Respiratory deposition patterns of salbutamol pMDI with CFC and HFA-134a formulations in a human airway replica.

This paper describes a technique that uses a well-defined human airway replica and gamma counting as a standard method for evaluating and comparing the performance of medical inhalers and spacers. High-fidelity replicas reproduced as needed from master casts made from human cadavers include the oropharyngeal cavity, larynx, trachea, and five to nine generations of bronchi. Deposition in the small airways and alveoli region of the cast is simulated by material that passes through the upstream airways and is collected on foam filters. Deposition patterns in the respiratory tract replica were obtained by using radiolabel in the medical inhaler and by gamma scintigraphy. This technique was used to determine respiratory deposition patterns of salbutamol in a pressurized metered dose inhaler (pMDI) with chlorofluorocarbon (CFC, in-house formulation) and HFA-134 formulations (Proventil hydrofluoroalkane [HFA]). At an inspiration flow of 30 L/min, patterns in the salbutamol/CFC formula showed a high deposition in the oropharyngeal airway (78%) and a 16% deposition in the lung, similar to in vivo measurements reported in the literature. However, the salbutamol/HFA formula showed lower oral deposition (56%) but higher lung deposition (24%). The difference in the oral deposition patterns may be attributed to lower initial spray velocity, initial droplet evaporation rate, and possibly initial droplet sizes of Proventil HFA. The small orifice diameter (0.25 mm) of the Proventil HFA actuator produced a softer plume with a smaller impact force, resulting in lower oropharyngeal deposition. Cascade impactor measurements showed similar aerodynamic particle size distribution of the CFC and HFA formulations. We also showed that using spacers in the Proventil HFA resulted in a lower oropharyngeal deposition and higher lung deposition, indicating beneficial effects. Comparison of oropharyngeal deposition and those predicted by artificial throats used in the impactor measurements showed that, in general, the artificial throat predicted a lower deposition.

Successful treatment of idiopathic colitis and proctitis using thalidomide in persons infected with human immunodeficiency virus.

Gastrointestinal ulcerations in persons infected with HIV have many causes, the most common being opportunistic infections and neoplasms. Recently, idiopathic ulcerative lesions of the colon and rectum have been described. Two cases are reported of idiopathic colonic and anorectal inflammation and ulceration which failed traditional therapies but responded to thalidomide with complete clinical and histologic resolution.

Lack of effect of age and dietary restriction on DNA single-stranded breaks in brain, liver, and kidney of (C3H x C57BL/10)F1 mice.

Single-stranded DNA breaks in brain, liver, and kidney of (C3H x C57BL/10)F1 mice 6 and 25 months of age on two dietary regimens (isonutrient diets at 85 and 50 kcal/week) were investigated by means of fluorometric analysis of DNA unwinding in alkaline solutions. No age-dependent alterations were found for either control or dietary restricted groups. Except for possible differences for liver in the young age groups, there were no significant differences in the amount of single-stranded DNA breaks between control and dietary restricted mice. These results suggest that the antiaging effects of dietary restriction in rodents are not mediated by a change in the number of accumulated nuclear DNA stranded breaks in internal organs.

Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan.

Seven male subjects housed in a controlled metabolic unit for 80 d were fed diets containing amounts of niacin and tryptophan ranging from 6.1 to 32 niacin equivalents (NE) per day. Erythrocyte nicotinamide adenine dinucleotide (NAD) and nicotinamide nucleotide phosphate (NADP), activity of nicotinic acid mononucleotide phosphoribosyltransferase (NMNPRT), plasma tryptophan levels and the urinary excretion of organic acids were measured during dietary periods of low (6.1 or 10.1), adequate (19) and high (25 or 32) NE intake. With both low NE diets, NAD levels in erythrocytes decreased by approximately 70% and increased during repletion with an adequate NE diet. NADP levels remained relatively unchanged. Plasma tryptophan levels decreased by 40% and 10% in subjects ingesting diets of 6.1 and 10.1 NE/d, respectively. A daily 7.8-g leucine supplement during repletion was not associated with changes in plasma tryptophan levels or erythrocyte NAD and NADP levels at the end of the period. No changes in NMNPRT activity or organic acid excretion were found during the study. The results indicate that the erythrocyte NAD level may serve as a sensitive indicator for the assessment of niacin status. Also, a niacin index, the ratio of erythrocyte NAD to NADP, below 1.0 may identify subjects at risk of developing a niacin deficiency.

Biochemical markers for assessment of niacin status in young men: urinary and blood levels of niacin metabolites.

Biochemical markers of niacin status were studied in healthy young men fed 6.1 to 32 niacin equivalents (NE) per day over an 11-wk period while residing in a metabolic unit. Methylated metabolites of niacin, N1-methylnicotinamide (NMN) and N1-methyl-2-pyridone-5-carboxamide (2-pyr), in urine and plasma were determined during periods of low (6.1 or 10.1 NE per day), adequate (19 NE per day = 1 RDA) and high (25 or 32 NE per day) niacin intakes and after small test doses of nicotinamide. Urine excretion of less than 1.2 mg/d of either NMN or 2-pyr was a reliable indicator of subjects receiving the lowest intake of 6.1 NE/d, but the NMN metabolite was a better marker of subjects ingesting 10.1 NE/d. The ratio of 2-pyr/NMN in urine was not as good a measure of the 6.1 NE/d intake as the individual metabolite excretions and was not responsive to the 10.1 NE/d intake. Plasma niacin metabolites were generally not as reliable as urinary metabolites for identifying subjects receiving low niacin intakes, however, values for plasma 2-pyr dropped quickly and were eventually nondetectable. After a 1 RDA oral dose of nicotinamide, increases in urine and plasma 2-pyr levels above pre-dose baseline values were significantly decreased in subjects receiving low, as compared to adequate, niacin intake. A leucine supplement had no effect on the rate of repletion of niacin-deficient subjects nor on the level of methylated niacin metabolites in urine or plasma.

Application of fuzzy set theory to biochemical processes--a new model for problem diagnosis.

Fuzzy set theory provides a helpful basis for study of model building in biochemical processes. A new approach to the field of problem diagnosis, based on fuzzy set theory, has been devised. This paper describes a practical diagnostic model for the problem of contamination in an industrial antibiotic production process. The results of theoretical analysis and on-site testing show that this approach can also be used as a prototype for modeling similar diagnostic problems.

Study on late effects of radioiodine on rats.

This paper describes the results observed on 850 male Wistar rats for two years after intraperitoneal injection with 131I, 132I or 125I of different radioactivities. The incidence of thyroid malignant tumor was 45.8% when the dose absorbed by the thyroid gland was 7.8 Gy in the 131I groups, and even tumors of lung and soft tissue, and malfunction of kidney and immune organs could be elicited when the radioiodine was overdosed. Both 132I and 125I have their optimal carcinogenic dose ranges and optimal doses of carcinogenesis. As the dosage decreases to a certain level, a low-limit dose incapable of inducing cancers may be present. 131I induced mainly papillary and mixed type carcinomas, 132I chiefly follicular and undifferentiated type carcinomas, while 125I induced follicular and medullary carcinomas. The paper also discusses cytochemical DNA quantitative assays of different histological types of thyroid gland carcinomas, holding that reference to such data as decreasing serum T4, elevating serum TSH and CIC may be helpful for early diagnosis of thyroid carcinomas.