Hyperalgesic response to noxious stimulation in genetically polydipsic mice.

Inbred mice, STR/N, are known to exhibit extreme polydipsia and polyuria but no abnormality in the response to exogenous vasopressin (AVP) and renal functions. Our previous studies have revealed that the brain opioid system is involved in the polydipsia of these mice. We here report that the STR/N mice show a decrease in the nociceptive threshold and a low, anti-nociceptive sensitivity to opioid receptors agonists. The paw-withdrawal latency (PWL) on a hot-plate in the STR/N mice was significantly shorter than that in their controls (BALB/c and C3H mice). This hyperalgesia was not affected by water restriction. Subcutaneous (s.c.) injections of morphine (5 mg/kg) and a kappa-opioid receptor agonist, U50,488H (16 mg/kg) had no effect on the PWL in the STR/N mice, whereas the control mice prolonged PWL after administration of the opioids. However, the STR/N mice gained the ability to show morphine analgesia after up-regulation of the opioid system by repeated administration of naltrexone (s.c., 5 mg/kg) for 3 consecutive days. The results suggest that the anti-nociceptive function of the opioid system is down-regulated in STR/N mice as is observed in chronic morphine-treated animals.

IL-1beta increases norepinephrine level in rat frontal cortex: involvement of prostanoids, NO, and glutamate.

The effects of local administration of interleukin-1beta (IL-1beta) were studied by using an intracerebral microdialysis technique in rats. A local injection of IL-1beta (3 and 10 ng) induced an elevation of norepinephrine (NE) concentration in the medial prefrontal cortex (mPFC). IL-1-receptor antagonist (800 ng) completely blocked the IL-1beta-induced NE increase. Diclofenac, a cyclooxygenase inhibitor (500 microM), and Nomega-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor (100 microM), applied through the dialysis probe, did not affect the initial rise in NE levels observed 20 min after injection of IL-1beta but completely suppressed the late phase of IL-1beta-induced NE increase at 40 min and thereafter. In contrast, local perfusion of 6-cyno-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartic acid (NMDA) glutamate-receptor antagonist (50 microM), but not DL-2-amino-5-phosphonovaleric acid, an NMDA-receptor antagonist (100 microM), blocked both phases of IL-1beta-induced NE increase. Furthermore, a microinjection of IL-1beta elevated the extracellular concentration of glutamate in the mPFC. These findings suggest that the IL-1beta-induced rise in NE levels in the mPFC is caused by activation of the glutamatergic system and the glutamate-induced increases in prostanoids and NO.

Endoscopic ultrasonography using a 15/20 MHz probe in a direct contact technique: evaluation and application in esophageal and gastric varices.

Endoscopic ultrasonography (EUS) has been recently developed as a new diagnostic technique for portal hypertension. However, its conventional water-filled balloon technique is not suitable for the evaluation of esophageal varices, because the vessel lumen is compressed by the inflated balloon. Particularly for small varices, the vessel tends to collapse and is difficult to display. A miniature ultrasonic probe for use via the forceps channel in EUS has been developed and is expected to overcome this difficulty. Here we report the efficacy of this new probe in patients with esophago-gastric varices. Instead of using a water-filled balloon for an acoustic window, we displayed the EUS findings from the new probe in direct contact with gastrointestinal wall by removing air from the lumen under vacuum. Both conventional endoscopy and the new EUS were performed on 3 patients with esophageal varices. The transforceps-channel ultrasonic probe visualized grade 1 varices in addition to the larger varices, confirming this technique to be a useful method for assessing of esophageal varices. Moreover, this method does not require a specially designed endoscope for EUS, rather it can be employed in combination with conventional endoscopy. We conclude that this new technique is a preferred diagnostic technique, and it should become more widely accepted for routine clinical applications.

Maffucci's syndrome associated with intracranial enchondroma and aneurysm: case report.

Maffucci's syndrome is a rare, congenital mesodermal dysplasia combined with dyschondroplasia and hemangiomatosis. Enchondromatous involvement of the skull bones is rare in this syndrome. A rare case of Maffucci's syndrome associated with enchondroma at the skull base, left internal carotid artery aneurysm, and goiter is reported. Two other previously reported cases of Maffucci's syndrome with associated aneurysms and the present case suggest that Maffucci's syndrome may be associated with aneurysm.

[Anti-ulcer effect of extract from phellodendri cortex].

In chinese medicine, Phellodendri Cortex (Phellodendron amurense Ruprecht) has been used to treat the patient who suffers from gastroenteritis, abdominal pain or diarrhea. Berberine has been identified as a major component in this plant, and it has biological activities, such as bactericidal activity, anti-cholera toxin effect, anti-inflammatory effect, stimulative effect of bile secretion or bilirubin discharge. In the previous study, we have shown the presence of anti-inflammatory activity in the berberine-free fraction of the extract from this plant. In the present study, we also found anti-ulcer activity in the fraction. The fraction significantly inhibited the formation of ethanol-induced ulcer, aspirin-induced ulcer (s.c., p.o.), pylorus-ligated ulcer (p.o., i.d.) in rats, as well as that of stress ulcer in restrained and water-immersed mice (p.o.). In addition, gastric acid secretion was significantly reduced in pylorus-ligated rats by subcutaneous or intraduodenal administration of the fraction, but not by oral administration. These findings suggest that the suppression of ulcer formation may be due to the additive effect of the cytoprotection effect and the reduction of gastric acid secretion by administration of the berberine-free fraction.

Accelerated expansion of antibody heterogeneity by complete Freund's adjuvant during the response to bacterial alpha-amylase.

Changes in the isoelectric focusing (IEF) spectra of specific antibodies were followed during the response of individual mice to bacterial alpha-amylase (B alpha A) in either incomplete or complete Freund's adjuvant (IFA or CFA). The response to a suboptimal dose of B alpha A was maximally enhanced by employing CFA at an optimal dose of Mycobacterium tuberculosis. Regardless of the strain difference in responsiveness to B alpha A between C3H/He (C3) and C57B1/6 (B6) mice, the enhancing effect of CFA was characterized by an accelerated expansion of IEF spectra and by the intensified stain of focused antibody, compared with the response of mice immunized with the same antigen dose in IFA. The manner and the rate of heterogeneity expansion during the enhanced antibody response to a low dose in CFA were quite similar to the strictly restricted expansion of spectra during a response of a high dose of B alpha A in IFA, although each mouse showed an individual banding pattern with a different degree of heterogeneity, depending on the antibody titre. Thus, CFA accelerated the expansion of IEF spectra during the response to B alpha A without affecting the general manner of sequential expansion of anti-B alpha A antibody heterogeneity.

Sequential expansion of antibody heterogeneity during the response to bacterial alpha-amylase.

By analyzing antibody heterogeneity during the primary immune response to bacterial a-amylase (B alpha A) in high-responder F1 hybrid mice between C57BL/6 (B6) and C3H/He (C3) mice with the use of isoelectric focusing (IEF), it was shown that the maturation of the primary IgG antibody response consisted of at least two stages. The response of every mouse tested was initiated with the production of specific antibody focused as a limited set of bands in a narrow pH range, and the subsequent rise in antibody titer was associated with the sequential expansion of the spectra involving the appearance of new bands in the pH gradient adjacent to the initial bands. A further rise was accompanied only by intensified staining of the pre-existing bands. These two stages were distinguishable regardless of the antigen dose, although increasing the dose led to widely distributed spectra of focused antibodies and an early shift from the first stage to the second. The sequential expansion of spectra following the appearance of initial antibodies with limited isoelectric point (pI) values was not unique to the anti-BaA antibody response, because similar results were obtained with the antibody response to an immunologically unrelated antigen, Taka-amylase A (TAA). Thus, the appearance of initial antibodies in a limited pH range, overlapping among all F1 hybrids tested, is not a direct reflection of similarity in the determinant specificities of these antibodies among different mice.

Isoelectric focusing of the inbred mouse antibody to bacterial alpha-amylase.

In the IgG antibody response to bacterial alpha-amylase (B alpha A) assayed by the enzymatic procedure, C3H/He (C3) mice were high and C57BL/6 (B6) mice were low responders. High responsiveness was inherited as a dominant characteristic in (B6XC3)F1 hybrid mice. In these strains, the primary antibody response was analyzed for heterogeneity by isoelectric focusing (IEF). The IEF spectra were visualized with the use of the capacity of antibody to inhibit the amylase activity of antigen. Increases in the antigen dose and in the time interval between immunization and bleeding resulted in increases in antibody titers accompanied by strong staining of focused antibodies and by the expansion of the pH range where antibodies were focused. High responsiveness in C3 and F1 hybrid mice was also associated with the increase in intensity of stain and the rapid expansion of pH range of focused antibodies. Another strain difference was noted in the isoelectric point (pI) values of antibodies taken early in the primary response. B6 antisera contained those fractions of antibodies focusing over a more alkaline area than C3 antibodies. A similar strain difference in the pI values of antibodies occurred in the response to an irrelevant antigen, Taka-amylase A (TAA), suggesting that the hypervariable regions of antibody molecules play no major part in the strain difference observed. Antisera from F1 hybrid mice displayed bands covering the combined pH ranges of B6 and C3 spectrotypes.