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1.
Cureus ; 15(12): e50820, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38249264

ABSTRACT

A 54-year-old male with severe hypoxia was transferred to our hospital after choking on a mochi. Chest computed tomography revealed negative pressure pulmonary edema without pneumothorax. Endotracheal intubation was performed, and pressure-controlled ventilation was initiated. Following admission to the intensive care unit, his respiratory condition was stable in both the supine and left decubitus positions. However, every time he was placed in the right decubitus position, the tidal volume decreased by half, and SpO2 dropped rapidly to 80%, which recovered soon after returning to the supine position. Chest radiography was performed the following day, revealing grade II right pneumothorax, and a chest tube placement stabilized his respiratory status in the right decubitus position. Air leakage ceased within a few hours. Extubation was successful on the fifth hospital day, and the chest tube was removed on the eighth hospital day. To our knowledge, there are no previous reports on position-dependent symptoms of pneumothorax during mechanical ventilation. Clinicians should consider the possibility of pneumothorax on that same side when respiratory deterioration is observed only in one lateral decubitus position during mechanical ventilation.

2.
World J Urol ; 38(9): 2307-2312, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31784774

ABSTRACT

PURPOSE: To identify risk factors by developing and internally validating a nomogram for preventing perioperative complications in overnight ureteral catheterization cases after fURS for kidney stones. METHODS: We retrospectively examined 309 patients with overnight ureteral catheterization after single fURS procedures for renal stones. fURS procedures were performed based on the fragmentation technique. The ureteral catheter was removed on postoperative day 1. Within this group, patients who experienced perioperative complications (complication group) were compared with those who did not experience complications (non-complication group). The complication group included 77 patients whose Clavien-Dindo classification score was I, II, III, or IV and/or those whose body temperature during hospitalization was over 37.5 °C. RESULTS: The overall stone volume, stone-free rate, incidence of perioperative complications, and procedure duration were 1.39 mL, 94.8%, 24.9%, and 62 min, respectively. Severe complications of a Clavien-Dindo level III or IV were observed in only four cases (1.3%). Multivariate assessment revealed five independent predictors of perioperative complications after fURS with overnight catheterization: age (p = 0.11), sex (p = 0.067), stone volume (p = 0.33), Hounsfield units (p = 0.16), and narrow ureter (p = 0.018). We developed a nomogram to predict perioperative complications after fURS using these parameters. CONCLUSIONS: We developed a predictive model for perioperative complications of patients with overnight catheterization after fURS for renal stones. This model could select patients who were at a low risk of complications.


Subject(s)
Kidney Calculi/surgery , Nomograms , Postoperative Complications/epidemiology , Ureteroscopy , Urinary Catheterization , Adult , Aged , Female , Humans , Male , Middle Aged , Postoperative Complications/prevention & control , Prognosis , Retrospective Studies , Risk Factors , Ureteroscopy/methods
3.
J Clin Invest ; 124(10): 4325-34, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25202983

ABSTRACT

Millions of patients worldwide are affected by craniofacial deformations caused by congenital defects or trauma. Current surgical interventions have limited therapeutic outcomes; therefore, methods that would allow cartilage restoration are of great interest. A number of studies on embryonic limb development have shown that chondrogenesis is initiated by cellular condensation, during which mesenchymal progenitors aggregate and form 3D structures. Here, we demonstrated efficient regeneration of avascular elastic cartilage from in vitro-grown mesenchymal condensation, which recapitulated the early stages of chondrogenesis, including transient vascularization. After transplantation of vascularized condensed progenitors into immunodeficient mice, we used an intravital imaging approach to follow cartilage maturation. We determined that endothelial cells are present inside rudimentary cartilage (mesenchymal condensation) prior to cartilage maturation. Recreation of endothelial interactions in culture enabled a recently identified population of adult elastic cartilage progenitors to generate mesenchymal condensation in a self-driven manner, without requiring the support of exogenous inductive factors or scaffold materials. Moreover, the culture-grown 3D condensed adult-derived progenitors were amenable to storage via simple freezing methods and efficiently reconstructed 3D elastic cartilage upon transplantation. Together, our results indicate that transplantation of endothelialized and condensed progenitors represents a promising approach to realizing a regenerative medicine treatment for craniofacial deformations.


Subject(s)
Cartilage/pathology , Cell Transplantation/methods , Chondrogenesis , Stem Cells/cytology , Tissue Culture Techniques/methods , Tissue Engineering/methods , Adult , Animals , Cartilage/cytology , Cartilage/metabolism , Chondrocytes/cytology , Cryopreservation , Freezing , Green Fluorescent Proteins/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Mesenchymal Stem Cells/cytology , Mesoderm/metabolism , Mice , Mice, Inbred C57BL , Mice, SCID , Regeneration , Time Factors
4.
Bioorg Med Chem Lett ; 17(23): 6579-83, 2007 Dec 01.
Article in English | MEDLINE | ID: mdl-17931864

ABSTRACT

A new series of non-peptidic, mono-acid protein tyrosine phosphatase 1B (PTP1B) inhibitors has been identified by structure-based design. Compounds with 2-(indol-3-yl)- and 2-phenyl-3,3,3-trifluoro-2-hydroxypropionic acid core units targeted at the enzyme's primary site and a hydrophobic chlorophenylthiazole extension in its 2 degrees site exhibit 3-60microM IC(50)s for PTP1B inhibition in an Sf9 cell-based assay.


Subject(s)
Enzyme Inhibitors/chemical synthesis , Propionates/chemistry , Propionates/classification , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Animals , Binding Sites , Cell Line , Enzyme Inhibitors/classification , Enzyme Inhibitors/metabolism , Ligands , Propionates/pharmacology , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Spodoptera/cytology
5.
Bioorg Med Chem ; 15(15): 5083-9, 2007 Aug 01.
Article in English | MEDLINE | ID: mdl-17540575

ABSTRACT

This study aimed to identify the crucial structural features of 2-substituted 8-methylpyrimido[4,5-b][1,5]oxazocine derivatives. Axially chiral 8-methylpyrimido[4,5-b][1,5]oxazocines bearing a substituent at the C-2 position were synthesized and evaluated as NK(1) antagonists. The results revealed that (aR, 8S)-stereochemistry and the substituent at the C-2 position are important for NK(1) receptor recognition.


Subject(s)
Neurokinin-1 Receptor Antagonists , Oxazocines/chemistry , Oxazocines/pharmacology , Animals , Dose-Response Relationship, Drug , Guinea Pigs , Ileum/drug effects , Molecular Structure , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Structure-Activity Relationship
6.
Bioorg Med Chem ; 14(3): 776-92, 2006 Feb 01.
Article in English | MEDLINE | ID: mdl-16214358

ABSTRACT

We describe the design, synthesis, and physicochemical and biological properties of a novel series of 7-heterocycle-6-trifluoromethyl-3-oxoquinoxaline-2-carboxylic acids bearing a substituted phenyl group joined through a urethane or urea linkage to the heterocycle at the 7 position. Introduction of the trifluoromethyl group at the 6 position conferred good biological activity, including neuroprotective effects, as well as good physicochemical properties. In terms of alpha-amino-3-hydroxy-5-methylisoxazole propionate receptor (AMPA-R) affinity, a urea linkage was equivalent to a urethane linkage and a pyrrole ring at the 7 position reduced affinity in comparison with an imidazole ring. Among this series, compound 14h (KRP-199), which has a 4-carboxyphenyl group joined through a urethane linkage to a 7-imidazolyl heterocycle, was found to possess high potency and selectivity for the AMPA-R in vitro and to exhibit good neuroprotective effects in vivo. Furthermore, the compound showed good physicochemical properties, including stability to light and good solubility in aqueous solutions.


Subject(s)
Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/pharmacology , Quinoxalines/chemical synthesis , Quinoxalines/pharmacology , Receptors, AMPA/antagonists & inhibitors , Animals , Brain Ischemia/pathology , Brain Ischemia/prevention & control , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Chemical Phenomena , Chemistry, Physical , Drug Design , Drug Stability , Evoked Potentials/drug effects , In Vitro Techniques , Male , Molecular Structure , Neuroprotective Agents/chemistry , Quinoxalines/chemistry , Radioligand Assay , Rats , Rats, Wistar , Solubility
7.
Bioorg Med Chem ; 13(20): 5841-63, 2005 Oct 15.
Article in English | MEDLINE | ID: mdl-15993606

ABSTRACT

We describe the design, synthesis, and biological properties of a novel series of 7-substituted 6-nitro-3-oxoquinoxaline-2-carboxylic acids. After designing, studying the structure-activity relationships, and evaluating the properties of various compounds, we found that 7-heterocyclic-6-nitro-3-oxoquinoxaline-2-carboxylic acids that contain a substituted phenyl group linked through urethane at the 7 position possess good alpha-amino-3-hydroxy-5-methylisoxazole propionate receptor (AMPA-R) antagonistic activity. Among the compounds tested, compound 29p (GRA-293), which has a 4-carboxy group on the terminal phenyl moiety, exhibited high potency and selectivity for the AMPA-R in vitro and good neuroprotective efficacy in vivo. It also showed good aqueous solubility.


Subject(s)
Excitatory Amino Acid Antagonists/chemistry , Excitatory Amino Acid Antagonists/pharmacology , Nitro Compounds/chemical synthesis , Nitro Compounds/pharmacology , Quinoxalines/chemical synthesis , Quinoxalines/pharmacology , Receptors, AMPA/antagonists & inhibitors , Animals , Brain Ischemia/prevention & control , Excitatory Amino Acid Antagonists/chemical synthesis , In Vitro Techniques , Magnetic Resonance Spectroscopy , Male , Models, Molecular , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Radioligand Assay , Rats , Rats, Wistar
8.
Bioorg Med Chem Lett ; 14(20): 5107-11, 2004 Oct 18.
Article in English | MEDLINE | ID: mdl-15380209

ABSTRACT

We describe the synthesis, physicochemical, and biological properties of a novel series of 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acids with a substituted phenyl group attached through a urethane linkage at the C-7 position. We found that the introduction of trifluoromethyl group at the C-6 position brought about good biological activity and physicochemical properties. Among them, compound 9k (KRP-199), which has a 4-carboxyphenyl group, was found to possess high potency and selectivity for the AMPA-R in vitro and to exhibit good neuroprotective effects in vivo. Furthermore, the compound showed good physicochemical properties such as stability to light and good solubility in aqueous solutions.


Subject(s)
Imidazoles/chemical synthesis , Neuroprotective Agents/chemical synthesis , Quinoxalines/chemical synthesis , Receptors, AMPA/antagonists & inhibitors , Animals , Brain Ischemia/drug therapy , Brain Ischemia/pathology , Disease Models, Animal , Imidazoles/chemistry , Imidazoles/pharmacology , In Vitro Techniques , Infusions, Intravenous , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Quinoxalines/chemistry , Quinoxalines/pharmacology , Rats , Solubility , Structure-Activity Relationship
9.
Bioorg Med Chem Lett ; 13(20): 3521-5, 2003 Oct 20.
Article in English | MEDLINE | ID: mdl-14505662

ABSTRACT

The synthesis and biological properties of a novel class of 7-heterocycle-substituted quinoxalinecarboxylic acids, which bear a substituted phenyl group through a urethane linkage at the C-7 position, are described. One of the synthesized compounds, 15l, which has a 4-carboxyphenyl carbamoyloxymethyl imidazole group at the C-7 position and is water-soluble, was found to possess high potency in vitro and showed excellent neuroprotective efficacy in vivo.


Subject(s)
Quinoxalines/chemical synthesis , Quinoxalines/pharmacology , Receptors, AMPA/antagonists & inhibitors , Animals , Quinoxalines/chemistry , Rats
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