[Effect of high flow nasal catheter oxygen to prevent hypoxemia in endoscopic retrograde cholangiopancreatography surgery in aged].

Objective: To explore the effect of high-flow nasal catheter oxygen inhalation in preventing hypoxemia during endoscopic retrograde cholangiopancreatography (ERCP) surgery in elderly patients. Methods: From September 2021 to September 2022, 116 elderly patients (aged ≥ 70 years) who underwent elective ERCP in the Northern Theater General Hospital were prospectively selected, then divided into general nasal catheter oxygen inhalation group [group C, 31 males and 27 females, aged (79.8±6.4) years] and high-flow nasal catheter oxygen inhalation group [group H, 33 males and 25 females, aged (81.4±6.7) years], with 58 patients in each group. All patients were monitored for anesthesia by target-controlled infusion of propofol and remifentanil. The main outcome index was the incidence of intraoperative subclinical hypoxemia (90% ≤ SpO2 < 95%, duration >5 s), hypoxemia (75% < SpO2 < 90%, 5 s < duration ≤ 60 s) and severe hypoxemia (SpO2 < 75% or SpO2 < 90%, duration > 60 s). Secondary observation measures were SpO2 from T0 to T5 (T0, before anesthesia induction; T1, immediately after anesthesia induction; T2, endoscopic introduction; T3, duodenal papula intubation; T4, endoscopic withdrawal; T5, postoperative awakening), the arterial oxygen partial pressure (PaO2), carbon dioxide partial pressure (PaCO2) and pH at T0, 15 min after the induction and T5. Results: The incidence of intraoperative subclinical hypoxemia in group C and group H was 12.0% (7/58) and 3.4% (2/58) respectively, which showed no significant statistical difference (P=0.165) from each other. The incidence of intraoperative hypoxemia in group H was 8.6% (5/58), which was significantly lower than 31.0% (18/58) of group C (P=0.003). Neither group had intraoperative severe hypoxemia. SpO2 of group H were (98.2±0.9)%, (98.2±0.9)%, (97.8±1.7)% and (97.7±1.7)% at T1, T2, T3, T4, which were higher than (96.8±2.1)%, (96.4±3.0)%, (96.1±2.9)% and (96.4±3.4)% in group C (all P<0.05). PaO2 at 15 min after induction in group H was (240.5±46.7) mmHg (1 mmHg=0.133 kPa), which was higher than that of group C (170.6±33.4) mmHg (P<0.001). There was no statistically significant difference in pH and PaCO2 between the two groups of patients at each timepoint. Conclusion: High flow nasal catheter oxygen can effectively reduce the incidence of hypoxemia in ERCP in elderly patients.

Temperature management of intraoperative cardiopulmonary bypass in valve replacement surgery: a retrospective analysis of the impact on postoperative organ function.

OBJECTIVE: This study aimed to systematically analyze the effects of cardiopulmonary bypass (CPB) at different temperatures on the function of different organs in patients after heart valve replacement and to investigate its safety and feasibility. PATIENTS AND METHODS: The data of 275 heart valve replacement surgery patients who underwent static suction compound anesthesia under CPB between February 2018 and October 2019 were retrospectively analyzed and divided into normothermic CPB anesthesia group (group 0), shallow hypothermic CPB anesthesia group (group 1), medium hypothermic CPB anesthesia group (group 2), and deep hypothermic CPB anesthesia group (group 3) according to the different intraoperative CPB temperatures. The basic preoperative conditions, cardiac resuscitation, number of defibrillations, postoperative ICU stay, postoperative hospital stay, and postoperative evaluation of different organ functions, such as heart, lung, and kidney functions, were analyzed and studied in each group. RESULTS: The comparison of preoperative and postoperative pulmonary artery pressure and left ventricular internal diameter (LVD) was statistically significant in each group (p < 0.05), and the postoperative pulmonary function pressure was statistically significant in group 0 compared with groups 1 and 2 (p < 0.05). The preoperative glomerular filtration rate (eGFR) and the eGFR on the first postoperative day were statistically significant in all the groups (p < 0.05), and the eGFR on the first postoperative day in groups 1 and 2 were statistically significant (p < 0.05). CONCLUSIONS: The control of appropriate temperature during CPB was associated with the recovery of organ function in patients after valve replacement. Intravenous compound general anesthesia with superficial hypothermic CPB might be more beneficial in recovering cardiac, pulmonary, and renal functions.

[Efficacy of simple continuous positive airway pressure on patients with obstructive sleep apnea].

Objective: To investigate the efficacy of simple device of continuous positive airway pressure (CPAP) in the treatment of obstructive sleep apnea (OSA). Methods: A double-blind study was performed on 53 OSA patients who received overnight simple CPAP and traditional CPAP in a random order during polysomnography. Pressure for CPAP treatment was manual titrated. The sleep apnea hypopnea index (AHI), arousal index (ArI), Oxygen desaturation Index (ODI), sleep structure and the preference for CPAP devices of the patients were observed. Results: AHI, ArI, ODI decreased significantly from 35.7 (18.1, 58.8)/h, (29.4±18.6)/h, 22.0 (13.9, 47.3)/h before treatment to 1.7 (0.7, 4.4)/h, (11.5±5.1) /h and 1.3 (0.4, 3.6)/h after treatment with simple CPAP, respectively (all P<0.05). There was no statistically significant difference in residual AHI [1.7 (0.7, 4.4)/h vs 1.9 (0.8, 4.3)/h], ArI [(11.5±5.1)/h vs (10.5±4.4)/h] and ODI [1.3 (0.4, 3.6)/h vs 1.3 (0.5, 4.2)/h] between treatment with simple CPAP and traditional CPAP (all P>0.05). The amount of time spent on deep sleep (stage Ⅲ) and rapid eye movement (REM) increased significantly from (6.2+ 6.6)% and (16.3+ 7.0)% before treatment to (11.7±8.5)% and (20.7±5.1)% during treatment with simple CPAP and (11.4±8.6)% and (20.9±5.0)% with traditional CPAP, respectively. The patients had no clear preference for two CPAP devices. Conclusion: Traditional CPAP can be replaced by the simple CPAP to treat patients with OSA.

The therapeutic effect of rosuvastatin on cardiac remodelling from hypertrophy to fibrosis during the end-stage hypertension in rats.

End-stage hypertensive heart disease is an increasing cause of cardiac mortality. Therefore, the current study focused on the cardiac remodelling from hypertrophy to fibrosis in old-aged spontaneously hypertensive rats (SHRs), and explored the therapeutic effects of Rosuvastatin and its possible mechanism(s) of action. Spontaneously hypertensive rats at age 52 weeks were randomly divided into three groups, the first two to receive Rosuvastatin at a dose of 20 mg/kg/day and 40 mg/kg/day, respectively, and the third to receive placebo, which was to be compared with Wistar-Kyoto as controls. After 2-month treatment, SBP, heart to body weight ratio (HW/BW%) and echocardiographic features were evaluated, followed by haematoxylin and eosin and Masson trichrome staining in conjunction with qPCR of foetal gene expressions. Transferase-mediated dUTP nick-end labelling assay and immunofluorescent labelling for active caspase-3 were used to detect the apoptotic cardiomyocytes. Signaling pathways involved were examined by using western blot. Old-aged SHR developed end-stage hypertensive heart disease characterized by significant enhancement of HW/BW%, LVAWd and LVPWd, and decreased LVEF and LVFS, accompanied by cardiomyocytes enlargement and fibrosis along with activation of foetal gene programme. Cardiac apoptosis increased significantly during the transition process. Rosuvastatin reduced hypertrophy significantly via AT(1) Receptor-PKCß2/α-ERK-c-fos pathway; protected myocardium against apoptosis via Akt-FOXO1, Bcl-2 family and survivin pathways and consequently suppressed the caspase-3 activity. The present study revealed that old-aged SHRs developed cardiac remodelling from hypertrophy to fibrosis via cardiac apoptosis during the end stage of hypertensive heart disease. These pathological changes might be the consequence of activation of AT(1) Receptor-PKCß2/α-ERK-c-fos and AKT-FOXO1/Bcl-2/survivin/Caspase3 signaling. Rosuvastatin effectively attenuated the structural changes by reversing the signaling transductions involved.

Neural drive during continuous positive airway pressure (CPAP) and pressure relief CPAP.

BACKGROUND: Pressure release continuous positive airway pressure (CPAP) is an evolution of CPAP that has been reported to improve patient comfort. We hypothesised the pressure release would lead to unloading of the inspiratory muscles and therefore conducted a prospective double-blind cross-over physiological study of autotitrating CPAP (APAP) against autotitrating pressure relief CPAP (PR-APAP). METHODS: Eleven patients with severe obstructive sleep apnoea (OSA; mean AHI 74.5+/-14.4/h) were studied. We assessed neural drive by recording the oesophageal pressure, gastric pressure, transdiaphragmatic pressure and the diaphragm EMG during overnight polysomnography. RESULTS: Both APAP and PR-APAP significantly reduced neural respiratory drive. Transdiaphragmatic pressure swings during apnoea (30.2+/-11.5 cm H2O) before treatment decreased to 9.1+/-5.3 cm H2O for PR-APAP and 8.5+/-3.7 cm H2O for APAP. The transdiaphragmatic pressure and the diaphragm EMG did not differ significantly between APAP and PR-APAP. The gastric pressure swing at expiration phase disappeared during both APAP and PR-APAP when sleep respiratory events were eliminated. CONCLUSIONS: PR-APAP is not superior to APAP in terms of reducing neural respiratory drive. It is unnecessary to replace conventional APAP with PR-APAP for patients who have been successfully treated with traditional APAP.

The role of calcium and phosphorylation of cytosolic phospholipase A2 in regulating arachidonic acid release in macrophages.

Arachidonic acid release is induced in macrophages with diverse agonists including calcium ionophores, phorbol myristate acetate (PMA), okadaic acid, and the phagocytic particle, zymosan, and correlates with activation of cytosolic phospholipase A2 (cPLA2). The role of calcium and phosphorylation of cPLA2 in regulating arachidonic acid release was investigated. Zymosan induced a rapid and transient increase in [Ca2+]i. This in itself is not sufficient to induce arachidonic acid release since ATP and platelet activating factor (PAF), agonists that induce transient calcium mobilization in macrophages, induced little arachidonic acid release. Unlike zymosan, which is a strong activator of mitogen-activated protein kinase (MAPK), ATP and PAF were weak MAPK activators and induced only a partial and transient increase in cPLA2 phosphorylation (gel shift). However, ATP or PAF together with colony stimulating factor-1 (CSF-1) synergistically stimulated arachidonic acid release. CSF-1 is a strong MAPK activator that induces a rapid and complete cPLA2 gel shift but not calcium mobilization or arachidonic acid release. Arachidonic acid release was more rapid in response to CSF-1 plus ATP or PAF than zymosan and correlated with the time course of the cPLA2 gel shift. Although low concentrations of ionomycin induced a lower magnitude of calcium mobilization than ATP, the response was more sustained resulting in arachidonic acid release. A23187 and ionomycin induced weak MAPK activation, and a partial and transient cPLA2 gel shift. The MAPK kinase inhibitor, PD 98059 suppressed A23187-induced MAPK activation and cPLA2 gel shift but had little effect on arachidonic acid release. These results indicate that in macrophages a transient increase in [Ca2+]i and sustained phosphorylation of cPLA2 can act together to promote arachidonic acid release but neither alone is sufficient. A sustained increase in calcium is sufficient for inducing arachidonic acid release. However, PMA and okadaic acid induce arachidonic acid release without increasing [Ca2+]i, although resting levels of calcium are required, suggesting alternative mechanisms of regulation.

Regulation of cytosolic phospholipase A2 phosphorylation and eicosanoid production by colony-stimulating factor 1.

A colony-stimulating factor 1 (CSF-1)-dependent murine macrophage cell line (BAC1.2F5) and peritoneal macrophages were used to investigate the relationship between growth factor-dependent phosphorylation/activation of the 85-kDa cytosolic phospholipase A2 (cPLA2) and arachidonic acid metabolism. The addition of CSF-1 to quiescent BAC1.2F5 cells was followed by the rapid phosphorylation, electrophoretic gel retardation, and stable increase in the specific activity of cPLA2 that correlated with the activation of ERK kinases. cPLA2 phosphorylation depended on the presence of growth factor and persisted throughout the cell cycle. CSF-1 inhibited prostaglandin E2 production and did not enhance arachidonic acid release or increase the levels of lysophosphatidylcholine or glycerophosphocholine. Treatment of BAC1.2F5 cells with the calcium ionophore A23187 plus CSF-1 did not stimulate eicosanoid release. Instead, CSF-1 enhanced the rate of exogenous arachidonic acid incorporation into phosphatidylcholine and its subsequent transfer to phosphatidylethanolamine suggesting that higher rates of arachidonic acid acylation may contribute to the suppression of prostaglandin production. In peritoneal macrophages, ERK kinase activity was stimulated and cPLA2 was phosphorylated and activated in response to CSF-1. However, CSF-1 did not trigger eicosanoid release but did augment arachidonic acid mobilization and prostaglandin E2 production elicited by zymosan and A23187. Thus, cPLA2 phosphorylation/activation and calcium mobilization are not the only determinants for eicosanoid release, and additional components in differentiated tissue macrophages are also required.

Protein kinase C-dependent and -independent pathways of mitogen-activated protein kinase activation in macrophages by stimuli that activate phospholipase A2.

The activation of mitogen-activated protein kinase (MAP kinase) in macrophages and the involvement of protein kinase C (PKC) in MAP kinase activation was investigated in macrophages exposed to agents that have previously been shown to activate the 85-kDa cytosolic phospholipase A2 (PLA2) and induce arachidonic acid release. Phorbol 12-myristate 13-acetate (PMA) and zymosan maximally stimulated MAP kinase activity by 5 and 15 min, respectively, whereas the response to okadaic acid was maximal by 60-90 min. MAP kinase activation correlated with tyrosine phosphorylation of p44 MAP kinase in PMA-stimulated cells and p44 and p42 MAP kinases in zymosan- and okadaic acid-stimulated cells. MAP kinase activity was not elevated in A23187-stimulated macrophages. Inhibition of PKC with the inhibitor, bisindolylmaleimide (GF109203X), or by prolonged exposure to PMA suppressed both arachidonic acid release and MAP kinase activation in PMA- and zymosan-stimulated macrophages but not in okadaic acid or A23187-treated cells. However, prolonged exposure to PMA did not suppress the increased cytosolic PLA2 activity in agonist-treated macrophages. This approach was complicated since initial exposure to PMA to down-regulate PKC increased cytosolic PLA2 activity which remained elevated for 16 h. In contrast, GF109203X treatment suppressed the increase in cytosolic PLA2 activity in response to zymosan and PMA but not to okadaic acid or A23187. The results demonstrate that PMA and zymosan trigger PKC activation that leads to the activation of MAP kinase and PLA2, whereas these responses are PKC independent in okadaic acid-treated cells. In addition, the results are consistent with a role for MAP kinase activation in regulating the activation of the 85-kDa PLA2 and arachidonic acid release in PMA-, zymosan-, and okadaic acid-stimulated cells, whereas these responses in A23187-treated cells are MAP kinase-and PKC-independent.

Regulation of phospholipase A2 activation by phosphorylation in mouse peritoneal macrophages.

The regulation of phospholipase A2 (PLA2) activation by phosphorylation, and phosphorylation of an 85-kDa, arachidonoyl-hydrolyzing PLA2 was investigated in mouse peritoneal macrophages. Phorbol 12-myristate 13-acetate (PMA) and okadaic acid, an inhibitor of serine/threonine phosphatases, stimulated arachidonic acid release, supporting a role for phosphorylation events in regulating PLA2 activation. In response to zymosan, PMA, or A23187, arachidonic acid was released at a linear rate up to 30-45 min after stimulation, whereas there was a 30-min lag preceding arachidonic acid release in response to okadaic acid. The 85-kDa PLA2 was phosphorylated on serine in the macrophages, and the level of phosphorylation increased in response to zymosan, PMA, okadaic acid, and, to a lesser extent, A23187. Two-dimensional phosphopeptide mapping revealed multiple phosphopeptides, several of which showed increased phosphorylation in response to zymosan, okadaic acid, and PMA. Zymosan, PMA, A23187, or okadaic acid stimulated time-dependent increases in PLA2 activity in the cytosolic fraction. PLA2 activation was most rapid in response to PMA, whereas activation in response to okadaic acid was delayed similar to the time course of arachidonic acid release. The cytosolic PLA2 had characteristics of the 85-kDa enzyme, including kinetic properties and substrate preference. Phosphatase treatment of the cytosols dephosphorylated the 85-kDa PLA2 and reversed the increase in activity. The results provide evidence that phosphorylation of the 85-kDa PLA2, induced by stimuli that induce arachidonic acid release, is an important mechanism for activation of the enzyme in macrophages.

Both purified human 1,N6-ethenoadenine-binding protein and purified human 3-methyladenine-DNA glycosylase act on 1,N6-ethenoadenine and 3-methyladenine.

We previously described a protein, isolated from human tissues and cells, that bound to a defined double-stranded oligonucleotide containing a single site-specifically placed 1,N6-ethenoadenine. It was further demonstrated that this protein was a glycosylase and released 1,N6-ethenoadenine. We now find that this enzyme also releases 3-methyladenine from methylated DNA and that 3-methyladenine-DNA glycosylase behaves in the same manner, binding to the ethenoadenine-containing oligonucleotide and cleaving both ethenoadenine and 3-methyladenine from DNA containing these adducts. The rate and extent of glycosylase activities toward the two adducts are similar.

Spin-label electron paramagnetic resonance and differential scanning calorimetry studies of the interaction between mitochondrial cytochrome c oxidase and adenosine triphosphate synthase complex.

The interaction between cytochrome c oxidase complex and adenosine triphosphate synthase (F1F0) complex in the purified, dispersed state and embedded in phospholipid vesicles was studied by differential scanning calorimetry and by spin-label electron paramagnetic resonance. The detergent-dispersed cytochrome oxidase and F1F0 complexes undergo endothermic thermodenaturation. However, when these complexes are embedded in phospholipid vesicles, they undergo exothermic thermodenaturation. The energy released is believed to result from the collapse of a strained interaction between unsaturated fatty acyl groups of phospholipids and an exposed area of the complex formed by the removal of interacting proteins. The exothermic enthalpy change of thermodenaturation of a protein-phospholipid exothermic enthalpy change of thermodenaturation of a protein-phospholipid vesicle containing both cytochrome oxidase complex and F1F0 was smaller than that of a mixture of protein-phospholipid vesicles formed from each individual electron transfer complex. This suggests specific interaction between cytochrome oxidase complex and F1F0 in the membrane. Further evidence for interaction between these two complexes is provided by saturation transfer EPR studies in which the rotational correlation time of spin-labeled cytochrome oxidase increases significantly when the complex is mixed with F1F0 prior to being embedded in phospholipid vesicles. From these results, it is concluded that at least a part of cytochrome oxidase and a part of F1F0 form a supermacromolecular complex in the inner mitochondrial membrane. No such supermacromolecular complex is detected between F1F0 and ubiquinol--cytochrome c reductase.

Partial purification of a human DNA glycosylase acting on the cyclic carcinogen adduct 1,N6-ethenodeoxyadenosine.

We previously reported that a variety of human cells and tissues contained a Mr35,000 DNA-binding protein which selectively recognized a single 1,N6-ethenoadenine in a defined 25-base double-stranded oligonucleotide (B. Rydberg et al., Proc. Natl. Acad. Sci. USA, 88: 6839-6842, 1991). We now demonstrate that incubation of the same duplex with 50-fold partially purified binding protein from human placenta results in release of the free 1,N6-ethenoadenine base, indicative of DNA glycosylase action. This enzyme activity appears unique in that it excises a cyclic adduct resulting from a known human carcinogen.

The Rhodospirillum rubrum cytochrome bc1 complex: redox properties, inhibitor sensitivity and proton pumping.

A detergent-solubilized, three-subunit-containing cytochrome bc1 complex, isolated from the photosynthetic bacterium R. rubrum, has been shown to be highly sensitive to stigmatellin, myxothiazol, antimycin A and UHDBT, four specific inhibitors of these complexes. Oxidation-reduction titrations have allowed the determination of Em values for all the electron-carrying prosthetic groups in the complex. Antimycin A has been shown to produce a red shift in the alpha-band absorbance maximum of one of the cytochrome b hemes in the complex and stigmatellin has been shown to alter both the Em and EPR g-values of the Rieske iron-sulfur protein in the complex. Western blots have revealed antigenic similarities between the cytochrome subunits of the R. rubrum complex and those of the related photosynthetic bacteria, Rb. capsulatus and Rb. sphaeroides. The R. rubrum complex has been incorporated into liposomes. These liposomes exhibit respiratory control and are able to couple electron transfer from quinol to cytochrome c to proton translocation across the liposome membrane in a manner consistent with a Q-cycle mechanism. It can thus be concluded that neither electron transport nor coupled proton translocation by the cytochrome bc1 complex requires more than three subunits in R. rubrum.

Spectra properties of rat liver mitochondrial choline dehydrogenase.

Choline dehydrogenase contains the prosthetic group FAD, non-haem iron and acid labile sulfur. However, the absorption spectra of the purified enzyme do not change after adding substrate. The reduced absorption spectra of choline dehydrogenase can only be determined after the addition of dithionite. Those choline dehydrogenases situated in the mitochondrial inner membrane can be reduced by substrate and exist in the reduced state. When cholate was used to solubilize the substrate-reduced choline dehydrogenase, the reduced spectra will gradually disappear. However, if solubilization is carried out under anaerobic conditions, the reduced spectra can be retained, suggesting that the solubilized choline dehydrogenase can use oxygen as an acceptor.