Meningitis is the inflammation of the membranes of the brain and spinal cord. This disease is considered life threatening and classified as a medical and emergency. Here we report a case of delayed meningitis occurred in a patient with craniotomy for traumatic brain injury fifteen years ago. Meanwhile, he had been well, however he complained of headache for five days. A brain computed tomographic scan showed air density on the frontal lobe with frontal sinus defect and pansinusitis. His mental state was suddenly changed to stuporous, despite a day of empirical antibiotics. Therefore, a successful cranialization was performed and he was gradually improved. This is a rare case report. Our case shows that surgical intervention is to be considered in some cases of posttraumatic meningitis for effective and rapid control of infection.
Anti-Bacterial Agents ; Brain ; Brain Injuries ; Craniotomy ; Dura Mater* ; Emergencies ; Frontal Lobe ; Frontal Sinus* ; Headache ; Humans ; Inflammation ; Membranes ; Meningitis* ; Spinal Cord ; Stupor

Meningitis is the inflammation of the membranes of the brain and spinal cord. This disease is considered life threatening and classified as a medical and emergency. Here we report a case of delayed meningitis occurred in a patient with craniotomy for traumatic brain injury fifteen years ago. Meanwhile, he had been well, however he complained of headache for five days. A brain computed tomographic scan showed air density on the frontal lobe with frontal sinus defect and pansinusitis. His mental state was suddenly changed to stuporous, despite a day of empirical antibiotics. Therefore, a successful cranialization was performed and he was gradually improved. This is a rare case report. Our case shows that surgical intervention is to be considered in some cases of posttraumatic meningitis for effective and rapid control of infection.
Anti-Bacterial Agents ; Brain ; Brain Injuries ; Craniotomy ; Dura Mater* ; Emergencies ; Frontal Lobe ; Frontal Sinus* ; Headache ; Humans ; Inflammation ; Membranes ; Meningitis* ; Spinal Cord ; Stupor

This study aims to develop new potential therapeutic moracin M prodrugs acting on lung inflammatory disorders. Potential moracin M prodrugs (KW01-KW07) were chemically synthesized to obtain potent orally active derivatives, and their pharmacological activities against lung inflammation were, for the first time, examined in vivo using lipopolysaccharide (LPS)-induced acute lung injury model. In addition, the metabolism of KW02 was also investigated using microsomal stability test and pharmacokinetic study in rats. When orally administered, some of these compounds (30 mg/kg) showed higher inhibitory action against LPSinduced lung inflammation in mice compared to moracin M. Of them, 2-(3,5-bis((dimethylcarbamoyl)oxy)phenyl)benzofuran-6-yl acetate (KW02) showed potent and dose-dependent inhibitory effect on the same animal model of lung inflammation at 1, 3, and 10 mg/kg. This compound at 10 mg/kg also significantly reduced IL-1β concentration in the bronchoalveolar lavage fluid of the inflamed-lungs. KW02 was rapidly metabolized to 5-(6-hydroxybenzofuran-2-yl)-1,3-phenylene bis(dimethylcarbamate) (KW06) and moracin M when it was incubated with rat serum and liver microsome as expected. When KW02 was administered to rats via intravenous or oral route, KW06 was detected in the serum as a metabolite. Thus, it is concluded that KW02 has potent inhibitory action against LPS-induced lung inflammation. It could behave as a potential prodrug of moracin M to effectively treat lung inflammatory disorders.

Tropomyosin receptor kinase A (TrkA) protein is a receptor tyrosine kinase encoded by the NTRK1 gene. TrkA signaling mediates the proliferation, differentiation, and survival of neurons and other cells following stimulation by its ligand, the nerve growth factor.Chromosomal rearrangements of the NTRK1 gene result in the generation of TrkA fusion protein, which is known to cause deregulation of TrkA signaling. Targeting TrkA activity represents a promising strategy for the treatment of cancers that harbor the TrkA fusion protein. In this study, we evaluated the TrkA-inhibitory activity of the benzoxazole compound KRC-108. KRC-108 inhibited TrkA activity in an in vitro kinase assay, and suppressed the growth of KM12C colon cancer cells harboring an NTRK1 gene fusion.KRC-108 treatment induced cell cycle arrest, apoptotic cell death, and autophagy. KRC-108 suppressed the phosphorylation of downstream signaling molecules of TrkA, including Akt, phospholipase Cγ, and ERK1/2. Furthermore, KRC-108 exhibited antitumor activity in vivo in a KM12C cell xenograft model. These results indicate that KRC-108 may be a promising therapeutic agent for Trk fusion-positive cancers.

Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.
Animals ; Asthma ; Bronchoalveolar Lavage ; Common Cold ; Granulocytes ; Heat-Shock Proteins* ; HeLa Cells ; Hot Temperature* ; Humans ; In Vitro Techniques ; Lung ; Mice ; Molecular Chaperones ; Monocytes ; Respiratory System ; Rhinovirus* ; RNA Viruses