Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)     

The isolated spinal cord-skin preparation of the newborn rat and effects of some algogenic and analgesic substances

We have developed an isolated spinal cord-skin preparation of the newborn rat. The spinal cord together with a piece of skin connected to the cord by the saphenous nerve was isolated from 1- to 4-day-old rats and separately superfused with artificial cerebrospinal fluid in two neighbouring chambers. Potentials were recorded extracellularly from the third lumbar ventral root. Application of capsaicin (0.5-2 μM) or KCl (60–350 mM) with brief pressure pulses to the perfusion bath of the skin evoked a depolarizing response of 20- to 40-s duration in the ventral root. The response was depressed by [Met⁵]enkcphalin (0.03–3 μM). morphine (0.1–2 μM) and a tachykinin antagonist, [D-Arg¹,D-Trp^7,9,Leu¹¹] substance P (spantide), 1–10 μM), applied to the spinal cord by superfusion, whereas the response was augmented by centrally administered calcitonin gene-related peptide (0.1–0.2 μM) or bicuculline (0.5–1 μM).     

Clinical and epidemiological aspects of enteritis due to Salmonella hadar. II. Environmental contamination by Salmonella hadar in Shizuoka Prefecture--studies on the feasibility of reducing S. hadar infection]

A systematic examination was performed for environmental food contamination by Salmonella in poultry farms, broiler chickens, broiler processing plants and meat on the market. Salmonella was isolated from 219 of 1197 samples and the serotypes showed a wide distribution. (Table 1-1). S. hadar accounted for 37.1% (96) of all isolations (259). The contamination rate of broiler chickens on arrival at broiler processing plants is relatively low. However, in the broiler processing plants, containers, processing machinery, cooling water and slaughters were highly contaminated by Salmonella, S. hadar being the most prominent serotype in the plants. 64% of chicken meat on the market was contaminated by Salmonella, S. hadar being the second most prominent serotype. 11% of the pork and none of the beef or horseflesh was contaminated by Salmonella. These results indicate that poultry is the main source of S. hadar infection in humans. However, no S. hadar was isolated from cultures of 119 samples of feed for chickens from each delivery (Table 1-1). Thus, as the main source of infection by S. hadar of broiler chickens, an association with the feed seems to be ruled out. S. hadar was isolated at three of 18 poultry farms within Shizuoka Prefecture. Follow-up studies were performed at the three poultry farms which revealed that in two of them, Salmonella was completely eradicated on completion of disinfection. In the other one farm, which is still being disinfected, various strains of Salmonella including S. hadar still survived. We conclude that the main cause of the problem is the magnification of contamination of Salmonella-free material during the process at the broiler processing plants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Limitation of transcatheter arterial chemoembolization using iodized oil for small hepatocellular carcinoma. A study in resected cases.

The radiologic and histologic findings are presented of the resection of 14 small hepatocellular carcinomas (HCC), less than 2 cm in maximum diameter, after transcatheter arterial chemoembolization (TCE) using iodized oil. The effect of TCE on small HCC depended on the morphologic type of the tumors. When no extracapsular invasion of tumor cells occurred, TCE was extremely effective against encapsulated tumors. However, in nine of the 14 resected specimens, viable tumor cells remained in or around the tumor. The authors suggest that small HCC are not always curable with TCE alone and that a multi-disciplinary approach is necessary for patients with small HCC.     

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling

1. Download high-res image (248KB)
2. Download full-size image

     

Momentary changes in the cardiovascular autonomic system during mental loading in patients with panic disorder: a new physiological index "rho(max)"

BACKGROUND: Although panic disorder (PD) is suggestive of autonomic nervous system dysfunction, especially in the cardiovascular autonomic system (CAS), the results in many previous studies are still controversial. Using a new physiological index which could well reflect emotional reaction to visual stimuli (Yoshizawa, M., Sugita, N., Tanaka, A., Abe, K., Yambe, T., Nitta, S., 2001. Quantiatative Physioligical Evaluation of Three Dimensional Images. The Seventh International Conference on Virtual Systems and Multumedia, 25-27.), we studied momentary changes in the CAS in patients with PD during audiovisual stimulation (AS) as mental loading. METHODS: During AS, exposed to a video of imaginary experiences such as driving a motor vehicle or diving into the sea, blood pressure (BP) and heart rate (HR) were measured in 12 remitted patients with PD and 19 age- and sex-matched normal controls (NC). We used the maximum cross-correlation coefficient (rho(max)) from the BP to the HR, whose frequency components were limited to around 0.1 Hz. RESULTS: The rho(max) was an available index which could detect the momentary changes in the CAS during AS in both groups. The two-way ANOVA disclosed significant group and time effects on the rho(max). The momentary response to emotional stimuli in the PD patients was slower than that in the NC subjects. LIMITATIONS: Antidepressants have a potential impact on the autonomic variables in this study. CONCLUSIONS: These findings suggest that there may be a dysfunction of the CAS in remitted PD patients and that the dysfunction may be one of the trait markers of PD. To confirm these findings, however, further studies with a large sample size are required.     

Urodynamics in acetone-induced cystitis of anesthetized rats

We examined the bladder function of cystitis models induced by intravesical acetone instillation in urethane-anesthetized rats. Acetone (0.35 ml) at 10, 30, or 50% concentration or deionized water (sham-treatment) was instilled into the bladder via the cannula which was inserted into the lumen. Acetone was withdrawn 90 sec after instillation and the bladder lumen was washed with saline after 15 min. One hour later, the cystometrogram induced by transvesical infusion of saline (3.3 ml/hr) was measured. During cystometrography of normal (non-treated) or sham-treated group, the time required to cause micturition, reflecting bladder capacity, was 9.6 +/- 0.9 (n = 7) or 10.0 +/- 0.8 min (n = 6), respectively. In the 10% acetone-treated group, the bladder capacity was similar to that in the normal or sham group. In the 30% acetone group, the time to micturition was 4.4 +/- 0.4 min (n = 7), indicating decreased bladder capacity, although the micturition pressure and the threshold pressure were not significantly different from those in the normal or sham group. However, in the 50% acetone group, the micturition reflex disappeared. In isolated rat bladder strips, contractile responses to carbachol or electrical field stimulation in the sham and 30% acetone group were similar. While, both responses in isolated strips from the 50% acetone group were reduced. The degree of damage from degeneration and desquamation of epithelium and hemorrhage in the bladder tissue from the 30% acetone group was less prominent than in the 50% acetone group. Additionally, some tissue from the 50% acetone group showed degeneration of muscle layer. The effects of three drugs were investigated in the 30% acetone group which showed increased urinary frequency. Baclofen (100 microg/kg, i.v.) and morphine (100 microg/kg, i.v.) increased significantly the bladder capacity and the threshold pressure. Atropine (10 microg/kg, i.v.) decreased the micturition pressure. These results suggest that cystitis models induced by intravesical instillation of 30% acetone may be valuable for evaluating drugs for the treatment of urinary frequency.     

Increasing Primary Care Physician Support for and Promotion of Cancer Clinical Trials

Only 2.5%–3% of adult cancer patients participate in cancer clinical trials, yet about 20% of cancer patients are medically eligible to participate. Research suggests that the primary care provider (PCP) can influence a patient''s awareness of, and potentially, his or her decision to consider a clinical trial. To address low cancer clinical trial accrual rates, ‘Imi Hale Native Hawaiian Cancer Network partnered with The Queen''s Cancer Center to provide and evaluate education on clinical trials to Hawai‘i PCPs. The educational materials were developed from a national curriculum and tailored to local audiences. Objectives of the curriculum were to educate PCPs about common myths (attitudinal barriers) around clinical trials and suggest ways that PCPs can introduce the concept of clinical trials to their patients with cancer or suspicion of cancer. The curriculum was tested on 128 PCPs in 2012. Knowledge of the PCP''s role and their willingness to mention clinical trials were measured through a post-test immediately following the presentation, which 74 (58%) PCPs completed. The post-test results suggested an increase in awareness among PCPs of their potential role in cancer clinical trial accrual, and an increase in PCP willingness to mention clinical trials to their patients with suspicion of cancer or diagnosed with cancer. Although findings suggest that this intervention is useful in increasing PCP receptivity to promoting cancer clinical trials, more research is needed to test if increased willingness results in increased accrual of cancer patients into clinical trials in Hawai‘i.     

Up-regulation of transferrin receptor 1 in chronic hepatitis C: Implication in excess hepatic iron accumulation.

BACKGROUND/AIMS:: To clarify the mechanism of excess hepatic iron accumulation in chronic hepatitis C, we investigated the expressions of transferrin receptor 1 and divalent metal transporter 1 in hepatocytes, both of which are involved in cellular iron uptake, in relation to the degree of hepatic iron accumulation and hepatic fibrosis by immunohistochemistrical study. METHODS:: Forty-six hepatic tissues with chronic hepatitis C and five normal hepatic tissues were examined. Chemical detection of hepatic iron accumulation was performed by Perl's Prussian blue stain. The immunohistochemistrical study was performed by avidin-biotin complex method with alkaline phosphatase. RESULTS:: In chronic hepatitis C: (1) Hepatic iron accumulation was significantly increased in relation to the advance of the fibrosis. (2) Divalent metal transporter 1 decreased significantly in relation to the advance of hepatic fibrosis. (3) Transferrin receptor 1 expression was always detected, although not in normal hepatic tissues; there was no relation between expression levels and the degree of hepatic fibrosis. CONCLUSIONS:: These data demonstrated that the transferrin receptor 1 expression was up-regulated irrespective of the degree of hepatic iron accumulation, suggesting that the up-regulation of transferrin receptor 1 might act as one of the key mechanisms implicated in the accumulation of hepatic iron in chronic hepatitis C.