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PubMed1984

Plasma and lipoprotein lipid responses to four hypolipid drugs.

The responses of 14 hyperlipidemic subjects to 4 hypolipidemic agents were compared by measuring cholesterol and triglyceride in whole plasma, very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL) monthly for 2 months before and 3 months during treatment with each of 4 drugs: clofibrate, 2 g/d; colestipol, 20 g/d; para-aminosalicylic acid-ascorbate (PAS-C), 6-8 g/d; and oxandrolone, 7.5 mg/d. Lipid responses proved to be stable by the first monthly evaluation both off and on each drug. Mean adherence was high and similar for all agents (81-92% of the prescribed dose). Clofibrate was associated with significant decreases in mean plasma cholesterol (-16%, p less than .01), plasma triglyceride (-51%, p less than .005), VLDL-cholesterol (-61%, p less than .005) and VLDL-triglyceride (-61%, P less than .005), while HDL cholesterol increased (+20%, p less than .01), and the LDL-cholesterol/HDL ratio declined (-24%, p less than .05). Colestipol was associated with decreases in mean plasma cholesterol (-15%, p less than .01) and LDL-cholesterol (-22%, p less than .05), while VLDL-triglyceride increased (+41%, p less than .05), and the LDL-cholesterol/HDL-cholesterol radio declined (-25%, p less than .05). PAS-C was associated with decreases in VLDL-cholesterol (-30%, p less than .05), and VLDL-triglyceride (-29%, p less than .05), while the LDL-cholesterol/HDL-cholesterol ratio remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1976

Effect of sodium para-aminosalicylate on oxygen affinity in normal, sickle and fetal human blood.

Sodium para-aminosalicylate (sodium salt of 2-hydroxy-4-aminobenzoic acid, Na-PAS) lowers the oxygen affinity of normal adult human placental, heterozygous and homozygous sickle cell anemic whole blood at 37 degrees C. The reduction of oxygen affinity is related to the type of hemoglobin in the blood. The mean P50 +/- S.E. at pH 7.40 for normal, placental, heterozygoud and homozygous sickle cell anemic blood in 26.2 +/- 0.1, 20.8 +/- 0.3, 26.8 +/- 0.3 and 31.0 +/- 0.5 mm Hg; in the presence of 5.7 mmol of Na-PAS per liter of blood the P50 values are increased to 28.0 +/- 0.3, 22.9 +/- 0.8, 30.5 +/- 0.6 and 33.9 +/- 0.3 mm Hg, respectively. The Bohr effect in normal and placental blood at this Na-PAS concentration is essentially unchanged: in heterozygous and homozygous sickle cell anemic blood, the Bohr factor (deta log P50/deta pH) is reduced from -0.48 +/- 0.02 to -0.41 +/- 0.01 and from -0.53 +/- 0.03 to -0.48 +/- 0.01. The Hill constants (n) of normal and placental blood are not affected by Na-PAS. In homozygous and heterozygous sickle blood, high concentrations of Na-PAS (22.9 mmol/l) decrease the Hill constant from 2.55 to 2.35 and from 2.56 to 2.28, respectively. Na-PAS is more firmly bound to red blood cells than to plasma. The binding of Na-PAS is probably primarily ionic in nature since the drug can be almost completely removed from blood components by dialysis. The changes in oxygen affinity caused by Na-PAS are consistent with conformational changes (R leads to T) which enhance the presence of deoxyhemoglobin.

Adult↗
PubMed1982

Short-term inhibition of fatty acid biosynthesis in isolated hepatocytes by mono-aromatic compounds.

An overview is presented of a selected number of mono-aromatic derivatives and their short-term effects on hepatic fatty acid biosynthesis. The compounds discussed in this paper are ortho-hydroxybenzoate (salicylate), meta-hydroxybenzoate, para-hydroxybenzoate, benzoate, para-t-butylbenzoate, para-aminosalicylate, clofibrate, halofenate, alpha-cyano-4-hydroxycinnamate and benfluorex. All of these drugs inhibit fatty acid biosynthesis by isolated rat liver cells, albeit with different effectiveness. In contrast, the compounds have differential effects on fatty acid esterification and oxidation by isolated hepatocytes. An attempt is made to describe in molecular terms the underlying mechanisms of the acute inhibitory effects of the mono-aromatic derivatives on hepatic lipogenesis. It is proposed that all of the drugs exert an inhibitory action at the level of acetyl-CoA carboxylase, the enzyme generally considered to catalyse the rate-limiting step in hepatic fatty acid synthesis. This inhibitory effect may be either direct, i.e. by an alteration of the enzyme's structure as a result of interaction between drug and enzyme, or indirect, i.e. through a drug-induced change in the cellular levels of allosteric effectors of acetyl-CoA carboxylase.

Acetyl-CoA Carboxylase↗
PubMedDate not supplied

Fractionated precipitation of acid macropolyanions by dialysis, a simple method for the estimation of DNA in complex biological samples.

After efficient extraction by para-aminosalicylate, chopping, grinding and eventual sonication, the macropolyanions are transformed into their cetyltrimethylammonium salts. These have differing solubilities, strongly depending on ionic strength. The cationic detergent-macropolyanionic salts are solubilized by high salt concentration. Salt is then dialysed out, rendering the polyanions highly insoluble in a sequential fashion. The insolubilized components are determined quantitatively by monitoring turbidity, which in case of DNA is strictly proportionate to its concentration. This relation is not affected by other components. This makes DNA determination possible even in crude aqueous extracts. The method has been applied to different objects, such as bacteria, plants, animals, soil and activated sludge. The method may prove to be especially useful in research of environmental poisons e.g. in rivers, lakes or clarifiers.

Animals↗
PubMed1977

P-aminosalicylate metabolism in cancer patients sensitive and resistant to chemotherapy.

A reduced response of a tumour to chemotherapy may be due to the host's drug metabolism. To test this hypothesis, we measured the metabolism of a model drug, para-aminosalicylate (PAS). Volunteers and cancer patients ingested a single oral dose (2 g) of PAS and we measured the plasma disappearance curve of the drug and its metabolite. In 7 patients suffering from lymphosarcoma, acute or chronic leukaemia and resistant to cancer chemotherapy, we observed low plasma PAS concentrations, an increase in PAS acetylation and an increased number (and a higher frequency) of abnormal liver-function tests. In 14 patients with malignant blood disease, yet responding well to chemotherapy, the metabolism of PAS is similar to that of healthy controls of the same age and sex. The plasma half-life of PAS is similar in sensitive and resistant patients, but slightly longer than in volunteers. Finally, in urine collected 120 min after drug administration, we observed the same results as in plasma. In conclusion, cancer patients resistant to chemotherapy do not metabolize the model drug PAS as volunteers or sensitive patients do, and this might be relevant to the terminal stage of the disease.

Acute Disease↗
PubMed1969

Intermittent chemotherapy for tuberculosis in an urban community.

A regimen designed for effective foolproof antituberculosis treatment, acceptable on a routine basis, was applied to all patients newly diagnosed at the Chest Clinic, Hammersmith Hospital, in 1963, 1964, and 1965. During the first three months of treatment patients received daily (six days a week) streptomycin 0.75 g. plus isoniazid 300 mg. plus sodium para-aminosalicylate (P.A.S.) 12 g. The P.A.S. was usually stopped when bacterial sensitivity reports made this possible. For a further 15 months streptomycin 1 g. plus isoniazid 600 mg. was given on three alternate days each week to complete a total of 18 months' treatment.Of the total of 140 patients (66% sputum-positive) 112 (80%) completed the planned 18 months with intermittent streptomycin plus isoniazid and a further eight completed treatment on alternative regimens (a total of 85%). The equivalent figures for one year are 88% and 94%. Excellent clinical and radiological results, together with sputum conversion, were achieved in 138 of the 140 patients (99%). Only two patients were lost from surveillance, because of failure to co-operate, before quiescence was obtained.It is concluded that the total efficiency of supervised intermittent treatment is greater than that of unsupervised daily regimens. Since 100% arrest of tuberculosis is possible with co-operative patients, less should not be accepted in developed countries.

Adolescent↗
PubMed1996

The effect of 5-aminosalicylate and para-aminosalicylate on the synthesis of prostaglandin E2 and leukotriene B4 in isolated colonic mucosal cells.

The effect of 5-aminosalicylate (5-ASA) and para-aminosalicylate (PAS) on the synthesis of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) was studied in 24 healthy volunteers. Both drugs are successfully used in the treatment of chronic inflammatory bowel disease, but the biochemical pathway of their anti-inflammatory action is still unknown. Biopsies were taken from the descending colon and were isolated biochemically. 5-ASA, PAS and a control were added to the suspension of isolated colonic mucosal cells and incubated over 0-45 min. Both 5-ASA and PAS did not alter the PGE2 production but, compared with PAS and the control, 5-ASA decreased the LTB4 synthesis in a dose-related fashion. As a result, the LTB4/PGE2 ratio was significantly diminished by 10(-4) mol/l 5-ASA. These findings are consistent with those of other authors, indicating that 5-ASA, at least in part, modulates the colonic eicosanoid synthesis. In contrast, PAS did not influence the mucosal production of PGE2 and LTB4 and therefore must exert some other biochemical action in order to explain its therapeutic effects in the treatment of Crohn's disease or ulcerative colitis.

Adult↗
PubMed1994

[Enhancement of rectal absorption of rifampicin by sodium para-aminosalicylate dihydrate in human subjects].

The suppositories of rifampicin (RFP) containing sodium para-aminosalicylate dihydrate (PAS-Na) were prepared in order to enhance the rectal absorption of RFP. By the addition of PAS-Na, the in vitro release of RFP from the suppositories was enhanced and the hardness of the suppositories decreased. The rectal absorption of RFP from the suppositories containing no PAS-Na (control suppositories) was significantly lower compared to oral administration of it (26%) in human subjects. When PAS-Na was added to the suppository (300 mg), both the area under the plasma concentration-time curve (AUC) and the maximum plasma concentration (Cmax) increased significantly compared to those of the control suppositories. The rectal absorption of PAS-Na itself from the suppositories seemed to be fast. PAS-Na might increase the absorption of RFP dissolved in the rectal fluid from the suppositories, but not affect the undissolved RFP.

Administration, Oral↗
PubMed1999

The effect of hemodialysis on cycloserine, ethionamide, para-aminosalicylate, and clofazimine.

STUDY OBJECTIVES: Determine hemodialysis clearances of the second-line antitubercular drugs cycloserine (CS), ethionamide (ETA), para-aminosalicylate (PAS), and clofazimine (CFZ). DESIGN: Open-label, pharmacokinetic study SETTING: Outpatient long-term hemodialysis unit PARTICIPANTS: Eight long-term hemodialysis patients Interventions: Single oral doses of CS, 500 mg, ETA, 500 mg, PAS, 4,000 mg, and CFZ, 200 mg, were given 2 h (4 h for PAS) prior to hemodialysis (median blood flow rate, 400 mL/min; median dialysate flow rate, 600 mL/min; median hemodialysis time, 3.5 h). MEASUREMENTS AND RESULTS: Arterial and venous serum samples were collected at the beginning and end of hemodialysis, and hourly during hemodialysis. Dialysate fluid was collected for the duration of hemodialysis. All samples were assayed for drug concentrations using validated high-performance liquid chromatography (for ETA and PAS), capillary electrophoresis (for CS), and colorimetry (for CFZ). Dialysate samples were analyzed for acetyl-PAS. Median recoveries of drug in dialysate were 56% (CS), 2.1% (ETA), 6.3% (PAS parent compound), and 0% (CFZ) of the doses administered. Acetyl-PAS was dialyzed to a greater extent than its parent compound. Median hemodialysis clearances calculated by dividing the amount recovered in dialysate by the serum area under the curve during dialysis were 189 (CS), 58 (ETA), 206 (PAS), and 0 (CFZ) mL/min. CONCLUSIONS: ETA, CFZ, and PAS were not significantly dialyzed. CS is significantly removed by hemodialysis and should be dosed after hemodialysis.

Adolescent↗