Effects of MPP+ on catecholamine levels in adrenal glands and heart of rats

The effects of MPP⁺ (2.5–20 mg/kg) on the adrenal glands and heart were investigated in rats. At various periods after s.c. drug administration the rats were decapitated and tissue catecholamine levels were determined by means of HPLC with electrochemical detection. Adrenal dopamine (DA) levels were reduced at 2–8 h after MPP⁺ administration, but this decrease was followed by an elevation after 16 h and return to the control values after one week. Three successive injections of MPP⁺ caused a statistically significant elevation in adrenal DA, one day, with a tendency to elevation four and seven days after the last injection, whereas a severe (up to 96%) decrease in heart noradrenaline (NA) was found one day after the last injection. Seven days after the last injection a 50% depletion of NA in the heart was still observed. Pretreatment with GBR 12909 (30 mg/kg, 4 h) blocked the MPP⁺ (10 mg/kg, 2 h) induced reduction of adrenal DA levels, but at the same time GBR 12909 failed to block the effects of MPP⁺ in the heart. One day after three successive daily injections of MPP⁺ (10 mg/kg each), the DA-uptake inhibitor GBR 12909 (30 mg/kg, 6 h) could still induce an increase in adrenal DA.MPP⁺ appears to lack persistent cytotoxic action in the adrenal medulla but rather to cause a transient inhibition of DA synthesis followed by a compensatory stimulation. The inhibition can be blocked by specific inhibitor of the DA-uptake mechanism, suggesting a direct effect of MPP⁺ taken up by adrenomedullary cells. The data obtained so far do not suggest any involvement of peripheral dopaminergic nerves in the action of MPP⁺ on the adrenal medulla. The long-lasting depletion of the heart NA, however, suggests a lesion of peripheral noradrenergic nerves.Part of this work was presented at 6th International Symposium on Chromaffin Cell Biology, Marburg, Germany, 18–23 August 1991 Correspondence to: M. Kujacic at the above address     

Prognostic significance of cytochemical analysis of leukemic M2 blasts

Cytochemical analysis of leukemic blasts from 46 patients with acute myeloblastic M2 leukemia (according to the FAB classification) was performed before and after cytostatic therapy, and compared with findings obtained in 20 age- and sex-matched control subjects. Cytochemical findings for myeloperoxidase (MPO), Sudan black B, acid phosphatase and alpha-naphthyl-acetate esterase (ANAE) were related to the achievement of the first complete remission (CR),i.e. data were compared after the patients had been divided into CR and non-CR groups. The analysis clearly showed that a high proportion of myeloperoxidase- and, to a lesser extent, Sudan black B-positive blasts before treatment may have constituted a significantly unfavourable prognostic factor.     

Acute changes in dopamine levels in rat adrenal glands after administration of dopamine receptor agonists and antagonists

The study was aimed at in vivo pharmacological identification of the possible dopamine (DA) receptor(s) involved in changes of the DA level in rat adrenal glands. Previous work in this laboratory has shown that the DA level is largely controlled by the rate of catecholamine synthesis. The rats were killed by decapitation after various periods of drug administration and the catecholamine content of adrenal glands and forebrain was measured by high-performance liquid chromatography with electrochemical detection. Administration of the DA D-1 + D-2 receptor agonist, apomorphine, induced a statistically significant increase in DA levels in the adrenal glands. The same effect was noted after administration of the DA D-2 receptor agonist, quinpirole. The DA D-2 receptor antagonist, raclopride, blocked the apomorphine-induced increase in adrenal DA levels but had no effect per se on these levels. The DA D-1 receptor agonist, SKF 38393, and the DA D-1 receptor antagonist, SCH 23390, did not have any effect on apomorphine-induced changes in DA content in the adrenals. The DA elevating effect of the DA D-2 receptor agonist, quinpirole, in the adrenals was completely blocked by the DA D-2 receptor antagonist, domperidone. This compound does not cross the blood-brain barrier readily and is thus supposed to act mainly on peripheral tissues. In support of this, the dose of domperidone used did not affect brain DOPAC levels. Our data, together with observations reported in the literature, indicate that the adrenal medulla contains DA receptors of the D-2 subtype, which are capable of controlling the DA level in rat adrenal glands.     

Dopamine receptors,controlling dopamine levels in rat adrenal glands — comparison with central dopaminergic autoreceptors

Summary Previous work in this laboratory, as well as observations reported in the literature, indicate that the adrenal medulla contains dopamine (DA) receptors of the D-2 subtype, which among other things are capable of controlling the DA level in rat adrenal glands. To further characterize the DA receptors involved in the control of the adrenal DA level, the effects of 9 DA receptor agonists with various intrinsic activities were compared. After various periods of drug administration the rats were killed by decapitation and the DA content of the adrenal glands and the DOPAC content of the forebrain were measured by high-performance liquid chromatography with electrochemical detection. All the investigated DA receptors agonists caused an increase in adrenal DA level, although statistical significance was not reached in one case /(–)-HW165/. Domperidone, a DA D-2 receptor antagonist which does not readily cross the blood brain barrier, blocked the DA-elevating effects of apomorphine, quinpirole, B-HT 920 and both enantiomers of 3-PPP. For the two ergolines terguride and SDZ 208-920 the blockade by domperidone was not complete, suggesting that their effects are mediated not only through DA, but also through other receptor systems. The dose of domperidone used (3 mg/kg) had but a marginal influence on brain DOPAC levels, supporting the almost exclusively peripheral effect of this agent. Our data indicate that the DA D-2 receptors which control the DA level in the adrenal medulla in rats, have characteristics similar to, though not identical with the autoreceptors in the forebrain.     

Evaluation and selection of candidates for renal transplantation at the Clinical Hospital Center in Rijeka

On December 31, 2001, 2486 patients with terminal renal failure received dialysis treatment in Croatia. Only one third of the patients are registered on the national waiting list for cadaveric kidney transplant. In most of the others, transplantation is impossible because of comorbidity. This is mainly due to the steadily growing age of the dialytic population and therefore a higher incidence of cardiovascular disease and diabetes. Still, evaluation of the potential recipients of cadaveric kidney transplant, registered on the waiting list, often reveals contraindications for transplantation. The aim of this study was to determine the incidence and type of contraindications in transplant candidates, found during immediate preoperative evaluation. Analysis of these data should help in determining how contraindications can be early detected and prevented. Before registering onto the national waiting list transplant candidates need to be thoroughly investigated including detailed history, physical examination, routine diagnostic procedures and additional examinations, if needed, to exclude or evaluate the possibly existing contraindications for transplantation. During the period from January 1997 until June 2002, 145 potential recipients from the national waiting list were referred to the Rijeka University Hospital Center and evaluated for kidney transplantation. Eighty-eight patients underwent transplantation. Preoperative evaluation revealed contraindications for transplantation in 52 (35.9%) candidates. Twenty-two (15.2%) patients had a positive cross-match with donor lymphocytes, 6 (4.1%) patients refused transplantation, and in 24 (16.6%) patients serious comorbidity was the reason for not being accepted for transplantation and for their withdrawal from the national waiting list. Comorbidity was mainly due to cardiovascular disease (12 patients--8.3%) and infection (8 patients--5.5%). These data show a high incidence of contraindications found during the immediate preoperative evaluation of potential kidney recipients. It was the case in more than one third of patients. During the evaluation of potential candidates for kidney transplantation special attention should be addressed to the presence of cardiovascular morbidity and infection. Peripheral vascular occlusive disease, cardiac status and/or cerebrovascular disease should be evaluated. Measures used to treat or reduce the development of complications include an optimal control of blood pressure, serum phosphate, hyperparathyroidism, dyslipidemia, and renal anemia. The sites of infection must be treated and eradicated, because immunosuppressive treatment is a threat to the transplant recipient's life. The second most common cause of refusal of potential candidates was a positive cross-match with donor lymphocytes. Sensitization to human leukocyte antigens can be prevented by the avoiding of blood transfusions and use of erythopoietin in treating renal anemia. To minimize the morbidity and mortality, the potential kidney recipients should undergo rigorous selection and thorough evaluation before including them into the waiting list for kidney transplantation. Afterwards, regular examinations are obligatory to reveal contraindications, proceed to medical interventions and treat concomitant diseases in time, which can influence the patient's survival. In case that contraindications for transplantation arise, the patient must be temporarily or definitely removed from the waiting list.     

CD4+CD56+ hematodermic neoplasms bear a plasmacytoid dendritic cell phenotype

CD4+CD56+ hematodermic neoplasms (HNs) with initial presentation in the skin are characterized by highly aggressive behavior and poor prognosis. Recent studies indicate that malignant cells, which are devoid of common T-, B-, NK-, and myeloid lineage markers, may be of plasmacytoid dendritic cell (pDC) origin. We undertook a study to assess the expression of several pDC-associated molecules on a series of 5 CD4+CD56+ HN cases. CD123 was expressed in all 5 cases, with some heterogeneity in individual cases. All but one case revealed fine membranous BDCA-2 staining of the dermal infiltrate. pDC-like phenotype of the malignant infiltrating cells was confirmed by costaining of BDCA-2+ cells with CD123 and CD4. MxA protein, representing the surrogate marker for lesional type I interferon activity, was expressed in 4 of 5 evaluated cases. Our findings further substantiate the putative pDC origin of CD4+CD56+ HNs.     

The time-course of ribavirin-provoked changes of basal and AMPH-induced motor activities in rats

The time-course of changes of basal and amphetamine (AMPH)-induced locomotor and stereotypic activities in adult male Wistar rats after a single ribavirin injection was studied. In the first set of experiments, 10, 20 or 30 mg ribavirin/kg body weight (b.w.) were injected i.p. to rats and their basal motor activities were recorded every 10 min for 2 h and compared with those of saline-treated controls. In the second set of experiments, the animals were pretreated with ribavirin and 20 min later i.p. injected with AMPH (1.5 mg/kg b.w.). The controls received AMPH 20 min after the saline injection. Motor activity was recorded after the first injection and until 120 min after AMPH administration. Ribavirin did not significantly affect the time-course of either basal locomotor or stereotypic activities. Pretreatment with any of the applied ribavirin doses decreased the AMPH-induced hyperlocomotor response. However, the most pronounced effect was observed with ribavirin doses of 20 mg/kg and 30 mg/kg when administered during the first 10 min and 30 min after the AMPH injection respectively. In contrast, the stereotypic activities of these animals were only slightly changed. These results indicate a different susceptibility of regions in the basal ganglia to ribavirin.     

Strain differences in peritoneal macrophage activity and susceptibility to experimental allergic encephalomyelitis induction in rats

The objective of the present study was to investigate the relevance of peripheral macrophage activity for the susceptibility to the induction of experimental allergic encephalomyelitis (EAE). Rats of EAE-susceptible Dark Agouti and EAEresistant Albino Oxford strain were immunized with guinea pig spinal cord homogenate (DA_GPSC and AO_GPSC), while non-immunized rats served as controls (DA_NIM, AO_NIM). On day 15 after immunization rats were sacrificed and their peritoneal macrophages tested for adherence capacity, zymosan phagocytosis and respiratory burst. Macrophages from AONIM rats exhibited lower adherence capacity and higher phagocytosis and H₂O₂ production when compared to macrophages from DANIM rats. Immunization with GPSC decreased adherence and phagocytosis and increased H₂O₂ production in macrophages from AO rats, but did not influence these activities in macrophages from DA rats. The results from the present study suggest that inflammatory activities of macrophages from AO rats could be considered as regulatory mechanisms connected with the resistance to EAE induction.