Publications by authors named "Joanna Kryst"

5 Publications

  • Page 1 of 1

A Search for Biomarkers of Early-life Stress-related Psychopathology: Focus on 70-kDa Heat Shock Proteins.

Neuroscience 2021 Mar 2. Epub 2021 Mar 2.

Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, Laboratory of Pharmacology and Brain Biostructure, Smętna Street 12, 31-343 Kraków, Poland. Electronic address:

Clinical studies clearly indicate that early-life stress (ELS) may cause physical and mental health problems later in life. Therefore, the identification of universal biomarkers of ELS-related diseases is very important. The 70-kDa heat shock proteins (HSP70s), specifically HSPA5 and HSPA1B, have been recently shown to be potentially associated with occurrence of anxiety, mood disorders, and schizophrenia; thus, we hypothesized that HSP70s are potential candidate biomarkers of ELS-induced psychopathologies. A maternal separation (MS) procedure in rats was used to model ELS, and the expression of HSPA5 and HSPA1B was investigated in the blood, medial prefrontal cortex (mPFC), and hippocampus of juvenile, preadolescent, and adult animals. We also studied the effects of MS on the long-term potentiation (LTP) and behavioral phenotypes of adult rats. We found that MS enhanced the expression of HSPA1B mRNA in the blood and mPFC of juvenile and preadolescent rats. This increase was accompanied by an increase in the HSPA1A/1B protein levels in the mPFC and hippocampus of juvenile rats that persisted in the mPFC until adulthood. MS juvenile and adult rats showed enhanced HSPA5 mRNA expression in the blood and increased HSPA5 protein expression in the mPFC (juveniles) and hippocampus (adults). Concurrently, MS adult rats exhibited aberrations in LTP in the mPFC and hippocampus and a less anxious behavioral phenotype. These results indicate that MS may produce enduring overexpression of HSPA1B and HSPA5 in the brain and blood. Therefore, both HSP70 family members may be potential candidate peripheral and brain biomarkers of ELS-induced changes in brain functioning.
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March 2021

Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials.

Pharmacol Rep 2020 Jun 16;72(3):543-562. Epub 2020 Apr 16.

Department of Internal and Community Nursing, Institute of Nursing and Midwifery, Faculty of Health Sciences, Jagiellonian University Medical College, Kraków, Poland.

Background: Due to unmet clinical needs for efficient drugs with a rapid onset of antidepressant effects, we aimed to evaluate the efficacy of single-dose ketamine in different subgroups of patients with major depression and establish whether repeated ketamine administration could be a viable strategy to maintain treatment gains.

Methods: Electronic databases (Medline via PubMed, Embase, Cochrane Library, Trip Database) were systematically searched until February 22, 2019, for published peer-reviewed randomized controlled trials (RCTs) concerning a single and repeated administration of ketamine in patients with major depression. All relevant RCTs were selected and critically appraised, and a meta-analysis of eligible studies was performed.

Results: A total of 20 studies were included in the meta-analysis. The largest effect of ketamine vs. controls in reducing depressive symptoms was observed at 24 h (SMD = - 0.89; 95% CI - 1.24; - 0.53; p < 0.00001); however, a significant difference was shown for up to 7 days after a single dose. Significant differences compared with controls were observed for up to 7 days in treatment-resistant patients and when ketamine was added to ongoing antidepressant treatment, while there were no significant differences at 7 days when ketamine was used as monotherapy. In patients with major depression, initial antidepressant effects of ketamine were maintained during repeated dosing. At 2-3 weeks of repeated ketamine treatment, significant reduction of depression severity scores was observed: SMD = - 0.70; 95% CI - 1.15; - 0.25 or SMD = - 0.81; 95% CI - 1.41; - 0.20 (depending on the dosing regimen used); p ≤ 0.009 vs placebo.

Conclusions: Our meta-analysis revealed rapid and robust antidepressant effects of single-dose ketamine in patients with treatment-resistant depression (TRD). By pooling data from RCTs, we showed for the first time that repeated ketamine administration is effective in sustaining initial antidepressant effects observed after single dosing.
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June 2020

Efficacy and safety of intranasal esketamine for the treatment of major depressive disorder.

Expert Opin Pharmacother 2020 Jan 30;21(1):9-20. Epub 2019 Oct 30.

Department of Neurobiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.

: In March 2019, intranasal esketamine was approved by the Food and Drug Administration (FDA) for the treatment of treatment-resistant depression (TRD) in adults. This review presents the results of clinical trials underlying the FDA approval of intranasal esketamine.: Esketamine's efficacy and safety in TRD were assessed in 5 phase III studies: three 4-week, placebo-controlled studies, and two long-term trials. One short-term trial showed statistically significant antidepressant effects of esketamine vs placebo, while a long-term withdrawal study showed that esketamine is significantly beneficial in terms of extending time to relapse, compared to placebo. Two other short-term trials did not meet the prespecified statistical tests for showing efficacy, although improvement in depressive symptoms from baseline to the end of week 4 favors esketamine over placebo.: Intranasal esketamine is a new treatment option for people with TRD. The main benefit of esketamine is rapid onset of antidepressant activity, but the effects of prolonged treatment are still preliminary. The main concerns relate to the safety aspects of prolonged esketamine therapy, when considering its abuse potential. While data for esketamine use over a long period of time is lacking, its use should be carefully monitored.
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January 2020

Efavirenz-Based Regimens in Antiretroviral-Naive HIV-Infected Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PLoS One 2015 1;10(5):e0124279. Epub 2015 May 1.

Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

Efavirenz, a non-nucleoside reverse-transcriptase inhibitor (NNRTI) is one of the most commonly prescribed antiretroviral drugs. The present article provides a systematic overview and meta-analysis of clinical trials comparing efavirenz and other active drugs currently recommended for treatment of HIV-infected, antiretroviral-naive patients. Electronic databases (Pubmed, Embase, the Cochrane Library, Trip Database) were searched up till 23 December 2013 for randomized controlled clinical trials published as a peer-reviewed papers, and concerning efavirenz-based regimens used as initial treatment for HIV infection. Thirty-four studies were included in the systematic review, while twenty-six trials were suitable for the meta-analysis. Efavirenz was compared with drugs from four different classes: NNRTIs other than efavirenz (nevirapine or rilpivirine), integrase strand transfer inhibitors (InSTIs), ritonavir-boosted protease inhibitors (bPI) and chemokine (C-C motif) receptor 5 (CCR5) antagonists (maraviroc), all of them were added to the background regimen. Results of the current meta-analysis showed that efavirenz-based regimens were equally effective as other recommended regimens based on NNRTI, ritonavir-boosted PI or CCR5 antagonist in terms of efficacy outcomes (disease progression and/or death, plasma viral HIV RNA <50 copies/ml) while statistically significant more patients treated with InSTI achieved plasma viral load <50 copies/ml at week 48. In comparison with both InSTI-based and CCR5-based therapy, efavirenz-based treatment was associated with a higher risk of therapy discontinuation due to adverse events. However, comparisons of efevirenz-based treatment with InSTI-based and CCR5-based therapy were based on a limited number of trials, therefore, conclusions from these two comparisons must be confirmed in further reliable randomized controlled studies. Results of our meta-analysis support the present clinical guidelines for antiretroviral-naive, HIV-infected patients, in which efavirenz is one of the most preferred regimens in the analyzed population. Beneficial safety profile of InSTI-based and CCR5-based therapy over efavirenz-based treatment needs further studies.
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January 2016

Nevirapine-based regimens in HIV-infected antiretroviral-naive patients: systematic review and meta-analysis of randomized controlled trials.

PLoS One 2013 7;8(10):e76587. Epub 2013 Oct 7.

Drug Management Department, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University, Krakow, Poland ; Centrum HTA Sp. z o.o. Sp. komandytowa, Krakow, Poland.

Background: Nevirapine belongs to the group of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and is commonly administered in first-line treatment of HIV infection.

Objective: Systematic review and meta-analysis was undertaken to compare effectiveness of nevirapine-based regimens with other antiretroviral schedules used as an initial treatment of HIV-infected antiretroviral-naive subjects.

Methods: Electronic databases (PubMed, EMBASE, the Cochrane Library, Trip Database) were searched up to 28 December 2012 for randomized controlled trials (RCTs) published as a full text and regarding nevirapine-based regimens used as a initial treatment for HIV infection. Meta-analysis was performed with RevMan(®) V 5.2 software.

Results: Twelve RCTs were included in the systematic review and all of them were suitable for meta-analysis. Results of the meta-analysis have shown that nevirapine, efavirenz, and ritonavir-boosted protease inhibitor, added to the background regimens, were equally effective in terms of reaching undetectable plasma HIV RNA level as well as risk of disease progression or death. Compared with ritonavir-boosted protease inhibitor-based regimens, nevirapine-based regimens statistically significantly increased the risk of discontinuation of assigned treatment (RR=3.10; 95% CI: 1.14-8.41; p<0.05).

Conclusions: Despite limited RCTs data available for particular comparisons, our results suggest that nevirapine-based regimens may be considered for first-line treatment of HIV-infected adults, due to their comparable efficacy to the other currently recommended initial antiretroviral therapies.
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August 2014