Hypertrophy of medial globus pallidus and substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA: Implication for L‐DOPA‐induced dyskinesia in Parkinson's disease

The medial globus pallidus plays a crucial role in generation of L‐DOPA‐induced dyskinesia in patients with Parkinson's disease. The 6‐hydroxydopamine‐lesioned rat exhibiting behavioral sensitization to L‐DOPA is one useful animal model for examining L‐DOPA‐induced dyskinesia. To determine neuropathological abnormality responsible for behavioral sensitization, the medial globus pallidus and the substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA were examined. Intermittent L‐DOPA treatment induced hypertrophy of the lesioned‐side of medial globus pallidus and substantia nigra reticulata of 6‐hydroxydopamine‐lesioned rats with behavioral sensitization to L‐DOPA. Additionally, coadministration of a 5‐HT_1A receptor agonist, 8‐hydroxy‐2(di‐n‐propylamino)tetralin with L‐DOPA, alleviated the hypertrophy with improvement of the behavioral sensitization. These results suggest that hypertrophy of the medial globus pallidus and substantia nigra reticulata is associated with induction of behavioral sensitization to L‐DOPA in 6‐hydroxydopamine‐lesioned rats. Therefore, neuropathological changes corresponding to hypertrophy might underlie L‐DOPA‐induced dyskinesia in patients with Parkinson's disease.     

Injection sites utilized for DPT immunizations in infants.

The purpose of this investigation was to determine the site utilized by nurses for administering Diphtheria and Tetanus Toxoids and Pertussis (DPT) injections to infants under 7 months of age. Twenty-six of the 28 agencies identified in a metropolitan area as administering DPT injections chose to participate in the study. Those individuals administering DPT injections in the agencies completed a questionnaire with a return rate of 69% (n = 55). Forty-four participants indicated that they used the anterolateral thigh, the recommended site, 100% of the time. The participants in the study administered a total of 1,453 DPT injections per month. Eighty-seven percent of those injections were administered in the anterolateral thigh, 3.6% were given in the deltoid, 5.1% were given in the dorsal gluteal, and 4% were given in the ventrogluteal. The estimated proportion of DPT injections administered at the correct site was 84.65% which is much lower than the critical value 94.06% for alpha = .05 (p less than .00001).     

Enzymes induced by ethanol differently affect the pharmacokinetics of trichloroethylene and 1,1,1-trichloroethane.

This study was undertaken to clarify the effect of enzymes induced by ethanol consumption on the pharmacokinetics of trichloroethylene (TRI, a highly metabolised substance) and 1,1,1-trichloroethane (1,1,1-TRI, a poorly metabolised substance). Rats maintained on a control liquid diet or a liquid diet containing ethanol (2 g/day/rat) for not less than three weeks were exposed to either TRI (50, 100, 500, and 1000 ppm) or 1,1,1-TRI (50, 100, and 500 ppm) by inhalation for six hours and the concentration of each compound in the blood and the urinary excretion of metabolites (trichloroethanol and trichloroacetic acid) were measured over several hours. Ethanol, which increased the in vitro metabolism of both compounds about fivefold, enhanced the in vivo metabolism of TRI only at high levels of exposure (marginally at 500 and considerably at 1000 ppm), whereas the metabolism of 1,1,1-TRI was enhanced at all concentrations tested. Moreover, there was a definite difference in the effect of induction of enzymes between the two solvents: the enhanced metabolism of TRI in vivo was shown by a decrease in the blood concentration of TRI as well as by an increase in the urinary excretion of its metabolites, whereas that of 1,1,1-TRI was shown by an increase in the urinary excretion of its metabolites alone. These results suggest that the induction of enzymes differentially affects the pharmacokinetics of TRI and 1,1,1-TRI in human occupational exposure: TRI metabolism may be increased only at concentrations much higher than the current occupational exposure limit (mostly 50 ppm), whereas 1,1,1-TRI metabolism may be increased at an exposure similar to occupational exposure.     

Lethal midline granuloma (peripheral T-cell lymphoma) after lymphomatoid papulosis.

A Japanese woman with an 8-year history of lymphomatoid papulosis (LP) had lethal midline granuloma (LMG) develop at the age of 51 years. There were histologic similarities between LP and LMG seen in this patient. Surface phenotypic studies on nasal and cutaneous lesions demonstrated a population of T-cells expressing CD2, CD4, CD25, CD30, and histocompatibility antigen-DR (HLA-DR). Genotypic analyses of nasal and skin biopsy specimens disclosed a clonal rearrangement of the beta T-cell receptor gene with the same rearrangement pattern. These data indicate that this patient had LMG characterized by clonal peripheral T-cell lymphoma, which probably resulted from progression of the LP.     

Inhibition of N-nitrosodiethylamine- and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced tumorigenesis in A/J mice by green tea and black tea.

The effect of p.o. administration of tea on nitrosamine-induced carcinogenesis was investigated. Female A/J mice were given N-nitrosodiethylamine (NDEA) (10 mg/kg) p.o. once a week for 8 weeks and were killed 16 weeks after the last dose. More than 90% of the mice had forestomach and lung tumors. The animals had an average of 8.3 forestomach and 2.5 lung tumors/mouse. With 0.63 or 1.25% green tea infusion (12.5 g green tea leaves brewed with 1 liter of boiling water) as the sole source of drinking water for the entire experimental period, the pulmonary tumor incidence was decreased by 18 or 44%, and the tumor multiplicity was reduced by 36 or 60%, respectively. The treatments also decreased the forestomach tumor incidence by 18 or 26% and tumor multiplicity by 59 or 63%, respectively. Administration of 0.63 or 1.25% green tea infusion, either during the NDEA treatment period only or starting 1 week after the completion of NDEA treatment, also decreased the pulmonary tumor incidence and multiplicity and the forestomach tumor multiplicity. The inhibitory effects of green tea infusion were also observed in a similar experiment using a higher dosage of NDEA (20 mg/kg). Treatment of female A/J mice with a single dose (103 mg/kg) of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) resulted in the formation of pulmonary adenomas in almost all of the animals with an average of 9.3 tumors/mouse after 16 weeks. When 0.6% decaffeinated green tea or black tea extract was given during the NNK-treatment period, tumor multiplicity was reduced by 67 or 65%, respectively. When the tea extract was given after the NNK-treatment period until the end of the experiment, 0.6% green tea extract decreased the tumor incidence and multiplicity by 30 and 85%, respectively. In this protocol, 0.6% black tea extract reduced tumor multiplicity by about 63% but did not significantly affect the tumor incidence. The results clearly demonstrated an inhibitory action of green tea and black tea on nitrosamine-induced tumorigenesis.     

Epirubicin is equivalent to adriamycin in vitro against many cancer cells but more effective against gastric cancer cells.

We compared the cytotoxic effects of two anthracycline derivatives, epirubicin (EPI) and adriamycin (ADM), against human tumor cells in vitro. Various tumor specimens, obtained at surgery, included 57 liver, 19 lung, 16 gastric, 10 colorectal and 7 breast cancer specimens. These tumor cells were exposed to the same concentration of EPI or ADM for 3 days. The chemosensitivity of each tumor cell type to each drug was then assayed using the in vitro succinate dehydrogenase inhibition (SDI) test. Sensitivity to the treatment was defined as a 50% or greater reduction in the succinate dehydrogenase (SD) activity of the tumor cells, relative to that of the control (untreated) cells. Each cell type, except for gastric cancer cells, was equally sensitive to EPI and ADM. Gastric cancer cells were more sensitive to EPI than to ADM (P less than 0.05). The rate of coincidence, the sum of the co-sensitive and co-resistant rates of all the tumors, was quite high (90.8%). Thus, these findings indicate that EPI and ADM are equally cytotoxic to each tumor cell type, but EPI is more cytotoxic than ADM to gastric cancer cells. Since EPI is reported to be less cardiotoxic than ADM, EPI may replace ADM in cancer chemotherapy.     

Sensitizing effects of bradykinin on the heat responses of the visceral nociceptor.

1. Whether bradykinin (BK), which is known as an endogenous pain-producing substance, induces augmentation of the discharges of polymodal receptors evoked by heat stimulation was investigated in in vitro canine testis-superior spermatic nerve preparations. 2. The heat response was significantly augmented by pretreatments with BK at concentrations greater than 0.094 nM, whereas BK induced significant increases in the mean discharge rates at concentrations above 9.4 nM. Both effects increased in a concentration-dependent manner. The augmenting effect of BK on the heat response diminished within 10 min after application of BK, regardless of concentration. 3. When 9.4 nM BK was applied in a mixture with 940 nM NPC349, a B2 receptor antagonist, the averaged mean discharge rate evoked by BK and the averaged augmenting effect were both significantly suppressed compared with those induced by BK given alone. 4. The augmenting effect of BK on the heat response of polymodal receptors could be observed even in the absence of BK-evoked discharges per se in several cases in which low concentrations of BK or BK plus B2 antagonists were given. 5. These findings suggest that the augmenting effects of BK on the heat response depend on B2 receptor-mediated intracellular processes acting in parallel to, but not directly on, the impulse-generation mechanism of the heat response of the polymodal receptor.