Gastric acid secretion stimulated by centrally injected nociceptin in urethane-anesthetized rats

Nociceptin is a preferred endogenous ligand for the orphan opioid receptor-like 1 (ORL1) receptor. Central administration of nociceptin showed various pharmacological effects on analgesia, cardiovascular and renal responses, food intake, and so on. In the present study, we investigated the effect of nociceptin injected into the central nervous system (CNS) on gastric acid secretion in the perfused stomach of urethane-anesthetized rats. Injection of nociceptin (0.55-5.52 nmol per rat) into the fourth cerebroventricle stimulated gastric acid secretion and the secretion was inhibited in atropine-treated (1 mg/kg, i.v.) and vagotomized rats. The secretion induced by nociceptin (1.65 nmol) was not inhibited by the central injection of naloxone (275 nmol, a non-selective antagonist of opioid receptors). The secretion was significantly inhibited by the central injection of [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) ([F/G]nociceptin-(1-13), 0.21 nmol, an antagonist of ORL1 receptor), although [F/G]nociceptin-(1-13) alone at higher doses (2.10 and 7.31 nmol) markedly stimulated gastric acid secretion. In the 0-40 min period, the secretion induced by nociceptin was inhibited at least partially by CompB (68.8 nmol, a nonpeptidic antagonist of ORL1 receptor). Injection of nociceptin (5.52 nmol) into the lateral cerebroventricle also stimulated the secretion. Injection of nociceptin did not modify gastric acid secretion stimulated by 2-deoxy-D-glucose (200 mg/kg, i.v.). In conclusion, nociceptin injected into the CNS stimulated gastric acid secretion in rats via the ORL1 receptors and through mechanisms involving the vagus nerve.     

Cholinergic neuronal loss in the basal forebrain and mesopontine tegmentum of progressive supranuclear palsy and corticobasal degeneration

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are clinically characterized by atypical parkinsonism and cognitive disorders and classified in the same histopathological category showing neuronal and glial neurofibrillary tangles (NFTs). To characterize the vulnerability of the forebrain and midbrain cholinergic systems in PSP and CBD, we performed a comparative study of cholinergic neuronal changes in the nucleus basalis of Meynert (NBM) and the laterodorsal tegmental and pedunculopontine tegmental nuclei (LdtgN and PptgN) of brains obtained at autopsy (three cases of PSP, one case of CBD and six cases without neurological diseases) by immunohistochemistry for choline acetyltransferase (ChAT) and Gallyas-Braak staining. In the NBM, the number of neurons and the ChAT-positivity rate of remaining neurons were decreased more in CBD than PSP. On the other hand, in the PptgN and LdtgN neurons were reduced much more, and more NFTs were observed in PSP than CBD. PSP showed a severe decrease of neurons and the ChAT-immunopositive neurons in the LdtgN but less in the PptgN. In CBD, there was a mild deletion of the ChAT-immunostained neurons in the PptgN, but not in the LdtgN. In PSP, cholinergic neurons in the LdtgN are likely to be more vulnerable than PptgN and NBM.     

Creeping eruption caused by a larva of the suborder Spirurina type X

We report a case of creeping eruption caused by a larva of the suborder Spirurina type X, which developed in a 46-year-old Japanese male. The patient ate small raw squids (Watasenia scintillans) 5 days before the onset of symptoms. On examination, an approximately 25-cm-long serpiginous red track with vesicles was observed from the right to the upper left side of the abdomen of the patient. Histological examination revealed the transverse section of a larval worm in the upper to middle dermis.The patient serum was positive only for the antibody against larvae of the suborder Spirurina type X in ELISA, and negative for all other anti-parasite antibodies. Because a considerable number of people are fond of eating raw or nearly-raw fish and shellfish in Japan, opportunities for developing creeping eruption cause by parasites present in raw fish and shellfish are relatively high.     

Somatosensory and skin temperature disturbances caused by infarction of the postcentral gyrus: a case report

Somatosensory functions are subdivided into 2 large groups: the elementary somatosensory functions, which consist of light touch, pain, thermal sensation, joint position sense, and vibration sense, and the intermediate somatosensory functions, which include 2-point discrimination, tactile localization, weight, texture, and shape perception. In this report, we describe a patient with somatosensory dysfunction after infarction of the postcentral gyrus. On physical examination a month after the onset of the infarction, voluntary movements were skillful, and both the elementary and intermediate somatosensory functions were disturbed in the right hand. The patient also displayed a decrease in the skin temperature of the right hand. The sensory-evoked potential in response to electrical stimulation of the right median nerve was normal, and brain MRI showed that the infarction was located in the posterior half of the left postcentral gyrus. These findings suggested that the lesion was situated at areas 1 and 2, and that area 3b was preserved. Thermography revealed that the skin temperature of the right hand was decreased predominantly on the ulnar side, and that recovery from cooling with ice water was delayed. By comparing the results of our patient with a case report that showed no disturbance of the elementary somatosensory functions with a localized lesion in the postcentral gyrus, we suggest that area 1 participates in the elementary somatosensory functions and that skin temperature may be controlled somatotopically in the somatosensory cortex.     

Pre-treatment with ketamine reduces incidence and severity of pain on propofol injection

The purpose of this study was to evaluate the effect of pre-treatment with ketamine on the reduction of pain during injection of propofol in adult patients. We conducted a prospective, randomized, double-blinded trial. Forty-three patients were randomly allocated to one of two groups according to the agents administered before hand; Group C, normal saline 2 ml and Group K, 1% ketamine 2 ml. The pain on injection was rated as none, mild, moderate, or severe. Sixty-eight percent of patients in the C group experienced pain, while 33% of patients experienced pain in the K group. Thirty-six percent of patients in the C group complained moderate to severe pain but only 9% of patients in the K group. The mechanisms of prevention by ketamine of the pain on propofol-injection could not be clarified from our study, but it may be related to central effects of ketamine. In conclusion, ketamine pre-treatment before propofol administration significantly reduces incidence and severity of pain associated with propofol injection.     

Carotenoids in cancer chemoprevention

Various natural carotenoids, besides -carotene, were proven to have anticarcinogenic activity, and some of them showed more potent activity than -carotene. Thus, these carotenoids (-carotene, lutein, zeaxanthin, lycopene, rbeta -cryptoxanthin, fucoxanthin, astaxanthin, capsanthin, crocetin and phytoene), as well as -carotene, may be useful for cancer prevention. In the case of phytoene, the concept of 'bio-chemoprevention', which means biotechnology-assisted method for cancer chemoprevention, may be applicable. In fact, establishment of mammalian cells producing phytoene was succeeded by the introduction of crtB gene, which encodes phytoene synthase, and these cells were proven to acquire the resistance against carcinogenesis. Antioxidative phytoene-containing animal foods may be classified as a novel type of functional food, which has the preventive activity against carcinogenesis, as well as the ability to reduce the accumulation of oxidative damages, which are hazardous for human health.     

Rapid accumulation and internalization of radiolabeled herceptin in an inflammatory breast cancer xenograft with vasculogenic mimicry predicted by the contrast-enhanced dynamic MRI with the macromolecular contrast agent G6-(1B4M-Gd)(256)

The rapid blood flow and perfusion of macromolecules in the inflammatory breast cancer xenograft (WIBC-9), which exhibits a "vasculogenic mimicry" type of angiogenesis without the participation of endothelial cells and expresses high levels of the HER-2/neu antigen, was evaluated in mice using 3D-micro-MR angiography using a novel macromolecular MR contrast agent [G6-(1B4M-Gd)(256)]. Herceptin, which recognizes the HER-2/neu antigen and has similar size (10 nm) to G6-(1B4M-Gd)(256), accumulated and internalized in the WIBC-9 tumors more quickly than in the control MC-5 tumors that progress with normal angiogenesis. Three dimensional micro-MRI with the G6-(1B4M-Gd)(256) macromolecular MRI contrast agent distinguishes between the different types of angiogenesis and is predictive of the rapid accumulation and internalization of Herceptin in the WIBC-9 inflammatory breast cancer xenograft.     

Poor prognosis associated with thrombocytosis in patients with gastric cancer

Background Thrombocytosis is commonly associated with malignant disease and has recently been suggested to be a poor prognostic indicator in patients with lung cancer and gynecological cancers. The prevalence of thrombocytosis in patients with gastric cancer was reviewed, and its association with poor prognosis was investigated. Methods Platelet count (PLT) and hemoglobin concentrations (Hb) were reviewed in 369 consecutive patients with histologically verified gastric cancer from 1994 to 2000. Differences between categories were analyzed with analysis of variance, and survival was compared by using the log-rank test on the Kaplan-Meier life table. Multivariate Cox regression analysis was used to evaluate whether thrombocytosis is an independent prognostic marker. Results Thrombocytosis was found in 42 patients, and anemia was found in 200 patients. PLT was negatively correlated with Hb. Mean PLT was significantly increased in patients with noncurative operations. There was a positive correlation between the depth of tumor invasion and PLT. One- and 3-year survival expectancies in patients with or without thrombocytosis were 52.4% and 23.4% and 85.7% and 72.9%, respectively. PLT was identified as an independent prognostic factor after lymph node metastasis and depth of tumor invasion. Conclusions Thrombocytosis is an independent prognostic indicator of survival in patients with gastric cancer. Presented at the 4th International Gastric Cancer Congress, New York, New York, April 29–May 2, 2001.