High prevalence of vitamin D insufficiency in healthy elderly people living at home in Argentina.

OBJECTIVE: To evaluate the nutritional status of vitamin D in urban populations of healthy elderly people living at home, in different regions of Argentina. DESIGN: Cross-sectional study. SUBJECTS: In total, 386 ambulatory subjects over 65 y of age from seven cities (between latitude 26 degrees S and 55 degrees S) were asked to participate between the end of winter and the beginning of spring. Of these, 369 accepted, 30 were excluded because of medical history or abnormal biochemical determinations. Finally, 339 subjects (226 women and 113 men) (X+/-s.d.) (71.3+/- 5.2 y) were included. RESULTS: Serum 25OHD levels were lowest in the South (latitude range: 41 degrees S-55 degrees S): 14.2+/-5.6 ng/ml (P<0.0001vs North and Mid regions); highest in the North (26 degrees S-27 degrees S): 20.7+/-7.4 ng/ml (P<0.03 vs Mid, P<0.0001vs South); and intermediate in the Mid region (33 degrees S-34 degrees S) 17.9+/-8.2 ng/ml. Serum mid-molecule PTH (mmPTH) and 25OHD were inversely related: (r=-0.24, P<0.001). A cutoff level of 25OHD at which serum mmPTH levels began to increase was established at 27 ng/ml. A high prevalence (87-52%) of subjects with 25OHD levels in the deficiency-insufficiency range (25OHD levels <20 ng/ml) was detected. CONCLUSION: This study shows that vitamin D deficiency/insufficiency in the elderly is a worldwide problem. Correction of this deficit would have a positive impact on bone health of elderly people.

Effect of unilateral superior cervical ganglionectomy on mandibular incisor eruption rate in rats.

To assess the effect of sympathectomy on rat tooth eruption, the effect of a unilateral superior cervical ganglionectomy (SCGx) on eruption rate of ipsi- and contralateral lower incisors was examined. Two experiments were performed. In a first experiment, the eruption rate of ipsilaterally denervated incisors was similar to that of contralaterally innervated incisors, when assessed for up to 28 days after surgery. In a second experiment, under conditions of unilateral unimpeded eruption of incisors performed ipsilaterally or contralaterally to a unilateral SCGx, a significantly lower eruption rate of denervated incisors at the impeded eruption side, and a significantly higher eruption rate of denervated incisors at the unimpeded side were observed, when computed every 2 days. Significant differences in individual Student's t tests at every time interval occurred mainly during the first and the last week of examination. When average daily eruption rate was computed in weekly intervals, a significant interaction between SCGx and the side of impeded or unimpeded eruption was found in a factorial ANOVA, that is, for each of the 4 weeks of examination, sympathetically denervated incisors showed lower eruption rates at the impeded eruption side, and higher eruption rates at the unimpeded side. These results indicate that incisor eruption is not modified by a local sympathetic denervation unless the contralateral lower rat incisor is cut out of occlusion.

Effect of melatonin on bone metabolism in ovariectomized rats.

To assess the effect of pharmacological dose of melatonin on bone metabolism in ovariectomized rats, urinary deoxypyridinoline (a marker of bone resorption) and calcium excretion, circulating levels of calcium, phosphorus and bone alkaline phosphatase activity (a marker of bone formation), and bone mineral density (BMD), mineral content (BMC) and bone area (BA) of total body, were measured in adult rats for up to 60 days after surgery. Rats received melatonin in the drinking water (25 microg/ml water) or drinking water alone. Urinary deoxypyridinoline increased significantly after ovariectomy by 51% (30 days after surgery) and by 47% (60 days after surgery). The increase in urinary deoxypyridinoline found 30 days after ovariectomy was not observed in melatonin-treated rats. Urinary calcium concentration was similar in the 4 experimental groups studied, as was the circulating calcium concentration at every time interval examined. Fifteen days after surgery, a significant increase in serum phosphorus and bone alkaline phosphatase levels occurred in ovariectomized rats receiving melatonin as compared to their controls. Sixty days after surgery BMD, BMC and BA decreased significantly in ovariectomized rats, an effect not modified by melatonin. Serum estradiol decreased significantly by 30 days after ovariectomy to attain values close to the limit of detection of the assay by 60 days after ovariectomy. The results support the conclusion that a pharmacological amount of melatonin modifies bone remodeling after ovariectomy and that the effect may need adequate concentrations of estradiol.

Effect of unilateral superior cervical ganglionectomy on bone mineral content and density of rat's mandible.

To assess the effect of a local sympathectomy on bone metabolism, the effect of a unilateral superior cervical ganglionectomy (Gx) on growth and bone mineral content and density of the ipsi- and contralateral mandibles was examined in female rats. A significant increase in the hemi-mandibular bone ipsilateral to Gx was found as compared to the contralateral, sham-operated side 30 days, but not 15 days, after surgery. Bone mineral content of the hemi-mandibular bones was significantly lower in the side ipsilateral to Gx in the group of rats killed on the 30th day after surgery. Since no difference in areas between innervated and denervated hemi-mandibles was found, bone mineral density was also significantly lower in the hemi-mandible ipsilateral to Gx. The results further support that a regional sympathectomy causes qualitative alterations in bone modeling and remodeling, leading to bone resorption.

Solar ultraviolet B radiation and photoproduction of vitamin D3 in central and southern areas of Argentina.

The incidence of nutritional rickets in the southern part of Argentina is 8-12 times higher than in the rest of the country. Winter 25(OH)D serum levels in normal population of southern areas are lower than in central and northern areas. To elucidate these differences, we compared the photoconversion of provitamin D3 (7-DHC) to previtamin D3 in two cities: Ushuaia (latitude 55 degrees S) and Buenos Aires (34 degrees S). Ampules containing 7-DHC were exposed to sunlight one day in the middle of each month either from 10:30 a.m. to 2:30 p.m. or from 8:00 a.m. to 5:00 p.m. The percentages of photoproducts formed were determined by high performance liquid chromatography (HPLC). Previous studies have proved that this is a valid model to assess "in vitro" the photoproduction of vitamin D3 in human skin. Previtamin D3 + vitamin D3 formed in Ushuaia were less (p < 0.02) than those found in Buenos Aires during all seasons: summer, (X +/- SEM) 6.4 +/- 0.8% vs. 13.2 +/- 1.8%; autumn, 1.2 +/- 0.7% vs. 6.3 +/- 1.3%; winter, 0.8 +/- 0.7% vs. 3.6 +/- 0.7%; spring, 3.4 +/- 0.5% vs. 9.1 +/- 1.1%. The photoproducts produced from 10:30 a.m. to 2:30 p.m. were similar for each month and latitude to those formed when the ampules were exposed from 8:00 a.m. to 5:00 p.m. We conclude that in Ushuaia there is a prolonged "vitamin D winter" during which cutaneous synthesis of vitamin D is absent, leading to lower serum values of 25(OH)D and contributing to the higher incidence of rickets.

Calcium metabolism and its regulating hormones in patients with leprosy.

Calcium metabolism was studied in 47 patients with borderline or lepromatous leprosy. Total and ionized calcium, phosphorus, creatinine, total alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxy vitamin D [25(OH)D], and 1,25-dihydroxy vitamin D [1,25(OH)2D] were measured in serum; calcium and total hydroxyproline were determined in urine. Total subperiosteal diameter and medullar cavity diameter were measured on an X-ray of the hand of all patients. Average values were within normal ranges for all of the biochemical determinations. Total serum calcium was moderately below the normal range in eight patients but ionized calcium levels were within the normal ranges in all of the patients. Four patients, all of them with lepromatous leprosy, had levels of 1,25(OH)2D higher than normal but none of them was hypercalcemic and PTH levels were within normal range. Although all values were within the normal ranges, lepromatous leprosy patients had lower total calcium, higher alkaline phosphatase, and higher urinary hydroxyproline than borderline leprosy patients (9.1 +/- 0.4 vs 9.4 +/- 0.3 mg%, p < 0.001; 10.3 +/- 2.9 vs 7.4 +/- 2.3 King-Armstrong units, p < 0.02 and 27.2 +/- 12 vs 19.4 +/- 5.6 mg/24 hr, p < 0.02, respectively). No differences were found between patients and controls in the average micrometric measurements of the second metacarpal bone but significant osteopenia was found in 19% of the patients. The main finding of the present study in a representative sample of leprosy patients is that the average total serum calcium was in the lowest limit of the normal range, but the ionized serum calcium was in the middle of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Precise measurement of bone mineral density in rats using dual-energy X-ray absorptiometry.

The dual X-ray absorptiometer (DEXA, Hologic ZDR-1000) in a high resolution mode was evaluated for measuring: Area (A), Bone Mineral Content (BMC) and Bone Mineral Density (BMD) in femur and tibia of adults rats at four regions: proximal (L1), diaphysis (L2-L3) and distal (L4). Reproducibility with and without repositioning was evaluated in femur after ten measurements in a water bath at depths between 2.0 and 2.5 cm. The whole coefficient of variation (CV = 100 x SD/mean) of BMD was 0.52% and 0.47% respectively. Accuracy was evaluated by comparing the BMC to bone ash weight. BMC was highly correlated with chemical analysis (r = 0.98, p < 0.001) for femur. The ability to detect changes in BMD was studied by comparing BMD of the right and left femurs and tibias of adult normal males and females rats. No significant differences were found between both sides. Nevertheless, when BMD (X +/- SE) of male and female rats were compared, female rats presented lower BMD at distal femur (0.263 +/- 0.021 vs. 0.315 +/- 0.009, p < 0.05) and proximal tibia (0.259 +/- 0.016 vs. 0.315 +/- 0.013 p < 0.02) than male rats. We also studied the ability to detect BMD changes in abnormal metabolic conditions. SHAM operated rats were compared to ovariectomized (OVX) rats and it was observed that femur of OVX showed a lower distal BMD than SHAM (0.217 +/- 0.005 vs. 0.263 +/- 0.021, p < 0.05). In summary, DEXA is a technique accurate and precise enough to detect changes on BMC and BMD in small animals permitting the experimental study of different metabolic bone conditions.

Precise measurement of bone mineral density in rats using dual-energy X-ray absorptiometry.

The dual X-ray absorptiometer (DEXA, Hologic ZDR-1000) in a high resolution mode was evaluated for measuring: Area (A), Bone Mineral Content (BMC) and Bone Mineral Density (BMD) in femur and tibia of adults rats at four regions: proximal (L1), diaphysis (L2-L3) and distal (L4). Reproducibility with and without repositioning was evaluated in femur after ten measurements in a water bath at depths between 2.0 and 2.5 cm. The whole coefficient of variation (CV = 100 x SD/mean) of BMD was 0.52

and 0.47

respectively. Accuracy was evaluated by comparing the BMC to bone ash weight. BMC was highly correlated with chemical analysis (r = 0.98, p < 0.001) for femur. The ability to detect changes in BMD was studied by comparing BMD of the right and left femurs and tibias of adult normal males and females rats. No significant differences were found between both sides. Nevertheless, when BMD (X +/- SE) of male and female rats were compared, female rats presented lower BMD at distal femur (0.263 +/- 0.021 vs. 0.315 +/- 0.009, p < 0.05) and proximal tibia (0.259 +/- 0.016 vs. 0.315 +/- 0.013 p < 0.02) than male rats. We also studied the ability to detect BMD changes in abnormal metabolic conditions. SHAM operated rats were compared to ovariectomized (OVX) rats and it was observed that femur of OVX showed a lower distal BMD than SHAM (0.217 +/- 0.005 vs. 0.263 +/- 0.021, p < 0.05). In summary, DEXA is a technique accurate and precise enough to detect changes on BMC and BMD in small animals permitting the experimental study of different metabolic bone conditions.

Involvement of the cervical sympathetic nervous system in the changes of calcium homeostasis during turpentine oil-induced stress in rats.

Hypocalcemia is a common finding during stress. The objective of this study was to examine: (a) the changes in circulating calcium, parathyroid hormone (PTH) and calcitonin (CT) concentration in rats stressed by being given a subcutaneous injection of turpentine oil, and (b) the involvement of the sympathetic cervical pathway in stress-induced changes of calcium homeostasis. Four hours after receiving turpentine oil or vehicle, rats were subjected either to hypocalcemia, by being given EDTA intraperitoneally, or to hypercalcemia, by being injected CaCl2 intraperitoneally. Significant changes in serum calcium (10% decrease), serum PTH (28% increase) and CT levels (40% decrease) were observed in stressed rats. EDTA administration brought about a significantly greater hypocalcemia, and a higher PTH secretory response in turpentine oil-stressed rats. During stress, the increase of serum calcium after CaCl2 was significantly smaller, and the rise of CT was greater than in controls. In the case of CT the changes were still observed in rats subjected to superior cervical ganglionectomy (SCGx) 14 days earlier. In the case of PTH, the increase found in stressed rats, but not the augmented response after EDTA, was blunted by SCGx. The potentiation of hypocalcemia brought about by turpentine oil was no longer observed in SCGx rats. In vehicle-treated controls, SCGx delayed PTH response to hypocalcemia, but did not affect the increased response of CT to CaCl2 challenge. The results indicate that a number of changes in calcium homeostasis arise during turpentine oil stress in rats. SCGx was effective to modify the set point for PTH release, but played a minor role in affecting the augmentation of CT release during stress.

Seasonal variations of 25 hydroxyvitamin D and parathyroid hormone in Ushuaia (Argentina), the southernmost city of the world.

Serum levels of calcium, phosphorus, alkaline phosphatase, 250HD, 1.25(OH)2D and PTH were studied in a group of 42 children aged 8.5 +/- 1.8 years (X +/- SD) from the city of Ushuaia (latitude 55 degrees S), at both the end of the winter and the end of summer. Calcium, phosphorus, alkaline phosphatase and 1.25(OH)2D serum levels were not different in summer and winter. The levels of serum 25OHD were significantly higher in summer (18.4 +/- 7.3 ng/ml) than in winter (9.8 +/- 3.8 ng/ml P < 0.001). The levels of 25OHD in children with fair or dark skin were similar in winter but were significantly higher in children with fair skin in summer (20.0 +/- 7.2 ng/l vs 15.3 +/- 5.1 ng/ml (P < 0.05). Serum levels of PTH were higher in winter (58.2 +/- 30.5 pg/ml) than in summer (47.9 +/- 28.3 pg/ml) (P < 0.03). The results demonstrate the existence of a population with low serum levels of 25OHD in winter. The higher levels of PTH in winter when serum 25OHD levels are lower could be the cause of the lack of seasonal variation in serum calcium and 1.25(OH)2D levels. Further studies are needed to establish whether these changes besides increasing the incidence of rickets, could also affect the mineral density of the skeleton in the population of this vitamin-D-deficient area.

Compensatory parathyroid hypertrophy after hemiparathyroidectomy in rats feeding a low calcium diet.

The functional and anatomic compensatory response of the parathyroid gland was examined in hemiparathyroidectomized (HPTx) rats whose parathyroid hormone (PTH) secretion was stimulated by a low calcium diet. These responses were compared with those observed in the thyroid gland of hemithyroidectomized (HTx) rats. Rats kept on a low calcium diet for 10 days were subjected to HPTx, HTx, or sham operations. Throughout the experiment (up to 28 days after surgery), serum calcium levels of HPTx rats were lower than the basal, with delta values (mg/dl, mean +/- SEM) of -0.66 +/- 0.17 and -0.84 +/- 0.17, (P less than 0.05) 3 and 28 days after surgery, respectively. Serum PTH decreased significantly from 7 to 21 days after HPTx, reaching normality at day 28 after surgery. In HTx rats, serum thyroxine (T4) levels diminished significantly 7 days after surgery, and attained normality thereafter. The mitotic index (number of metaphases/1,000 cells) in parathyroid glands of colchicine-treated HPTx rats increased significantly in comparison to sham-operated controls, when examined 2 or 40 days after surgery. The mitotic index of thyroid follicular cells was significantly higher than that of their respective controls, 2 but not 40 days after HTx. These results indicate that after HPTx, a delayed compensatory response is found when the animals are kept under a low calcium diet. Parathyroid response is both delayed and of a minor degree compared to that found in the thyroid gland after HTx.

[Winter serum levels of 25-hydroxy-vitamin D in Ushuaia and Buenos Aires]. / Niveles séricos invernales de 25-hidroxi-vitamina D en Ushuaia y Buenos Aires.

Public Health Annals recording diagnosis of nutritional rickets in patients admitted in Public Hospitals disclosed that from birth to age 14, in the period 1980-1981, the incidence was 2.7 higher in the Patagonia (latitude 39 degrees S to 55 degrees S) compared with the Pampeana Region and 8.5 higher than in the rest of the country. After informed parental consent 37 healthy children of Buenos Aires (34 degrees S) with an age of (Av +/- 1 SD) 7.0 +/- 1.2 years, 29 with an age of 13.1 +/- 1.5 years and 63 of Ushuaia (55 degrees S) with an age of 7.1 +/- 0.8 years were studied at the end of winter (August). Serum levels of 25-OH-D were as follows (mean +/- SE): Buenos Aires: 21.1 +/- 2.03 ng/ml (Average: seven years old), 19.0 +/- 1.18 ng/ml (children of thirteen years old) and Ushuaia: 9.3 +/- 0.64 ng/ml (p less than 0.001) (Fig. 2). Serum levels were below 8 ng/ml in 52% of the children in Ushuaia but only in 9% in Buenos Aires. Serum calcium and alkaline phosphatase levels were similar in the two groups but serum phosphate was higher in Ushuaia (Table 1). The calcium intake was greater in Ushuaia (811 +/- 49 mg/day) than in Buenos Aires (634 +/- 61 mg/day) and was correlated with 25-OH-D levels in children of Ushuaia (r = 0.50, p less than 0.001) but not in Buenos Aires (r = 0.08). The main source of calcium intake was vitamin D fortified milk. These results disclosed a significantly diminished level of serum 25-OH-D in Ushuaia.(ABSTRACT TRUNCATED AT 250 WORDS)

Niveles séricos invernales de 25-hidroxi-vitamina D en Ushuaia y Buenos Aires. / [Winter serum levels of 25-hydroxy-vitamin D in Ushuaia and Buenos Aires]

Public Health Annals recording diagnosis of nutritional rickets in patients admitted in Public Hospitals disclosed that from birth to age 14, in the period 1980-1981, the incidence was 2.7 higher in the Patagonia (latitude 39 degrees S to 55 degrees S) compared with the Pampeana Region and 8.5 higher than in the rest of the country. After informed parental consent 37 healthy children of Buenos Aires (34 degrees S) with an age of (Av +/- 1 SD) 7.0 +/- 1.2 years, 29 with an age of 13.1 +/- 1.5 years and 63 of Ushuaia (55 degrees S) with an age of 7.1 +/- 0.8 years were studied at the end of winter (August). Serum levels of 25-OH-D were as follows (mean +/- SE): Buenos Aires: 21.1 +/- 2.03 ng/ml (Average: seven years old), 19.0 +/- 1.18 ng/ml (children of thirteen years old) and Ushuaia: 9.3 +/- 0.64 ng/ml (p less than 0.001) (Fig. 2). Serum levels were below 8 ng/ml in 52

of the children in Ushuaia but only in 9

in Buenos Aires. Serum calcium and alkaline phosphatase levels were similar in the two groups but serum phosphate was higher in Ushuaia (Table 1). The calcium intake was greater in Ushuaia (811 +/- 49 mg/day) than in Buenos Aires (634 +/- 61 mg/day) and was correlated with 25-OH-D levels in children of Ushuaia (r = 0.50, p less than 0.001) but not in Buenos Aires (r = 0.08). The main source of calcium intake was vitamin D fortified milk. These results disclosed a significantly diminished level of serum 25-OH-D in Ushuaia.(ABSTRACT TRUNCATED AT 250 WORDS)

Raquitismo nutricional en la Argentina / Nutritional ricketts in Argentina

Se estudiaron niños sanos con una edad promedio de 7,0 años (rango 4 a 9), a fines del invierno (agosto) en tres cuidades argentinas: Buenos Aires, Ushuaia y Tucumán. Los resultados obtenidos revelan una significativa disminución en los niveles séricos de 25-OH-D en Ushuaia (la ciudad más acestral del mundo), debido a la escasez del número de horas de brillo solar y la diminución de la exposición solar de la piel en duración y superficie. La población depende entonces de la ingesta exógena de vitamina D y de la disponibilidad de los depósitos corporales para compensar el déficit de la síntese endógena. Bajo estas circunstancias, la incidencia del raquitismo en niños es significativamente mayor que en otras regiones del país. Con excepcion de grupos etnicos que residen fuera de su medio original, los niveles de 25-OH-D hallados a fines del invierno en niños sanos de Ushuaia son los más bajos comunicados en la literatura

Raquitismo nutricional en la Argentina / Nutritional ricketts in Argentina

Se estudiaron niños sanos con una edad promedio de 7,0 años (rango 4 a 9), a fines del invierno (agosto) en tres cuidades argentinas: Buenos Aires, Ushuaia y Tucumán. Los resultados obtenidos revelan una significativa disminución en los niveles séricos de 25-OH-D en Ushuaia (la ciudad más acestral del mundo), debido a la escasez del número de horas de brillo solar y la diminución de la exposición solar de la piel en duración y superficie. La población depende entonces de la ingesta exógena de vitamina D y de la disponibilidad de los depósitos corporales para compensar el déficit de la síntese endógena. Bajo estas circunstancias, la incidencia del raquitismo en niños es significativamente mayor que en otras regiones del país. Con excepcion de grupos etnicos que residen fuera de su medio original, los niveles de 25-OH-D hallados a fines del invierno en niños sanos de Ushuaia son los más bajos comunicados en la literatura (AU)

Calcitonin is a competitive inhibitor of the hydrosmotic effect of oxytocin in toad bladder.

The effects of calcitonin (CT) on the water transfer in the toad (Bufo arenarum) urinary bladder, an epithelial barrier commonly employed as a model of the mammalian nephron, were studied. The net transmembrane water flux was measured at minute intervals, while the endogenous adenosine 3',5'-cyclic monophosphate (cAMP) levels were determined in isolated epithelial cells. It was observed that 1) CT, up to 10(-6) M, did not have any effect on water permeability. 2) Preincubation with CT, between 10(-7) and 10(-8) M, inhibited the hydrosmotic response to a supramaximal dose of oxytocin (OXT; 2 x 10(-8) M), used here as an antidiuretic hormone (ADH) analogue. This inhibition was reversible and concentration related. Nevertheless, although the magnitude of the response was reduced, its time course of evolution did not change. 3) When CT was added on the previously developed response to OXT, inhibition was also dose dependent with a time course not distinguishable from hormonal washout. 4) CT, up to 10(-6) M, did not modify the hydrosmotic response to 8-bromo cAMP, a potent analogue of the ADH second messenger. 5) CT and OXT increased the intracellular cAMP levels, but both effects were not cumulative. The increase induced by CT plus OXT was significantly lower than the one elicited by OXT alone. It is concluded that CT is a competitive inhibitor to the hydrosmotic effect of OXT in toad urinary bladder. Its action must be located prior to cAMP formation.

Antiarthritic synergism of combined oral and parenteral chrysotherapy. I. Studies in adjuvant-induced arthritis in rats.

In comparative clinical studies of auranofin (AF, oral gold) and parenteral gold in the treatment of rheumatoid arthritis, no difference in efficacy was detected. Since the pharmacologic profiles of these compounds are different, we studied their combined effect on adjuvant arthritis (AA). The effect of AF alone and combined with gold sodium thiomalate (GTM) or gold sodium thiosulfate (GTS) on the excretion of urinary hydroxyproline (UHP) and urinary calcium (UCa), and the articular index of arthritic rats was followed during five weeks of treatment. The excretion of UHP and UCa was significantly inhibited (P less than 0.005) in rats treated with AF combined with GTM or GTS as compared with animals treated with the individual gold compounds. However, the articular index only decreased significantly (P less than 0.02) in the group of rats treated with AF + GTS. The present studies open the possibility that combined treatment with oral and injectable gold provide a new approach for chrysotherapy with an increased antiarthritic potency.

Antiarthritic synergism of combined oral and parenteral chrysotherapy. II. Increased inhibition of activated leukocyte oxygen burst by combined gold action.

We have observed an antiarthritic effect of combined chrysotherapy in adjuvant arthritis. Since superoxide radicals (O2-) are potent mediators of rheumatoid inflammation, we studied the combined effect of auranofin (AF) and injectable golds on luminol-dependent chemiluminescence (LDCL) and O2- generation by cytochrome-c reduction of activated leukocytes by different receptor-mediated stimuli: phorbol myristic acetate, 10(-6) M; f-Met-Leu-Phe, 10(-6) M; and poly-L-histidine, 10(-5) M. AF, 0.6 and 0.9 micrograms Au/ml, inhibited 34 and 58% of O2- generation, respectively; the addition to AF of 0.3 micrograms Au/ml of gold thiosulfate (GTS) increased this inhibition to 84 and 97% of the oxygen burst. Similar synergistic potentiation inhibition was obtained by LDCL. When the inhibition of O2- generation by the combined action of AF and GTS was compared with AF + gold sodium thiomalate (GTM), only GTS showed an activation on AF's inhibition of the oxygen burst of human leukocytes. The ligand thiosulfate in equimolar concentrations to GTS had a statistically significant (P less than 0.01) inhibitory effect on AF's blockade of O2- generation during the first 5 min of the interaction with the PMNs; thiomalate had no effect. Sequential pretreatment of PMNs with AF and GTS on O2- generation revealed that for synergism of combined gold action to take place, the cell membrane had to be subjected first to the action of oral gold or to the simultaneous combined action of oral and parenteral gold.(ABSTRACT TRUNCATED AT 250 WORDS)