Comparison of Non-ephedrine Constituents from Ephedra Plants Cultivated in Japan.

Ephedra plants, the main components of which are ephedrine alkaloids, are used as traditional medicines in Eastern Asian countries. In this study, we isolated non-ephedrine constituents from various Ephedra plant species cultivated in Japan. HPLC analysis suggested that kynurenic acid and its derivatives accumulated in a wide range of Ephedra plant species. Furthermore, a large amount of (2R,3S)-O-benzoyl isocitrate has been isolated from E. intermedia. This study suggests that Ephedra plants have diverse non-ephedrine constituents.

Oral midodrine for prophylaxis against post-spinal anesthesia hypotension during hip arthroplasty in elderly population: a randomized controlled trial.

BACKGROUND: We aimed to evaluate the efficacy of midodrine as a prophylaxis against post-spinal hypotension in elderly patients undergoing hip arthroplasty. METHODS: This randomized controlled trial included elderly patients undergoing hip arthroplasty under spinal anesthesia. Ninety minutes before the procedure, patients were randomized to receive either 5-mg midodrine or placebo (metoclopramide). After spinal anesthesia, mean arterial pressure (MAP) and heart rate were monitored every 2 min for 20 min then every 5 min until the end of the procedure. Post-spinal hypotension (MAP < 80% baseline) was treated with 10 mg ephedrine. The primary outcome was intraoperative ephedrine consumption. Secondary outcomes were the incidence of post-spinal hypotension, bradycardia, and hypertension (MAP increased by > 20% of the baseline reading). RESULTS: We analyzed 29 patients in the midodrine group and 27 in the control group. The intraoperative ephedrine consumption was lower in the midodrine group than in the control group (median [quartiles]: 10 [0, 30] mg versus 30 [20, 43] mg, respectively, P-value: 0.002); and the incidence of intraoperative hypotension was lower in the midodrine group than that in the control group. The incidence of hypertension and bradycardia were comparable between the two groups. CONCLUSION: The use of 5 mg oral midodrine decreased the vasopressor requirements and incidence of hypotension after spinal anesthesia for hip surgery in elderly patients. CLINICAL TRIAL REGISTRATION: This study was registered on September 22, 2022 at clinicaltrials.gov registry, NCT05548985, URL: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05548985 .

Impurities in over-the-counter pseudoephedrine leading to methcathinone detection in urine.

Methcathinone, a psychoactive substance with stimulant properties, has raised concerns in recent years due to its presence in urine screenings, even among individuals with no history of drug abuse. To prevent misjudgment, this work aims to explore the source of methcathinone in urine. A total of 58 urine samples tested positive for methcathinone in the National Taiwan University Hospital cohort, with 27 linked to illicit drug use and 31 from individuals with no drug use history. Co-occurrence analysis revealed a strong association between methcathinone and over-the-counter cold medications containing pseudoephedrine or ephedrine. In an in vivo experiment, participants who consumed pseudoephedrine-containing drugs showed the presence of methcathinone in their urine, suggesting a connection between these substances. Additionally, tests on pharmaceutical products containing pseudoephedrine detected small amounts of methcathinone as impurities. The findings suggest that the presence of methcathinone in nonillicit drug users may be attributed to impurities in over-the-counter pseudoephedrine-containing medications. This raises concerns about potential misinterpretations of drug screening results and underscores the need for more comprehensive criteria for assessing drug use. This study contributes to our understanding of the origin of methcathinone in urine, which has implications for legal justice and drug screening practices.

Risk factors of more severe hypotension after spinal anesthesia for cesarean section.

BACKGROUND: The aim of this study was to examine the risk factors associated with the use of vasopressors to prevent hypotension that occurs after spinal anesthesia during cesarean section. Although the prophylactic use of vasopressors is already suggested as routine care in many parts of the world, the occurrence of spinal anesthesia-induced hypotension (SAIH) is still common in parturients. METHODS: This retrospective study included parturients receiving elective cesarean deliveries under spinal anesthesia from April 2016 to March 2020. Risk factors related to ephedrine dosage were analyzed using a hurdle model, and risk factors related to SAIH were further analyzed with logistic regression. RESULTS: Five risk factors, namely maternal body mass index (BMI, p < 0.001), baseline systolic blood pressure (SBP, p < 0.001), baseline heart rate (HR, p = 0.047), multiparity ( p = 0.003), and large fetal weight ( p = 0.005) were significantly associated with the requirement for ephedrine. Furthermore, a higher ephedrine dosage was significantly associated with maternal BMI ( p < 0.001), baseline SBP ( p < 0.001), baseline HR ( p < 0.001), multiparity ( p = 0.027), large fetal weight ( p = 0.030), maternal age ( p = 0.009), and twin pregnancies ( p < 0.001). Logistic regression analysis also showed that the same five risk factors-maternal BMI ( p = 0.030), baseline SBP ( p < 0.001), baseline HR ( p < 0.001), multiparity ( p < 0.001), and large fetal weight ( p < 0.001)-were significantly associated with SAIH, even in cases where vasopressors were administered. CONCLUSION: These findings can be useful for clinicians when deciding the dose of prophylactic ephedrine or phenylephrine to prevent SAIH.

Non-invasive imaging of sympathetic innervation of the pancreas in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: Compromised pancreatic sympathetic innervation has been suggested as a factor involved in both immune-mediated beta cell destruction and endocrine dysregulation of pancreatic islets. To further explore these intriguing findings, new techniques for in vivo assessment of pancreatic innervation are required. This is a retrospective study that aimed to investigate whether the noradrenaline (norepinephrine) analogue 11C-hydroxy ephedrine (11C-HED) could be used for quantitative positron emission tomography (PET) imaging of the sympathetic innervation of the human pancreas. METHODS: In 25 individuals with type 2 diabetes and 64 individuals without diabetes, all of whom had previously undergone 11C-HED-PET/CT because of pheochromocytoma or paraganglioma (or suspicion thereof), the 11C-HED standardised uptake value (SUVmean), 11C-HED specific binding index (SBI), pancreatic functional volume (FV, in ml), functional neuronal volume (FNV, calculated as SUVmean × FV), specific binding index with functional volume (SBI FV, calculated as SBI × FV) and attenuation on CT (HU) were investigated in the entire pancreas, and additionally in six separate anatomical pancreatic regions. RESULTS: Generally, 11C-HED uptake in the pancreas was high, with marked individual variation, suggesting variability in sympathetic innervation. Moreover, pancreatic CT attenuation (HU) (p<0.001), 11C-HED SBI (p=0.0049) and SBI FV (p=0.0142) were lower in individuals with type 2 diabetes than in individuals without diabetes, whereas 11C-HED SUVmean (p=0.15), FV (p=0.73) and FNV (p=0.30) were similar. CONCLUSIONS/INTERPRETATION: We demonstrate the feasibility of using 11C-HED-PET for non-invasive assessment of pancreatic sympathetic innervation in humans. These findings warrant further prospective evaluation, especially in individuals with theoretical defects in pancreatic sympathetic innervation, such as those with type 1 diabetes.

In vitro anti-severe acute respiratory syndrome coronavirus 2 effect of Ephedra przewalskii Stapf extract.

ETHNOPHARMACOLOGICAL RELEVANCE: The terrestrial stems of Ephedra (Ephedra spp.; including Ephedra sinica Stapf and Ephedra przewalskii Stapf) extracts are used in traditional medicines in East Asia. In Japan, the Kampo formula containing E. sinica extract is prescribed for the treatment of the common cold, influenza virus infections, and mild symptoms of coronavirus disease 2019 (COVID-19). Although ephedrine alkaloids in E. sinica exert antitussive effects, they may have side effects associated with the sympathetic nervous system. E. przewalskii extract, a drug used in traditional Uyghur and Mongolian medicine, is considered to be free of ephedrine alkaloids and is a promising candidate for the treatment of infectious diseases. However, its use is currently limited because evidence of its antiviral efficacy remains inconclusive. AIM OF THE STUDY: We compared the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effects of E. przewalskii and E. sinica extracts in vitro. Additionally, we examined the differences in their antiviral effects against different SARS-CoV-2 strains. MATERIALS AND METHODS: VeroE6/TMPRSS2 cells were infected with SARS-CoV-2 (Conventional, Delta, and Omicron strains-BA.1, BA.2, BA.4, and BA.5), and lysates prepared from each herbal extract were added. The infectious titer was determined using the 50% tissue culture infectious dose (TCID50) method; in turn, the half-maximal inhibitory concentration (IC50) was calculated for each extract to compare the antiviral efficacy of E. sinica and E. przewalskii extracts. Further, the extracts were compared with remdesivir for their antiviral efficacy against the conventional viral strain. To verify the effect of the inactivation of virus particles, these extracts were added to each SARS-CoV-2 strain, and the infectious titers were determined using the TCID50 method. RESULTS: The antiviral efficacy (i.e., IC50) of the E. przewalskii extract against each SARS-CoV-2 strain was 2.7-10.8-fold greater than that of the E. sinica extract. The antiviral efficacy of the E. przewalskii extract against conventional viral strains was compared with that of remdesivir, which was 1/27.6 of remdesivir's efficacy. The E. sinica extract showed minimal inactivation of virus particles of each strain, whereas the E. przewalskii extract resulted in substantial viral inactivation. CONCLUSIONS: The E. przewalskii extract showed higher antiviral activity against SARS-CoV-2 than the E. sinica extract. Overall, our study suggests that E. przewalskii extract can be used for the treatment of viral infections, including COVID-19.

Evaluation of the Influence of Genetic and Environmental Factors on the Ephedrine Alkaloids Content of Ephedra sinica.

Ephedra herb, a dried terrestrial stem of Ephedra sinica, is used in traditional Japanese medicine (Kampo) and Chinese medicine to treat the common cold, headaches, bronchial asthma, and nasal inflammation. E. sinica predominantly contains two ephedrine alkaloids-(-)-ephedrine and (+)-pseudoephedrine-which are crucial for its medicinal effects. This study aimed to reveal the influence of genetic and environmental factors on ephedrine alkaloids content using statistical genetic analyses. To evaluate the influence of genetic factors on ephedrine alkaloids content, 25 clonal lines were cultivated in Ibaraki and the broad-sense heritability of the traits was estimated. The heritabilities of (-)-ephedrine, (+)-pseudoephedrine, and "total alkaloids" (TA) content were 0.871, 0.969, and 0.865, respectively. The heritabilities of ephedrine alkaloids content were high. To evaluate the influence of environmental factors on ephedrine alkaloids content, four clonal lines which have different genotypes were cultivated in three locations (Ibaraki, Shizuoka, and Yamanashi prefectures). The effects of genotype (G), location (L), and genotype by environment (G × E) interactions on ephedrine alkaloids content were found to be significant (p < 0.05) by two-way ANOVA, and, in particular, the genotypic effects were found to be the largest. Our results indicate that the ephedrine alkaloids content in E. sinica is under relatively strong genetic control and remains stable under various environments. These findings suggest that E. sinica with a higher and stable ephedrine alkaloids content could be cultivated in different locations through selective breeding.

Ephedrine and cocaine cause developmental neurotoxicity and abnormal behavior in zebrafish.

Ephedrine (EPH) and cocaine (COC) are illegal stimulant drugs, and have been frequently detected in aquatic environments. EPH and COC have negative effects on the nervous system and cause abnormal behaviors in mammals and fish at high concentrations, but their mechanisms of neurotoxicity remain unclear in larvae fish at low concentrations. To address this issue, zebrafish embryos were exposed to EPH and COC for 14 days post-fertilization (dpf) at 10, 100, and 1000 ng L-1. The bioaccumulation, development, behavior, cell neurotransmitter levels and apoptosis were detected to investigate the developmental neurotoxicity (DNT) of EPH and COC. The results showed that EPH decreased heart rate, while COC increased heart rate. EPH caused cell apoptosis in the brain by AO staining. In addition, behavior analysis indicated that EPH and COC affected spontaneous movement, touch-response, swimming activity and anxiety-like behaviors. EPH and COC altered the levels of the neurotransmitters dopamine (DA) and γ-aminobutyric acid (GABA) with changes of the transcription of genes related to the DA and GABA pathways. These findings indicated that EPH and COC had noticeable DNT in the early stage of zebrafish at environmentally relevant concentrations.

[Separation, characterization, and antiviral activity of colloidal phase state of Maxing Shigan Decoction].

This study focused on the separation, characterization, content determination, and antiviral efficacy research on colloidal particles with different sizes in Maxing Shigan Decoction(MXSG). The mixed colloidal phase of MXSG was initially separated into small colloidal particle segment(S), medium colloidal particle segment(M), and big colloidal particle segment(B) using ultrafiltration. Further fine separation was performed using size-exclusion chromatography. Dynamic light scattering(DLS) and transmission electron microscopy(TEM) were employed to characterize the size and morphology of the separated colloidal particles. UPLC-MS/MS was used to determine the content of ephedrine, amygdalin, glycyrrhizic acid, and the EDTA complexometric titration was used to measure the calcium(Ca~(2+)) content in different colloidal phases. Finally, a respiratory syncytial virus(RSV) infection mouse model was established using intranasal administration. The experimental groups included a blank group, a model group, a ribavirin group, an MXSG group, an S group, an M group, and a B group. Oral administration was given for treatment, and pathological changes in mouse lung tissue and organ indices were evaluated. The results of the study showed that the distribution of ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) content was not uniform among different colloidal segments. Among them, the B segment had the highest proportions of the three components, except for Ca~(2+), accounting for 46.35%, 53.72%, and 92.36%, respectively. Size-exclusion chromatography separated colloidal particles with uniform morphology in the size range of 100-500 nm. Compared to the S and M segments, the B segment showed an increased lung index inhibition rate(38.31%), spleen index, and thymus index in RSV-infected mice, and it improved the infiltration of inflammatory cells and lung injury in the lung tissue of mice. The complex components in MXSG form colloidal particles of various sizes and morphologies through heating, and small-molecule active components such as ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) participate in the assembly to varying degrees. The main material basis for the antiviral effect of MXSG is the colloidal particles with certain particle sizes formed by the assembly of active components during the heating process.

Ephedrine alleviates bleomycin-induced pulmonary fibrosis by inhibiting epithelial-mesenchymal transition and restraining NF-κB signaling.

Pulmonary fibrosis is a lethal and progressive pulmonary disorder in human beings. Ephedrine is a compound isolated from Ephedra and plays a regulatory role in inflammatory response. This study focused on the anti-pulmonary fibrosis effect of ephedrine and its potential molecular mechanism. After a mouse model of pulmonary fibrosis was established through bleomycin (BLM) induction, the survival percentage, body weight, and pulmonary index were measured. Hematoxylin-eosin staining and Masson's trichrome staining for lung tissues were performed to observe the pathological alterations. The viability of lung epithelial BEAS-2B cells, intracellular production of reactive oxygen species, and the levels of pro-inflammatory cytokines were examined by cell counting kit-8 assays, 2',7'-dichlorofluorescein diacetate (DCF-DA) staining, and enzyme-linked immunosorbent assay, respectively. Immunofluorescence staining was performed to determine E-cadherin and vimentin expression after BLM or ephedrine treatment. The mRNA and protein levels of cytokeratin-8, E-cadherin, α-SMA, and vimentin were subjected to quantitative polymerase chain reaction and immunoblotting. Experimental results revealed that ephedrine treatment rescued the repressive impact of BLM on BEAS-2B cell viability, and ephedrine inhibited BLM-induced overproduction of reactive oxygen species and inflammatory response in BEAS-2B cells. Additionally, ephedrine suppressed epithelial-mesenchymal transition (EMT) process stimulated by BLM treatment, as demonstrated by the reduced α-SMA and vimentin levels together with the increased cytokeratin-8 and E-cadherin levels in BLM + Ephedrine group. In addition, ephedrine inhibited NF-κB and activated Nrf-2 signaling in BLM-treated BEAS-2B cells. Moreover, ephedrine ameliorated pulmonary fibrosis in BLM-induced mice and improved the survival of model mice. In conclusion, ephedrine attenuates BLM-evoked pulmonary fibrosis by repressing EMT process via blocking NF-κB signaling and activating Nrf-2 signaling, suggesting that ephedrine might become a potential anti-pulmonary fibrosis agent in the future.

Chemical decontamination of methamphetamine and ephedrine using an activated peroxide-containing cleaning solution.

Manufacture and recreational use of methamphetamine can result in widespread chemical contamination throughout a property. Hydrogen peroxide (H2O2)-based cleaning products have shown success against a number of chemical contaminants including agents of chemical warfare, and biological contaminants such as anthrax. They are considered to be environmentally friendly and economically viable and, as such, are used by many companies within the methamphetamine decontamination industry. The oxidative decontamination of methamphetamine and ephedrine hydrochloride was investigated in this current study, employing a commercially available H2O2-based decontamination product, Bio-Oxygen® Chem Decon. Methamphetamine and ephedrine were observed to degrade following pseudo-first order kinetics of (1.9 ± 0.4) × 10-2 min-1 and (2.2 ± 0.3) × 10-2 min-1, respectively. Major oxidation products identified through GC-MS analyses were phenylacetone oxime (from methamphetamine) and benzaldehyde (from ephedrine). LC-MS analysis revealed the presence of a number of N-oxygenated intermediates which allowed for the elucidation of an N-oxidation decomposition pathway reminiscent of flavin-containing monooxygenase enzymes. Using this information, further targeted research can be performed to understand the behaviour and persistence of these reaction products and accurate assessments can be achieved to estimate their impact on the exposure risks associated with chemical decontamination of amphetamine-type stimulants (ATS).

Comparing the Effect of Spinal and General Anesthesia for Hip Fracture Surgery in Older Patients: A Meta-analysis of Randomized Clinical Trials.

OBJECTIVE: Hip fractures are the most common fractures among older adults, with most patients undergoing surgery. The debate regarding the type of anesthetic technique for hip fracture surgery is still ongoing. This meta-analysis aimed to compare the intraoperative and postoperative outcomes of spinal and general anesthesia in older patients undergoing hip fracture surgery. METHODS: Eligible studies that compared the effects of spinal and general anesthesia were systematically searched from PubMed, Embase, and the Cochrane Library until May 27, 2022. The intraoperative and postoperative outcomes of the two anesthesia techniques were compared. Quality assessment, heterogeneity analysis, and publication bias of the studies were also assessed. RESULTS: Nine articles of methodological quality were included in the meta-analysis. The pooled results revealed that there were significant differences in hypotension (risk ratio [RR] (95% confidence interval [CI]) = 0.81 (0.68, 0.97), p = 0.02) and ephedrine dose (weighted mean difference [WMD] [95%CI] = -20.94 [-37.50, -4.37] mg, p = 0.01) between the spinal and general anesthesia groups. However, no significant differences were observed in the use of ephedrine (RR [95% CI] = 0.77 [0.19, 3.05]), blood loss (WMD [95%CI] = -34.38 [-89.56, 20.80) mL], myocardial infarction (RR [95% CI] = 0.78 [0.31, 1.94] mL), heart failure (RR [95% CI] = 0.87 [0.17, 4.36] mL), stroke (RR [95%CI) = 0.65 [0.22, 1.95] mL), postoperative nausea and vomiting (RR [95% CI] = 0.88 [0.17, 4.35] mL), delirium (RR [95% CI] = 1.08 [0.89, 1.31] mL), and mortality (RR [95% CI] = 1.10 [0.72, 1.68] mL) (all p < 0.05). No publication bias was observed in any of the included studies. CONCLUSION: Compared to general anesthesia, spinal anesthesia was associated with a lower risk of intraoperative hypotension and lower doses of ephedrine in older patients undergoing hip fracture surgery.

Ephedrine and pseudoephedrine in Ephedra saxatilis on the vertical altitude gradient changed in southern Tibet Plateau, China.

Ephedra is one of the world's most important plants, used in medicine, plants and ecology. Most Ephedra grows in plain areas and is stable. But the plateau environment is special, with the change of altitude, the variety difference of plateau Ephedra saxatilis is very obvious. E. saxatilis metabolism on the Tibetan Plateau is not only affected by altitude, but also environmental conditions such as climate conditions and different soil components. However, the change mechanism of E. saxatilis alkaloids in special ecological environment is still unclear. Therefore, we analyzed the metabolic and altitude of E. saxatilis species in the Tibetan Plateau. Through the functional analysis of Kyoto Metabolism and Metabolomic Encyclopedia (KEGG), we can determine that the number of E. saxatilis metabolites decreases with the increase of altitude, and there are differences in metabolism among the three mountains. This was confirmed by univariate analysis of the top five metabolic pathways. Based on the analysis of soil and metabolomics, it was found that soil water content was also a factor affecting E. saxatilis metabolism. According to the difference of vertical height gradient, ephedrine and pseudephedrine showed the same change in vertical altitude under different mountains. Ephedrine increased as the altitude gradient increased, and pseudoephedrine decreased as the altitude gradient decreased. Our results provide valuable information for further study of metabolic mechanism and efficacy stability. It provides useful reference for the research of E. saxatilis planting in special area.

The preventive effect of 5-hydroxytryptamine-3 receptor antagonist on blood pressure reduction and postoperative nausea and vomiting during general anesthesia induction: A double-blinded, randomized controlled trial.

STUDY OBJECTIVE: Administering a 5-hydroxytryptamine-3 receptor (5-HT3) at anesthesia induction may aid in achieving hemodynamic stability during general anesthesia induced using opioids. Therefore, we aimed to evaluate the effect of ramosetron, a 5-HT3 antagonist, administered on hypotension at the induction of total intravenous anesthesia (TIVA) with propofol and remifentanil. Additionally, we aimed to compare the impact of ramosetron administration at anesthesia induction versus that at the end of the surgery on postoperative nausea and vomiting (PONV). DESIGN: Patients were randomly allocated to the Induction group (administration of ramosetron [0.3 mg/5 ml] at anesthesia induction and normal saline [5 ml] at the end of the surgery) or End group (administration of normal saline [5 ml] at anesthesia induction and ramosetron [0.3 mg/5 ml] at the end of the surgery). Hemodynamic status, PONV, and postoperative pain were assessed. SETTING: Operating room, post-anesthetic care unit, and general ward. PATIENTS: In total, 176 non-smoking patients without any past medical history undergoing laparoscopic gynecological surgeries under TIVA were included in the study. MEASUREMENTS: Blood pressure (BP), heart rate, PONV, visual analog scale (VAS). MAIN RESULTS: The Induction group exhibited significantly higher BP at anesthesia induction and required significantly lower doses of phenylephrine and ephedrine during anesthesia than the End group had. However, PONV and postoperative pain were similar between the two groups. CONCLUSIONS: Administering ramosetron at anesthesia induction resulted in significantly better hemodynamic stability with significantly lesser requirement of phenylephrine and ephedrine than administering at the end of the surgery did. Therefore, we recommend ramosetron administration at anesthesia induction rather than at the end of the surgery to prevent PONV and the decrease in the mean BP during TIVA with propofol and remifentanil.

Hemodynamic impact of ephedrine on hypotension during general anesthesia: a prospective cohort study on middle-aged and older patients.

BACKGROUND: Ephedrine is a mixed α- and ß-agonist vasopressor that is frequently used for the correction of hypotension during general anesthesia. ß-responsiveness has been shown to decrease with age; therefore, this study aimed to determine whether aging would reduce the pressor effect of ephedrine on hypotension during general anesthesia. METHODS: Seventy-five patients aged ≥ 45 years were included in this study, with 25 patients allocated to each of the three age groups: 45-64 years, 65-74 years, and ≥ 75 years. All patients received propofol, remifentanil, and rocuronium for the induction of general anesthesia, followed by desflurane and remifentanil. Cardiac output (CO) was estimated using esCCO technology. Ephedrine (0.1 mg/kg) was administered for the correction of hypotension. The primary and secondary outcome measures were changes in the mean arterial pressure (MAP) and CO, respectively, at 5 min after the administration of ephedrine.  RESULTS: The administration of ephedrine significantly increased MAP (p < 0.001, mean difference: 8.34 [95% confidence interval (CI), 5.95-10.75] mmHg) and CO (p < 0.001, mean difference: 7.43 [95% CI, 5.20-9.65] %) across all groups. However, analysis of variance revealed that the degree of elevation of MAP (F [2, 72] = 0.546, p = 0.581, η2 = 0.015 [95% CI, 0.000-0.089]) and CO (F [2, 72] = 2.023, p = 0.140, η2 = 0.053 [95% CI, 0.000-0.162]) did not differ significantly among the groups. Similarly, Spearman's rank correlation and multiple regression analysis revealed no significant relation between age and the changes in MAP or CO after the administration of ephedrine. CONCLUSION: The administration of ephedrine significantly increased MAP and CO; however, no significant correlation with age was observed in patients aged > 45 years. These findings suggest that ephedrine is effective for the correction of hypotension during general anesthesia, even in elderly patients. TRIAL REGISTRATION: UMIN-CTR (UMIN000045038; 02/08/2021).

The composition characteristics of endophytic communities and their relationship with metabolites profile in Ephedra sinica under wild and cultivated conditions.

Ephedra sinica is one of the most famous Chinese medicinal plants. The insufficient supply of wild resources has led to the increased use of cultivated products. However, the related medicinal quality differs significantly. Although the influence of external environment on the quality of E. sinica has been studied, the impact of endophytic microbes on it remains vague. This study characterized differential metabolites and microbial community compositions in wild and cultivated E. sinica by combining metabolomics with microbiomics, and explored the effect of endophytes on the formation of differential metabolites further. The results showed that the difference in quality between wild and cultivated E. sinica was mainly in the productions of alkaloids, flavonoids, and terpenoids. The associated endophytes had special compositional characteristics. For instance, the distribution and abundance of dominant endophytes varied between wild and cultivated E. sinica. Several endophytes had significant or highly significant correlations with the formations of ephedrine, pseudoephedrine, D-cathinone, methcathinone, coumarin, kaempferol, rhamnetin, or phenylacetic acid. This study will deepen our understanding of the plant-endophyte interactions and provide a strategy for the quality control of E. sinica products.

Conversion of Similar Xenochemicals to Dissimilar Products: Exploiting Competing Reactions in Whole-Cell Catalysis.

Many enzymes have latent activities that can be used in the conversion of non-natural reactants for novel organic conversions. A classic example is the conversion of benzaldehyde to a phenylacetyl carbinol, a precursor for ephedrine manufacture. It is often tacitly assumed that purified enzymes are more promising catalysts than whole cells, despite the lower cost and easier maintenance of the latter. Competing substrates inside the cell have been known to elicit currently hard-to-predict selectivities that are not easily measured inside the living cell. We employ NMR spectroscopic assays to rationally combine isomers for selective reactions in commercial S. cerevisiae. This approach uses internal competition between alternative pathways of aldehyde clearance in yeast, leading to altered selectivities compared to catalysis with the purified enzyme. In this manner, 4-fluorobenzyl alcohol and 2-fluorophenylacetyl carbinol can be formed with selectivities in the order of 90%. Modification of the cellular redox state can be used to tune product composition further. Hyperpolarized NMR shows that the cellular reaction and pathway usage are affected by the xenochemical. Overall, we find that the rational construction of ternary or more complex substrate mixtures can be used for in-cell NMR spectroscopy to optimize the upgrading of similar xenochemicals to dissimilar products with cheap whole-cell catalysts.

The effect of intravenous granisetron on prophylactic ephedrine for preventing hypotension after general anaesthesia induction in elderly patients: a randomized controlled trial.

Serotonin 3 receptor antagonists, a commonly used drug for preventing postoperative nausea and vomiting, have recently been reported to decrease the incidence of hypotension and the need for vasoactive drugs after spinal anaesthesia in obstetric surgery. However, it remains unknown whether they could also prevent hypotension after induction of general anaesthesia. In the current study, we aimed to investigate the effect of intravenous granisetron on prophylactic ephedrine for preventing hypotension after general anaesthesia induction in elderly patients. Sixty elderly patients were randomly assigned to receive granisetron or saline control 30 min before induction of general anaesthesia. The first patient in each group received a prophylactic dose of ephedrine (0.15 mg kg-1) to prevent hypotension. The prophylactic dose for each patient was increased or decreased by 0.05 mg/kg based on the efficacy results of the previous patient. The up-down sequential allocation analysis and probit regression was used to calculate the effective dose for 50% of patients (ED50) with prophylactic ephedrine. In the up-down sequential allocation analysis, the ED50 of ephedrine was significantly lower in group granisetron (0.08 mg kg-1 [95% CI, 0.06-0.11 mg kg-1]) when compared with group control (0.14 mg kg-1 [95% CI, 0.13-0.16 mg kg-1]) (P < 0.001). The conclusion was further supported by probit regression analysis (0.09 mg kg-1 [95% CI, 0.05-0.12 mg kg-1] in group granisetron and 0.14 mg kg-1 [95% CI, 0.12-0.16 mg kg-1] in group control). Intravenous granisetron reduced the requirement of prophylactic ephedrine in preventing hypotension after general anaesthesia induction in elderly patients.

A Modified 1H-NMR Quantification Method of Ephedrine Alkaloids in Ephedrae Herba Samples.

A previous 1H-NMR method allowed the quantification of ephedrine alkaloids; however, there were some disadvantages. The cyclized derivatives resulted from the impurities of diethyl ether were identified and benzene was selected as the better extraction solvent. The locations of ephedrine alkaloids were confirmed with 2D NMR. Therefore, a specific 1H-NMR method has been modified for the quantification of ephedrine alkaloids. Accordingly, twenty Ephedrae Herba samples could be classified into three classes: (I) E. sinica-like species; (II) E. intermedia-like species; (III) others (lower alkaloid contents). The results indicated that ephedrine and pseudoephedrine are the major alkaloids in Ephedra plants, but the concentrations vary greatly determined by the plant species and the collection locations.