5-Hydroxytryptamine-induced outward currents mediated via 5-HT(1A) receptors in neurons of the rat dorsolateral septal nucleus

Effects of 5-hydroxytryptamine (5-HT) on neurons of the rat dorsolateral septal nucleus (DLSN) were examined by intracellular and whole-cell patch-clamp recording techniques. An outward current was induced by 5-HT (1-100 microM) in a concentration-dependent manner. The EC(50) for 5-HT was 4.8 microM. Also, 8-OH-DPAT (10-100 microM) produced the outward current an EC(50) of 17 microM. Amplitudes of the outward currents produced by 5-HT (100 microM) and 8-OH-DPAT (100 microM) were 117+/-4 (n=6) and 58+/-8 pA (n=6), respectively. Fluvoxamine (200 nM), a specific serotonin re-uptake inhibitor, enhanced the 5-HT (1 microM)-induced outward current: the EC(50) for 5-HT was 0.5 microM in the presence of fluvoxamine (200 nM). L-694247 (100 microM) and CP 93129 (100 microM) also produced outward currents with amplitudes of 33+/-3 (n=4) and 18+/-5 pA (n=4), respectively in DLSN neurons. DOI (100 microM) and RS 67333 (100 microM) did not produce outward currents. NAN-190 shifted, in a parallel manner, the concentration-response relationship of 5-HT to the right. The Lineweaver-Burk plot of the concentration-response curve showed that NAN-190 depressed the 5-HT-induced current in a competitive manner. The current-voltage relationship indicates that the 5-HT-induced current reversed polarity at a potential close to the equilibrium potential of K(+). Ba(2+) (100 microM-1 mM) partially depressed the outward current produced by 5-HT. These results suggest that 5-HT induces multiple K(+) currents via 5-HT(1A) receptors in DLSN neurons.     

Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: a multicenter,placebo-controlled,double-blind,randomized study in patients with gynecologic cancer receiving paclitaxel and carboplatin

Background

Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model. Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently, may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in patients receiving paclitaxel and carboplatin (TC) combination chemotherapy.

Methods

We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant or placebo together with both a 5-HT₃ receptor antagonist and dexamethasone prior to chemotherapy. The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the proportion of patients with “no vomiting”, “no significant nausea”, and complete response, respectively.

Results

Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group) were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not significantly different between the groups. The percentage of “no vomiting” patients (78.2 vs. 54.8 %; P < 0.0001), “no significant nausea” patients (85.4 vs. 74.7 %; P = 0.014), and patients showing complete response (61.6 vs. 47.3 %, P = 0.0073) was significantly higher in the aprepitant group than in the placebo group.

Conclusion

The administration of aprepitant did not have a prophylactic effect on the HSR but was effective in reducing nausea and vomiting in gynecologic cancer patients receiving TC combination chemotherapy.

     

Whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography images before and after chemotherapy for Kaposi sarcoma and highly active antiretrovirus therapy

Kaposi sarcoma is an acquired immunodeficiency syndrome-related disease that mainly involves the skin, gastrointestinal gut, and lungs. Whole-body 18F-fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT) scanning is useful for simultaneous detection of multiple lesions of Kaposi sarcoma. We present a 67-year-old man with a history of infection with human immunodeficiency virus who presented with numerous cutaneous lesions. FDG-PET/CT images showed lesions in the skin, lung, and lymph nodes. The gastrointestinal lesions were detected using gastric fiberscopy (GF) and colon fiberscopy (CF). After Kaposi sarcoma therapy, the uptake in the lesions of the skin, lung, and lymph nodes decreased, but new lesions were detected in the pancreas and lumbar spine. He had pancreatitis and Candida spondilitis. Whole-body FDG-PET/CT is useful for detecting lesions and determining the extension to which the disease has spread, adding the gastrointestinal lesions by GF and CF. After therapy, FDG-PET/CT can be used to demonstrate which lesions remain active and to determine the overall response to treatment. In this case, we show how useful FDG-PET/CT is and how difficult it is to treat Kaposi sarcoma.     

Gliomas with dural invasion: computed tomography and angiography

This report is a review of the findings of computed tomography and angiography of eight supratentorial gliomas with dural invasion. Computed tomography revealed localized increases in the thickness of ring enhancements at the sites of dural invasion in four cases, which was attributed to increased blood supplies by the meningeal vessels. Angiographically, feeders from the meningeal vessels entered the tumors mostly through relatively broad areas of tumor-dura attachment. A sunburst type of neovascularity from a meningeal artery was seen in only one case. In most such cases the differential diagnosis from meningioma was possible by the computed tomographic and angiographic findings. Selective external carotid angiography was the most important examination for diagnosing dural invasion by gliomas.     

Infantile multiple sclerosis with extensive white matter lesions

A boy developed a right hemiparesis at 13 months of age which disappeared spontaneously at 19 months. Computed tomography and magnetic resonance imaging revealed extensive low-density areas with left-sided predominance in the white matter at age 17 months. The flash visual evoked potential revealed abnormal findings of wave V. At 20 months of age, paraplegia developed; as it receded 3 months later, a left hemiparesis developed. At that time, computed tomography demonstrated a new low-density area in the right centrum semiovale which disappeared at 28 months of age concomitant with the recovery of the left hemiparesis. Overall, he had experienced 3 independent episodes, 2 of which corresponded to each of the lesions depicted by computed tomography and magnetic resonance imaging. Multiple sclerosis was diagnosed at 23 months of age which is earlier than in any previously reported patient. Unlike most typical findings of multiple sclerosis on computed tomography and magnetic resonance imaging studies, our patient demonstrated extensive white matter lesions.     

A case of spinal dural arteriovenous malformation associated with the broad lesion within spinal cord--diagnostic value of MRI with Gd-DTPA enhancement

A 70-year-old man, with slowly progressive gait disturbance, numbness in his lower limbs and dysuria, was admitted to our hospital in July, 1988. Neurological examination revealed flaccid paraparesis, hyperesthesia below the level of Th-10 combined with the disturbance of pain and temperature sensations below the level of Th-11, and neurogenic bladder. Midsagittal Tl-weighed image of MRI did not reveal any abnormal finding except for a mild enlargement of the conus medullaris. With Gadolinium (Gd)-DTPA injection, however, the spinal cord was diffusely enhanced below the level of the 9th thoracic spine. This enhancement effect was particularly remarkable at the periphery of the spinal image showing several high intensity spots in the posterior aspect of the spinal cord, which was thought to be incompatible with the spinal cord neoplasm. The angiographic examination of the selective Th-7 intercostal artery on the left showed vascular malformation lying adjacent to the 7th intervertebral foramen with markedly dilated tortuous spinal veins going upwards and downwards, which was compatible with spinal dural arteriovenous malformation (AVM). After the artificial embolization, draining veins as well the nidus of AVM had completely disappeared on angiogram. There was an improvement on his neurological findings and Gd-DTPA enhancement had been diminished on MRI. It was suggested that Gd-DTPA enhancement on MRI was due to the dilated and remarkably congestive spinal veins, and that both the elevated venous pressure and reduction of intramedullary arteriovenous pressure gradient were the cause of the development of clinical symptoms.     

Accuracy of diagnosis on death certificates for underlying causes of death in a long-term autopsy-based population study in Hisayama, Japan; with special reference to cardiovascular diseases

Major categorical diagnosis by International Classification of Diseases and type-specific diagnosis for cardiovascular diseases in death certificates were compared to the diagnosis made at autopsy in 864 consecutive autopsy cases aged 20 or over, among the Japanese residents in Hisayama town. Cerebral stroke was correctly diagnosed in 84%, malignant neoplasms in 78% and cardiac disease in 66%. Cerebral stroke and cardiac disease tended to be overdiagnosed, while malignant neoplasms were underdiagnosed. The validation of certified diagnosis was less reliable in the aged population, and in type-specific diagnosis of cardiovascular diseases. Cerebral hemorrhage with false negative or false positive diagnoses was usually classified into type unspecified stroke or different categories of cerebral stroke, while those misdiagnosed as cases of cerebral infarction frequently had no significant lesions in the autopsied brain. Finally, the relationship between the validation of diagnosis on the death certificates and the secular trend in cardiovascular disease in the Japanese vital statistics was discussed.     

Effect of ONO-1101, a novel short-acting β-blocker on hemodynamic responses to isoflurane inhalation and tracheal intubation

Purpose We investigated the effect of a new ultrashort-acting β-blocker, ONO-1101, on hemodynamic responses to isoflurane inhalation and tracheal intubation. Methods Fifty-four ASA PS 1 or 2 patients were randomly allocated to receive either ONO-1101, 0.04 mg·kg⁻¹·min⁻¹, or saline prior to tracheal intubation. Anesthesia was induced with thiamylal, 4 mg·kg⁻¹, and vecuronium, 0.15 mg·kg⁻¹. Tracheal intubation was carried out after 3 min controlled mask ventilation with 66% N₂O and 3% inspired isoflurane in oxygen. Heart rate and blood pressure were continuously recorded from the start of induction until 5 min after intubation. Plasma concentrations of catecholamines were measured before induction, 3 min after initiating inhalation of isoflurane, and 1 min after tracheal intubation. Results Significant increases in heart rate occurred in both groups in response to isoflurane inhalation and tracheal intubation, but the magnitude of the increase was significantly less in the ONO-1101 group. Blood pressure increased after tracheal intubation in the saline group but remained unchanged in the ONO-1101 group. Plasma concentrations of norepinephrine increased after induction and intubation in both groups, with no significant difference between the groups. Conclusion ONO-1101 infusion is effective for the attenuation of hemodynamic responses to isoflurane inhalation and tracheal intubation.     

Enhanced effect of intraperitoneal administration of CDDP combined with caffeine against peritoneal metastasis

The enhanced effect of CDDP combined with caffeine against P-388 leukemia was investigated. No synergistic effect was shown after one hour simultaneous treatment with CDDP and caffeine. But the growth inhibition was enhanced by the addition of caffeine after one hour treatment with CDDP. It is suggested that caffeine inhibits DNA repair by the reduction of CDDP-induced elongation of G2 + M phase. The increase in life span of mice after ip transplantation was observed by frequent ip injections of caffeine after CDDP injection. It is suggested that the effect of intraperitoneal administration of CDDP against peritoneal metastasis is enhanced by combination with caffeine.