P2X7 receptor regulates leukocyte infiltrations in rat frontoparietal cortex following status epilepticus

<p>Abstract</p> <p>Background</p> <p>In the present study, we investigated the roles of P2X7 receptor in recruitment and infiltration of neutrophil during epileptogenesis in rat epilepsy models.</p> <p>Methods</p> <p>Status epilepticus (SE) was induced by pilocarpine in rats that were intracerebroventricularly infused with either saline, 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP), or IL-1Ra (interleukin 1 receptor antagonist) prior to SE induction. Thereafter, we performed immunohistochemical studies for myeloperoxidase (MPO), CD68, interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2).</p> <p>Results</p> <p>In saline-infused animals, neutrophils and monocytes were observed in frontoparietal cortex (FPC) at 1 day and 2 days after SE, respectively. In BzATP-infused animals, infiltrations of neutrophils and monocytes into the FPC were detected at 12 hr and 1 day after SE, respectively. In OxATP-infused animals, neutrophils and monocytes infiltrated into the FPC at 1 day and 2 days after SE, respectively. However, the numbers of both classes of leukocytes were significantly lower than those observed in the saline-infused group. In piriform cortex (PC), massive leukocyte infiltration was detected in layers III/IV of saline-infused animals at 1-4 days after induction of SE. BzATP or OxATP infusion did not affect neutrophil infiltration in the PC. In addition, P2X7 receptor-mediated MCP-1 (released from microglia)/MIP-2 (released from astrocytes) regulation was related to SE-induced leukocyte infiltration in an IL-1β-independent manner.</p> <p>Conclusions</p> <p>Our findings suggest that selective regulation of P2X7 receptor-mediated neutrophil infiltration may provide new therapeutic approaches to SE or epilepsy.</p

Results of Air Caloric and Other Vestibular Tests in Patients with Chronic Otitis Media

ObjectivesAir caloric results are supposed to be influenced by anatomic changes of the middle ear. The aims of our study were to evaluate the incidence and characteristics of abnormal air caloric results in patients with unilateral chronic otitis media and without any history of vertigo, and to compare caloric results with there of other vestibular function tests (VFTs).MethodsTwenty five patients with unilateral chronic otitis media (COM) who were scheduled for surgery underwent VFTs preoperatively. Hearing was assessed using pure-tone audiometry and vestibular function was assessed using a set of VFTs: air caloric, head-shaking nystagmus (HSN), vibration-induced nystagmus (VIN), and subjective visual vertical (SVV) tests.ResultsSix patients (24%) showed pathologic canal paresis (CP) on COM-sided ears. Two patients showed pathologic CP on the contralateral side. However, both of the two showed inverted nystagmus to warm air stimulation on the COM-side and hyperactive nystagmus to cold air stimulation on the COM-side, which means that the COM-sided ear was stimulated too much. There was pathologic HSN in 12 patients (48%), pathologic VIN in 7 (28%), and pathologic SVV in 5 (20%). Overall, 20 (80%) patients showed abnormal findings through a set of VFTs. Patients with an interaural difference of bone-conduction hearing thresholds ≥10 dB tended to show more abnormal VFT results than those for whom the interaural difference of bone-conduction hearing thresholds was <10 dB.ConclusionOur data show that one-fourth of patients with unilateral COM show abnormal caloric results on the COM side. However, subclinical latent vestibular imbalances were found to be common, which might be related to the gradual vestibular involvement in inflammatory processes, regardless of the caloric results. Results of a set of VFTs should be referred to when determining vestibular imbalance in patients with COM

Initial serum sodium concentration determines the decrease in sodium level after terlipressin administration in patients with liver cirrhosis

BACKGROUND: Terlipressin, as a prodrug of vasopressin, has agonistic effects on the V1 receptor and partial agonistic effects on renal vasopressin V2 receptors. However, its effects on serum sodium concentration are controversial. METHODS: This study retrospectively investigated 127 patients with liver cirrhosis to examine the incidence and risk factors for the decrease in serum sodium level following terlipressin administration. RESULTS: Terlipressin was prescribed for bleeding control (99) and management of hepatorenal syndrome (28). Serum sodium level decreased from 134.0 ± 6.5 mmol/L to 130.4 ± 6.2 mmol/L during or after terlipressin treatment (P < 0.001) in all patients. In 45 patients (35.4%), the serum sodium concentration decreased by > 5 mmol/L, in 29 patients (22.8%); by 5–10 mmol/L; and in 16 patients (12.6%), by > 10 mmol/L. Five patients in the latter group showed neurological manifestations. In the univariate analysis, several factors including age, purpose of use, serum creatinine, and Model for End-Stage Liver Disease score, representing liver function, were significantly associated with the decrease in serum sodium after terlipressin administration. However, a multivariate analysis revealed that only initial sodium level was the most powerful predictor of terlipressin-induced reduction in serum sodium. CONCLUSION: An acute reduction in serum sodium concentration was not uncommon during terlipressin treatment, and the baseline serum sodium level was closely related to the reduction in serum sodium concentration

Effects of creatine and β-guanidinopropionic acid and alterations in creatine transporter and creatine kinases expression in acute seizure and chronic epilepsy models

<p>Abstract</p> <p>Background</p> <p>In order to confirm the roles of creatine (Cr) in epilepsy, we investigated the anti-convulsive effects of Cr, creatine transporter (CRT) and creatine kinases (CKs) against chemical-induced acute seizure activity and chronic epileptic seizure activity.</p> <p>Results</p> <p>Two hr after pilocarpine (PILO)-seizure induction, ubiquitous mitochondrial CK (uMtCK) immunoreactivity was unaltered as compared to control level. However, brain-type cytoplasm CK (BCK) immunoreactivity was decreased to 70% of control level. CRT immunoreactivity was decreased to 60% of control level. Following Cr or Tat-CK treatment, uMtCK or CRT immunoreactivity was unaffected, while BCK immunoreactivity in Cr treated group was increased to 3.6-fold of control levels. β-Guanidinopropionic acid (GPA, a competitive CRT inhibitor) reduced BCK and CRT expression. In addition, Cr and tat-BCK treatment delayed the beginning of seizure activity after PILO injection. However, GPA treatment induced spontaneous seizure activity without PILO treatment. In chronic epilepsy rats, both uMtCK and CRT immunoreactivities were reduced in the hippocampus. In contrast, BCK immunoreactivity was similar to that observed in control animals. Cr-, GPA and tat-BCK treatment could not change EEG.</p> <p>Conclusion</p> <p>Cr/CK circuit may play an important role in sustaining or exacerbating acute seizure activity, but not chronic epileptic discharge.</p

Identification of Domains Directing Specificity of Coupling to G-proteins for the Melanocortin MC3 and MC4 Receptors

The melanocortin receptors, MC3R and MC4R, are G protein-coupled receptors that are involved in regulating energy homeostasis. Using a luciferase reporter gene under the transcriptional control of a cAMP-responsive element (CRE), the coupling efficiency of the MC4R and MC3R to G-proteins was previously shown to be different. MC4R exhibited only 30-50% of the maximum activity induced by MC3R. To assess the role of the different MC3R and MC4R domains in G-protein coupling, several chimeric MC3R/MC4R receptors were constructed. The relative luciferase activities, which were assessed after transfecting the chimeric receptors into HEK 293T cells, showed that the i3 (3rd intracellular) loop domain has an essential role in the differential signaling of MC3R and MC4R. To reveal which amino acid residue was involved in the MC4R-specific signaling in the i3 loop, a series of mutant MC4Rs was constructed. Reporter gene analysis showed that single mutations of Arg220 to Ala and Thr232 to either Val or Ala increased the relative luciferase activities, which suggests that these specific amino acids, Arg220 and Thr232, in the i3 loop of MC4R play crucial roles in G-protein coupling and the subtype-specific signaling pathways. An examination of the inositol phosphate (IP) levels in the cells transfected with either MC3R or MC4R after being exposed to the melanocortin peptides revealed significant stimulation of IP production by MC3R but no detectable increase in IP production was observed by MC4R. Furthermore, none of the MC4R mutants displayed melanocortin peptide-stimulated IP production. Overall, this study demonstrated that MC3R and MC4R have distinct signaling in either the cAMP- or the inositol phospholipid-mediated pathway with different conformational requirements

An exclusively dopamine secreting paraganglioma in the retroperitoneum: a first clinical case in Korea

Exclusively dopamine producing retroperitoneal paragangliomas are extremely rare. We have experienced the first Korean case managed successfully based on the proper evaluation. A 26-year-old female patient came to our attention after the accidental detection of an adrenal mass. She had no symptoms and denied any family history. Laboratory evaluations were normal but serum dopamine (425 ng/L) and 24-hour urine dopamine levels (1,565.3 µg/day) were elevated. She underwent laparoscopic right adrenalectomy. Histopathological diagnosis was a paraganglioma. After operation, dopamine levels in serum and 24-hour urine dropped to 0.09 ng/L and 388.4 µg/day. Dopamine producing paraganglioma elicit no clinical symptoms. Only the dopamine level is elevated in serum and 24-hour urine samples. Surgical resection without using preoperative alpha blockage is the treatment of choice. The prognosis for patients with this tumor tends to be poor because the diagnosis is usually delayed due to lack of symptoms