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At least 181 records · Page 10Linked to original sources
PubMed2004

TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are potent inhibitors of human immunodeficiency virus type 1 (HIV-1); however, currently marketed NNRTIs rapidly select resistant virus, and cross-resistance within the class is extensive. A parallel screening strategy was applied to test candidates from a series of diarylpyrimidines against wild-type and resistant HIV strains carrying clinically relevant mutations. Serum protein binding and metabolic stability were addressed early in the selection process. The emerging clinical candidate, TMC125, was highly active against wild-type HIV-1 (50% effective concentration [EC50] = 1.4 to 4.8 nM) and showed some activity against HIV-2 (EC50 = 3.5 microM). TMC125 also inhibited a series of HIV-1 group M subtypes and circulating recombinant forms and a group O virus. Incubation of TMC125 with human liver microsomal fractions suggested good metabolic stability (15% decrease in drug concentration and 7% decrease in antiviral activity after 120 min). Although TMC125 is highly protein bound, its antiviral effect was not reduced by the presence of 45 mg of human serum albumin/ml, 1 mg of alpha1-acid glycoprotein/ml, or 50% human serum. In an initial screen for activity against a panel of 25 viruses carrying single and double reverse transcriptase amino acid substitutions associated with NNRTI resistance, the EC50 of TMC125 was <5 nM for 19 viruses, including the double mutants K101E+K103N and K103N+Y181C. TMC125 also retained activity (EC50 < 100 nM) against 97% of 1,081 recent clinically derived recombinant viruses resistant to at least one of the currently marketed NNRTIs. TMC125 is a potent next generation NNRTI, with the potential for use in individuals infected with NNRTI-resistant virus.

Cell Line↗
PubMed2004

Molecular detection and genotyping of male-specific coliphages by reverse transcription-PCR and reverse line blot hybridization.

In recent years, there has been increased interest in the use of male-specific or F+ coliphages as indicators of microbial inputs to source waters. Sero- or genotyping of these coliphages can also be used for microbial source tracking (MST). Among the male-specific coliphages, the F+ RNA (FRNA) viruses are well studied, while little is known about the F+ DNA (FDNA) viruses. We have developed a reverse line blot hybridization (RLB) assay which allows for the simultaneous detection and genotyping of both FRNA as well as FDNA coliphages. These assays included a novel generic duplex reverse transcription-PCR (RT-PCR) assay for FRNA viruses as well as a generic PCR for FDNA viruses. The RT-PCR assays were validated by using 190 field and prototype strains. Subsequent DNA sequencing and phylogenetic analyses of RT-PCR products revealed the classification of six different FRNA clusters, including the well-established subgroups I through IV, and three different FDNA clusters, including one (CH) not previously described. Within the leviviruses, a potentially new subgroup (called JS) including strains having more than 40% nucleotide sequence diversity with the known levivirus subgroups (MS2 and GA) was identified. We designed subgroup-specific oligonucleotides that were able to genotype all nine (six FRNA, three FDNA) different clusters. Application of the method to a panel of 351 enriched phage samples from animal feces and wastewater, including known prototype strains (MS2, GA, Q beta, M11, FI, and SP for FRNA and M13, f1, and fd for FDNA), resulted in successful genotyping of 348 (99%) of the samples. In summary, we developed a novel method for standardized genotyping of F+ coliphages as a useful tool for large-scale MST studies.

Animals↗
PubMed2006

Cooperation between reverse transcriptase and integrase during reverse transcription and formation of the preintegrative complex of Ty1.

Reverse transcriptase (RT) and integrase (IN) play a central role in the replication and transposition of retroelements. Increasing evidence suggests that the interaction between these two enzymes is functional and plays an important role in replication. In the yeast Saccharomyces cerevisiae retrotransposon Ty1, the interaction of IN with RT is critical for the formation of an active conformation of RT. We show here that the RT associated with VLPs is active only if it is in close interaction with IN. To probe the IN-RT cis-trans relationship, we have used a complementation assay based on coexpressing two transposons. We show that IN acts in cis to activate RT and that a functional integrase provided in trans is not able to complement replication and transposition defects of IN deletion or IN active-site mutant elements. Our data support a model in which IN not only interacts closely with RT during reverse transcription but also remains associated with RT during the formation of the preintegrative complex.

Binding Sites↗
PubMed2002

Insertions in the reverse transcriptase increase both drug resistance and viral fitness in a human immunodeficiency virus type 1 isolate harboring the multi-nucleoside reverse transcriptase inhibitor resistance 69 insertion complex mutation.

Recent studies have shown that the accumulation of multiple mutations associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance may be grouped as multi-NRTI resistance (MNR) complexes. In this study, we have examined the viral fitness of recombinant viruses carrying the reverse transcriptase (RT) of a human immunodeficiency virus type 1 (HIV-1) primary isolate harboring mutations comprising the MNR 69 insertion complex. Different RT mutants were prepared in the sequence context of either the wild-type RT sequence of the HIV-1(BH10) isolate or the sequence found in a clinical HIV-1 isolate with the MNR 69 insertion mutation. As expected, in the presence of zidovudine, recombinant viruses harboring the MNR RT from the patient were more fit than wild-type viruses. However, in the absence of drug, the virus with the RT from the original clinical isolate (SS) was more fit than (i) the wild-type virus with an engineered serine insertion between residues 69 and 70 (T69SSS) and (ii) the recombinant virus with the MNR RT where the insertion was removed (2S0S). These results suggest that RT insertions, in the right sequence context (i.e., additional mutations contained in the MNR 69 insertion complex), enhance NRTI resistance and may improve viral fitness. Thus, comparing complex mutation patterns with viral fitness may help to elucidate the role of uncharacterized drug resistance mutations in antiretroviral treatment failure.

Adult↗
PubMed2003

Human immunodeficiency virus type 2 reverse transcriptase activity in model systems that mimic steps in reverse transcription.

Human immunodeficiency virus type 2 (HIV-2) infection is a serious problem in West Africa and Asia. However, there have been relatively few studies of HIV-2 reverse transcriptase (RT), a potential target for antiviral therapy. Detailed knowledge of HIV-2 RT activities is critical for development of specific high-throughput screening assays of potential inhibitors. Here, we have conducted a systematic evaluation of HIV-2 RT function, using assays that model specific steps in reverse transcription. Parallel studies were performed with HIV-1 RT. In general, under standard assay conditions, the polymerase and RNase H activities of the two enzymes were comparable. However, when the RT concentration was significantly reduced, HIV-2 RT was less active than the HIV-1 enzyme. HIV-2 RT was also impaired in its ability to catalyze secondary RNase H cleavage in assays that mimic tRNA primer removal during plus-strand transfer and degradation of genomic RNA fragments during minus-strand DNA synthesis. In addition, initiation of plus-strand DNA synthesis was much less efficient with HIV-2 RT than with HIV-1 RT. This may reflect architectural differences in the primer grip regions in the p66 (HIV-1) and p68 (HIV-2) palm subdomains of the two enzymes. The implications of our findings for antiviral therapy are discussed.

Base Sequence↗
PubMed2003

Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine.

The methionine-to-valine mutation in codon 184 (M184V) in reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) or simian immunodeficiency virus (SIV) confers resistance to (-)-2'-deoxy-3'-thiacytidine (3TC; lamivudine) and increased sensitivity to 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir). We have used the SIV model to evaluate the effect of the M184V mutation on the emergence of resistance to the combination of 3TC plus PMPA. A site-directed mutant of SIVmac239 containing M184V (SIVmac239-184V) was used to select for resistance to both 3TC and PMPA by serial passage in the presence of increasing concentrations of both drugs. Under these selection conditions, the M184V mutation reverted in the majority of the selections. Variants resistant to both drugs were found to have the lysine-to-arginine mutation at codon 65 (K65R), which has previously been associated with resistance to PMPA in both SIV and HIV. Similarly, in rhesus macaques infected with SIVmac239-184V for 46 weeks and treated daily with (-)-2'-deoxy-5-fluoro-3'-thiacytidine [(-)-FTC], there was no reversion of M184V, but this mutation reverted to 184 M in all three animals within 24 weeks of treatment with (-)-FTC and PMPA. Although the addition of PMPA to the (-)-FTC therapy induced a decrease in virus loads in plasma, these loads eventually returned to pre-PMPA levels in each case. All animals receiving this combination developed the K65R mutation. These results demonstrate that the combination of PMPA with 3TC or (-)-FTC selects for the K65R mutation and against the M184V mutation in SIV RT.

Adenine↗
PubMed2003

Human telomerase reverse transcriptase mRNA expression assessed by real-time reverse transcription polymerase chain reaction predicts chemosensitivity in patients with ovarian carcinoma.

PURPOSE: To evaluate in vivo whether the expression of the human telomerase reverse transcriptase (hTERT) gene, the catalytic subunit of the telomerase complex, is predictive of response to chemotherapy in ovarian cancer patients. PATIENTS AND METHODS: Fifty-nine advanced-stage ovarian cancer patients who were treated with platinum-based chemotherapy were studied. hTERT levels were evaluated by real-time reverse transcriptase polymerase chain reaction (RT-PCR) on tumor specimens obtained before the treatment. Variables were analyzed by the chi(2) and Fisher's exact tests. Logistic regression analysis was also performed to account for the effects of all the covariates investigated (residual disease, stage, histotype, and grade). RESULTS: Twenty-eight (47%) of the 59 tumors showed low hTERT levels, whereas 31 (53%) tumors displayed high hTERT levels. Seventy-five percent of complete responders showed high levels of hTERT expression, whereas 66% of partial responders or nonresponders exhibited low hTERT levels (P =.002). Only residual disease and hTERT expression were independent predictors of response (odds ratios, 13.455 and 7.586, respectively). The combination of these two parameters provides powerful predictive information: 18 of the 20 patients with residual disease more than 2 cm and low hTERT levels were partial responders or nonresponders, whereas 11 of the 12 patients with residual disease less than 2 cm and high hTERT levels showed a complete response (chi(2) = 21,416; P <.00001). CONCLUSION: Our data indicate that hTERT expression, measured by real-time RT-PCR, is a possible independent marker of response to platinum-based therapy in advanced stage ovarian cancer patients. Prospective validation of this marker will be required to further define its predictive value.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Detection of hepatitis C virus and hepatitis G virus RNA by multiplex reverse transcription-polymerase chain reaction and microtiter plate reverse hybridization].

Multiplex reverse transcription-polymerase chain reaction for the simultaneous detection of HCV and HGV RNA has been established, in which primers were deduced from high conservative region of HCV and HGV and PCR amplicons were detected by microtiter plate reverse hybridization with HCV or HGV specific probe. Sequence analyses showed that amplicons of HCV were 93.1%-94.1% and 92.5%-93.7% of nucleotide homology compared with Takamizawa and Choo, and amplicons of HGV were 90.7%-92.5%, 92.0%-92.1% and 94.3%-94.5% of nucleotide homology with Simons, Linnen and Chang. The detective sensitivity was 100 times over that of electrophoretic assay with single amplification. CVs of HCV and HGV were 8.9% and 9.8%, respectively, and the optimal concentration of NaOH for hybridization was 0.1-0.15 mol/L. The optimal time for hybridization was 30-50 minutes. The results of detection with multiplex PCR showed the presence of infection with HCV or HGV alone and coinfection with both % them.

DNA Probes↗
PubMed1991

Structural and functional smooth muscle injury after surgical preparation of reversed and non-reversed (in situ) saphenous vein bypass grafts.

Intimal hyperplasia and isolated stenoses are major factors in determining the long-term patency of reversed and in situ vein grafts. Surgical handling causes functional endothelial damage in reversed vein grafts but the effects of valvulotome use are unknown. Saphenous vein samples were taken after minimal dissection (control), distension with saline, or after the passage of a valvulotome. Rectangular strips of vein were mounted in an organ bath and cumulative noradrenaline (10(-8)-10(-5) M) dose contraction curves were performed. Compared with controls there was a significant reduction in the contractile response of both the distended and valvulotome-prepared veins (P less than 0.05). Histological studies revealed partial endothelial cell loss in the distended group and total endothelial cell loss with patchy necrosis of the smooth muscle in the valvulotome group. These results suggest that the current use of a valvulotome not only renders the valves incompetent but also seriously damages the function of the smooth muscle layer.

Aged↗
PubMed1996

Micropolarity of Reversed Micelles: Comparison between Anionic, Cationic, and Nonionic Reversed Micelles

The interface polarity of benzyl-n-hexadecyldimethylammonium chloride (BHDC) cationic reversed micelles in benzene was studied and compared with those of the anionic systems of sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT) in benzene and hexane. The nonionic reversed micelles of the poly(oxyethylene)n dodecyl ethers type surfactants Brij 30 in benzene, cyclohexane, and decane and C12E5 in hexane, heptane, and decane were also investigated. 1-Methyl-8-oxyquinolinium betaine (QB) was used as optical probe. The influence of surfactant concentration and W = [H2O]/[surfactant] were analyzed as a function of the absorption bands shifts in the visible, B1, and in the UV, B2, and the absorbances ratio of these bands. At W = 0 the polarity sensed in the micelle interfaces of AOT-hexane and AOT-benzene is entirely similar while for BHDC-benzene is quite smaller. The detected interaction between the QB and BHDC may favor the entrance of QB into the oil side of the micelle interface thus sensing a less polar environment. At W >/= 10 once the polar heads of the surfactants are completed hydrated, the anionic as well as the cationic surfactants show the same behavior. The polarity of Brij 30 and C12E5 in the aliphatic hydrocarbons is comparable. However at W = 0 their micropolarity is higher than that of AOT-hexane, showing that the formation of hydrogen bond between QB and the free OH groups of these surfactants is the major factor affecting the microenvironment. In all the studied systems even at the maximum possible W, the polarity sensed by QB never reaches the value of pure water, that is, never reaches the bulk water phase prevailing in the micellar core.

Journal Article↗
PubMed1993

Reversible contractile dysfunction in reversible experimental cardiac allograft rejection: alterations in the beta-receptor-stimulated adenylylcyclase pathway.

Alterations in the beta-adrenergic receptor adenylylcyclase (AC) pathway are well known in heart failure. Previous studies by our group have demonstrated impaired function of the AC pathway and contractile reserve when stimulated with isoproterenol (ISO) or forskolin (F) in cardiac allografts with moderate or severe rejection. To determine if recovery of the AC pathway occurs when rejection is reversed, we used a rat heterotopic heart transplant model. Lewis (L) rats received either isografts or Lewis-Brown Norway (LBN) allografts (ALLO). The hearts were explanted on Day 4 and reimplanted into a recipient syngeneic with the original donor (L to L, LBN to LBN). Grafts were harvested 2 days later and analyzed. Receptor-mediated modulation of AC activity was investigated using ISO, F, and the metabolic inhibitor of AC, R-N6-(2-phenylisopropyl)-adenosine (R-PIA). ISO- and F-mediated stimulation of AC were significantly impaired in ALLO (see Table). CARB and R-PIA remained unchanged. [table: see text] Reimplanted hearts had no histologic evidence of rejection and had normal cAMP production in response to ISO and F. In conclusion, AC alterations are concordant with histologic changes in this reversible model of heart failure. Such alterations may be a component in the contractile dysfunction associated with rejection.

Adenylyl Cyclases↗
PubMed1986

Islet transplants in diabetic Lewis rats prevent and reverse diabetes-induced increases in vascular permeability and prevent but do not reverse collagen solubility changes.

The effects of islet transplantation on diabetes-induced increases in vascular permeability and collagen solubility were examined in new granulation tissue vessels and collagen formed after induction of streptozotocin diabetes in male Lewis rats. Albumin permeation was increased by 50% (p less than 0.001) and collagen solubility was decreased by 50% (p less than 0.001) in granulation tissue from untreated diabetic animals as compared with controls. The islet transplants reversed diabetes-induced vascular permeability increases in tissues formed prior to islet transplantation (tissue to blood isotope ratio = 2.1 +/- 0.1 - SD for controls, 3.2 +/- 0.2 for diabetic rats and 2.0 +/- 0.2 for diabetic rats given islets) and prevented permeability increases in new tissues formed following transplantation (tissue to blood isotope ratio = 2.1 +/- 0.1 for controls, 3.3 +/- 0.8 for diabetic rats and 1.9 +/- 0.2 for diabetic rats given islets). In contrast, while islet transplants prevented diabetes-induced decreased collagen solubility in tissues formed after transplantation (controls = 24%, diabetic rats = 12%, and diabetic rats given islets = 24%), collagen solubility in tissues formed prior to islet transplantation was virtually unaffected. These findings indicate that collagen changes induced by the diabetic milieu are not nearly as readily reversed by normalization of the diabetic milieu as (diabetes-induced) alterations in vascular functional integrity.

Animals↗
PubMed2003

Is reversible posterior leukoencephalopathy with severe hypertension completely reversible in all patients?

Leukoencephalopathy with severe hypertension is a recently described entity in nephrology, with only a few case reports to date in children. We prospectively studied 18 children with severe hypertension to evaluate the clinical features, severity, reversibility, and prognosis. All were subjected to clinical and biochemical tests, magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA). Headache was reported in 16 children, 13 had confusion and drowsiness, 12 had nausea and vomiting, and 9 had visual disturbances, seizure, and dyspnea. Only 2 had focal neurological deficit (1 with right facial palsy and another with right lateral rectus palsy). Of these 18 children, 14 patients had hypertensive retinopathy and 4 had normal fundus. MRI revealed leukoencephalopathic changes in 16 of 18 patients. These changes were bilateral occipito-parietal in 9 patients, diffuse white/gray matter lesion in 2, brain stem hyperintensity in 2, and hemorrhagic lesion in 3. On MRA, 11 of 18 patients had attenuation of cerebral arteries of different degree. On follow-up, MRI findings resolved in all except 3 patients and all patients had normal MRA, except for 1 with persistent minimal attenuation and another with spasm in all vessels. We conclude that leukoencephalopathy with severe hypertension is reversible both clinically and radiologically in the majority of children after the control of hypertension. However, a few patients may have residual damage and may need psychometric analysis and follow-up for neurodevelopmental sequelae.

Adolescent↗
PubMed1975

[Modification of the high frequency of reversion of the nicotonic-2 mutant of Coprinus radiatus. II. Polymorphism of strains with low frequencies of reversion (author's transl)].

The nic2 mutation of Coprinus radiatus is unstable at meiosis. Strains derived from the initial mutant can be divided intto two classes: the "neutral genomes" which all revert at meiosis with different frequencies but in an autonomous way; and the "aggressive genomes", which inhibit the reversion of neutral genomes, present a large polymorphism in their own reversion and lose their aggressiveness at meiosis, becoming neutral genomes. The characteristics and the relationships of these two strains are presented in this paper.

Agaricales↗
PubMed1989

Microtubules, organelle transport, and steroidogenesis in cultured adrenocortical tumor cells. 2. Reversibility of taxol's inhibition of basal and ACTH-induced steroidogenesis is unaccompanied by reversibility of taxol-induced changes in cell ultrastructure.

Taxol inhibits the basal and ACTH-stimulated steroidogenesis of cultured mouse adrenocortical tumor cells, presumably by preventing the arrival of cholesterol in mitochondria. In these cells, taxol polymerizes and rearranges microtubules, disperses SER masses, disrupts the Golgi, and impedes the formation of cholesterol-containing lysosomes. However, taxol's alterations in ultrastructure appear likely to permit both a microtubule-based organelle transport proposed to bring mitochondria of unstimulated cells close to alternate sources of cholesterol--the SER and lipid droplets--and postulated ACTH-caused increases in these encounters. Conceivably, taxol may prevent the transfer of cholesterol from the SER and lipid droplets to mitochondria, once the meetings are achieved. To investigate this possibility, we determined the reversibility of taxol's ultrastructural effects and inhibition of steroidogenesis. Primary cultured adrenal tumor cells were incubated for 4 hr with and without ACTH (10 mU/ml). with taxol (50 micrograms/ml), and with ACTH and taxol 50 simultaneously. Some cultures from each set were washed with fresh medium and re-incubated for 1.5 hr. with and without ACTH. Media taken from cultures at the ends of pre- and post-washout incubations were analyzed for the presence of secreted steroids. Sample cultures were fixed for electron microscopy at the ends of both incubations. Data derived from pre-washout incubations confirmed previous reports of taxol's ultrastructural changes and inhibition of steroidogenesis. When cells recovered from taxol in the absence of ACTH, the inhibition of steroidogenesis was completely reversed. In the presence of ACTH, ex-taxol-treated cells demonstrated a "rounding up' and an increased steroid production that are characteristic responses to the hormone. However, in all cases, there was a persistence of taxol's alterations in organelle numbers and arrangements. Our findings establish that the ultrastructural effects of taxol which we recorded cannot prevent mitochondria of unstimulated and ACTH-stimulated adrenal tumor cells from gaining cholesterol. They strengthened the possibility that in pre-washout incubations, taxol allowed organelle motility to bring mitochondria adjacent to cholesterol-containing SER tubules and lipid droplets, but inhibited steroidogenesis by preventing the cholesterol transfer. Taxol might limit the availability of a protein required for the transfer, an effect not visible in our electron micrographs.

Adrenal Cortex Hormones↗
PubMed1992

Characterisation of visna virus reverse transcriptase: a micro scale reverse transcriptase assay adapted for use with an automated cell harvester.

The reverse transcriptase of the sheep lentivirus visna/maedi virus has been characterised. Optima for magnesium ion concentration (5-10 mM), potassium ion concentration (150 mM) and pH (8.25) for this enzyme are very similar to those previously described for the human immunodeficiency viruses. The assay used for this work makes use of a cell harvester to speed up the processing of multiple samples. It is small scale, requiring 15 microliters of sample, is rapid, and is able to detect virus at titres below 10(3)/ml. Harvesting the assay onto either DEAE paper or using TCA and glass fibre mats make it suitable for use with either tissue culture media or infected cell lysates, but not with body fluids. It has been used to detect cell-associated reverse transcriptase in choroid plexus cells within 36 h of visna infection.

Animals↗
PubMed1993

Protein-protein interactions in reverse micelles: trypsin shows superactivity towards a protein substrate alpha-chymotrypsinogen A in reverse micelles of sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in isooctane.

Protein-protein interactions in reverse micelles of sodium bis(2-ethylhexyl)sulfosuccinate (AOT), in isooctane containing varying amounts of Tris buffer are studied by using activation of alpha-chymotrypsinogen A by trypsin (EC 3.4.21.4) to alpha-chymotrypsin (EC 3.4.21.1) as a model reaction. It has been found that protein-protein interactions are strongly dependent on the water content of the medium. At an optimum water content the activation reaction in reverse micelles is faster than reaction in water by a factor of 21.3. At lower water content both reaction rates and the conversion of alpha-chymotrypsinogen A into alpha-chymotrypsin decrease with decrease in water content of the reaction medium.

Catalysis↗
PubMed2005

Effect of intensive lipid lowering on progression of coronary atherosclerosis: evidence for an early benefit from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial.

Statins reduce both atherogenic lipoproteins and high-sensitivity C-reactive protein (hsCRP). The optimal strategy for administration of lipid-lowering agents has evolved considerably during the past 2 years. Several studies have compared the effects of intensive versus moderate lipid lowering in secondary prevention of coronary events. The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study was a double-blind, randomized trial comparing the effect that 2 different statins, administered for 18 months, had on atherosclerotic burden measured by intravascular ultrasound (IVUS). At 34 centers in the United States, 654 patients were randomized to moderate lipid lowering using pravastatin 40 mg or intensive treatment with atorvastatin 80 mg. IVUS was performed during baseline catheterization and repeated after 18 months of treatment. Efficacy parameters included changes in atheroma burden determined by IVUS, lipoprotein levels, and CRP levels. Baseline low-density lipoprotein (LDL) cholesterol (mean, 3.9 mmol/L [150.2 mg/dL]) levels were reduced to 2.8 mmol/L (110 mg/dL) in the pravastatin 40-mg group compared with 2.0 mmol/L (79 mg/dL) in the atorvastatin 80-mg arm (p <0.0001). CRP decreased 5.2% with pravastatin and 36.4% with atorvastatin (p <0.0001). Changes in atheroma burden showed a significantly lower progression rate in the intensive arm for all 3 prespecified IVUS efficacy measures. For all IVUS end points, progression occurred in the moderate-treatment cohort. However, plaque volume was unchanged in the intensive arm, indicating absence of progression. Post hoc analyses demonstrated that greater reductions in both lipid levels and hsCRP were associated with slower disease progression. The slowest progression occurred in patients with above-median reductions in both LDL cholesterol and CRP. For patients with coronary artery disease, intensive treatment with atorvastatin 80 mg reduced progression of coronary atherosclerosis compared with a more moderate regimen consisting of pravastatin 40 mg. Compared with baseline, intensively treated patients had no change in atheroma burden, whereas moderately treated patients showed progression. These differences are related to the greater reduction in atherogenic lipoproteins and CRP in intensively treated patients.

Atorvastatin↗