Zdravko Lackovic- MD PhD Professor of Pharmacology in Permanent Position / Honorary Member of ORPHEUS / Honorary Professor of Karaganda Medical State University
- 1976-1980 Assistant 1980-1986 Dozent 1986-1998 Full Professor in Permanent Position / retired 2017 but stil active at Faculty of Medicine University of Zagreb
Zdravko Lackovic
- MD PhD Professor of Pharmacology in Permanent Position / Honorary Member of ORPHEUS / Honorary Professor of Karaganda Medical State University
- 1976-1980 Assistant 1980-1986 Dozent 1986-1998 Full Professor in Permanent Position / retired 2017 but stil active at Faculty of Medicine University of Zagreb
Lecturing at Ph. Program "Biomedicine and Health", Mentors Workshop, Neurology Course / writing papers, Lab research
About
177
Publications
26,206
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Introduction
Zdravko Lackovic, MD, Ph.D., Professor of Pharmacology since 1986, Zagreb University School of Medicine. Besides research in neuropharmacology, I have many responsibilities in the policy of science in Croatia and Europe (for example, founding president (2004-2014) of ORPEHES etc.). Some publications are related to that.
The most important focus of research since 2005 has been related to the mechanism of analgesic action of clostridial toxins (primarily botulinum toxin)
Current institution
Faculty of Medicine University of Zagreb
Current position
- 1976-1980 Assistant 1980-1986 Dozent 1986-1998 Full Professor in Permanent Position / retired 2017 but stil active
Additional affiliations
March 1972 - April 1976
Position
- Reseach Fellow (Ph.D. candidate)
Description
- Research (spectrofluorimetrically) on 5-HIAA, the main metabolite of serotonin in cerebrospinal fluid (CSF) and spinal cord, under the mentorship of leading Croatian Scientist Marin Bulat, who proposed a new theory of CSF movement opposite to the classical view of CSF circulation. Work on experimental animals and human tissue collected post-mortem. Co-authoring several papers in highest ranking journals)
February 1994 - February 1995
Position
- Distinquished Visiting Scientist (sabbatical)
Description
- Searching for the molecular basis of compensatory growth of rat ovary and adrenal gland. (Previously, in Zagreb Laboratory, this phenomenon was found to be neuronally regulated). Learning how to use for that time new methods of molecular research in Pharmacology.
September 1979 - March 1981
Position
- Visiting Scientist (higher position for foreing scholars)
Description
- Using Mass Spectrometry (GCMS), High-Pressure Liquid Chromatography (HPLC), and Receptor Binding Assay to investigate dopamine, its metabolites, and receptors in the peripheral nervous system. Discovering intensive dopamine catabolism in the peripheral nervous system and proposing a theory that it is connected with the putative peripheral dopaminergic nervous system.
Editor roles
Education
September 1971 - April 1974
University of Zagreb: Postgraduate Study for Scientific Perfection
Field of study
- Experimental Biology
September 1966 - September 1971
Univesity of Zagreb School of Medicine
Field of study
- Medicine
Publications
Publications (177)
Driven by the clinical success of botulinum toxin serotype A (BoNT/A) and the need for improved chronic pain management, researchers attempted to develop re-designed botulinum toxin (BoNT)-based molecules as novel analgesics. Various recombinant protein expression strategies including retargeted binding domains, and chimeric toxins combining differ...
In vivo studies of botulinum neurotoxin type A (BoNT-A) enabled characterization of its activity in the nociceptive sensory system separate from its preferred action in motor and autonomic nerve terminals. However, in the recent rodent studies of arthritic pain which employed high intra-articular (i.a.) doses (expressed as a total number of units (...
Botulinum neurotoxin type A1 (BoNT-A) reduces the peripheral peptide and cytokine upregulation in rats with antigen-evoked persistent immunogenic hypersensitivity (PIH) of the temporomandibular joint (TMJ). Herein, we examined the effects of two preparations of BoNT-A, abobotulinumtoxinA (aboBoNT-A; Dysport) and onabotulinumtoxinA (onaBoNT-A; Botox...
The discovery of bacterial viruses able to kill bacteria, named bacteriophages (phages), more than a century ago, contributed to combating bacterial infections during the first three decades of the 20th century. Vladimir Sertić, a Croatian microbiologist, was one of the pioneers in bacteriophages investigation, who performed significant scientific...
The chapter was inadvertently published without a more specific title according to SEO guidelines. A chapter title needs to be understandable when seen as a stand-alone item, e.g. on PubMed. The chapter title has now been corrected as ‘Botulinum Toxin and Pain’.
Background
Nasal cavity and sinus disorders, such as allergic rhinitis, rhinosinusitis, or certain anatomical defects, are often associated with transient or ongoing headaches. On the other hand, migraine headache patients often exhibit pain referral over the area of nasal sinuses and typical nasal autonomic symptoms involving congestion and rhinor...
The use of botulinum toxin type A (BoNT-A) in pain conditions is continuously growing largely because of its long-lasting effect after local application and safety profile. These unique features distinguish BoNT-A from other conventional and adjuvant analgesic drugs. Furthermore, BoNT-A diminishes only the pathological pain, without affecting the n...
Chronic parenteral administration of D-galactose has been used to model oxidative stress-related pathophysiological mechanisms driving senescence and neurodegeneration in rodents for several decades, especially in animal research on potential anti-aging therapeutics. The exact mechanism responsible for the oxidative stress induced by galactose stil...
This chapter is focused on analgesic mechanism of action of botulinum toxin type A (BoNT-A) including the action beyond peripheral nerve endings. With the exception of the meninges and possibly urinary bladder, the presence of BoNT-A activity in the periphery, cleaving SNAP25 as a target molecule, up to now was not convincingly shown. In contrast m...
In 2010, Kissin concluded pessimistically that of the 59 new drugs introduced in the fifty-year period between 1960 and 2009 and still in use, only seven had new molecular targets. Of these, only one, sumatriptan, was effective enough to lead to the introduction of multiple drugs targeting the same target molecules (triptans) (Kissin, 2010). Morphi...
Vladimir Sertić was a pioneer of bacteriophage research in the period between the two world wars. He was born and educated in Croatia, where he made his initial discoveries, and joined Félix d'Hérelle's Laboratoire du Bactériophage in Paris in 1928. Original documents and a box with hundreds of sealed bacteriophage samples were kept in Sertić's Zag...
Botulinum toxins (BoNTs) are a product of the bacteria Clostridium botulinum. By entering nerve endings, they cleave and inactivate SNARE proteins, which are essential for neurotransmitter release. Prevention of acetylcholine release at the neuromuscular junction causes long-lasting and potentially fatal flaccid paralysis—a major feature of botulis...
Botulinum neurotoxin Type A (BoNT/A) is an effective treatment for several movement disorders, including spasticity and dystonia. BoNT/A acts by cleaving synaptosomal-associated protein of 25 kDa (SNAP-25) at the neuromuscular junction, thus blocking synaptic transmission and weakening overactive muscles. However, not all the therapeutic benefits o...
Background: Dural neurogenic inflammation (DNI) is generally recognized as important event in pathophysiology of migraine pain. However, we discovered that in rat DNI, consisting of plasma protein extravasation and inflammatory cells infiltration, can be evoked by different forms of pain in trigeminal area like formalin injection; infraorbital nerv...
Background:
Although botulinum toxin type A (BT-A) is approved for chronic migraine treatment, its site and mechanism of action are still elusive. Recently our group discovered that suppression of CGRP release from dural nerve endings might account for antimigraine action of pericranially injected BT-A. We demonstrated that central antinociceptive...
Background:
Atropa belladonna (Engl. deadly nightshade, Cro. velebilje, bunika) is a plant containing pharmacologically active, potentially toxic alkaloids: atropine, hyocyamine and scopolamine. The risk of poisoning in children is important because of possible confusion of black/dark blue belladonna fruit berries with other edible berries. There...
The antinociceptive action of botulinum toxin type A (BoNT/A) has been demonstrated in behavioral animal studies and clinical settings. It was shown that this effect is associated with toxin activity in CNS, however, the mechanism is not fully understood. Substance P (SP) is one of the dominant neurotransmitters in primary afferent neurons transmit...
In the last decade, a new surgical treatment modality was developed for frontal secondary headache, based on the assumption that the trigger of this pain entity is the entrapment of peripheral sensory nerves. The surgery entails a procedure, where an endoscopic approach is used to decompress the supraorbital and supratrochlear nerve branches, which...
“Mirror pain” or mirror-image pain (MP) is pain opposite to the side of injury. Mechanism and frequency in humans are not known. There is no consent on therapy. Here we report that unilaterally injected botulinum toxin type A (BT-A) has bilateral effect in experimental MP, thus deserves to be investigated as therapy for this condition. We examined...
In the motor system, botulinum toxin type A (BoNT/A) actions were classically attributed to its well-known peripheral anticholinergic actions in neuromuscular junctions. However, the enzymatic activity of BoNT/A, assessed by the detection of cleaved synaptosomal-associated protein 25 (SNAP-25), was recently detected in motor and sensory regions of...
The value and benefits of research are vitally dependent on the integrity of research. While there can be and are national and disciplinary differences in the way research is organized and conducted, there are also principles and professional responsibilities that are fundamental to the integrity of research wherever it is undertaken. Principles Ho...
Science is becoming more and more competitive endeavor. Researcher compete for publication, funding, advancement in career. In such ”publish or perish “ environment some scientist do not hesitate to become involved in fabrication, falsification or plagiarism. New information technologies enable new forms of scientific misconduct including self-revi...
Background and purpose:
Although botulinum toxin type A (BoNT/A) is approved for chronic migraine treatment, its mechanism of action is still unknown. Dural neurogenic inflammation (DNI) commonly used to investigate migraine pathophysiology can be evoked by trigeminal pain. Here we investigated the reactivity of cranial dura to trigeminal pain, an...
Botulinum neurotoxin type A (BoNT/A), the most potent toxin known in nature which causes botulism, is a commonly used therapeutic protein. It prevents synaptic vesicle neuroexocytosis by proteolytic cleavage of Synaptosomal-Associated Protein of 25 kDa (SNAP-25). It is widely believed that BoNT/A therapeutic or toxic actions are exclusively mediate...
Visceral pain, especially in the abdominal region, represents one of the most common types of pain. Its chronic form is usually very hard to treat by conventional analgesic agents and adjuvants. We investigated the antinociceptive effect of botulinum toxin type A (BTX-A) in male Wistar rats in two models of visceral pain: peritonitis induced by int...
Unlike most classical analgesics, botulinum toxin type A (BoNT/A) does not alter acute nociceptive thresholds, and shows selectivity primarily for allodynic and hyperalgesic responses in certain pain conditions. We hypothesized that this phenomenon might be explained by characterizing the sensory neurons targeted by BoNT/A in CNS after its axonal t...
The mechanism of botulinum toxin type A (BTX-A) antinociceptive action in the central nervous system is little known. The potential interaction between BTX-A and GABAergic system has not been investigated previously. In the present study, we demonstrate prevention of BTX-A antinociceptive effect on formalin-induced inflammatory pain and partial sci...
Up to now, dural neurogenic inflammation (DNI) has been studied primarily as a part of migraine pain pathophysiology. A recent study from our laboratory demonstrated the occurrence of DNI in response to peripheral trigeminal nerve injury. In this report, we characterize the occurrence of DNI after different peripheral nerve injuries in and outside...
The PhD Program Biomedicine and Health Sciences stipulate PhD candidates to publishing in peer-reviewed journals: at least three articles are required prior to the degree awarding including one in CC-indexed journal with impact factor ≥1 and first authorship. In March 2013 we analysed Web of Science citations of papers published by 44 candidates wh...
Botulinum toxin A (BTX-A) is approved for treatment of chronic migraine and has been investigated in various other painful conditions. Recent evidence demonstrated retrograde axonal transport and suggested the involvement of CNS in antinociceptive effect of BTX-A. However, the mechanism of BTX-A central antinociceptive action is unknown. In this st...
Long-term effectiveness and repeated administration of botulinum toxin A are the basis for its use in both neuromuscular disorders and certain painful conditions. Botulinum toxin A has been recently approved for migraine treatment, and its off-label use extends to other craniofacial pain disorders. However, recently it was reported that, after repe...
Description of ORPEHUS (www. orpheus-med.org) and standards for Doctoral Education
Infraorbital nerve constriction (IoNC) is an experimental model of trigeminal neuropathy. We investigated if IoNC is accompanied by dural extravasation and if botulinum toxin type A (BoNT/A) can reduce pain and dural extravasation in this model.
Rats which developed mechanical allodynia 14 days after the IoNC were injected with BoNT/A (3.5 U/kg) in...
Botulinum toxin A (BTX-A) is approved for treatment of different cholinergic hyperactivity disorders, and, recently, migraine headache. Although suggested to act only locally, novel observations demonstrated bilateral reduction of pain after unilateral toxin injection, and proposed retrograde axonal transport, presumably in sensory neurons. However...
В статье приведены сведения о работе Европейского общества кандидатских исследований в области биомедицины и здравоохранения, которое было организовано в 2004 г. Общество занимается вопросами унификации кандидатских исследований в рамках развития Болонскойд екларации и создания единого образовательного пространства Европы.
We investigated antinociceptive activity of botulinum toxin type A (BTX-A) in a model of diabetic neuropathic pain in rats. Male Wistar rats were made diabetic by a single intraperitoneal injection of streptozotocin (80mg/kg). Sensitivity to mechanical and thermal stimuli was measured with the paw-pressure and hot-plate test, respectively. The form...
This review article summarizes the current knowledge about the metabolism, pharmacological effect, traditional and modern therapeutic use and safety of S. divinorum. Salvia divinorum is a plant of the Lamiaceae family which has a psychoactive, hallucinogenic effect. The main psychoactive ingredient is diterpene salvinorin A which is considered the...
Here we provide behavioural evidence for an axonal transport and the central origin of the antinociceptive effect of botulinum toxin type A (BTX-A). In rats we investigated the effectiveness of BTX-A on "mirror pain" induced by unilateral repeated intramuscular acidic saline injections (pH 4.0). Since experimental evidence suggest that bilateral pa...
A single injection of low doses of botulinum toxin type A (3.5 U/kg) completely abolished secondary mechanical hyperalgesia throughout its duration in a model of post surgical pain after gastrocnemius incision in rat.
It is generally believed that the cholinergic system plays an important role in normal cognitive functioning. Botulinum toxin is the most potent toxin of the peripheral cholinergic system and today it is used in the treatment of a variety of neurological disorders. However, it is surprising that its effect on cognitive processes has been investigat...
Botulinum toxin type A (BTX-A) has a long-lasting antinociceptive activity and less clear effect on inflammation. It was proposed that these two effects share the same mechanism--the inhibition of neurotransmitter exocytosis from peripheral nerve endings. However, till now possible anti-inflammatory action of BTX-A did not evoke much attention. In...
Anaerobic bacterium Clostridium botulinum produces seven different serotypes of botulinum neurotoxins (A-G), which specifically act at the peripheral cholinergic nerve terminals blocking the release of acethylcholine. Primary site of action of botulinum toxin type A (BT-A) is neuromuscular end plate where it specifically cleaves SNAP-25, one of the...
It is believed that oxidative stress plays a central role in the pathogenesis of metabolic diseases like diabetes mellitus
(DM) and its complications (like peripheral neuropathy) as well as in neurodegenerative disorders like sporadic Alzheimer’s
disease (sAD). Representative experimental models of these diseases are streptozotocin (STZ)-induced di...
It is believed that oxidative stress (OS) plays a central role in the pathogenesis of metabolic diseases like diabetes mellitus (DM) and its complications (like peripheral neuropathy) as well as in neurodegenerative disorders like sporadic Alzheimer's disease (sAD). Representative experimental models of these diseases are streptozotocin (STZ)-induc...
The influence of psychoactive drugs on neuroplasticity, especially on neurogenesis is reviewed. From psychopharmacological point of view most interesting results are those showing neurogenesis that neurogenesis is increased by SSRI. However, the role of serotonin system in neurogenesis as well as significance of neurogenesis in the beneficial effec...
It is believed that oxidative stress plays a central role in the pathogenesis of metabolic diseases like diabetes mellitus
(DM) and its complications (like peripheral neuropathy) as well as in neurodegenerative disorders like sporadic Alzheimer’s
disease (sAD). Representative experimental models of these diseases are streptozotocin (STZ)-induced di...
The influence of psychoactive drugs on neuroplasticity, especially on neurogenesis is reviewed. From psychopharmacological point of view most interesting results are those showing neurogenesis that neurogenesis is increased by SSRI. However, the role of serotonin system in neurogenesis as well as significance of neurogenesis in the beneficial effec...
By means of oral glucose tolerance test (OGTT), we investigated glucose tolerance in rats pre-treated with intracerebroventricular and subcutaneous non-diabetogenic dose of betacytotoxic drug alloxan 7 days before OGTT. Being normoglycemic and normoinsulinemic pre-OGTT, at 30 minutes post-OGTT, alloxan intracerebroventricularly-treated rats had a l...
To test antinociceptive properties of botulinum toxin type A (BTX-A) in rats with carrageenan- and capsaicin-induced pain and inflammation.
Pain was provoked with carrageenan (1%) or capsaicin (0.1%) injection into the plantar surface of the rat paw-pad. The effect of BTX-A 5 U/kg on carrageenan- and capsaicin-induced mechanical and thermal hyperse...
To evaluate the content of household drug supplies and self-medication practice among medical and pharmacy students at Zagreb University in 2001, and to relate the findings to a previous survey in 1977.
A cross-sectional anonymous questionnaire-based survey included 287 students who inventoried drug supplies in their family households and interview...
A peripheral application of botulinum toxin type A (7 U/kg) has significantly reduced thermal and mechanical hypersensitivity in rats with the partial sciatic nerve transection as a classical model of surgical neuropathy.
In the present experiments, unilateral ovariectomy (ULO) induced compensatory hypertrophy (COH) of the remaining rat ovary (60%-85% increase in ovarian weight, total proteins, and total RNA and DNA). An increased thymidine uptake preceded the organ enlargement. COH was inhibited by i.p.-administered muscarinic antagonist propantheline (dose-depende...
7 3 _g J Neural Transm Q003) 110: 15-29 -Journal of -Neural Transmission Printed in Austria rntracerebroventricurar adrninistration of betacytotoxics arters expression of brain monoamine transporter genes Received.February 6,2fr02; accepted Julv l. Ztx)2 Published online November 22,2N2: O Spring;r_Verlag 2002 srm,nary. Intracerebroventricular (icv...
To estimate the exposure of Zagreb University medical students to psychoactive substances in 2000 and compare it with data collected in 1989.
Students were surveyed in 2000 (n=775) and 1989 (n=986) by means of a self-reporting questionnaire. The 2000 survey also included 136 non-medical students. General demographic data and data on experience with...
Intracerebroventricular (icv) administration of betacytotoxics alters brain monoamine neurotransmission, without producing hyperglycemia. By means of in situ hybridization, we have investigated the expression of dopamine, noradrenaline and serotonin transporter (DAT, NAT, 5-HTT, respectively) mRNAs, in the brain of alloxan- and streptozotcin-icv tr...
Hemicastration induces growth of the remnant ovary in the rat. As evidenced by the effects of total abdominal vagotomy, vagal innervation markedly influences this compensatory ovarian growth. In the present experiments, vagotomy inhibited compensatory ovarian growth when performed immediately after hemicastration, but not when delayed until 4.5 hr...
The Internet is becoming an ever more important source of information in pharmacology and medicine. Little is known, however, about which Internet pharmacology resources are actually used by the pharmacologists - and to what extent - and how they estimate the Internet information quality and evaluation. This pilot study used an anonymous questionna...
We surveyed 3 generations (1996-1998) of the 3rd year medical students at the University of Zagreb for their contact with tobacco, alcohol and illicit substances of abuse using an anonymous questionnaire. Of 464 participants 25-30% were smokers, 60-70% confirmed that they had got drunk and 31% that they had used illicit substances at least once in...
Questions
Questions (14)
I am professor of Pharmacology and they invited me to:
.....We would like to invite you to submit research article in the 8th Joint International Conference organised by Institute of Research Engineers and Doctors at Paris, France. The theme for the 2018 Paris conference is to bring together innovative academics and industrial experts to a common forum. We would be delighted to have you present at this conference to hear what the technology experts and researchers have to share about the technology advancements and their impact on our daily lives.
Joint International Conference Consists of following tracks:
Track 1: International Conference in Advances in Computing, Control and Networking - ACCN 2018 Official Weblink: www.accn.theired.org <http://tracking.theired.org/tracking/click?d=6mRl6wyd-s6aZAgiUcBKA6DWCCxIc58wMi0vVVGjsKAs7XvvQhGco0avuIpP6r73QlNUnh9G3Yn69I82UGGuKbejumPJkjbzMVMYtORv1FB50>
Track 2: International Conference in Advances in Civil, Structure and Mechanical Engineering - ACSM 2018
Official Weblink: www.acsm.theired.org <http://tracking.theired.org/tracking/click?d=6mRl6wyd-s6aZAgiUcBKA9D6B7Gq-8s7WCmzLBOkQiE7Ke-x5X7ObZSz7t2AaI3-ukxY_QsTDY5R7pcjLv26vP4Qq9eWtI5cgC4Ncf2_whST0>
Track 3: International Conference in Advances in Applied Sciene and Environmental Technology - ASET 2018 Official Weblink: www.aset.theired.org <http://tracking.theired.org/tracking/click?d=6mRl6wyd-s6aZAgiUcBKAz9Q-CL1X56QeDm_XAYFrrWXe9y0PF6zU0i3uQopi06BBYFbNaZszRX84ba8FwvHs2ITCdchddDxRyl3sScrj6I90>
Track 4: International Conference in Advances in Economics, Social Sciene and Human Behaviour Study - ESSHBS 2018 Official Weblink: www.esshbs.theired.org <http://tracking.theired.org/tracking/click?d=6m6JkkFA7VMZYXOhpFVEssytuWGgEJLd3a0yIVvj92YLGwtoiomaPawqbPjeYA2Hsc-j3f20Z1eM97RmRpo9iS1Sjc84IMm2SLLVXSL6eZO8fzGib5VjJLUxp8QDFE1BsQ2>
Conference City: Paris , France
Conference Date: 23 - 24 June 2018
Traditionally, in the Soviet Union and associated countries, there are two doctorates: "Aspiratura" ("Candidate Nauk") and "Doktor Nauk". What of that corresponds to the European academic degree PhD. Is there any consensus about that?
There were several comments, even declarations (DORA for example), questioning the value of citation as indicator of resech quality.
In wich circumstances id nuber of ciation acceptable indicator and when is withouth a value?
It is believed that PhD program for medical professionals shoud ncrease ther research competencies, medical practice qulity, future reseach productivity. Are there scientific proof for that?
In "continental Europe" according to Bologna process in high education UK terminology is used. However it seems with much different meanings. What is then the meaning of MD in those countries? Where is a place for PhD?
Should it be a part "scandinavian type" of PhD Thesis? Can such a monograph alone be considered eaquaal to PhD Thesis?
Most my colleagues think that case report has no scientific value becaue it is based only on individual observation. However what then with other observational reseach, for exampe in astronomy?
In some contries, practically all universities in Germany it is not possible to make clinical bed side research for MDs
I would appreciate experiences of international collaboration that are promoting "brain circulation" instead of brain drain. Forms and axamples of youg scientiest who return home after obtainig international experinece abroad.
Are there programs promoting that in receiving countries? What cantries where brain drain occurs can do to promote return of such scientist. I am interested for real examples.
Best regars
Zdravko
In some univerities supervisors (mentors, tutors) have major role in evaluation of PhD Thesis (most universaities in Germany). In some other Univerisities they can not participate in evaluations at all because this is mconsidered a conflict of interest PhD Standards of ORPEHUS for biomedicine and helath sciences (www.orpheus-med.org)
