Síndrome de infusión de propofol y COVID-19. Reporte de caso / Propofol and COVID-19 infusion syndrome. Case report

Resumen: La forma grave de neumonía por SARS-CoV-2 (COVID-19) cursa en la mayoría de los casos con un síndrome de dificultad respiratoria aguda (SDRA). Es necesario emplear sedación durante su ventilación mecánica, el propofol es el que más de utiliza por su farmacocinética y farmacodinamia. El propofol es un anestésico que se usa ampliamente en las unidades de cuidados intensivos. Su empleo puede provocar un efecto adverso poco frecuente, pero en extremo grave, conocido como síndrome por infusión de propofol (SIP), el cual se encuentra estrechamente asociado a la velocidad de infusión aunado a factores de riesgos propios del paciente. Se caracteriza principalmente por inestabilidad hemodinámica, acidosis láctica y por progresión a disfunción multiorgánica. Se presenta un caso de SIP en paciente con síndrome de dificultad respiratoria aguda (SDRA) secundario a SARS-CoV-2 que desarrolla esta complicación asociada a la sedación. Se discute fisiopatológica clínica y consideraciones que deberán tomarse en cuenta al momento de su utilización en infusión continua.

Abstract: The severe form of SARS-CoV-2 pneumonia (COVID-19) occurs in most cases with acute respiratory distress syndrome (ARDS), requiring the use of sedation during mechanical ventilation, with propofol being the most widely used for its pharmacokinetics and pharmacodynamics. Propofol is a widely used anesthetic in intensive care units (ICU). Its use can cause an infrequent but extremely serious adverse effect, known as propofol infusion syndrome (PRIS), which is closely associated with the speed of infusion coupled with risk factors specific to the patient, the clinical features of PRIS are hemodynamic instability, lactic acidosis and with progression to multi-organ dysfunction. We present a case of SIP in a patient with acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 who develops this complication associated with sedation, discusses clinical pathophysiology and considerations that should be taken into account when using it in continuous infusion.

Verification of Differential Expression Genes after CacyBP/SIP Nuclear Translocation in Colon Carcinoma Cell Line / 天津医药

Objective To verify the genes screened by the polymerase chain reaction (PCR) chip of cell cycle. Methods The colon cancer cells SW480 were randomized into two groups, the test group (with gastrin stimulation) and con-trol group (without gastrin stimulation). The method of Western blot was used to detect the expression of calcylin binding pro-tein/Siah-1 interacting protein (Cacybp/SIP) before and after gastrin stimulation. The differential expression genes, cyclin de-pendent kinase 8 (CDK8) and cyclin dependent kinase subunit (CKS2), were verified by using real-time quantitative PCR (qRT-PCR). Results It was found that before the stimulation, CacyBP/SIP was located and expressed in cytoplasm, and then in both cytoplasm and nucleus after gastrin stimulation. The qRT-PCR results of CDK8 and CKS2 genes were consis-tent with those of microarray detection. The expressions of CDK8 and CKS2 were up-regulated (P < 0.05). Conclusion The stimulation of human gastrin can lead to the nuclear translocation of CacyBP/SIP. The results of microarray are reliable, and the differentially expressed genes screened through gene chip deserve further study.

The Significance of Interstitial Cells in Neurogastroenterology

Smooth muscle layers of the gastrointestinal tract consist of a heterogeneous population of cells that include enteric neurons, several classes of interstitial cells of mesenchymal origin, a variety of immune cells and smooth muscle cells (SMCs). Over the last number of years the complexity of the interactions between these cell types has begun to emerge. For example, interstitial cells, consisting of both interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor alpha-positive (PDGFRalpha+) cells generate pacemaker activity throughout the gastrointestinal (GI) tract and also transduce enteric motor nerve signals and mechanosensitivity to adjacent SMCs. ICC and PDGFRalpha+ cells are electrically coupled to SMCs possibly via gap junctions forming a multicellular functional syncytium termed the SIP syncytium. Cells that make up the SIP syncytium are highly specialized containing unique receptors, ion channels and intracellular signaling pathways that regulate the excitability of GI muscles. The unique role of these cells in coordinating GI motility is evident by the altered motility patterns in animal models where interstitial cell networks are disrupted. Although considerable advances have been made in recent years on our understanding of the roles of these cells within the SIP syncytium, the full physiological functions of these cells and the consequences of their disruption in GI muscles have not been clearly defined. This review gives a synopsis of the history of interstitial cell discovery and highlights recent advances in structural, molecular expression and functional roles of these cells in the GI tract.

The Expression of the Ca++ Channel alpha2delta Subunit and TRPM8 in the Dorsal Root Ganglion of Sympathetically Maintained Pain and Sympathetic Independent Pain Rat Models / 대한통증학회지

BACKGROUND: Peripheral nerve injury induces up-regulation of the calcium channel alpha2delta (alpha2delta) subunit and TRPM8 in the dorsal root ganglion (DRG) which might contribute to allodynia development. We investigated the expression of the alpha2delta subunit and TRPM8 in the DRG of sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) rat model. METHODS: For the SMP model, the L5 and L6 spinal nerves were ligated tightly distal to the DRG. For the SIP model, the tibial and sural nerves were transected, while the common peroneal nerve was spared. After a 7 day postoperative period, tactile and cold allodynia were assessed using von Frey filaments and acetone drops, respectively. Expression of the alpha2delta subunit and TRPM8 in the L5 and L6 DRG were subsequently examined by a Western blot. RESULTS: There were no significant differences between the two models for the thresholds of tactile and cold allodynia. Expression of the alpha2delta subunit in the ipsilateral DRG to the injury was increased as determined on a Western blot as compared to that in the contralateral or sham-operated DRG of the SMP model, but there was no difference in expression seen with the use of the SIP model. There was no difference in the expression of TRPM8 in the ipsilateral DRG to the injury and the contralateral or sham-operated DRG of either model. CONCLUSIONS: Up-regulation of the alpha2delta subunit in injured DRG may play a role that contributes to tactile allodynia development in SMP, but not TRPM8 to cold allodynia after peripheral nerve injury.

Antiallodynic Effect of Pregabalin in Rat Models of Sympathetically Maintained and Sympathetic Independent Neuropathic Pain

Pregabalin binds to the voltage-dependent calcium channel alphadelta subunit and modulates the release of neurotransmitters, resulting in analgesic effects on neuropathic pain. Neuropathic pain has both sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) components. We studied the antiallodynic effects of pregabalin on tactile allodynia (TA) and cold allodynia (CA) in SMP-and SIP-dominant neuropathic pain models. Allodynia was induced by ligation of the L5 & L6 spinal nerves (SMP model) or by transection of the tibial and sural nerves (SIP model) in rats. For intrathecal drug administration, a PE-10 catheter was implanted through the atlantooccipital membrane to the lumbar enlargement. Pregabalin was administered either intraperitoneally (IP) or intrathecally (IT) and dosed up incrementally until an antiallodynic effect without sedation or motor impairment was apparent. TA was assessed using von Frey filaments, and CA was assessed using acetone drops. IP-administered pregabalin dose-dependently attenuated TA in both models and CA in the SMP model, but not CA in the SIP model. IT-administered pregabalin dose-dependently attenuated both TA and CA in both models. However, the dose response curve of IT-administered pregabalin in SMP was shifted to left from that of SIP and the ED50 of IT-administered pregabalin for CA in SMP was about 900 times less than that in SIP. These findings suggest that pregabalin exerts its antiallodynic effect mainly by acting at the spinal cord, and that IT-administered pregabalin has more potent antiallodynic effects in SMP. The alphadeltasubunit might be less involved in the CA in SIP.

Construction of The Antigen Expression Vector Used for Library-library Screening / 生物化学与生物物理进展

Selectively infective phage (SIP) technology was developed for screening interacting protein-protein pairs. The in vivo SIP strategy would in principle be suitable for??library-library??selections, and the co-packaged polyphage may be a suitable approach. In order to construct the antigen expression vector which can be co-packaged into polyphage with phage displaying vectors, plasmid TG10 was chosen as the basic vector which is compatible with antibody display vector. The interval sequence of phage genome was amplified with PCR and cloned into TG10 to provide the packaging signal. It was named pTMI and it can be packaged into phage particles in 1011 level. The N1N2 region of gene ￠? was amplified and cloned into pTMI under the control of lac promoter to give pTMIN. Promoter trc was synthesized and replaced the lac promoter to give pTTMIN which permits the fusion expression of antigen with N1N2. To test its ability for fusion expression, gene code for ten-peptide of c-myc was synthesized and inserted into pTTMIN downstream to N1N2. After induction expression, the results of ELISA and SDS-PAGE showed that it has been expressed successfully. When pTTMIN was transfected into cell carrying antibody display vector p3MHHB3, it was copackaged into phage particles in 0.3% to 55% after rescuing with helper phage VCSM13.From the results it can concluded that the antigen expression vector was constructed successfully and it can be used for library-library screening in theory.

Characterization of a Monoclonal Antibody Specific to Human Siah-1 Interacting Protein

BACKGROUND: A human orthologue of mouse S100A6-binding protein (CacyBP), Siah- 1-interacting protein (SIP) had been shown to be a component of novel ubiquitinylation pathway regulating beta-catenin degradation. The role of the protein seems to be important in cell proliferation and cancer evolution but the expression pattern of SIP in actively dividing cancer tissues has not been known. For the elucidation of the role of SIP protein in carcinogenesis, it is essential to produce monoclonal antibodies specific to the protein. METHODS: cDNA sequence coding for ORF region of human SIP gene was amplified and cloned into an expression vector to produce His-tag fusion protein. Recombinant SIP protein and monoclonal antibody to the protein were produced. The N-terminal specificity of anti-SIP monoclonal antibody was conformed by immunoblot analysis and enzyme linked immunosorbent assay (ELISA). To study the relation between SIP and colon carcinogenesis, the presence of SIP protein in colon carcinoma tissues was visualized by immunostaining using the monoclonal antibody produced in this study. RESULTS: His-tag-SIP (NSIP) recombinant protein was produced and purified. A monoclonal antibody (Korea patent pending; #2003-45296) to the protein was produced and employed to analyze the expression pattern of SIP in colon carcinoma tissues. CONCLUSION: The data suggested that anti-SIP monoclonal antibody produced here was valuable for the diagnosis of colon carcinoma and elucidation of the mechanism of colon carcinogenesis.

The Effect of MK-801 and Naloxone in a Sympathetically Independent Neuropathic Pain Rat Model

OBJECTIVE: The authors evaluate the effects of each spinally administered MK-801, naloxone and coadministerd both drugs on the neuropathic pain states in the sympathetically independent pain(SIP) model induced by unilateral sural and tibial nerve transection of the sciatic nerve branches in the rat. METHODS: Pain sensitivity was measured with a von Frey filament for mechanical allodynia and acetone applied to the sensitive area for cold hyperalgesia. We evaluated the ability of the spinally applied MK-801 to spinal cord after laminectomy on T12, T13 and L1 to alleviate neuropathic pain either by itself of when spinally or intravenously administerd together with naloxone and coincidentally measured the behavioral test. RESULTS: Twenty out of 25 rats in which the tibial and sural nerves were injured showed well-developed neuropathic pain behaviors. The response rates of the rat models to the von Frey filament and acetone spray in hindlimbs by MK-801 were significantly reduced but, by naloxone were not changed. The pharmacological inhibition to mechanical allodynia and cold hyperalgesia for MK-801 when co-adminstered naloxone was reversed. CONCLUSION: MK-801 has been shown to alleviate neuropathic pain in SIP but, co-administered naloxone reversed the N-methyl-D-aspartate blocking effects of MK-801. These findings suggest that naloxone, which does not specifically relieve neuropathic pain, can reverse the neuropathic pain-relieving action of MK-801.

Effects of Motivation-Enhancing Program on Health Behaviors, Cardiovascular Risk factors, and Functional status for Institutionalized Elderly Women / 간호학회지

This study was to compare changes in health behaviors, motivational factors, cardiovascular risk factors, and functional status (SIP) after implementing the 6-month motivation-enhancing program to institutionalized elderly women. METHODS: Sixty-four elderly women participated. Face to face interviews with blood sampling and anthropometric assessment were conducted at the pretest, 10 weeks and 6 months during the program. RESULTS: 1. The program participants showed significantly better health behaviors over 6 months. The mean motivational level was also significantly improved, especially for perceived benefits, perceived barriers, and emotional salience. 2. The mean of cardiovascular risk factors for the participants was 21.8 at the level of low to moderate risk. After completing the program, total risk score was significantly decreased to 18.7 at 10 weeks, and further to 17.7 at 6 months. A significant reduction was also found in HDL and LDL-cholesterol levels, blood pressure, obesity, inactivity, and stress. 3. The functional status (SIP) was 11% at the baseline and significantly changed in positive direction at 10 weeks (M=9.3) and at 6 month (M=6.3). The significant improvement was also found in physical and psychosocial dimensions and sleep/rest dimension. CONCLUSION: The motivation enhancing program was effective to reduce cardiovascular risks and to improve the functional status of institutionalized elderly women by motivating them to perform better health behaviors.