Cavernous sinus involvement in recurrent Nelson's syndrome

Summary Two cases of meningiomas, which are considered to have been caused by the preceding irradiation, are reported. In both cases, the cytokinetic study of the tumour using bromodeoxyuridine (BrdU) was performed. The percent of the tumour cells in the S phase of the cell cycle was less than 1% in both cases. The low labelling indices might suggest a relatively slow growing potential of these tumours, though the radiation-induced meningiomas were reported as being rapidly growing and malignant.     

Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem,caudate/putamen and cortex,and on dopamine D1 and D2 receptors in the caudate/putamen

Summary Rats were treated with desipramine 5mg/kg, nomifensine 10mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D₁ (³[H]SCH 23390) and D₂ (³[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither³[H]SCH 23390 nor³[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/ putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.     

Biochemical evidence for the involvement of central serotonergic neurotransmission in the action of the antidepressant drug Medifoxamine

Medifoxamine, an antidepressant agent which has an original chemical structure, has been shown through in vitro studies, utilising radioligand binding in tissue homogenates, to bind with moderately high affinity to 5-HT_1c and 5-HT₂ receptor subtypes and to 5-HT uptake sites (IC₅₀ 950, 980, and 1,500 nM, respectively). It has been shown to bind in vivo to rat brain 5-HT₂ receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 μmol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 μmol/kg), a decrease in the capacity of [³H]-5-HT uptake and a dose-dependent down-regulation of 5-HT₂ receptors in rat cerebral cortex were observed. These results indicate that medifoxamine, which has been shown previously to act through dopaminergic systems, interacts also with central serotonergic neurotransmission and particularly with the 5-HT₂ receptors, which could contribute to its antidepressant effect.     

重质石油中含氮化合物的形态及分布分析Ⅱ．含氦杂环化合物的定性方法

探索了色谱保留值与质谱信息相结合的定性分析方法。用ＳＥ－５４柱代替ＳＥ－５２柱，选用六个多环芳烃化合物作为标准计算保留指数，从而改善了Ｍ．Ｌ．Ｌｅｅ保留指数的应用条件和范围；用文献值转换扩充了Ｌｅｅ的含氮杂环化合物保留指数表，并利用保留时间与沸点的关系作定性佐证。应用该法鉴定了重质石油样品子组分及萘油中的４６个含氮杂环化合物及其异构体，为质谱在异构体鉴定以及缺乏标样所产生的困难提供了可信、简便的定性鉴定方法。     

Benzodiazepine concentrations in brain directly reflect receptor occupancy: studies of diazepam,lorazepam, and oxazepam

Groups of male CF-1 mice received 3 and 10 µmol/kg diazepam, lorazepam, and oxazepam intravenously. Between 1 min and 24 h after injection, benzodiazepine concentrations were determined by gas chromatography (GLC) in plasma and in one brain hemisphere; in the other hemisphere, ex vivo benzodiazepine receptor occupancy was measured using³H-flunitrazepam displacement. Based on GLC data, diazepam entered brain rapidly, and was also cleared rapidly, yielding desmethyldiazepam and oxazepam as metabolites in plasma and brain. However, lorazepam and oxazepam entered brain slowly, with brain:plasma equilibrium achieved at 30–60 min; thereafter, the drugs were eliminated from plasma and brain in parallel. The time course and extent of ex vivo occupancy were highly consistent with GLC data (for diazepam, GLC levels were expressed as the sum of diazepam, desmethyldiazepam, and oxazepam, with metabolite concentrations, normalized for molecular weight and for in vitro benzodiazepine receptor affinity.) Between-method correlations were 0.95 or higher. Thus benzodiazepine receptor occupancy is highly dependent on benzodiazepine concentrations in brain. Differences in the time-course of onset and duration of pharmacologic activity between the highly lipophilic benzodiazepine diazepam and the less lipophilic hydroxylated derivatives lorazepam and oxazepam are largely explained by differences in systemic kinetics and in the rate of uptake into brain.Supported in part by grants MH-34223, DA-05258, and AG-00106 from the United States Public Health Service     

ONCOCYTES OF THE THYROID: A NEUTRAL RED DYE UPTAKE STUDY

Oncocytosis and oncocytomas have attracted attention because on the one hand there have been reports of the favourable prognosis and generally benign nature of oncocytic tumours, while on the other hand, Hurthle cell change in thyroid neoplasms have been reported to be correlated with aggressive biological behaviour and a significantly worse clinical course. Presently, there appear to be two schools of thought on the significance of oncocytosis: (i) a process where there is redifferentiation of cells with involvement in the pathogenesis of cancer; and (ii) a compensatory process for ‘functional exhaustion’ of the cell. Many aspects of oncocytosis seem unclear. In this study, transmission electron microscopy is used to demonstrate the presence of thyroid oncocytes in the hemithyroidectomy specimen of a patient with focal lymphocytic thyroiditis. Tissue sections from this specimen did not display preferential uptake of neutral red dye, a distinctive characteristic of M-phase cancer cells which was previously reported. The findings seem to suggest that oncocytes are not cells with distinctive proliferative potentials. If that were the case, then oncogenesis or cancer cell progression and oncocytosis may not be convergent processes.     

Daily nutrient intake represents a modifiable determinant of nutritional status in chronic haemodialysis patients.

BACKGROUND: In maintenance haemodialysis patients, daily food intake is changeable; however, its relationship with nutritional status is unexplored. This study aimed to evaluate the isolated, long-term effect of daily nutrient intake on nutritional status in haemodialysis patients. METHODS: We performed a prospective 1-year controlled study in 27 chronic haemodialysis patients, without recognized risk factors for malnutrition. Each day for 1 week, four times in the year, we measured protein nitrogen appearance, and assessed dietary protein (DPI) and energy (DEI) intake from dietary diaries. We compared the nutritional outcome of patients spontaneously reducing nutrient intake below the threshold of 0.8 g/kg body weight/day for DPI and 25 kcal/kg body weight/day for DEI during the week (LOW, n = 8), with controls at adequate nutrient intake (CON, n = 19). An interventional 6-month study was then carried out in LOW to verify the cause-effect relationship. RESULTS: All patients showed a day-by-day reduction of whole nutrient intake during interdialytic period, which was mostly relevant in the third interdialytic day (L3). During the 1-year study, even in the presence of adequate dialysis dose and normal inflammatory indexes, body weight (68.0 +/- 5.5 to 65.8 +/- 5.9 kg), serum albumin (3.96 +/- 0.07 to 3.66 +/- 0.06 g/dl) and creatinine (9.2 +/- 1.1 to 8.1 +/- 0.7 mg/dl) significantly decreased in LOW but not in CON. Diaries evidenced in LOW a reduced number of meals at L3 that was explained by the fear of excessive interdialytic weight gain. During the interventional study, daily DPI and DEI increased at L3; this was associated with a significant increment of body weight, and serum albumin and creatinine levels. CONCLUSIONS: In maintenance haemodialysis patients the persistent, marked reduction of daily nutrient intake, even if limited to a single day of the week, is an independent determinant of reversible impairment of nutritional status.     

Haemodynamics as a determinant of the pharmacokinetics of and the plasma catecholamine responses to isoprenaline

Summary The total body clearance and fractional extraction of isoprenaline (ISO) have been determined, and the relation between these parameters and cardiac output established. Whether desipramine, an inhibitor of neuronal uptake, altered the plasma catecholamine response to ISO was also investigated.Seven healthy subjects were given i.v., infusions of ISO in two, consecutive 25-min periods, at constant dose rates of 31–43 and 80–124 pmol·kg^–1·min^–1, respectively. The total-body (ER), pulmonary (ER_p) and forearm (ER_f) fractional extractions and the total body clearance (CL) of ISO were obtained from measurements of cardiac output and the steady-state ISO concentration in mixed central venous, arterial and forearm venous plasma.ISO-induced increases in cardiac output resulted in increases in CL, decreases in ER and no consistent change in ER_f. ER_p did not differ from zero. ISO also produced a dose-dependent increase in the mixed venous plasma concentrations of noradrenaline and 3,4-dihydroxyphenylglycol (DOPEG), and a decrease in that of adrenaline. Pretreatment with desipramine did not alter any of the pharmacokinetic parameters of ISO. Desipramine, however, reduced the mixed venous baseline plasma levels of noradrenaline (47%) and DOPEG (40%), and tended to reduce that of adrenaline (34%). It enhanced the plasma noradrenaline response 2.4-fold, abolished the plasma DOPEG response and did not alter the plasma adrenaline response to ISO.Hence, owing to its haemodynamic effects, ISO modifies its own pharmacokinetics which involve non-neuronal removal processes only. The increased DOPEG in plasma resulting from the ISO-induced increase in noradrenaline release was presynaptic in origin. Desipramine appears to reduce sympathetic activity. The enhancement by desipramine of the ISO-induced increase in plasma noradrenaline points towards recapture by neuronal uptake of at least 58% of the noradrenaline released in response to ISO.     

Scintigraphic evaluation of myocardial uptake of thallium 201 and technetium 99m pyrophosphate utilizing a rat model of chronic doxorubicin cardiotoxicity

To evaluate the usefulness of myocardial scintigraphy as a monitoring tool for chronic doxorubicin (DXR) cardiotoxicity, a rat model was used to investigate the relationship between the myocardial uptake of thallium 201 (Tl) or rechnetium 99m pyrophosphate (^99mTc-PPi) and histological changes of the heart. Although there was no significant difference in myocardial Tl uptake between control and DXR-treated rats at an early phase after Tl injection, late-phase Tl uptake was significantly higher in the DXR-treated rats than in the control rats, indicating a slow wash-out of Tl from the myocardium. The wash-out rate calculated from scintigraphic examination of DXR-treated rats was significantly decreased with increasing degree of cardiomyopathy. Since the Tl wash-out rate was sharply decreased even in animals with minimal histological changes, it may be a possible monitoring tool for the early detection of chronic DXR cardiotoxicity. On the other hand, myocardial^99mTc-PPi images could be obtained only in rats with severe myocardial changes and hence would not useful for early detection.