Studies of the biogenic amine transporters. IV. Demonstration of a multiplicity of binding sites in rat caudate membranes for the cocaine analog [125I]RTI-55

The drug 3 beta-[4'-iodophenyl]tropan-2 beta-carboxylic acid methyl ester (RTI-55) is a cocaine congener with high affinity for the dopamine transporter (Kd < 1 nM). The present study characterized [125I]RTI-55 binding to membranes prepared from rat, monkey and human caudates and COS cells transiently expressing the cloned rat dopamine (DA) transporter. Using the method of binding surface analysis, two binding sites were resolved in rat caudate: a high-capacity binding site (site 1, Bmax = 11,900 fmol/mg of protein) and a low-capacity site (site 2, Bmax = 846 fmol/mg of protein). The Kd (or Ki) values of selected drugs at the two sites were as follows: (Ki for high-capacity site and Ki for low-capacity site, respectively): RTI-55 (0.76 and 0.21 nM), 1-[2-diphenyl-methoxy)ethyl]-4-(3-phenylpropyl)piperazine (0.79 and 358 nM), mazindol (37.6 and 631 nM), 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (45.0 and 540 nM) and cocaine (341 and 129 nM). Nisoxetine, a selective noradrenergic uptake blocker, had low affinity for both sites. Serotonergic uptake blockers had a high degree of selectivity and high affinity for the low-capacity binding site (Ki of citalopram = 0.38 nM; Ki of paroxetine = 0.033 nM). The i.c.v. administration of 5,7-dihydroxytryptamine to rats pretreated with nomifensine (to protect dopaminergic and noradrenergic nerve terminals) selectively decreased the Bmax of site 2, strongly supporting the idea that site 2 is a binding site on the serotonin (5-HT) transporter. This serotonergic lesion also increased the affinity of [125I]RTI-55 for the DA transporter by 10-fold. The ligand selectivity of the caudate 5-HT transporter was different from the [I125]RTI-55 binding site on the 5-HT transporter present in membranes prepared from whole rat brain minus caudate. The [125I]RTI-55 binding to the DA transporter was further resolved into two components, termed sites 1a and 1b, by using human and monkey (Macaca mulatta) caudate membranes but not the membranes prepared from rat caudate or COS cells that transiently expressed the cloned cocaine-sensitive DA transporter complementary DNA. Similar experiments also resolved two components of the caudate 5-HT transporter. Viewed collectively, these data provide evidence that [125I]RTI-55 labels multiple binding sites associated with the DA and 5-HT transporters.     

Neural correlates of the episodic encoding of pictures and words

A striking characteristic of human memory is that pictures are remembered better than words. We examined the neural correlates of memory for pictures and words in the context of episodic memory encoding to determine material-specific differences in brain activity patterns. To do this, we used positron emission tomography to map the brain regions active during encoding of words and pictures of objects. Encoding was carried out by using three different strategies to explore possible interactions between material specificity and types of processing. Encoding of pictures resulted in greater activity of bilateral visual and medial temporal cortices, compared with encoding words, whereas encoding of words was associated with increased activity in prefrontal and temporoparietal regions related to language function. Each encoding strategy was characterized by a distinctive activity pattern, but these patterns were largely the same for pictures and words. Thus, superior overall memory for pictures may be mediated by more effective and automatic engagement of areas important for visual memory, including medial temporal cortex, whereas the mechanisms underlying specific encoding strategies appear to operate similarly on pictures and words.     

Effect of wheat bran in treatment of chronic nonorganic constipation. A double-blind controlled trial

An experiment was conducted to define the seasonal changes in LH secretion in ovariectomized does with oestrogen implants and the effect of immunization against melatonin. Fifteen mature Australian cashmere goats were ovariectomized and given either no further treatment or one or two implants containing oestradiol; another similar group of 15 does were immunized against melatonin before ovariectomy and oestrogen treatment. LH concentrations and livemasses were recorded every week for 2 years. Livemasses of both groups showed a distinct seasonal pattern with a summer maximum and a winter minimum irrespective of treatment. LH concentrations also showed distinct seasonal patterns with a significant interaction between the number of implants and the time of the year. In the nonimmunized does, the presence of a constant low dose of oestrogen (one implant) resulted in low concentrations of LH except from May to August, the normal period of spontaneous ovulatory activity in intact does. In contrast, nonimmunized does receiving a high dose of oestrogen (two implants) showed a rise in LH concentrations in February, and concentrations remained high until August. Immunization against melatonin abolished this differential LH secretory pattern, and both doses of oestrogen were associated with a short period of high LH concentration between May and September. These results indicate that a negative feedback effect of oestrogen results in low LH secretion for most of the year and that hypothalamic sensitivity to LH decreases for only a short period between May and August.(ABSTRACT TRUNCATED AT 250 WORDS)     

Product activation of human erythrocyte AMP deaminase

Maternal magnesium requirements increase during pregnancy because of the synthesis of new tissue--both fetal and maternal. Magnesium takes part in almost 300 enzymatic reactions in the human body and regulates membrane permeability and protein bio-synthesis by promoting initiation and dissociation factors. The absorption velocity of magnesium differs from one tissue to another in animal experiments. It is highest in the liver, kidney, heart and is low in skeletal muscle, the brain and erythrocytes. It obeys and follows the Michaelis-Menten Kinetic law. 15 mmol of magnesium is consumed daily depending on the types of food takenin. The main sources of magnesium are vegetables and meats. Many Nigerian women are not able to afford enough of these. The amount of magnesium reabsorbed depends on the magnesium intake and not on magnesium needed which is about 10-40% of the intake. In this study, we examined the short-term effect of magnesium asphat HCL (614.18 mgMG), magnesium diasporal (magnesium citrate 610 mg + magnesium laevalitat 30 mg = 100 mg magnesium = 8.2 mval), ferrous gluconate (300 mg) plus folic acid and chemiron, a new combination hematinic agent (ferrous fumarate 300 mg, folic acid 5 mg, vitamin B12 10 mg, vitamin C 25 mg, magnesium sulfate 0.3 mg and zinc sulfate 0.3 mg) on plasma magnesium concentration during early pregnancy in Nigerian women. Significant increases of plasma magnesium concentrations were found in these groups (magnesium asphat HCL, 0.83 +/- 0.12 to 0.96 +/- 0.14 mmol/l, magnesium diasporal 0.843 +/- 0.14 to 0.891 +/- 0.14 mmol/l and chemiron 0.848 +/- to 0.866 +/- 0.16 mmol/l after five days. The ferrous gluconate and folic acid treated group showed no significant changes. This study shows that a chemiron supplement leads to increased magnesium plasma levels whereas ferrous gluconate and folic acid do not. These results suggest that the low level of magnesium is a normal physiological adjustment of pregnancy and that iron supplementation does not influence this unless magnesium salt is given.     

Localization of gallium-67 citrate in salivary glands following radiation therapy

Gallium-67 citrate was found to localize in the salivary glands of eight patients after therapeutic doses of radiation to a treatment field including the glands. In two patients, autopsy evidence to the effect that no primary disease was present to explain such uptake was obtained. In another two patients the abnormal uptake was not observed on follow-up. The recognition that radiation sialadenitis is a potential cause of false-positive gallium scintiscans is important in their interpretation.     

Kinetic evaluation of the propranolol-quinidine combination

The kinetics of quinidine and propranolol, administered singly and in combination, were evaluated in 5 healthy subjects. The orally administered doses resulted in plasma concentrations within the therapeutic range. For each drug the average steady-state plasma concentration, maximal plasma concentration, and time of maximum plasma concentration were not altered by the presence of the other drugs. This study shows no kinetic interaction between quinidine and propranolol in normal subjects.     

Heritable chromosome rearrangements induced in rat spermatids by x-irradiation

The induction of reciprocal translocations by an exposure of rat spermatids to X-irradiation has been studied by cytological examination of dividing spermatocytes of F1 sons. The incidence of F1 translocated males was found to vary from 7.89% after exposure to 125 R to 22.44% after exposure to 500 R.     

Gallium-67 scintigraphy in multisystem malignant melanoma

In a prospective study of the value of gallium-67 scintigraphy in cases of multisystem malignant melanoma, 69 scans were obtained for 36 patients. No abnormality was found in 18 scans; in only 3 was there other evidence of disease. Of 54 sites of disease demonstrated by scintigraphy, 40 were correlated with other investigations: biopsy (5), surgery (7), autopsy (7), radiographic (13), or clinical (8). Metastatic melanoma was found in 37 (69%) of the sites; no such disease was found in 3 (5.7%). The life expectancy of patients with an abnormal scan was shorter than that of patients with a normal scan. Gallium studies reliably indicated the extent of multisystem melanoma, and are of value in clinical management.