Prospective randomized controlled trial comparing treatment efficacy and tolerance of picosecond alexandrite laser with a diffractive lens array and triple combination cream in female asian patients with melasma.

BACKGROUND: Recent evidence suggests melasma to be a photoaging disorder. Triple combination creams (TCC: fluocinolone acetonide 0.01%, hydroquinone 4% and tretinoin 0.05%) remain the gold standard treatment. Picosecond alexandrite laser treatment using a diffractive lens array (DLA) has been identified to be effective for improving photoaging conditions. OBJECTIVE: We aimed to compare the efficacy and tolerance of the picosecond alexandrite laser with those of DLA and TCC in female Asian patients with melasma. METHODS: Twenty-nine patients were randomly assigned to group A1 (3 laser sessions at 4-week intervals), A2 (5 laser sessions at 4-week intervals) or B (TCC daily for at least 8 weeks and then tapered until the final evaluation). The Melasma Area, Severity Index (MASI) score and VISIA were assessed at baseline, week 12 and week 20. By week 20, the follow-up periods for groups A1 and A2 were 3 months and 1 month, respectively. RESULTS: Nine, 11 and 6 participants in groups A1, A2 and B completed the study, respectively. MASI scores were significantly improved in all 3 groups at weeks 12 and 20. In groups A1, A2 and B, the improvement rates at week 20 were 53%, 38% and 50%, respectively. VISIA® analysis additionally revealed a significant improvement in spots, porphyria, pores and brown spots after 3 laser sessions (P < 0.05). Group A2 showed greater improvements than group A1 in terms of spots, wrinkles and pores; however, only red areas were significantly different (P < 0.001). All side-effects in the 3 groups were transient and gradually subsided after 1-3 months. CONCLUSION: Picosecond alexandrite laser treatment using DLA showed comparable efficacy with TCC for the treatment of melasma. Improvements in texture, spots, wrinkles and pores were observed in the laser groups. Patients with melasma lesions that exhibit telangiectasia may benefit from additional laser treatment sessions.

[Effect of exendin-4 on lipid deposition in skeletal muscle of diet-induced obese mice and its underlying mechanism].

Objective: To investigate the effect of exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, on reducing lipid deposition and improving insulin resistance in skeletal muscle and the underlying mechanisms in high-fat diet (HFD)-induced obese mice. Methods: Twelve male C57BL/6J mice were challenged with HFD for 12 weeks to induce obesity and then randomly divided into two groups: exendin-4 group (intraperitoneal injection of 24 nmol·kg-1·d-1 exendin-4 for 4 weeks) and HFD group (intraperitoneal injection of normal saline for 4 weeks), with 6 mice in each group. Additional 6 mice were also selected as control group. Body weight, fasting blood glucose were recorded. Serum triglyceride (TG), total cholesterol (TC), insulin and skeletal muscle triglyceride levels were measured by enzyme-linked immunosobent assay (ELISA). Oil red O staining was used for morphologic changes of frozen sections from skeletal muscle. The protein levels of lipid metabolic pathway mediated by AMP-activated protein kinase (AMPK) and insulin signailing pathway were determined by Western blot. Results: Compared with mice in HFD group, exendin-4 significantly decreased body weight[(37.68±1.80) vs (46.03±5.00) g, P<0.025], fasting blood glucose[(5.40±0.33) vs (7.65±1.92) mmol/L, P<0.025], serum TG[(37.78±7.14) vs (80.76±34.22) mg/dl, P<0.025], TC[(180.13±18.75) vs (217.57±22.52) mg/dl, P<0.025], insulin[(0.58±0.01) vs (1.67±1.23) ng/ml, P<0.025]and skeletal muscle TG levels[(9.84±1.08) vs (19.35±7.44) mg/g, P<0.025]of obese mice. Oil red O staining revealed that exendin-4 alleviated the accumulation of larger lipid droplets in skeletal muscle. The protein expressions of lipolysis and lipid oxidation mediated by AMPK and insulin signailing pathway were up-regulated, and the protein expressions of lipogenesis mediated by AMPK were down-regulated after intervention of exendin-4. Conclusion: Exendin-4 reduces lipid deposition and insulin resistance in skeletal muscle of HFD-induced obese mice via activating AMPK and up-regulating insulin signailing pathway.

Increased risk of sudden sensorineural hearing loss in patients with depressive disorders: population-based cohort study.

OBJECTIVES: To evaluate the incidence rates and risk of sudden sensorineural hearing loss among patients with depressive disorders. METHOD: Data for 27 547 patients with newly diagnosed depressive disorders and 27 547 subjects without depressive disorders between 2001 and 2008 were yielded from the Taiwan National Health Insurance Research Database. Sudden sensorineural hearing loss incidence at the end of 2011 was determined. Cumulative incidence and adjusted hazard ratio were computed. RESULTS: Sudden sensorineural hearing loss incidence was 1.45 times higher in the depressive disorders group compared to the non-depressive disorders group (p = 0.0041), with an adjusted hazard ratio of 1.460. A significant increased risk of developing sudden sensorineural hearing loss was noted in patients with diabetes mellitus, chronic kidney disease and hyperlipidaemia (p < 0.05). CONCLUSION: The results suggest an increased risk of developing sudden sensorineural hearing loss in patients with depressive disorders. Co-morbidities such as diabetes mellitus, chronic kidney disease and hyperlipidaemia significantly aggravated the risk. Depressive disorders might be considered a risk factor for sudden sensorineural hearing loss. It remains to be seen whether control of depressive disorders can decrease the incidence of sudden sensorineural hearing loss in patients with depressive disorders.

ABC transporters coordinately expressed during lignification of Arabidopsis stems include a set of ABCBs associated with auxin transport.

The primary inflorescence stem of Arabidopsis thaliana is rich in lignified cell walls, in both vascular bundles and interfascicular fibres. Previous gene expression studies demonstrated a correlation between expression of phenylpropanoid biosynthetic genes and a subset of genes encoding ATP-binding cassette (ABC) transporters, especially in the ABCB/multi-drug resistance/P-glycoprotein (ABCB/MDR/PGP) and ABCG/pleiotropic drug resistance (ABCG/PDR) subfamilies. The objective of this study was to characterize these ABC transporters in terms of their gene expression and their function in development of lignified cells. Based on in silico analyses, four ABC transporters were selected for detailed investigation: ABCB11/MDR8, ABCB14/MDR12, ABCB15/MDR13, and ABCG33/PDR5. Promoter::glucuronidase reporter assays for each gene indicated that promoters of ABCB11, ABCB14, ABCB15, and ABCG33 transporters are active in the vascular tissues of primary stem, and in some cases in interfascicular tissues as well. Homozygous T-DNA insertion mutant lines showed no apparent irregular xylem phenotype or alterations in interfascicular fibre lignification or morphology in comparison with wild type. However, in abcb14-1 mutants, stem vascular morphology was slightly disorganized, with decreased phloem area in the vascular bundle and decreased xylem vessel lumen diameter. In addition, abcb14-1 mutants showed both decreased polar auxin transport through whole stems and altered auxin distribution in the procambium. It is proposed that both ABCB14 and ABCB15 promote auxin transport since inflorescence stems in both mutants showed a reduction in polar auxin transport, which was not observed for any of the ABCG subfamily mutants tested. In the case of ABCB14, the reduction in auxin transport is correlated with a mild disruption of vascular development in the inflorescence stem.

Molecular Identification and Characterization of Tomato zonate spot virus in Tobacco in Guangxi, China.

In Guangxi Province of southwest China, diseases caused by Tospoviruses (family Bunyaviridae) pose a serious threat to tobacco (Nicotiana tobacum) production. During surveys conducted annually at Xinrong Village in Jingxi County from 2008 to 2010, more than 130 ha of fields were found to have 10 to 50% of plants exhibiting symptoms similar to spotted wilt caused by Tomato spotted wilt virus (TSWV). During this period, disease symptoms at similar prevalence and incidence were also found at Fushan, Debao County in most of the cultivars produced in these areas, including Yunyan 85, 87, 92, 97, and K326. Symptoms on tobacco varied but commonly included dwarfing, midrib browning, distorted apical buds, and concentric ringspots that coalesced to form large areas of dead leaf tissue. Mechanical inoculation from diseased tobacco leaves with concentric ringspots back to tobacco cv. Yunyan 85 or 87, resulted in 12 of 16 plants with symptoms similar to those observed in the field. No symptoms on plants developed following inoculation with buffer only. Symptoms found in the field resembled those caused by TSWV. However, testing using TSWV-specific antiserum was shown to be negative by double-antibody sandwich-ELISA (Agdia, Elkhart, IN). Total RNA was extracted from 27 diseased tobacco plants collected from different regions in Guangxi using Trizol reagent (Invitrogen, Carlsbad, CA) according to the manufacturer's instructions. RNA extracts were amplified by reverse transcription (RT)-PCR using the degenerate primers T2740 (ATGGGDATNTTTGATTTCATG) and T3920c (TCATGCTCATSAGRTAAATYTCTCT) designed to target the partial RNA-dependent RNA polymerase (RdRp) sequence of members in the genus Tospovirus (3). Amplification was performed at 42°C for 60 min, followed by 35 cycles of PCR (30 s denaturation at 94°C, 45 s annealing at 55°C, and 30 s extension at 72°C) and a 7-min final extension at 72°C. A PCR product of approximately 1.2 kb was amplified from 21 diseased plants. RT-PCR amplicons were cloned into the pUC19-T Simple Vector (TaKaRa, Dalian, China) and sequenced in both directions. Sequences were assembled and analyzed by DNAStar 5.01 (DNASTAR, Madison, WI). Sequences of representative isolates were deposited in GenBank (Accession Nos. JN020022 to JN020027). The 1.2-kb partial RdRp sequences of these isolates were shown to have 94.4 to 95.3% nucleotide identity and 96.5 to 97.5% amino acids identity to Tomato zonate spot virus (TZSV) (GenBank Accession No. NC_010491) (1). Among these TZSV isolates from Guangxi, the partial RdRp sequences have 98.0 to 99.4% nucleotide identity and 98.8 to 100% amino acids identity with each other. The presence of TZSV was further confirmed in diseased tobacco plants by indirect ELISA using antiserum of TZSV (provided by Prof. Zhongkai Zhang, Agricultural Academy of Yunnan, China). TZSV has been characterized as a novel tospovirus on various hosts including tobacco in Yunnan province (1,2). To our knowledge, this is the first report of TZSV-associated disease on tobacco in Guangxi Province, southwest China. Further work is necessary to study the epidemiology and management of the disease. References: (1) J. Dong et al. Arch. Virol. 153:855, 2008. (2) J. Dong et al. J. Insect Sci. 10:166, 2010. (3) Y. Lin. Master Thesis. National Chung Hsing University, Taichung, Taiwan, Republic of China, 2007.

The effects of benzene exposure on apoptosis in epithelial lung cells: localization by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and the immunocytochemical localization of apoptosis-related gene products.

Although benzene, a well-known human carcinogen, has been shown to induce apoptosis in vitro, no studies have been carried out to confirm and characterize its role in activating apoptosis in vivo. The present study investigated the effects of benzene inhalation on the epithelial cells lining the respiratory tract including bronchioles, terminal bronchioles, respiratory bronchioles and alveoli of male Sprague-Dawley rats. Inhalation of benzene 300 ppm for 7 days induced apoptotic changes in the parenchymal components in the lung that significantly exceeded the events of programmed cell death in normal control tissues. Apoptosis was confirmed by the electrophoretic analysis of internucleosomal DNA fragmentation of benzene-exposed lung tissues, which exhibited 180-200 bp laddering subunits indicative of genomic DNA degradation. Furthermore, semi-quantitative analysis of intracellular localization of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling TUNEL) showed a significant (p < 0.001) increase in the apoptotic index calculated for bronchiolar 73.5%, terminal bronchiolar (65%), and respiratory bronchiolar 60.8% segmental epithelial components as well as alveolar (55%) epithelia. Analysis of immunohistochemical expression of apoptosis-related gene products also supported the hypothesis that benzene can induce apoptosis in chemosensitive target cells in the lung parenchyma. Quantitative immunhistochemistry showed a statistically significant increase p < 0.001 in the immunoreactive staining index for cytochrome c, Apaf-1 (apoptosis activating factor-1), DNA fragmentation factor, and representative cysteine proteases including caspase-1, caspase-2L, caspase-8 and caspase-9. Thus this is the first study of the respiratory system that demonstrates that benzene inhalation induces lung cell apoptosis as confirmed by DNA electrophoresis, in situ nick end labeling, and the upregulation of apoptosis-related gene products that facilitate caspase-cleaved enzymes which lead to cell degradation via programmed cell death. These responses may represent an important defense mechanism within the parenchymal cells of the respiratory system that reduce mutational hazard and the potential carcinogenic effects of benzene-initiated pathogenesis.

Adaptive filtering of evoked potentials using higher-order adaptive signal enhancer with genetic-type variable step-size prefilter.

An adaptive signal enhancer based on third-order statistics with a genetic-type, variable step-size prefilter is introduced to recover evoked potentials (EPs). EPs are usually embedded in the ongoing electroencephalogram with a very low signal-to-noise ratio (SNR). As a higher-order statistics technique has a natural tolerance to Gaussian noise, it is applicable for filtering EPs. An adaptive signal enhancer based on third-order statistics was used as the major filter in this study. However, the efficiency of the adaptive signal enhancer was reduced when the total power of uncorrelated noises was large. To improve the performance for EPs under poor SNR, a low-noise signal is required. Therefore a prefilter with a genetic-type, variable step-size algorithm was employed to enhance the SNR of the signal in this study. The fundamental idea of a genetic-type, variable step-size algorithm is that its step-sizes are regularly readjusted to optimum. Therefore this algorithm can be used as a prefilter with different noise levels. Experimental results showed that, for filtering EPs, the proposed scheme is superior to the adaptive signal enhancer with a normalised least mean square algorithm.

Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells.

The cytotoxicity of homocysteine derivatives on chromosomal damage in somatic cells is not well established. The present study used reactive homocysteine derivative of homocysteine thiolactone (Hcy) to investigate its causal effect on apoptotic DNA injury in human promyeloid HL-60 cells. Our results demonstrated that Hcy induced cell death and features of apoptosis including increased phosphotidylserine exposure on the membrane surface, increased apoptotic cells with hypoploid DNA contents, and internucleosomal DNA fragmentation, all of which occurred in a time- and concentration-dependent manner. Hcy treatment also significantly increased intracellular reactive oxygen species H2O2, which coincided with the elimination of caspase 3 proenzyme levels and increased caspase 3 activity at the time of the appearance of apoptotic DNA fragmentation. Preincubation of Hcy-treated HL-60 cells with catalase completely scavenged intracellular H2O2, thus inhibiting caspase 3 activity and protecting cells from apoptotic DNA damage. In contrast, superoxide dismutase failed to inhibit Hcy-induced DNA damage. Taken together, these results demonstrate that Hcy exerted its genotoxic effects on HL-60 cells through an apoptotic pathway, which is mediated by the activation of caspase 3 activity induced by an increase in intracellular hydrogen peroxide.

Renormalization group analysis for thermal turbulent transport.

In this study, we continue with our previous renormalization group analysis of incompressible turbulence, aiming at determination of various thermal transport properties. In particular, the temperature field T is considered a passive scalar. The quasinormal approximation is assumed for the statistical correlation between the velocity and temperature fields. A differential argument leads to derivation of the turbulent Prandtl number Pr(t) as a function of the turbulent Peclet Pe(t) number, which in turn depends on the turbulent eddy viscosity nu(t). The functional relationship between Pr(t) and Pe(t) is comparable to that of Yakhot et al. [Int. J. Heat Mass Transf. 30, 15 (1987)] and is in close consistency with direct-numerical-simulation results as well as measured data from experiments. The study proceeds further with limiting the operation of renormalization group analysis, yielding an inhomogeneous ordinary differential equation for an invariant thermal eddy diffusivity sigma. Simplicity of the equation renders itself a closed-form solution of sigma as a function of the wave number k, which, when combined with a modified Batchelor's energy spectrum for the passive temperature T, facilitates determination of the Batchelor constant C(B) and a parallel Smagorinsky model and the model constant C(P) for thermal turbulent energy transport.

Factors affecting gentamicin pharmacokinetics in septic patients.

BACKGROUND: This prospective, comparative study was designed to estimate the volume of distribution (Vd) and elimination rate constant (K(e)) of gentamicin and to determine the clinical factors affecting the pharmacokinetics of gentamicin in different stages of sepsis. METHOD: Seventy-seven critically ill patients treated with gentamicin for gram-negative sepsis were included. These septic patients were divided into hyperdynamic septic and hypodynamic septic groups according to cardiac index. Twenty-seven patients who received postoperative prophylactic gentamicin were recruited as controls. RESULTS: Fifty-two patients in the hyperdynamic septic group had a significantly larger Vd than those in the hypodynamic septic and control groups. The Vd was correlated significantly with both Acute Physiological Score (APS) (r=0.340, P<0.01) and cardiac index (r=0.394, P<0.01). The K(e) of gentamicin correlated significantly with both blood urea nitrogen (BUN) (r= 0.565, P<0.01) and serum creatinine level (r=0.563, P<0.01). CONCLUSION: The increased Vd in the septic patients was related to the severity of illness and magnitude of cardiac output. The K(e) of gentamicin was correlated with the serum creatinine level.

Peri-anhepatic phase oxygen kinetics in porcine liver transplantation.

BACKGROUND: We applied a liver transplantation animal model to examine the relationship between oxygen delivery and consumption. The presence of pathologic flow-dependent oxygen consumption was investigated during and after the anhepatic phase. The effect of venous-to-venous bypass on oxygen kinetics was evaluated. METHODS: Twelve pigs were randomly divided into two groups. The non-bypass group consisted of six pigs that were subjected to clamping of the hepatic artery, portal vein, and the superior and inferior vena cava to produce an anhepatic phase. The bypass group consisted of six pigs that underwent vascular clamping and liver transplantation with venous bypass. Hemodynamics, oxygen delivery index (DO2) and oxygen consumption index (VO2) were recorded during the peri-anhepatic phase. Best-fit regression lines were calculated for DO2 vs VO2. RESULTS: In the pigs without venous bypass, the blood pressure, cardiac index and VO2 dropped significantly after vascular clamping and lactic acidosis developed. In pigs with venous bypass, vascular clamping induced a significant decline of cardiac output and DO2 but VO2 was maintained by a compensatory increase in oxygen extraction ratio. DO2 and VO2 after the release of vascular clamping increased significantly higher than that before vascular clamping. The O2 supply-dependent regression line was drawn from the points below critical oxygen delivery with a slope of 0.232 (95% CI = 0.110-0.354, r2 = 0.50, p = 0.010). The pathologic supply-dependent line was drawn from the points with supranormal DO2 and VO2 with a slope of 0.185 (95% CI = 0.050-0.333, r2 = 0.510, p = 0.029). The slope of the supply-independent line was 0.0089 (95% CI = -0.030-0.050, r2 < 0.009, p = 0.12). CONCLUSIONS: Oxygen delivery dropped below the critical level and flow-dependent oxygen consumption developed during the anhepatic phase without venous bypass. Venous-to-venous bypass is necessary to maintain a critical DO2 and stable hemodynamics during porcine liver transplantation. Pathologic flow-dependent oxygen consumption developed after the anhepatic phase.

Ultrasound-guided cannulation of the internal jugular vein for dialysis vascular access in uremic patients.

BACKGROUND: A reliable temporary vascular access is always required for hemodialysis when a permanent vascular access is not available. However, techniques for creating temporary vascular accesses remain imperfect. This study utilized the 'SiteRite' ultrasound device to improve both success and complication rates of jugular venous cannulation for temporary access. METHODS: This prospective, comparative study recruited 104 uremic patients receiving ultrasound-guided and 86 patients undergoing landmark-guided percutaneous internal jugular venous cannulation of dual-lumen dialysis catheters. Success rate, number of puncture attempts, access time, and the complication rate of the ultrasound technique, in comparison with the landmark-guided technique, were studied. RESULTS: The ultrasound-guided cannulation was superior to the external landmark-guided cannulation in overall success rate (99.0 vs. 86.0%, p < 0.01), success rate of the first puncture attempt (80.8 vs. 34.9%, p < 0.01), average puncture (access) times (15.8 vs. 43.7 s, p < 0.01), puncture trials (1.39 vs. 2.58, p < 0.01), and traumatic complication rate (1.9 vs. 1 1.6%, p = 0.015). The incidence of infective complications for the ultrasound group was not different from that of the landmark-guided groups (2.9 vs. 2.3%, p = 0.589). CONCLUSION: The ultrasound-guided technique offers both safety and convenience in inserting jugular venous dialysis catheters. It represents a valuable technique in creating temporary dialysis hemoaccesses.

Anatomical variation of the internal jugular vein and its impact on temporary haemodialysis vascular access: an ultrasonographic survey in uraemic patients.

BACKGROUND: Creation of a reliable haemoaccess is a critical problem for practicing nephrologists once haemodialysis has been considered. A double-lumen internal jugular-vein catheter is favoured in most cases requiring temporary haemoaccess. However, numerous complications, even lethal ones, may occur with the cannulating procedure. Using ultrasound, we attempted to describe the occult anatomical variations of vessels which may be responsible for complications. METHODS: A 'SiteRite' ultrasonographic device was used to inspect the anatomical structure of the internal jugular veins (IJV) in 104 consecutive uraemic patients undergoing creation of internal jugular vein temporary angioaccess. Images of the vessels and demographic data of patients were recorded and analysed. RESULTS: Anatomical variations of the right and left IJVs were found in 19 (18.3%) and 17 (16.4%) uraemic patients respectively. Unilateral IJV variations were found in 18 patients (17.3%) and bilateral variations were discovered in nine patients (8.7%). A total of 27 patients (26.0%) had IJV anatomical variations that might contribute to difficulty in external landmark-guided IJV cannulation. CONCLUSIONS: The external anatomical landmarks for cannulating the IJV are not reliable in about one-quarter of uraemic patients. An ultrasound survey on the IJV anatomy is recommended for selecting proper puncture site and reducing risks of insertion complications for IJV dialysis catheters.

Building a strategic forecasting system for hospital foodservice operations.

Forecasting, which involves the manipulation of operational data, is a critical task in foodservice management. We propose a strategic forecasting system for foodservice management, which may be expedited by using decision support systems. The most notable potential for improved forecast performance and decision flexibility may rest with increasing forecasting information. This article provides a framework for building a strategic forecasting system that can help managers select and use appropriate forecasting models for foodservice operations.

Antinociceptive interaction between opioids and medetomidine: systemic additivity and spinal synergy.

The antinociceptive interaction on the tail flick (TF) and hot plate (HP) tests between opioid analgesics and medetomidine after intravenous (iv) or intrathecal administration were examined by isobolographic analysis. Male Sprague-Dawley rats received fixed ratios of medetomidine to morphine, fentanyl, and meperidine of 1:10 and 1:30, 10:1, and 1:3, respectively, by iv administration or 10:1, 3:1 and 10:1, and 1:3 by intrathecal administration, respectively. Data were expressed as the percentage maximal possible effect (%MPE). The A50 (dose producing 50% MPE) for each drug or drug combination was determined from the dose-response curve. Isobolographic analysis revealed that the effect of medetomidine combined with fentanyl, morphine, or meperidine was additive after iv administration. The intrathecal administration of combinations of medetomidine with the opioids produced a synergistic antinociceptive effect in the TF but not HP test. These data confirmed that the interaction between medetomidine and opioids in producing antinociception may be additive or synergistic, depending on the route of administration, drug ratio administered, and level of processing of the nociceptive input (i.e., spinal vs. supraspinal). Moreover, these results were consistent with a spinal role for alpha-2 adrenoceptors in mediating antinociception. The authors suggest that the interaction between the opioid and alpha-2 adrenergic receptors occurs within the spinal cord.

500-MHz proton NMR studies of the medium-dependent conformational preference of prostaglandin F2 alpha analogues.

The complete assignments of the 1H NMR spectra of 2-10 mM D2O solutions of prostaglandin F2 alpha (PGF2 alpha), its C-15 epimer, and analogues bearing a gem-dimethyl group at C-16 or C-17 are presented. PGF2 alpha and its 1,9- and 1,15-lactones were similarly studied in CDCl3 solution. The assignments follow from extensive scalar decoupling and difference NOE spectra and the examination of a specifically deuterated analogue. These studies also define the conformation (including cyclopentane pseudorotational preference) from C-5 through C-16 in each system. The macrolides show little or no conformational freedom at C-4----C-1, but extensive rotational averaging occurs in the terminal portions of both side chains in the monocyclic compounds. The conformational features so determined are contrasted to those seen in crystal structures and those postulated to occur upon binding to PGF2 alpha-recognizing receptors. The NMR data run counter to the DeTitta hypothesis that changes in the orientation of the C-13,14 pi-bond nodal plane relative to the cyclopentane ring and the C-15-O bond are recognition determinants at PGF2 alpha-specific receptors and account for the medium-dependent chiroptical spectral changes previously reported.

Temperature and field dependent 1H-NMR relaxation data as probes of prostaglandin motional parameters in aqueous media.

Proton resonance correlation times (tau eff) for PGF2 alpha and a more rigid analog have been derived from the field-strength dependence of spin-lattice relaxation times ( T1D ) using 200 and 500 MHz observation. Those hydrogens showing tau eff less than the value calculated for whole molecule tumbling (which applies for H-5----H-15) also show a significantly greater temperature dependence for T1D at 500 MHz. Minor wagging may occur at the C-7 and C-10 methylenes , and gradually increasing segmental motion is observed toward both side chain termini. A current model for the aqueous geometry of PGF2 alpha is developed from this data and studies of relaxation rate changes upon specific deuteration.