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Biomedical subjects

J J Braszko

Publications and source records attributed to J J Braszko.

At least 19 recordsLinked to original sources
PubMed2006

D2 dopamine receptor blockade prevents cognitive effects of Ang IV and des-Phe6 Ang IV.

Angiotensins, especially angiotensin IV (Ang IV), have recently been found to be potent cognitive enhancers in rodents. However, the precise mechanisms of their memory improving effects remain unknown. In this study we tested the hypothesis that D2 dopamine receptors at least partially mediate cognitive effects of Ang IV and its derivative des-Phe6 Ang IV. Namely, the well known cognitive effects of both peptides [facilitation of a conditioned avoidance responses (CARs) acquisition, increase of a passive avoidance behavior (PAB) retrieval, and improvement of object recognition] were evaluated in rats either pretreated or not with a selective D2 dopamine receptor antagonist remoxipride {(S)-(-)-3-Bromo-N-[(1-ethyl-2-pyrrolidinylOmethyl]2,6-dimethoxybenzamide hydrochloride}. To control for the unspecific motor and emotional effects of our treatments that could confound results of the memory tests we used respectively, 'open' field and elevated 'plus' maze tests. Ang IV as well as des-Phe6 Ang IV remarkably improved learning of CARs, recall of PAB and recognition of the previously seen objects. D2 receptors blockade by remoxipride abolished all these effects of both peptides. In the elevated 'plus' maze remoxipride abolished anxiogenic effects of both Ang IV and des-Phe6 Ang IV. Also, the drug followed by Ang IV decreased number of crossings and by des-Phe6 Ang IV number of crossings and rearings. The results point to importance of the functional D2 dopamine receptors in cognitive effects of Ang IV and its naturally occurring product devoid of C-terminal Phe6.

Analysis of Variance↗
PubMed2003

Effects of angiotensin II and its receptor antagonists on motor activity and anxiety in rats.

The neuropeptide angiotensin II (Ang II) has been recently found to be involved in cognitive processes. Both AT1 and AT2 angiotensin receptors seem to mediate this action. However, unspecific behavioural effects of the peptide, particularly motor and emotional, appear to influence the interpretation of cognition-oriented tests and contribute to considerable differences in opinions of various authors on the subject. In this study, aimed specifically at the assessment of these effects, we found small and insignificant changes in motor performance measured in open field after intracebroventricular injections of Ang II and its receptor subtype-specific antagonists; losartan (AT1) and PD 123319 (AT2). However, Ang II was found to increase substantially anxiety measured in elevated 'plus' maze and impair motor coordination measured in 'chimney test'. Interestingly, both antagonists abolished Ang II generated anxiety and only losartan counteracted impaired motor coordination caused by the peptide. The AT2 receptor antagonist PD 123319 impairing motor coordination on its own, nonetheless partly diminished that caused by Ang II. Therefore it appears safe to conclude that mood but not motor effects of AT1 and AT2 receptor affecting drugs may significantly bias interpretation of the cognition-oriented tests on these drugs.

Angiotensin II↗
PubMed2003

Therapy increases poly-ADP-ribose and p53-Ser392-P levels in recurrent squamous cell lung cancer.

p53 protein is a critical regulator of the cell cycle and apoptosis and its levels and functions change in response to many stimuli. To assess whether the cytotoxic drugs induce DNA changes, affect phosphorylation and stability of p53 protein, we determined poly-ADP-ribose levels, the expression of p53 protein and its carboxyl-terminal Ser-392 phosphate levels in fiberoptic bronchoscopy biopsy samples taken from patients suffering from recurrent squamous cell lung cancer before and after radiotherapy and chemotherapy. All 14 patients included in this study were in IA-IIIA clinical stage prior to surgery. Radiation/chemotherapy decreased G2/M cell numbers but increased S-phase cells by almost 50% compared to ploidy status before therapy, while median p53 expression was doubled (109% increase). p53 phosphorylated on Ser-392 was also increased by approximately 70% in patients treated with radiotherapy and with chemotherapy and correlated with elevated poly-ADP-ribose levels. Our data suggest that apart from changes in p53 quantity, posttranslational phosphorylation/dephosphorylation-mediated alterations may play an important role in neoplastic cell proliferation as well as in antiproliferative activity of drugs inducing DNA damage and apoptosis.

Aged↗
PubMed2001

Diverse effects of prolonged physical training on learning of the delayed non-matching to sample by rats.

The physiological effects of physical exercise have been extensively studied. Nevertheless, its influence on cognitive functioning remains a matter of controversy. In this study we have attempted to assess the effects of repeated exercise (6 weeks of daily treadmill running, meant to resemble human physical training), on parallel learning of a complex task [delayed non matching to sample (DNMS)] by rats. The trained rats appeared to learn the procedure slower and made a significantly lower percentage of correct choices (P<0.01) as compared to those in the non-trained control group. However, when only those rats, from both the groups, which reached the criterion of 80% correct choices in two consecutive sessions were compared, no significant differences were observed. These results suggest an adverse influence of long term physical exercise on rats' ability to learn complex tasks, but only by the 'poor performers'. The 'good performers' were insensitive to the deleterious effects of the exercise.

Animals↗
PubMed2001

Proliferating activity, DNA ploidy changes of lung cancer cells before and after chemotherapy.

To assess proliferating activity, DNA ploidy changes of lung cancer cells before and after chemotherapy, we performed a flow cytometry analysis (FC) using fresh bronchoscopy specimens from 38 patients with lung cancer. Among 33 males and 5 females, squamous cell carcinoma (NSLC) was recognized in 12 males, 15 males had small cell lung cancer (SCLC) and 6 males had lung cancer with no histological type (LC) defined. Three women had SCLC, 1 had NSCLC and one had LC. Control consisted of 11 COPD patients. The percentage of diploid cells was significantly lower and cells with hypoploid cells were significantly higher in study group before treatment. High percentage of G2M cells characterised NSCLC and LC groups, whether high number of S phase cells characterised NSCLC and SCLC group before treatment. The treatment lowered percentage of G2M cells in NSCLC and CA group, whether diploid, hypoploid and S phase cells did not differ than those from before treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Acetaldehyde cytotoxicity in cultured rat astrocytes.

The effect of acetaldehyde on astrocytes have been investigated because not only do they play an important role in brain maturation but also recent reports have shown their delayed proliferation following both 'in vivo' and 'in vitro' ethanol exposure. Biochemical parameters related to apoptotic and necrotic processes were examined in primary cultures of rat astrocytes exposed for 4 days to acetaldehyde generated from ethanol by co-cultured alcohol dehydrogenase-transfected Chinese hamster ovary cells. Acetaldehyde levels in the culture media attained concentrations of approximately 450 microM. To study ethanol effects, alcohol oxidation was inhibited by 4-methylpyrazole (an inhibitor of alcohol dehydrogenase). Acetaldehyde but not ethanol increased intracellular calcium levels by 155%. Moreover, significant DNA fragmentation was detected using a random oligonucleotide primed synthesis assay, by flow cytometry and when using agar gel electrophoresis. Transglutaminase activity was elevated in the cells treated with acetaldehyde but when acetaldehyde formation was inhibited by 4-methylpyrazole the enzyme activity was unaffected. Nitrate levels in the culture media were unchanged. Additionally, microscopic examination of cell nuclei revealed chromatin condensation in astrocytes exposed to acetaldehyde. It can be concluded, that in 'in vitro' acetaldehyde exposed rat astrocytes apoptotic pathways are activated.

Acetaldehyde↗
PubMed1999

Flow cytometric examination of DNA ploidy, p53 and bcl-2 expression in primary squamous epithelial pulmonary carcinoma.

The aim of this study was answering the question whether cytofluorimetric determining of DNA ploidy, p53 and bcl-2 expression in tumour cells may enhance the diagnosis of squamous epithelial lung carcinoma. Samples of neoplastic tissue were taken from 11 operated patients. DNA staining was performed with propidium iodide. p53 and bcl-2 expression was evaluated by using monoclonal antibodies. By assessing of DNA ploidy we observed increased proliferative activity and, at the same time, high rate of the cell necrosis. In the analysis of p53 protein the presence of antigen was observed on average in 7.1 +/- 2.4, 15.1 +/- 3.9, and 19.8 +/- 4.1% of normal cells of the pulmonary tissue, the peripheral part of the tumour and cells of the central part of the tumour, respectively. bcl-2 was found on average in 7.3 +/- 2.2, 9.9 +/- 3.1, and 12.4 +/- 3.19% of the above cells, respectively. These results show that the technique of cytofluorimetric evaluation of p53 and bcl-2 proteins can be useful in diagnosis of pulmonary cancer in addition to classic histological and immunohistochemical methods.

Adult↗
PubMed1998

CGP 42112A antagonism of the angiotensin II and angiotensin II(3-7) facilitation of recall in rats.

An involvement of the angiotensin AT2 receptors in some behavioural effects of angiotensin II (Ang II) and its 3-7 fragment [Ang II(3-7)] in rats was studied. To inhibit AT2 receptors we used their selective antagonist CGP 42112A (nicotinic acid-Tyr-N-benzoxyl-carbonyl-Arg-Lys-His-Pro-Ile-OH). Ang II and Ang II(3-7), given intracerebroventricularly (i.c.v.) at the dose of 1 nmol each, significantly enhanced recall of the passive avoidance behaviour and learning of the conditioned avoidance responses (CARs). CGP 42112A (2 micrograms i.c.v.), inactive on its own in all tests, significantly attenuated facilitation of recall of passive avoidance caused by Ang II and Ang II(3-7). Also, CGP 42112A diminished Ang II improvement of CARs acquisition but not that caused by Ang II(3-7). None of the treatments produced significant anxiolysis in an elevated 'plus' maze. Likewise, in an open field no statistically significant differences were recorded except for the abolishment of the Ang II(3-7)-induced increase of rearings and bar approaches by CGP 42112A. It appears that the cognition improving activity of Ang II and Ang II(3-7) is mediated by similar mechanisms and angiotensin AT2 receptors are engaged in these processes.

Angiotensin II↗
PubMed1998

6-OHDA lesions to amygdala and hippocampus attenuate memory-enhancing effect of the 3-7 fragment of angiotensin II.

We have previously shown that facilitatory effect of angiotensin II (AII) on the retrieval of memory is mediated by the dopaminergic system. In the present study, we searched for the influence of the 3-7 fragment of angiotensin II [AII(3-7)] on the retrieval processes in a passive avoidance situation after bilateral 6-OHDA lesions to the central amygdala (CA) and the CA4 field of the hippocampus (HI). AII(3-7) given 15 min before the retention testing, at the intracerebroventricular dose of 1 nmol, significantly prolonged avoidance latencies in sham-operated rats (i.e. improved retrieval of memory for the electric footshock experienced during the learning trial). Bilateral lesions to CA totally abolished, and to HI significantly diminished, this facilitatory effect. An increase of spontaneous locomotor activity in rats lesioned to CA and a decrease in rats lesioned to HI were unlikely to interfere with the cognitive effect of AII (3-7). These results suggest that the anatomical substrate of facilitating retrieval of information activity of AII(3-7) is closely related to the dopaminergic projection from the ventral tegmental area and substantia nigra to CA and HI.

Adrenergic Agents↗
PubMed1997

Losartan influences behavioural effects of angiotensin II(3-7) in rats.

We have previously shown that angiotensin II(3-7) [Ang II(3-7)] stimulates behavioural activity of rats similar to angiotensin II (Ang II). The involvement of AT1 angiotensin receptors in stimulating the behavioural activity of rats, using their selective ligand losartan (DUP 753), was examined. Ang II(3-7), given intracerebroventricularly (i.c.v.) at a dose of 1 nmol, significantly enhanced recall of a passive avoidance behaviour, object recognition, learning of conditioned avoidance responses (CARs) and apomorphine (1 mg kg-1, i.p.) stereotypy. Losartan (1 microgram, i.c.v.) did not alter any of the behaviours except for that measuring anxiety which was diminished both, in peptide treated and in control rats. On the other hand, losartan abolished Ang II(3-7) facilitation of recall of the passive avoidance, object recognition and the increase in apomorphine stereotypy. Losartan did not influence the increased rate of CARs acquisition after the peptide. None of the treatments significantly changed locomotor activity estimated in an open field. These data point to some involvement of AT1 angiotensin receptors in the behavioural activity of Ang II(3-7).

Angiotensin II↗
PubMed1997

Dopaminergic projection to the septum mediates facilitatory effect of angiotensins on recognition memory in rats.

We have previously reported that the dopaminergic projection from A10 ventral tegmental neurons to the central amygdala is, in part, responsible for the facilitatory effect of angiotensin II (AII) and its 3-7 fragment [AII(3-7)] on the retrieval of information in memory motivated affectively and also on recognition memory. In this study, the influence of both angiotensins, given intracerebroventricularly at the dose of 1 nmol each, in rats lesioned with 6-OHDA to the nucleus accumbens septi (NAS) and to the nucleus septi lateralis (NSL) on recognition memory was evaluated. AII and its 3-7 fragment significantly improved object recognition in sham-operated to NAS and to NSL groups of rats. Bilateral 6-OHDA lesions to NAS totally abolished and to NSL significantly attenuated the facilitatory effect of both angiotensins on object recognition. These results suggest that the dopaminergic projection arriving to the septal structures. NAS and NSL takes part in the facilitatory effect of angiotensins on recognition memory.

Angiotensin II↗
PubMed1997

Acetaminophen metabolism and cytotoxicity in PC12 cells transfected with cytochrome P4502E1.

Although a number of studies confirm the important role of metabolites in the cytotoxicity of acetaminophen, its precise mechanisms remain unknown. Acetaminophen is metabolized by microsomal enzymes. Cytochrome P4502E1 (CYP2E1) mediated N-hydroxylation results in the formation of N-acetyl-benzo-quinoneimine, a highly reactive intermediate. We examined biochemical parameters related to necrotic and apoptotic processes in acetaminophen-exposed PC12 cells is and in a PC12 cell line genetically engineered to express human CYP2E1. Both the [3H]thymidine incorporation test and the protein assay uniformly showed dose- and time-related significant growth retardation in both cell lines exposed to the drug. This was more evident in CYP2E1-transfected cells. Moreover, the cytotoxic effect of acetaminophen was increased as evidenced by lactate dehydrogenase activity in the culture medium. Both random oligonucleotide primed synthesis assay and enzyme-linked immunosorbent assay revealed significant DNA fragmentation in both cell lines, which was greater in transfected cells, reaching about 11% of total cellular DNA. These results were confirmed by flow cytometry and microscopic examination of cell nuclei. Intracellular calcium levels were increased only in transfected cells, approximately threefold when 5 mM acetaminophen was administered for 48 h. These results indicate the cytotoxic effects of acetaminophen via apoptosis, necrosis, and growth retardation. While the precise mechanism remains obscure, it seems that DNA fragmentation and apoptotic cascade represent a preliminary biochemical event in acute cell death, and that acetaminophen bio-transformation by CYP2E1 stimulates this pathway.

Acetaminophen↗
PubMed1997

6-OHDA lesions to the central amygdala abolish angiotensins facilitation of object recognition in rats.

1. We have previously reported that the dopaminergic projection from A10 ventral tegmental neurons and A9 neurons of substantia nigra to the central amygdala (CA) is, in part, responsible for the facilitatory effect of angiotensin II (AII) and its 3-7 fragment [AII(3-7)] on the retrieval of information in memory that is motivated affectively. 2. In this study, the influence of both angiotensins, given intracerebroventricularly at the dose of 1 nmol each in rats lesioned with 6-OHDA to CA, on recognition memory, was tested. 3. AII and its 3-7 fragment significantly improved object recognition in sham-operated groups of rats. Bilateral 6-OHDA lesions to CA totally abolished the facilitatory effect of both angiotensins on object recognition. As insignificant increase of spontaneous locomotor activity in rats lesioned to CA did not interfere with the cognitive effect of AII and AII(3-7). 4. These results suggest that the dopaminergic projection at the CA takes part in the facilitatory effect of angiotensins on recognition memory.

Amygdala↗
PubMed1997

CGP 42112A abolishes facilitation of recognition caused by angiotensin II and angiotensin II(3-7) in rats.

The role of the angiotensin AT2 receptors in some behavioural effects of angiotensin II (Ang II) and its 3-7 fragment [Ang II(3-7)], using their selective antagonist CGP 42112A, was assessed. Ang II and Ang II(3-7), given intracerebroventricularly (icv) at the dose of 1 nmole each, substantially improved object recognition memory and enhanced apomorphine (1 mg/kg) stereotypy. Pre-treatment of rats with CGP 42112A (2 micrograms), per se ineffective in all tests, abolished activity of both peptides. None of the treatments significantly changed behaviour of rats in open field. The results point to the considerable involvement of the AT2 angiotensin receptors in the improvement of recognition memory caused by Ang II and Ang II(3-7).

Angiotensin II↗
PubMed1996

Solcoseryl improves learning and memory in rats.

Our previous experiments have shown that Solcoseryl (S), a protein-free extract of calves' blood stimulates locomotor activity and decreases haloperidol catalepsy in rats. In this study the influence of S on acquisition, consolidation, and recall of both, conditioned avoidance responses (CARs) and passive avoidance behaviour was tested. S at the intraperitoneal (i.p.) dose of 1.25 ml/kg significantly improved acquisition and at the dose of 1.0 ml/kg recall of CARs. In the passive avoidance situation the significant effect on acquisition and recall of information was observed after i.p. injection of 1.0 ml/kg of S, and on consolidation after 0.75 ml/kg. These data indicate that S may positively affect the CNS processes responsible for learning and memory.

Actihaemyl↗
PubMed1996

Solcoseryl stimulates behavioural activity of rats.

The influence of Solcoseryl (S), a protein-free extract of calves' blood given intraperitoneally (i.p.) on the behavioural measures of activity of the central nervous system of male Wistar rats was examined. The drug (1.0 ml/kg i.p.) given 60 min before testing the animals in electromagnetic motimeter significantly enhanced overall and vertical motility of rats. S at the doses of 0.5, 1.0 and 2.0 ml/kg did not significantly influence the activity of rats in "open field". 1.0 ml/kg of S given 15, 45 and 60 min before thiopental (30 mg/kg i.p.) did not change the onset and time of sleep following the latter drug, except for the significant shortening of the time of sleep of animals injected with S 15 min before thiopental. S at the dose of 1.0 ml/kg did not change stereotypies produced by apomorphine (2.0 mg/kg i.p.) and amphetamine (6.5 mg/kg i.p.) but decreased intensity of haloperidol (1.0 mg/kg i.p.) catalepsy.

Actihaemyl↗
PubMed1995

Angiotensin II and its 3-7 fragment improve recognition but not spatial memory in rats.

The effects of angiotensin II (AII), its 3-7 fragment [AII(3-7)] and the substituted 3-7 fragment [Leu-5,AII(3-7)] given intracerebroventricularly (ICV) at the dose of 1 nmole each, on spatial memory and recognition were tested. AII(3-7) increased while Leu-5,AII(3-7) slightly decreased session to session foot shock reinforced runtime to the goal in a complex 6 chamber maze. The animals treated with AII performed in the maze similarly to saline injected controls. Overall number of errors was unchanged in all peptide treated groups in comparison with the control group. Object recognition was significantly improved in all the peptide treated groups except for the Leu-5,AII(3-7) group. The results point to the facilitation of recognition and lack of influence on, or even attenuation of, spatial memory by AII and its 3-7 fragment. Leu-5,AII(3-7) caused similar though less pronounced effects.

Amino Acid Sequence↗