Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry

BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination. METHODS: In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair- fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.      

Use of soluble recombinant TNF receptor to improve detection of TNF secretion in cultures of tumor infiltrating lymphocytes.

The accurate quantitation of picogram amounts of TNF is possible by ELISA and is useful in many areas of biomedical research, including studies of TNF release in vitro by stimulated lymphocytes and macrophages, and of serum levels in patients with cancer and sepsis. However, we show in this report that the detection of recombinant TNF standards by ELISA falls over time with incubation at 37 degrees C, and is further decreased when incubated with tumor infiltrating lymphocytes (TIL), making accurate quantitation difficult. We demonstrate that the soluble dimeric form of the TNF receptor can prevent this decrease, both in the presence and absence of TIL. In contrast, the soluble monomeric TNF receptor was much less effective in preventing this decrease. In addition, the dimeric but not the monomeric TNF receptor was found to inhibit bioactivity of TNF as measured by L929 cytotoxicity. The dimeric TNF receptor does not interfere with the detection of recombinant TNF standards by ELISA, and entirely stabilizes TNF levels incubated over 48 h at 37 degrees C in the presence and absence of TIL. This protection is specific, and the TNF receptor does not stabilize interferon-gamma. The dimeric form of the soluble TNF receptor has proven useful in detecting TNF released by TIL transduced with the TNF cDNA that are currently being used in studies of the gene therapy of cancer with TIL. The dimeric TNF receptor may also prove useful in the accurate quantitation of TNF released by stimulated lymphocytes and macrophages in vitro, and in the quantitation of serum TNF levels in patients.     

Evaluation of RGS4 as a candidate gene for schizophrenia.

Several studies have suggested that the regulator of G-protein signaling 4 (RGS4) may be a positional and functional candidate gene for schizophrenia. Three single nucleotide polymorphisms (SNP) located at the promoter region (SNP4 and SNP7) and the intron 1 (SNP18) of RGS4 have been verified in different ethnic groups. Positive results have been reported in these SNPs with different numbers of SNP combinatory haplotypes. In this study, these three SNP markers were genotyped in 218 schizophrenia pedigrees of Taiwan (864 individuals) for association analysis. Among these three SNPs, neither SNP4, SNP7, SNP18 has shown significant association with schizophrenia in single locus association analysis, nor any compositions of the three SNP haplotypes has shown significantly associations with the DSM-IV diagnosed schizophrenia. Our results fail to support the RGS4 as a candidate gene for schizophrenia when evaluated from these three SNP markers.     

Staging work-up and post-treatment surveillance of patients with melanoma

Strategies based on evidence are required to accurately stage and effectively follow patients with melanoma. The goal of staging is to define the extent of disease at the time of presentation to direct and assign prognosis. Patient surveillance is performed to assess treatment results and detect recurrences amenable to further treatment. Staging and surveillance require careful use of resources to be cost effective. This article addresses preoperative staging and post-treatment surveillance of patients with melanoma and outlines a method of follow-up based on available data.     

Systemic chemotherapy

The main use of systemic chemotherapy in metastatic melanoma remains palliative. Dacarbazine (dimethyl-1-triazeno imidazole-4-carboxamide [DTIC]) is the standard chemotherapy agent for advanced disease. The combination chemotherapy and biochemotherapy regimens have achieved higher response rates, but have not led to durable remission or improved survival. The field of systemic therapy remains in need of a more effective and less toxic treatment strategy.     

Sperm morphology analysis using strict criteria as a prognostic factor in intrauterine insemination

The objective of this study was to investigate the predictive value of Kruger's criteria for sperm morphology on intrauterine insemination (IUI) outcome. A total of 209 infertile patients underwent 244 IUI treatment cycles. These include 75 couples (80 cycles) with teratozoospermia and 134 couples (164 cycles) with unexplained infertility. The pregnancy rates per IUI cycle were 3.8 (1/26), 18.5 (10/54) and 29.9% (49/164) in patients with sperm morphology with <4, 4-9 and >9% normal forms, respectively, according to Kruger's criteria. A statistical difference in outcome was seen between couples with <4 and >9% normal forms (p = 0.005). Although the difference in pregnancy rates between those with 4-9 and <4% normal forms was not statistically significant, the pregnancy rate for those with 4-9% normal forms was acceptable and still higher than in those with <4% normal forms. Therefore, we suggest that IUI is a reasonable first-line therapy for patients with sperm morphology >4% normal forms, while couples with <4% normal forms should be advised to use in vitro fertilization with intracytoplasmic sperm injection instead of IUI.     

High triglyceride level is associated with severe coronary artery disease in hypertensive subjects

Background. The contribution of triglycerides (TG) to the extent of coronary artery disease (CAD) in hypertensive patients remained unclear. Methods. Consecutive 821 (aged 64.5±11.5 years, 482 males) hypertensive patients undergoing coronary angiography were included. The relationship of TG levels (<150 vs. ≥150 mg/dl) to the extent of CAD in all patients was examined by multiple logistic regression, adjusting for other CAD risk factors. In the lipid group, low levels of HDL were also adjusted. Results. Higher levels of TG were found in subjects with severe CAD compared to those with no or minimal CAD. The adjusted odds ratios for high levels of TG in the severe CAD subgroup versus the no or minimal CAD subgroup were 5.20 (95% CI, 3.13 to 8.63) in all patients and 7.51 (95% CI, 3.19 to 17.65) in the lipid group. Conclusions. High levels of TG are strong clinical markers of greater extent of CAD in hypertensive subjects undergoing coronary angiography. The results may have clinical relevance for physicians in therapeutic decision making.