-related infection was suspected because of redness and localized tenderness at the catheter site. The patient gradually recovered after removal of the catheter and appropriate antimicrobial treatment with latamoxef 1.5 g intravenously every 8 hours for 10 days.

Aged↗

The amiloride-sensitive Na+/H+ exchange antiporter and control of intracellular pH in hippocampal brain slices.

The intracellular pH, 7.54 +/- 0.03 (mean +/- S.D., n = 15), determined with the Neutral red method, of the hippocampal brain slice preparation under baseline incubation conditions is considerably more alkaline than the bath buffer pH. Neutralization by amiloride suggests that the alkalinity was due to Na+/H+ exchange antiporter activation. To characterize the brain Na+/H+ exchange antiporter we compared the inhibitory effects of MIA, amiloride and other 5-N substituted analogues on proton extrusion after acid loading by transient exposure to ammonium chloride in the isolated hippocampal brain slice preparation. The potencies of amiloride compounds on the initial recovery rate of intracellular pH after acid-loading were DMA > MIA > HMA = MHA > or = IPA-HCI > IPA > MNPA = Amil > Benzamil. The greater potency of the 5-N substituted analogs of amiloride over amiloride and benzamil strongly suggest that Na+/H+ exchange antiporter is the mechanism responsible for alkalinization in the isolated hippocampal brain slice in vitro.

Acids↗

Human astrocytoma U138MG cells express predominantly type-A endothelin receptor.

Endothelin-1 (ET-1) binding to human astrocytoma U138MG cells was time-dependent, and bound [125I]ET-1 was difficult to dissociate. The B(max) and Kd values of [125I]ET-1 binding were 70 fmol/mg and 0.07 nM, respectively. Interestingly, different from other astrocytoma cells and astrocytes, the U138MG cells expressed predominantly ETA receptor as shown by RT-PCR results and binding studies. ET-1, FR139317, BQ123, PD142893 and Ro46-2005 inhibited specific [125I]ET-1 binding with Ki values of 0.10, 0.53, 4.3, 22, and 320 nM, respectively. ETB selective ligands ET-3 and IRL1620 were much less potent. The inhibitory effects of antagonists BQ123 and PD142893 on [125I]ET-1 binding diminished following the incubation time. ET-1 binding caused a modest stimulation in phosphatidylinositol hydrolysis with an EC50 value of 24 nM. In comparison to the human U373MG cells, ET-1-induced receptor internalization in U138MG cells was less efficient with 42% of bound ET-1 internalized after 30 min of incubation. These results imply that human astrocytoma cells/astrocytes are able to express either ETA or ETB receptor under different pathophysiological conditions.

Astrocytoma↗

Effects of immortalization upon the induction of matrix metalloproteinases in rabbit synovial fibroblasts.

Induction of stromelysin and collagenase mRNAs in response to phorbol myristate acetate (PMA) and autocrine factors (CAF) was compared in primary cultures of lapine synovial fibroblasts and an immortalized line of these cells known as HIG-82. In both cell types, message induction was quicker for CAF than for PMA. Appearance of both stromelysin and collagenase mRNAs occurred earlier in HIG-82 cells and, unlike primary cells, HIG-82 cells partially resisted inhibition by cycloheximide. To determine whether differences in AP-1 activity could account for these observations, the induction of c-fos and c-jun mRNAs was studied in conjunction with gel shift assays for AP-1 binding. Both inducers increased the abundance of c-fos mRNA, although the response was weaker in HIG-82 cells. However, the increase in c-jun mRNA was more marked in HIG-82 cells; furthermore, this increase was sustained for over 6 h. Gel shift assays confirmed that in both types of cells PMA and CAF increased AP-1 binding activity. In primary cells, this activity was sensitive to cycloheximide, but in HIG-82 cells, there was only partial sensitivity to cycloheximide. The gel shift analyses and data from experiments using an AP-1-CAT reporter construct revealed, in many cultures, constitutive AP-1 activity in the absence of stromelysin and collagenase expression, suggesting that AP-1 alone is insufficient for matrix metalloproteinase induction. Antisense oligonucleotides to c-fos and c-jun strongly inhibited the induction of stromelysin mRNA in primary cells treated with PMA, but was only weakly active against message induction in HIG-82 cells. In neither primary cells nor HIG-82 cells did antisense oligonucleotides strongly inhibit stromelysin induction in response to CAF. These data suggest there may exist an AP-1-independent route to message induction or that factors other than c-FOS and c-JUN may be used in certain circumstances. Western blot analyses detected no marked difference between HIG-82 cells and primary cells in their resting levels of c-FOS and c-JUN. Thus the differences reported here between HIG-82 cells and primary cells in their resting levels of c-FOS and c-JUN. Thus the differences reported here between HIG-82 cells and primary cells in the kinetics and cycloheximide sensitivity of MMP induction may reside in their abilities to modify posttranslationally the relevant transcription factors.

Animals↗

A novel 66-kilodalton protein complexes with Rrn6, Rrn7, and TATA-binding protein to promote polymerase I transcription initiation in Saccharomyces cerevisiae.

We report the cloning of RRN11, a gene coding for a 66-kDa protein essential for transcription initiation by RNA polymerase I (Pol I) in the yeast Saccharomyces cerevisiae. Rrn11 specifically complexes with two previously identified transcription factors, Rrn6 and Rrn7 (D. A. Keys, J. S. Steffan, J. A. Dodd, R. T. Yamamoto, Y. Nogi, and M. Nomura, Genes Dev. 8:2349-2362, 1994). The Rrn11-Rrn6-Rrn7 complex also binds the TATA-binding protein and is required for transcription by the core domain of the Pol I promoter. Therefore, we have designated the Rrn11-Rrn6-Rrn7-TATA-binding protein complex the yeast Pol I core factor. A two-hybrid assay was used to demonstrate involvement of short leucine heptad repeats on both Rrn11 and Rrn6 in the in vivo association of these two proteins. This assay also verified the previously described strong association between Rrn6 and Rrn7, independent of the Rrn6 leucine repeat.

Amino Acid Sequence↗

ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson's disease.

(-)-Trans 9,10-hydroxy-2-propyl-4,5,5a,6,7,11b-hexahydro-3-thia-5- azacyclopent-1-ena[c]phenanthrene hydrochloride (A-86929) is a potent and selective full agonist at the dopamine (DA) D1-like receptor. Judging by its binding affinities to the D1 and D2 classes of receptors, the compound is approximately 20-fold D1 receptor-selective, whereas relative potencies based on functional in vitro assays indicate that A-86929 is greater than 400-fold D1-selective. A-86929 has moderate to weak (Ki > 1 microM) affinity at other monoaminergic and peptidergic receptors, at ion channels and at monoamine uptake sites. The catechol of A-86929 was bis-acetylated to produce the prodrug, (-)-trans 9,10-acetoxy-2-propyl-4,5,5a,6,7,11-b-hexahydro-3-thia- 5-azacyclopent-1-ena[c]phenanthrene hydrochloride (ABT-431), which is more chemically stable yet is rapidly converted to the parent compound with a half-life of less than 1 min in plasma. Both A-86929 and ABT-431 produced contralateral rotation in rats bearing unilateral 6-hydroxydopamine lesions, with ED50 values of 0.24 mumol/kg s.c. and 0.54 mumol/kg s.c., respectively. A-86929 and ABT-431 improved behavioral disability scores and increased locomotor activity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmoset model of Parkinson's disease in a dose-dependent manner (the minimum effective dose was 0.10 mumol/kg s.c.). When administered three times daily for 30 consecutive days to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmosets, A-86929 significantly improved disability scores throughout the duration of the study. Current Parkinson's disease therapy includes L-dopa, which stimulates both classes of DA receptors by virtue of its conversion to DA in vivo, and direct-acting D2-selective agonists. Stimulation of the D2 receptor, which is associated with all current DA agonist-based therapies, may contribute to their dose-limiting side effects. An agent such as A-86929 (or its prodrug ABT-431), which selectively stimulates the D1 receptor, may represent a novel mechanism for Parkinson's disease therapy with the potential for an improved side-effect profile and, consequently, improved patient compliance.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Persistent activation of the dopamine D1 receptor contributes to prolonged receptor desensitization: studies with A-77636.

A-77636 is a dopamine (DA) D1 receptor-selective agonist that was previously shown to elicit beneficial responses in animal models of Parkinson's disease (PD) (Kebabian et al.: Eur. J. Pharmacol. 229: 203, 1992). However, A-77636 is of limited potential for PD therapy because it induces rapid tolerance in vivo. To understand the basis of rapid onset of tolerance to the compound, we conducted studies to compare the in vitro properties of A-77636 and A-81686; the latter is a structurally related D1 agonist that did not induce significant tolerance in vivo under similar experimental conditions. With SK-N-MC, a neuroblastoma cell line, as an in vitro model for the D1 receptor, significant differences in D1 receptor function were noted after pretreatment with the two compounds. Specifically, 1-hr pretreatment with A-77636 resulted in significant residual cAMP production, even after the drug solution was removed and the cells were washed. The residual cAMP activity was selectively inhibited by SCH 23390, a selective D1 antagonist. The residual cAMP activity declined with pretreatment time, and after 4-hr pretreatment, little residual cAMP production was observed. Cotreatment of SK-N-MC cells with SCH 23390 and A-77636 did not prevent residual cAMP production by A-77636. In contrast, A-81686 did not elicit residual cAMP production is SK-N-MC cells. Although A-77636 treated cells were devoid of agonist response 4 hr after drug removal, A-81686-treated cells exhibited significant cAMP response after drug removal. Preincubation of rat striatal membranes with A-77636 resulted in a large decrease in D1 receptor binding, despite repeated washings, whereas A-81686 pretreatment caused only a small reduction in D1 receptor binding. On the basis of the present data, we conclude that A-77636 dissociates slowly from the D1 receptor. The continued activation of the D1 receptor by A-77636 leads to inability of the receptor to recover its responsivity, which may explain its long duration of action and its ability to induce rapid behavioral tolerance in vivo.

Adamantane↗

Octopus S-crystallins with endogenous glutathione S-transferase (GST) activity: sequence comparison and evolutionary relationships with authentic GST enzymes.

S-Crystallin is a major protein present in the lenses of cephalopods (octopus and squid). To facilitate the cloning of this crystallin gene, cDNA was constructed from the poly(A)+ mRNA of octopus lenses, and amplified by PCR for nucleotide sequencing. Sequencing of 10 of 15 positive clones coding for this crystallin revealed three distinct S-crystallin isoforms with 61-64% identity in nucleotide sequences and 42-58% similarity in amino acid sequences when compared with homologous crystallins in squid lenses. These charge-isomeric crystallins also show between 26 and 33% amino acid sequence identity to four major classes of glutathione S-transferase (GST), a major detoxification enzyme present in most mammalian tissues. For further analysis, expression of one of the S-crystallin cDNAs was carried out in the bacterial expression system pQE-30, and the S-crystallin protein produced in Escherichia coli was purified to homogeneity to determine the enzymic properties. We found that the expressed octopus S-crystallin possessed much lower GST activity than the authentic GSTs from other tissues. Sequence comparison and construction of phylogenetic trees for S-crystallins from squid and octopus lenses and various classes of GSTs revealed that S-crystallins represent a multigene family which is structurally related to Alpha-class GSTs and probably derived from the ancestral GST by gene duplication and subsequent multiple mutational substitutions.

Amino Acid Sequence↗

Rapid recovery of rat brain intracellular pH after cardiac arrest and resuscitation.

We studied the intracellular pH in rat cerebral cortex of rats subjected to reversible total cerebral ischemia by cardiac arrest and resuscitation. Brain acidoses was more pronounced during ischemia in hyperglycemic rats (6.21 +/- 0.14) than in normoglycemic rats (6.56 +/- 0.07). Brain tissue lactate accumulated proportionally. Nevertheless, within 5 min of reperfusion, pHi in both normoglycemic and hyperglycemic groups had recovered to baseline levels, i.e. near 7.1-7.2, despite the fact that lactate concentrations were still elevated. These results demonstrate a rapid reversal of ischemic acidosis during recovery from 10 min of cardiac arrest, and suggest that acidosis, per se, may not be responsible for neuronal damage following cardiac arrest and resuscitation, even in hyperglycemic conditions.

Acidosis↗