Functional changes in piriform cortex pyramidal neurons in the chronic methamphetamine-treated rat.

Chronic treatment of rats with methamphetamine (MAP) causes a range of functional changes to the central nervous system (CNS), including a toxicity that is widespread throughout the brain (Frost and Cadet 2000; Fasihpour et al. 2013). In this report, we examined the effect of chronic MAP treatment on pyramidal neurons of the rat piriform cortex, an area involved in sensory processing, associative learning and a model system for studies on synaptic plasticity. MAP treatment significantly depolarized the membrane potential and decreased neuronal input resistance. Furthermore, the voltage-dependence of both AMPA and NMDA responses was disturbed by chronic MAP treatment, and the extent of long-term potentiation (LTP) was decreased. Morphological changes of MAP-treated rat pyramidal neurons were observed as blebbing of the dendrite trees. The changes we observed represent detrimental effects on the function of piriform cortical neurons further illustrating deficits in synaptic plasticity extend beyond the hippocampus. These changes may contribute to behavioural deficits in chronic MAP-treated animals.

Reduction of cystic cavity, promotion of axonal regeneration and sparing, and functional recovery with transplanted bone marrow stromal cell-derived Schwann cells after contusion injury to the adult rat spinal cord.

OBJECT: The authors previously reported that Schwann cells (SCs) could be derived from bone marrow stromal cells (BMSCs) in vitro and that they promoted axonal regeneration of completely transected rat spinal cords in vivo. The aim of the present study is to evaluate the efficacy of transplanted BMSC-derived SCs (BMSC-SCs) in a rat model of spinal cord contusion, which is relevant to clinical spinal cord injury. METHODS: Bone marrow stromal cells were cultured as plastic-adherent cells from the bone marrow of GFPtransgenic rats. The BMSC-SCs were derived from BMSCs in vitro with sequential treatment using beta-mercaptoethanol, all-trans-retinoic acid, forskolin, basic fibroblast growth factor, platelet derived-growth factor, and heregulin. Schwann cells were cultured from the sciatic nerve of neonatal, GFP-transgenic rats. Immunocytochemical analysis and the reverse transcriptase-polymerase chain reaction were performed to characterize the BMSC-SCs. For transplantation, contusions with the New York University impactor were delivered at T-9 in 10- to 11-week-old male Wistar rats. Four groups of rats received injections at the injury site 7 days postinjury: the first received BMSCSCs and matrigel, a second received peripheral SCs and matrigel, a third group received BMSCs and matrigel, and a fourth group received matrigel alone. Histological and immunohistochemical studies, electron microscopy, and functional assessments were performed to evaluate the therapeutic effects of BMSC-SC transplantation. RESULTS: Immunohistochemical analysis and reverse transcriptase-polymerase chain reaction revealed that BMSC-SCs have characteristics similar to SCs not only in their morphological characteristics but also in their immunocytochemical phenotype and genotype. Histological examination revealed that the area of the cystic cavity was significantly reduced in the BMSC-SC and SC groups compared with the control rats. Immunohistochemical analysis showed that transplanted BMSCs, BMSC-SCs, and SCs all maintained their original phenotypes. The BMSC-SC and SC groups had a larger number of tyrosine hydroxilase-positive fibers than the control group, and the BMSC-SC group had more serotonin-positive fibers than the BMSC or control group. The BMSC-SC group showed significantly better hindlimb functional recovery than in the BMSC and control group. Electron microscopy revealed that transplanted BMSC-SCs existed in association with the host axons. CONCLUSIONS: Based on their findings, the authors concluded that BMSC-SC transplantation reduces the size of the cystic cavity, promotes axonal regeneration and sparing, results in hindlimb functional recovery, and can be a useful tool for spinal cord injury as a substitute for SCs.

[Trial to stimulate learning motivation of medical students in the dissection practice "teaching assistant system"].

At the Medical School of Chiba University, educational dissection tours have been conducted for intra- and extramural students in other programs, such as students of nursing. In the 2006 school year there were more than 1,500 students. As presented in a previous report, we tested an educational program in which our medical students teach other students parts of splanchnology, neurology, and myology to promote student understanding of human physiology through their own teaching. Since this system, termed the "teaching assistant system," was fairly laborious for many medical students, we attempted to improve it by decreasing the students' load and reducing the frequency of teaching from several times to once during the one-term dissection practice. We assessed the improved method with questionnaires for medical students who had studied at the school in 2006 and 2007 (n = 206) before and after teaching other students. The response rate for the questionnaires was 91.3% (n = 188). The results were as follows. (1) Most medical students (69.7%) realized that the task of teaching had stimulating effects on their own learning motivation. (2) According to most of their evaluations (80.4%), the duties of teaching involved in the previous assistant system were laborious. In contrast, the ratio of medical students who considered teaching to be laborious decreased by about half (55.3%) in the present improved system. (3) Most students (79.8%) were satisfied with the teaching assistant system. We concluded that the improved teaching assistant system was effective for the dissection practice.

[Risk assessment for outpatients for cancer chemotherapy].

Outpatient treatment in the cancer chemotherapy center was begun in April 2005 at the University of Occupational and Environmental Health Hospital. Drugs were prescribed 2,590 times during the past year. Times for intravenous drip for various regimens and outpatient chemotherapy desired by patients showed a rough. The number of incidents was three (0.12%) and no accidents occurred. There were 74 consultations with pharmacists about prescriptions (2.6%) and 286 (11.0%) with nurses. Both types of consultation decreased and their contents were different. The number of consultations about prescriptions by special staff at the cancer chemotherapy center was less than at other departments. Therefore, a system assuring safe management is critically required for the establishment of a system for outpatient cancer chemotherapy treatment.

[What do cancer chemotherapy outpatients want?--results of a questionnaire survey].

We conducted a questionnaire survey to evaluate patients at the cancer chemotherapy center of the university of occupational and environmental health hospital from January to March 2006. Thirty-three (61.1%) and 5 (9.2%) of 54 patients wished to receive chemotherapy on an outpatient basis and as inpatients, respectively. Among the reasons for wishing to be treated as outpatients were the following: Keeping in touch with family, not wanting to be hospitalized, a desire to work, and the wish to continue hobbies, at 45.5 (15/33), 36.4 (12/33), 24.2 (8/33), and 24.2 (8/33), respectively. Twenty-four (44.4%) patients voiced concerns about chemotherapy at an outpatient clinic in terms of associated adverse events, feeling bad about causing trouble to their family, and the desire to have consultations at night or on holidays. Thirty-eight (70.4%) patients wished to have chemotherapy within 3 hours, and 42 (77.7%) of them requested improvements in the examinations, time, duration of chemotherapy, and the effect of chemotherapy. These findings indicate that a major part of patients wish to receive cancer chemotherapy at an outpatient clinic within 3 hours. However, they also have serious reservations about any associate adverse events. We therefore need to improve the overall environment for cancer chemotherapy patients in order to allow them to feel safe when undergoing such treatments.

Formaldehyde exposure in a gross anatomy laboratory--personal exposure level is higher than indoor concentration.

GOAL, SCOPE AND BACKGROUND: Cadavers for gross anatomy laboratories are usually prepared by using embalming fluid which contains formaldehyde (FA) as a principal component. During the process of dissection, FA vapors are emitted from the cadavers, resulting in the exposure of medical students and their instructors to elevated levels of FA in the laboratory. The American Conference of Governmental Industrial Hygienists (ACGIH) has set a ceiling limit for FA at 0.3 ppm. In Japan, the Ministry of Health, Labour and Welfare has set an air quality guideline defining two limit values for environmental exposure to FA: 0.08 ppm as an average for general workplaces and 0.25 ppm for specific workplaces such as an FA factory. Although there are many reports on indoor FA concentrations in gross anatomy laboratories, only a few reports have described personal FA exposure levels. The purpose of the present study was to clarify personal exposure levels as well as indoor FA concentrations in our laboratory in order to investigate the relationship between them. METHODS: The gross anatomy laboratory was evaluated in the 4th, 10th and 18th sessions of 20 laboratory sessions in total over a period of 10 weeks. Air samples were collected using a diffusive sampling device for organic carbonyl compounds. Area samples were taken in the center and four corners of the laboratory during the entire time of each session (4-6 hours). Personal samples were collected from instructors and students using a sampling device pinned on each person's lapel, and they were 1.1 to 6 hours in duration. Analysis was carried out using high performance liquid chromatography. RESULTS AND DISCUSSION: Room averages of FA concentrations were 0.45, 0.38 and 0.68 ppm for the 4th, 10th and 18th sessions, respectively, ranging from 0.23 to 1.03 ppm. These levels were comparable to or relatively lower than the levels reported previously, but were still higher than the guideline limit for specific workplaces in Japan and the ACGIH ceiling limit. The indoor FA concentrations varied depending on the contents of laboratory sessions and seemed to increase when body cavity or deep structures were being dissected. In all sessions but the 4th, FA levels at the center of the room were higher than those in the corners. This might be related to the arrangement of air supply diffusers and return grills. However, it cannot be ruled out that FA levels in the corners were lowered by leakage of FA through the doors and windows. Average personal exposure levels were 0.80, 0.45 and 0.51 ppm for instructors and 1.02, 1.08 and 0.89 ppm for students for the 4th, 10th and 18th session, respectively. The exposure levels of students were significantly higher than the mean indoor FA concentrations in the 4th and 10th sessions, and the same tendency was also observed in the 18th session. The personal exposure level of instructors was also significantly higher than the indoor FA level in the 4th session, while they were almost the same in the 10th and 18th sessions. Differences in behavior during the sessions might reflect the differential personal exposure levels between students and instructors. CONCLUSION: The present study revealed that, if a person is close to the cadavers during the gross anatomy laboratory, his/her personal exposure level is possibly 2 to 3-fold higher than the mean indoor FA concentration. This should be considered in the risk assessment of FA in gross anatomy laboratories. RECOMMENDATION AND OUTLOOK: If the risk of FA in gross anatomy laboratories is assessed based on the indoor FA levels, the possibility that personal exposure levels are 2 to 3-fold higher than the mean indoor FA level should be taken into account. Otherwise, the risk should be assessed based on the personal exposure levels. However, it is hard to measure everyone's exposure level. Therefore, further studies are necessary to develop a method of personal exposure assessment from the indoor FA concentration.

[Out-patient treatment for cancer patients at cancer chemotherapy centers in university hospitals].

At present, one-third of people die of cancer and the number is still increasing in Japan. A safe and effective treatment system is critically required. Recently, the discovery of new drugs and the development of medical oncology promotes out-patient treatment for cancer patients. Out-patient treatment in the cancer chemotherapy center of the University of Occupational and Environmental Health Hospital has been started, and many chemotherapy regimens were verified in this center. Not only different organ-specific chemotherapies but also summarizing the oncology team are necessary for performance of the mission. We describe in this review the characteristics of the cancer chemotherapy center.

Essential role of D1 but not D2 receptors in methamphetamine-induced impairment of long-term potentiation in hippocampal-prefrontal cortex pathway.

Methamphetamine (MA) abuse induces deficits in cognitive performance that are related to dysfunction of the prefrontal cortex (PFC). The medial portion of the prefrontal cortex (mPFC) in rats that is crucial for cognitive function has been shown to undergo long-term potentiation (LTP) in the projections from the hippocampus. However, no study has been performed to evaluate the influence of MA on synaptic plasticity in the hippocampal-mPFC pathways. In the present experiments, we investigated the effects of repeated MA administration on hippocampal-mPFC LTP, together with MA-induced stereotyped behaviors. Repeated MA administration produced behavioral sensitization and LTP impairment in the hippocampal-mPFC pathways. The MA-induced impairment of hippocampal-mPFC LTP was prevented by the pretreatment of dopamine 1 (D1) but not dopamine 2 (D2) receptor antagonists, while D1 and D2 receptor antagonists attenuated the MA-induced stereotyped behaviors. These findings suggest that D1 receptors are crucial for the MA-induced deterioration of synaptic plasticity in the hippocampal-mPFC circuits. Impairment of LTP associated with D1 receptor dysfunction may underlie cognitive deficits in MA-dependent subjects.

Neurotoxic morphological changes induced in the medial prefrontal cortex of rats behaviorally sensitized to methamphetamine.

The present study examined whether the development in rats of behavioral sensitization to methamphetamine (MAP) is related to the development of neurotoxic morphological changes presumably induced in the medial prefrontal cortex (MFC). Male rats were intraperitonieally injected with MAP (5 mg/kg) once a day for 12 days (day 1-day 12), and then the drug was withdrawn for 7-42 days (WD7-WD42). The MAP- treatment caused hypersensitivity of a successive head-movement stereotypy, which reached a basic plateau level on day 4, and rose successively to a higher level by day 12. Morphological changes were histochemically and morphometrically examined in the MFC. In the strata covering layers II and III, the densities of tyrosine hydroxylase (TH)-immunoreactive axons decreased on a daily basis to 50% of the control on day 4 and then to 40% on days 6 and 12. The densities of dopamine-,beta-hydroxylase (DBH)-immunoreactive axons did not change during the injection period. A few TUNEL-positive cells were observed in a unit area (0.25 mm2) covering layers II-V on day 6 and they increased to 19 and 16 on day 12 and WD7, respectively. These observations demonstrate a role for the neurotoxic changes in the MFC in the processes of behavioral sensitization of a stereotypy to a low dose of MAP.

In vitro metabolism of fenthion and fenthion sulfoxide by liver preparations of sea bream, goldfish, and rats.

The in vitro metabolism of fenthion and its sulfoxide (fenthion sulfoxide) in sea bream (Pagrus major) and goldfish (Carassius auratus) was investigated and compared with that in rats. Fenthion was oxidized to fenthion sulfoxide and the oxon derivative, but not to its sulfone, in the presence of NADPH by liver microsomes of sea bream, goldfish, and rats. These liver microsomal activities of the fish were lower than those of rats but were of the same order of magnitude. The NADPH-linked oxon- and sulfoxide-forming activities of liver microsomes of the fish and rats were inhibited by SKF 525-A, metyrapone, alpha-naphthoflavone, and carbon monoxide. The oxidizing activity to fenthion sulfoxide was also inhibited by alpha-naphthylthiourea. Several cytochrome P450 isoforms and flavin-containing monooxygenase 1 exhibited these oxidase activities. Fenthion sulfoxide was reduced to fenthion with liver cytosol of the fish and rats upon addition of 2-hydroxypyrimidine, N(1)-methylnicotinamide, or butyraldehyde, each of which is an electron donor of aldehyde oxidase, under anaerobic conditions. The activity was inhibited by menadione, beta-estradiol, and chlorpromazine, which are inhibitors of aldehyde oxidase. The activities in the fish livers were similar to those of rat liver. Aldehyde oxidase purified from the livers of sea bream and rats exhibited the reducing activity. Thus, fenthion and fenthion sulfoxide are interconvertible in fish and rats through the activities of cytochrome P450, flavin-containing monooxygenase, and aldehyde oxidase.

Rapid structural remodeling of shaft synapses associated with long-term potentiation in the cat superior cervical ganglion in situ.

Synaptic plasticity associated with long-term potentiation was studied electrophysiologically and ultrastructurally in the cat superior cervical ganglion in situ. The preganglionic nerve fiber was stimulated at 10 Hz for 50 s for conditioning and then at 1 Hz for 1-3 h to monitor changes in the postganglionic compound action potential (PGP). The present material has shown the long-term potentiation (LTP), around 120% of the control, which lasted for up to 3 h. Fifteen of 18 ganglia (83%) have shown LTP. Ultrastructural studies demonstrated the synaptic structural remodeling: (1) The preganglionic nerve terminals ordinarily made mainly asymmetrical type of shaft synapses directly with dendrites of the ganglion cells that lacked dendritic spines; (2) conditioning tetanus rapidly remodeled simple shaft synapses into perforated ones characterized by perforations in the postsynaptic density (PSD), some of which had synaptic spinules associated with the perforated PSDs, i.e. spinule-synapses; (3) a rapid increase in the number of both structures was detected immediately after the tetanus. Perforated synapses and the spinule-synapses increased from 5% and 0% in the control to 27 and 9% at 0 min, respectively. Spinule-synapses occurred about one-third of the perforated shaft synapses; (4) Increased numbers of restructured shaft synapses was maintained for 15 min in ganglia expressing LTP; (5) Remodeled synapses did not increase in ganglia that did not express LTP or ganglia that were activated at 0.5 or 1 Hz. It was suggested a rapid increase in the number of remodeled synapses associated with the onset of LTP and its durability at its earlier phases in the cat SCG.