Literature regarding the biochemistry of aluminum and eight similar ions is reviewed. Close and hitherto unknown similarities were found. A hypothetical model is presented for the metabolism, based on documented direct observations of Al3+ and analogies from other ions. Main characteristics are low intestinal absorption, rapid urinary excretion, and slow tissue uptake, mostly in skeleton and reticuloendothelial cells. Intracellular Al3+ is probably first confined in the lysosomes but then slowly accumulates in the cell nucleus and chromatin. Large, long-lived cells, e.g., neurons, may be the most liable to this accumulation. In heterochromatin, Al3+ levels can be found comparable to those used in leather tannage. It is proposed that an accumulation may take place at a subcellular level without any significant increase in the corresponding tissue concentration. The possible effects of this accumulation are discussed. As Al3+ is neurotoxic, the brain metabolism is most interesting. The normal and the lethally toxic brain levels of Al3+ are well documented and differ only by a factor of 3-10. The normal brain uptake of Al3+ is estimated from data on intestinal uptake of Al3+ and brain uptake of radionuclides of similar ions administered intravenously. The uptake is very slow, 1 mg in 36 years, and is consistent with an assumption that Al3+ taken up by the brain cannot be eliminated and is therefore accumulated. The possibility that Al3+ may cause or contribute to some specific diseases, most of them related to aging, is discussed with the proposed metabolic picture in mind.

Metabolism and possible health effects of aluminum.

Viability measurements in mammalian cell systems.

In proliferating cell populations, the inability to reproduce indefinitely is the only relevant criterion to assess cell lethality. The in vitro colony formation technique (CF) used to determine reproductive death is, however, too slow and has several technical limitations. For finding suitable, more rapid techniques that assessed drug-induced cell killing, a human lymphoma cell line was exposed in vitro to increasing concentrations of adriamycin, bleomycin, and 1,3-bis(2-chloroethyl)-1-nitrosourea for 1 hr. Survival was assayed immediately after treatment and at regular intervals thereafter. Data from CF were compared to those resulting from the following tests: doubling time, labeling index, dye exclusion, 51Cr release, and rate of [3H]thymidine uptake (scintillation index). Dye exclusion and 51Cr release failed to demonstrate any killing effect for the 3 drugs. The percentage of killing calculated from doubling time determinations, although dose dependent, failed to correlate with CF. Scintillation and labeling index values displayed similar temporal fluctuations but were not clearly dose dependent and did not correlate with CF. Thus, CF appears as the most reliable, dose-dependent index of cell lethality. Tests that measure metabolic death grossly overestimate or underestimate killing activity induced by 3 of the most effective antitumor drugs.

https://cancerres.aacrjournals.org/content/canres/36/7_Part_1/2182.full.pdf

Comparison of in vitro methods to determine drug-induced cell lethality.

Neutrophils are the most abundant white blood cells and are indispensable for host defense. Recently, they have also been implicated in immune regulation and suppression. The latter functions seem hard to reconcile with the widely held view that neutrophils are very short-lived, with a circulatory half-life of <7 h. To reopen the discussion on the average neutrophil half-life, we review and discuss experiments performed in the 1950s, 1960s, and 1970s, as well as recent in vivo labeling experiments. We reappraise the current knowledge on neutrophil half-lives, including their production in the bone marrow, their residency in the circulation and marginated pool, and their exit from the circulation.

https://jlb.onlinelibrary.wiley.com/doi/pdf/10.1189/jlb.1112571

What's your age again? Determination of human neutrophil half-lives revisited.

Grip strength, ring size, duration of morning stiffness, and the number of tender joints improved significantly in 9 patients with severe rheumatoid arthritis during prolonged continuous removal of thoracic duct lymphocytes through a surgical fistula. There was no improvement in 4 subjects in whom surgery failed to establish satisfactory lymph drainage. Reinfusion of unlabeled or 51Cr-labeled autologous lymphocytes resulted in transient exacerbation of disease activity in 3 subjects. Following reinfusion, some 51Cr-labeled lymphocytes could be found in the inflamed synovium and synovial fluid by autoradiography, and radioactivity was detected over the joints by surface counting of gamma radiation. Active rheumatoid arthritis recurred in all subjects at variable intervals after cessation of lymph drainage. These findings are compatible with the hypothesis that some of the lymphocytes in the thoracic duct lymph are essential for the continued activity of the inflammation associated with rheumatoid arthritis.

Peter M. Ronai

Papers

The elution of 51Cr from labelled leukocytes--a new theory.

High resolution autoradiography with 51Cr

51Cr labelling of mouse peritoneal cells: selective labelling of peritoneal macrophages

Detection of Allograft Sensitivity in Mice Using 51Cr-Labelled Peritoneal Macrophages