Biology of aging. Current state of knowledge

The nature of the primary aging processes has yet to be defined. Mortality and aspects of longevity (eg, life expectancy) do not provide significant information about aging. The maximum life span potential of a species does provide information about the comparative rate of aging between species, however, and also is a good marker for evaluating interventions aimed at modulating the rate of aging in a particular species. Physiological deterioration occurs with age, but it is not known how much is due to aging per se and how much is secondary to age-related disease and life-style. There are similar reservations about the changes in body composition that have been noted with increasing age. Many diseases are age related in terms of prevalence, but how these diseases relate to the primary aging processes remains to be defined. Finally, many claims have been made concerning interventions that will retard the aging processes; of these, only food restriction in rodents has been unequivocally shown to retard the aging processes of a mammalian species.     

In vivo electrochemical demonstration of potassium-evoked monoamine release from rat cerebellum

In vivo electrochemical methods were employed to study the potassium (K⁺-evoked release of monoamines from the cerebellum of the chloral hydrate anesthetized rat. K⁺-evoked releases were elicited using micropipette-Nafion-coated graphite epoxy electrode arrays in the granule/Purkenje cell layer, molecular layer, and white matter. These recorded releases were generally found to be reversible, moderately dose-dependent, and reproducible. However, the temporal dynamics of the releases were different for the cell layer versus molecular layer records. Releases were infrequently observed in cerebellar white matter, an area which is relatively devoid of monoamine containing terminals. The signals recorded from the cell and molecular layers were significantly attenuated by pretreatment with nomifensine, a potent catecholamine reuptake blocker, significantly prolonged the K⁺-evoked signals observed in both the granule/Purkenje cell and molecular layers. These data, taken together with earlier reports on the electrophysiological responses to activation of cerebellar noradrenergic inputs, support the conjecture that in vivo electrochemical recording methods have the sensitivity and spatial resolution for studies of functional monoamine release from brain regions that have a diffuse or laminated monoamine innervation.     

Binocular contrast detection with unequal monocular illuminance

Binocular summation was measured in eight normal subjects by means of psychometric functions for contrast detection. An average 47% increase in binocular over monocular performance was obtained. Our data agreed with the simple summation model of Signal Detection Theory (Legge, 1984). Binocular psychometric functions were also measured when the sensitivity of one eye was decreased by means of a 1.0 neutral density (ND) filter. We found that binocular detectability in this case was reduced to below that of the better eye. This binocular inhibition was seen in all subjects. The slope of a contrast detection function gives a measure of the rate of change in detectability with contrast. If the slopes of two functions are equal, then the difference in detectability between these functions remains constant for all the contrast values used. When the slopes of the measured functions were analysed, no significant differences were found under any of the testing conditions. This indicates that the magnitude of summation (with equal monocular sensitivities), and of inhibition (with unequal monocular sensitivities), remains constant across the range of stimulus contrasts. The clinical implications of binocular inhibition are discussed.     

A Leydig cell stimulatory factor produced by human testicular tubules

It is demonstrated that tubular fragments derived from human testes and cultured in vitro produce a factor that stimulates the production of testosterone by human interstitial cells and by Percoll-purified Leydig cells from rat and mouse origin. The active principle in the conditioned media is a thermo-labile and trypsin-sensitive protein with an MW greater than 10,000. The factor is active in the presence as well as in the absence of maximally effective concentrations of LH and its activity is not accompanied by measurable changes in cAMP production. There are several points of analogy between this factor and a Leydig cell stimulatory protein produced by rat Sertoli cells. Molecular weight fractionation of spent media from human testicular tubules using an Amicon ultrafiltration system results in a 38- to 102-fold increase in Leydig cell stimulatory activity in a fraction corresponding to a molecular weight of 10,000 up to 30,000. These figures are comparable to those observed after molecular weight fractionation of spent media from rat Sertoli cells. Dose-response curves with partially purified preparations from human and rat origin yield parallel dose-response curves. In rat Sertoli cells as well as in human testicular tubules, the production of the active principle is stimulated by FSH and dibutyryl cAMP. Finally, maximally effective concentrations of the active principles of human and rat origin display no additive effects whereas additive effects are clearly evident with other Leydig cell stimulatory factors such as LHRHa and EGF. The hypothesis is advanced that the Leydig cell stimulatory factors from tubular origin may act as paracrine regulatory molecules responsible for the effects of FSH on Leydig cell function.     

Radiotherapy in the management of pancreatic islet cell tumors

Malignant islet cell tumors are commonly treated with surgical resection. Chemotherapy is reserved for residual, unresectable, or metastatic disease. The role for radiotherapy has not been clearly defined. This article describes three cases of advanced islet cell tumors treated effectively with radiotherapy. This experience, in addition to that from other published reports, suggests that radiotherapy is a useful mode for treating advanced islet cell carcinoma.     

Antineuroblastoma activity of desferoxamine in human cell lines

That ferritin, an iron storage protein, can be produced by neuroblastoma cells raises the possibility that iron may have some role in promoting tumor cell growth. To explore this possibility, we studied the effects of desferoxamine, a compound which chelates iron, on viability of CHP 126 and CHP 100, two human neuroblastoma cell lines. Cells (5 X 10(4)) were incubated with graded amounts of desferoxamine or ferrioxamine, an iron-saturated analogue of desferoxamine. Within 5 days of exposure to 60 microM desferoxamine, approximately 90% of cells from each of these cell lines were dead. This effect was dose dependent, was not seen with ferrioxamine, and could be prevented by coincubation with greater than stoichiometric amounts of ferric citrate. As determined by binding of OK-T9, desferoxamine also resulted in increased expression of receptors for transferrin, an iron transport protein. Desferoxamine had only minimal effects on viability of several non-neuroblastoma cell lines. These results suggest that iron is required for growth of neuroblastoma and that desferoxamine has potent, specific, antineuroblastoma activity in vitro.     

Effect of different levels of oral pyridoxine supplementation on plasma pyridoxal-5'-phosphate and pyridoxal levels and urinary vitamin B-6 excretion

Plasma pyridoxal-5'-phosphate and pyridoxal levels increased significantly (p less than 0.05) when single, oral bolus doses of pyridoxine were increased from 10 to 25 and from 25 to 50 mg in nine female volunteers. However, when the dose was increased to 100 mg, plasma pyridoxal-5'-phosphate levels did not differ significantly from those recorded after the 50 mg dose. Within 3 h plasma pyridoxal levels rose with a factor of 3.85 compared with the 50 mg dose but high pyridoxal levels were eliminated from the circulation. Renal clearance of pyridoxal remained a constant, low percentage (less than 2.0%) of each pyridoxine supplement in spite of the observed very high circulating pyridoxal levels. Pyridoxine supplementation is discussed in relation to circulating pyridoxal-5'-phosphate and pyridoxal availability for cellular metabolism.     

Therapeutic potential of choline magnesium trisalicylate as an alternative to aspirin for patients with bleeding tendencies

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p less than 0.005), AA (p less than 0.01) and spontaneous aggregation (p less than 0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.     

Diabetes mellitus and open heart surgery

A method, based on bedside determinations of blood glucose by nursing staff, was designed to control the administration of insulin to diabetic patients during and following open heart surgery. A computer-controlled intravenous infusion pump was used to deliver the insulin. Excellent control of the hyperglycaemia normally associated with open heart surgery was achieved, with 84 percent of measured blood glucose values falling within 2 mmol/litre of the target value of 6 mmol/litre. The method proved to be simple, effective, and safe.