ABSTRACT
We thank the authors for their insightful and thoughtful commentary on our recent publication [...].
ABSTRACT
Remimazolam is a novel general anesthetic and its safety in patients with malignant hyperthermia (MH) is unknown. We used myotubes derived from the skeletal muscle of patients with MH to examine the response to ryanodine receptor 1 (RYR1) agonist and remimazolam in MH-susceptible patients. Patients underwent muscle biopsy for the Ca2+-induced Ca2+ release (CICR) rate test, a diagnostic tool for MH in Japan. Ten patients had myotubes obtained from skeletal muscle cultures, and the genes associated with malignant hyperthermia in these patients were analyzed. The EC50 of caffeine, cresol, and remimazolam to induce intracellular calcium concentration change were compared between myotubes from CICR-negative genetic test patients and myotubes from other patients. Eight of the ten were CICR-positive, five of whom had RYR1 causative gene mutations or variants. Two patients had CICR-negative genetic tests, and as expected had the highest EC50 (the concentration of a drug that gives a half-maximal response) in response to caffeine, 4CmC and remimazolam. Three patients had a positive CICR but no known variants in RYR1 or CACNA1S (voltage-gated calcium channel subunit alpha1S). Myotubes in these patients had significantly lower EC50s for all agents than myotubes in CICR-negative patients. When myotubes from a patient who was CICR-negative and had no gene variant were used as a control, myotubes from CICR-positive patients were more hyper-responsive than controls to all stimulants used. The EC50 for remimazolam was lowest for myotubes from CICR-positive, RYR1-mutant patients, at 206 µM (corresponding to 123 µg/mL). The concentration was more than 80-times higher than the clinical concentration. RYR1 gene variants in R4645Q and W5020G were shown to be causative gene mutations for MH. Intracellular calcium in myotubes from MH patients are elevated at high concentrations of remimazolam but not at clinically used concentrations of remimazolam. Remimazolam appears to be safe to use in patients with MH.
Subject(s)
Malignant Hyperthermia , Ryanodine Receptor Calcium Release Channel , Humans , Ryanodine Receptor Calcium Release Channel/genetics , Malignant Hyperthermia/drug therapy , Malignant Hyperthermia/genetics , Calcium/metabolism , Caffeine/pharmacology , Muscle Fibers, Skeletal/metabolismABSTRACT
BACKGROUND: Remimazolam is a novel, ultrashort-acting benzodiazepine that can be antagonized by flumazenil. This study aimed to determine whether remimazolam-based anesthesia with flumazenil provides a more rapid emergence than propofol-based anesthesia in older patients undergoing spinal surgery. METHODS: This was a prospective, single-blind, randomized controlled trial. Forty-four patients > 75 years old who had undergone spinal surgery were enrolled in this study. They were randomly assigned to the remimazolam or propofol group (1:1) using a computer randomization system stratified by age and body weight. For anesthesia induction and maintenance, remifentanil was administered at a defined dose in both groups, and remimazolam or propofol was adjusted to maintain the bispectral index or state entropy monitoring within 40-60. All anesthetics were discontinued simultaneously after the postoperative X-ray and 0.5 mg flumazenil was administered to the remimazolam group. The primary outcome was extubation time after discontinuing anesthesia, and the secondary outcomes were time to eye opening, obeying commands, and achieving a white fast-track score (WFTS) of 12. RESULTS: Thirty-nine patients were finally analyzed: remimazolam group (n = 20), propofol group (n = 19). There were no significant differences in intraoperative variables, such as operative time, anesthesia time, and patient background, between the 2 groups. Extubation times were significantly shorter in the remimazolam group than in the propofol group (4 vs 8 minutes, P < .001). The time to eye opening, obeying commands, and achieving a WFTS of 12 were significantly shorter in the remimazolam group (P < .001, for all comparisons). CONCLUSION: Remimazolam-based anesthesia with flumazenil resulted in a faster emergence than propofol-based anesthesia in older patients undergoing spinal surgery.
Subject(s)
Propofol , Humans , Aged , Flumazenil , Anesthetics, Intravenous , Prospective Studies , Single-Blind Method , Benzodiazepines , Anesthesia, GeneralABSTRACT
Ropivacaine is an amide local anesthetic with rare reports of anaphylaxis. To our knowledge, this is the first report of delayed nonimmune anaphylaxis induced by ropivacaine. A 70-year-old man underwent general anesthesia with a nerve block for a total knee arthroplasty. The patient developed symptoms of anaphylaxis 3.5 hours after receiving ropivacaine for femoral and tibial nerve blocks. A basophil activation test (BAT) revealed ropivacaine as the causative agent. Notably, anaphylaxis can be caused by medications even hours after their administration, and all administered drugs should be suspected of potentially causing anaphylaxis.
Subject(s)
Anaphylaxis , Nerve Block , Male , Humans , Aged , Ropivacaine/adverse effects , Anesthetics, Local/adverse effects , Anaphylaxis/chemically induced , Amides/adverse effects , Nerve Block/adverse effectsABSTRACT
(1) Background: Remimazolam is a novel benzodiazepine that prevents postoperative nausea and vomiting (PONV), is more effective than volatile anesthetics, and was recently approved for use in Japan. (2) Methods: This prospective, double-blind, randomized controlled trial study aimed to compare the efficacy of remimazolam and propofol as general anesthetics in terms of the incidence of PONV after laparoscopic gynecological surgery (UMIN000046237). High-risk female patients who underwent general anesthesia with either remimazolam or propofol for the maintenance of anesthesia were enrolled. The primary outcome was the incidence of PONV in the two groups (i.e., REM versus PROP) 2 h and 24 h after surgery. The incidence of vomiting without nausea, rescue antiemetic use, and the severity of nausea were also evaluated. (3) Results: No significant differences in PONV were identified between the REM and PROP groups at 2 h or 24 h. Furthermore, no differences were observed in any of the measured parameters, and no adverse events were reported. (4) Conclusions: The results of the present study suggest that remimazolam may be as effective as propofol in preventing PONV; however, further investigation is necessary to identify possible differences between these two agents.
ABSTRACT
Purpose: Malignant hyperthermia (MH) is a rare genetic disorder but one of the most severe complications of general anesthesia. The mortality rate of MH has dropped from 70% in the 1960s to 15% because of dantrolene, the only currently accepted specific treatment for MH. In this study, we retrospectively identified the optimal dantrolene administration conditions to reduce MH mortality further. Methods: Our database performed a retrospective analysis of patients with MH clinical grading scale (CGS) grade 5 (very likely) or 6 (almost certain) between 1995 and 2020. We examined whether dantrolene administration affected mortality and compared the clinical variables associated with improved prognosis. Furthermore, a multivariable logistic regression analysis was used to identify specific variables associated with improved prognosis. Results: 128 patients met the inclusion criteria. 115 patients were administered dantrolene; 104 survived, and 11 died. The mortality rate of patients who were not administered dantrolene was 30.8%, which was significantly higher than those of patients who were administered dantrolene (P = 0.047). Among patients administered dantrolene, the interval from the first sign of MH to the start of dantrolene administration was significantly longer in the deceased than in the survivors (100 min vs. 45.0 min, P < 0.001), and the temperature at the start of dantrolene administration was also significantly higher in the deceased (41.6°C vs. 39.1°C, P < 0.001). There was no significant difference in the rate of increase in temperature between the two, but there was a substantial difference in the maximum temperature (P < 0.001). The multivariable analysis also showed that the patient's temperature at dantrolene administration and interval from the first MH sign to dantrolene administration was significantly associated with improved prognosis. Conclusions: Dantrolene should be given as rapidly as possible once MH has been diagnosed. Beginning treatment at a more normal body temperature can prevent critical elevations associated with a worse prognosis.
Subject(s)
Dantrolene , Malignant Hyperthermia , Humans , Retrospective Studies , Body Temperature , East Asian People , Rare DiseasesABSTRACT
BACKGROUND Hemophagocytic syndrome (HPS) is a rare syndrome characterized by abnormal activation of histiocytes and hemophagocytosis. We report the clinical management of recurrent HPS following 2 cesarean sections in the same patient. CASE REPORT A 33-year-old primiparous mother presented during her second trimester of pregnancy, and HPS was diagnosed based on pancytopenia, hyperferritinemia (13 170 ng/ml), and hemophagocytosis in bone marrow examination. Despite steroid therapy, her HPS did not improve. Following the delivery of a healthy premature infant, there was no improvement in HPS, and immunochemotherapy was started 4 days postoperatively. Thrombocytopenia and hyperferritinemia persisted but normalized over the next 2 months, and immunochemotherapy was discontinued after 6 months. About 1 year after chemotherapy, the patient became pregnant with her second child. At 35 weeks of gestation, recurrence of HPS was suspected, and a C-section was performed at 36 weeks of gestation. The surgery was complicated by placenta previa, and general anesthesia was initiated after successful delivery of the infant. Epidural anesthesia was not performed due to concerns for postoperative thrombocytopenia. CONCLUSIONS Interestingly, HPS was likely triggered twice by pregnancy in this patient. Although reports of HPS during pregnancy are rare, there have been reports of rapid deterioration and death. Early diagnosis and therapeutic intervention are essential.
Subject(s)
Hyperferritinemia , Lymphohistiocytosis, Hemophagocytic , Pancytopenia , Thrombocytopenia , Female , Infant , Child , Pregnancy , Humans , Adult , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/therapy , Lymphohistiocytosis, Hemophagocytic/complications , Pregnant Women , Hyperferritinemia/complications , Pancytopenia/etiology , Thrombocytopenia/complicationsABSTRACT
Introduction: We compared the hemodynamics during general anesthesia with remimazolam and conventional anesthetics in patients with severe aortic stenosis (AS). Methods: This was a retrospective single-center analysis. We reviewed the records of 42 patients who underwent transcatheter aortic valve implantation with a transfemoral artery approach under general anesthesia from January to December 2020. Patients were divided into three groups based on the general anesthetic used for (induction/maintenance) remimazolam/remimazolam (Group R/R), propofol/sevoflurane (Group P/S), and midazolam/propofol (Group M/P). Vasopressor use (ephedrine, phenylephrine, and noradrenaline) was compared among the groups. Results: The number of patients in each group was 15 (Group R/R), 13 (Group P/S), and 14 (Group M/P), with no significant difference in background characteristics and intraoperative vital signs. For anesthesia induction, doses of ephedrine and phenylephrine used were significantly lower in Group R/R (ephedrine [mg]: Group R/R 2 [0-4] vs. Group P/S 8 [8-12], P < 0.001, Group R/R vs. Group M/P 5 [0-15], P = 0.39; phenylephrine (mg): Group R/R 0 [0-0.08] vs. Group P/S 0.15 [0.10-0.20], P = 0.03, Group M/P 0.21 [0.04-0.40], P = 0.08). For anesthesia maintenance, the noradrenaline dose used was low in the Group R/R (noradrenaline [µg/kg/min]: Group R/R 0.019 [0.015-0.039], Group P/S 0.042 [0.035-0.045], P = 0.02, Group M/P 0.048 [0.040-0.059], P < 0.01). Conclusion: In patients with severe AS, induction and maintenance of anesthesia with remimazolam resulted in less overall vasopressor use than conventional general anesthetics.
Subject(s)
Anesthetics, General , Aortic Valve Stenosis , Propofol , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/methods , Propofol/therapeutic use , Retrospective Studies , Ephedrine , Anesthesia, General/methods , Aortic Valve Stenosis/drug therapy , Aortic Valve Stenosis/surgery , Phenylephrine/therapeutic use , Norepinephrine/therapeutic use , Aortic Valve/surgeryABSTRACT
Background and aimsâ :â Severe aortic stenosis (AS) has been normally treated with surgical aortic valve replacement (AVR) whereas recently, transcatheter aortic valve implantation (TAVI) has been introduced as a minimally invasive operation for patients with high surgical risk and frailty. In this study, we have evaluated postoperative physical function and nutrition intake in the patients following AVR and TAVI. Methodsâ :â This prospective observational study involved 9 patients with surgical aortic valve replacement (AVR) and 7 patients with transcatheter aortic valve implantation (TAVI). Body composition was measured one day prior surgery, postoperative day (POD) 1, POD 3, POD 5 and POD 7. Hand grip strength, calf circumference and gait speed were measured one day before surgery and on the day of discharge. Resultsâ :â Skeletal muscle was significantly decreased in AVR patients at postoperative day 3 and 7, while there was no change in TAVI patients. Patients with TAVI showed higher dietary intake after surgery compared to patients with AVR, and they maintained hand grip strength and calf circumference at discharge. Conclusionsâ :â In elderly patients with AS, TAVI can improve post-operative recovery maintaining nutritional status and physical function even. J. Med. Invest. 67 : 139-144, February, 2020.
Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Heart Valve Prosthesis Implantation , Nutritional Status , Transcatheter Aortic Valve Replacement , Aged , Aged, 80 and over , Aortic Valve Stenosis/physiopathology , Body Composition , Female , Hand Strength , Humans , Male , Postoperative Period , Prospective Studies , Walking SpeedABSTRACT
The aim of this work was to investigate the effect of oral carbohydrate with amino acid [oral nutritional supplement (ONS)] solution on oxidative stress in healthy persons. Fourteen healthy volunteers were segregated into control and ONS groups. Volunteers in the ONS group ingested 250 ml of Arginaid Water (Nestle Japan, Tokyo, Japan) in the evening before the experiment and at 7:00 am on the day of the experiment. Volunteers in the control group fasted after dinner and drank only water until 7:00 am on the day of the experiment. In both groups, blood was collected at 9:00 am. The serum total oxidant levels and antioxidant capacity were assessed by d-ROMs (derivatives of reactive oxygen metabolites) test and BAP (biological antioxidant potential) test, respectively. In the ONS group, the serum d-ROMs level was significantly lower than in the control group (297 ± 43 and 327 ± 41 U.CARR, respectively, p = 0.018), while the serum BAP level was significantly higher than the control group (2410 ± 432 and 1979 ± 397 µmol/l, respectively, p = 0.005). The OXY level of Arginaid Water was much higher than preOp drink (Nutricia, Ireland). In conclusion, our study showed that an ONS with arginine loading could decrease oxidative stress and increase antioxidant capacity in healthy volunteers.
Subject(s)
Amino Acids/administration & dosage , Antioxidants/metabolism , Carbohydrates/administration & dosage , Oxidative Stress/drug effects , Cross-Over Studies , Fasting , Humans , Japan , Reactive Oxygen Species/metabolismABSTRACT
CASE: Toshi, a 14-year-old Japanese boy, had uncontrolled asthma after relocating from Japan with his family 1 year ago. In Japan, he was diagnosed with moderate, persistent asthma, which was controlled with salmeterol and albuterol on an as needed basis. Since moving to the United States, Toshi complained of frequent dyspnea.Initially, he was seen by a Japanese physician who prescribed 200 mg of fluticasone 3 times a day and albuterol nebulization as needed. When Toshi came to the Pediatric Primary Care Clinic, he reported using his nebulizer up to 25 times daily. A physical examination revealed a thin, anxious, jittery, hypertensive, and tachycardic adolescent with hyperreflexia and dysmetria. Toshi complained of difficulty breathing, in the absence of wheezing or respiratory distress; peak flow recordings in the office were normal. Furthermore, he had a history of "panic attacks," being a "worrier," and stopped attending school, playing sports, and socializing over the past 6 months due to his "breathing difficulties."Citalopram was prescribed for anxiety, but the family's apprehension about mental health disorders led to resistance to treatment recommendations. With motivational interviewing and negotiation, Toshi and his family agreed to a trial of citalopram. Three months later, he no longer took fluticasone or albuterol. The tachycardia, hypertension, and neurological symptoms improved. As he gained weight and improved his strength, he attended classes and participated in sports.A few months later, with improvement of his health, Toshi and his parents decided to discontinue citalopram. He then developed behaviors consistent with generalized anxiety and obsessive-compulsive disorder. Currently, his symptoms associated with anxiety have worsened, but he and his family are resistant to medication or initiating cognitive behavioral therapy due to their cultural beliefs regarding mental health disorders.
Subject(s)
Anti-Asthmatic Agents/adverse effects , Anxiety Disorders/ethnology , Asthma/drug therapy , Cultural Competency , Prescription Drug Overuse/adverse effects , Adolescent , Humans , Japan/ethnology , Male , Obsessive-Compulsive Disorder/ethnology , Panic Disorder/ethnologyABSTRACT
Caveolin-3 (Cav-3) plays a critical role in organizing signaling molecules and ion channels involved in cardiac conduction and metabolism. Mutations in Cav-3 are implicated in cardiac conduction abnormalities and myopathies. Additionally, cardiac-specific overexpression of Cav-3 (Cav-3 OE) is protective against ischemic and hypertensive injury, suggesting a potential role for Cav-3 in basal cardiac electrophysiology and metabolism involved in stress adaptation. We hypothesized that overexpression of Cav-3 may alter baseline cardiac conduction and metabolism. We examined: (1) ECG telemetry recordings at baseline and during pharmacological interventions, (2) ion channels involved in cardiac conduction with immunoblotting and computational modeling, and (3) baseline metabolism in Cav-3 OE and transgene-negative littermate control mice. Cav-3 OE mice had decreased heart rates, prolonged PR intervals, and shortened QTc intervals with no difference in activity compared to control mice. Dobutamine or propranolol did not cause significant changes between experimental groups in maximal (dobutamine) or minimal (propranolol) heart rate. Cav-3 OE mice had an overall lower chronotropic response to atropine. The expression of Kv1.4 and Kv4.3 channels, Nav1.5 channels, and connexin 43 were increased in Cav-3 OE mice. A computational model integrating the immunoblotting results indicated shortened action potential duration in Cav-3 OE mice linking the change in channel expression to the observed electrophysiology phenotype. Metabolic profiling showed no gross differences in VO2, VCO2, respiratory exchange ratio, heat generation, and feeding or drinking. In conclusion, Cav-3 OE mice have changes in ECG intervals, heart rates, and cardiac ion channel expression. These findings give novel mechanistic insights into previously reported Cav-3 dependent cardioprotection.
Subject(s)
Caveolin 3/metabolism , Heart/physiology , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Animals , Computer Simulation , Electrocardiography , Heart Rate/physiology , Immunoblotting , Mice , Mice, Inbred C57BL , Mice, TransgenicABSTRACT
BACKGROUND: This study investigated plasma concentrations of substance P (SP) in patients undergoing general anesthesia (GA) and postoperative nausea and vomiting (PONV). This prospective, observational, cohort study included 23 patients who underwent scheduled surgery under general anesthesia. Blood was collected from the radial artery at predetermined time points (15-30 mins prior anesthesia, 15-30 mins after surgery/GA, and 24 h after surgery). PONV, SP concentrations, risk factors, and analgesics used were measured. FINDINGS: Nine of 23 patients experienced PONV. In patients without PONV, SP concentrations significantly decreased (P < 0.0001) at the end of surgery/GA, compared to baseline, and recovered at 24 h after surgery/GA (452.9 ± 146.2 vs. 666.9 ± 176.5 vs. 580.7 ± 168.6 pg/mL, respectively), whereas SP levels were unchanged during surgery/GA and increased at 24 hours after surgery (P = 0.020) in patients with PONV (726.1 ± 167.8 vs. 655.8 ± 168.0 vs. 779.7 ± 220.7 pg/mL, respectively). CONCLUSIONS: These finding suggest that SP levels may be utilized as an objective marker for PONV.
ABSTRACT
BACKGROUND: Sepsis and septic shock syndrome are among the leading causes of death in critically ill patients. Lipopolysaccharide (LPS) released by bacteria within the colon may translocate across a compromised epithelium, leading to oxidative stress, inflammation, sepsis, and eventually death. METHODS: We examined the effects of a whey-based enteral formula high in cysteine (antioxidant precursor) and the addition of ω-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), against a mouse model of LPS-induced sepsis. Mice were fed either a whey-based diet with EPA-DHA (PAF), a whey-based diet without EPA-DHA (PSTD), or a casein-based control diet (CONT). RESULTS: Mice fed PAF or PSTD were protected against LPS-induced weight loss. Whey-based diets suppressed inflammatory cytokine release and oxidative stress damage. Furthermore, PAF and PSTD were able to inhibit autophagy, a mechanism in which the cell recycles damaged organelles. These anti-inflammatory and antioxidative effects of PSTD and PAF resulted in decreased liver inflammation and intestinal damage and promoted protective microbiota within the intestines. CONCLUSIONS: These data suggest a clinical role for whey peptide-based diets in promoting healing and recovery in critically ill patients.
Subject(s)
Critical Illness/therapy , Enteral Nutrition , Fatty Acids, Omega-3/therapeutic use , Intestines/drug effects , Liver/drug effects , Sepsis/drug therapy , Whey Proteins/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Autophagy/drug effects , Cysteine/pharmacology , Cytokines/metabolism , Docosahexaenoic Acids/pharmacology , Docosahexaenoic Acids/therapeutic use , Eicosapentaenoic Acid/pharmacology , Eicosapentaenoic Acid/therapeutic use , Fatty Acids, Omega-3/pharmacology , Food, Formulated , Gastrointestinal Microbiome/drug effects , Intestines/microbiology , Intestines/pathology , Lipopolysaccharides , Liver/pathology , Mice , Mice, Inbred C57BL , Peptides/pharmacology , Peptides/therapeutic use , Sepsis/chemically induced , Sepsis/metabolism , Sepsis/pathology , Shock, Septic , Weight Loss/drug effects , Whey , Whey Proteins/pharmacologyABSTRACT
AIMS: Geranylgeranylacetone (GGA) is commonly utilized to protect the gastric mucosa in peptic ulcer disease. Recently GGA has been shown to protect the myocardium from ischemia/reperfusion by activating heat shock proteins. However, the exact mechanism as to how GGA activates these protective proteins is unknown. Caveolae and caveolin-3 (Cav-3) have been implicated in ischemia, anesthetic, and opioid induced cardiac protection. Given the lipophilic nature of GGA it is our hypothesis that GGA induced cardiac protection requires caveolae and Cav-3. MAIN METHODS: We used an in vivo mouse model of ischemia-reperfusion injury and performed biochemical assays in excised hearts. KEY FINDINGS: GGA treated control mice revealed increased caveolae formation and caveolin-3 in buoyant fractions, mediating heat shock protein 70 activation. Furthermore, control mice treated with GGA were protected against ischemia/reperfusion injury whereas Cav-3 knockout (Cav-3 KO) mice were not. Troponin levels confirmed myocardial damage. Finally, Cav-3 KO mice treated with GGA were not protected against mitochondrial swelling whereas control mice had significant protection. SIGNIFICANCE: This study showed that caveolae and caveolin-3 are essential in facilitating GGA induced cardiac protection by optimizing spatial and temporal signaling to the mitochondria.
Subject(s)
Cardiotonic Agents/pharmacology , Caveolae/drug effects , Caveolin 3/metabolism , Diterpenes/pharmacology , Myocardial Reperfusion Injury/metabolism , Animals , Cardiotonic Agents/therapeutic use , Caveolin 3/genetics , Diterpenes/therapeutic use , Male , Mice , Mice, Knockout , Mitochondrial Swelling/drug effects , Myocardial Reperfusion Injury/drug therapy , Myocardium/metabolism , Myocardium/ultrastructure , Troponin/metabolismABSTRACT
PURPOSE: Pharmacological preconditioning, including that with geranylgeranylacetone (GGA) and volatile anesthetics, has been shown to confer cardiac protection from ischemia/reperfusion injury although the mechanisms for this protection are poorly understood. Caveolins, integral membrane proteins that act as scaffolding proteins in caveolar membranes, localize molecules involved in cardiac protection. We have tested the hypothesis that caveolin-3 (Cav-3), the predominant isoform in cardiac myocytes, is essential for the synergistic effect observed between GGA and volatile anesthetics. METHODS: Mice were randomly assigned to receive GGA, isoflurane [0.5 and 1.0 minimum alveolar concentration (MAC)], or GGA + isoflurane (0.5 MAC). An in vivo mouse model of ischemia/reperfusion injury was tested in wild-type and Cav-3 knockout mice, and the infarct size was determined. Biochemical assays were also performed in excised hearts. RESULTS: Geranylgeranylacetone and therapeutic isoflurane (1.0 MAC) independently reduced infarct size (31.6 ± 6.1 and 28.0 ± 5.0% of the area at risk, respectively; n = 10) as compared to the controls (45.8 ± 9.4%; n = 10). The combination GGA + sub-therapeutic isoflurane (0.5 MAC) further decreased the infarct size to 19.3 ± 5.1% (n = 10). Preconditioning [GGA, isoflurane (1.0 MAC), and GGA + isoflurane] increased the amount of Cav-3 protein in the discontinuous sucrose-gradient buoyant fractions. Additionally, cardiac protection was not observed in Cav-3 knockout mice following the administration of GGA, isoflurane, and GGA + isoflurane. CONCLUSIONS: Combined administration of GGA + isoflurane had a synergistic effect, enhancing the protection against myocardial infarction to a greater extent than either drug alone. This beneficial effect is mediated by Cav-3 expression.
Subject(s)
Anesthetics, Inhalation/pharmacology , Diterpenes/pharmacology , Isoflurane/pharmacology , Myocardial Infarction/prevention & control , Anesthetics, Inhalation/administration & dosage , Animals , Caveolae/metabolism , Caveolin 3/genetics , Caveolin 3/metabolism , Diterpenes/administration & dosage , Drug Synergism , Isoflurane/administration & dosage , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Myocardial Reperfusion Injury/drug therapy , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolismABSTRACT
CASE: Toshi, a 14-year-old Japanese boy, had uncontrolled asthma after relocating from Japan with his family 1 year ago. In Japan, he was diagnosed with moderate, persistent asthma, which was controlled with salmeterol and albuterol on an as needed basis. Since moving to the United States, Toshi complained of frequent dyspnea.Initially, he was seen by a Japanese physician who prescribed 200 mg of fluticasone 3 times a day and albuterol nebulization as needed. When Toshi came to the Pediatric Primary Care Clinic, he reported using his nebulizer up to 25 times daily. A physical examination revealed a thin, anxious, jittery, hypertensive, and tachycardic adolescent with hyperreflexia and dysmetria. Toshi complained of difficulty breathing, in the absence of wheezing or respiratory distress; peak flow recordings in the office were normal. Furthermore, he had a history of "panic attacks," being a "worrier," and stopped attending school, playing sports, and socializing over the past 6 months due to his "breathing difficulties."Citalopram was prescribed for anxiety, but the family's apprehension about mental health disorders led to resistance to treatment recommendations. With motivational interviewing and negotiation, Toshi and his family agreed to a trial of citalopram. Three months later, he no longer took fluticasone or albuterol. The tachycardia, hypertension, and neurological symptoms improved. As he gained weight and improved his strength, he attended classes and participated in sports.A few months later, with improvement of his health, Toshi and his parents decided to discontinue citalopram. He then developed behaviors consistent with generalized anxiety and obsessive-compulsive disorder. Currently, his symptoms associated with anxiety have worsened, but he and his family are resistant to medication or initiating cognitive behavioral therapy due to their cultural beliefs regarding mental health disorders.
Subject(s)
Antidepressive Agents/pharmacology , Asthma/psychology , Bronchodilator Agents/administration & dosage , Dyspnea/psychology , Medication Adherence/ethnology , Adolescent , Albuterol/administration & dosage , Androstadienes/administration & dosage , Anxiety Disorders/complications , Anxiety Disorders/drug therapy , Anxiety Disorders/ethnology , Asthma/drug therapy , Citalopram/pharmacology , Cultural Competency , Dyspnea/drug therapy , Fluticasone , Humans , Japan , Male , United StatesABSTRACT
Caveolae are flask-like invaginations of the cell surface that have been identified as signaling epicenters. Within these microdomains, caveolins are structural proteins of caveolae, which are able to interact with numerous signaling molecules affecting temporal and spatial dimensions required in cardiac protection. This complex moiety is essential to the mechanisms involved in volatile anesthetics. In this review we will outline a general overview of caveolae and caveolins and their role in protective signaling with a focus on the effects of volatile anesthetics. These recent developments have allowed us to better understand the mechanistic effect of volatile anesthetics and their potential in cardiac protection.
Subject(s)
Anesthetics, Inhalation/pharmacology , Caveolae/metabolism , Heart Diseases/prevention & control , Animals , Caveolins/metabolism , Heart Diseases/physiopathology , Humans , Signal Transduction/drug effects , Signal Transduction/physiologyABSTRACT
Patients with renal failure often experience decreased serum zinc that remains uncorrected after dialysis. A complication of this depletion is taste impairment, which can detrimentally influence diet and nutrition. However, because more than half of all serum zinc is bound to albumin, we hypothesized that normalizing serum zinc to albumin levels may be associated with taste impairment. A total of 65 patients undergoing dialysis but not receiving supplementary zinc and 120 control patients not undergoing dialysis (60 malnourished patients and 60 healthy controls) were tested for their receptiveness to saltiness using various salt concentrations. Patients' total protein and albumin levels were measured, and linear regressions were extrapolated between serum zinc levels and total protein or albumin. Patients undergoing dialysis had significantly lower levels of total serum zinc compared with control patients. However, uncorrected zinc levels were not correlated with taste impairment. Normalizing zinc levels against total protein or albumin resulted in extrapolated equations that revealed a significant correlation with taste impairment. Our data suggest a statistical correlation between zinc and albumin in both healthy subjects and patients undergoing maintenance hemodialysis, or protein-energy malnutrition without hemodialysis, allowing for a quantitative measure for taste impairment.
Subject(s)
Renal Dialysis/adverse effects , Serum Albumin/analysis , Taste Disorders/blood , Zinc/blood , Adult , Aged , Aged, 80 and over , Female , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Male , Middle Aged , Serum Albumin/metabolism , Taste Disorders/etiologyABSTRACT
OBJECTIVE: Malnutrition is frequent in the geriatric population and is often undetected and untreated. Although we often use serum albumin as a nutritional marker, it has limitations in elderly patients in terms of predicting diseases and infections. Anthropometric measurements are not commonly used, despite their simple, easy, and effective characteristics. We evaluated the associations between anthropometric measurements with other nutritional factors and examined its relationship with mortality, decubitus ulcer, length of hospital stay and antibiotic usage. RESEARCH METHODS AND PROCEDURES: We enrolled 223 patients, performed anthropometric measurements and then followed them for a mean of 24 months. RESULTS: Patients with hypoalbuminemia but with normal body measurements tended to increase serum albumin levels over the next 24 months and had more favorable outcomes including being discharged. Patients with normal albumin but decreased body measurements resulted in a progressive drop in serum albumin and had a higher mortality rate. Additionally, patients with hypoalbuminemia had higher antibiotic usage than patients without hypoalbuminemia. Decreases in anthropometric measurements were related to mortality, length of hospital stay, and decubitus ulcer. CONCLUSIONS: Anthropometric measurements are easily obtained and closely associated with mortality, decubitus ulcer, and length of hospital stay. Anthropometric measurements used in conjunction with serum albumin are more predictive of patient outcome then serum albumin alone.