Facilitated uptake of zinc into human erythrocytes. Relevance to the treatment of sickle-cell anaemia

The ability of a number of heterocyclic metal chelators to deliver zinc into red cells, to release the liganded zinc to haemoglobin and thereby cause a left shift in the oxygen dissociation curve of intact red cells has been investigated. Incubation of neutrally charged zinc-pyrone and zinc-pyridin-2-one complexes with red cells led to the rapid accumulation of zinc within cells, whereas unliganded zinc in the form of zinc acetate, zinc chloride or zinc sulphate accumulated only slowly. The rate at which zinc was delivered to red cells by pyrone and pyridin-2-one ligands increased with increasing lipid solubility of the ligands. The uptake of zinc into both normal adult and sickle red cells was associated with a dose-dependent increase in the oxygen affinity of haemoglobin. The degree of left shift in the oxygen dissociation curve following the incubation of red cells with zinc-pyrone and -pyridin-2-one complexes suggests that these complexes may find application as agents to increase the oxygen affinity of haemoglobin in sickle cell disease and thereby decrease the probability of intravascular sickling at low tissue oxygen tensions. Ethylmaltol appears to be a particularly useful agent due to its known low toxicity.     

Diets rich in n-9, n-6 and n-3 fatty acids differentially affect the generation of inositol phosphates and of thromboxane by stimulated platelets, in the rabbit

We have studied the effects of semi-synthetic diets rich in either n-9 (olive oil, OO) or n-6 (corn oil, CO), or n-3 (fish oil, FO, as MaxEPA) fatty acids on the levels of major PUFA in platelet lipids, on the generation of inositol phosphates by [3H]inositol labelled platelets after stimulation with thrombin and of thromboxane B2 (TxB2) by platelet rich plasma (PRP) after stimulation with collagen. The predicted elevations of oleic (OA), linoleic (LA) and eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were observed in platelet lipids of each animal group, but in the MaxEPA fed group accumulation of EPA was associated with depletion of linoleic acid (LA) rather than of arachidonic acid (AA). Basal levels of inositol-tris-phosphate (IP3) in platelets were lowest in the OO group and highest in the CO group, whereas the increment after thrombin stimulation (1 unit/ml NIH) was maximal in the OO group and minimal in the FO group. Instead, when generation of TxB2 by stimulated platelets was evaluated, no appreciable difference among the various groups could be detected, in accordance with the limited modifications of platelet AA content induced by the diets. The overall data indicate that dietary fatty acids modulate the pathway of inositol phosphate generation in rabbit platelets, independently of modifications of TxB2 production.     

Corneal endothelial cell loss following trephination

The amount of endothelial cell loss that occurs to the donor cornea during the trephination process was evaluated in 40 porcine eyes. A vital staining technique (alizarin red S and acid violet 19) was used to quantify the extent of endothelial damage and removal. Two types of corneal punches (Weck and H&I0 were used for trephination. The average amount of endothelial loss from the peripheral cornea was 7.9%, accounting for only a 3% loss of endothelial cells over the total surface area of the corneal button. a comparison of the Weck and H&I corneal punches showed no significant difference (P greater than 0.1) by Student's test for both endothelial cell damage and removal.     

Increased (L+)-lactic acid production in lysozyme-inactivated suspensions of human dental plaque

The effect of lysozyme-inactivation on L(+)-lactic acid (LA) production in dental plaque suspensions was evaluated. From 10 children 24-h plaque was collected and lysozyme activity inhibited by addition of goat antiserum to human lysozyme. Acid production was stimulated by addition of glucose. The results showed significantly increased LA levels (50-150%) in lysozyme-inactivated plaque suspensions from 8 of the subjects compared to untreated controls. The increase in acid production activity was not related to plaque lysozyme levels. The findings indicate that the presence of lysozyme may be limiting on acid production in the early dental plaque.     

Levodopa up-regulates platelet alpha 2-adrenoceptors

Treatment of dogs for 21 days with oral levodopa (100 mg b.i.d.) plus benserazide (25 mg b.i.d.) induced a significant increase in the number of platelet alpha 2-adrenoceptors labelled by [3H] yohimbine with no change in Kd. The rise was maximal at the end of the treatment and remained significant during the month following the cessation of treatment. Plasma catecholamine levels did not vary. Competition experiments showed a low affinity of both dopamine and levodopa for platelet alpha 2-adrenoceptors. These results suggest that levodopa treatment regulates alpha 2-adrenoceptor number in dog platelets.     

Mental health and older women

Currently it is estimated that up to 25 percent of the elderly manifest symptoms of mental disorder. The recognition of the seriousness of the problem has lead to a growing body of research in the field of geriatric mental health. This paper presents an overview of early gerontological studies of life satisfaction and morale of older persons and of the two most prevalent mental health problems of the aged, depression and dementia. Mental health service delivery and utilization issues are also considered.     

ACETALDEHYDE ADDUCTS WITH HAEMOGLOBIN: DETERMINATION OF ACETALDEHYDE RELEASED FROM HAEMOGLOBIN BY ACID HYDROLYSIS

Acetaldehyde, the first metabolite of ethanol, reacts with haemoglobinin vitro to produce acetaldehyde—haemoglobin adducts.Some clinical studies on the minor haemoglobins have suggestedthat these adducts may be formed in people abusing alcohol.Under hydrolysis of haemoglobin, with oxalic acid at 100°Cin sealed vials, some acetaldehyde was released and then specificallydetermined by HPLC. The kinetics of hydrolysis were studiedusing haemoglobin previously labelled with ¹⁴[C] acetaldehyde.The maximum liberation of ¹⁴[C] acetaldehyde was obtained after3 hr 30 min hydrolysis and this time factor was then utilizedin the analysis of alcoholic and control haemoglobin. Thus,we have confirmed the formation of acetaldehyde haemoglobinadducts in vivo. It must be noted that the released acetaldehydecorresponds only to an index of the stable adducts. The levelswere higher in alcoholics than in controls (1.417±0.171and 1.295±0.139 nmol/mg Hb, respectively, P<0.001).In conclusion, this marker is not a convenient tool for themonitoring of alcohol exposure levels because of the low differencesbetween alcoholic and control haemoglobins.     

Population screening and referral for hypercholesterolemia

To determine the potential effect of screening on referral patterns, an adult population sample (4,404 men, 5,164 women, 20-69 years of age) was systematically recruited and screened for hypercholesterolemia and then analyzed by different cholesterol referral recommendations. Using levels suggested by the Lipid Research Clinics Coronary Primary Prevention Trial (greater than or equal to 265 mg/dL), 7.3% of men and 5.8% of women would be referred for follow-up. With the suggested recommendations of the National Cholesterol Education Program (NCEP), (greater than or equal to 200 mg/dL), 49.2% of men and 40.2% of women would be referred. The use of age-related definitions of the NIH Consensus Conference on Lipid Lowering results in 28.0% referrals in men and 21.8% in women. From this population, hypercholesterolemia subjects (greater than or equal to 265 mg/dL at screening; n = 624) were invited for a second cholesterol determination (58% returned), which found 36% below the 265 mg/dL level. Population screening for cholesterol is likely to produce large numbers of patients for follow-up, with the actual numbers strongly dependent on cutoff levels and age-sex distributions. Referral and follow-up of these patients may place a significant load on an unprepared health care community.     

Severe herpetic keratitis. I: Prevalence of visual impairment in a clinic population.

We report a prevalence study of the best visual acuity in the affected eye of 100 selected patients with herpetic keratitis seen during a two-year period. Sixty-two patients retained an acuity of 6/9 or better without requiring penetrating keratoplasty (PK). The prevalence of reduced visual acuity severe enough to warrant PK was 33%. Patients requiring PK for whom full clinical records were available suffered a mean of 6.8 episodes of keratitis. In this group of patients the vision of 18 fell from 6/6 to 6/60 over a mean period of 8.5 years. Once visual acuity was permanently reduced to 6/12, 78% of patients proceeded to lose vision to 6/60. Unilateral visual impairment occurs in at least a third of patients with severe herpetic keratitis. Once vision falls permanently to 6/12, the long-term prognosis for vision appears to be poor.