Krystyna Makowska

T2 Toxin-Induced Changes in Cocaine- and Amphetamine-Regulated Transcript (CART)-Like Immunoreactivity in the Enteric Nervous System Within Selected Fragments of the Porcine Digestive Tract

T-2 toxin is a mycotoxin produced by some Fusarium species, which may affect the synthesis of DNA and RNA and causes various pathological processes. Till now, the influence of T-2 toxin on the enteric nervous system (ENS) located in the wall of gastrointestinal tract has not been studied. On the other hand, cocaine- and amphetamine-regulated transcript (CART) is one of enteric neuronal factors, whose exact functions in the intestines still remain not fully explained. The present study describes the influence of low doses of T-2 toxin on CART-positive neuronal structures in porcine stomach, duodenum, and descending colon. Distribution of CART was studied using the double immunofluorescence technique in the plexuses of the ENS, as well as in nerve fibers within the circular muscle and mucosal layers of porcine gastrointestinal tract. Generally, after T-2 toxin administration the greater number of CART-LI structures were studied, but intensity of changes depended on part of the ENS and digestive tract fragment studied. The obtained results show that even low doses of T-2 toxin may change the expression of CART in the ENS.

The Influence of Low Doses of Zearalenone and T-2 Toxin on Calcitonin Gene Related Peptide-Like Immunoreactive (CGRP-LI) Neurons in the ENS of the Porcine Descending Colon

The enteric nervous system (ENS) can undergo adaptive and reparative changes in response to physiological and pathological stimuli. These manifest primarily as alterations in the levels of active substances expressed by the enteric neuron. While it is known that mycotoxins can affect the function of the central and peripheral nervous systems, knowledge about their influence on the ENS is limited. Therefore, the aim of the present study was to investigate the influence of low doses of zearalenone (ZEN) and T-2 toxin on calcitonin gene related peptide-like immunoreactive (CGRP-LI) neurons in the ENS of the porcine descending colon using a double immunofluorescence technique. Both mycotoxins led to an increase in the percentage of CGRP-LI neurons in all types of enteric plexuses and changed the degree of co-localization of CGRP with other neuronal active substances, such as substance P, galanin, nitric oxide synthase, and cocaine- and amphetamine-regulated transcript peptide. The obtained results demonstrate that even low doses of ZEN and T-2 can affect living organisms and cause changes in the neurochemical profile of enteric neurons.

Co-localization of zinc transporter 3 (ZnT3) with sensory neuromediators and/or neuromodulators in the enteric nervous system of the porcine esophagus

Zinc transporter 3 (ZnT3) is one of the zinc transporters family. It is closely connected to the nervous system, where enables the transport of zinc ions from the cytoplasm to synaptic vesicles. This substance has been described within the central and peripheral nervous system, especially in the enteric nervous system (ENS). The aim of the present study was to describe the co-localization of ZnT3 with selected neuromediators and/or neuromodulators participating in sensory stimuli conduction in neurons of the ENS within the porcine esophagus. Co-localization of ZnT3 with substance P (SP), leucine enkephalin (LENK) and calcitonin gene-related peptide (CGRP) was studied using standard double-immunofluorescence technique. The obtained results show that ZnT3, SP and/or LENK may occur in the same enteric neurons, and the degree of co-localization of these substances clearly depends on the fragment of esophagus studied and the type of enteric ganglia. In contrast, the co-localization of ZnT3 with CGRP was not observed during the present investigation. The obtained results suggest that ZnT3 in the ENS may be involved in the conduction of sensory and/or pain stimuli.

Cocaine- and Amphetamine-Regulated Transcript (CART ) Peptide in Mammals Gastrointestinal System – A Review

Abstract Since its first description over 30 years ago, cocaine- and amphetamine-regulated transcript (CART) peptide has been the subject of many studies. Most of these investigations pertain to occurrence and functions of CART within the central nervous system, where this peptide first of all takes part in regulation of feeding, stress reactions, as well as neuroprotective and neuroregenerative processes. However, in recent years more and more studies concern the presence of CART in the gastrointestinal system. This peptide has been described both in stomach and intestine, as well as in other digestive organs such as pancreas or gallbladder. Particularly much information relates to distribution of CART in the enteric nervous system, which is located within the wall of digestive tract. Other studies have described this peptide in intestinal endocrinal cells. Moreover, it is known that CART can be present in various types of neuronal cells and may co-localize with different types of other neuronal active substances, which play roles of neuromediators and/or neuromodulators. On the other hand precise functions of CART in the gastrointestinal system still remain unknown. It is assumed that this peptide is involved in the regulation of gastrointestinal motility, intestinal blood flow, secretion of intestinal juice, somatostatin and/or insulin, as well as takes part in pathological processes within the gastrointestinal tract. The large number of recent studies concerning the above mentioned problems makes that knowledge about occurrence and functions of CART in the digestive system rather piecemeal and requires clarifying, which is the aim of the present article.

The Influence of Inflammation and Nerve Damage on the Neurochemical Characterization of Calcitonin Gene-Related Peptide—Like Immunoreactive (CGRP-LI) Neurons in the Enteric Nervous System of the Porcine Descending Colon

The enteric nervous system (ENS), localized in the wall of the gastrointestinal tract, regulates the functions of the intestine using a wide range of neuronally-active substances. One of them is the calcitonin gene-related peptide (CGRP), whose participation in pathological states in the large intestine remains unclear. Therefore, the aim of this study was to investigate the influence of inflammation and nerve damage using a double immunofluorescence technique to neurochemically characterize CGRP-positive enteric nervous structures in the porcine descending colon. Both pathological factors caused an increase in the percentage of CGRP-positive enteric neurons, and these changes were the most visible in the myenteric plexus after nerve damage. Moreover, both pathological states change the degree of co-localization of CGRP with other neurochemical factors, including substance P, the neuronal isoform of nitric oxide synthase, galanin, cocaine- and amphetamine-regulated transcript peptide and vesicular acetylcholine transporter. The character and severity of these changes depended on the pathological factor and the type of enteric plexus. The obtained results show that CGRP-positive enteric neurons are varied in terms of neurochemical characterization and take part in adaptive processes in the descending colon during inflammation and after nerve damage.

The Influence of High and Low Doses of Bisphenol A (BPA) on the Enteric Nervous System of the Porcine Ileum

Bisphenol A, used in the production of plastic, is able to leach from containers into food and cause multidirectional adverse effects in living organisms, including neurodegeneration and metabolic disorders. Knowledge of the impact of BPA on enteric neurons is practically non-existent. The destination of this study was to investigate the influence of BPA at a specific dose (0.05 mg/kg body weight/day) and at a dose ten times higher (0.5 mg/kg body weight/day), given for 28 days, on the porcine ileum. The influence of BPA on enteric neuron immunoreactive to selected neuronal active substances, including substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), vesicular acetylcholine transporter (VAChT—used here as a marker of cholinergic neurons), and cocaine- and amphetamine-regulated transcript peptide (CART), was studied by the double immunofluorescence method. Both doses of BPA affected the neurochemical characterization of the enteric neurons. The observed changes depended on the type of enteric plexus but were generally characterized by an increase in the number of cells immunoreactive to the particular substances. More visible fluctuations were observed after treatment with higher doses of BPA. The results confirm that even low doses of BPA may influence the neurochemical characterization of the enteric neurons and are not neutral for living organisms.

The Impact of T-2 Toxin on Vasoactive Intestinal Polypeptide-Like Immunoreactive (VIP-LI) Nerve Structures in the Wall of the Porcine Stomach and Duodenum

T-2 toxin is a secondary metabolite of some Fusarium species. It is well-known that this substance can harmfully impact living organisms. Among others, thanks to the ability of crossing the blood–brain barrier, T-2 toxin can affect the central nervous system. Mycotoxins mostly get into the organism through the digestive tract; therefore, first of all they have to break the intestinal barrier, wherein the important component is the enteric nervous system (ENS). However, knowledge about the impact of T-2 toxin on the ENS is rather scant. As a result of the influence of various physiological and pathological agents, ENS can undergo adaptive and reparative processes which manifest as changes in the immunoreactivity of perikaryons for neuronal active substances. So, the aim of the present investigation was to study how low doses of T-2 toxin affect vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) nervous structures in the ENS of the porcine stomach and duodenum. Obtained results have shown that T-2 toxin causes an percentage increase of VIP-LI nerve cells and nerve fibers in every enteric plexus in both fragments of gastrointestinal tract studied. This shows that even low doses of T-2 toxin can have an influence on living organisms.

Levels of zearalenone and its metabolites in sun-dried kapenta fish and water of Lake Kariba in Zambia — A preliminary study

Contamination of food with mycotoxins and the associated possibilities of human intoxication is a serious problem in Africa. One of the most widespread mycotoxins is zearalenone (ZEN), which usually occurs in food of vegetable origin. On the other hand, information about ZEN in products of animal origin in African countries is extremely scanty. During the present study, levels of ZEN and its analogs: α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL) were measured by high performance liquid chromatography (HPLC) with fluorescence detection in sun-dried kapenta fish - traditional Zambian food, as well as in the water of Lake Kariba - the main source of kapenta fish in Zambia. This study revealed that levels of ZEN in sun-dried kapenta fish fluctuated from 27.2 μg·kg-1 to 53.9 μg·kg-1, whereas the contamination of water from Lake Kariba with ZEN is rather minimally similar to the content of ZEN analogs in both kapenta fish and water. The obtained results have shown that sun-dried kapenta fish of Lake Kariba contain ZEN and may contribute to the exposure of consumers to this substance.

Waclaw Blaise Orlowsky and his unacknowledged discovery in neurology

“glasslike” were observed within the anterior horns of the spinal cord [4]. Unfortunately, Orlowsky did not perform studies on the brain (maybe such studies were to be performed at a later date). Orlowski sent his results to the Pasteur Institute in Paris. Unfortunately, the studies of the young scientist were not recognized in France [1, 2]. Orlowsky never got an answer from Paris. Probably the achievement of the very young man from foreign Poland—the country under partitions—which did not even exist on the map was just ignored. We do not know how Orlowsky reacted to the discovery of Adelchi Negri, who in 1903 described inclusion bodies in neuronal cells of cerebellum during rabies. It should be pointed out that bodies described by Negri in the brain were identical to the ones observed by Orlowski within the medulla oblongata 11 years earlier. The fact of the matter is that Orlowsky stopped the work concerning neurological changes in rabies and saw about bacteriology. In the summer of 1892, Orlowksy went to Lublin to fight an outbreak of cholera [1]. During this stay he worked on new types of Vibrio cholerae, which later was named Bacillus choleroides ß Orlowsky [2]. Orlowsky got a medical degree on January 18, 1894. He went for a two-year internship, during which he worked at the Jagiellonian University in Cracow and at the University in Graz [1]. In 1896, Orlowsky came back to Warsaw and broke off a career in the sciences, what may be connected with his earlier disappointment. However, Orlowsky was still interested in rabies. In 1896, he took a job in the Warsaw Pasteur’s Center founded by Bujwid. In 1897, Orlowsky moved to Vilnius, where he opened and took on management at the Pasteur Center [1]. According to statistics carried out by Orlowsky, the Vilnius Pasteur Center between 1897 and 1939 vaccinated 15,000 persons bit by rabid dogs [2]. After the second world war, Vilnius stayed within the borders of Waclaw Blaise Orlowsky (Fig. 1) was born on February 2, 1868 in Brzeziny, not far from Lodz in Poland [1]. He attended elementary and middle school in Lublin. In 1888, Orlowsky went to Warsaw to study at the Faculty of Medicine in the Imperial University of Warsaw [1, 2]. During his studies, he showed interests in neurology and bacteriology. In February 1890, Orlowsky came into contact with Odo Bujwid, who was the pioneer of anti-rabies vaccination in Poland [3]. A common work of Bujwid and Orlowsky resulted in the important discovery in neurology and the histopathology of rabies. This discovery came on March 15, 1892, when Orlowski was a young, 24-year-old fourth year medical student who gave a lecture entitled “Changes in neuronal cells during rabies” during a session of the Warsaw Medical Society [1, 2]. This lecture was published in the scientific journal “Gazeta Lekarska” [4], as well as Orlowsky’s experiment was described by Bujwid in the book “Rabies in people and preventive treatment according to the method of Pasteur” [5]. Orlowsky performed his experiment on rabbits, which were infected with rabies by trepanation and injections under the dura mater with rabies germ (during the time-period of Orlowsky, scientists did not know that rabies is caused by a virus) [4]. The cervical spinal cord and medulla oblongata were collected immediately after the death of the animals (7–9 days after infection). The majority of inclusion bodies, which Orlowsky described in these words: “agleam” or

Józef Polikarp Brudziński (1874–1917)

Józef Polikarp Brudziński (Fig. 1) was born into a noble family with patriotic traditions on 26 January 1874 in Bolewo in Płock Governorate [1]. After finishing middle school in Warsaw, Brudziński started his medical studies at the University in Dorpat (currently Tartu in Estonia) in 1891, but in 1894 he moved to Moscow, where he received his medical degree in 1897 and decided to specialize in pediatrics [2]. After graduation, Brudziński went for a 3-year foreign internship. At first, he worked in a pediatric clinic in Cracow (situated at that time in Austro-Hungarian Empire), and then he continued his education in Graz, Paris, London, Berlin and Vienna. During the internship, Brudziński more than once worked with world-renowned scientists and surgeons, including Theodor Escherich, Jacques Granscher and Antion Marfan [3]. Brudziński returned to Warsaw in 1900 and took a job in Rev. G. P. Baudouin’s Foster Care Centre at Warsaw’s Infant Jesus Hospital [3, 4]. In 1903, he received a proposal to take up the position of a general surgeon at the newly built Anna Maria Pediatric Hospital in Lodz. Brudziński again went abroad for a couple of months to learn about organization and operating procedures of modern pediatric hospitals in Europe. He started work at Anna Maria Hospital in 1905 [3]. Not long afterward, this hospital became an important scientific center in Polish lands. Brudziński worked at Anna Maria Hospital until 1910, when he received an invitation to participate in the design and building of a new modern pediatric hospital in Warsaw from the foundation of Zofia Szlenkierówna, the pioneer of nursing in Poland. Before the move to Warsaw, Brudziński again went away on a tour of European pediatric hospitals for a few weeks. Building of the pediatric hospital in Warsaw, named after the parents of the founder, Karol and Maria Szlenkier Hospital, started in 1911, and in 1913 the first patients were admitted. Brudziński directed the hospital until 1915, when he became involved in the reactivation of Polish higher education in Warsaw to replace the Russian language Imperial Warsaw University, which was moved to Rostov-on-Don at the beginning of the First World War [1]. Brudziński was elected rector of Warsaw University on 2 November 1915, and in 1916 he started lectures with students in the newly created medical faculty [2]. Unfortunately, the hard work impaired Brudziński’s health. He died of nephritis and uremia in Warsaw on 18 December 1917 at the age of only 43 years. Józef Brudziński was not only a pediatrician, but also a scientist. He was the author of 55 scientific articles published in Polish and European medical journals, including “Gazeta Lekarska”, “Medycyna”, “Wiener klinische Rundschau”, “Revue Neurologique” and “Terapie der gegenwart” [3, 4]. Articles by Brudziński dealt with nutrition, bacteriology of the gastrointestinal tract, various contagious childhood diseases and organization of work in the hospital [1, 4]. However, the most important scientific works by Brudziński relate to neurology [1, 4]. During his medical practice at Anna Maria Hospital in Lodz, Brudziński observed and described symptoms specific to meningitis. In 1908, he published in the pages of “Medical Review” (original Polish title “Przegląd Lekarski”) his first work concerning this subject [5], where he described “contralateral reflex symptom” occurring mainly in hemiparesis but also during meningitis. This sign, according to Brudziński, consisted of the straightening of a paralyzed limb after passive flexion of the contralateral healthy limb. His next article, published in 1909 in “Pediatric Review” (original Polish title “Przegląd Pediatryczny”) [6], described a neck sign in meningitis, in which forced flexion of the neck causes a reflex flexion of the hips. His final publication about signs in meningitis was published in 1916 in “Medical Gazette” (original Polish title “Gazeta Lekarska”), describing cheek and symphyseal signs [1, 3]. In the first of these, pressure on the cheek elicits a reflex rise and flexion of the * Krystyna Makowska krystyna.makowska@uwm.edu.pl