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The Wollastonite Skarn northeast of Pitcairn has been a productive locality for mineral collectors for nearly 140 years. It is still an active fee locality and one worth visiting. We have detailed ...

Warwickite has been discovered in the Edwards and Balmat #3 mines in the Balmat-Edwards mining district, St. Lawrence County, New York, located in the Adirondack Lowlands. The samples from the two mines are similar in chemistry and atomic arrangement but differ chemically from previously described samples; they are among the most Fe-poor samples described to date. The warwickite in the Edwards Mine sample occurs as 1–2 mm-diameter green crystals associated with pink spinel, forsterite, phlogopite, and pyrite in an impure dolomitic marble, whereas warwickite in the specimens from the Balmat #3 mine, approximately 10 km distant, occurs as brown to amber colored, slender, elongate, millimeter-size crystals in a calcitic marble in association with pink spinel, phlogopite, anhydrite, pyrite, and galena. Chemical analyses of the two specimens by electron microprobe show similar empirical formulas of (Mg1.43Ti0.36Al0.18Cr3+0.02Zr0.01)Σ2.00B0.98O4 (Edwards Mine) and (Mg1.39Ti0.40Al0.18Cr3+0.01Zr0.01Fe2+0.01)Σ2.00B0.94O4 (Balmat mine). The atomic arrangement of a specimen from each mine was determined, and the high-precision refinements provide new insight into the warwickite structure. The M1 site in warwickite is split into two sites to accommodate two occupants with differing bonding requirements; the M1 site contains Mg and the M1′ site hosts Ti, with the two sites being separated by approximately 0.2 Å. The optimized structural formula for both warwickite samples is similar to [M1(Mg0.84Al0.14Ti0.024+)2.74M1′(Ti0.914+Mn0.082+Mg0.01)1.30]Σ4.04M2(Mg0.86Al0.10Ti0.044+)4.00B4O16], demonstrating ordering of Mg at M1 and M2 and Ti at M1′. The site-splitting demonstrates how divalent Mg and tetravalent Ti can exist at a site in solid solution by ordering the two cations at split sites.

Some Grenville-age rocks exposed in the uplifted region of the Hudson Highlands of southern New York are amphibole-dominant igneous rocks. The amphibole-rich rocks, which are locally pegmatitic in nature, are associated with magnetite ore and coarse-grained syenite; the ore was discovered and mined from the middle of the 18th century to the end of the 19th century. The amphiboles have attracted the attention of many researchers for nearly two centuries. Chemical analyses demonstrate that they are pargasite or hastingsite in composition and are particularly rich in Cl and K. High-precision crystal structure analyses of 11 Cl-rich amphiboles from the Hudson Highlands (0.0134

ObjectiveSeverity of coeliac disease depends in part on the extent of small intestinal mucosa injury. Patients with the most abnormal pathology have loss of duodenal villi CYP3A4, a drug-metabolising enzyme that inactivates many drugs. These patients are hypothesised to have greater systemic concentrations of felodipine, a drug which normally has low oral bioavailability secondary to intestinal CYP3A4-mediated metabolism. It serves as a representative for a class containing many medications.DesignA phase I, open-label, single-dose, pharmacokinetic study.SettingLondon, Ontario, Canada.ParticipantsPatients with coeliac disease (n=47) with positive serology and healthy individuals (n=68).Main outcome measuresPatients with coeliac disease—upper gastrointestinal endoscopy and oral felodipine pharmacokinetics study within a 3-week period. Healthy individuals—oral felodipine pharmacokinetics study with water and grapefruit juice.ResultsCoeliac stratification categories: Group A (n=15, normal), B+C (n=16, intraepithelial lymphocytosis with/without mild villous blunting) and D (n=16, moderate/severe villous blunting). Groups A, B+C and D had linear trends of increasing felodipine AUC0–8; mean±SEM, 14.4±2.1, 17.6±2.8, 25.7±5.0; p0–8(11.9±0.9 vs 26.9±0.9, p=0.0001) and Cmax (2.9±0.2 vs 7.7±0.2, p=0.0001) relative to those receiving grapefruit juice.ConclusionsIncreased felodipine concentrations in patients with coeliac disease were most probably secondary to decreased small intestinal CYP3A4 expression. Patients with severe coeliac disease and healthy individuals with grapefruit juice had equivalently enhanced effect. Thus, patients with severe coeliac disease would probably experience similarly altered drug response, including overdose toxicity, from many important medications known to be metabolised by CYP3A4. Patients with coeliac disease with severe disease should be considered for other clinical drug management, particularly when there is the potential for serious drug toxicity.

Select early medieval period (400–1100 CE) Irish people pursued lifestyles of ascetic devotion leading to the establishment of ecclesiastical communities on small islands along Ireland's western coastline. These communities were separated by rough ocean waters, unpredictable Atlantic storms and rocky coastlines. Nevertheless, contemporary textual evidence and shared patterns of architecture, technology, and artisanship, including carved cross stones indicate that these communities were nodes in regional networks of institutional affiliation, shared religious practice, and material procurement or exchange. This study uses geochemical characterization of rock lithologies by hand-held, portable x-ray fluorescence (HHpXRF) in conjunction with routine petrographic analysis to assess the inter-island distribution of rock types used to produce early medieval cross stones in an effort to better define this integrated seascape. The cross stones were produced from a wide range of different geologic materials, including sedimentary limestones to high-grade metamorphic schists. The goal of this study was to determine what proportion of the cross stones were produced from materials locally available on each of the individual islands, and what proportion were produced from imported, non-local lithologies. This study demonstrates that in-field use of portable HHpXRF instrumentation provides semi-quantitative chemical data that can be used in conjunction with visually obtained petrographic data to broadly discriminate and identify different bedrock lithologies. Our results indicate that approximately 25% of the 41 cross stones analyzed were produced from non-local lithologies. Results of this study suggest that early medieval inhabitants primarily used locally procured (on-island) material for cross stone production; non-locally obtained (off-island) rock was used less frequently. These results are consistent with other recent archaeological interpretations that highlight western Ireland seascapes as a connective network between members of early medieval communities who used open-water seafaring and raw material procurement/exchange as a means to maintain regional connections.

The iron oxide-apatite (IOA) deposits of the eastern Adirondack Mountains consist of intrusive sheets or dikes of magnetite, fluorapatite, augitic pyroxene, quartz, and microcline. Other trace mineral phases include ilmenite with hematite exsolution, V-rich titanite rimming magnetite, zircon, monazite-(Ce), stillwellite-(Ce), lanthanite-(Ce), allanite-(Ce), and thorite. Observations under transmitted light show polygonal and cumulate textures. The ore bodies, each with knife-edge contacts with the host gneisses, are closely associated in time with A-type leucogranites and granitic gneisses ( ca . 1070–1050 Ma). Backscattered electron (BSE) images highlight the following types of fluorapatite-monazite-(Ce) relations that formed as a result of metamorphism and fluid-rock interaction: (1) areas of relatively low BSE intensities containing tiny secondary monazite-(Ce) and thorite crystals developed within brighter apatite grains and along crystal margins and fractures; (2) areas of low BSE intensity within larger fluorapatite grains; (3) oriented rods of quartz in fluorapatite; (4) monazite-(Ce) rimming fluorapatite; and (5) multi-domain clusters of fluorapatite in unzoned fluorapatite. Fluorapatite samples from these IOA deposits were analyzed by electron microprobe and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) for major and trace elements. All grains contain high concentrations of light and heavy rare earth elements and yttrium, and samples from some deposits are exceptionally enriched in heavy rare earth elements and yttrium. The crystal structures of the fluorapatites from Cheever, Mineville, Palmer Hill, Arnold Hill, and Rutgers mine were analyzed. Rare earth elements (REE) are dominant at the Ca2 site, and in the most REE-rich sample, from Cheever, 5.7% of the Ca2 sites and 3.5% of the Ca1 sites are occupied by REEs. We consider that the most likely geological scenario for the incorporation of the REEs in fluorapatite includes high concentrations of incompatible elements in a dense iron- and phosphorus-rich melt that formed by immiscibility with the silicate melt of the Lyon Mountain granite. The high REE concentration appears to have been accommodated in the fluorapatite structure through a coupled substitution with Si 4+ . A later, low-temperature stage of fluid infiltration, probably at greenschist facies conditions, re-mobilized the REE and produced secondary minerals within the ore, including low-actinide bearing monazite-(Ce), tremolite, ferro-actinolite, chlorite, rutile, and hematite.

Two syenite sills intrude the local Paleozoic strata of eastern New York State and are exposed along the western shore of Lake Champlain. The sills are fine-grained, alkali feldspar syenites and quartz syenites, with phenocrysts of sanidine and albite. The two sills are compositionally distinct, with crossing rare earth element profiles and different incompatible element ratios, which eliminates the possibility of a simple petrogenetic relationship. Zircon extracted from the upper sill yields a U–Pb age of 131.1 ± 1.7 Ma, making the sills the youngest known igneous rocks in New York State. This age is similar to that of the earliest intrusions in the Monteregian Hills of Quebec, >100 km to the north. Sr and Nd radiogenic isotope ratios are also similar to those observed in some of the syenitic rocks of the eastern Monteregian Hills. The Cannon Point syenites have compositions typical of A-type, within-plate granitoids. They exhibit unusually high Ta and Nb concentrations, resulting in distinct trace element signatures that are similar to those of the silicic rocks of the Valles Caldera, a large, rift-related magmatic system. We suggest that the Cannon Point syenites were melts derived primarily by anatexis of old, primitive, lower crustal material in response to Mesozoic rifting and to the intrusion of mantle-derived magmas. The sills indicate that the effects of continental rifting were spatially and temporally extensive, resulting in the reactivation of basement faults in the Lake Champlain Valley hundreds of kilometers west of the active rift boundary, and crustal melting >50 Ma after the initiation of rifting.

Boron is a biologically important element, but its distribution in the natural environment and its behavior during many geological processes is not fully understood. In most metamorphic and igneous environments, boron is incorporated into minerals of the tourmaline supergroup. In high-grade metamorphic terranes like that of the Adirondack region of northern New York State, uncommon rock compositions combined with unusual and variable geologic conditions resulted in the formation of many additional boron-bearing minerals. This paper reviews the occurrences and geological settings of twelve relatively uncommon boron-bearing minerals in the southern Grenville Province of upstate New York and provides new chemical and Raman spectral data for seven of these minerals. The boron minerals range from relatively simple metal borates (e.g., vonsenite), to chemically complex borosilicates (e.g., prismatine), to a relatively rare borosilicate-carbonate (e.g., harkerite). Some are of primary igneous origin, while others are formed by a variety of prograde and retrograde metamorphic processes or by metasomatic/hydrothermal processes. Most of the boron minerals are formed within, or adjacent to, metasedimentary lithologies that surround the anorthositic massifs of the central Adirondacks. The metasedimentary rocks are thought to be the source of most of the boron, although additional boron isotope studies are needed to confirm this and to constrain the mechanisms of the formation of these unusual minerals.

Monazite crystals, intergrown with allanite, fluorapatite, and quartz from the Cheever Mine iron oxide-apatite (IOA-type) deposit in Essex County, New York, USA, display rare symplectite textures. Electron probe wavelength-dispersive spectrometry (WDS) mapping and major and trace element characterization of these features reveal a natural experiment in fluid-mediated monazite recrystallization. Two types of monazite with symplectite intergrowths have been recognized (Type I and II). Both types of symplectite development are associated with a decrease in HREE, Si, Ca, Th, and Y, but an increase in both La and Ce in monazite. Electron microprobe Th-U-total Pb analysis of Type I monazite with suitable ThO2 concentrations yielded a weighted mean age of 980 &plusmn, 5.8 Ma (MSWD: 3.3), which is interpreted as the age of monazite formation and the onset of symplectite development. Both types of monazite formed during a series of reactions from fluorapatite, and possibly britholite, to produce the final assemblage of monazite, allanite, and fluorapatite. Monazite formation was likely a response to evolving fluid conditions, which favored monazite stability over fluorapatite at ca. 980 Ma, possibly a NaCl brine. A subsequent transition to a Ca-dominated fluid may have then promoted the consumption of monazite to produce another generation of allanite and fluorapatite. Our results indicate that recrystallized monazite formed during fluid-mediated processes that, over time, trended towards an increasingly pure end-member composition. Regionally, these data are consistent with a magmatic-origin followed by fluid-mediated remobilization of select phases at subsolidus conditions for the Adirondack IOA deposits.

Exposures of tremolite, fluor-uvite, and associated minerals along an east-west-trending ridge of Precambrian crystalline rocks south of Selleck Road near the village of West Pierrepont constitute ...

As a cost-effective and non-destructive method for multi-element analysis, portable X-ray fluorescence spectrometry (pXRF) has the potential for broad archeological application; however, recent applications of pXRF remain inconsistent. For example, sourcing studies using pXRF have irradiated artifacts and geologic source materials for widely varying amounts of time. In this study, we investigate the effect of count time on the precision and accuracy of pXRF data obtained for two geologic standards, as well as for obsidian, fine-grained volcanic (e.g., andesites, dacites), metamorphic, and chert specimens from the North American Great Basin. We find that the precision and reliability of pXRF data does not improve significantly at count times greater than 180 s. Our analysis also indicates that count time has little bearing on the accuracy or validity of pXRF data, as expected from the mathematical relationships between count time, intensity, and concentration. Finally, we demonstrate that a well-calibrated pXRF instrument generates compositional data comparable to data obtained using other analytical methods. We offer this study as a step toward the development of a consistent and rigorous analytical protocol for archeological applications of pXRF.

THE DANBURITE OCCURRENCE south of the village of Russell in St. Lawrence County, New York (fig. 2), is one of the classic localities of the northeastern United States. After the original discovery ...

Mesozoic kimberlitic magmatism was geographically widespread across central New York State, and nearly 90 distinct intrusions have been discovered since the first “serpentinite body” was described over 175 years ago. Most of the intrusions are narrow ( The intrusions can be divided into four distinct groups on the basis of both mineralogy and geochemistry, and previously published radiometric age dates suggest that these four groups may also have distinct emplacement ages. Group A intrusions are exposed on the western margin of Cayuga Lake near Ithaca, and are characterized by olivine and phlogopite macrocrysts in a serpentine and phlogopite-rich matrix. These intrusions are relatively Ti-rich and contain abundant perovskite grains in the groundmass that yielded U–Pb crystallization ages of ~ 146 Ma ( Heaman and Kjarsgaard, 2000 ). Group B intrusions are exposed over a relatively large area surrounding Ithaca, and are characterized by having a diverse macrocryst assemblage that includes pyrope, diopside, and spinel in addition to olivine and phlogopite. These intrusions are the most incompatible and REE enriched, and are chemically similar to the Kirkland Lake kimberlites in eastern Ontario. Intrusion ages for this group cluster between 125 and 110 Ma. Group C intrusions are all found within the city of Syracuse, and are similar to the Group B intrusions in both mineralogy and chemistry. They appear to be somewhat older, with intrusion ages of 135–125 Ma. Finally, Group D intrusions are geographically distant from the other three groups, being exposed in East Canada Creek nearly 100 km east of the Syracuse dikes. They are characterized mineralogically by abundant olivine and sparse, but large, phlogopite macrocrysts, and chemically by having the lowest incompatible element and rare earth element (REE) concentrations, and the highest 87 Sr/ 86 Sr ratios. Intrusion ages for these dikes are poorly constrained, but appear to be contemporaneous with, or slightly older than, the ~ 146 Ma Group A intrusions. All of the kimberlitic intrusions in central New York State have initial Sr and Nd isotope ratios close to bulk earth. This fact, combined with the observed macrocryst assemblages and incompatible trace element ratios, indicates that these magmas were derived primarily from an asthenospheric, garnet lherzolite source. Episodic intrusion of small volume, volatile-rich kimberlitic magmas into the Paleozoic sedimentary platform rocks of central New York appears to have occurred along ancient crustal structures that were reactivated by the far field stresses related to the opening of the North Atlantic Ocean.

BENSON MINES is a Grenville-aged (about 1.1 billion-year-old), gneiss-hosted iron deposit located in the Adirondack Mountains, St. Lawrence County, New York. It was mined as an open pit that grew t...

Silicocarbonate pegmatites from the southern Grenville Province have provided exceptionally large crystal specimens for more than a century. Their mineral parageneses include euhedral calc&ndash, silicate minerals such as amphibole, clinopyroxene, and scapolite within a calcite matrix. Crystals can reach a meter or more in long dimension. Minor and locally abundant phases reflect local bedrock compositions and include albite, apatite, perthitic microcline, phlogopite, zircon, tourmaline, titanite, danburite, uraninite, sulfides, and many other minerals. Across the Adirondack Region, individual exposures are of limited aerial extent (&lt, 10,000 m2), crosscut metasedimentary rocks, especially calc&ndash, silicate gneisses and marbles, are undeformed and are spatially and temporally associated with granitic pegmatites. Zircon U&ndash, Pb results include both Shawinigan (circa 1165 Ma) and Ottawan (circa 1050 Ma) intrusion ages, separated by the Carthage-Colton shear zone. Those of Shawinigan age (Lowlands) correspond with the timing of voluminous A-type granitic magmatism, whereas Ottawan ages (Highlands) are temporally related to orogenic collapse, voluminous leucogranite and granitic pegmatite intrusion, iron and garnet ore development, and pervasive localized hydrothermal alteration. Inherited zircon, where present, reflects the broad range of igneous and detrital ages of surrounding rocks. Carbon and oxygen isotopic ratios from calcite plot within a restricted field away from igneous carbonatite values to those of typical sedimentary carbonates and local marbles. Collectively, these exposures represent a continuum between vein-dyke and skarn occurrences involving the anatexis of metasedimentary country rocks. Those of Ottawan age can be tied to movement and fluid flow along structures accommodating orogenic collapse, particularly the Carthage-Colton shear zone.

Figure 1. Map showing the location of the Scott farm prospect, southeast of Fine in St. Lawrence County, New York. Unless otherwise noted, all photos by Steven C. Chamberlain of specimens from his ...

Pegmatites in New York State are largely restricted to areas of exposed Precambrian basement rocks, including the Adirondack Mountains and the Hudson Highlands. In the Adirondacks, they were emplaced into rocks that were metamorphosed during the Grenville orogeny to either the upper amphibolite facies (Adirondack Lowlands) or the granulite facies (Adirondack Highlands). Their mineral assemblages range from simple to complex, with localized occurrences of: (a) Be-, Al-, and B-rich species such as beryl, chrysoberyl, sillimanite, dumortierite, and tourmaline-supergroup minerals, (b) rare-element- and rare-earth-element-bearing minerals such as columbite-(Fe), uranopolycrase, fergusonite-(Y), uraninite, xenotime-(Y), and monazite-(Ce), (c) Ca-, F-, and K-dominant amphiboles, (d) phosphates (fluorapatite, isokite, wagnerite), (e) sulfides (bismuthinite, molybdenite), and (f) tungstates (scheelite). The pegmatite bodies from southern New York State and from some of the southern Adirondack locations display mineralogical zoning, typically with a quartz-rich core. Post-emplacement metamorphic features are observed in pegmatites in the northwestern Adirondack Lowlands, but are negligible or obscured in most of those from the southern and eastern Adirondacks. On the basis of the metamorphic grade of the host rocks, all New York pegmatites belong to the Abyssal class, whereas on the basis of mineralogy and inferred tectonic setting, they show affiliations to the NYF and mixed NYF–LCT pegmatite families. Pegmatites in the Adirondack Lowlands are related to the calc-alkaline arc magmatism of the Antwerp–Rossie granite suite and yield U–Pb zircon crystallization ages that indicate intrusion during the late Shawinigan orogeny (~1195 Ma); currently there are no known pegmatites related to the Ottawan and Rigolet orogenies in the Lowlands. Pegmatites in the Highlands yield U–Pb zircon crystallization ages that correspond to: (a) emplacement during the late Elzevirian (~1222 Ma), and metamorphism during the late Shawinigan (~1178 Ma) orogenies; (b) emplacement during the early (1098 Ma) and mid to late Ottawan orogeny (~1062–1025 Ma); (c) intrusion during the early Rigolet orogeny (1009–1003 Ma), and finally, (d) intrusion related to a thermal pulse at 949 Ma, possibly associated with the Cathead Mountain leucocratic dike swarm (935 ± 9.2 Ma). Few, if any, granitic pegmatites were intruded between 1178 and 1098 Ma in the Adirondack Highlands. The main pegmatite bodies in the Adirondack Highlands occur in association with extensional A-type granites such as the Hawkeye and Lyon Mountain Granite suites. These rocks were emplaced in response to orogenic collapse following the Ottawan orogeny. At present, relatively little can be concluded about the tectonic setting of pegmatites in southern New York.

Our research group discovered the interaction between grapefruit and certain medications more than 20 years ago.[1][1]–[3][2] Currently, more than 85 drugs, most of which are available in Canada, are known or predicted to interact with grapefruit. This interaction enhances systemic drug

Integrating portable X-ray fluorescence (pXRF) instrumentation into archaeological investigations has generated as much interest as skepticism because several characteristics of the technique limit analytical accuracy and precision. This paper seeks to explore inter-instrument performance in order to assess the potential pXRF instrumentation has in examining the elemental composition of lithic raw materials. Two pXRF instruments, Delta and Omega models both manufactured by Olympus Innov-X Systems, were utilized to obtain the trace element signatures of five fine-grained volcanic sources and four obsidian sources in the Great Basin. We compared the two portable instruments to a wavelength-dispersive instrument extensively calibrated with geologic standards and to a commercial benchtop energy-dispersive system. Our results suggest that the relationships between the data produced by these different instruments are complex, and as we look to the future of pXRF use in archaeological analysis we argue that that the same strict protocols applied in laboratory-based XRF analyses, involving instrument calibration, evaluation of inter-instrument performance, and comparison to accepted geologic standards, need to be applied in pXRF analysis.

Analyzing technological patterns and source provenance of stone tools, Jones, Beck, Jones, and Hughes (2003) argue that Paleoarchuic groups of the central Great Basin moved within an extensive home range, perhaps reaching 400 km in its longest dimension. The Eastern Conveyance Zone, as they refer to this territory, was aligned with the predominantly north-south trending mountains and valleys of the province. To evaluate this model of mobility, artifacts were collected from the southern part of the Eastern Conveyance Zone for geochemical characterizations. X-ray fluorescence spectrometry of 183 obsidian and fine-grained volcanic artifacts identified 12 known rock sources, all from the southern and central sections of the zone. No northern sources are represented among artifacts studied. Revisions of the Eastern Conveyance Zone model are considered in light of these results.

A new type of interaction in which fruit juices diminish oral drug bioavailability through inhibition of uptake transport is the focus of this review. The discovery was based on an opposite to anticipated finding when assessing the possibility of grapefruit juice increasing oral fexofenadine bioavailability in humans through inhibition of intestinal MDR1-mediated efflux transport. In follow-up investigations, grapefruit or orange juice at low concentrations potentially and selectively inhibited in vitro OATP1A2-mediated uptake compared with MDR1-caused efflux substrate transport. These juices at high volume dramatically depressed oral fexofenadine bioavailability. Grapefruit was the representative juice to characterize the interaction subsequently. A volume–effect relationship study using a normal juice amount halved average fexofenadine absorption. Individual variability and reproducibility data indicated the clinical interaction involved direct inhibition of intestinal OATP1A2. Naringin was a major causal component suggesting that other flavonoids in fruits and vegetables might also produce the effect. Duration of juice clinical inhibition of fexofenadine absorption lasted more than 2 h but less than 4 h indicating the interaction was avoidable with appropriate interval of time between juice and drug consumption. Grapefruit juice lowered the oral bioavailability of several medications transported by OATP1A2 (acebutolol, celiprolol, fexofenadine, talinolol, L-thyroxine) while orange juice did the same for others (atenolol, celiprolol, ciprofloxacin, fexofenadine). Juice clinical inhibition of OATP2B1 was unresolved while that of OATP1B1 seemed unlikely. The interaction between grapefruit juice and etoposide also seemed relevant. Knowledge of both affected uptake transporter and drug hydrophilicity assisted prediction of the clinical interaction with grapefruit or orange juice.

(2009). Minerals of The Silurian Lockport Group Central and Western New York State. Rocks & Minerals: Vol. 84, No. 4, pp. 326-337.

Objective. C-reactive protein (CRP) and homocysteine are markers of cardiovascular risk that may have inflamma- tory effects. HMG coenzyme A reductase inhibitors (statins) have anti-inflammatory effects in vitro, but it is not clear if such responses in vivo are secondary to lipid lowering. We examined the hypothesis that CRP and homocysteine would stimulate cytokine release in human whole blood and that short-term treatment with a statin would inhibit it. Methods. The time course of IL-6 and MCP-1 production was determined in whole blood incubated with saline, 1 mg/mL lipopolysaccaride (LPS), 50 and 100 mM/L DL-homocysteine, and 5 mg/mL human recombinant CRP for 24 hours at 37°C under 5% CO2 atmosphere. Cytokine responses were determined in blood drawn from 15 healthy volunteers before and after administration of pravastatin 40 mg daily for 2 days. Results. Both human recombinant CRP and LPS significantly increased the production of IL-6 and MCP-1 in whole blood samples more than 4-fold (P < 0.001) but homocysteine did not. Oral administration of pravastatin, 40mg daily for 2 days, decreased CRP-stimulated IL-6 production by approximately 20% (P = 0.02) 6 hours after incubation, but did not affect MCP-1 production (P = 0.69). Pravastatin treatment did not affect LPS-stimulated MCP-1 but increased IL-6 modestly. Conclusions. CRP stimulated the production of the proatherogenic mediators MCP-1 and IL-6 in human whole blood, but homocysteine did not. CRP-stimulated production of IL-6, but not MCP-1, was modestly attenuated by short-term treatment with pravastatin.

We showed previously that grapefruit and orange juices inhibited human enteric organic anion-transporting polypeptide (OATP)1A2 in vitro and lowered oral fexofenadine bioavailability clinically. Inhibition of OATP1A2 transport by flavonoids in grapefruit (naringin) and orange (hesperidin) was conducted in vitro. Two randomized, crossover, pharmacokinetic studies were performed clinically. In one study, 120 mg of fexofenadine was ingested with 300 ml grapefruit juice, an aqueous solution of naringin at the same juice concentration (1,200 microM), or water. In the other study, fexofenadine was administered with grapefruit juice, with or 2 h before aqueous suspension of the particulate fraction of juice containing known clinical inhibitors of enteric CYP3A4, but relatively low naringin concentration (34 microM), or with water. Naringin and hesperidin's half-maximal inhibitions were 3.6 and 2.7 microM, respectively. Fexofenadine area under the plasma drug concentration-time curves (AUCs) with grapefruit juice and naringin solution were 55% (P

Background: The cytochrome P450 3A4 (CYP3A4) inhibitor clarithromycin may also inhibit liver-specific organic anion–transporting polypeptides (OATP1B1 and OATP1B3). We studied whether concurrent use of clarithromycin and a statin not metabolized by CYP3A4 was associated with an increased frequency of serious adverse events. Methods: Using large health care databases, we studied a population-based cohort of older adults (mean age 74 years) who were taking a statin not metabolized by CYP3A4 (rosuvastatin [76% of prescriptions], pravastatin [21%] or fluvastatin [3%]) between 2002 and 2013 and were newly prescribed clarithromycin ( n = 51 523) or azithromycin ( n = 52 518), the latter an antibiotic that inhibits neither CYP3A4 nor OATP1B1 and OATP1B3. Outcomes were hospital admission with a diagnostic code for rhabdomyolysis, acute kidney injury or hyperkalemia, and all-cause mortality. All outcomes were assessed within 30 days after co-prescription. Results: Compared with the control group, patients co-prescribed clarithromycin and a statin not metabolized by CYP3A4 were at increased risk of hospital admission with acute kidney injury (adjusted relative risk [RR] 1.65, 95% confidence interval [CI] 1.31 to 2.09), admission with hyperkalemia (adjusted RR 2.17, 95% CI 1.22 to 3.86) and all-cause mortality (adjusted RR 1.43, 95% CI 1.15 to 1.76). The adjusted RR for admission with rhabdomyolysis was 2.27 (95% CI 0.86 to 5.96). The absolute increase in risk for each outcome was small and likely below 1%, even after we considered the insensitivity of some hospital database codes. Interpretation: Among older adults taking a statin not metabolized by CYP3A4, co-prescription of clarithromycin versus azithromycin was associated with a modest but statistically significant increase in the 30-day absolute risk of adverse outcomes.