Oxidative stress and immune response in eumenorrheic underweight patients

Malnutrition is known to induce a state of immunodeficiency and a predisposition to death from infectious diseases. During fasting or starvation, it appears that oxidative stress is decreased. The goal of our study was to assess the interrelation between nutritional factors, oxidative stress and immune response. The malondialdehyde (MDA)-marker of lipid peroxidation, white blood cell count, differential count and hormonal status (FSH, LH, and cortisol) were followed in eumenorrheic underweight patients. MDA was significantly lower and lymphocyte count was significantly increased in eumenorrheic underweight patients as compared to normal weight patients. Gonadal and adrenal axes were found normal in eumenorrheic underweight patients. Body mass index was positively correlated with MDA and negatively correlated with lymphocyte count. Low levels of lipid peroxidation and non-suppressed immune function in underweight patients may be explained by an increased sensitivity to leptin but further studies are requested.     

Serum p53 antibodies in drainage blood from the azygos vein in patients with esophageal carcinoma

BACKGROUND: Serum p53 antibodies (p53-Ab) have been detected in some cancers. The possible correlation between serum p53-Ab levels in drainage blood from the azygos vein in patients with esophageal carcinoma and prognosis was investigated. MATERIALS AND METHODS: Serum p53-Ab levels were examined in both the peripheral and azygos veins of 57 patients, and in the peripheral vein of 17 healthy volunteers. Serum p53-Ab levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The positive rate of serum p53-Ab in the peripheral vein of the patients was 31.6%, significantly higher than that of the normal volunteers. There were no significant correlations between the clinicopathological features and the serum p53-Ab in either the peripheral or azygos veins. Serum p53-Ab levels in either vein did not correlate with prognosis in the univariate survival analysis, although the levels in the two veins were significantly correlated. CONCLUSION: Serum p53-Ab levels in the azygos vein did not reflect the tumor status or prognosis more directly or accurately than those in the peripheral vein, since levels in the two veins were similar. Therefore, measurement of serum p53-Ab in the azygos vein does not appear to be necessary.     

Ameliorating effect of FK614, a novel nonthiazolidinedione peroxisome proliferator-activated receptor gamma agonist, on insulin resistance in Zucker fatty rat

Effect of 3-(2,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3H-benzimidazole-5-carboxamide (FK614), a novel nonthiazolidinedione peroxisome proliferator-activated receptor (PPAR) gamma agonist, on glucose tolerance and insulin resistance in peripheral tissues and in liver using Zucker fatty rats (genetically obese and insulin-resistant) was evaluated and compared to other insulin sensitizers. FK614 (0.32, 1 and 3.2 mg/kg), two thiazolidinedione PPAR gamma agonists, rosiglitazone (0.1, 0.32, 1 and 3.2 mg/kg) and pioglitazone (1, 3.2 and 10 mg/kg), and a biguanide, metformin (320 and 1000 mg/kg), were orally administered to Zucker fatty rats once a day for 14 days. Zucker fatty rats treated with FK614 and rosiglitazone were subjected to evaluation by oral glucose tolerance test. Ameliorating effect of each compound on peripheral and hepatic insulin resistance was evaluated using a euglycemic-hyperinsulineamic clamp procedure. FK614 and rosiglitazone dose-dependently improved impaired glucose tolerance in Zucker fatty rats. In addition, FK614 dose-dependently ameliorated peripheral and hepatic insulin resistance in Zucker fatty rats, with the degree of its effect in peripheral tissues almost equivalent to that in liver when compared at each dose tested. Similar data indicating ameliorating effects on insulin resistance was obtained for rosiglitazone and pioglitazone. Metformin showed less potent effects than other insulin sensitizers and its effect in liver tended to be greater than that in peripheral tissues. These findings suggest clinical potential for FK614 as a treatment of type 2 diabetes, acting by ameliorating insulin resistance both in peripheral tissues and liver.     

Cocaine-induced thrombotic vasculopathy

Cocaine has been associated with a number of cutaneous manifestations, and most reports in the literature have described cocaine-induced vasculitis. However, not all reactive patterns secondary to cocaine use are vasculitic in nature. Recently, there has been a disturbing trend of "cutting" cocaine with pharmacologically active substances, the most common being levamisole. This agent is known to cause serious adverse effects including agranulocytosis and cutaneous eruptions. The authors describe a 52-year-old woman who acutely developed an extensive bullous rash in the lower extremities after she snorted cocaine. The clinical, hematological and serological findings were suggestive of levamisole-induced vasculitis, but histopathology of the skin showed thrombogenic vasculopathy with no inflammatory infiltrate. A skin biopsy is an essential component in the diagnosis of cocaine-related syndromes and can aid in the distinction from true autoimmune vasculitis.     

Exploiting nutrient transporters at the blood-brain barrier to improve brain distribution of small molecules

The blood-brain barrier (BBB) is a major physiological barrier for drugs that target CNS receptors or enzymes. Several methods exist by which permeability to the CNS can be increased, one of which is using native nutrient transporters to carry these drugs through the endothelial cells of the BBB. In this review, we focus on work that characterizes the use of nutrient transporters of the BBB in delivering drugs to the CNS.     

Farm-scale evaluation of the impacts of transgenic cotton on biodiversity, pesticide use, and yield

Higher yields and reduced pesticide impacts are needed to mitigate the effects of agricultural intensification. A 2-year farm-scale evaluation of 81 commercial fields in Arizona show that use of transgenic Bacillus thuringiensis (Bt) cotton reduced insecticide use, whereas transgenic cotton with Bt protein and herbicide resistance (BtHr) did not affect herbicide use. Transgenic cotton had higher yield than nontransgenic cotton for any given number of insecticide applications. However, nontransgenic, Bt and BtHr cotton had similar yields overall, largely because higher insecticide use with nontransgenic cotton improved control of key pests. Unlike Bt and BtHr cotton, insecticides reduced the diversity of nontarget insects. Several other agronomic and ecological factors also affected biodiversity. Nevertheless, pairwise comparisons of diversity of nontarget insects in cotton fields with diversity in adjacent noncultivated sites revealed similar effects of cultivation of transgenic and nontransgenic cotton on biodiversity. The results indicate that impacts of agricultural intensification can be reduced when replacement of broad-spectrum insecticides by narrow-spectrum Bt crops does not reduce control of pests not affected by Bt crops.     

Presynaptic regulation of extracellular dopamine levels in the medial prefrontal cortex and striatum during tyrosine depletion

Rationale

Available neurochemical probes that lower brain dopamine (DA) levels in man are limited by their tolerability and efficacy. For instance, the acute lowering of brain tyrosine is well tolerated, but only modestly lowers brain DA levels. Modification of tyrosine depletion to robustly lower DA levels would provide a superior research probe.

Objectives

The objective of this study was to determine whether the subthreshold stimulation of presynaptic DA receptors would potentiate tyrosine depletion-induced effects on extracellular DA levels in the medial prefrontal cortex (MPFC) and striatum of the rat.

Methods

We administered quinpirole, a predominantly DA type 2 (D2R) receptor agonist, into the MPFC and striatum by reverse dialysis. A tyrosine- and phenylalanine-free neutral amino acid mixture [NAA(?)] IP was used to lower brain tyrosine levels. DA levels in the microdialysate were measured by HPLC with electrochemical detection.

Results

Quinpirole dose-dependently lowered DA levels in MPFC as well as in the striatum. NAA(?) alone transiently lowered DA levels (80 % baseline) in the striatum, but had no effect in MPFC. The co-administration of NAA(?) and a subthreshold concentration of quinpirole (6.25 nM) lowered DA levels (50 % baseline) in both the MPFC and striatum. This effect was blocked by the mixed D2R/D3R antagonist haloperidol at IP doses that on their own did not affect DA levels (10.0 nmol/kg in the MPFC and 0.10 nmol/kg in the striatum).

Conclusions

Pharmacological stimulation of inhibitory D2R receptors during tyrosine depletion markedly lowers the extracellular DA levels in the MPFC and striatum. The data suggest that combining tyrosine depletion with a low dose of a DA agonist should robustly lower brain regional DA levels in man.     

Assessment of the potential of a boron-fructose additive in counteracting the toxic effect of Fusarium mycotoxins

Trichotecenes are mycotoxins produced by Fusarium sp., which may contaminate animal feeds and human food. A feeding trial was conducted to evaluate the effect of a fusarotoxin-contaminated diet, and to explore the counteracting potential of a calcium fructoborate (CFrB) additive on performance, typical health biochemistry parameters and immune response in weaned pigs. A naturally contaminated maize, containing low doses of deoxynivalenol, zearalenone, fumonisins and T-2/HT-2 toxins (1790, 20, 0·6 and 90 parts per billion), was included in a maize-soyabean meal diet, and given ad libitum to eight weaned piglets (two groups: four pigs/group) for a period of 24 d. CFrB was administered to one of the contaminated groups and to another four piglets as a daily supplement, following the manufacturer's recommendation. A decrease in performance was observed in contaminated animals at this concentration of feed toxins, which was ameliorated by the dietary CFrB supplementation. Fusarium toxins also altered the pig immune response by increasing (P < 0·05) the ex vivo peripheral blood mononuclear cell proliferation (111·7 % in comparison with control), the respiratory burst of porcine granulocytes (15·4 % for responsive cells v. 5·1 % for unstimulated cells and 70·95 v. 22·65 % for stimulated cells, respectively), the percentage of peripheral T, CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) subsets and the synthesis of IL-1β, TNF-α and IL-8 (123·8, 217·1 and 255·1 %, respectively). The diet containing the CFrB additive reduced these exacerbated cellular immune responses induced by Fusarium toxins. However, consumption of CFrB did not counteract the effect of mycotoxins on biochemistry parameters, and increased plasma IgM and IgG of contaminated pigs.