ABSTRACT
Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is among the most fatal postoperative complications of lung resection in patients with IPF. Non-small-cell lung cancer (NSCLC) with IPF exhibits basal segment dominance. Treatment options for these lesions include lobectomy or basal segment segmentectomies. However, these procedures potentially increase risks of AE due to surgical stress including prolonged operative time and loss of pulmonary function. Therefore, as an alternative to these procedures, we developed a simple and practical deep wedge resection technique for basal segments. Our technique is minimally invasive and quick and simple approach in patients with NSCLC and IPF.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Idiopathic Pulmonary Fibrosis , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Humans , Idiopathic Pulmonary Fibrosis/complications , Idiopathic Pulmonary Fibrosis/surgery , Lung/pathology , Lung Neoplasms/complications , Lung Neoplasms/pathology , Lung Neoplasms/surgeryABSTRACT
BACKGROUND: As of 2014, routine vaccination strategies in Japan have included the varicella vaccine. Given the widespread use of the vaccine, it is important to investigate the safety profile of the vaccine strain, Oka/Biken varicella, in Japanese patients. METHODS: Reports of adverse events associated with varicella vaccination between 2005 and 2015 were retrospectively reviewed. Virological analysis was performed on clinical specimens collected from some of the reported cases to determine whether the etiological agent was the wild-type or Oka vaccine-strains. RESULTS: There were 351 reports (3.71/100,000 doses) of adverse events during the observation period. Among the 351 reports, there were 88 reports (0.93/100,000 doses) of varicella-like and 66 reports (0.70/100,000 doses) of zoster-like skin rashes. The wild-type strain induced varicella-like skin rashes earlier than the Oka vaccine strain. The Oka vaccine strain induced zoster-like skin rashes in younger patients compared to the wild-type strain. The onset of zoster-like skin rashes after vaccination was earlier in patients vaccinated with the Oka vaccine-type strain. CONCLUSION: The Oka/Biken vaccine is generally safe and well tolerated in Japan. Clinical aspects of adverse reactions caused by the Oka vaccine strain were consistent with previous reports from the United States and Europe.
Subject(s)
Chickenpox Vaccine/adverse effects , Exanthema/virology , Herpes Zoster/chemically induced , Product Surveillance, Postmarketing , Adolescent , Adult , Aged , Child , Child, Preschool , Drug-Related Side Effects and Adverse Reactions/epidemiology , Female , Humans , Infant , Japan/epidemiology , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
α-synuclein (SNCA) is an established susceptibility gene for Parkinson's disease (PD), one of the most common human neurodegenerative disorders. Increased SNCA is considered to lead to PD and dementia with Lewy bodies. Four single-nucleotide polymorphisms (SNPs) in SNCA 3' region were prominently associated with PD among different ethnic groups. To examine how these SNPs influence disease susceptibility, we analyzed their potential effects on SNCA gene expression. We found that rs356219 showed allele-specific features. Gel shift assay using nuclear extracts from SH-SY5Y cells showed binding of one or more proteins to the protective allele, rs356219-A. We purified the rs356219-A-protein complex with DNA affinity beads and identified a bound protein using mass spectrometry. This protein, YY1 (Yin Yang 1), is an ubiquitous transcription factor with multiple functions. We next investigated SNCA expression change in SH-SY5Y cells by YY1 transfection. We also analyzed the expression of antisense noncoding RNA (ncRNA) RP11-115D19.1 in SNCA 3'-flanking region, because rs356219 is located in intron of RP11-115D19.1. Little change was observed in SNCA expression levels; however, RP11-115D19.1 expression was prominently stimulated by YY1. In autopsied cortices, positive correlation was observed among RP11-115D19.1, SNCA and YY1 expression levels, suggesting their functional interactions in vivo. Knockdown of RP11-115D19.1 increased SNCA expression significantly in SH-SY5Y cells, suggesting its repressive effect on SNCA expression. Our findings of the protective allele-specific YY1 and antisense ncRNA raised a novel possible mechanism to regulate SNCA expression.
Subject(s)
3' Untranslated Regions , Nuclear Proteins/metabolism , RNA, Antisense/biosynthesis , RNA, Untranslated/biosynthesis , Transcription Factors/metabolism , alpha-Synuclein/metabolism , Adult , Aged , Asian People , Cell Cycle Proteins , Female , Humans , Male , Middle Aged , Nuclear Proteins/chemistry , Polymorphism, Single Nucleotide , Protein Binding , RNA, Antisense/genetics , RNA, Untranslated/genetics , Transcription Factors/chemistry , White People , alpha-Synuclein/geneticsABSTRACT
The mechanism of agonist-induced GABA(B) receptor (GABA(B) R) internalization is not well understood. To investigate this process, we focused on the interaction of GABA(B) R with ß-arrestins, which are key proteins in the internalization of most of the G protein-coupled receptors, and the agonist-induced GABA(B) R internalization and the interaction of GABA(B) R with ß-arrestin1 and ß-arrestin2 were investigated in real time using GABA(B) R and ß-arrestins both of which were fluorescent protein-tagged. We then compared these profiles with those of µ-opioid receptors (µOR), well-studied receptors that associate and cointernalize with ß-arrestins. When stimulated by the specific GABA(B) R agonist baclofen, GABA(B) R composed of GABA(B1a) R (GB(1a) R) and fluorescent protein-tagged GABA(B2) R-Venus (GB2 R-V) formed functional GABA(B) R; they elicited G protein-activated inwardly rectifying potassium channels as well as nontagged GABA(B) R. In cells coexpressing GB(1a) R, GB2 R-V, and ß-arrestin1-Cerulean (ßarr1-C) or ß-arrestin2-Cerulean (ßarr2-C), real-time imaging studies showed that baclofen treatment neither internalized GB2 R-V nor mobilized ßarr1-C or ßarr2-C to the cell surface. This happened regardless of the presence of G protein-coupled receptor kinase 4 (GRK4), which forms a complex with GABA(B) R and causes GABA(B) R desensitization. On the other hand, in cells coexpressing µOR-Venus, GRK2, and ßarr1-C or ßarr2-C, the µOR molecule formed µOR/ßarr1 or µOR/ßarr2 complexes on the cell surface, which were then internalized into the cytoplasm in a time-dependent manner. Fluorescence resonance energy transfer assay also indicated scarce association of GB2 R-V and ß-arrestins-C with or without the stimulation of baclofen, while robust association of µOR-V with ß-arrestins-C was detected after µOR activation. These findings suggest that GABA(B) Rs failure to undergo agonist-induced internalization results in part from its failure to interact with ß-arrestins.
Subject(s)
Arrestins/metabolism , Baclofen/pharmacology , GABA-B Receptor Agonists/pharmacology , Receptors, GABA-B/metabolism , Animals , Cell Line , Cricetinae , Fluorescence Resonance Energy Transfer , G Protein-Coupled Inwardly-Rectifying Potassium Channels/metabolism , Humans , Rats , beta-ArrestinsABSTRACT
Copper (Cu) is an essential element for cereals, playing important roles as a cofactor of several enzymes. Copper and four other metals (Fe, Mn, Zn and Mo) taken up by roots are efficiently delivered to the shoots via xylem and phloem. Here we investigated the concentrations of Cu, Fe, Mn, Zn and Mo in the xylem and phloem saps as well as in tissues of rice (Oryza sativa L.) seedlings when they were grown under different Cu levels in culture solution. Although the Cu concentrations in the roots and the Mn concentrations in the mature shoot tissues were increased with the increase of the Cu level in the culture solution, the concentrations of Cu and the other four metals in the xylem and phloem saps and the Cu contents in the shoot tissues were only slightly affected by moderate increases in the Cu medium level. The results of our analyses using membrane filtration, size-exclusion chromatography and electrospray ionisation time-of-flight mass spectrometry indicate that Cu in the xylem sap is dominantly complexed by 2'-deoxymugineic acid, whereas Cu in the phloem sap is bound to several compounds, i.e. nicotianamine, histidine and other >3-kDa compounds.
ABSTRACT
The benzo[b]furan derivative MU314 inhibits in vitro bone resorption as potently as ß-estradiol (E(2)). Here, we examined the point of action on the anti-osteoporotic effects of MU314. MU314 (10 nM) suppressed lacunae formation by osteoclastic cells and ICI-182,780, a pure E(2) antagonist, inhibited this effect. Specifically, we ovariectomized (OVX) Wistar female rats and subcutaneously injected them with either MU314 (30 or 100 µg/kg) or E(2) (100 µg/kg) over an 8-week period. Bone mineral content (BMC) in the proximal end of the tibia was significantly decreased (14%) in OVX rats, and MU314 (100 µg/kg) and E(2) significantly suppressed the decline in BMC. OVX rats exhibited decreased cancellous bone in the proximal end of the tibia and induced destruction of its trabecular structure. MU314 suppressed these changes. OVX also reduced the mechanical strength of the femoral neck, which was also recovered by MU314 and E(2). E(2) completely protected against OVX-induced uterine atrophy, but MU314 had no effect. These results strongly indicate that MU314 acts as a selective estrogen receptor modulator.
Subject(s)
Benzofurans/pharmacology , Osteoporosis/prevention & control , Selective Estrogen Receptor Modulators/pharmacology , Animals , Female , Rats , Rats, WistarABSTRACT
BACKGROUND: Intrathecal baclofen therapy is an established treatment for severe spasticity. However, long-term management occasionally results in the development of tolerance. One of the mechanisms of tolerance is desensitization of γ-aminobutyric acid type B receptor (GABABR) because of the complex formation of the GABAB2 subunit (GB2R) and G protein-coupled receptor kinase (GRK) 4 or 5. The current study focused on S(+)-ketamine, which reduces the development of morphine tolerance. This study was designed to investigate whether S(+)-ketamine affects the GABABR desensitization processes by baclofen. METHODS: The G protein-activated inwardly rectifying K channel currents induced by baclofen were recorded using Xenopus oocytes coexpressing G protein-activated inwardly rectifying K channel 1/2, GABAB1a receptor subunit, GB2R, and GRK. Translocation of GRKs 4 and 5 and protein complex formation of GB2R with GRKs were analyzed by confocal microscopy and fluorescence resonance energy transfer analysis in baby hamster kidney cells coexpressing GABAB1a receptor subunit, fluorescent protein-tagged GB2R, and GRKs. The formation of protein complexes of GB2R with GRKs was also determined by coimmunoprecipitation and Western blot analysis. RESULTS: Desensitization of GABABR-mediated signaling was suppressed by S(+)-ketamine in a concentration-dependent manner in the electrophysiologic assay. Confocal microscopy revealed that S(+)-ketamine inhibited translocation of GRKs 4 and 5 to the plasma membranes and protein complex formation of GB2R with the GRKs. Western blot analysis also showed that S(+)-ketamine inhibited the protein complex formation of GB2R with the GRKs. CONCLUSION: S(+)-Ketamine suppressed the desensitization of GABABR-mediated signaling at least in part through inhibition of formation of protein complexes of GB2R with GRK 4 or 5.
Subject(s)
Analgesics/pharmacology , G-Protein-Coupled Receptor Kinases/metabolism , Ketamine/pharmacology , Receptors, GABA-B/metabolism , Signal Transduction/drug effects , Animals , Baclofen/pharmacology , Blotting, Western , Cells, Cultured , Cricetinae , Drug Interactions , Drug Tolerance , Electrophysiological Phenomena , Fluorescence Resonance Energy Transfer , G Protein-Coupled Inwardly-Rectifying Potassium Channels/drug effects , G Protein-Coupled Inwardly-Rectifying Potassium Channels/metabolism , G-Protein-Coupled Receptor Kinases/drug effects , GABA-B Receptor Agonists/pharmacology , Kidney/drug effects , Kidney/metabolism , Mice , Microscopy, Confocal , Rats , Receptors, GABA-B/drug effects , XenopusABSTRACT
Muscle injury was studied to test the hypotheses that maintaining the soleus muscle at a long muscle length during contraction prevents muscle injuries and that the prevention of initial muscle injuries reduces subsequent muscle damage. The rat sciatic nerve was stimulated for 30 min with plantar or dorsal flexion of the foot, and the time course of contraction-induced injuries was examined. The soleus muscle injuries were first classified into one of five types, and the percentages of aberrant sarcomere areas observed in the soleus muscle were then separately quantified by electron microscopy at 0, 1, 6, 12, and 24 h (n = 3) post-stimulation. At a short muscle length (plantar flexion) during contraction, the soleus muscle showed sarcomere hypercontraction (9.8 ± 2.5%, mean ± standard error) and Z-band disarrangement (31.0 ± 4.5%) at 0 h, sarcomere hypercontraction (6.7 ± 1.9%), Z-band disarrangement (28.0 ± 4.9%), and sarcomere hyperstretching (1.3 ± 1.3%) at 1 h, the absence of sarcomere hypercontraction, but Z-band disarrangement (6.7 ± 1.9%) and sarcomere hyperstretching (5.0 ± 1.8%) at 6 h, and myofilament disorganization at 12 and 24 h (5.2 ± 1.5 and 2.5 ± 1.0%, respectively). In contrast, the soleus muscles at a long muscle length (dorsal flexion) during contraction using a self-made brace showed alterations in 1.2-2.4% of sarcomeres at 0 h and afterwards. Desmin disappeared, and α-actinin immunostaining was weaker in areas of sarcomere hypercontraction, whereas dystrophin was always detected along the sarcoplasmic membrane, suggesting that the integrity of the sarcolemma was intact. These results indicate that initial and subsequent muscle injuries were significantly reduced at long muscle length during contraction, probably through the prevention of sarcomere hypercontraction, and that initial muscle injuries rapidly progress to other injuries or normal structure.
Subject(s)
Muscle Contraction/physiology , Muscle, Skeletal/injuries , Actins/metabolism , Animals , Desmin/metabolism , Dystrophin/metabolism , Male , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/physiology , Rats , Rats, Wistar , Sarcomeres/metabolism , Sarcomeres/pathology , Sciatic Nerve/physiologyABSTRACT
Charge/discharge processes of organic radical batteries based on the radical polymer's redox reaction are largely influenced by carbon fibers consisting in the composite electrodes to help electron transfer. To find the optimal structure of the composite electrodes, the dominant electron transfer processes were determined by ac impedance measurement of the composite electrodes. A strong correlation between the overall electron transfer resistance of the composite electrodes and the materials of the current collector suggests that the electric conduction to the current collector through the contact resistance should be crucial. It was also confirmed that the charge/discharge performance of the composite electrode was related to the overall electron transfer resistance of the composite electrode. These results indicated that the charge/discharge performance of the radical battery was dominated by the interfacial electron transfer processes at the current collector/carbon fiber interface and that the rate performance would be much improved by suitably designing the interfacial structure.
ABSTRACT
Baclofen, a GABA(B)-receptor (GABA(B)R) agonist has been proposed to be useful as therapeutic agent for the management of gastro-esophageal reflux disease, but whether the compound acts directly at the lower esophageal sphincter (LES) remains to be elucidated. We performed the present study to assess the presence of GABA(B)R in human LES. Western blot analysis showed that both proteins of GABA(B1(a))/GABA(B1(b)) and GABA(B2) subunits were present in the muscle layer of LES. Immunohistochemical findings showed that both GABA(B1)- and GABA(B2)-subunit proteins were located on the neurons within the myenteric plexus, and furthermore, both proteins were observed in the same neurons. Reverse transcriptase-polymerase chain reaction analysis also revealed the presence of mRNAs for both subunits of GABA(B)R and also mRNAs for 6 isoforms of GABA(B1) subunits, from GABA(B1(a)) to GABA(B1(g)), except GABA(B1(d)), in human LES. Thus, the functional GABA(B)R-forming heterodimers with subunits of GABA(B1) and GABA(B2) are located on the myenteric neurons in human LES, suggesting that GABA(B)R agonists and antagonists act at least, at the level of the peripheral nervous system.
Subject(s)
Esophageal Sphincter, Lower/metabolism , Receptors, GABA-A/metabolism , Receptors, GABA-B/metabolism , Actins/biosynthesis , Aged , Aged, 80 and over , Blotting, Western , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mucin 5AC/biosynthesis , Muscle, Smooth/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
PURPOSE: This study was carried out to evaluate the postoperative analgesic effects of preoperative intravenous flurbiprofen in patients undergoing arthroscopic rotator cuff repair under general anesthesia. METHODS: We studied 44 patients who underwent an elective arthroscopic rotator cuff repair in a prospective, randomized, and double-blind fashion. The patients were divided into two groups. Group A (n = 22) received lipid emulsion 0.1 ml kg(-1) as a placebo, and group B (n = 22) received flurbiprofen 1 mg kg(-1) before the surgery. Intralipid or flurbiprofen was given intravenously 5 min before the surgery. General anesthesia was maintained with sevoflurane and nitrous oxide, and 10 ml of 0.75% ropivacaine was administered intraarticularly at the end of the surgery. Postoperative analgesia was supplied with intravenous 0.1 mg buprenorphine according to the patient's demand. The effectiveness of flurbiprofen's analgesic effect was measured by a visual analog scale (VAS) and by the amount of buprenorphine consumption at 0.5, 1, 2, 4, 6, 12, and 24 h after the surgery. Time to the first analgesic was also recorded. RESULTS: VAS in group B was significantly (P < 0.01) lower than that in group A during the first 6 h postoperatively. The amount of buprenorphine consumption in group B was also significantly (P < 0.01) less than that in group A within the first 2 h postoperatively. The time to first analgesic request in group B was significantly (P < 0.01) longer than that in group A. CONCLUSION: These results show that preoperative intravenous flurbiprofen facilitates the analgesic effect in the early postoperative period after arthroscopic rotator cuff repair.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthroscopy , Flurbiprofen/therapeutic use , Pain, Postoperative/drug therapy , Rotator Cuff/surgery , Adult , Aged , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Anesthesia, General , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Buprenorphine/administration & dosage , Buprenorphine/therapeutic use , Female , Flurbiprofen/administration & dosage , Flurbiprofen/adverse effects , Humans , Injections, Intravenous , Male , Middle Aged , Pain Measurement , Preoperative Care , Young AdultABSTRACT
PURPOSE: It is known that an optimal dose of intrathecal morphine for analgesia after total hip arthroplasty in older patients is 0.1 mg. On the other hand, minidose intrathecal morphine (0.05 mg) is useful for analgesia after the transurethral resection of the prostate in elderly patients. We evaluated the postoperative analgesic effect of minidose intrathecal morphine after bipolar hip prosthesis in seniors (age 85 years or more) undergoing spinal anesthesia. METHODS: Twenty seniors undergoing bipolar hip prosthesis under spinal anesthesia were randomly allocated to one of two groups. Group A (n = 10) received intrathecal injection of 0.5% isobaric bupivacaine, 2.8 ml, and group B (n = 10) received intrathecal injection of 0.5% isobaric bupivacaine, 2.8 ml, plus morphine, 0.05 mg. Pain, nausea, and itching were evaluated using a numerical rating scale, ranging from 0 to 10, at 0, 4, 8, 12, and 24 h after the operation. RESULTS: The values on the numerical rating scale for pain in group B were significantly lower than those in group A at 4, 8, and 12 h after the operation. There were no significant differences between the groups in the values on the numerical rating scale for nausea or itching throughout the time course of the study. No patient in either group showed hypoxemia or respiratory depression throughout the time course. CONCLUSION: The results show that minidose intrathecal morphine provides a good analgesic effect without side effects, and it would be an effective and safe procedure for bipolar hip prosthesis in seniors.
Subject(s)
Analgesics, Opioid/therapeutic use , Arthroplasty, Replacement, Hip , Morphine/therapeutic use , Pain, Postoperative/drug therapy , Aged, 80 and over , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Anesthetics, Local/therapeutic use , Bupivacaine/therapeutic use , Female , Humans , Injections, Spinal , Male , Morphine/administration & dosage , Morphine/adverse effects , Pain Measurement , Postoperative Nausea and Vomiting/epidemiology , Pruritus/chemically inducedABSTRACT
Hemokinin-1 (HK-1) is a novel peptide described as a member of the tachykinin family. Substance P (SP), a representative member of the tachykinin family, has been well characterized and is thought to play a part in inflammation and pain. While several studies indicate that HK-1 is involved in inflammation and pain, the biological functions of HK-1 are not fully understood. In the present study we investigated the expression of HK-1 mRNA (TAC4) and SP mRNA (TAC1) in the dorsal spinal cord of rat after inducing peripheral inflammation by administering complete Freund's adjuvant (CFA) into the hind paw, using real-time RT-PCR. In the behavioral studies, the thresholds of withdrawal response of the hind paw to thermal stimulation significantly decreased on the ipsilateral side, but not on the contralateral side, 6 hours after CFA injection and thermal hyperalgesia persisted until 4 days after CFA injection. The level of HK-1 mRNA expression significantly increased on the bilateral sides of the dorsal spinal cord 6 hours after CFA injection and returned to the base level 1 day after injection. On the other hand, the level of SP mRNA expression did not change in the spinal cord 6 hours and 1 day after CFA injection. These results indicate that HK-1 may contribute to inflammatory pain, in the early phase, in a different manner from SP.
Subject(s)
Inflammation/metabolism , Spinal Cord/chemistry , Tachykinins/analysis , Animals , Male , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
A reaction of 2-acetyl-3-acylaminobenzo[b]furans (9d-o) with Vilsmeier (VM) reagent afforded a mixture of (E)- and (Z)-{(E)-2-aralkenylbenzo[b]furo[3,2-d][1,3]oxazin-4-ylidene}acetaldehydes (5) with a characteristic exo-formylmethylene group on the oxazine ring. The Z-isomer was more stable than the E-isomer. The Z-isomers ((Z)-5) were reacted with phosphonate reagents under two different conditions to obtain various butadiene derivatives (12) containing benzo[b]furo[3,2-d][1,3]oxazine skeleton. Typical compounds (5 and 12) were evaluated for their anti-osteoclastic bone resorption activity, antagonistic activity for the cysLT1 receptor and growth inhibitory activity for MIA PaCa-2 and MCF-7. Compounds 12f and 12j showed potent anti-osteoclastic bone resorption activity comparable to E(2) (17beta-estradiol).
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Osteoblasts/drug effects , Oxazines/chemical synthesis , Oxazines/pharmacology , Animals , Antineoplastic Agents/chemistry , Bone Resorption , Breast Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Humans , Male , Mice , Molecular Structure , Oxazines/chemistry , Pancreatic Neoplasms/drug therapyABSTRACT
BACKGROUND AND OBJECTIVE: It is known that esmolol, a short-acting beta1-blocker, reduces anaesthetic requirement. In this study, we evaluated whether a low dose of landiolol, a new ultra-short-acting beta1-blocker, can reduce the sevoflurane requirement. METHODS: Twenty-five patients undergoing hip surgery were randomly divided into two groups. Group A (n = 13) received landiolol (bolus injection of 0.031 mg.kg(-1) and continuous infusion at a rate of 0.01 mg.kg(-1).min(-1)). Group B (n = 12) received physiological saline. Landiolol and physiological saline were started before the induction of anaesthesia and continued until the end of anaesthesia. Anaesthesia was maintained with sevoflurane, 60% N(2)O and fentanyl. Sevoflurane concentration was controlled to keep the bispectral index at approximately 50. The end-tidal sevoflurane concentration and haemodynamics were measured during anaesthesia. RESULTS: The average end-tidal sevoflurane concentration in group A was significantly lower than that in group B (1.2 +/- 0.30 vs. 1.8 +/- 0.3%, P < 0.01). Maximum values of systolic arterial pressure showed no difference between the groups, whereas the maximum value of heart rate in group A was significantly less than that in group B (61 +/- 10 vs. 76 +/- 14 beats min(-1), P < 0.05). CONCLUSION: The results suggest that a low dose of landiolol significantly reduces the intraoperative sevoflurane requirement during sevoflurane/N(2)O/fentanyl anaesthesia in patients undergoing hip surgery.
Subject(s)
Adrenergic beta-Antagonists/pharmacology , Anesthesia/methods , Anesthetics/pharmacology , Hip/surgery , Morpholines/pharmacology , Urea/analogs & derivatives , Aged , Aged, 80 and over , Female , Fentanyl/pharmacology , Humans , Male , Methyl Ethers/pharmacology , Middle Aged , Nitrous Oxide/pharmacology , Sevoflurane , Time Factors , Urea/pharmacologyABSTRACT
PURPOSE: Adequate volume therapy is essential for stable hemodynamics and sufficient urinary output perioperatively. Hydroxyethyl starch (HES) has been reported to attenuate the microvascular hyperpermeability which occasionally occurs in surgical patients. This study was carried out to evaluate the effect of low-molecular-weight HES on the urinary microalbumin/creatinine ratio (MACR), a marker of microvascular permeability, in surgical patients. METHODS: In a prospective, controlled, and randomized clinical trial, 21 patients undergoing abdominal surgery were divided into two groups. Group HES (n = 10) received HES at 2 ml x kg(-1) x h(-1) during surgery and at 1 ml x kg(-1) x h(-1) after surgery, and additionally they received acetated Ringer's solution (AR) at a rate to keep central venous pressure (CVP) 5 mm Hg. Group AR (n = 11) received AR at a rate to keep CVP at 3-5 mmHg. MACR, soluble intercellular adhesion molecule-1 (sICAM-1), and urinary output were measured intermittently in the perioperative period. RESULTS: MACR was significantly increased during surgery in both groups. There was no significant difference in MACR between the two groups throughout the study period. The serum concentration of sICAM-1 decreased during surgery in both groups, and that in group HES was significantly lower than that in group AR at the end of surgery. Postoperative urinary output in group HES was greater than that in group AR. The intensive care unit (ICU) stay in group HES was shorter than that in group AR. CONCLUSION: Although low-molecular-weight HES does not improve microvascular hyperpermeability, the expansion of the intravascular volume by HES results in higher urinary output in the postoperative period than that seen with crystalloid solution. The lower concentration of sICAM-1 after surgery may be due to hemodilution.
Subject(s)
Abdomen/surgery , Capillary Permeability/drug effects , Hydroxyethyl Starch Derivatives/pharmacology , Isotonic Solutions/pharmacology , Plasma Substitutes/pharmacology , Abdomen/anatomy & histology , Aged , Albuminuria/chemically induced , Anesthesia, General , Blood Loss, Surgical , Body Temperature/drug effects , Creatinine/urine , Crystalloid Solutions , Double-Blind Method , Female , Hemodynamics/drug effects , Humans , Hydroxyethyl Starch Derivatives/chemistry , Intercellular Adhesion Molecule-1/blood , Male , Molecular Weight , Plasma Substitutes/chemistry , Prospective StudiesABSTRACT
Interactions between mu-opioid receptor (muOR) and cannabinoid CB1 receptor (CB1R) were examined by morphological and electrophysiological methods. In baby hamster kidney (BHK) cells coexpressing muOR fused to the yellow fluorescent protein Venus and CB1R fused to the cyan fluorescent protein Cerulean, both colors were detected on the cell surface; and fluorescence resonance energy transfer (FRET) analysis revealed that muOR and CB1R formed a heterodimer. Coimmunoprecipitation and Western blotting analyses also confirmed the heterodimers of muOR and CB1R. [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) or CP55,940 elicited K+ currents in Xenopus oocytes expressing muOR or CB1R together with G protein activated-inwardly rectifying K+ channels (GIRKs), respectively. In oocytes coexpressing both receptors, either of which was fused to the chimeric Galpha protein Gqi5 that activates the phospholipase C pathway, both DAMGO and CP55,940 elicited Ca2+-activated Cl(-) currents, indicating that each agonist can induce responses through Gqi5 fused to either its own receptor or the other. Experiments with endogenous Gi/o protein inactivation by pertussis toxin (PTX) supported the functional heterodimerization of muOR/CB1R through PTX-insensitive Gqi5(m) fused to each receptor. Thus, muOR and CB1R form a heterodimer and transmit a signal through a common G protein. Our electrophysiological method could be useful for determination of signals mediated through heterodimerized G protein-coupled receptors.
Subject(s)
Cell Membrane/metabolism , Fluorescence Resonance Energy Transfer , Patch-Clamp Techniques , Receptor, Cannabinoid, CB1/metabolism , Receptors, Opioid, mu/metabolism , Signal Transduction , Animals , Blotting, Western , Calcium/metabolism , Cell Line , Cell Membrane/drug effects , Chloride Channels/metabolism , Cyclohexanols/pharmacology , Dose-Response Relationship, Drug , Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology , G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics , G Protein-Coupled Inwardly-Rectifying Potassium Channels/metabolism , GTP-Binding Protein alpha Subunits, Gq-G11/metabolism , Humans , Immunoprecipitation , Membrane Potentials , Pertussis Toxin/pharmacology , Protein Multimerization , Rats , Receptor, Cannabinoid, CB1/genetics , Receptors, Opioid, mu/drug effects , Receptors, Opioid, mu/genetics , Recombinant Fusion Proteins/metabolism , Signal Transduction/drug effects , Transfection , Type C Phospholipases/metabolism , XenopusABSTRACT
Redox polymer layers with 2,2,6,6-tetramethylpiperidin-1-oxyl-4-yl (TEMPO) groups showed nernstian adsorbate-like electrochemical behaviors up to submicrometer thicknesses, based on a fast charge propagation within the bulk layer and persistency in electrolyte solutions.
ABSTRACT
OBJECTIVE: To determine the prevalence and the prognostic significance of microalbuminuria in patients after aneurysmal subarachnoid hemorrhage (SAH). DESIGN: Prospective and observational clinical study. SETTING: Multidisciplinary intensive care unit. PATIENTS: Fifty-one consecutive patients who underwent aneurysm clipping or endovascular surgery after SAH; 8 patients who underwent surgical clipping for unruptured intracerebral aneurysm served as control. INTERVENTION: None. MEASUREMENTS AND RESULTS: General clinical and neurological data were recorded on admission. Urine was collected preoperatively and daily for up to 7 days postoperatively for measuring the urinary microalbumin/creatinine ratio. The Glasgow Coma Scale (GCS) score was also determined on admission and daily for up to 7 days after operation. Neurological outcome was assessed using the Glasgow Outcome Scale (GOS) at 3 months after stroke. The prevalence rates of microalbuminuria were 74.5% in SAH and 37.5% in the control. Among the 51 patients, 25 had unfavorable neurological outcome (GOS 1-3). The areas under the receiver operator characteristic curves showed that the highest urinary microalbumin/creatinine ratio and the lowest GCS score during the first 8 days were the significant predictors of unfavorable neurological outcome. The threshold value, sensitivity, specificity, and likelihood ratio for the highest urinary microalbumin/creatinine ratio were 200 mg/g, 60% [95% confidence interval (CI) 41-79], 96% (95% CI 88-100), and 15.6 (95% CI 9.1-26.7), respectively. CONCLUSIONS: This study confirms a high prevalence of microalbuminuria in the SAH patients, and it suggests that the highest urinary microalbumin/creatinine ratio > 200 mg/g during the first 8 days is a significant predictor of unfavorable neurological outcome.