Common variants of the G protein-coupled receptor type 4 are associated with human essential hypertension and predict the blood pressure response to angiotensin receptor blockade.

Non-synonymous GRK4 variants, R65L, A142V and A486V, are associated with essential hypertension in diverse populations. This study replicated the association of GRK4 variants, including GRK4(142V), with human essential hypertension in a Japanese population (n=588; hypertensive, n=486 normotensive controls) and determined whether the presence of GRK4 variants predicted the blood pressure (BP) response to angiotensin receptor blockers (ARBs) in patients with essential hypertension. We analyzed 829 patients and compared the response to ARBs between individuals with no GRK4 variants (n=136) and those with variants at one or any of the three loci (n=693). Carriers of hGRK4(142V) had a greater decrease in systolic BP in response to ARBs than non-carrier hypertensive patients. By contrast, those with variants only at GRK4(486V) were less likely to achieve the BP goal in response to an ARB than those with no variants. These studies showed for the first time the association between GRK4(142V) and a larger decrease in BP with ARBs in hypertensive patients.

Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects.

This study aimed to evaluate the effects of green tea on the pharmacokinetics and pharmacodynamics of the ß-blocker nadolol. Ten healthy volunteers received a single oral dose of 30 mg nadolol with green tea or water after repeated consumption of green tea (700 ml/day) or water for 14 days. Catechin concentrations in green tea and plasma were determined. Green tea markedly decreased the maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-48)) of nadolol by 85.3% and 85.0%, respectively (P < 0.01), without altering renal clearance of nadolol. The effects of nadolol on systolic blood pressure were significantly reduced by green tea. [(3)H]-Nadolol uptake assays in human embryonic kidney 293 cells stably expressing the organic anion-transporting polypeptides OATP1A2 and OATP2B1 revealed that nadolol is a substrate of OATP1A2 (Michaelis constant (K(m)) = 84.3 µmol/l) but not of OATP2B1. Moreover, green tea significantly inhibited OATP1A2-mediated nadolol uptake (half-maximal inhibitory concentration, IC(50) = 1.36%). These results suggest that green tea reduces plasma concentrations of nadolol possibly in part by inhibition of OATP1A2-mediated uptake of nadolol in the intestine.

Lower plasma arginine in enteral tube-fed patients with pressure ulcer and improved pressure ulcer healing after arginine supplementation by Arginaid Water.

OBJECTIVES: To determine the presence or extent of arginine deficiency in pressure ulcer (PU) patients on percutaneous endoscopic gastrostomy (PEG) feeding and to examine the effects of arginine supplementation on PU healing. DESIGN: All eligible PEG patients, with and without PU, were cross-sectionally assessed for plasma arginine. Three-month supplementation with arginine-enriched water (Arginaid Water) was performed on a subset of patients with PU. This intervention study was a prospective, non-controlled trial with 5 PU patients. SETTING: Geriatric ward of a rural clinical hospital in Japan. PARTICIPANTS: Thirty-nine inpatients with PEG feeding were assessed for plasma arginine. Five of the 13 patients with PU and five of 26 patients without PU underwent amino acid profiling. INTERVENTION: Five of the patients with PU received Arginaid Water supplementation. MEASUREMENTS: Plasma amino acid measurements and biochemical analyses were performed. For those with PU on Arginaid Water supplementation, plasma arginine concentration and PU status were monitored every month. RESULTS: Patients with PU showed significantly lower plasma arginine concentration compared to those without PU (control vs. PU; 80.2±21.3 vs 62.8±14.7 nmol/ml, p<0.01). After the addition of Arginaid Water, plasma arginine concentration increased (before vs 3 months later; 57.9±1.8 vs 83.1±8.5, p<0.01), and PU area, perimeter, DESIGN-R and PUSH scores significantly improved. CONCLUSION: Plasma arginine was lower in PEG patients with PU. The healing rate of PU is improved with Arginaid Water supplementation. The findings from this study support the use of arginine supplementation in PEG patients with PU.

Comparison of the APTIMA CT and GC assays with the APTIMA combo 2 assay, the Abbott LCx assay, and direct fluorescent-antibody and culture assays for detection of Chlamydia trachomatis and Neisseria gonorrhoeae.

The Gen-Probe APTIMA Combo 2 (AC2) is a Food and Drug Administration-cleared nucleic acid amplification test (NAAT) for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae from urine and urogenital swab specimens. The Centers for Disease Control and Prevention have recommended confirmation of positive NAAT results in low-prevalence populations. APTIMA CT (ACT) and APTIMA GC (AGC) are two discrete NAATs for C. trachomatis and N. gonorrhoeae detection that are suitable for confirming AC2-positive results because they target different nucleic acid sequences. Our objective was to determine if ACT and AGC could be used as confirmatory tests for AC2 and to correlate the APTIMA assays with culture, direct fluorescent-antibody (DFA), and LCx CT and GC assays. Urine and swab specimens (1,304) were initially tested with either culture, DFA, or LCx, followed by AC2. A subset (675) was then tested with ACT and AGC. There was absolute concordance between ACT-AGC and AC2. LCx did not detect 1 of 14 AC2-ACT- and 1 of 6 AC2-AGC-positive urine samples, and it yielded one C. trachomatis- and one N. gonorrhoeae-positive swab result that were not detected by AC2 and ACT-AGC. Culture failed to detect 5 of 20 AC2-ACT and 3 of 4 AC2-AGC positives, and DFA missed 4 of 4 AC2-ACT positives. Thus, ACT and AGC relative sensitivity compared to that of AC2 was 100%. All APTIMA assays detected more confirmed positive results than culture, DFA, and LCx. The performance of APTIMA assays was not altered by the use of various swab types and by long-term storage of specimens. All APTIMA assays are highly sensitive and rapid. ACT and AGC can be recommended for confirmation of positive results from other NAATs, such as AC2 and LCx.

Permanence of Fungi-Fluor epifluorescence stain to detect microsporidia.

OBJECTIVE: Epifluorescence microscopy, a methodology for the screening of bodily fluids and tissue specimens for microsporidia species, was directed to evaluate the retention of epifluorescence of fixed and stained specimens over time. METHODS: Thirty samples of stool, bodily fluids, duodenal touch preparations, and biopsies, were tested for the retention of their epifluoresence using the Fungi-Fluor procedure. Specimens were examined under a 330- to 380-nm UV filter at the time of preparation, 3 wk later, and then at monthly intervals for 18 months. All specimens were reevaluated for the presence or absence of fluorescence and any decrement of fluorescence over time. No special preservation techniques were used on any of the slides. RESULTS: All 30 specimens maintained their epifluorescence from the time of slide preparation to 18 month later. No decrement in fluorescence was noted in any sample examined. Accuracy and ease of spore identification was maintained. CONCLUSIONS: Epifluorescence microscopy demonstrates the utility of this technique for archival study of microsporidia-containing specimens over prolonged periods of time.

Direction-independent block of bi-directional Na+/Ca2+ exchange current by KB-R7943 in guinea-pig cardiac myocytes.

1. We investigated the inhibitory effect of KB-R7943 on 'bi-directional' Na+/Ca2+ exchange current (iNCX) with the reversal potential of iNCX (ENCX) in the middle of the ramp voltage pulse employed. 2. Bi-directional iNCX was recorded with 'full' ramp pulses given every 10 s from the holding potential of -60 mV over the voltage range between 30 and -150 mV under the ionic conditions of 140 mM [Na]o, 20 mM [Na]i, 1 mM [Ca]o and 433 nM [Ca]i with calculated ENCX at -50 mV. 3. KB-R7943 (0.1 - 100 mirconM) concentration-dependently inhibited the current, which reversed near the calculated ENCX, indicating that the blocked current was iNCX. 4. The inhibition levels were not significantly different between outward and inward iNCX measured at 0 and -120 mV, respectively. IC50 of KB-R7943 was approximately 1 micronM for both directions of iNCX. 5. Under the bi-directional ionic conditions, only an outward or inward iNCX was induced by positive or negative 'half' ramp pulses, respectively, from the holding potential of -60 mV. KB-R7943 inhibited both direction of iNCX and the concentration-inhibition relations were superimposable to the ones obtained by 'full' ramp pulses. 6. These results indicate that KB-R7943 inhibits iNCX direction-independently under bi-directional conditions. This conclusion is different from that of our previous results obtained from iNCX under uni-directional ionic conditions, where KB-R7943 inhibited iNCX direction-dependently. The difference could be attributed to slow dissociation of the drug from the exchanger.

Effects of a novel cardioprotective drug, JTV-519, on membrane currents of guinea pig ventricular myocytes.

We investigated effects of a novel cardioprotective drug, JTV-519 (4-[3-(4-benzylpiperidin-1-yl)propionyl]-7-methoxy-2,3,4,5-tetrahy dro-1,4-benzothiazepine monohydrochloride) on membrane currents of guinea pig ventricular myocytes by whole-cell voltage and current clamp methods. The fast Na+ current (iNa) was activated by ramp pulses from various holding potentials of -90, -80 or -60 mV to 10 mV with various intervals. At 0.2 Hz, JTV-519 inhibited iNa in a concentration-dependent manner with an IC50 of approximately 1.2 and 2 microM at the holding potential of -60 and -90 mM, respectively, implicating a voltage-dependent block. Increasing the pulse frequency from 1 to 2 or 3.3 Hz in the presence of 1 microM JTV-519 shortened the time-course and increased the level of iNa block, indicating a frequency-dependent block. The time-course of iNa blocking by JTV-519 was slower than that of lidocaine and similar to that of quinidine. Ca2+ current (iCa) and the inwardly rectifying K+ current (iK1) were also inhibited by JTV-519. JTV-519 decreased the duration and the height of the plateau of the action potential. We conclude that JTV-519 has frequency- and voltage-dependent blocking effects on iNa as well as inhibition of iCa and iK1.

Dientamoeba fragilis, a protozoan parasite in adult members of a semicommunal group.

Dientamoeba fragilis is an intestinal protozoan parasite associated with gastrointestinal symptoms. This study was undertaken in a semicommunal group reported to have a high prevalence of this parasite. Stools were collected from 81 adult group members. Intestinal parasites were observed in stool specimens of 45 (56%) of the 81 adults; D. fragilis was found in 33 (41%) subjects. This paper describes the clinical findings and treatment of 26 adults with D. fragilis alone or with a commensal. Gastrointestinal symptoms were observed in 22 (85%) of infected subjects; abdominal pain and excessive flatus were significantly more common in this group. diiohydroxyquin 650 mg three times a day for 20 days eliminated the parasite in 10 (83%) of the 12 treated, although three subjects required a second course of therapy. Parasitic infection should be considered in patients with vague gastrointestinal symptoms, especially those living in endemic areas, in close proximity, or with a history of foreign travel.

Intestinal protozoan infection in a semicommunal group.

A survey was conducted to determine the prevalence of protozoan parasites in a large semicommunal group in Los Angeles. Protozoan parasites were observed in 151 (69%) of the 220 group members in the study. Parasites were observed in stool specimens from 105 (76%) of the 138 children and 46 (56%) of the 82 adults. Dientamoeba fragilis was observed in 115 (52%), Giardia lamblia in 50 (23%), Entamoeba histolytica in 9 (4%), and commensals in 61 (28%). Parasitic infection was infrequent in infants less than 1 year old, was demonstrated in 33 (89%) of the 2- to 4-year-olds, 69 (78%) of the 89 school age children 8-15 years of age, and in 46 (56%) of the 82 adults. G. lamblia was most prevalent in children younger than 6 years; whereas D. fragilis was common in all age groups. The fecal-oral route was the most likely means for parasite transmission. Since the group at times serves meals to the public, spread of parasites outside the community is a potential public health problems. Diagnosis of parasitic infection is dependent on optimal stool collection, proper laboratory techniques and trained personnel.

Isolation of an obligately anaerobic Streptococcus pneumoniae from blood culture.

An obligately anaerobic strain of Streptococcus pneumoniae was isolated from blood culture in a 14-month-old child with an upper respiratory tract infection.