The issue of applying marketing on the pharmaceutical market has the features of subject-based approach, with the intention to appreciate the specific nature of the products, as well as the special ...characteristics of the complexly formed demand. The relevance of the issue is related to the above-average performance of the pharmaceutical industry, its role in the generation of humanity's demographic transition, and specific development routes of marketing as a scientific and practical discipline. The sensitive nature of a pharmaceutical product on the one hand generates the intense legislation on this market, whereas on the other, the circumstances of its use generate a specific environment in which the production/consumption of the products of pharmaceutical industry is intensively reflected as a specific medical, cultural, economic and even political phenomenon.
The impact of heroin on visual memory Mitrovic, S Martinović; Vuckovic, N; Dickov, A ...
European review for medical and pharmacological sciences
15, Issue:
5
Journal Article
Peer reviewed
Heroin abuse can lead to organic damage of cerebral structures, including sequels in cognitive and affective sphere, which are in positive relation with the duration of substance usage. Memory is one ...of the cognitive functions which is highly sensitive to opiate toxic effects. The aim of this research was determination of heroin impact on the visual memory of addicts, as well as the existence of specific relation of potential deficiencies in visual memory with the duration of substance use.
The research included 90 examinees, divided into three groups, depending on the duration of heroin intake. We used questionnaire for basic socio-demographic and addictological traits of examinees; Wechsler's scale for the assessment of the intelligence and Visual Memory Test (TVP), for the assessment of the visual memory.
The achievements of heroin addicts with different duration of the substance abuse differ significantly (F = 1.83; df = 12; p < 0.05). Total number of errors examinees make in the first series of TVP (immediate visual memory) grows, almost linearly in the function of the duration of heroin abuse (p < 0.05), but in neither of groups meets criteria for the visual memory impairment. Deficiency of the delayed visual memory occurs in examinees who use heroin for one (total number of errors = 6.46; participation of typical organic errors = 31.7%) and longer than five years (total number of errors = 7.66; participation of typical organic errors = 26.7%). Univariate covariance analysis separates the average daily dosage of heroin as the most significant variable that contributes to the expression of the aforementioned deficiencies (F = 4.21; df = 2; p < 0.05).
Heroin abuse leads to damage of delayed visual memory, whereby for the observed effect intake of the substance for a period longer than one year is necessary.
Alcohol delirium tremens suggests dysfunction of numerous brain regions. Several Authors suggest that alcohol and withdrawal from alcohol could cause neurotoxic lesions in the frontal lobe and ...thereby affect cognitive function. However, it is not that well known whether the consequences of the damage following delirium are only quantitative or qualitative.
Thirty alcohol-dependent patients after alcohol delirium (ADT-n1 = 30), and 30 alcohol-dependent patients without alcohol delirium (ALC-n2=30) were compared with neuropsychological test-battery. (Wechsler Bellevue Intelligence Scale - WB form I, Wechsler memory scale and Rey Auditory Verbal Learning Test (RAVLT). Examinees were selected as equivalent pairs, in such a manner that they were of approximately same age, i.e. age difference was 0-5 years, they were of the same education level, and difference in the duration of drinking was not more than 3 years.
In the group of ADT patients, IQ was 97.53, while it is 109.53 for ALC patients. Mental deterioration of the examined group is 40, and in the control group 13. Group of ADT patients had significantly lower achievements on subtests: arithmetic, block design and digit symbol. ADT patients' average memory quotient (MQ) is 81.8, which is three standard deviations lower compared to ALC patients (MQ 102.2) and standard values, according to Wechsler. In the first repetition of the series of 15 words RAVLT, is no difference (t-test=1.88; p > 0.05), while the difference in other repetitions is significant. Difference is also statistically significant regarding recollection after 30 minutes (t-test=3.66; p < 0.05).
There is qualitative difference in cognitive deficiencies in alcoholics with delirium tremens and those with no alcohol delirium, while the predominant pathology of the cognitive-amnestic deficiency is in compliance with the dysfunction of the prefrontal lobe. Following alcohol delirium, verbal memory disorders occur within the intellectual decrease and attention disorder in general.
Background: Extracellular adenine nucleotides and nucleosides, such as ATP and
adenosine, are among the most recently identified and least investigated diffusible signaling factors
that contribute to ...the structural and functional remodeling of the brain, both during embryonic
and postnatal development. Their levels in the extracellular milieu are tightly controlled by
various ectonucleotidases: ecto-nucleotide pyrophosphatase/phosphodiesterases (E-NPP), alkaline
phosphatases (AP), ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) and ecto-5'-
nucleotidase (eN).
Methods: Studies related to the expression patterns of ectonucleotidases and their known features
during brain development are reviewed, highlighting involvement of these enzymes in synapse
formation and maturation in physiological as well as in pathological states.
Results: During brain development and in adulthood all ectonucleotidases have diverse expression
pattern, cell specific localization and function. NPPs are expressed at early embryonic days, but the
expression of NPP3 is reduced and restricted to ependymal area in adult brain. NTPDase2 is dominant
ectonucleotidase existing in the progenitor cells as well as main astrocytic NTPDase in the
adult brain, while NTPDase3 is fully expressed after third postnatal week, almost exclusively on
varicose fibers. Specific brain AP is functionally associated with synapse formation and this enzyme
is sufficient for adenosine production during neurite growth and peak of synaptogenesis. eN is
transiently associated with synapses during synaptogenesis, however in adult brain it is more glial
than neuronal enzyme.
Conclusion: Control of extracellular adenine nucleotide levels by ectonucleotidases are important
for understanding the role of purinergic signaling in developing tissues and potential targets in developmental
disorders such as autism.
Sustained activation of pro-apoptotic signaling due to a sudden and prolonged disturbance of cerebral blood circulation governs the neurodegenerative processes in prefrontal cortex (PFC) of rats ...whose common carotid arteries are permanently occluded. The adequate neuroprotective therapy should minimize the activation of toxicity pathways and increase the activity of endogenous protective mechanisms. Several neuroprotectants have been proposed, including progesterone (P
4
). However, the underlying mechanism of its action in PFC following permanent bilateral occlusion of common carotid arteries is not completely investigated. We, thus herein, tested the impact of post-ischemic P
4
treatment (1.7 mg/kg for seven consecutive days) on previously reported aberrant neuronal morphology and amount of DNA fragmentation, as well as the expression of progesterone receptors along with the key elements of Akt/Erk/eNOS signal transduction pathway (Bax, Bcl-2, cytochrome C, caspase 3, PARP, and the level of nitric oxide). The obtained results indicate that potential amelioration of histological changes in PFC might be associated with the absence of activation of Bax/caspase 3 signaling cascade and the decline of DNA fragmentation. The study also provides the evidence that P
4
treatment in repeated regiment of administration might be effective in neuronal protection against ischemic insult due to re-establishment of the compromised action of Akt/Erk/eNOS-mediated signaling pathway and the upregulation of progesterone receptors.
Alprazolam (ALP), a benzodiazepine (BDZ) used to treat anxiety, panic, and sleep disorders, is one of the most prescribed psychotropic drugs worldwide. The side effects associated with long-term ...(mis)use of ALP have become a major challenge in pharmacotherapy, emphasizing the unmet need to further investigate their underlying molecular mechanisms. Prolonged BDZ exposure may induce adaptive changes in the function of several receptors, including the primary target, gammaaminobutyric acid receptor type A (GABA
R), but also other neurotransmitter receptors such as glutamatergic. The present study investigated the potential effects of prolonged ALP treatment on components of glutamatergic neurotransmission, with special emphasis on N-Methyl-D-aspartate receptor (NMDAR) in the hippocampus of adult male Wistar rats. The study revealed behavioral changes consistent with potential onset of tolerance and involvement of the glutamatergic system in its development. Specifically, an increase in NMDAR subunits (NR1, NR2A, NR2B), a decrease in vesicular glutamate transporter 1 (vGlut1), and differential modulation of excitatory amino acid transporters 1 and 2 (EAAT1/2, in vivo and in vitro) were observed, alongside a decrease in α1-containing GABA
R following the treatment. By describing the development of compensatory actions in the glutamatergic system, the present study provides valuable information on neuroadaptive mechanisms following prolonged ALP intake.
Highlights • eN activity and protein level fluctuates across the estrus cycle in the hippocampal synaptosomes. • E2 upregulated synaptic eN activity and protein abundance. • E2 action is mediated by ...estrogen receptor-α and -β. • E2 had to enter into the intracellular compartment to activate ER(s). • ERα induced upregulation of eN protein level and activity, while ERβ increased only eN activity.
17 beta -Estradiol (E2) crucially affects several processes in the hippocampus of both sexes. E2 acts upon estradiol receptors ER alpha and ER beta , influencing target gene expression and/or ...modulates intracellular signaling cascades. Another potent modulator of hippocampal function is nucleoside adenosine, the final product of ectonucleotidase cascade, enzymes which hydrolyze extracellular ATP to adenosine. The last and rate-limiting step of the hydrolysis is catalyzed by membrane-bound ecto-5'-nucleotidase (eN). Previous findings obtained on adenosine metabolism in brain suggest that eN may be modulated by ovarian steroids. Therefore, the present study reports that the activity and protein abundance of membrane-bound eN fluctuates across the estrus cycle in the hippocampal synaptosomes of female rats. Further, we analyzed the role of E2 and its intracellular receptors on the expression of eN in ovariectomized females. We found that E2 upregulated eN activity and protein abundance in the hippocampal synaptosomes. Application of nonspecific ER antagonist, ICI 182,780 and selective ER alpha and ER beta agonists, PPT and DPN, respectively, demonstrated the involvement of both receptor subtypes in observed actions. Selective ER alpha receptor agonist, PPT, induced upregulation of both the protein level and activity of eN, while application of selective ER beta receptor agonist, DPN, increased only the activity of eN. In both cases, E2 entered into the intracellular compartment and activated ER(s), which was demonstrated by membrane impermeable E2-BSA conjugate. Together these results imply that E2-induced effects on connectivity and functional properties of the hippocampal synapses may be in part mediated through observed effect on eN.
•I/R-induced HIP vGluT1, NR1, NR2B subunits increase and PSD-95 decrease.•CA1 neuronal damage accompanies detected protein level changes.•NR1 subunit reduction in PFC is associated with layer III ...neuronal damage.•DHEA in physiological condition doesn’t affect protein level or neuronal morphology.•DHEA restores I/R-induced changes of HIP PSD-95 and PFC NR1 protein level.
Excessive glutamate efflux and N-methyl-D-aspartate receptor (NMDAR) over-activation represent well-known hallmarks of cerebral ischemia/reperfusion (I/R) injury, still, expression of proteins involved in this aspect of I/R pathophysiology show inconsistent data. Neurosteroid dehydroepiandrosterone (DHEA) has been proposed as potent NMDAR modulator, but its influence on I/R-induced changes up to date remains questionable. Therefore, I/R-governed alteration of vesicular glutamate transporter 1 (vGluT1), synaptic NMDAR subunit composition, postsynaptic density protein 95 (PSD-95) and neuronal morphology alone or following DHEA treatment were examined. For that purpose, adult male Wistar rats were treated with a single dose of vehicle or DHEA (20 mg/kg i.p.) 4 h following sham operation or 15 min bilateral common carotid artery occlusion. Western blot was used for analyses of synaptic protein expressions in hippocampus and prefrontal cortex, while neuronal morphology was assessed using Nissl staining. Regional-specific postischemic changes were detected on protein level i.e. signs of neuronal damage in CA1 area was accompanied with hippocampal vGluT1, NR1, NR2B enhancement and PSD-95 decrement, while histological changes observed in layer III were associated with decreased NR1 subunit in prefrontal cortex. Under physiological conditions DHEA had no effect on protein and histological appearance, while in ischemic milieu it restored hippocampal PSD-95 and NR1 in prefrontal cortex to the control level. Along with intact neurons, ones characterized by morphology observed in I/R group were also present. Future studies involving NMDAR-related intracellular signaling and immunohistochemical analysis will reveal precise effects of I/R and DHEA treatment in selected brain regions.
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