Non-linear tissue binding of amikacin in rats: the effect of renal impairment

Amikacin levels in serum and tissues were determined in 115 Wistar rats, 70 with normal renal function (NRF) and the remaining 45 with terminal renal impairment (TRI). The results obtained in the animals with NRF show an accumulation of the antibiotic in all the tissues studied as compared with plasma levels, specially in the renal cortex and medulla. In the rats with TRI important alterations in the plasma and tissue kinetics of the antibiotics were observed. The plasma kinetics of amikacin in rats with TRI are characterised by significant alterations in the pharmacokinetic parameters, specially those defining the distribution processes of the antibiotic. In the tissues of the latter, a significant increase in the antibiotic concentration takes place, particularly in the renal cortex. The average half-lives of the antibiotic in the tissues of rats with TRI increase compared with the group of rats with NRF, though the difference are not so significant as in the case of the plasma half-life. The use of a specific kinetic distribution model, with linear and non-linear tissue binding, showed that significant variations occur in the partition coefficient and in the Michaelis-Menten parameters, which characterize the saturable binding of Amikacin to tissue in rats with NRF and TRI.     

Correlations between the functional activity and proliferation of the thyroid parenchyma. The proliferative forms of the parenchyma of the thyroid

Multiple thyroid adenomas formed by straight or coiled epithelial cords developed in experiments on adult male rats as a result of prolonged intermittent 6-MTU administration. Such epithelial cords could be sometimes observed in thyroid parenchyma regeneration after partial thyroidectomy. These cords originated from thyrocytes of the follicle epithelium. In the proliferating thyroid parenchyma DNA replication mainly terminated in endomitoses (previously reported data) which in thyrocytes of prismatic form resulted in their separation from proximal and distal daughter cells. Proximal daughter cells kept contact with the follicle lumen but distal ones lost it, hence their iodine uptake and origination weakened. Therefore, the biosynthesis of thyroglobulin decreased in cytoplasm of distal daughter cells but the formation of thyroalbumin increased. In consequence the distal daughter cells with this shift in protein biosynthesis underwent hypertrophy and further originated the proliferation of extra follicular epithelial cords. The formation of new follicles mainly took place with the differentiation of interfollicular islets separated from proliferating extrafollicular epithelial cords. Thyrotropin, the principal stimulator of hormonopoietic thyrocyte activity, did not necessarily influence the activation of thyroid parenchyma proliferative processes.     

Glutathione localisation in benign and malignant human breast lesions

Reduced glutathione (GSH) has been demonstrated in benign and malignant human breast lesions using a newly developed histofluorescence technique. GSH was present in every lesion and in each case was localised to the epithelium. A semi-quantitative assessment revealed a moderate amount of GSH in normal epithelium and fibroadenoma and a high level in apocrine metaplasia, epitheliosis and intraduct carcinoma. Invasive ductal carcinoma contained a variable amount of GSH. Correlation between fluorescence intensity and histological grade of ductal carcinomas was almost statistically significant but a relationship to oestrogen receptor status was not detected. The rapid assessment of GSH in breast cancer may aid in the selection of optimum chemotherapeutic regimens.     

The adrenergic inhibitors

Although most of the centrally and peripherally-acting adrenergic inhibitors have been available for several years, they continue to contribute importantly to antihypertensive therapy. There are remarkably few contraindications to their use. They are useful in hypertension of all grades of severity, and are also valuable in complicated forms of hypertension, such as those associated with renal insufficiency, diabetes mellitus, and chronic obstructive lung disease. They can produce some fairly predictable side effects in patients, but generally do not cause significant metabolic changes. These drugs also seem to be tolerated well by physically active patients. They appear to have desirable effects on cardiac structure. In general, the adrenergic inhibitors cause regression of a left ventricular hypertrophy, which may well be a valuable property, especially in older hypertensive patients.     

Organ-sparing operations in pyloroduodenal stenosis caused by peptic ulcer

An experience with the treatment of 106 patients with pyloroduodenal stenosis of ulcerous etiology by vagotomy with draining operations has shown high efficiency of these measures resulting in lower rate of postoperative lethality. Selective proximal and stem vagotomy does not aggravate gastric atony in patients with stenosis. Electro-stimulation was found to be an effective method of treatment of this complication in the postoperative period of patients with gastric atony.