ß-actin contributes to open chromatin for activation of the adipogenic pioneer factor CEBPA during transcriptional reprograming.

Adipogenesis is regulated by a cascade of signals that drive transcriptional reprogramming in adipocytes. Here, we report that nuclear actin regulates the chromatin states that establish tissue- specific expression during adipogenesis. To study the role of ß-actin in adipocyte differentiation, we conducted RNA sequencing on wild-type and ß-actin knockout mouse embryonic fibroblasts (MEFs) after reprograming to adipocytes. We found that ß-actin depletion affects induction of several adipogenic genes during transcriptional reprograming. This impaired regulation of adipogenic genes is linked to reduced expression of the pioneer factor Cebpa and is rescued by reintroducing NLS-tagged ß-actin. ATAC-Seq in knockout MEFs revealed that actin-dependent reduction of Cebpa expression correlates with decreased chromatin accessibility and loss of chromatin association of the ATPase Brg1. This, in turn, impairs CEBPB's association with its Cebpa promoter-proximal binding site during adipogenesis. We propose a role for the nuclear ß-actin pool in maintaining open chromatin for transcriptional reprogramming during adipogenic differentiation.

Triterpenoid saponins from Schefflera arboricola.

Nine triterpenoid saponins were isolated from the leaves and stems of Schefflera arboricola. The saponins were characterised, on the basis of chemical and spectral evidence, as 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucuronopyranosyl] oleanolic acid, 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucuronopyranosyl] echinocystic acid, 3-O-[beta-D-apiofuranosyl-(1-->4)-beta-D-glucuronopyranosyl] oleanolic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L-ramnopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid, 3-O-alpha-L-rhamnopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->4)-[beta-D-galactopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid, 3-O-alpha-L-rhamnopyranosyl-(1-->4)-[beta-D-galactopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester, 3-O-beta-D-apiofuranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid and 3-O-beta-D-apiofuranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester.

Acylated flavonol glycosides from Eugenia jambolana leaves.

Two acylated flavonol glycosides and 15 known polyphenols have been isolated and identified from the leaves of Eugenca jambolana Lam. The structures of the new compounds were identified as 3-O-(4"-O-acetyl)-alpha-L-rhamnopyranoside of mearnsetin (myricetin 4'-methyl ether) and myricetin 3-O-(4"-O-acetyl-2"-O-galloyl)-alpha-L-rhamnopyranoside. The complete structure elucidation of all isolated metabolites based on chemical and spectroscopic methods of analysis (UV, 1D and 2D NMR) as well as negative ESI-MS with and without CID in-source fragmentation.

Plasma concentration following oral and intramuscular atropine in children and their clinical effects.

In a paediatric population, we compared i.m. v oral atropine premedication to a control group without atropine and determined atropine plasma concentrations (APC). Forty-five children were randomly assigned to one of three groups. Group I received atropine, 20 micrograms.kg-1 i.m., 15 min prior to induction. Group II received atropine, 30 micrograms.kg-1 orally, group III received no atropine. APC (expressed as percent of muscarine-2 receptor subtype occupancy), heart rate, rectal temperature, and salivation were determined before atropine, and 15, 25, 45, 60, 90, 120 (no APC), and 150 min following atropine. Only 10-20% of the M2-cholinoceptors were occupied after oral atropine with a peak at 90 min compared to 60-70% occupancy with a peak 25 min after i.m. atropine. The peak in M2-cholinoceptor occupation in group I was paralleled by a peak percentage change in heart rate of 15% from baseline. The peak in receptor occupation in group II did not correspond to the peak increase in heart rate. The percentage change of heart rate over time was not significantly different from baseline values in any of the groups. Bradycardia or temperature changes did not occur in any of the groups. Antisialogogue effects were observed only in group I. We conclude that atropine; 30 micrograms.kg-1 orally is not an equipotent dosage to atropine, 20 micrograms.kg-1 i.m.

Saponins from Fagonia arabica.

Seven new triterpenoid saponins were isolated and identified from the aerial parts of Fagonia arabica. They were characterized as 3-O-beta-D-xylopyranosyl(1-->2)-[beta-D-glucopyranosyl(1-->3)]-alpha-L- arabinopyranosyl oleanolic acid 28-O-beta-D-glucopyranoside, 3-O-beta-D-glucopyranosyl(1-->2)-[beta-D-glucopyranosyl(1-->3)]-alpha-L- arabino pyranosyl oleanolic acid 28-O-beta-D-glucopyranoside, 3-O-beta-D-xylopyranosyl(1-->2)-[beta-D-glucopyranosyl (1-->3)]-alpha- L-arabinopyranosyl oleanolic acid, 3-O-beta-D-glucopyranosyl(1-->2)-[beta-D-glucopyranosyl(1-->3)]-alpha-L- arabino pyranosyl oleanolic acid, 3-O-beta-D-xylopyranosyl(1-->2)-[beta-D-glucopyranosyl (1-->3)]-alpha-L-arabinopyranosyl 27-hydroxyoleanolic acid, 28-O-beta-D-glucopyranoside, 3-O-beta-D-xylopyranosyl(1-->2)-[beta-D-glucopyranosyl(1-->3)]-alpha-L- arabinopyranosyl ursolic acid 28-O-beta-D-glucopyranoside and 3-O-beta-D-xylopyranosyl (1-->2)-[beta-D-glucopyranosyl (1-->3)-alpha-L-arabinopyranosyl 27-hydroxyursolic acid 28-O-beta-D-glucopyranoside. The structures of the saponins were established by analyses of their 1H and 13C NMR spectra with the aid of 2D experiments. The two genins, 27-hydroxyoleanolic acid and 27-ursolic acid, are new.

[Analgesia and sedation in neurosurgical intensive care patients]. / Analgosedierung bei neurochirurgischen Intensivpatienten.

Different concepts for analgosedation of neurosurgical patients are recommended during postoperative ventilation. In 30 neurosurgical patients (2 groups of 15 patients), we studied a continuous i.v. application of alfentanil (Rapifen) and midazolam (Dormicum) compared to an application of continuously given alfentanil with discontinuously given midazolam. A good analgosedation (i.e. sufficient sedation with good neurological judgement) was more frequently achieved (8/15 patients) by continuous application of both substances (alfentanil 0.023 mg/kg b.w./h, midazolam 0.10 mg/kg b.w./h), compared to discontinuous application of midazolam (4.5/15 patients; alfentanil 0.028 mg/kg b.w./h, midazolam 0.13 mg/kg b.w./h). No differences in extubation times were observed. We conclude from our results that a continuous application of both substances is superior to a discontinuous application of midazolam with continuously given alfentanil. A lower dosage of each substance is necessary to maintain a better state of analgosedation.

[Fentanyl versus sufentanil basic anesthesia. Hypnotic effect, muscle rigidity and efficacy of competitive muscle relaxants]. / Fentanyl- versus Sufentanil-Basisanaesthesie. Hypnotischer Effekt, Muskelrigidität und Wirksamkeit kompetitiver Muskelrelaxantien.

As induction agents for cardioanesthesia, sufentanil (S) and fentanyl (F) are usually employed in combination with nondepolarizing muscle relaxants. We investigated potential interactions of these opioids with the relaxant component, paying special regard to the role of muscular rigidity and opioid-induced alterations of hemodynamics. Narcotic anesthesia was induced randomly in 45 coronary artery bypass patients with either F (20 micrograms/kg) or S (4 micrograms/kg). After 6 min, neuromuscular blockade was initiated within each group randomly with either vecuronium (V) or pancuronium (P) (0.01 mg/kg each). During opiate administration, the times for cessation of spontaneous respiration and loss of responsiveness to verbal and tactile stimuli were measured. The degree of opiate-induced muscular rigidity, simultaneous changes in arterial paCO2, cardiac indices (CI) prior to opioid and relaxant administration, onset and recovery from neuromuscular blockade (by electromyographic train-of-four registration), and motor response to laryngoscopy and intubation were recorded. The onset of spontaneous apnea (TK = time to breathing upon command only) and unresponsiveness (TM = time to controlled mask ventilation) was significantly faster with S than with F. Muscular rigidity was moderate in 25% of patients and severe in 35%-40%, during the administration of both narcotics. No significant differences between S and F were observed. During ventilation by face mask, patients with clinically apparent rigidity showed a statistically significant mean increase in paCO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Double inlet left ventricular main chamber, subaortic small left sided right ventricle and interrupted aortic arch type A. What operation is indicated when?

A case of a 23 year old female patient who suffered from the complex congenital heart lesion of a double inlet left ventricular main chamber, subaortic small left sided right ventricle and interrupted aortic arch type A is reported. With equally high blood pressures, the perfusion in the upper half of the body was maintained through the ascending aorta while the lower half and the lungs were supplied through the pulmonary artery and a patent ductus arteriosus (PDA). Angiographically, the bulbo-ventricular foramen appeared to be nonrestrictive. However, distinct signs of muscular subaortic stenosis were detected. The hemodynamic status principally allowed surgical correction when this became necessary because of increasing left heart failure. Treatment for this complex lesion undoubtedly required reduction of pulmonary perfusion, even when associated with the danger of increasing cyanosis. Various forms of surgical treatment (functional correction, palliative procedures) were discussed. The most elegant was performed without cardiopulmonary bypass: this consisted in connection of the pulmonary artery with the descending aorta using a 16 mm Dacron tube, reconstruction of the aortic arch by a prostheso-subclavian synthetic graft, suture ligation of the PDA, and banding of the pulmonary artery trunk distal to the origin of the prosthesis. One year after the operation, the patient's physical performance has improved. Moreover, despite the disappearance of cardiac failure she has not become more cyanotic during exertion.