Modulation of infection-induced inflammation and locomotive deficit and longevity in senescence-accelerated mice-prone (SAMP8) model by the oligomerized polyphenol Oligonol.

Oligonol is produced from the oligomerization of polyphenols (typically proanthocyanidin from a variety of fruits such as lychees, grapes, apples, persimmons, etc.) and contains catechin-type monomers and oligomers of proanthocyanidins. The ability of Oligonol to affect infection-dependent eye inflammation, locomotion and longevity in senescence-accelerated prone mice (SAMP8) (a model of senescence acceleration and geriatric disorders with increased oxidative stress and neuronal deficit) was investigated. Oligonol (60mg/kg) significantly modulated the extent of inflammation scores in the eye of SAMP8 mice. Examination of the mice indicated infection with mouse hepatitis virus and pinworm (Syphacia obvelata) in both males and females and with the intestinal protozoa (trichomonad) in males. A comparison of the two groups (using log-rank test) and the difference in the mean life span between groups (using Student's t-test) indicated significant differences in survival (p=0.043) and the mean life span (p=0.033) in male SAMP8 mice. Oligonol increased the mean life span and this was statistically significant. In the open-field locomotive test, the 7-week-old SAMP8 mice crossed more than 40 partitioned lines in 1min. At 48-week-old control untreated male SAMP8 crossed 2 lines. The Oligonol-treated 48-week-old male SAMP8 mice crossed 17 lines however. The improved locomotive activity was statistically significant even after 36weeks in the Oligonol-treated male SAMP8 but this was not the case throughout the time course of the study in the Oligonol-treated female SAMP8. Thus Oligonol treatment to SAMP8 mice modulated the severity of infection-dependent inflammation, prolonged life-span and significantly improved locomotive activity indicating potential benefit to aging-associated diseases such as Alzheimer's or Parkinson's diseases. This presents potential for further research to define infection-dependent inflammation associated with degenerative conditions and the molecular mechanism of dietary antioxidant protection.     

A case of corticobasal degeneration presenting with visual hallucination]

We report a case of corticobasal degeneration (CBD) presenting with visual hallucination. A 65-year-old woman showed clumsiness of the left hand. Clinical symptoms slowly progressed to include rigidity, which was left side dominant, limb-kinetic apraxia of the left hand, disorder of construction and dressing, unilateral spatial neglect, cortical sensory loss and alien limb phenomenon. Cranial MRI showed atrophy of the parietal and medial aspect of the frontal lobes, which was more severe on the right than on the left. SPECT images showed hypoperfusion in the parietal, frontal and temporal lobes, which were similarly more severe on the right than on the left. We diagnosed the patient as having CBD based on the clinical symptoms. Two years' later, she developed recurrent visual hallucinations that were typically well formed and detailed. Since patients with CBD generally do not experience visual hallucination, this case is considered the very rare and indicates the possibility that visual hallucination may be one of the clinical symptoms of CBD.     

Small extra-adrenal pheochromocytoma causing severe hypertension in an elderly patient.

We report the case of a 67-year-old woman with severe hypertension caused by an extra-adrenal pheochromocytoma. The tumor was detected by 131I metaiodobenzylguanidine scintigraphy and it was found to be small (2 cm ?) by enhanced CT. After the extirpation of the tumor, the blood pressure of the patient immediately normalized. It should be taken into account that a small extra-adrenal pheochromocytoma can be one of the causes of secondary hypertension in elderly patients. Since small extra-adrenal pheochromocytomas are difficult to detect, it is also important to perform suitable examinations to establish the diagnosis. Furthermore, we emphasize the importance of an accurate diagnosis in elderly patients with pheochromocytoma, for they often have less symptomatology and more severe cardiovascular complications due to refractory hypertension than younger patients.     

Monitoring myocardial reperfusion injury with NADH fluorometry.

Using NADH fluorometry to monitor myocardial metabolism, the mechanism of reperfusion injury was investigated after the delivery of an experimental reperfusate. Using an isolated working heart preparation, rat hearts underwent 15 min of global ischemia at 37 degrees C. Following the ischemic insult, an oxygenated enriched reperfusion solution was given for 5 min. The hearts were then returned to a working state and aortic flow recorded to evaluate recovery. NADH levels were monitored throughout the experiment with a fluorometer and glycogen, AMP, ADP, and ATP were measured biochemically pre- and postischemia, after reperfusion and after recovery. In this study, reperfusion injury was best abated by an enriched reperfusate. Our results indicate the mechanism for this amelioration is not high-energy phosphate replenishment. Rather, as indicated by NADH fluorescence, the hearts attain an intermediate level of metabolism that permits glycogen to be restored and functional recovery to be improved.     

Interleukin-4 as a potent down-regulator for human alveolar macrophages capable of producing tumour necrosis factor-alpha and interleukin-1.

The effects of recombinant human interleukin-4 (IL-4) on the production of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha) by human alveolar macrophages (AM) and autologous peripheral blood monocytes (PBM) in response to lipopolysaccharide (LPS) were examined. AM and PBM were obtained by bronchoalveolar lavage and centrifugal elutriation, respectively, from healthy donors. The production of IL-1 (alpha and beta) and TNF alpha by human AM and PBM were quantitated by enzyme immunoassays (EIA). When activated with LPS, AM secreted much more TNF alpha, but less IL-1 beta than PBM. The production of IL-1 (alpha and beta) by activated AM and autologous PBM was suppressed dose-dependently by IL-4. The inhibitory effect of IL-4 was greatest when it was added to AM or PBM simultaneously with LPS or within 3 h after LPS. The suppressive effect of IL-4 was completely neutralized by pretreatment with rabbit anti-IL-4 antiserum. IL-4 also suppressed the production of IL-1 and TNF alpha by monocyte-derived macrophages. As measured by thymocyte co-stimulation assay, the production of cell-associated IL-1 was inhibited by coculture of AM plus LPS with IL-4. Northern blot analysis showed suppression by IL-4 of expression of messenger ribonucleic acid (mRNA) for IL-1 and TNF alpha in LPS-stimulated AM. We conclude that IL-4 is a potent down-regulator for human alveolar macrophages capable of producing IL-1 and TNF alpha.     

Renal responses to magnesium lithospermate B

Renal responses to magnesium lithospermate B isolated from Salviae miltiorrhizae radix were examined in normal rats. Urinary sodium, potassium, prostaglandin E2 and kallikrein excretion was significantly increased after magnesium lithospermate B administration, whereas excretion of urinary 6-keto-prostaglandin F1 alpha and thromboxane B2 was unchanged. Rats administered with the drug also revealed a slight elevation of plasma renin activity and the levels of angiotensins I and II. Plasma aldosterone was decreased slightly. No significant changes were observed in angiotensin-converting enzyme or blood pressure.     

Clinicopathologic Study of Angiogenesis in Japanese Patients with Breast Cancer

p = 0.0007) and tumor necrosis (TN) (HMC: p = 0.0050). Univariate analysis showed that AMC or HMC was a statistically significant predictor of overall survival in all patients ( p = 0.0086 and p = 0.0307, respectively). Multivariate analysis showed that AMC was an independent predictor of node status when we fitted a model with node status, BVI, and either AMC or HMC; but HMC was not independent. However, when we fitted a model including all 11 of the other indicators and AMC or HMC, the node status, HG, and LI were independent predictors, but AMC and HMC were not. Although AMC was a better method than HMC for evaluating angiogenesis, we cannot confirm angiogenesis as a significant independent prognostic factor associated with long-term survival in Japanese breast cancer patients.     

Effect of intravenous alpha-difluoromethylornithine on the polyamine levels of normal tissue and a transplantable fibrosarcoma

The effect of a continuous i.v. infusion of alpha-difluoromethylornithine (DFMO) on the polyamine metabolism of tumor and normal host tissue was determined. Non-tumor-bearing Fischer 344 rats or rats bearing a transplantable fibrosarcoma received continuous infusions of DFMO through a central venous catheter at three dose levels. Treatment with DFMO resulted in a time- and dose-dependent, cytostatic effect on the growth of the tumor. In fibrosarcoma-bearing rats the tumor putrescine levels were reduced after 6 and 12 days of DFMO treatment. Tumor spermidine levels were consistently reduced after 6 and 12 days of treatment with the reduction being dose dependent. The decrease in tumor ornithine decarboxylase activity was dose dependent. Erythrocyte putrescine levels were decreased in tumor- and non-tumor-bearing rats, suggesting that DFMO reduces the tumor contribution to the erythrocyte pool. Erythrocyte spermidine levels of fibrosarcoma- and non-tumor-bearing rats were elevated at the lower DFMO doses administered for 12 days but returned to normal as the dose was increased. Erythrocyte spermine levels were elevated in both groups of rats at all DFMO doses. Although normal host tissue weights were not affected by treatment with DFMO, the putrescine and spermidine levels of liver, spleen, and kidney and ornithine decarboxylase activity of the liver and kidney were decreased. These data demonstrate that i.v. DFMO has a cytostatic effect toward a rapidly growing fibrosarcoma associated with the depletion of both tumor putrescine and spermidine levels.