Metallothionein induction by cadmium and zinc in rat secretory organs

Metallothionein (MT) levels were determined in four secretory organs of the rat following administration of zinc (Zn) and cadmium (Cd). The concentrations of MT in the lacrimal, parotid and adrenal glands of untreated rats were in the range of 2.2-4.9 micrograms/g wet weight tissue while in the pancreas it was shown to be 15.2 micrograms/g. Injection of zinc at total doses of 16, 32 and 80 mg/kg resulted in a 1.8-, 3.2- and 5.9-fold increase in lacrimal MT content, respectively, while a 10.2- and 13.1-fold elevation was observed following treatment with 4 and 8 mg/kg of Cd, respectively. Similar findings were found in the adrenal gland. The parotid MT was elevated 5.9 and 17 times following Zn treatment at doses of 16 and 80 mg/kg respectively, whereas 4 mg/kg of Cd increased MT 14.4 times in this gland. Pancreatic MT was elevated by 39- and 40-fold after injection of Zn at doses of 16 and 32 mg/kg respectively, whereas 4 and 8 mg/kg of Cd caused a 9.8- and 17.9-fold induction, respectively. These results may indicate that secretory organs participate in metabolism of heavy metals in the mammalian body.     

Adrenocortical metabolism and plasma corticosterone in soman intoxicated rabbits

Summary The organophosphate neurotoxin soman produced impairments in adrenocortical RNA and protein metabolism. Fasciculate and reticular cell RNA and protein contents were supporessed with sublethal to acutely lethal dosages (20, 30 and 40 g/kg, s.c.) during the acute excitatory phase of intoxication and at 6–8 h post injection. All three dosages produced ca 90% inactivation of plasma cholinesterase. A transient elevation of plasma corticosterone occurred with 20 g/kg soman whereas there was a protracted increase with 30 g/kg. Corticosterone was not significantly elevated with 40 g/kg, but death occurred at 13±4 min. Thus, the magnitude and/or nature of soman-induced metabolic impairments does not appear to prevent adrenal activation.Supported by US Army Medical Research and Development Command Contract DAMD 17-81-C-1202.     

Prostaglandin E1 induced salivary secretion

Summary PGE₁ but not PGF₂ at 500–1000 g/kg induced a slow and sparse flow from the parotid and no flow at all from submaxillary glands. Composition of PGE₁-induced parotid saliva was quite different from that evoked by any autonomic agonists. The present study suggests that PGE₁ might act directly on parotid acinar cells.Acknowledgment. This work was supported by NIDR grant DE05633. The authors wish to thank Ms Sonya Wynn for her technical assistance.     

The enhanced induction of metallothionein by zinc,its half-life in the marine fishPleuronectes platessa,and the influence of stress factors on metallothionein levels

Summary Intraperitoneal injection of zinc raised levels of a hepatic metallothionein-like species. Assuming that this species was metallothionein (MT) then levels were raised from approximately 20 g/g to 300 g/g in 7 days, and levels thereafter remained high for the next 4 weeks. The half-lives of the protein in liver and kidney from starved fish, measured using in vivo incorporation of³⁵S cysteine at 11°C, were approximately 27 days and 32 days respectively. The following agents failed to stimulate synthesis of MT in plaice: stress (due to catching), endotoxin, dexamethasone, cortisol and turpentine.     

Amylin given by central or peripheral routes decreases gastric emptying and intestinal transit in the rat

The effect of rat amylin on gastric emptying and intestinal transit in the rat was examined. Amylin administered intracerebroventricularly (1, 2, 2.5 or 4 g/rat) produced the maximal decrease in gastric emptying and intestinal transit at the dose of 2.5 g/rat. Higher doses produced a lower effect. Peripheral administration (25, 50 or 100 g/kg) produced dose-dependent effects. Pre-treatment with neostigmine blocked the effect of amylin when it was centrally injected, while the effect of amylin given peripherally was partially reduced. Pre-treatment with domperidone decreased the inhibitory effect of peripherally injected amylin, but no effect was observed when the peptide was centrally injected.     

The influence of peripheral or central administration of ondansetron on stress-induced gastric ulceration in rats

Ondansetron (0.08, 0.15 or 0.3 mg/kg) injected s.c., every 12h with the fourth dose given 0.5 h before experiments, dose-dependently lessened gastric glandular mucosal ulceration produced by cold-restraint stress for 2h. When given intracerebrally (i.c.) (0.1, 0.5 or 1g), using the same treatment regimen, infusion of ondansetron 1 g into the nucleus amygdaloideus centralis decreased stress-evoked ulcers; in contrast, injection of the same dose into the nucleus accumbens intensified these lesions. The associated stress-induced stomach wall mast cell degranulation was unaffected by all s.c. or i.c. doses of ondansetron. Pretreatment with disodium cromoglycate i.p. alone, or concurrently with ondansetron s.c., prevented not only ulceration but also mast cell degranulation. 5-Hydroxytryptamine₃ receptor antagonism appears to inhibit stress-evoked ulcers mainly by blocking the peripheral effects of the amine after its release from the gastric mucosal mast cells.     

Serotoninantagonismus an der Placenta

Summary The placentae of 17 to 19 days pregnant mice respond to subcutaneous serotonin (15 mg/kg) with vascular changes which lead to the death of the fetuses in 3–4 h. Pretreatment of the females withd-lysergic acid derivatives preserves the life of the young. Thus, LSD showed an ED₅₀ of only 30 g/kg, while UML (Deseril®) gave an ED₅₀ of 3.7 g/kg. PML takes an intermediate position. At a 50% efficiency level, UML (Deseril®) antagonises the effect of a 4000 times higher dose of serotonin.     

Alpha adrenergic control of growth hormone in adult male rats

Summary Intravenous injection of 0.1 mg/kg clonidine into rats under urethane anaesthesia induced a prompt and long-lasting release of growth hormone, estimated by radioimmunoassay (IRGH), which could be abolished by 0.2 mg/kg phentolamine given into the 3rd ventricle. Injection of 3 g/kg clonidine into the 3rd ventricle stimulated also the release of IRGH significantly. Intravenous administration of 0.32 mg/kg phenylephrine caused a small and transient release of IRGH only. These results provide evidence that central -adrenergic stimulation resulting in an increased GH secretion is one importantmechanism in the regulation of this hormone in the rat.     

Cadmium-induced changes in renal hemodynamics in the domestic fowl

Summary Low i.v. doses of cadmium chloride (15 g Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed.It is suggested that the renal changes following the i. v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.     

Bombesin promotes pancreatic growth in suckling rats

Summary The pancreatic growth promoting effect of long term administration of bombesin was investigated in suckling rats. The authors showed that bombesin given in 10 g/kg b.wt doses s.c. every 8 h for 10 days from the day of parturition stimulated pancreatic growth: it increased pancreatic weight, protein and DNA content, trypsin and amylase activity and trypsin/DNA ratio. Conclusion: Bombesin is an effective stimulator of pancreatic growth in suckling rats.     

Biodegradation of bitumen used for nuclear waste disposal

Summary Studies have been carried out to test microbial degradation of bitumen used for encapsulating radioactive waste in Sweden. Microorganisms have been isolated that degrade bitumen. In ong-term tests under conditions simulating those in the silo part of the final repository for low-and intermediate-level radioactive waste, both aerobic and anaerobic degradation of bitumen has been found, equivalent to 0.6–1.5 moles CO₂/month·mg bitumen and 1.1–1.5 moles CO₂/month·mg bitumen, respectively.     

Effects of female sex hormones on polyamine-oxidizing enzyme activities and polyamine concentrations in immature rat uterus and liver

17-estradiol (E₂) and progesterone (P) treatment of immature female rats (10 g/100 g body weight) respectively resulted in 1.38-fold (p<0.02) and 1.42-fold (p<0.02) increase in the uterine polyamine oxidase activity, and 2.45-fold (p<0.001) and 1.43-fold (p<0.02) increase in the uterine diamine oxidase activity, as compared to the controls. E₂ caused a 5-fold (p<0.05) and a 1.36-fold (p<0.05) increase in putrescine and spermidine concentration respectively in rat uterus. Increases of 1.7-fold (p<0.02) and 1.6-fold (p<0.05) in putrescine and spermine concentration were determined in the P-treated uterus, as compared to the controls. The spermidine/spermine ratio, which is regarded as an index of growth rate, was higher in the E₂-treated uterus and lower in the P-treated uterus than in the control uterus. No statistically significant hormonal effects were estimated in the immature liver. The data reported suggest the possibility of an involvement of polyamine-oxidizing enzymes in the modulation of polyamine concentrations in rat uterus by the female sex hormones.     

The instability of dietary iodine supply over time in an affluent society

In the Bernese region, where goiter was formerly endemic, alimentary salt has been supplemented by increasing amounts of potassium iodide (KI): 5, 10, 20 mg KI/kg in 1922, 1965 and 1980 respectively. Ioduria rose from <30 g I/g creatinine in 1920 to >100g I/g creatinine in the 1980s. In 1992 ioduria was estimated in 55 healthy volunteers (group A and individual B) and 234 thyroid carcinoma patients after thyroidectomy: hypothyroid patients with (C) and without thyroid remnants (D) and euthyroid patients on T4^** substitution (E). The arithmetic mean iodine excretion of the healthy volunteers in group A and individual B was found to be 87±40 g I/g creatinine. This is insufficient according to the recommendations of the WHO. In all groups, the iodine excretion reached the recommended level only in some members: 24% (A, B), 19% (C), 38% (D) and 81% (E).It was thought in the 1980s that in a formerly iodine-deficient society, iodinated salt would continue to provide an adequate supply of iodine. However, iodine intake in this affluent society has proved to be unstable. This can be attributed to modifications of eating habits, which include a reduction of total salt consumption, combined with a growing consumption of manufactured food of cosmopolitan origin, prepared using salt containing little or no iodine.     

Extraction from hog duodenum of a high molecular weight protein with gastric antisecretory activity

Riassunto Un nuovo metodo di estrazione ha condotto alla parziale purificazione dal duodeno di maiale di una proteina ad alto peso molecolare, fortemente attiva nell'inibire la secrezione gastrica nel ratto a piloro legato. 250 g/kg e 100 g/kg inibiscono del 50% rispettivamente il volume di secrezione gastrica e l'acidità cloridrica.     

Dopamine and cerebral cortical blood flow in the rat

Summary Dopamine topically applied to the cerebral cortex (1–20 g/ml) or administered i.v. (0.5–64 g/kg/min) has no effects on cerebral cortical blood flow in the rat.     

D-ala2-Metenkephalinamide blocks the synaptically elicited cortical spreading depression in rats

Summary Spreading depression (SD) was elicited in rats anesthetized with pentobarbital by a train of 8 electrical pulses (0.1 ms, 10 Hz) applied to parietal cortex. Local application of 50 g of D-ala²-metenkephalinamide (DAME) on the stimulated area evoked one or two SD waves followed by an increase of SD threshold from 40 V to 90 V. This effect could be partly prevented by naloxone (1 mg/kg i.p.) and reversed by local application of 4-aminopyridine (10^–3 M, 2 l), which reduced SD threshold to 5 and 20 V in normal and DAME-treated cortex, respectively. It is argued that DAME exerts an inhibitory effect on cortical neurons and that the initial SD facilitation is due to initial blockade of inhibitory neurons in the superficial cortical layers.supported by the European Training Program in Brain and Behavior Research.     

The dopamine autoreceptor agonist B-HT 920 markedly stimulates sexual behavior in male rats

Summary B-HT 920, a selective agonist at dopamine (DA) autoreceptors, strongly increased the incidence of penile erections (PE) in male rats, an effect which was dose-related and antagonized by haloperidol. B-HT 920 at 100 and 200 g/kg i.p. significantly altered the copulatory pattern of sexually active male rats, reducing the number of mounts and intromissions as well as the latency to the first ejaculation, a stimulant effect which was confirmed in sluggish males at a dose of 100 g/kg.     

Influence of phenobarbital and TCDD on the hepatic metabolism of TCDD in the dog

Summary The influence of phenobarbital and TCDD pretreatment on the formation and biliary excretion of TCDD-metabolites following single doses of³H-TCDD was investigated. Without pretreatment, 24.5% of the absorbed³H-TCDD dose was excreted in the bile within 110 h. Phenobarbital did not influence this rate, whereas a single dose of 10 g of unlabeled TCDD/kg b.wt nine days earlier resulted in a doubling of the amount of radioactive material eliminated in the bile (47.4%).     

Stimulation of gastric secretion by prostaglandin F2 α in rats

Summary In rats with chronic gastric fistulas, prostaglandin F₂ stimulated the gastric acid secretion in graded doses of 50. 100, 200 and 400 g/kg b. wt, while higher doses above 1 mg/kg b. wt tended to inhibit significantly. The gastric antisecretory effect of prostaglandin E₁ could not be altered or modified by subsequent treatment of prostaglandin F₂ , while the latter alone without any prior treatment of the former, stimulated output of gastric juice, HCl and pepsin without significantly affecting the concentration of these components.Acknowledgement. The gift of the prostaglandin E₁ and prostaglandin F₂ is acknowledged to Dr J.E. Pike, Upjohn, USA. This paper was read at the IXth Annual Conference of the Indian Pharmacological Society held at Benares (1976) and abstracted in the Indian J. Pharmac.9, 73 (1977).