Preemptive analgesia for endoscopic sinus surgery: a retrospective study.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common disease, and endoscopic sinus surgery (ESS) is widely performed. However, there is no consensus regarding postoperative pain control after ESS, and postoperative opioid abuse is a problem in many countries. Acetaminophen is reportedly effective for postoperative pain control. Preemptive analgesia has received more attention lately, wherein pain is prevented before it occurs. In this study, we assessed the use of acetaminophen for preemptive analgesia during the perioperative period in ESS. METHODOLOGY: This is a retrospective study of 175 patients who underwent ESS, septoplasty, and bilateral inferior turbinate mucosal resection at our hospital from April 2016 to February 2018. In total, 82 patients received 1,000 mg of acetaminophen during surgery and 4 hours after the first dose, while 93 patients did not receive it routinely. We compared these two groups. The primary outcome was the need to use additional analgesics prescribed by the ward physician and the secondary outcomes included postoperative pain, postoperative bleeding, reoperation, blood pressure, and body temperature. RESULTS: The use of additional oral and intravenous analgesics was significantly reduced in the patients who received acetaminophen perioperatively. CONCLUSION: Preemptive analgesia during the perioperative period of ESS could lead to satisfactory postoperative pain control.

Smallest Optical Gap for Pt(II)-Pt(IV) Mixed-Valence Pt-Cl and Pt-Br Chain Complexes Achieved by Using a Multiple-Hydrogen-Bond Approach.

A multiple-hydrogen-bond approach was applied to shorten Pt-X-Pt distances in Cl- and Br-bridged Pt chain complexes. [Pt(dabdOH)2Cl]Cl2 (5) and [Pt(dabdOH)2Br]Br2 (6) (dabdOH = (2 S,3 S)-2,3-diaminobutane-1,4-diol) contain hydroxy groups, which form additional hydrogen bonds with counteranions. 5 has the shortest Pt-Cl-Pt distance (5.0747(8) Å) of all Cl-bridged Pt chain complexes reported to date. Furthermore, the smallest optical gap (1.45 eV for 5 and 1.19 eV for 6) in any Cl- or Br-bridged Pt chain complex was achieved. 6 has the highest electrical conductivity (1.9 × 10-5 S cm-1 at room temperature) of all Br-bridged Pt chain complexes. This study shows that the introduction of additional hydrogen bonds between the ligands and halides is effective to enhance the electronic properties of halogen-bridged metal complexes.

Excitation-photon-energy selectivity of photoconversions in halogen-bridged Pd-chain compounds: Mott insulator to metal or charge-density-wave state.

Ultrafast photoinduced transitions of a one-dimensional Mott insulator into two distinct electronic phases, metal and charge-density-wave (CDW) state, were achieved in a bromine-bridged Pd-chain compound [Pd(en)2Br](C5-Y)2H2O (en=ethylenediamine and C5-Y=dialkylsulfosuccinate), by selecting the photon energy of a femtosecond excitation pulse. For the resonant excitation of the Mott-gap transition, excitonic states are generated and converted to one-dimensional CDW domains. For the higher-energy excitation, free electron and hole carriers are produced, giving rise to a transition of the Mott insulator to a metal. Such selectivity in photoconversions by the choice of initial photoexcited states opens a new possibility for the developments of advanced optical switching and memory functions.

Trefoil factor family 2 deficiency and immune response.

The protective effect of Trefoil Factor Family (TFF) proteins in the gastrointestinal tract by promoting the healing of injured mucosa is well known. An increasing body of evidence connects TFFs, especially, TFF2 and TFF3, with a possible role in immune regulation. TFF2 is able to inhibit lipopolysaccharide-induced nitric oxide production in monocytes and can potently limit leukocyte recruitment at the site of injury. An analysis of gene expression in gastrointestinal tissue of TFF2-deficient mice reveals some new aspects of TFF2's role in the immune response.

Involvement of tumor necrosis factor alpha in intestinal epithelial cell proliferation following Paneth cell destruction.

BACKGROUND: An intravenous injection of diphenylthiocarbazone (dithizone), a zinc chelator, induces selective killing of Paneth cells which have a large amount of zinc in their cytoplasmic granules. A transient wave of intestinal epithelial cell proliferation occurs at 12 h after the injection. Paneth cells have tumor necrosis factor (TNF)-alpha protein in their cytoplasmic granules, and TNF-alpha has a proliferative effect on intestinal epithelial cells in vitro. The aim of this study is to clarify the in vivo role of TNF-alpha in intestinal epithelial cell proliferation using a dithizone-treated rat model. METHODS: Male Wistar rats received a dithizone (100 mg/kg of body weight) injection with or without TNF-alpha inhibitor, pentoxifylline (100 mg/kg), neutralizing anti-TNF-alpha antibody (2 mg/kg), or nuclear transcription factor kappaB (NF-kappaB) inhibitors: pyrrolidine dithiocarbamate (100 mg/kg) or N-acetyl-L-cystein (100 mg/kg). The activation of NF-kappaB was examined by the electrophoretic mobility shift assay, and cellular proliferation by BrdU labeling. RESULTS: Without any inhibitors, dithizone treatment evoked NF-kappaB activation in the ileal mucosa with its peak level at 2 h after the injection. TNF-alpha inhibition reduced the NF-kappaB activation, and blocked a transient wave of epithelial cell proliferation 12 h after the injection. NF-kappaB inhibitors also reduced the NF-kappaB activation and epithelial cell proliferation. CONCLUSIONS: TNF-alpha released from degenerated Paneth cells was, in part, responsible for the intestinal cell proliferation through the activation of NF-kappaB, suggesting its proliferative effect on intestinal epithelial cells.

Identification of xanthine dehydrogenase/xanthine oxidase as a rat Paneth cell zinc-binding protein.

Paneth cells are zinc-containing cells localized in small intestinal crypts, but their function has not been fully elucidated. Previously, we showed that an intravenous injection of diphenylthiocarbazone (dithizone), a zinc chelator, induced selective killing of Paneth cells, and purified a zinc-binding protein in Paneth cells. In the present study, we further characterized one of these proteins, named zinc-binding protein of Paneth cells (ZBPP)-1. Partial amino acid sequences of ZBPP-1 showed identity with rat xanthine dehydrogenase (XD)/xanthine oxidase (XO). Anti-rat XD antibody (Ab) recognized ZBPP-1, and conversely anti ZBPP-1 Ab recognized 85 kDa fragment of rat XD in Western blotting. Messenger RNA and protein levels of XD were consistent with our previous data on the fluctuation of Paneth cell population after dithizone injection. Thus, ZBPP-1 is an 85 kDa fragment of XD/XO in Paneth cells. XD/XO in Paneth cells may play important roles in intestinal function.

Enhanced expression of transforming growth factor (TGF) -alpha precursor and TGF-beta1 during Paneth cell regeneration.

An intravenous injection of diphenylthiocarbazone (dithizone), a zinc chelator, induces selective killing and rapid regeneration of Paneth cells, which have a large amount of zinc in their cytoplasmic granules. We examined the expression pattern of transforming growth factor (TGF) -alpha and TGF-beta1 in this regenerative process. Messenger RNA expression of TGF-alpha and TGF-beta1 reached their peaks at 12 and 24 hr after dithizone injection, respectively. Protein expression of TGF-alpha precursor and TGF-beta1 increased to a maximum at 24 and 72 hr, respectively. Their immunoreactivities were localized in the epithelial cells in the vicinity of Paneth cells, whereas they were prominent in the upper half of the crypts in control rats. In conclusion, destruction of Paneth cells induced TGF-alpha precursor expression, followed by an increase of TGF-beta1 especially in the crypt bases. This unique expression pattern of two growth factors may be involved in rapid regeneration of Paneth cells.

Structures of 4-aryl-coumarin (neoflavone) dimers isolated from Pistacia chinensis BUNGE and their estrogen-like activity.

Activity-guided fractionation of twigs of Pistacia chinensis resulted in the isolation and characterization of two novel ingredients as potent estrogen agonists. On the basis of spectral analysis and comparison with a related compound their structures were elucidated as 3,3''-dimers of 4-aryldihydrocoumarins (3,4-dihydro-4-(4'-hydroxyphenyl)-7-hydroxycoumarin) differing only in the stereochemical disposition of the linkage between the two 4-arylcoumarin moieties. These compounds are the first examples of bis-flavonoids which have been proven to possess estrogen-like activity.

Isolation of 10-hydroxycoronaridine from Tabernaemontana penduliflora and its estrogen-like activity.

The methanol extract of Tabernaemontana penduliflora was found to appreciably inhibit [3H]-estradiol binding to estrogen receptors. Activity-guided fractionation led to the isolation of two known alkaloids, 10-hydroxycoronaridine (1) and its 10-O-methyl ether, voacangine (2). These alkaloids together with other related alkaloids were tested for their estrogenic activities. Among these molecules, 1 was found to be the most potent estrogen agonist and is distinctly more active than genistein.

Stereochemistry of cis- and trans-hinokiresinol and their estrogen-like activity.

Naturally occurring phenylpropanoids, hinokiresinol (trans-hinokiresinol) and nyasol (cis-hinokiresinol) were found to possess appreciable estrogen receptor binding activity. Strong differences in activity were observed between the geometrical isomers and enantiomers. Among these, (3S)-cis-hinokiresinol displayed the highest activity, one order of magnitude greater than the activity of genistein. Furthermore, cis- and trans-hinokiresinol stimulated the proliferation of estrogen-dependent T47D breast cancer cells, and their stimulatory effects were blocked by an estrogen antagonist, indicating that the compounds are estrogen agonists. In addition, the absolute configuration of C-3 in (+)-cis-hinokiresinol has been assigned as S by comparison with the circular dichroism spectra of the hydrogenated products prepared from cis and trans ((3S)-trans-hinokiresinol: previously assigned) isomers. These results incidentally provide us with an unambiguous answer to contradictory reports regarding the assignment of the full stereochemisry of cis- and trans-hinokiresinol that have existed in the literature for more than two decades.

Identification of a novel alternative splicing of human FGF receptor 4: soluble-form splice variant expressed in human gastrointestinal epithelial cells.

Among four closely related members of the FGF receptor family, FGFR 1, 2, and 3 have alternative splicing forms encoded by different exons for the C-terminal half of the third Ig-like domain, but FGFR 4 has no such alternative exon. Furthermore, FGFR 1, 2, and 3 have another splice variant of nontransmembrane type; however, such a variant has not been reported for FGFR 4. While searching for a novel receptor-type tyrosine kinase by RT-PCR, we identified a non-transmembrane-type receptor of FGFR 4 in human intestinal epithelial cell lines (Intestine 407 and Caco-2). Sequence analysis of this receptor revealed that exon 9 coding the single transmembrane domain was displaced by intron 9. Consequently, this variant form was 120 bp shorter than the normal form and had no transmembrane portion. Moreover, the signal sequence in exon 2 was maintained, suggesting that this splice variant is a soluble receptor. This soluble receptor was detected in human gastrointestinal epithelial cells and pancreas, and also in gastric, colon, and pancreatic cancer cell lines. Single cell RT-PCR showed that this soluble receptor was expressed simultaneously with the transmembrane-type receptor in the same cell. Western blot analysis revealed that this receptor was secreted from the transfected COS7 cells. Thus, a soluble-form splice variant of FGFR 4 was identified in human gastrointestinal epithelial cells and cancer cells. This is the first report of alternative splicing of FGFR 4.

B-90063, a novel endothelin converting enzyme inhibitor isolated from a new marine bacterium, Blastobacter sp. SANK 71894.

A novel endothelin-converting enzyme (ECE) inhibitor, B-90063, was isolated from the culture supernatant of the newly discovered marine bacterium Blastobacter sp. SANK 71894. Based on spectral analyses and chemical reactions, the structure of B-90063 was determined to be bis[6-formyl-4-hydroxy-2-(2'-n-pentyloxazol-4'-yl)-4-pyridon -3-yl]-disulfide (1a). Human and rat ECEs were inhibited more potently by B-90063, with respective IC50 values of 1.0 and 3.2 microM, than were other neutral endopeptidases such as NEP and type-I and -IV collagenases. B-90063 also inhibited the binding of ET-1 to rat ET(A) and bovine ET(B) receptors, though its antagonistic activities were weak. B-90063, thus, may abolish the physiological actions of endothelins through the ECE inhibitory and receptor antagonistic mechanisms.

Prenylflavonoids: a new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin and an initial study on its structure-activity relationship.

Bioassay-guided fractionation of a methanolic extract of a Thai crude drug, derived from heartwood of Anaxagorea luzonensis A. Gray (Annonaceae), resulted in the isolation of 8-isopentenylnaringenin (1) as an estrogen agonist with a activity of about an order of magnitude greater than genistein. Various flavonoids possessing isopentenyl side chains in the A-ring have been prepared and evaluated for their ability to bind estrogen receptor. In addition, enantiomers of 1 were separated and the respective enantiomers were assayed. These studies have demonstrated that the presence of an 8-isopentenyl group is an important factor for binding. Flavones, flavanones and flavonols having an isopentenyl substituent at C-8 exhibited an appreciable affinity for estrogen receptor. Conversely, isoflavones possessing an 8-isopentenyl substituent at C-8 did not show this activity. Movement of the isopentenyl group from position 8 to 6 resulted in loss of the activity. No significant difference was observed between 2(S)- and 2(R)-enantiomers of 1 in their binding affinity. Prenylflavonoids are reported to possess a wide range of biological activities; however, estrogenic activity has not been described.

Retrodihydrochalcones and homoisoflavones isolated from Thai medicinal plant Dracaena loureiri and their estrogen agonist activity.

Biological evaluation of the extract prepared from the stem wood of Dracaena loureiri, a Thai folkloric medicine called "Chan-daeng", revealed a significant capacity to inhibit [3H]-estradiol binding to the estrogen receptor. During the course of separation, two novel (1 and 2) and two known retrodihydrochalcones (3 and 4), in addition to three known homoisoflavones (5, 6, and 7), were isolated. The structures of compounds 1 and 2 were established by NMR and MS studies by correlating their spectroscopic properties with those of 3 and 4. Each isolate was assessed for its estrogenic activity. Compounds 1 and 6 exhibited activity comparable to that of genistein and daidzein.

Structure-activity relationships of phomactin derivatives as platelet activating factor antagonists.

Phomactins, natural products isolated from the culture broth of marine fungus Phoma sp., were found to be active as PAF antagonists. This unique carbon skeleton led us to investigate the structure-activity relationship demonstrating that the lipophilicity at C-(7-8), acetoxy, (methoxycarbonyl)oxy, and 3-isoxazolyloxy substitution at C-20, and 2-beta-OH configuration at C-2 are all required for the enhancement of inhibitor activity.

Dependence of biphasic heart rate response to sustained hypoxia on magnitude of ventilation in man.

We studied the dynamic profile of respiratory and circulatory activities during sustained isocapnic hypoxia in healthy males. In response to end-tidal PO2 depression to about 55 Torr, minute ventilation first increased briskly and then depressed. Such biphasic response to hypoxia was also observed in the heart rate. A significantly positive correlation was found between the magnitudes of ventilatory and heart rate responses. No significant increases were found in arterial noradrenaline and potassium, but adrenaline significantly increased gradually with time. Furthermore, when VT and f were intentionally maintained constant so as to prevent the biphasic ventilatory change, the biphasic heart rate response previously seen in spontaneous hypoxic breathing disappeared. We suggest that the heart rate is mainly determined by the pulmonary vagal inflation reflex. Putative neurochemicals to elicit hypoxic ventilatory depression, and arterial catecholamine and potassium concentrations may not be directly related to the specific profile of the biphasic heart rate response during moderate hypoxia.

[A clinical evaluation of reconstruction methods after pancreatoduodenectomy from a view of fat digestion and absorption].

The purpose of this study was to evaluate the reconstruction methods of modified Imanaga procedure and modified Child procedure from a point of fat digestion and absorption in patients who received pancreatoduodenectomy by using 13C-labelled medium chain fat. The 13CO2 abundances were elevated rapidly after oral ingestion of 13C-octanoic acid and 13C-trioctanoin in modified Imanaga procedure group. The peak 13CO2 abundances appeared earlier in modified Imanaga procedure group than in modified Child procedure group. No significant difference was seen between two groups in the percent recovery of 13CO2 in the breath after oral loading of 13C-octanoic acid. But modified Imanaga procedure group showed significantly higher recovery rate of 13CO2 of 13C-trioctanoin when compared to modified Child procedure group. These results suggest that modified Imanaga procedure would have a benefit for fat digestion and absorption after pancreatoduodenectomy.

Dynamic profile of cardiovascular activity in relation to augmented ventilation and humoral agents during hypercapnic hypoxia.

A time course of cardiovascular activity in 8 healthy males in relation to augmented ventilatory activity and humoral factors was observed during step CO2 elevation with constant hypoxia. During the first step increase, by 3 Torr in end-tidal PCO2 (PETCO2), the heart rate (HR) initially tended to decrease, then slowly increased to slightly below that of the previous eucapnic level, whereas ventilation maintained a gradual rise throughout this period. On the other hand, during second step PETCO2 elevation, by a further 3 Torr, both HR and ventilation progressively increased. The plasma catecholamine (CA) concentration was also significantly elevated during this period, suggesting a concomitant enhancement in sympathetic activity. Blood pressure (Bp) was progressively augmented throughout the entire hypoxic challenge. We conclude that 1) the characteristic profile of HR change may be explained by the observation that initial HR depression by peripheral chemoreceptor stimulation is gradually overridden by delayed hyperventilation, CA elevation, and enhanced sympathetic activity; 2) Bp augmentation may be elicited by increased CA release and sympathetic activity; and 3) plasma K+ concentration does not change so as to affect cardiovascular and respiratory activity.

Ventilatory responses to chemosensory stimuli in quadriplegic subjects.

We tested the hypothesis that interruption of motor traffic running down the spinal cord to respiratory muscle motoneurons suppresses the ventilatory response to increased chemical drive. We compared the hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses, based on the rebreathing technique, before and during inspiratory flow-resistive loading in 17 quadriplegic patients with low cervical spinal cord transection and in 17 normal subjects. The ventilatory response was evaluated from minute ventilation (VE) and mouth occlusion pressure (P0.2) slopes on arterial oxygen saturation (SaO2) or on end-tidal PCO2 (PACO2), and from absolute VE values at SaO2 80% or at PACO2 55 mmHg. We found no difference in the unloaded HVR or HCVR between the quadriplegic and normal subjects. In the loaded HVR, the delta VE/delta SaO2 slope tended to decrease similarly in both groups of subjects. The delta P0.2/delta SaO2 slope was shifted upwards in normal subjects, yielding a significantly higher P0.2 at a given SaO2. In contrast, this rise in the P0.2 level during loaded HVR was absent in quadriplegics. Loaded HCVR yielded qualitatively similar results in both groups of subjects; delta VE/delta PACO2 decreased and delta P0.2/delta PACO2 increased significantly. The results show that the ventilatory chemosensory responses were unsuppressed in quadriplegics, although they displayed a disturbance in load-compensation, as reflected by occlusion pressure, in hypoxia. We conclude that the descending drive to respiratory muscle motoneurons is not germane to the operation of the chemosensory reflexes.