Reminder effects: the molecular cascade following a reminder in young chicks does not recapitulate that following training on a passive avoidance task

Memory traces, once established, are no longer sensitive to disruption by metabolic inhibitors. However, memories reactivated by reminder are once again vulnerable, in a time-dependent manner, to amnestic treatment. To determine whether the metabolic events following a reminder recapitulate those following initial training we examined the temporal dynamics of amnesia induced by the protein synthesis inhibitor anisomycin and the glycosylation inhibitor 2-deoxygalactose. The effects of both were transient and dependent on time of reminder post-training and time of injection relative to reminder, and differed from those following initial training. 2-[(14)C]-deoxyglucose uptake increased in two brain regions, the intermediate medial hyperstriatum ventrale (IMHV) and lobus parolfactorius (LPO) following reminder as it did following training, but the increase was bilateral rather than confined to the left hemisphere and was more marked in LPO than IMHV. C-fos expression after reminder was increased only in the LPO, the chick brain region associated with a late phase of memory processing and recall. Thus although, like initial consolidation, memory processing after reminder is sensitive to inhibitors of protein synthesis and glycosylation, the temporal and pharmacological dynamics indicate differences between these two processes.     

Degeneration of microglial cells in frontal and temporal lobes of chronic schizophrenics

Schizophrenia is a social disease that occurs in 0.5-1% of the population. It shows a high variability in both clinical picture and theory of its pathogenesis. Its clinical manifestations are accompanied by biochemical, immunological and structural changes. A pivotal role in the development of psychotic disorders is attributed to the impaired limbic system. The aim of this study was to find out whether, and if so, to what extent immunocompetent cells of the central nervous system (microglia) are involved in the process of degeneration occuring in these structures. The study was carried out on 12 brains of female chronic schizophrenics. Sections of frontal and temporal cortex were subjected to ultrastructural as well as histochemical and immunohistochemical examinations by light microscopy. In the structures under study, a large number of ramified microglial cells showing on their surface the expression of the major histocompatibility complex class II (MHC II) was observed. Most cells showed degenerative traits (cytoplasm shrinkage, thinning, shortening and fragmentation of their processes) up to apoptotic changes. Perivascular microglia displayed the lowest intensity of degenerative changes. Ultrastructurally, some damaged microglial cells contained phagosomes and/or degenerated mitochondria. Most abnormal microglia showed morphological signs of the former normal function of immunocompetent and phagocytosing cells. Degeneration of microgial cells, resulting most likely from the primary impairment of the neuron-glia communication that damages their immunocompetent function, may lead to the exacerbation of structural damage and psychotic symptoms. Treatment of chronic schizophrenics should involve the supply of agents to prevent degeneration of microglia and/or long-term immunotherapy.     

Effect of 1,2,3,4,-tetrahydroisoquinoline administration under conditions of CYP2D inhibition on dopamine metabolism, level of tyrosine hydroxylase protein and the binding of [3H]GBR 12,935 to dopamine transporter in the rat nigrostriatal, dopaminergic system

Current concepts of Parkinson's disease (PD) postulate that interaction between neurotoxins and specific genetic background may play an important role in pathogenesis of PD. Therefore, the effect of multiple administration of 1,2,3,4-tetrahydroisoquinoline (TIQ) under conditions of CYP2D blockade on the expression of key markers of PD was studied in the rat striatum (STR) and substantia nigra (SN). TIQ administered alone (50 mg/kg i.p. twice daily for 14 days) markedly decreased the level of tyrosine hydroxylase protein (TH) in the STR; however, this effect was not accompanied by reduction of dopamine (DA) concentration and [(3)H]GBR 12,935 binding to dopamine transporter (DAT). Administration of CYP2D inhibitor, quinine, jointly with TIQ lowered the levels of TH and DA in that structure, but slightly increased DAT binding. In the SN, treatment with TIQ alone did not change TH level although it enhanced DA content and decreased [(3)H]GBR 12,935 binding to DAT in the substantia nigra pars compacta (SNc). Neither the TH level nor DA concentration was affected by the combined treatment, although DAT binding was still reduced in the SN. TIQ did not change the total DA catabolism in the STR, but caused its inhibition in the SN. It strongly depressed the levels of intraneuronal DA metabolite DOPAC and enhanced that of extraneuronal 3-MT in either structure. TIQ more weakly affected the levels of both DA metabolites in the presence of quinine. Our results suggest that endogenous TIQ may act rather as neuromodulator but not as parkinsonism-inducing neurotoxin in the rat brain.     

Disposition of 1,2,3,4,-tetrahydroisoquinoline in the brain of male Wistar and Dark Agouti rats

Direct evidence for accumulation of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo- and exogenous substance suspected of producing Parkinsonism in humans, has not yet been shown. This study aimed to examine TIQ disposition in the whole rat brain and in the striatum and substantia nigra (SN). TIQ was administered to male Wistar and Dark Agouti rats (20, 40 and 100 mg/kg i.p.) alone or jointly with specific CYP2D inhibitor quinine (20, 40, 80 mg/kg i.p.), acutely or chronically. TIQ concentration in brain of both strains was several-fold higher than in plasma. The level of its metabolite, 4-OH-TIQ, was very low in the brain and plasma of TIQ-treated Wistar while in those receiving additionally quinine or in Dark Agouti rats, 4-OH-TIQ was absent or negligible. Inhibition of CYP2D catalyzing TIQ 4-hydroxylation in the liver had no influence on TIQ accumulation in the brain. Exogenous TIQ was actively transported from periphery into the brain by the organic cation transporter system, mainly OCT3, and quickly eliminated from it by P-glycoprotein. TIQ accumulation after chronic injection to Wistar rats was short-lasting and limited to SN. High concentration of TIQ in SN induces while in the liver inhibits the nigral and hepatic activity CYP2D, respectively.     

Therapeutic doses of topiramate are not toxic to the developing rat brain

Antiepileptic drugs (AEDs) used to treat seizures in pregnant women, infants, and young children may cause cognitive impairment. One of the implicated mechanisms is enhancement of apoptotic neuronal death, which occurs physiologically in the developing brain. We investigated whether topiramate, one of the newer antiepileptic drugs, has neurotoxic properties in the developing rat brain. Topiramate slightly but significantly enhanced apoptotic neuronal death in the 7-day-old rat brain at doses of 50 mg/kg and above. These doses are several folds higher than reported ED(50) doses in infant rodent seizure models that respond to topiramate. Electron microscopy confirmed that dying neurons following topiramate treatment displayed the same morphological features as neurons undergoing physiological cell death during development. When compared to the neurotoxicity profile of phenytoin, valproate, and phenobarbital, the separation between the effective anticonvulsant dose and the neurotoxic dose was greater for topiramate and the neurotoxic effect was lower.     

Posterior capsule opacification as a complication of the posterior chamber intraocular lens implantation

PURPOSE: The aim of the study was to evaluate factors possibly effecting the posterior capsule opacification (PCO), after extra-capsular cataract extraction with the posterior chamber intra-ocular lens (IOL) implantation. Age of patients, refractive errors, technique of cataract extraction, intra- and postoperative complications and coexisting diseases were taken into consideration. In 1992-98 posterior laser Nd:YAG capsulotomy was performed in 222 eyes of 222 patients (134 women and 88 men) previously operated in 1st and IInd Eye Clinic. PCO occurred in 5.8% patients, who underwent cataract extraction in this period, in 5.7% patients operated with phacoemulsification method and in 5.8% patients where extra-capsular cataract extraction with nucleus expulsion was performed. PCO was diagnosed in 12.7% patients at the age below 30, in 17% aged 31-40, in 7.8% aged 41-55 and in 5.1% patients older than 55 years. Among the patients, who developed PCO, in 6.3% myopia was present, in 8% primary open angle glaucoma, 16.6% were treated for diabetes mellitus. In 7.6% eyes the intra-operative cortical clean up was not efficient. CONCLUSION: PCO occurred in young patients (under 40) twice as often as in the other groups of age. Technique of cataract extraction had an influence on the incidence of PCO as well.     

Influence of exercise induced hyperlactatemia on retinal blood flow during normo- and hyperglycemia

PURPOSE: Short term hyperglycemia has previously been shown to induce a blood flow increase in the retina. The mechanism behind this effect is poorly understood. We set out to investigate whether exercise-induced hyperlactatemia may alter the response of retinal blood flow to hyperglycemia. METHODS: We performed a randomized, controlled two-way cross over study comprising 12 healthy subjects, performed a 6-minutes period of dynamic exercise during an euglcaemic or hyperglycaemic insulin clamp. Retinal blood flow was assessed by combined vessel size measurement with the Zeiss retinal vessel analyzer and measurement of red blood cell velocities using bi-directional laser Doppler velocimetry. Retinal and systemic hemodynamic parameters were measured before, immediately after and 10 and 20 minutes after isometric exercise. RESULTS: On the euglycemic study day retinal blood flow increased after dynamic exercise. The maximum increase in retinal blood flow was observed 10 minutes after the end of exercise when lactate plasma concentration peaked. Hyperglycemia increased retinal blood flow under basal conditions, but had no incremental effect during exercise induced hyperlactatemia. CONCLUSIONS: Our results indicate that both lactate and glucose induce an increase in retinal blood flow in healthy humans. This may indicate a common pathway between glucose and lactate induced blood flow changes in the human retina.     

Procalcitonin as a marker of perinatal infection in newborn--preliminary data

Intrauterine and intrapartum infections in newborn infants are still difficult to recognise. The newborn does not manifest the classic clinical signs of infection usually observed in children and adults and up to now there is no good laboratory marker. In the last few years, procalcitonin (PCT) has been found to increase during different inflammatory processes, especially bacterial ones. In this study we analysed the clinical value of PTC in parturient, umbilical cord and newborn blood for predicting perinatal infection. MATERIAL AND METHODS: Thirty parturients with symptoms of intrauterine infection were classified for this study. Blood samples were obtained from the mother, the umbilical cord and the newborn on the second day of life. Serum was stored at -70 degrees C and thawed at the time of analysis. Among the newborns there were 21 infants without and 9 with symptoms and signs of infection. PCT concentration was measured by immunoluminometric assay--LUMI test PCT (BRAHMS). RESULTS: Statistically significant results were found on the second day of life: 5.83 (4.70) ng/ml in ill, 1.41 (0.68) ng/ml in healthy (p < 0.0005). We observed a significant correlation between PCT concentration in mother and umbilical cord blood (y = 0.40x + 1.06; p < 0.05), as well as between umbilical cord blood and venous blood on the second day of life in newborns (y = 0.16x 1.21; p < 0.01). CONCLUSIONS: Measurement of PCT concentration in perinatal period in the mother and in umbilical cord blood of the newborn may be useful for early diagnosis and monitoring of infectious complications in neonates. We need more data on reference ranges of PCT concentration in pregnant women, parturients and umbilical cord blood.