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Cannabinoid-based medicines have therapeutic potential for the treatment of pain. Augmentation of levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is analgesic in models of acute and inflammatory pain states. The aim of this study was to determine whether local inhibition of FAAH alters nociceptive responses of spinal neurons in the spinal nerve ligation model of neuropathic pain. Electrophysiological studies were performed 14-18 d after spinal nerve ligation or sham surgery, and the effects of the FAAH inhibitor cyclohexylcarbamic acid 3-carbamoyl biphenyl-3-yl ester (URB597) on mechanically evoked responses of spinal neurons and levels of endocannabinoids were determined. Intraplantar URB597 (25 µg in 50 µl) significantly (p < 0.01) attenuated mechanically evoked responses of spinal neurons in sham-operated rats. Effects of URB597 were blocked by the cannabinoid 1 receptor (CB1) antagonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1 H-pyrazole-3-carboxamide] (30 µg in 50 µl) and the opioid receptor antagonist naloxone. URB597 treatment increased levels of anandamide, 2-arachidonyl glycerol, and oleoyl ethanolamide in the ipsilateral hindpaw of shamoperated rats. Intraplantar URB597 (25 µg in 50 µl) did not, however, alter mechanically evoked responses of spinal neurons in spinal nerve ligated (SNL) rats or hindpaw levels of endocannabinoids. Intraplantar injection of a higher dose of URB597 (100 µg in 50 µl) significantly (p < 0.05) attenuated evoked responses of spinal neurons in SNL rats but did not alter hindpaw levels of endocannabinoids. Spinal administration of URB597 attenuated evoked responses of spinal neurons and elevated levels of endocannabinoids in shamoperated and SNL rats. These data suggest that peripheral FAAH activity may be altered or that alternative pathways of metabolism have greater importance in SNL rats. [ABSTRACT FROM AUTHOR]

Peripheral cannabinoid 2 receptors (CB2 receptors) modulate immune responses and attenuate nociceptive behaviour in models of acute and persistent pain. The aim of the present study was to investigate whether peripheral CB2 receptors modulate spinal processing of innocuous and noxious responses and to determine whether there are altered roles of CB2 receptors in models of persistent pain. Effects of local administration of the CB2 receptor agonist JWH-133 (5 and 15 µg/50 µL) on mechanically evoked responses of spinal wide dynamic range (WDR) neurons in noninflamed rats, rats with carrageenan-induced hindpaw inflammation, sham operated rats and spinal nerve-ligated (SNL) rats were determined in anaesthetized ratsin vivo. Mechanical stimulation (von Frey filaments, 6–80 g) of the peripheral receptive field evoked firing of WDR neurons. Mechanically evoked responses of WDR neurons were similar in noninflamed, carrageenan-inflamed, sham-operated and SNL rats. Intraplantar injection of JWH-133 (15 µg), but not vehicle, significantly (P < 0.05) inhibited innocuous and noxious mechanically evoked responses of WDR neurons in all four groups of rats. In many cases the selective CB2 receptor antagonist, SR144528 (10 µg/50 µL), attenuated the inhibitory effects of JWH-133 (15 µg) on mechanically evoked WDR neuronal responses. The CB1 receptor antagonist, SR141716A, did not attenuate the inhibitory effects of JWH-133 on these responses. Intraplantar preadministration of JWH-133 also inhibited (P < 0.05) carrageenan-induced expansion of peripheral receptive fields of WDR dorsal horn neurons. This study demonstrates that activation of peripheral CB2 receptors attenuates both innocuous- and noxious-evoked responses of WDR neurons in models of acute, inflammatory and neuropathic pain. [ABSTRACT FROM AUTHOR]

The presence of cannabinoid1 (CB1 ) receptors on primary afferent fibres may provide a novel target for cannabinoid analgesics. The present study investigated the ability of peripheral CB1 receptors to modulate innocuous and noxious transmission in noninflamed rats and rats with peripheral carrageenan inflammation. Effects of peripheral injection of arachidonyl-2-choroethylamide (ACEA; 10 and 30 µg in 50 µL), a selective CB1 receptor agonist, on mechanically evoked responses of dorsal horn neurons were studied in noninflamed rats and rats with peripheral carrageenan inflammation. Peripheral injection of ACEA (30 µg in 50 µL) significantly inhibited innocuous (12 g) mechanically evoked responses of spinal neurons in noninflamed (27 ± 4% of control; P < 0.01) and inflamed (12 ± 8% of control; P < 0.05) rats. Similarly, noxious (80 g) mechanically evoked responses of spinal neurons were inhibited by peripheral injection of ACEA (30 µg in 50 µL) in noninflamed rats (51 ± 9% of control; P < 0.01) and rats with peripheral carrageenan inflammation (21 ± 8% of control; P < 0.01). Inhibitory effects of ACEA were significantly greater in rats with peripheral carrageenan inflammation than in noninflamed rats ( P < 0.05). Inhibitory effects of ACEA were significantly blocked by coadministration of the CB1 receptor antagonist SR141716A in both groups of rats. Peripheral injection of SR141716A alone did not alter mechanically evoked responses of spinal neurons in either group of rats. These data demonstrate that activation of peripheral CB1 receptors can inhibit innocuous and noxious somatosensory processing. Furthermore, following peripheral inflammation there is an enhanced inhibitory effect of a peripherally administered CB1 receptor agonist on both innocuous and noxious mechanically evoked responses of spinal neurons. [ABSTRACT FROM AUTHOR]

Primary mucinous adenocarcinomas of the appendix represent 8.0% of all carcinomas of the appendix. As a group, primary appendiceal malignancies represent 0.5% of all intestinal tumors and are important because they are rarely diagnosed before surgery. Two cases of carcinoid tumors of the appendix have been described; however, no tumors have been described using transvaginal ultrasonography in a female patient. [ABSTRACT FROM AUTHOR]

Members of the human Zyxin family are LIM domain-containing proteins that perform critical cellular functions and are indispensable for cellular integrity. Despite their importance, not much is known about their structure, functions, interactions and dynamics. To provide insights into these, we used a set of in-silico tools and databases and analyzed their amino acid sequence, phylogeny, post-translational modifications, structure-dynamics, molecular interactions, and functions. Our analysis revealed that zyxin members are ohnologs. Presence of a conserved nuclear export signal composed of LxxLxL/LxxxLxL consensus sequence, as well as a possible nuclear localization signal, suggesting that Zyxin family members may have nuclear and cytoplasmic roles. The molecular modeling and structural analysis indicated that Zyxin family LIM domains share similarities with transcriptional regulators and have positively charged electrostatic patches, which may indicate that they have previously unanticipated nucleic acid binding properties. Intrinsic dynamics analysis of Lim domains suggest that only Lim1 has similar internal dynamics properties, unlike Lim2/3. Furthermore, we analyzed protein expression and mutational frequency in various malignancies, as well as mapped protein-protein interaction networks they are involved in. Overall, our comprehensive bioinformatic analysis suggests that these proteins may play important roles in mediating protein-protein and protein-nucleic acid interactions. [ABSTRACT FROM AUTHOR]

During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaque in the arterial wall and cause its rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, apoE\(^{−/−}\) mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. When seeking the source of surplus monocytes in plaque, we found that myocardial infarction liberated hematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signaling. The progenitors then seeded the spleen yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.

Postpartum haemorrhage is a major challenge in obstetrics. Although the main risk factors for postpartum haemorrhage have been well-recognised and established in scientific literature, there is less information regarding the effect of specific factors in certain situations, such as in cases where postpartum haemorrhage that becomes severe, or in cases refractory to medical therapy. The primary trial investigated the effect of carbetocin versus oxytocin for the prevention of postpartum haemorrhage on over 90 000 mothers from ten different countries. [Extracted from the article]

The hepatitis B virus (HBV) chronically infects over 250 million people worldwide and is one of the leading causes of liver cancer and hepatocellular carcinoma. HBV persistence is due in part to the highly stable HBV minichromosome or HBV covalently closed circular DNA (cccDNA) that resides in the nucleus. As HBV replication requires the help of host transcription factors to replicate, focusing on host protein–HBV genome interactions may reveal insights into new drug targets against cccDNA. The structural details on such complexes, however, remain poorly defined. In this review, the current literature regarding host transcription factors' interactions with HBV cccDNA is discussed. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to evaluate and compare erythropoietin levels as related to obstetric conditions, including acute and chronic bleeding, preeclampsia, and multiple gestations.Study Design: During April 1999 all women in the labor and delivery unit with delivery expected to occur within 24 to 72 hours of admission had erythropoietin and hematocrit values obtained. First-trimester hematocrit values, obstetric problems, medications, and history of vaginal bleeding were obtained from patient interview, examination, and the prenatal record. Statistics were analyzed by the Student t test and chi(2).Results: During a 1-month period, 302 consecutive women were divided into 5 groups on the basis of obstetric events. Group 1 consisted of women with normal, uncomplicated term singleton gestations (n = 230); group 2, women with acute vaginal bleeding (n = 10); group 3, women with chronic vaginal bleeding (n = 29); group 4, women with multiple gestations (n = 13); and group 5, women with preeclampsia (n = 16). The mean erythropoietin level in group 1 (20. 2 +/- 10.3 mU/mL) was significantly different from values in the other 4 groups (group 2, 74.2 +/- 29.2 mU/mL; group 3, 65.0 +/- 33.0 mU/mL; group 4, 34.8 +/- 16.8 mU/mL; group 5, 43.4 +/- 11.4 mU/mL; P <.001). The admission hematocrit for group 1 (0.369 +/- 0.029) was significantly greater than for groups 2 and 3 (group 2, 0.323 +/- 0. 024; group 3, 0.321 +/- 0.023; P <.001) and significantly lower than for group 5 (0.384 +/- 0.022; P <.05).Conclusion: The maternal serum erythropoietin level varies depending on the events occurring during gestation. Acute and chronic bleeding, multiple gestations, and preeclampsia are all associated with various serum erythropoietin levels. [ABSTRACT FROM AUTHOR]

Background: Wearable and connected health devices along with the recent advances in mobile and cloud computing provide a continuous, convenient-to-patient, and scalable way to collect personal health data remotely. The Wavelet Health platform and the Wavelet wristband have been developed to capture multiple physiological signals and to derive biometrics from these signals, including resting heart rate (HR), heart rate variability (HRV), and respiration rate (RR). Objective: This study aimed to evaluate the accuracy of the biometric estimates and signal quality of the wristband. Methods: Measurements collected from 35 subjects using the Wavelet wristband were compared with simultaneously recorded electrocardiogram and spirometry measurements. Results: The HR, HRV SD of normal-to-normal intervals, HRV root mean square of successive differences, and RR estimates matched within 0.7 beats per minute (SD 0.9), 7 milliseconds (SD 10), 11 milliseconds (SD 12), and 1 breaths per minute (SD 1) mean absolute deviation of the reference measurements, respectively. The quality of the raw plethysmography signal collected by the wristband, as determined by the harmonic-to-noise ratio, was comparable with that obtained from measurements from a finger-clip plethysmography device. Conclusions: The accuracy of the biometric estimates and high signal quality indicate that the wristband photoplethysmography device is suitable for performing pulse wave analysis and measuring vital signs. [ABSTRACT FROM AUTHOR]