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The determination of antibiotics in the renal tissue is of real value only if the blood and the residue urine are removed from the kidney. The Authors report a new technique dealing with the washing of the organ "in situ" by means of an artery-vein perfusion succeeded by the sucking of the residue urine from the ureter. The experiments were carried on male albino rats with the following antibiotics: indanylcarbenicillin, tobramycin, fosfomycin and cefazolin.

Modifications in prolactin specific binding in the rat liver induced by different non-steroidal anti-inflammatory drugs (indomethacin, piroxicam, ketoprofen, phenylbutazone, mefenamic acid and acetylsalicylic acid) have been studied. All caused a dose-dependent inhibition of prolactin binding capacity whereas no change was found in dissociation constant values. The inhibitory effect is reversible and highly specific, since insulin binding to the same membrane preparation is not affected. The degree of inhibitory activity on prolactin binding is related to the anti-inflammatory activity of each drug, which supports the hypothesis of an involvement of prostaglandin synthesis.

A number of amines derived from 1,3-bis(3,4-methylen-dioxyphenoxy)propane have been prepared from 1,3-bis-(3,4-methylendioxy-phenoxy)propan-2-one. The acute toxicity and the activity of these compounds on isolated guinea pig ileum have been studied. The majority of the compounds showed clear antagonist activity towards BaCl2, histamine and acetylcholine contracting responses, generally grater than that of papaverine; on the contrary, their antagonist activity towards 5-HT responses was slightly lower.

Specific binding sites for prolactin (PRL) have been studied in human peripheral lymphocytes and erythrocytes of normal adult volunteers and of term cord bloods. In erythrocytes from healthy adult subjects of both sexes a very low specific binding of 125I-human PRL was found (0.24%), whereas a higher binding was found in term cord blood (1.1%). The binding was hormone specific, the binding capacity was 2.6 fmol/4 X 10(9) cells and the Kd was 3.4 X 10(-10) M. In lymphocytes of both adults and term cord bloods an evident specific binding was observed (male adults: 1.6%; female adults: 1.7%; cord blood: 1.8%). The binding was specific for lactogenic hormones and the binding capacity was 3.7 fmol/2 X 10(6) cells and the Kd was 3.9 X 10(-10) M. The presence of specific binding sites for PRL on human erythrocytes and lymphocytes could be used to study PRL binding on blood cells of patients in different physiological or pathological situations.

Histology and cytometrics were evaluated in 50 cases of human breast infiltrating carcinomas (44 ductal, 6 lobular) assayed for the presence of prolactin receptors (PR). The tumors were considered PR positive when the level of specific binding reached or exceeded 0.5%. Twenty-six ductal infiltrating carcinomas and 4 lobular ones were PR positive. No strict correlation was found between PR and degree of histologic differentiation (expressed in grades) or menopausal status. Better differentiated (grade I) ductal carcinomas were, however, mostly PR negative. Evaluation of the mean nuclear diameter (MND) and of the maximal epithelial cellularity (MEC) revealed that in ductal carcinomas a high level of PR (greater than 3% specific binding) was significantly correlated with a high MND. It is concluded that, contrary to that observed in estrogen receptor-positive tumors, PR-positive human ductal carcinomas are more likely to have large nuclei, i.e., cytologically anaplastic, whereas better differentiated (grade I) carcinomas are generally PR negative.

The binding of 125I-labeled ovine prolactin (125I-oPRL) to membranes from different brain regions of pigeon, rabbit, rat, pig, calf, horse, and ewe was studied. The hypothalamus from rabbit, pig, horse, and pigeon showed a low but specific binding for 125I-oPRL clearly different from the other brain regions examined (cortex and cerebellum), whereas in the brain from rat, calf, and ewe the binding was very small and quite uniform in the various regions. Also the membranes from choroid plexus of rabbit, pig, calf, and horse showed an evident specific binding for prolactin. The binding of 125I-oPRL to hypothalamus and choroid plexus membranes from rabbit and horse was inhibited in a dose-dependent manner by unlabeled oPRL and hGH but not by many other polypeptide hormones. Scatchard analysis of the binding revealed the presence of binding sites with low capacity and high affinity for ovine ligand.

In the present research we have extended our work on the presence of binding sites for prolactin in the rabbit brain focusing our attention on the brain areas with high dopamine cell bodies density. Among these areas the hypothalamus showed the highest specific binding of labeled ovine prolactin (oPRL). Clearly detectible specific binding was observed also in substantia nigra, whereas in other brain regions the specific binding was very small, except for the striatum where a low but not negligible binding was found in female rabbits. The binding of 125I-oPRL showed a hormonal specificity and Scatchard analysis of the binding showed no clear difference in dissociation constant (Kd) between hypothalamus, nigra and striatum.

The acute toxicity and the activity on isolated guinea pig ileum of some derivatives of 1,5-bis-(3,4-methylendioxyphenyl)-n.pentane are reported. The majority of such compounds showed clear antagonist activity towards BaCl2, acetylcholine, histamine and 5-HT contracting responses, generally greater than that of papaverine. In almost all cases the therapeutic index of these compounds, calculated as the ratio between mouse i.v. LD50 and ileum ED50, was greater than the therapeutic index of papaverine.

Modifications in prolactin and insulin specific binding in the mouse liver induced by repeated administrations of ovine prolactin (oPRL) or indomethacin were studied. oPRL induced a dose-dependent and reversible increase of prolactin binding capacity. No change was observed in dissociation constant values. Conversely, insulin binding capacity to the same liver membranes was not modified by the treatment with oPRL. The increase in the binding induced by oPRL was not influenced by cycloheximide and it is therefore not dependent on protein synthesis. On the other hand, indomethacin caused a dose-dependent inhibition of prolactin binding capacity, without changes in dissociation constant values. The inhibitory effect was specific since at the doses used insulin binding to the same membranes was not affected. When indomethacin treatment was associated to oPRL administration it was able to counteract the increase in binding capacity caused by oPRL, even at doses ineffective in reducing the binding in non oPRL-treated mice. Our results suggest that drug-induced membrane modifications can selectively affect prolactin receptors and could consequently modify the ability of the target cell to respond to different physiological or pharmacological situations.

In this study we compared the effects of systemic administration of haloperidol (HAL), a typical dopaminergic antagonist and of domperidone (DOM), a dopamine (DA) receptor blocker which does not cross the blood brain barrier but has a potency similar to HAL at DA receptors, on hypothalamic and striatal DA system turnover (evaluated by means of HVA and DOPAC levels) and prolactin (PRL) secretion in male rats. In accordance with previous data, we found that HAL (1 mg/kg, i.p.) raised DOPAC and HVA levels whereas DOM (1 mg/kg, i.p.) did not alter DA turnover in striatum. Both DOM and HAL affected the hypothalamic DA system, increasing DOPAC levels in a pattern similar to that observed in PRL secretion. An intracerebroventricular (icv) injection of DOM and HAL (4 micrograms/10 microliters/rat) was then made to investigate its effect on DA turnover in this experimental condition at striatal and hypothalamic level. DOM stimulated DA turnover a little in the striatum though its action was delayed; no effects were seen on HVA and DOPAC concentrations in the hypothalamus at any of the tested times. On the other hand, an equal amount of HAL induced an increase in striatal HVA and DOPAC levels, with no significant effects on hypothalamic DA metabolites. These results show that systematically administered DOM and HAL may affect the hypothalamic tuberoinfundibular DA system, probably acting through PRL release. Furthermore DOM, even when injected icv, shows only weak antidopaminergic action on DA turnover in both central areas.

The number of prolactin (PRL) receptors in the hypothalamus and substantia nigra of aged rabbits is significantly lower than the number measured in young animals. The treatment of aged rabbits for 30 days with S-adenosyl-L-methionine (SAM) restored the number of PRL binding sites to levels found in the hypothalamus and substantia nigra from young animals. We did not observe a clear-cut difference between the dissociation constants of untreated young, and untreated or SAM-treated aged rabbits, whereas the binding capacity varied. Moreover, in vitro addition of SAM to hypothalamic membranes from aged rabbits resulted in a significant increase in the number of binding sites. This in vitro effect was antagonized by S-adenosyl-L-homocysteine, a specific in vitro inhibitor of methyltransferase activity. The reduction in the number of PRL receptors is assumed to be related to the decrease in membrane fluidity induced by aging, while its increase after SAM treatment might be ascribed to the ability of this methyl donor to increase the fluidity of cell membranes by stimulating phospholipid synthesis.