Artificial Space Weathering to Mimic Solar Wind Enhances the Toxicity of Lunar Dust Simulants in Human Lung Cells.

During NASA's Apollo missions, inhalation of dust particles from lunar regolith was identified as a potential occupational hazard for astronauts. These fine particles adhered tightly to spacesuits and were unavoidably brought into the living areas of the spacecraft. Apollo astronauts reported that exposure to the dust caused intense respiratory and ocular irritation. This problem is a potential challenge for the Artemis Program, which aims to return humans to the Moon for extended stays in this decade. Since lunar dust is "weathered" by space radiation, solar wind, and the incessant bombardment of micrometeorites, we investigated whether treatment of lunar regolith simulants to mimic space weathering enhanced their toxicity. Two such simulants were employed in this research, Lunar Mare Simulant-1 (LMS-1), and Lunar Highlands Simulant-1 (LHS-1), which were added to cultures of human lung epithelial cells (A549) to simulate lung exposure to the dusts. In addition to pulverization, previously shown to increase dust toxicity sharply, the simulants were exposed to hydrogen gas at high temperature as a proxy for solar wind exposure. This treatment further increased the toxicity of both simulants, as measured by the disruption of mitochondrial function, and damage to DNA both in mitochondria and in the nucleus. By testing the effects of supplementing the cells with an antioxidant (N-acetylcysteine), we showed that a substantial component of this toxicity arises from free radicals. It remains to be determined to what extent the radicals arise from the dust itself, as opposed to their active generation by inflammatory processes in the treated cells.

Lymphocytic responses to streptococcal antigens in glomerulonephritic patients.

The lymphocytes from patients with progressive glomerulonephritis showed significant inhibition of cell migration in the presence of group A streptococcal particulate antigens. Marked increases in the level of DNA synthesis of these lymphocytes were also observed after contact with these antigens. Lymphocytes from patients with unrelated renal disorders exhibited minimum reactivity to streptococcal antigens.

Carotid baroreflexes during hemodialysis.

In 9 regular hemodialysis patients, the carotid baroreceptor reflex was studied using standardized carotid sinus stimulation by neck suction. All patients were studied during predialysis conditions (recirculation), and during dialysis using dialyzate sodium concentrations of 145 and 133 mmoles/l. Baroreceptor stimulation was performed during the recirculation period and after 120-266 minutes of combined dialysis and ultrafiltration. Dialysis alone with either sodium concentration tended to decrease blood pressure. Heart rate as well as plasma renin activity increased significantly during dialysis with either procedure. In contrast to the findings in healthy subjects, heart rate was not influenced by neck suction, possibly reflecting a vagal neuropathy in uremic patients. However, carotid sinus stimulation decreased systolic pressure during recirculation to the same extent as has been found in healthy subjects. Furthermore, the blood pressure response to neck suction was enhanced during dialysis. These findings suggest that the blood pressure decrease during dialysis can not be explained by defective blood pressure control by the carotid sinus baroreceptors.

The influence of dialysis fluid composition on the blood pressure response during dialysis.

To elucidate the relative role of osmolar (sodium) and acetate shifts during dialysis, 6 patients with problems of overhydration underwent rapid ultrafiltration for 1 hr (mean weight reduction 2.0 kg), using the 1 m2 RP 6 dialyzer. Ultrafiltration was carried out at the beginning of each of 5 dialysis treatments at weekly intervals. Ultrafiltration was undertaken without dialysis (controls) and with simultaneous dialysis using acetate (40 mmoles/1) or bicarbonate (25 mmoles/1) in the dialysis fluid with dialyzate sodium concentration of 133 and 145 mmoles/1. The systolic blood pressure and mean arterial pressure which were stable with ultrafiltration only fell slightly when a high dialyzate sodium concentration was used and much further when the dialyzate sodium concentration was kept low. These changes were apparently related to the changes in plasma osmolality. Acetate had no effect on blood pressure at the higher sodium concentration, but a slight (insignificant) additive effect when used in the low-sodium dialyzate. Shifts in osmolality (sodium concentration) seem to be more important than the effect of acetate in inducing dialysis-associated hypotension.

Fulminating anti-A autoimmune hemolysis with anuria in a renal transplant recipient: a therapeutic role of plasma exchange.

In this communication we present a case of fulminating anti-A autoimmune hemolysis with anuria occurring during the postoperative course after a successful renal transplantation. The patient was treated with repeated plasma exchange in an effort to remove antibodies directed against the red cells and also to eliminate the products of hemolysis known to cause acute renal failure. Subsequently the hemolysis receded and the patient regained graft function. Repeated plasma exchange, in addition to immunosuppression, appeared to have contributed to the ultimate recovery of the patient.

Backdiffusion or bicarbonate may stimulate complement activation during haemodialysis with low-flux membranes.

Backdiffusion of dialysate during haemodialysis with low-flux membranes and the use of bicarbonate dialysatebase, may increase the risk for contamination. The influence on the complement system was studied by altering the flux of acetate or bicarbonate dialysate base across the membrane. Eight patients were dialysed with a transmembrane pressure of 100 mm Hg (group I) during the first 60 min to standardize the ultrafiltration (UF) and acetate as dialysate. In eight other patients (group II) the UF was "set at zero" ml during the first 60 min using an FCM 10-1 monitor (Gambro) and bicarbonate as base. The groups were dialysed three times on two hollow-fiber membranes made of Hemophan and cellulose acetate (CA). Blood samples were taken at 0, 15, 60 and 180 min, and analysed for plasma protein, haematocrit and complement C3d. In group II there was a reduction in plasma protein concentration at 15 and 60 min (p < 0.002) for Hemophan and at 60 min (p < 0.01) using CA. C3d was increased at 15 min for both filters (p < 0.03). The reduction of protein in group II was followed by changes in the haematocrit, indicating a backdiffusion of dialysate, which may contribute to the concomittant increase in C3d.

Granulocyte elastase, beta-thromboglobulin, and C3d during acetate or bicarbonate hemodialysis with Hemophan compared to a cellulose acetate membrane.

Twenty-two patients were dialysed in a cross-over design using Hemophan or cellulose acetate membranes. The dialysate buffer was acetate (n = 12) or bicarbonate (n = 10). Blood was sampled at 0, 15, 60 and 180 min and mean values were adjusted for changes in total protein in each sample. At 15 min during dialysis a decrease in leukocytes and platelets occurred with both membranes, irrespective of the buffer (Wilcoxon, p less than 0.006). During dialysis, increases were found in granulocyte elastase inhibitor complex (E- alpha 1-PI), beta-thromboglobulin and C3d. beta 2-microglobulin was not significantly changed in blood after dialysis with Hemophan or cellulose acetate membranes with bicarbonate buffer. Side effects were more pronounced at 180 min during dialysis with bicarbonate in patients using cellulose acetate than with Hemophan (p = 0.021, n = 8). Hemophan seemed to be more favourable than cellulose acetate membranes in regard to leukopenia and E- alpha 1-PI. The dialysate buffer may also alter membrane biocompatibility.

Pheochromocytoma and renovascular hypertension. A case report on a review of the literature.

A case of hypertension with simultaneous occurrence of a para-aortal pheochromocytoma and a functionally significant membranous renal artery stenosis is reported. The pheochromocytoma was excised surgically and a vein patch angioplasty was performed. Postoperatively the BP returned to normal. Three years after surgery the patient is normotensive and urinary catecholamines are normal. On the basis of this case and 27 previously reported cases of pheochromocytoma and renal artery stenosis, the possible relationship between the two conditions is discussed.

Evaluation of impedance technique for fluid-volume monitoring during hemodialysis.

Fluid-volume changes during hemodialysis were studied in 30 patients at four separate treatments in each patient. Readings of fluid-volume changes obtained by a fluid-balance monitor with non-invasive tetrapolar impedance technique were compared to changes in weight caused by the treatment. A correlation coefficient of r = 0.90 (p less than 0.001) was found. A survey of papers describing impedance measurements during hemodialysis or diuresis is also presented.

[Hemodynamic changes during ultrafiltration and hemodialysis in uremia]. / Hämodynamische Veränderungen während Ultrafiltration und Hämodialyse bei Urämikern.

1. The ultrafiltration causes a reduction of blood pressure and minute output of the heart which is compensated by vasoconstriction and thus a decrease of blood pressure is prevented. 2. Changes in the salt concentrations with reduction of the osmolarity during the dialysis without simultaneous ultrafiltration lead to vasodilation and hypotension despite increase of the minute output of the heart. 3. During a usual haemodialysis (i.e. dialysis with simultaneous ultrafiltration) the vasodilating effect of the dialysis may abolish the vasoconstrictive effect of the ultrafiltration and thus may be the cause of the hypotension.

Hemodynamic changes during sequential ultrafiltration and dialysis.

Seven patients on regular dialysis were studied to elucidate the hemodynamic changes during ultrafiltration and dialysis, performed sequentially, the period of ultrafiltration (1 hour) either preceding or following dialysis (3 hours). During dialysis ultrafiltration was prevented by applying positive pressure in the dialysate compartment. Cardiac index (dye dilution: indocyanine green), heart rate, stroke volume index, blood pressure, and total peripheral vascular resistance index were measured. During ultrafiltration, cardiac index and stroke volume index decreased, but heart rate was not significantly changed. Total peripheral vascular resistance increased, resulting in unchanged blood pressure. During dialysis, the total peripheral vascular resistance decreased, but cardiac index and heart rate increased. BP decreased when the increase in cardiac index was insufficient to compensate for the decrease in total peripheral vascular resistance. PRA increased during ultrafiltration due to hypovolemia and decreased during dialysis, presumably due to decreased sympathetic activity which may also be a cause of dialysis-induced vasodilation.

Influence of dialysate composition on cardiovascular function in isovolaemic haemodialysis.

Haemodynamic studies were made in eight patients before and during isovolaemic dialysis with five different dialysis solutions which varied with regard to concentration of sodium, acetate, bicarbonate and urea. Low sodium (133mmol/L) in the dialysate induced a fall in blood pressure both with and without urea removal, but no significant fall in peripheral vascular resistance. Acetate in the dialysate at higher sodium concentration (140mmol/L) resulted in peripheral vasodilation but no fall in blood pressure due to a compensatory increase in heart rate and cardiac output. We conclude that a fall in plasma tonicity (sodium) is the most important pathogenetic factor in dialysis associated hypotension; fall in total osmolality (mainly urea) is of no importance and acetate vasodilation can be compensated for haemodynamically provided that tonicity is kept stable.

Clinical investigation of the new dialyzer Gambro PRO-3.

A new plate dialyzer, Gambro PRO-3, with a polycarbonate-polyether membrane (Gambrane) was tested. The membrane thickness is 16 micron and the dialyzer surface area 0.77 m2. 11 regular hemodialysis patients who were treated 3 times per week were studied and 32 dialyses were performed. Clearances of urea, creatinine, uric acid and inorganic phosphate at different blood flows were measured early and late in dialysis. Pulse rate and blood pressure were observed. Ultrafiltration rate and the residual blood volume were also measured. The performance of the dialyzer with regard to clearances was similar to that of the standard GLP 11.5 micron but inorganic phosphate clearance was slightly higher in PRO-3. The ultrafiltration of PRO-3 is about the same as for the GLP 11.5 micron dialyzer. No membrane leaks were observed, neither any adverse reactions in the patients.

beta 2-Microglobulin and granulocyte elastase.

Plasma beta 2-M was measured by radioimmunoassay in samples obtained before and after dialysis with seven different dialysers, tested according to the protocol of the International Cooperative Biocompatibility Study (ICBS). Plasma beta 2-M was corrected for contraction of its distribution volume, which was assumed to be equal to the extracellular fluid volume. The uncorrected plasma beta 2-M concentration increased with all conventional dialysers, including the G10-3N, (cuprammonium cellulose plate), G120 M (cuprammonium cellulose hollow fibre), CD 4000 (cellulose acetate) and T 150 (polymethylmethacrylate). However, no significant differences were found between the predialysis and the corrected postdialysis plasma beta 2-M concentrations with these conventional dialysers, and thus no evidence of net generation or release of beta 2-M was found in this study. With high-permeability membranes, the corrected postdialysis beta 2-M values were decreased by 27.1% with the Duo-Flux Artificial Kidney, 53.5% with F 60, and 34.6% with Filtral, indicating that dialysers with these membranes eliminate plasma beta 2-M to a certain extent. The complex of granulocyte elastase with alpha 1-antiproteinase in plasma was also measured in samples from the arterial blood line collected before, and after 30 and 120 min of dialysis with each of the seven dialysers in this study. All dialysers elicited an increase in the mean plasma elastase concentrations which was more than twice as high with cuprammonium cellulose plate than with all of the others. The change of elastase at 120 min of dialysis varied considerably with each dialyser and was statistically significant with all except CD 4000, F 60, and Filtral.(ABSTRACT TRUNCATED AT 250 WORDS)

Repeated application of EMLA cream 5% for the alleviation of cannulation pain in haemodialysis.

The analgesic effect and the occurrence of local reactions after repeated application of a lidocaine/prilocaine cream (EMLA 5%) were investigated in 31 haemodialysis patients. The cream was used for alleviation of cannulation pain prior to the haemodialysis (HD) for a period of 1-1.5 years. In each patient 300 to 312 applications of the cream were made during the period. Local skin reactions were recorded after the cream applications and the analgesic effect was evaluated with double-blind, crossover placebo controls at regular intervals. Seventeen patients completed the study. EMLA gave considerable pain relief and was significantly better than placebo at all effect evaluations but one. The frequency of local reactions was low and not correlated to the number of applications of EMLA. Two patients, however, interrupted their treatment due to local irritation.