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Biomedical subjects

B Li

Publications and source records attributed to B Li.

At least 217 records · Page 12Linked to original sources
PubMed2000

DRG represents a family of two closely related GTP-binding proteins.

In a previous publication we identified a novel human GTP-binding protein that was related to DRG, a developmentally regulated GTP-binding protein from the central nervous system of mouse. Here we demonstrate that both the human and the mouse genome possess two closely related drg genes, termed drg1 and drg2. The two genes share 62% sequence identity at the nucleotide and 58% identity at the protein level. The corresponding proteins appear to constitute a separate family within the superfamily of the GTP-binding proteins. The DRG1 and the DRG2 mRNA are widely expressed in human and mouse tissues and show a very similar distribution pattern. The human drg1 gene is located on chromosome 22q12, the human drg2 gene on chromosome 17p12. Distantly related species including Caenorhabditis elegans, Schizosaccharomyces pombe and Saccharomyces cerevisiae also possess two drg genes. In contrast, the genomes of archaebacteria (Halobium, Methanococcus, Thermoplasma) harbor only one drg gene, while eubacteria do not seem to contain any. The high conservation of the polypeptide sequences between distantly related organisms indicates an important role for DRG1 and DRG2 in a fundamental pathway.

Amino Acid Sequence↗
PubMed2000

Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression.

Previously we reported that proteasome inhibitors were able to overcome Bcl-2-mediated protection from apoptosis. Here we show that inhibition of the proteasome activity in Bcl-2-overexpressing cells accumulates the proapoptotic Bax protein to mitochondria/cytoplasm, where it interacts to Bcl-2 protein. This event was followed by release of mitochondrial cytochrome c into the cytosol and activation of caspase-mediated apoptosis. In contrast, proteasome inhibition did not induce any apparent changes in Bcl-2 protein levels. In addition, treatment with a proteasome inhibitor increased levels of ubiquitinated forms of Bax protein, without any effects on Bax mRNA expression. We also established a cell-free Bax degradation assay in which an in vitro-translated, (35)S-labeled Bax protein can be degraded by a tumor cell protein extract, inhibitable by addition of a proteasome inhibitor or depletion of the proteasome or ATP. The Bax degradation activity can be reconstituted in the proteasome-depleted supernatant by addition of a purified 20S proteasome or proteasome-enriched fraction. Finally, by using tissue samples of human prostate adenocarcinoma, we demonstrated that increased levels of Bax degradation correlated well with decreased levels of Bax protein and increased Gleason scores of prostate cancer. Our studies strongly suggest that ubiquitin/proteasome-mediated Bax degradation is a novel survival mechanism in human cancer cells and that selective targeting of this pathway should provide a unique approach for treatment of human cancers, especially those overexpressing Bcl-2.

Adenosine Triphosphate↗
PubMed2000

Homologous expression of recombinant cellobiose dehydrogenase in Phanerochaete chrysosporium.

Cellobiose dehydrogenase (CDH) is a novel extracellular hemoflavoenzyme from Phanerochaete chrysosporium and is produced only in cultures supplemented with cellulose. In this report, CDH from P. chrysosporium has been homologously expressed in cultures supplemented with glucose as the sole carbon source when no endogenous CDH is expressed. This was achieved by placing the cdh-1 gene under the control of the D-glyceraldehyde-3-phosphate dehydrogenase (gpd) promoter (1.1 kb) fused upstream of the ATG start codon of cdh-1. The gpd promoter-chd-1 construct was inserted into the multiple cloning site of the expression vector pOGI18, which contained the Schizophyllum commune ade5 as a selectable marker. The P. chrysosporium ade1 auxotrophic strain OGC107-1 was transformed with the pAGC1 construct, and the prototrophic transformants were assayed for CDH activity. Approximately 50% of the Ade(+) transformants exhibited CDH activity in the extracellular medium of stationary cultures. At least one of the transformants produced high levels (500-600 U/liter) of recombinant CDH (rCDH). Purification by ammonium sulfate precipitation, Sephacryl S-200 chromatography, and FPLC using a Mono-Q 5/5 column yielded homogeneous rCDH. Physical, spectral, and kinetic characteristics of purified homologously expressed rCDH were similar to those of wild-type CDH. This expression system will enable site-directed mutagenesis studies to be carried out on CDH.

2,6-Dichloroindophenol↗
PubMed2000

Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage.

Hypertension, a remediable risk factor for stroke, cardiovascular disease, and renal failure, affects 50 million individuals in the United States alone. African Americans (blacks) have a higher incidence and prevalence of hypertension and hypertension-associated target organ damage compared with Caucasian Americans (whites). Herein, we explored the hypotheses that transforming growth factor-beta(1) (TGF-beta(1)) is hyperexpressed in hypertensives compared with normotensives and that TGF-beta(1) overexpression is more frequent in blacks compared with whites. These hypotheses were stimulated by our recent demonstration that TGF-beta(1) is hyperexpressed in blacks with end-stage renal disease compared with white end-stage renal disease patients and by the biological attributes of TGF-beta(1), which include induction of endothelin-1 expression, stimulation of renin release, and promotion of vascular and renal disease when TGF-beta(1) is produced in excess. TGF-beta(1) profiles were determined in black and white hypertensive subjects and normotensive controls and included circulating protein concentrations, mRNA steady-state levels, and codon 10 genotype. Our investigation demonstrated that TGF-beta(1) protein levels are highest in black hypertensives, and TGF-beta(1) protein as well as TGF-beta(1) mRNA levels are higher in hypertensives compared with normotensives. The proline allele at codon 10 (Pro(10)) was more frequent in blacks compared with whites, and its presence was associated with higher levels of TGF-beta(1) mRNA and protein. Our findings support the idea that TGF-beta(1) hyperexpression is a risk factor for hypertension and hypertensive complications and provides a mechanism for the excess burden of hypertension in blacks.

Black or African American↗
PubMed2000

On-line coupling of subcritical water extraction with high-performance liquid chromatography via solid-phase trapping.

Although ambient water is very polar and cannot dissolve many organic species, water at elevated temperatures behaves like a polar organic solvent. Thus, subcritical water has been proven to be an effective extraction fluid for several classes of organic compounds. While solvent trapping was used to collect the extracted analytes in most of previous subcritical water extractions, sorbent trapping has also been developed for subcritical water extraction. In this study, an on-line system for subcritical water extraction and high-performance liquid chromatography (HPLC) was built and tested. A sorbent trap was used as the interface between subcritical water extraction and HPLC. Several shut-off valves have been utilized to switch the system from one mode to another (e.g., from the extraction mode to HPLC mode). The coupling technique of subcritical water extraction and HPLC eliminates the liquid-liquid extraction used in solvent trapping subcritical water extraction and provides higher sensitivity. Compared to the off-line system reported in an earlier work, the operation of this on-line system is even easier. Some peak broadening occurred after the coupling the water extraction with HPLC for the analytes studied. The performance of this on-line system was evaluated by the extraction and determination of caffeine, nitrotoluenes, polychlorinated biphenyls, chlorophenols and anilines.

Aniline Compounds↗
PubMed2000

Photocrosslinking of benzophenone-labeled single cysteine troponin I mutants to other thin filament proteins.

The interaction sites of rabbit skeletal troponin I (TnI) with troponin C (TnC), troponin T (TnT), tropomyosin (Tm) and actin were mapped systematically using nine single cysteine residue TnI mutants with mutation sites at positions 6, 48, 64, 89, 104, 121, 133, 155 or 179 (TnI6, TnI48 etc.). Each mutant was labeled with the heterobifunctional photocrosslinker 4-maleimidobenzophenone (BP-Mal), and incorporated into the TnI.TnC binary complex, the TnI.TnC.TnT ternary troponin (Tn) complex, and the Tn.Tm.F-actin synthetic thin filament. Photocrosslinking reactions carried out in the presence and absence of Ca(2+) yielded the following results: (1) BP-TnI6 photocrosslinked primarily to TnC with a small degree of Ca(2+)-dependence in all the complex forms. (2) BP-TnI48, TnI64 and TnI89 photocrosslinked to TnT with no Ca(2+)-dependence. Photocrosslinking to TnC was reduced in the ternary versus the binary complex. BP-TnI89 also photocrosslinked to actin with higher yields in the absence of Ca(2+) than in its presence. (3) BP-TnI104 and TnI133 photocrosslinked to actin with much higher yields in the absence than in the presence of Ca(2+). (4) BP-TnI121 photocrosslinked to TnC with a small degree of Ca(2+)-dependence, and did not photocrosslink to actin. (5) BP-TnI155 and TnI179 photocrosslinked to TnC, TnT and actin, but all with low yields. All the labeled mutants photocrosslinked to TnC with varying degrees of Ca(2+)-dependence, and none to Tm. These results, along with those published allowed us to construct a structural and functional model of TnI in the Tn complex: in the presence of Ca(2+), residues 1-33 of TnI interact with the C-terminal domain hydrophobic cleft of TnC, approximately 48-89 with TnT, approximately 90-113 with TnC's central helix, approximately 114-125 with TnC's N-terminal domain hydrophobic cleft, and approximately 130-150 with TnC's A-helix. In the absence of Ca(2+), residues approximately 114-125 move out of TnC's N-terminal domain hydrophobic cleft and trigger the movements of residues approximately 89-113 and approximately 130-150 away from TnC and towards actin.

Actins↗
PubMed2000

Comparison of three treatment options for single brain metastasis from lung cancer.

Whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and the combination of both treatment methods were used for the management of single brain metastasis from lung cancer. The purpose of this study is to compare these three different treatment options in terms of local response, survival, and quality of life. From June 1995 to July 1998, 70 lung cancer patients with new diagnosed single brain metastasis were treated with either WBRT alone (n = 29), or SRS alone (n = 23), or the combination of both methods (n = 18). Multiple endpoints, including survival, freedom from local progression (FFLP), freedom from new brain metastasis (FFNBM), local control, Karnofsky performance status (KPS), and causes of death, were measured from the date of treatment completion and compared using univariate and multivariate analyses. For patients treated with WBRT-alone, SRS-alone, and SRS+WBRT, the median survivals were 5.7, 9.3, and 10.6 months, the median FFLP were 4.0, 6.9, and 8.6 months, the median FFNBM were 4.1, 6.7, and 8.6 months, and the local response rates were 55.6, 87.0, and 88.9%, respectively. Four of the 29 patients treated with WBRT-alone continued with progression of disease. The post treatment KPS showed improvement in 41.4, 82.6, and 88.9% of patients treated with WBRT-alone, SRS-alone, and SRS+WBRT, respectively. The progression of new and/or recurred metastatic brain tumor as the cause of death accounted for 51.7%, 50. 0%, and 28.3% of the patients treated with WBRT-alone, SRS-alone, and SRS+WBRT, respectively. Univariate analyses showed that the significant differences among the three treatment arms were observed based on all of the above mentioned endpoints. However, the comparison between SRS-alone and SRS+WBRT groups indicated that adding WBRT only improves FFNBM (P = 0.0392). Cox regression analyses revealed no significant difference in both of the KPS (P = 0.1082) and causes of death (P = 0.081) among the three arms. Both SRS alone and SRS+WBRT seem better in prolonging life and improving quality of life than WBRT alone for patients with single brain metastasis from lung cancer. But the combined therapy did not show significant advantage over SRS alone in improving survival, enhancing local control, and quality of life except for a more favorable FFNBM. Further investigation via a randomized trial is needed to access the value of adding WBRT to SRS in the management of this group of patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 37-45 (2000).

Adult↗
PubMed2000

TNF-alpha induced over-expression of GFAP is associated with MAPKs.

Increased levels of tumor necrosis factor-alpha (TNF-alpha), a pluripotent cytokine that is reportedly mitogenic to astrocytes, are associated with the expression of glial fibrillary acidic protein (GFAP), the most specific marker for astrocytes, in many neuropathological conditions, including brain injury, CNS infection, Creutzfeldt-Jakob disease and Alzheimer's disease. Here, we show that treatment of cultured astrocytes with TNF-alpha resulted in dramatic over-expression of GFAP, associated with a substantial activation of the mitogen activated protein kinase (MAPK) Erk2 (extracellular signal-regulated protein kinase). We also demonstrate that TNF-alpha-induced over-expression of GFAP was significantly attenuated by the MAPK inhibitor PD98059. We conclude that TNF-alpha may upregulate GFAP through the MAPK signaling pathway. Because increased GFAP is a hallmark of reactive gliosis, understanding the mechanisms that regulate GFAP expression may facilitate development of strategies to minimize the gliosis associated with many brain diseases.

Animals↗
PubMed2000

The RDP (Ribosomal Database Project) continues.

The Ribosomal Database Project (RDP-II), previously described by Maidak et al., continued during the past year to add new rRNA sequences to the aligned data and to improve the analysis commands. Release 7.1 (September 17, 1999) included more than 10 700 small subunit rRNA sequences. More than 850 type strain sequences were identified and added to the prokaryotic alignment, bringing the total number of type sequences to 3324 representing 2460 different species. Availability of an RDP-II mirror site in Japan is also near completion. RDP-II provides aligned and annotated rRNA sequences, derived phylogenetic trees and taxonomic hierarchies, and analysis services through its WWW server (http://rdp.cme.msu.edu/ ). Analysis services include rRNA probe checking, approx-i-mate phylogenetic placement of user sequences, screening user sequences for possible chimeric rRNA sequences, automated alignment, production of similarity matrices and services to plan and analyze terminal restriction fragment length polymorphism (T-RFLP) experiments.

Databases, Factual↗
PubMed2000

Lyophilization of cationic lipid-protamine-DNA (LPD) complexes.

Cationic lipid-based gene delivery systems have shown promise in transfecting cells both in vitro and in vivo. However, these systems tend to form aggregates in liquid formulation during storage, which has limited their clinical applications. As a result, lyophilization of these systems has recently become a subject of increasing interest. In this paper, lyophilization of LPD, a novel cationic lipid-based gene delivery system, was studied. Both particle size and transfection efficiency could be preserved in the presence of sufficient amount of appropriate lyoprotectant. A series of monosaccharides and disaccharides, including dextrose, galactose, mannose, lactose, maltose, sucrose and trehalose, were evaluated for their lyoprotective effect and disaccharides showed more superior protection to monosaccharides. The effect of different freezing protocols for lyophilization was also evaluated and no significant difference was found. However, for freeze-thawing, fast freezing caused less aggregation. Finally, nonlyophilized LPD and LPD lyophilized with 10% sucrose were stored at different temperatures and their stability was followed for eight weeks. Lyophilized LPD could be stored at room temperature without significant change in particle size or loss of transfection efficiency.

Animals↗
PubMed2000

N36, a synthetic N-terminal heptad repeat domain of the HIV-1 envelope protein gp41, is an activator of human phagocytes.

Human immunodeficiency virus type 1 (HIV-1) envelope protein gp41 mediates viral fusion with human host cells. In this study we show that N36, a synthetic peptide derived from the N-terminus of gp41, induced directional migration and calcium mobilization in human monocytes and neutrophils. The activity of N36 on phagocytes was pertussis toxin sensitive, suggesting involvement of a Gi-coupled seven-transmembrane receptor(s). Since high concentrations of the bacterial chemotactic peptide fMet-Leu-Phe (fMLF) partially desensitized the calcium mobilizing activity of N36 in phagocytes, we postulated that N36 might use a low-affinity fMLF receptor. By using cells stably expressing fMLF receptor FPR or FPRL1, we demonstrate that N36 uses FPRL1 as a functional receptor. Our results suggest that HIV-1 gp41 may contain a fragment(s) that activates the innate host immune cells through FPRL1. Since the activation of FPRL1 in monocytes has been shown to heterologously desensitize chemokine receptors, the reduced phagocyte response to chemoattractants seen in AIDS patients may be attributed, at least in part, to heterologous desensitization.

Anti-HIV Agents↗
PubMed2000

SCF, IL-1beta, IL-1ra and GM-CSF in the bone marrow and serum of normal individuals and of AML and CML patients.

This study compared cytokine transcript and protein levels in BM cells of normal individuals and leukemic patients. AML differed from normal in that: (1) AML marrow cells contain more IL-1beta protein than normal cells, (2) IL-1ra transcripts are absent from AML marrow cells, (3) AML marrow serum contains less IL-1ra protein than normal, (4) peripheral blood and marrow serum of AML patireents contains more SCF protein than normal serum, and (5) SCF transcripts have been detected in AML marrow biopsies and not in aspirate cells. These data suggest that unbalanced cytokine production may make a significant contribution to the abnormal behaviour of AML cells.

Biopsy↗
PubMed2000

Signal transduction mechanisms involved in ischemic preconditioning in the rat retina in vivo.

Ischemic preconditioning (IPC) protects the rat retina against the injury that ordinarily follows severe ischemia. We showed previously that release of adenosine and de novo protein synthesis were required for IPC protection. The mechanisms of IPC were studied in the rat retina by examining the signal transduction mediators responsible, in particular, those theorized to be downstream of adenosine receptors. In addition, we examined the hypothesis that nitric oxide and hydroxyl radicals were involved in the IPC protective phenomenon. Retinal ischemia was produced for 60 min in ketamine/xylazine-anesthetized Sprague-Dawley rats, and recovery was measured using electroretinography. We tested the effects on the protective effect of IPC resulting from antagonism of protein kinase C, potassium ATP channels, nitric oxide synthase, or hydroxyl radicals. The effects of the inhibition of de novo protein synthesis or of protein kinase C, and blockade of potassium ATP channels on the mimicking of IPC by adenosine receptor agonists was examined.IPC protection was strongly attenuated by inhibition of protein kinase C and by blockade of potassium ATP channels, but unaffected by the inhibition of hydroxyl radicals. Blockade of nitric oxide synthase produced a trend toward enhancement of IPC protection. Mimicking of IPC protection by adenosine receptor agonists was inhibited by blockade of protein synthesis or of protein kinase C, as well as by potassium ATP channel antagonism. These results demonstrate that protein kinase C and potassium ATP channels are mediators of the protective effect produced by IPC. In addition, the results show that stimulation of adenosine receptor subtypes A1 and A2a is responsible for IPC protection via downstream stimulation of protein kinase C, the opening of potassium ATP channels, and de novo protein synthesis.

Adenosine↗
PubMed2000

Rat beta 1-adrenergic receptor regulatory region containing consensus AP-2 elements recognizes novel transactivator proteins.

beta 1-Adrenergic receptors (beta1-ARs) serve as important regulators of central nervous system (CNS)-mediated behavior and several neural functions, including mood, memory, neuroendocrine control, and stimulation of autonomic function. Using beta 1-AR-luciferase reporter recombinants, we have previously determined that important beta 1-AR genetic elements controlling expression within the C6 glioma cell line are contained within the region -396 to -299, relative to the translational start site. By conducting progressive internal deletions of the rat beta 1-AR 5' flanking region and with the use of beta 1-AR-luciferase recombinants, we have verified that this region contains the primary beta 1-AR promoter and/or major regulatory elements. To begin the identification of protein factors involved in beta 1-AR transcriptional activity conferred by this beta 1-AR region and flanking sequences, we conducted electrophoretic mobility shift assays using defined beta 1-AR DNA subregion probes. One probe (GS-1), encompassing the region -396 to -367, was found to produce two major and two minor mobility shift complexes when bound to nuclear extracts from the beta 1-AR expresser C6 cell line. UV-crosslinking of DNA-protein complexes, coupled with DNase I digestion, indicated that this beta 1-AR region interacts with one major protein of approximately 117 kDa molecular weight and additional minor proteins. GS-1 DNA-protein complexes were observed using beta 1-AR expresser tissues in the CNS, including cortex, hippocampus, and olfactory bulb. No DNA-protein complexes were observed when using nuclear extracts from beta 1-AR nonexpresser tissues; in some cases, using L6 cells, previously characterized to express little or no beta1-ARs, a reduction in intensities of the DNA-protein complexes was observed. Competition experiments indicate that nuclear protein binds to one of two subregions within the GS-1 sequence that contain AP-2-like consensus elements. Recombinant AP-2 protein will bind to both the beta 1-AR GS-1 promoter fragment and commercially available AP-2 consensus element control probes. Interestingly, using antibody supershift and immunoblotting experiments, no supershifts were observed and the major 117-kDa protein was not immunoreactive to antibodies recognizing either AP-2 alpha or AP-2 beta. These results support our contention that this beta 1-AR regulatory region contains AP-2 consensus elements that recognize novel transactivator proteins.

Animals↗
PubMed2000

Up-regulation of AT(1) and AT(2) receptors in postinfarcted hypertrophied myocytes and stretch-mediated apoptotic cell death.

To determine whether up-regulation of AT(1) and AT(2) receptors occurred in hypertrophied myocytes after infarction and whether AT(2) played a role in stretch-mediated apoptosis, left ventricular myocytes were dissociated from the surviving portion of the wall 8 days after coronary occlusion and cardiac failure in rats. Control cells were obtained from sham-operated animals. Myocytes were stretched in an equibiaxial stretch apparatus and angiotensin II (Ang II) formation and cell death were measured 3 and 12 hours later. AT(1) and AT(2) proteins were evaluated in freshly isolated myocytes and after stretch. The effects of AT(1) and AT(2) antagonists on stretch-induced Ang II synthesis and apoptosis were also established. Myocardial infarction increased AT(1) and AT(2) in myocytes and stretch further up-regulated these receptors. Ang II levels were higher in postinfarcted myocytes and this peptide increased with the duration of stretch in both groups of cells. Similarly, apoptosis increased with time in control and postinfarcted myocytes. Absolute values of Ang II and apoptosis were greater in myocytes from infarcted hearts at 3 and 12 hours after stretch. Addition of AT(1) blocker to cultures inhibited stretch-activated apoptosis in both myocyte populations as well as the generation of Ang II in postinfarcted myocytes. In contrast, AT(2) antagonists had no impact on these cellular events. In conclusion, Ang II stimulated cell death through AT(1) receptor activation, whereas ligand binding to AT(2) receptor did not alter Ang II concentration and apoptosis in normal and postinfarcted hypertrophied myocytes.

Angiotensin II↗
PubMed2000

Further evaluation on long-term depot-medroxyprogesterone acetate use and bone mineral density: a longitudinal cohort study.

Cross-sectional studies on the effects of depot-medroxyprogesterone acetate (DMPA) on bone mineral density (BMD) have been controversial. The present longitudinal cohort study on 59 Chinese women over a period of 3 years has shown that their annual rate of bone loss at 3 sites (0.44% in lumbar spine, 0.40% in neck of femur, 1.05% in Ward's triangle) was substantially less than the projected values (1.1% in lumbar spine, 2.3% in neck of femur, 3.5% in Ward's triangle) in a cross-sectional study that had demonstrated a significant reduction in BMD in DMPA users than the non-user population. The trochanter BMD measurement did not show the projected annual bone loss of 2.4%. The rate of bone loss is probably non-linear, with a rapid loss in the first 5 years and a leveling off afterwards. The duration of DMPA use was not significantly correlated with the rate of bone loss. Multiple linear regression analysis demonstrated that age and body mass index were significant variables in modeling the rate of bone loss in the lumbar spine and neck of femur, but not in the trochanter and Ward's triangle areas. The Z scores also suggested a retardation in bone loss with time and potentially due to the effect of progesterone in decreasing bone turnover that is similar to the situation in postmenopausal women. The present data provide another aspect of reassurance to the long-term use of DMPA.

Adult↗
PubMed2000

Increased optic nerve head blood flow after 1 week of twice daily topical brinzolamide treatment in Dutch-belted rabbits.

OBJECTIVES: Using a three-way crossover study design, we compared the effects of brinzolamide 2%, dorzolamide 2%, and placebo (vehicle) on microvascular optic nerve head (ONH) blood flow, intraocular pressure (IOP), blood pressure, heart rate, and acid-base balance in nine acepromazine-tranquilized Dutch-belted rabbits. METHODS: Baseline measurements were taken before treatment and after drug-free washout periods of 7-14 days. Microvascular ONH blood flow was measured with a fundus camera-based laser Doppler flowmeter (LDF). Intraocular pressure was measured with a Tono-Pen XL. One drop of brinzolamide, dorzolamide, or vehicle was administered twice daily (9 A.M. and 5 P.M.) in right eyes only for 7 days. Experimental measurements were made 90 minutes after the 9 A.M. topical dose was administered on day 8. RESULTS: ONH blood flow was significantly increased (P< or =0.05) in carbonic anhydrase inhibitor (CAI)-treated rabbits, as compared with vehicle-treated controls. The percent increase from baseline was 11.2+/-1.8% in brinzolamide-treated animals and 8.4+/-4.3% in dorzolamide-treated animals. Compared with controls, IOP in the brinzolamide- and dorzolamide-treated groups was significantly decreased (P< or =0.05). The changes in ONH blood flow and IOP were not significantly different between the CAI treatment groups. Small but significant changes in systemic blood gas tensions and pH were present in both CAI treatment groups, as compared with the vehicle group. Systemic blood pressure and heart rate were not significantly changed. CONCLUSIONS: Topical ocular CAI treatment for 1 week with either brinzolamide or dorzolamide significantly reduced IOP and significantly increased ONH blood flow in tranquilized Dutch-belted rabbits, while eliciting minimal systemic acid-base balance disturbances.

Animals↗