Subchronic Toxicity Study in Rats with 1-Methyl-3-propylimidazole-2-thione (PTI): Effects on the Thyroid

A 90-day gavage study was performed to evaluate the sub-chronictoxicity of 1-methyl-3-propylimidazole-2-thione (PTI) when administeredto Crl:CD BR rats. PTI is a chemical catalyst and is structurallysimilar to the thioureas, which are known to adversely affectthe thyroid. Therefore, this study was designed to investigatethe effects of PTI on the thyroid. Male and female rats weredosed with 0,5,10,25, or 75 mg PTI/kg/day for 13 weeks. Clinicalpathology examinations and pathology examination were performedand the following were measured periodically: serum T₃, T₄,and TSH, hepatic UDP- glucuronyltransferase activity, and cellproliferation of the thyroid and liver. Under the conditionsof this study, the overall no-observed-adverse-effect level(NOAEL) for the subchronic effects of PTI in male and femalerats was 10 mg PTI/kg/day. The NOAEL was based on the effectson the thyroid gland in male and female rats dosed with 25 and75 mg PTI/kg/day, as well as the hepatic centrilobular fattychange, increased severity of chronic progressive nephropathy,fatty change in the adrenal medulla, and the substantial reductionin body weight and body weight gain. The primary target organswere the thyroid and liver. Alterations in thyroid hormones(T₃, T₄, and TSH) occurred predominantly at 25 and 75 mg/kg/day.Toxicologically significant alterations in T₃, T₄, and TSH levels,cell proliferation, and UDP-glucuronyltransferase activity occurredin rats dosed with 25 and 75 mg/kg/day, which correlated withorgan weight and histopathological effects. Additionally, theeffect of PTI on thyroid peroxidase activity, a key step inthyroid hormone synthesis, was evaluated in vitro using microswinethyroid microsomes. PTI was shown to inhibit thyroid peroxidase,with an IC50 of 0.02 M. These data suggest that PTI enhancesthe excretion of T₄ via induction of glucuronyltransferase andinhibits thyroid hormone synthesis via a direct affect on thyroidperoxidase. Both of these effects contribute to the disruptionof the hypo-thalamic-pituitary-thyroid axis and result in sustainedelevation of TSH and the corresponding thyroid hypertrophy andhyperplasia.     

Presence of Several Elements in Normal and Pathological Human Semen Samples and its Origin

Summary:  Spectroscopic analysis of seventeen normal and pathological semen samples was done to reveal the different elements present in it. The sensitivity of the instrument was 1 μg/g. The observed elements include sodium, potassium, magnesium, calcium, phosphorus, iron, manganese, zinc, copper, boron, silicon, thalium, vanadium, aluminium, mercury and gold. This is the richest source of gold reported in biological materials. An attempt was done to locate the origin of these elements. Thus gold is released from caput epididymis.
Zusammenfassung:  Das Vorhandensein verschiedener Spurenelemente im normalen und pathologischen Spermaplasma und ihre Herkunft
Spektroskopische Analysen von siebzehn normalen und pathologischen Spermaproben wurden vorgenommen, um die darin enthaltenen Spurenelemente nachzuweisen. Die Empfindlichkeit des instrumentes betrug 1 μg/g. Die beobachteten Spurenelemente umfaßten Natrium, Magnesium, Kalzium, Phosphor, Eisen, Mangan, Zink Kupfer, Bor, Silicium, Thallium, Vanadium, Aluminium, Quecksilber und Gold. Es handelt sich um den größten Goldanteil, der in biologischen Materialien nachgewiesen wurde. Es wurde der Versuch unternommen, die Herkunft dieser Spurenelemente zu lokalisieren. Dabei zeigte sich, daß Gold vom Nebenhodenkopf freigesetzt wird.     

Behavioural sciences and the real world: report of a community interview scheme for medical students

Summary. A community interview scheme was designed to provide preclinical medical students with an opportunity to investigate the role of social and psychological variables in patient care and gain insight into interpersonal aspects of the interview process. Evaluation of the scheme showed that students and community interviewees found their participation valuable. Eighty per cent of interviewees were willing to take part in the scheme in the following year. The strongest predictor of willingness to participate was interviewees' rating of the extent to which they had enjoyed the experience. Students valued the opportunity to meet ‘real people’, to explore social and psychological determinants of health and illness and to develop communication skills. A significant positive change in perceived interviewing competence was observed. It is suggested that the scheme might be further developed by using feedback from interviewees to provide students with evidence of both their own skill development and the benefits of self-disclosure to the patients involved.     

GRISEOFULVIN THERAPY IN LICHEN PLANUS

Summary.— Thirty-four patients with lichen planus were treated in a double-blind trial in which either 500 mg of griseofulvin-FP or a placebo was issued to the patients on a random distribution basis. A significant difference was found between the results obtained with griseofulvin and those with the placebo. The favourable response to the treatment was accompanied by more or less typical histopathological features. No untoward effects, or recurrence in lesions were noted in the course of the trial.     

The Activation of Factor X by Extracts of Rabbit Brain

Thromboplastic preparations were obtained from rabbit brain. The dataindicate that standard acetone-dried reagent functions by activating factorX, with factor VII as an accelerator. When crude tissue reagent was fractionated by butanol treatment and saline extraction, a water-soluble materialwas obtained which similarly activated factor X. In each case, a source ofphosphatide was necessary for activated factor X to yield full clotting activity;this phosphatide was provided in the crude tissue reagent but it was lacking in the water-soluble extract.

The extract was further purified and characterized. It appears to be aprotein and it evidently activates factor X enzymatically. The data thusindicate that brain thrombloplastin contains two separable clotting activities:one of these activates factor X, the other supplies phosphatide.

Submitted on July 21, 1963 Accepted on November 16, 1963     

Effects of induced hypotension on breathing pattern in halothane-anaesthetized man

Abstract. The effects of hypotension induced by trimetaphan on ventilatory control were assessed in sixteen normal subjects under halothane anaesthesia. The breathing pattern, mouth occlusion pressures, lung mechanics, acid-base balance, and arterial blood gases were analysed before and during trimetaphan infusion. During induced hypotension, the only significant change in the ventilatory variables was an increase in the ratio of inspiratory duration to total cycle duration from 0.39 ± 0.05 (SD) to 0.42 ± 0.03; P < 0.01. The average minute ventilation remained unchanged. No modification in lung mechanics was observed, but all subjects developed a slight but significant hypocapnic alkalosis: PaCO₂ was reduced from 5.5 ± 0.4 to 5.2 ± 0.4 kPa ( P ± 0.001) and pH increased from 7.34 to 7.36 ( P < 0.05), without change in standard bicarbonate concentration.
Our data indicate that the reduction in sympathetic nervous system activity induced by trimetaphan infusion in spontaneously breathing man causes only a minor alveolar hyperventilation. The weak respiratory response to hypotension suggests that changing peripheral afferent activity has little influence on the typically rapid breathing pattern induced by halothane.     

REHABILITATION OF AMPUTEES WITH PROGRESSIVE VASCULAR DISEASE

Amputees with progressive vascular disease constitute about76% of the total patients who were rehabilitated in this departmentduring the years 1959 to 1969. The total group of 147 patientswith progressive vascular disease was divided into three subgroupsfor evaluation of results: Group A, diabetic vascular disease—averageage at amputation, 66 years; Group B, arteriosclerosis oblkerans(ASO)—average age at amputation, 62 years; and Group C,Buerger's disease—average age at amputation, 41 years.Of the 147 patients 67% were diabetic, which represents an unusuallyhigh proportion; the majority were known to have suffered fromdiabetes for six years or more. There was a clear preponderanceof men in the three subgroups. The death rate among the diabeticand ASO patients was particularly high in the first five yearsafter amputation. Evaluation of rehabilitation results amongthe patients was determined according to their independence.This independence is related to the aetiological factors andthe level of amputation. Myocardial infarction reduces the rehabilitationpossibilities, and cerebrovascular accidents diminish them evenfurther. Increasing age does not appear to be a deterring factorin relation to success in rehabilitation. Diabetic retinopathydoes not affect the chances of successful rehabilitation; however,the high percentage of diabetic retinopathy suggests that illnessdamages capillaries in amputees.