Prospective Evaluation of Ultrasonic Surgical Dissectors in Hepatic Resection: A Cooperative Multicenter Study

Blood loss is the major cause of postoperative mortality and morbidity associated with hepatic resection. A prospective multicenter study was conducted to determine if ultrasonic dissectors (USD) were useful in hepatic resection and could reduce this hemorrhagic risk. Forty-seven hepatic resections were performed in 42 consecutive patients during a two month period in 11 public, surgical centers. Twenty-one patients had primary or secondary malignancies, six had benign tumors, two had biliary cysts, one had cholangiocarcinoma, one had Caroli’s disease, and 11 had hydatid cysts of the liver. Two different USD devices were evaluated (CUSA System-Lasersonics and NIIC-DX 101 T). The hepatic resections tested included a wide range of procedures. Each surgeon had the possibility of choosing between the USD and his own usual technique for each operative step and according to local conditions. The average volume of blood infused, irrespective of the underlying pathology or the procedure performed, was 1.0 L (range 0-4.8 L). Fourteen patients required no transfusions. No operative or immediate postoperative deaths were recorded. Five major complications, all unrelated to the use of the USD, developed in three patients. Access to intra and extraparenchymal arterial and venous tributaries and particularly the control of the hepatic veins were facilitated by USD. While transection of hepatic parenchyma was neither easier nor faster than with conventional techniques, it was found to be less hemorrhagic. Overall appraisal was expressed on an analog scale; the USD was found to be helpful or very helpful in 75 percent of all resections. With regard to the pathology being treated, total or partial excision of hydatid cysts was greatly enhanced by the use of the USD while this benefit was not found for wedge resections of other hepatic lesions. With regard to user friendliness and maintenance, the NIIC-DX 101 T device was preferred. We conclude that the USD facilitates formal hepatic resections. Converging opinions emerging from various surgical centers reinforce this conclusion

Effect of cardiopulmonary bypass on activated partial thromboplastin time waveform analysis, serum procalcitonin and C-reactive protein concentrations

Abstract Introduction Systemic inflammatory response syndrome (SIRS) is a frequent condition after cardiopulmonary bypass (CPB) and makes conventional biological tests fail to detect postoperative sepsis. Biphasic waveform (BPW) analysis is a new biological test derived from activated partial thromboplastin time that has recently been proposed for sepsis diagnosis. The aim of this study was to investigate the accuracy of BPW to detect sepsis after cardiac surgery under CPB. Methods We conducted a prospective study in American Society of Anesthesiologists' (ASA) physical status III and IV patients referred for cardiac surgery under CPB. Procalcitonin (PCT) and BPW were recorded before surgery and every day during the first week following surgery. Patients were then divided into three groups: patients presenting no SIRS, patients presenting with non-septic SIRS and patients presenting with sepsis. Results Thirty two patients were included. SIRS occurred in 16 patients (50%) including 5 sepsis (16%) and 11 (34%) non-septic SIRS. PCT and BPW were significantly increased in SIRS patients compared to no SIRS patients (0.9 [0.5-2.2] vs. 8.1 [2.0-21.3] ng/l for PCT and 0.10 [0.09-0.14] vs. 0.29 [0.16-0.56] %T/s for BPW; P < 0.05 for both). We observed no difference in peak PCT value between the sepsis group and the non-septic SIRS group (8.4 [7.5-32.2] vs. 7.8 [1.9-17.5] ng/l; P = 0.67). On the other hand, we found that BPW was significantly higher in the sepsis group compared to the non-septic SIRS group (0.57 [0.54-0.78] vs. 0.19 [0.14-0.29] %T/s; P < 0.01). We found that a BPW threshold value of 0.465%T/s was able to discriminate between sepsis and non-septic SIRS groups with a sensitivity of 100% and a specificity of 93% (area under the curve: 0.948 +/- 0.039; P < 0.01). Applying the previously published threshold of 0.25%T/s, we found a sensitivity of 100% and a specificity of 72% to discriminate between these two groups. Neither C-reactive protein (CRP) nor PCT had significant predictive value (area under the curve for CRP was 0.659 +/- 0.142; P = 0.26 and area under the curve for PCT was 0.704 +/- 0.133; P = 0.15). Conclusions BPW has potential clinical applications for sepsis diagnosis in the postoperative period following cardiac surgery under CPB

Biological and phytochemical investigations of extracts from Pterocarpus erinaceus Poir (Fabaceae) root barks

Background: Pterocarpus erinaceus Poir. belonging to Fabacae familly is used as medicinal plant in Burkina Faso’s folk medicine. Roots of P. erinaceus are used to treat ulcer, stomach ache and inflammatory diseases. The objective of the present study was to carry out phytochemical composition of methanol (MeOH) and dichloromethane (DCM) extracts from Pterocarpus erinaceus roots, to isolate pure compounds, and to evaluate their pharmacological activities.Methods: Chromatographic fractionation led to the isolation of active components of the extracts. The structures were established by NMR analysis and comparison with data from literature. The anti-inflammatory activity was evaluated using croton oil-induced edema of mice ear as well as the effect of extracts against lipoxygenase and lipid peroxidation was evaluated. 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Cupric-reducing antioxidant capacity (CUPRAC) methods were used to evaluate the antioxidant activity of the extracts.Results: Friedelin (1), 3α-hydroxyfriedelan-2-one (2), α-sophoradiol (3) and stigmasterol (4) were isolated from DCM extract and maltol-6-O-apiofuranoside-glucopyranoside (5) isolated from MeOH. DCM extract and friedelin, 3α-hydroxyfriedelan-2-one, α- sophoradiol showed a significant anti-inflammatory effect against ear edema. Friedelin (1), α-sophoradiol (3) and maltol-6-O-apiofuranoside-glucopyranoside (5) exhibited lipoxygenase inhibition. MeOH extract (100 μg/mL) inhibited lipoxygenase and lipid peroxidation activities at 45.1 ± 3% and 30.7 ± 0.5% respectively. MeOH extract, ethyl acetate fraction and butanol fraction exhibited antioxidant property with both two methods used.Conclusion: The results suggested that the extracts and compounds from roots of Pterocarpus erinaceus possessed local antiinflammatory effect, antioxidant properties and inhibitor effect against lipoxygenase and lipid peroxidation activities.Keywords: Pterocarpus erinaceus, triterpenes, anti-inflammatory, antioxidant, lipoxygenas

BIOLOGICAL AND PHYTOCHEMICAL INVESTIGATIONS OF EXTRACTS FROM PTEROCARPUS ERINACEUS POIR (FABACEAE) ROOT BARKS

Background: Pterocarpus erinaceus Poir. belonging to Fabacae familly is used as medicinal plant in Burkina Faso’s folk medicine. Roots of P. erinaceus are used to treat ulcer, stomach ache and inflammatory diseases. The objective of the present study was to carry out phytochemical composition of methanol (MeOH) and dichloromethane (DCM) extracts from Pterocarpus erinaceus roots, to isolate pure compounds, and to evaluate their pharmacological activities. Methods: Chromatographic fractionation led to the isolation of active components of the extracts. The structures were established by NMR analysis and comparison with data from literature. The anti-inflammatory activity was evaluated using croton oil-induced edema of mice ear as well as the effect of extracts against lipoxygenase and lipid peroxidation was evaluated. 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Cupric-reducing antioxidant capacity (CUPRAC) methods were used to evaluate the antioxidant activity of the extracts. Results: Friedelin (1), 3α-hydroxyfriedelan-2-one (2), α-sophoradiol (3) and stigmasterol (4) were isolated from DCM extract and maltol-6-O-apiofuranoside-glucopyranoside (5) isolated from MeOH. DCM extract and friedelin, 3α-hydroxyfriedelan-2-one, α- sophoradiol showed a significant anti-inflammatory effect against ear edema. Friedelin (1), α-sophoradiol (3) and maltol-6-Oapiofuranoside- glucopyranoside (5) exhibited lipoxygenase inhibition. MeOH extract (100 μg/mL) inhibited lipoxygenase and lipid peroxidation activities at 45.1 ± 3% and 30.7 ± 0.5% respectively. MeOH extract, ethyl acetate fraction and butanol fraction exhibited antioxidant property with both two methods used. Conclusion: The results suggested that the extracts and compounds from roots of Pterocarpus erinaceus possessed local antiinflammatory effect, antioxidant properties and inhibitor effect against lipoxygenase and lipid peroxidation activities

CBX4-mediated SUMO modification regulates BMI1 recruitment at sites of DNA damage

Polycomb group (PcG) proteins are involved in epigenetic silencing where they function as major determinants of cell identity, stem cell pluripotency and the epigenetic gene silencing involved in cancer development. Recently numerous PcG proteins, including CBX4, have been shown to accumulate at sites of DNA damage. However, it remains unclear whether or not CBX4 or its E3 sumo ligase activity is directly involved in the DNA damage response (DDR). Here we define a novel role for CBX4 as an early DDR protein that mediates SUMO conjugation at sites of DNA lesions. DNA damage stimulates sumoylation of BMI1 by CBX4 at lysine 88, which is required for the accumulation of BMI1 at DNA damage sites. Moreover, we establish that CBX4 recruitment to the sites of laser micro-irradiation-induced DNA damage requires PARP activity but does not require H2AX, RNF8, BMI1 nor PI-3-related kinases. The importance of CBX4 in the DDR was confirmed by the depletion of CBX4, which resulted in decreased cellular resistance to ionizing radiation. Our results reveal a direct role for CBX4 in the DDR pathway

Targeting Bone Alleviates Osteoarthritis in Osteopenic Mice and Modulates Cartilage Catabolism

Subchondral bone modifications occur early in the development of osteoarthritis (OA). The level of bone resorption might impact cartilage remodeling. We therefore assessed the in vivo and in vitro effects of targeting bone resorption in OA and cartilage metabolism.OA was induced by meniscectomy (MNX) in ovariectomized osteopenic mice (OP) treated with estradiol (E2), pamidronate (PAM), or phosphate buffered saline (PBS) for 6 weeks. We assessed the subchondral bone and cartilage structure and the expression of cartilage matrix proteases. To assess the involvement of bone soluble factors in cartilage metabolism, supernatant of human bone explants pre-treated with E2 or PAM were transferred to cartilage explants to assess proteoglycan release and aggrecan cleavage. OPG/RANKL mRNA expression was assessed in bone explants by real-time quantitative PCR. The role of osteoprotegerin (OPG) in the bone-cartilage crosstalk was tested using an OPG neutralizing antibody.Bone mineral density of OP mice and osteoclast number were restored by E2 and PAM (p<0.05). In OP mice, E2 and PAM decreased ADAMTS-4 and -5 expression, while only PAM markedly reduced OA compared to PBS (2.0±0.63 vs 5.2±0.95; p<0.05). OPG/RANKL mRNA was increased in human bone explants treated with both drugs (2.2-3.7-fold). Moreover, supernatants from bone explants cultured with E2 or PAM reduced aggrecan cleavage and cartilage proteoglycan release (73±8.0% and 80±22% of control, respectively, p<0.05). This effect was reversed with osteoprotegerin blockade.The inhibition of bone resorption by pamidronate in osteopenic mice alleviates the histological OA score with a reduction in the expression of aggrecanases. Bone soluble factors, such as osteoprotegerin, impact the cartilage response to catabolic factors. This study further highlights the importance of subchondral bone in the regulation of joint cartilage damage in OA

Regional cortical volumes and congenital heart disease: a MRI study in 22q11.2 deletion syndrome

Children with congenital heart disease (CHD) who survive surgery often present impaired neurodevelopment and qualitative brain anomalies. However, the impact of CHD on total or regional brain volumes only received little attention. We address this question in a sample of patients with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition frequently associated with CHD. Sixty-one children, adolescents, and young adults with confirmed 22q11.2 deletion were included, as well as 80 healthy participants matched for age and gender. Subsequent subdivision of the patients group according to CHD yielded a subgroup of 27 patients with normal cardiac status and a subgroup of 26 patients who underwent cardiac surgery during their first years of life (eight patients with unclear status were excluded). Regional cortical volumes were extracted using an automated method and the association between regional cortical volumes, and CHD was examined within a three-condition fixed factor. Robust protection against type I error used Bonferroni correction. Smaller total cerebral volumes were observed in patients with CHD compared to both patients without CHD and controls. The pattern of bilateral regional reductions associated with CHD encompassed the superior parietal region, the precuneus, the fusiform gyrus, and the anterior cingulate cortex. Within patients, a significant reduction in the left parahippocampal, the right middle temporal, and the left superior frontal gyri was associated with CHD. The present results of global and regional volumetric reductions suggest a role for disturbed hemodynamic in the pathophysiology of brain alterations in patients with neurodevelopmental disease and cardiac malformations

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20 : G protein- coupled receptors

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14748. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.Peer reviewe

Serotonergic Contribution to Boys' Behavioral Regulation

Animal and human adult studies reveal a contribution of serotonin to behavior regulation. Whether these findings apply to children is unclear. The present study investigated serotonergic functioning in boys with a history of behavior regulation difficulties through a double-blind, acute tryptophan supplementation procedure.Participants were 23 boys (age 10 years) with a history of elevated physical aggression, recruited from a community sample. Eleven were given a chocolate milkshake supplemented with 500 mg tryptophan, and 12 received a chocolate milkshake without tryptophan. Boys engaged in a competitive reaction time game against a fictitious opponent, which assessed response to provocation, impulsivity, perspective taking, and sharing. Impulsivity was further assessed through a Go/No-Go paradigm. A computerized emotion recognition task and a staged instrumental help incident were also administered.Boys, regardless of group, responded similarly to high provocation by the fictitious opponent. However, boys in the tryptophan group adjusted their level of responding optimally as a function of the level of provocation, whereas boys in the control group significantly decreased their level of responding towards the end of the competition. Boys in the tryptophan group tended to show greater perspective taking, tended to better distinguish facial expressions of fear and happiness, and tended to provide greater instrumental help to the experimenter.The present study provides initial evidence for the feasibility of acute tryptophan supplementation in children and some effect of tryptophan supplementation on children's behaviors. Further studies are warranted to explore the potential impact of increased serotonergic functioning on boys' dominant and affiliative behaviors

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate