Vitamin E and fatty acids in the grey seal (Halichoerus grypus)

Summary Vitamin E levels in serum, liver and blubber (subcutaneous adipose tissue) were determined for 66 male and female grey seals of varying age in the pupping colony on Sable Island in the Northwest Atlantic by high-performance liquid chromatography (HPLC). Fatty acid concentrations were determined for all blubber specimens. Adult males and pups had significantly higher levels of vitamin E and cholesterol in serum than females and juveniles. A close relationship between vitamin E and cholesterol in serum could be observed. Suckling pups had significantly higher levels of vitamin E in liver (191 mg·kg^–1) than juveniles and adults (21–41 mg·kg^–1). Levels of vitamin E in blubber showed an age-dependent increase, with the highest levels being found in adult males; overall, these levels were much lower than in man. Vitamin E levels in blubber and liver of lactating females were only half that of adult males. This might be due to an intensive transfer of vitamin E from mother to pup during lactation, a process which may also explain the much higher levels of vitamin E in serum and liver of nursing pups. The low levels of vitamin E in blubber of seals might be a result of its high percentage of unsaturated fatty acids (79%). Highest percentage was represented by 18:1, 16:1, 22:6 and 16:0. Pups had lower values of monounsaturated, and a higher percentage of saturated fatty acids compared to mothers.     

肝再生的调控及原癌基因表达

肝脏再生过程中受到多种体液因素的调控。肝细胞生长因子（ＨＧＦ）、肝刺激因子（ＨＳＳ）等对肝细胞有促分裂作用;转化生长因子β１（ＴＧＦβ１）等则具有抑制作用。此外,肝再生还需要去甲肾上腺素（ＮＥ）、胰岛素等辅助分裂原的存在,共同调节肝再生。肝细胞分裂增殖与原癌基因表达密切相关。肝细胞从静息期进入细胞周期,以及在整个细胞周期中,某些原癌基因有特征性的表达。     

A preliminary report on the use of transfer factor for treating stage D3 hormone-unresponsive metastatic prostate cancer

As conventional treatments are unsuccessful, the survival rate of stage D3 prostate cancer patients is poor. Reports have suggested the existence of humoral and cell-mediated immunity (CMI) against prostate cancer tumour-associated antigens (TAA). These observations prompted us to treat stage D3 prostate cancer patients with an in vitro produced transfer factor (TF) able to transfer, in vitro and in vivo, CMI against bladder and prostate TAA. Fifty patients entered this study and received one intramuscular injection of 2–5 units of specific TF monthly. Follow-up, ranging from 1 to 9 years, showed that complete remission was achieved in 2 patients, partial remission in 6, and no progression of metastatic disease in 14. The median survival was 126 weeks, higher than the survival rates reported in the literature for patients of the same stage.     

Efficacy of transfer factor in treating patients with recurrent ocular herpes infections

Recurrent ocular herpes is an insoluble problem for the clinician. As cellular immunity plays an important role in controlling herpes relapses, and other studies have shown the efficacy of HSV-specific transfer factor (TF) for the treatment of herpes patients, an open clinical trial was undertaken in 134 patients (71 keratitis, 29 kerato-uveitis, 34 uveitis) suffering from recurrent ocular herpetic infections. The mean duration of the treatment was 358 days, and the entire follow-up period 189121 before, and 64062 days after TF treatment. The cell-mediated immune response to the viral antigens, evaluated by the lymphocyte stimulation test (LST) and the leucocyte migration test (LMT) (P<0.001), was significantly increased by the TF treatment. The total number of relapses was decreased significantly during/after TF treatment, dropping from 832 before, to 89 after treatment, whereas the cumulative relapse index (RI) dropped, during the same period, from 13.2 to 4.17 (P<0.0001). No side effects were observed. It is concluded that patients with relapsing ocular herpes can benefit from treatment with HSV-specific TF.     

Effect of anti-herpes specific transfer factor

Using a blood cell separator, lymphocytes were collected from otherwise healthy convalescents suffering from herpetic infections. A specific anti-herpes dialysate (AH-DLE) was prepared from the lymphocytes, using standard procedures. Patients with recurrent herpetic infections were treated with a single dose of the dialysate, at the initial signs of herpetic infection (group A), with two doses (group B) or with three doses (group C). A total number of 37 patients (29 women, 8 men, age range 15–73 years) were treated. No improvement was observed in 7 patients (18.9%), whilst 7 patients did not manifest any exacerbation of their herpetic infection in the course of the one-year follow-up. The remaining 62.2% of the patients showed a marked improvement: decrease of the frequency and/or duration or relapses. Before AH-DLE administration, the mean number of herpes relapses in this group of patients was 12 p.a.. After therapy, the number of relapses decreased to 3.5 p.a.. No statistically significant difference was observed between groups A and B. The least favourable results were registered in group C. However, this group included 6 female patients extremely resistant to the previously therapeutic attempts, including inosiplex, non-specific DLE or acyclovir. Thus, even in this group, the therapy was successful in 50% of the patients.     

Antisporozoite Antibodies with Protective and Nonprotective Activities: In Vitro and In Vivo Correlations Using Plasmodium gallinaceum, an Avian Model

ABSTRACT. A correlation was observed between in vivo and in vitro activity of six monoclonal antibodies (mAb) against the major circumsporozoite protein of the avian malaria Plasmodium gallinaceum as follows. (1) Two mAb were protective, totally abrogating sporozoite infectivity to chicks, its natural host, in vivo; they caused 100% inhibition of sporozoite invasion (ISI) in vitro to SL-29 chicken fibroblasts and intense ISI to cultured chicken macrophages, as well as inhibited the exoerythrocytic development of sporozoites taken up by macrophages, the initial cell host of P. gallinaceum sporozoites. (2) Two mAb were partially protective in that they reduced sporozoite infectivity to chicks, caused partial ISI to SL-29 and macrophage cells and partial inhibition to the exoerythrocytic development of sporozoites in macrophages in vitro. (3) Two mAb were totally inactive in vivo although they both bound to the sporozoite antigens as detected by indirect immunofluorescence, western blot, and ELISA; they both failed to induce ISI or inhibit the exoerythrocytic development in macrophages. The possible participation of macrophages as the initial cell type involved in sporozoite destruction in the presence of anti-circumsporozoite antibodies is discussed.     

大阪鲫鱼两种卵黄蛋白免疫细胞化学的研究

以电泳提纯的卵黄脂磷蛋白和卵黄蛋白Ｌ制备兔抗两种蛋白的抗血清,采用ＰＡＰ法对性腺成熟雌性大阪鲫鱼的肝细胞和卵母细胞进行两种蛋白免疫细胞化学位研究。肝细胞的粗面内质网上有强烈的卵黄脂磷蛋白的阳性反应,特别是在线粒体的基质中也发现卵黄脂磷蛋白的阳性反应,而另外一种类似于卵黄高磷蛋白的卵黄蛋白－卵黄蛋白Ｌ在肝细胞的粗面内质网和线粒体均呈现阴性反应,提示卵黄脂磷蛋白的前体物质存在于肝细胞的粗面内质网和线粒     

Metabolic activation of unsaturated derivatives of valproic acid. Identification of novel glutathione adducts formed through coenzyme A-dependent and -independent processes

The ability of 2-n-propyl-4-pentenoic acid (Δ⁴-VPA) and 2-n-propyl-2(E)-pentenoic acid ([E]-Δ²-VPA), two unsaturated metabolites of valproic acid (VPA), to form reactive intermediates, deplete hepatic glutathione (GSH) and cause accumulation of liver triglycerides was investigated in the rat. With the aid of ionspray liquid chromatography-tandem mass spectrometry (LC-MS/MS), three GSH adducts were detected in the bile of Δ⁴-VPA-treated animals and were identified as 4-hydroxy-5-glutathion-S-yl-VPA-γ-lactone, 5-glutathion-S-yl-(E)-Δ³-VPA and 3-oxo-5-glutathion-S-yl-VPA. A fourth conjugate was identified tentatively as 4-glutathion-S-yl-5-hydroxy-VPA. Quantitative analysis of the corresponding N-acetylcysteine (NAC) conjugates in urine indicated that metabolism of Δ⁴-VPA via the GSH-dependent pathways accounted for approximately 20% of an acute dose (100 mg kg⁻¹ i.p.). In contrast, when rats were given an equivalent dose of (E)-Δ²-VPA, only one GSH adduct (5-glutathion-S-yl-(E)-Δ³-VPA) was detected at low concentrations in bile. In vitro experiments with rat liver mitochondria demonstrated that Δ⁴-VPA undergoes coenzyme A- and ATP-dependent metabolic activation in this organelle via the β-oxidation pathway to intermediates which bind covalently to proteins. When liver homogenates and hepatic mitochondria from rats injected with Δ⁴-VPA, (E)-Δ²-VPA or VPA were analyzed for GSH content, it was found that only Δ⁴-VPA depleted GSH pools significantly. Treatment of rats with Δ⁴-VPA and (to a lesser extent) VPA led to an accumulation of liver triglycerides, whereas (E)-Δ²-VPA had no measurable effect. It is concluded that Δ⁴-VPA undergoes metabolic activation by both microsomal cytochrome P-450-dependent and mitochondrial coenzyme A-dependent processes, and that the resulting electrophilic intermediates, which are trapped in part by GSH, may mediate the hepatotoxic effects of this compound. In contrast, (E)-Δ²-VPA is not transformed to any appreciable extent to reactive metabolites, which thus accounts for the apparent lack of hepatotoxicity of this positional isomer in the rat.     

Dietary zinc-methionine enhances mononuclear-phagocytic function in young turkeys

The ability of dietary zinc-methionine (Zn-Met) to enhance mononuclear-phagocytic function againstSalmonella arizona andenteritids was investigated in young turkeys. Feed/gain and body wt gain at 21 d of age were not affected by Zn-Met. The addition of 30 or 45 ppm Zn from Zn-Met to a Zn adequate diet significantly increased cutaneous basophil hypersensitivity to phytohemagglutinin-P. The clearance of intravenously administeredS. enteritidis from blood was not affected by 30 ppm of supplemental Zn from Zn-Met. However, 30 ppm Zn from Zn-Met increased the reduction of intravenously administeredS. arizona from spleen. Percentages of myeloid and mononuclear-phagocytic cells before and afterS. enteritidis infection were not affected by supplemental Zn-Met. Turkeys supplemented with Zn-Met showed enhanced in vitro phagocytosis ofS. enteritidis by Sephadex-elicited abdominal exudate cells. The phagocytosis ofS. arizona was unaffected by Zn-Met.     

Weak antioxidant defenses make the heart a target for damage in copper-deficient rats

Copper deficiency causes more salient pathologic changes in the heart than in the liver of rats. Although oxidative stress has been implicated in copper deficiency-induced pathogenesis, little is known about the selective toxicity to the heart. Therefore, we examined the relationship between the severity of copper deficiency-induced oxidative damage and the capacity of antioxidant defense in heart and liver to investigate a possible mechanism for the selective cardiotoxicity. Weanling rats were fed a purified diet deficient in copper (0.4 μg/g diet) or one containing adequate copper (6.0 μg/g diet) for 4 weeks. Copper deficiency induced a 2-fold increase in lipid peroxidation in the heart (thiobarbituric assay) but did not alter peroxidation in the liver. The antioxidant enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase were, respectively, 3-, 50- and 1.5-fold lower in the heart than in the liver, although these enzymatic activities were depressed in both organs by copper deficiency. In addition, the activity of glutathione reductase was 4 times lower in the heart than in the liver. The data suggest that a weak antioxidant defense system in the heart is responsible for the relatively high degree of oxidative damage in copper-deficient hearts.