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Neuronal cells usually utilize glucose as a principal metabolic fuel and monocarboxylates including lactate and pyruvate are alternative energetic substrates in the central nervous system. In the present study, we investigated the synaptic utilization of lactate/pyruvate in the hippocampal slices from adult and aged guinea pig brains. Synaptic activity was estimated in terms of the amplitude of field population spikes (PS) recorded in the granular cell layer of the hippocampal dentate gyrus. Replacement of extracellular glucose with lactate suppressed the synaptic activity, followed by spontaneous recovery of PS amplitudes in the slices from 3-4-weeks old guinea pigs. In the presence of chelerythrine, an inhibitor of protein kinase C (PKC), substitution of lactate for glucose did not maintain synaptic activity. In contrast, application of H-89 and lavendustin A. inhibitors of cAMP-dependent protein kinase and tyrosine kinase, respectively, did not influence the synaptic utilization of lactate. In the hippocampal dentate gyrus from 24-months old guinea pigs, extracellular lactate did not sustain the synaptic function. These results indicate that the PKC-dependent metabolic process is involved for the synaptic utilization of lactate in the adult brain, and that lactate metabolism in synapse is impaired in the aged brain.

In Alzheimer's disease, brain glucose metabolic ratio decreases, whereas the brain lactate metabolic ratio increases. To investigate possible synaptic dysfunction in Alzheimer's disease, we examined the effects of exogenous glucose deprivation and replacement of glucose with lactate on the synaptic transmission, synaptic plasticity, and the morphological integrity of hippocampal neurons. Synaptic activity was estimated by the amplitude of the population spike (PS) recorded in the granular cell layer in the hippocampal slices from guinea pig and rat. Exogenous glucose deprivation caused the immediate depression of PS. Replacement of glucose with lactate induced transient decrease of PS, followed by spontaneous recovery of synaptic transmission. Neural activity recovered from transient glucose deprivation became resistant to the replacement of glucose with exogenous lactate. Glucose-supported synaptic transmission exhibited approximately 140% enhancement of PS (LTP). However, lactate-supported synaptic activity yielded approximately 110% potentiation of PS. Effects of exogenous glucose and lactate on the cell viability were examined by the propidum iodide uptake and LDH release in the organotypic hippocampal slice cultures. Hippocampal slice cultures incubated in medium containing 10 mM lactate suppressed the cell death during 48 h observation as well as those in the 10-30 mM glucose containing medium. These results indicate that lactate can sustain the neural transmission and support the morphological integrity of hippocampal neurons, but failed to induce LTP, which could at least in part, cause the memory impairment in Alzheimer's disease.

Objective: To investigate the value of screening for early diagnosis of primary liver cancer (PLC)., Methods: A total of 18,816 persons, who were high-risk population of PLC, were divided randomly to allocated screening group and control group. In the screening group every individual was checked up by serum AFP test and ultrasound every 6 months but those in the control group were not., Results: Eighty-six patients with PLC were detected in the screening group, while 51 patients with PLC occurred in the control group. In patients from the screening group 60.5% were in the early stage, 45.3% of them were with small liver cancer. However, in the control group the figures were 0 and 0 respectively. In the screening group, 57 patients with PLC were detected by follow-up screening every 6 months, 77.2% patients of this series were in the early stage. However in the screening group the other 29 patients with PLC were detected by screening but they were not followed up every 6 months. Early-stage patients were only 27.6% in this series., Conclusion: This suggests mass screening, especially continual screening every 6 months in fixed population can diagnose PLC early.

The relationship between streptomycin (SM) susceptibility and rpsL mutations of Mycobacterium tuberculosis strains was studied. Of 18 clinically isolated SM-resistant M.tuberculosis strains, mutation was suspected in 9 strains (50%) with SM MICs of > or = 256 micrograms/ml by PCR-single strand conformation polymorphism targeting rpsL gene. On the other hand, using PCR-direct sequence method, amino acid substitution caused by single nucleotide point mutation in rpsL gene was demonstrated in 11 out of 18 strains (61%). The same amino acid substitution at codon 43 (Lys-->Arg) was observed in all 11 strains with SM MICs of > or = 256 micrograms/ml. In addition, PCR products obtained from these 11 strains could not be cut by a restriction enzyme, Mbo II, while H37Rv strain and the other 32 strains with SM MICs of < 256 micrograms/ml were cut into 2 fragments. In conclusion, our results suggest that highly SM-resistant M.tuberculosis strains with MICs of > or = 256 micrograms/ml could be rapidly and easily detected by the restriction enzymatic method.

Pleural fluids obtained from 26 patients with tuberculous pleurisy (T-group), 11 with parapneumonic pleurisy (B-group) and 21 with malignant pleurisy (M-group) were tested for their biologic parameters and cytokine concentrations. 1) The average age of T-group was over 10 years lower than that of M-group with a statistically significant difference. 2) The average CRP value of B-group and the positivity on PPD skin test of T-group were higher than those of the other groups, respectively. 3) Yellowish pleural fluids were mainly observed in T- and B-group, while bloody pleural fluids were mostly seen in M-group with a statistically significant difference. The average total protein amount and adenosine deaminase value in pleural fluid significantly increased in T-group. The percentage of polymorphonuclear leukocytes showed a significant increase in B-group, while lymphocytes significantly increased in T-group with a statistically significant difference. 4) Although no significant difference in concentrations of IL-1 beta, IL-2, IFN-gamma and TNF-alpha in serum was noticed among the three groups, the average concentrations of IFN-gamma and TNF-alpha in pleural fluid in T-group were significantly higher than those in the other groups. 5) TNF-alpha-mRNA of mononuclear cells in pleural fluid was strongly expressed in 3 out of 11 patients of T-group, while no expression was observed in 6 patients of M-group. In conclusion, the measurement of concentrations of two kinds of cytokines in pleural fluid, IFN-gamma and TNF-alpha, may be clinically useful for the differential diagnosis of tuberculous pleurisy from parapneumonic pleurisy and malignant pleurisy.