Publications by authors named "Jan Homolak"

14 Publications

  • Page 1 of 1

A CROSS-SECTIONAL STUDY OF HEPATITIS B AND HEPATITIS C KNOWLEDGE AMONG DENTAL MEDICINE STUDENTS AT THE UNIVERSITY OF ZAGREB.

Acta Clin Croat 2021 Jun;60(2):216-230

1Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia; 2University of Zagreb School of Dental Medicine, Zagreb, Croatia; 3Department of Environmental and Occupational Health and Sports, Andrija Štampar School of Public Health, University of Zagreb School of Medicine, Zagreb, Croatia; 4Department of Periodontology, University of Zagreb School of Dental Medicine, Zagreb, Croatia; 5Gastroenterology and Hepatology Division, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia; 6Department of Internal Medicine, University of Zagreb School of Medicine, Zagreb, Croatia; 7Cardiovascular Division, Zagreb University Hospital Centre, Zagreb, Croatia; 8Gastroenterology Unit, Dr. Ivo Pedišić General Hospital, Sisak, Croatia; 9Department of Internal Medicine, University of Zagreb School of Dental Medicine, Zagreb, Croatia.

Dental health care workers, particularly dental medicine students (DMS), are at an increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. The aim of our study was to assess the level of knowledge on HBV and HCV, estimate needlestick injury (NSI) prevalence and reporting practice in DMS at the University of Zagreb, and analyze how enrolment in obligatory and supplemental courses affects knowledge and NSI reporting practice. The knowledge was assessed by our questionnaires based on the Centers for Disease Control general handouts. Additional information was collected to examine the prevalence and reporting practice of NSI. Data were analyzed by descriptive statistical analysis, independent-samples t-test, proportion analyses, and combined factor analyses of categorical and quantitative variables in SPSS and R. In total, 206 students participated in the survey. The overall level of HBV- and HCV-related knowledge was poor, with the mean scores of 61.90% and 51.35%, respectively. Moreover, students enrolled in the first year demonstrated significantly lower levels of knowledge in comparison with their older peers. Of all participants, 18.2% had sustained a NSI and the majority of them (78.95%) had never reported the injury. In conclusion, DMS have low levels of knowledge on important occupational pathogens and poor NSI reporting practice. Moreover, formal education in the current form has failed to significantly improve student competence and theoretical knowledge translates poorly into more conscientious injury reporting practice. We should look for a better way to increase student awareness and level of knowledge on this topic.
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http://dx.doi.org/10.20471/acc.2021.60.02.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564850PMC
June 2021

Is Galactose a Hormetic Sugar? An Exploratory Study of the Rat Hippocampal Redox Regulatory Network.

Mol Nutr Food Res 2021 Nov 9;65(21):e2100400. Epub 2021 Sep 9.

Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia.

Scope: Galactose, a ubiquitous monosaccharide with incompletely understood physiology is often exploited for inducing oxidative-stress mediated aging in animals. Recent research demonstrates that galactose can conserve cellular function during periods of starvation and prevent/alleviate cognitive deficits in a rat model of sporadic Alzheimer's disease. The present aim is to examine the acute effects of oral galactose on the redox regulatory network (RRN).

Methods And Results: Rat plasma and hippocampal RRNs are analyzed upon acute orogastric gavage of galactose (200 mg kg ). No systemic RRN disbalance is observed; however, a mild pro-oxidative shift accompanied by a paradoxical increment in tissue reductive capacity suggesting overcompensation of endogenous antioxidant systems is observed in the hippocampus. Galactose-induced increment of reductive capacity is accompanied by inflation of the hippocampal pool of nicotinamide adenine dinucleotide phosphates indicating ROS detoxification through disinhibition of the oxidative pentose phosphate pathway flux, reduced neuronal activity, and upregulation of Leloir pathway gatekeeper enzyme galactokinase-1.

Conclusion: Based on the observed findings, and in the context of previous work on galactose, a hormetic hypothesis of galactose is proposed suggesting that the protective effects may be inseparable from its pro-oxidative action at the biochemical level.
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http://dx.doi.org/10.1002/mnfr.202100400DOI Listing
November 2021

Failure of the Brain Glucagon-Like Peptide-1-Mediated Control of Intestinal Redox Homeostasis in a Rat Model of Sporadic Alzheimer's Disease.

Antioxidants (Basel) 2021 Jul 13;10(7). Epub 2021 Jul 13.

Department of Pharmacology, University of Zagreb School of Medicine, 10 000 Zagreb, Croatia.

The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer's disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model.
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http://dx.doi.org/10.3390/antiox10071118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301063PMC
July 2021

Circadian changes in Alzheimer's disease: Neurobiology, clinical problems, and therapeutic opportunities.

Handb Clin Neurol 2021 ;179:285-300

Department of Pharmacology, and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.

The understanding of Alzheimer's disease (AD) pathophysiology is an active area of research, and the traditional focus on hippocampus, amyloid and tau protein, and memory impairment has been expanded with components like neuroinflammation, insulin resistance, and circadian rhythm alterations. The bidirectional vicious cycle of neuroinflammation and neurodegeneration on a molecular level may cause functional deficits already long before the appearance of overt clinical symptoms. Located at the crossroads of metabolic, circadian, and hormonal signaling, the hypothalamus has been identified as another brain region affected by AD pathophysiology. Current findings on hypothalamic dysfunction open a broader horizon for studying AD pathogenesis and offer new opportunities for diagnosis and therapy. While treatments with cholinomimetics and memantine form a first line of pharmacological treatment, additional innovative research is pursued toward the development of antiinflammatory, growth factor, or antidiabetic types of medication. Following recent epidemiological data showing associations of AD incidence with modern societal and "life-style"-related risk factors, also nonpharmacological interventions, including sleep optimization, are being developed and some have been shown to be beneficial. Circadian aspects in AD are relevant from a pathophysiological standpoint, but they can also have an important role in pharmacologic and nonpharmacologic interventions, and appropriate timing of sleep, meals, and medication may boost therapeutic efficacy.
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http://dx.doi.org/10.1016/B978-0-12-819975-6.00018-2DOI Listing
July 2021

Insulin Resistance as a Common Link Between Current Alzheimer's Disease Hypotheses.

J Alzheimers Dis 2021 ;82(1):71-105

Department of Neurosciences and Behavioral Sciences, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.

Almost 115 years ago, Alois Alzheimer described Alzheimer's disease (AD) for the first time. Since then, many hypotheses have been proposed. However, AD remains a severe health public problem. The current medical approaches for AD are limited to symptomatic interventions and the complexity of this disease has led to a failure rate of approximately 99.6%in AD clinical trials. In fact, no new drug has been approved for AD treatment since 2003. These failures indicate that we are failing in mimicking this disease in experimental models. Although most studies have focused on the amyloid cascade hypothesis of AD, the literature has made clear that AD is rather a multifactorial disorder. Therefore, the persistence in a single theory has resulted in lost opportunities. In this review, we aim to present the striking points of the long scientific path followed since the description of the first AD case and the main AD hypotheses discussed over the last decades. We also propose insulin resistance as a common link between many other hypotheses.
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http://dx.doi.org/10.3233/JAD-210234DOI Listing
September 2021

GLP-1 receptor - Do we really know what we're looking at?

Acta Histochem 2021 07 18;123(5):151732. Epub 2021 May 18.

Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia; Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.

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http://dx.doi.org/10.1016/j.acthis.2021.151732DOI Listing
July 2021

The effect of a color tattoo on the local skin redox regulatory network: an N-of-1 study.

Authors:
Jan Homolak

Free Radic Res 2021 Mar 15;55(3):221-229. Epub 2021 Apr 15.

Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia.

Biomedical aspects of tattooing have been extensively discussed in literature, however pathophysiological effects of tattoo inks in the human body are still unexplored. Oxidative stress is considered responsible for the adverse effects of tattooing, however no experimental evidence for tattoo ink-related oxidative stress in the human body currently exists. The aim was to examine the effect of a blue tattoo on skin redox regulatory network (RRN) parameters in a single human subject. Skin surface oxidation-reduction potential (ORP) was analyzed with a PH60F flat probe. Interstitial and intracellular fluid enriched capillary blood from the tattoo and the control area was extracted and analyzed with I2/KI-stabilized microORP, nitrocellulose redox permanganometry (NRP), carbonato-cobaltate (III) formation-derived H2O2 dissociation rate assay, 1,2,3-trihydroxybenzene autoxidation assay, thiobarbituric reactive substances (TBARS) assay and 5,5,'-dithio-bis-(2-nitrobenzoic acid) (DTNB)-based determination of free thiol content in low molecular weight and protein precipitate fractions. Surface ORP analysis revealed a greater antioxidant capacity of tattooed skin in comparison with the control (CTR). Capillary blood analysis confirmed greater reductive capacity in the tattoo sample both by microORP (-4.33 mV vs CTR) and NRP (+10.8%). Hydrogen peroxide dissociation rate (+11.8%), and protein sulfhydryl content (+8.5%) were increased, and lipid peroxidation (-15%) was reduced in the tattoo sample in comparison with the CTR. In this N-of-1 study, RRN of tattooed skin was shifted toward a more reductive state with all parameters indicating reduced levels of oxidative stress in comparison with nontattooed skin. The local antioxidant effect of copper(II) phthalocyanine provides one possible explanation of the observed effects.
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http://dx.doi.org/10.1080/10715762.2021.1912340DOI Listing
March 2021

An Additional Perspective on Proton Pump Inhibitors as Risk Factors for COVID-19.

Clin Drug Investig 2021 03 19;41(3):287-289. Epub 2021 Feb 19.

Department of Pharmacology, University of Zagreb School of Medicine, 10 000, Zagreb, Croatia.

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http://dx.doi.org/10.1007/s40261-021-01007-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892720PMC
March 2021

Additional methodological considerations regarding optimization of the dose of intracerebroventricular streptozotocin A response to: "Optimization of intracerebroventricular streptozotocin dose for the induction of neuroinflammation and memory impairments in rats" by Ghosh et al., Metab Brain Dis 2020 July 21.

Metab Brain Dis 2021 01 27;36(1):97-102. Epub 2020 Oct 27.

Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia.

A recent article by Ghosh et al. entitled "Optimization of intracerebroventricular streptozotocin dose for the induction of neuroinflammation and memory impairments in rats" provides an important new set of information on neuroinflammation and cognitive deficit in a rat model of sporadic Alzheimer's disease (sAD) based on intracerebroventricular administration of streptozotocin (STZ-icv) in Charles-Foster rats in the early post-treatment period of 21 days. This comment is supposed to supplement the aforementioned manuscript by providing additional perspective on important factors that should be taken into account in the process of optimization of the streptozotocin (STZ) dose for intracerebroventricular treatment, and provides a brief overview of possible sources of variation of experimental results reported by different groups working with STZ-icv rodent models.
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http://dx.doi.org/10.1007/s11011-020-00637-9DOI Listing
January 2021

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease.

J Neural Transm (Vienna) 2020 02 6;127(2):231-250. Epub 2020 Feb 6.

Department of Pharmacology, University of Zagreb School of Medicine, Salata 11, 10 000, Zagreb, Croatia.

Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common chronic neurodegenerative disorders, characterized by motoric dysfunction or cognitive decline in the early stage, respectively, but often by both symptoms in the advanced stage. Among underlying molecular pathologies that PD and AD patients have in common, more attention is recently paid to the central metabolic dysfunction presented as insulin resistant brain state (IRBS) and altered cerebral glucose metabolism, both also explored in animal models of these diseases. This review aims to compare IRBS and alterations in cerebral glucose metabolism in representative non-transgenic animal PD and AD models. The comparison is based on the selectivity of the neurotoxins which cause experimental PD and AD, towards the cellular membrane and intracellular molecular targets as well as towards the selective neurons/non-neuronal cells, and the particular brain regions. Mitochondrial damage and co-expression of insulin receptors, glucose transporter-2 and dopamine transporter on the membrane of particular neurons as well as astrocytes seem to be the key points which are further discussed in a context of alterations in insulin signalling in the brain and its interaction with dopaminergic transmission, particularly regarding the time frame of the experimental AD/PD pathology appearance and the correlation with cognitive and motor symptoms. Such a perspective provides evidence on IRBS being a common underlying metabolic pathology and a contributor to neurodegenerative processes in representative non-transgenic animal PD and AD models, instead of being a direct cause of a particular neurodegenerative disorder.
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http://dx.doi.org/10.1007/s00702-020-02152-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035309PMC
February 2020

Circadian Rhythm and Alzheimer's Disease.

Med Sci (Basel) 2018 Jun 21;6(3). Epub 2018 Jun 21.

Department of Pathophysiology, University of Zagreb School of Medicine, Kišpaticeva 12, Zagreb 10 000, Croatia.

Alzheimer's disease (AD) is a neurodegenerative disorder with a growing epidemiological importance characterized by significant disease burden. Sleep-related pathological symptomatology often accompanies AD. The etiology and pathogenesis of disrupted circadian rhythm and AD share common factors, which also opens the perspective of viewing them as a mutually dependent process. This article focuses on the bi-directional relationship between these processes, discussing the pathophysiological links and clinical aspects. Common mechanisms linking both processes include neuroinflammation, neurodegeneration, and circadian rhythm desynchronization. Timely recognition of sleep-specific symptoms as components of AD could lead to an earlier and correct diagnosis with an opportunity of offering treatments at an earlier stage. Likewise, proper sleep hygiene and related treatments ought to be one of the priorities in the management of the patient population affected by AD. This narrative review brings a comprehensive approach to clearly demonstrate the underlying complexities linking AD and circadian rhythm disruption. Most clinical data are based on interventions including melatonin, but larger-scale research is still scarce. Following a pathophysiological reasoning backed by evidence gained from AD models, novel anti-inflammatory treatments and those targeting metabolic alterations in AD might prove useful for normalizing a disrupted circadian rhythm. By restoring it, benefits would be conferred for immunological, metabolic, and behavioral function in an affected individual. On the other hand, a balanced circadian rhythm should provide greater resilience to AD pathogenesis.
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http://dx.doi.org/10.3390/medsci6030052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164904PMC
June 2018

Inducing hypertrophic effects of type I skeletal muscle fibers: A hypothetical role of time under load in resistance training aimed at muscular hypertrophy.

Med Hypotheses 2018 Mar 2;112:40-42. Epub 2018 Feb 2.

Department of Health Sciences, CUNY Lehman College, Bronx, NY, USA.

An emerging body of evidence is starting to suggest that the hypertrophy of skeletal muscle fibers might be load specific. In other words, it may be that resistance training with high loads (i.e., ≥60% of 1 repetition maximum [RM]) emphasizes a greater growth of type II muscle fibers, while resistance training with low loads (i.e., <60% of 1RM) might primarily augment hypertrophy of type I muscle fibers. Type I and type II muscle fibers possess certain distinct characteristics, with type II muscle fibers having faster calcium kinetics, faster shortening velocities, and ability to generate more power than type I muscle fibers. Alternatively, compared to type II fibers, type I muscle fibers have a higher oxidative capacity and a higher fatigue threshold. Due to the lower fatigability of type I muscle fibers, it may be hypothesized that a greater time under load is necessary to stimulate an accentuated growth of these fibers. An increase in time under load can be achieved when training with lower loads (e.g., 30% of 1RM) and to momentary muscular failure. The present paper discusses the hypothesis that a greater hypertrophy of type I muscle fibers may be induced with low load resistance training.
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http://dx.doi.org/10.1016/j.mehy.2018.01.012DOI Listing
March 2018
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