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Probiotic functional food in improving gut health


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Probiotic functional food in improving gut health
L. Petrusevska-Tozi, K. Mladenovska
Faculty of Pharmacy, Vodnjanska 17, 1000, University “Ss. Cyril and Methodious”, Skopje, Macedonia
Recent molecular-based investigations have confirmed the species diversity and metabolic complexity of
the human gut microbiota. It is also increasingly clear that the human gut microbiota plays a crucial role in host
health, both as a source of infection and environmental insult and, conversely, in protection against disease and main-
tenance of gut function. The demonstration that immune and epithelial cells can discriminate between different micro-
bial and bioactive plant species has extended the known mechanism(s) of action of nutraceuticals and probiotics
beyond simple nutrition and/or antimicrobial effects. The progressive unravelling of these plant and bacterial effects
on systemic immune and intestinal epithelial function has led to new credence for the use of probiotics and nutraceu-
ticals in clinical medicine. Level I evidence now exists for the therapeutic use of probiotics in infectious diarrhoea
in children, recurrent Clostridium difficile-induced infections and post-operative pouchitis. Additional evidence is
being acquired for the use of probiotics in other GI infections, irritable bowel syndrome and inflammatory bowel
diseases. Possible health effects include also cholesterol lowering and prevention of cancer recurrence.
Probiotics are marketed as capsules, powders, but mostly as enriched diary and meet products. Most common-
ly they have been lactobacilli and bifidobacteria. Before a probiotic can benefit human health it must fulfil several cri-
teria. It must have good technological properties so that it can be manufactured and incorporated into food products
without loosing viability and functionality or creating unpleasant flavours or textures. It must survive passage through
the upper GI tract and arrive alive at its site of action, and it must be able to function in the gut environment.
Several aspects, including safety, functional and technological characteristics have to be taken into consid-
eration in the selection process of probiotics. Safety aspects include specifications such as origin, non-pathogenici-
ty and antibiotic resistance characteristics. Functional aspects include viability, including acid tolerance and toler-
ance to human gastric juice, bile tolerance, adherence to epithelial surfaces and persistence in the human GI tract,
immunostimulation, but no pro-inflammatory effect, antagonistic activity against pathogens, antimutagenic and anti-
carcinogenic properties. Careful screening of probiotic strains for their technological suitability can also allow selec-
tion of strains with the best manufacturing and food technology characteristics. 
In the production of probiotic diary products, selected probiotic cultures should be used to: produce concen-
trated cultures of each specific strain in level above 10
10 
with good storage properties at low temperature, produce
probiotc food with the help of a supporter culture, ferment milk together with at least some supporter cultures with-
out inhibition of the growth of any of the added strains, produce probiotic foods with levels of the specified probi-
otic strain up to 10
8
cells/g product, with high and constant levels of the probiotic strain when stored at low temper-
ature, with an acceptable taste and flavour through the storage time, and an acceptable stability and viscosity. However,
insufficient viability and survival of these bacteria has been both a marketing and technological concern for many
food industrial producers. By selecting better functional probiotic strains and adopting improved methods to enhance
survival, including the use of appropriate prebiotics and the optimal combination of probiotics and prebiotics (syn-
biotics), an increased delivery of viable bacteria in fermented products to the consumers can be achieved. The microen-
capsulation technology for probiotic provides also promising prospects for improved culture performance. Valid
techniques for ensuring probiotic stability and for optimizing fermentation procedures are important. The stress fac-
tors influencing the viability and functionality of organisms need to be explored and controlled. The packaging mate-
rials used and the conditions under which the products are stored are important for the quality of the products con-
taining probiotics. Factors related to the sensory aspects of probiotic food production are of utmost importance since
only by satisfying consumers’ demands, the food industry will succeed in promoting the consumption of functional
probiotic food. The probiotic concept is today widely spread in the scientific and industrial fields. However, further
scientific input is required.
Macedonian pharmaceutical bulletin 53 (1,2) 274-275 (2007)
SOP - 7
274
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Uloga na funkcionalnata probiotska hrana 
vo podobruvawe na ~ovekovoto zdravje 
L. Petru{evska-Tozi, K. Mladenovska
Farmacevtski fakultet, Vodwanska 17, 1000, Univerzitet ”Sv. Kiril i Metodi”, Skopje, Makedonija
Sovremenite istra`uvawa na molekularno nivo ja potvrduvaat raznolikosta i metaboli~kata kom-
pleksnost na humanata intestinalna mikrobiota. Stanuva sé pove}e jasno deka istata ima klu~na uloga vo
~ovekovoto zdravje, i kako izvor na infekcii i o{tetuvawa i sprotivno, kako za{titnik od zaboluvawa
i odr`uva~ na intestinalnata funkcija. Soznanijata za ulogata na imunite i epitelnite kletki vo razli-
kuvaweto na soevite gi pro{irija soznanijata za mehanizmite na dejstvo, odnosno za ulogata na probiotska-
ta hrana vo odr`uvaweto i podobruvaweto na ~ovekovoto zdravje so {to se aktuelizira nivnata primena
vo klini~kata medicina. Zasega postoi dokaz na nivo I za terapevtskata korist od probioticite kaj pedijat-
riskata infektivna dijarea, infekcii predizvikani so Clostridium difficile i postoperativen puh. Se istra-
`uvaat dopolnitelni dokazi za korista od primenata na probioticite vo drugi zaboluvawa i sostojbi
(drugi GI infekcii, iritira~ki creven sindrom, inflamatorni crevni zaboluvawa, namaluvawe na nivo-
to na holesterol i spre~uvawe na pojava na rak).
Probioticite, glavno soevi na Lactobacili Bifidobacteria, se raspolo`livi kako kapsuli, pra{oci,
no i kako zbogateni mle~ni i mesni hranlivi prozvodi i napitoci. Vo izborot na probiotikot treba da
bidat zemeni predvid bezbednosta, funkcionalnite i tehnolo{kite karakteristiki. Bezbednosta gi
vklu~uva potekloto, nepatogenosta i otpornosta kon antibiotici. Funkcionalnite aspekti se odnesuvaat
na vitalnosta, vklu~itelno i otpornosta kon kiselini, `eludo~na kiselina, `ol~ni soli, ponatamu ather-
entnosta za epitelnite povr{ini i opstojuvaweto vo GIT, imunostimulacijata bez proinflamatorni
efekti, antagonisti~kata aktivnost kon patogeni, antimutagenite i antikarcinogenite svojstva. 
Vo proizvodstvoto na probiotski hranlivi proizvodi, izbranite probiotski kulturi treba da
ovozmo`at razmno`uvawe na sekoj probiotski soj vo koncentracija nad 10
10 
so dobri svojstva vo tekot na
~uvaweto na niski temperaturi, da obezbedat proizvodstvo na probiotska hrana so pomo{ na kulturi-
poddr`uva~i na rastot, da go fermentiraat mlekoto zaedno so najmalku edna kultura-poddr`uva~ bez da
go inhibiraat rastot na dodadenite soevi, da ovozmo`uvaat rast na specifi~nite probiotski soevi do 10
8
kletki/g hranliv proizvod, da obezbeduvaat visoki i konstantni nivoa na probiotikot koga proizvodot
se ~uva na niski temperaturi, proizvodot da bide so prifatliv vkus, miris i tekstura za vreme na ~uvawe-
to i prifatliva stabilnost i viskoznost. 
Me|utoa, nedovolnata vitalnost i opstanok na ovie bakterii pretstavuva i marketin{ki i tehno-
lo{ki problem za mnogu proizveduva~i na probiotska hrana. So izbor na podobar soj i usvojuvawe na meto-
di za podobruvawe na opstanokot, vklu~itelno koristewe na prebiotici i optimalna kombinacija na pro-
i prebiotici (sinbiotici), mo`e da se zgolemi isporakata na vitalni bakterii so fermentirani hran-
livi proizvodi. Tehnologijata na mikroinkapsulirawe na probioticite nudi, isto taka, sé u{te nedovol-
no istra`eni monosti. Potrebni se validni tehniki za obezbeduvawe na stabilnosta i funkcionalnosta
i za optimizirawe na procesot na fermentacija. Stres fatktorite treba dobro da se prou~at i kontroli-
raat. Materijalite za pakuvawe i uslovite za ~uvawe se, isto taka, va`ni za kvalitetot na probiotskata
hrana. Faktorite povrzani setilata se od osobeno zna~ewe, bidej}i samo so zadvoluvawe na barawata na
potro{uva~ite, prehranbenata industrija }e uspee vo promoviraweto na vnesuvaweto funkcionalna pro-
biotska hrana. 
Konceptot na probiotici e dlaboko navlezen vo nau~nata i industriskata sfera. Me|utoa, neophod-
no e ponatamo{no i poobemno prisustvo na naukata. 
Macedonian pharmaceutical bulletin 53 (1,2) 274-275 (2007)
SOP - 7
275
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Biochemical assessment of the toxicity to liver, hearth and kidneys
of Teucrium polium extracts in the treatment of diabetic rats
Gjoshe Stefkov, Todor Gruev, Svetlana Kulevanova
Faculty of Pharmacy, Vodnjanska 17, Skopje, Macedonia
After ten days of intragastal treatment of streptozotocin-diabetic rats with Teucrium polium extracts, we have
evaluate their toxicity to the functionality of the liver, hearth and kidneys through examination of plasma concentra-
tions of  aspartat-transaminase (AST), alanine-transaminase (ALT), alkaline-phosphatase (ALP), lactate-dehydro-
genase (LDH), creatine-kinase (CK), creatinine (KREA), total proteins (T.PRO), albumins (ALB), urea (UREA),
potasium (K) and sodium (Na). The evaluation was based on comparison of the results obtained from both groups
of streptozotocin-diabetic rats treated with extracts of Teucrium polium (T1, T2) with the results from the control
group of health rats (K), untreated streptozotocin-diabetic rats (D) and streptozotocin-diabetic rats treated with oral
antidiabetic drug glibenclamide (GLC).
Table 1. Activity and concentrations of the examined parameters in the plasma of experimental animals 
after ten days of treatment
The values of the examined parameters in the plasma do not show any physiological alterations and toxic
effect on the function of liver, hearth and kidneys of the examined animals, after ten days of treatment with extracts
of  Teucrium polium.
Macedonian pharmaceutical bulletin 53 (1,2) 276-277 (2007)
SOP - 8
276
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION
(U/L) 
T1 
T2 
GLC 


AST 
139,20 
130,00 
163,67 
101,17 
80,40 
ALT 
50,20 
67,00 
55,33 
60,67 
51,60 
ALP 
68,20 
114,00 
64,40 
183,67 
56,80 
LDH 
169,33 
145,00 
324,20 
303,00 
74,75 
CK 
206,60 
245,00 
151,20 
117,83 
43,00 
UREA 
6,40 
15,38 
9,62 
9,85 
6,10 
KREA 
47,40 
47,25 
50,00 
52,17 
38,20 
T.PRO 
53,60 
51,50 
52,50 
61,50 
55,00 
ALB 
21,20 
28,50 
22,33 
22,67 
20,20 
Na 
133,80 
137,00 
132,00 
133,50 
123,46 

3,50 
3,83 
3,62 
3,97 
3,16 

Biohemiska procenka na toksi~nosta vrz funkcijata na
crniot drob,  srceto i bubrezite na ekstrakti od 
Teucrium polium pri tretman na dijabeti~ni staorci
\o{e Stefkov, Todor Gruev, Svetlana Kulevanova
Farmacevtski fakultet, Ul.Vodwanska 17, Skopje, Makedonija
Po desetdneven intragastralen tretman na streptozotocin-dijabeti~ni staorci so ekstrakti od
Teucrium polium izvr{ena e procenka na nivnata toksi~nost vrz funkcijata na crniot drob,  srceto i
bubrezite preku merewe na plazma-koncentraciite na aspartat-transaminaza (AST), alanin-transaminaza
(ALT), alkalna fosfataza (ALP), laktat dehidrogenaza (LDH), kreatin kinaza (CK), kreatinin (KREA),
vkupni proteini (T.PRO), albumini (ALB), urea (UREA), kalium (K) i natrium (Na). Procenkata e izvr{ena
vrz osnova na sporeduvawe na rezultatite dobieni od dvete grupi (T1, T2) streptozotocin-dijabeti~ni
staorci tretirani so ekstrakt od Teucrium polium i sporedeni so rezultatite od grupata na zdravi staor-
ci (K), streptozotocin-dijabeti~ni  netretirani staorci (D) i streptozotocin-dijabeti~ni staorci tre-
tirani so  oralen antidijabetik glibenklamid (GLC). 
Tabela 1. Aktivnost i koncentracii na ispituvanite parametri vo plazma od eksperimentalni 
`ivotni posle 10-dneven tretman
Vrednostite na analiziranite parametri vo plazma ne uka`uvaat na patolo{ki promeni i toksi~no
dejstvo vrz funkcijata na crniot drob, srceto i bubrezite kaj ispituvanite `ivotni, posle desetdneven
tretman so ekstrakti od Teucrium polium.
Macedonian pharmaceutical bulletin 53 (1,2) 276-277 (2007)
SOP - 8
277
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION
(U/L) 
T1 
T2 
GLC 


AST 
139,20 
130,00 
163,67 
101,17 
80,40 
ALT 
50,20 
67,00 
55,33 
60,67 
51,60 
ALP 
68,20 
114,00 
64,40 
183,67 
56,80 
LDH 
169,33 
145,00 
324,20 
303,00 
74,75 
CK 
206,60 
245,00 
151,20 
117,83 
43,00 
UREA 
6,40 
15,38 
9,62 
9,85 
6,10 
KREA 
47,40 
47,25 
50,00 
52,17 
38,20 
T.PRO 
53,60 
51,50 
52,50 
61,50 
55,00 
ALB 
21,20 
28,50 
22,33 
22,67 
20,20 
Na 
133,80 
137,00 
132,00 
133,50 
123,46 

3,50 
3,83 
3,62 
3,97 
3,16 

Medicinal mushrooms as a source of biological active compounds 
and their beneficial impact on health
Biljana Bauer Petrovska
1
, Mitko Karadelev
2
, Svetlana Kulevanova
1
1
Faculty of Pharmacy, Ss Cyril and Methodius University, Vodnjanska 17; 
2
Institute of Biology, Faculty of Natural Science and Mathematics, Ss Cyril and Methodius University, 
Gazi Baba bb, P.O. Box 162, 1000 Skopje, Republic of Macedonia
The number of mushrooms on Earth is estimated at 140,000, yet maybe only 10% (approximately 14,000
named species) are known. Upon the investigations, up to now in the Republic of Macedonia approximately 1,200
species of macromycetes have been recorded. The majority of them belong to the phyla Ascomycota (130) and
Basidiomycota (1,050). From the Basidiomycota, most recorded species are from the orders Aphyllophorales (450)
and Agaricales (550). It could be presumed that this number is 10 times higher in the Republic of Macedonia, com-
pared with other countries with similarly territory and climatic conditions. 
Mushrooms comprise a vast and yet largely untapped source of powerful new active compounds. In partic-
ular, and most importantly for modern medicine, they represent an unlimited source of biological active compounds
with beneficial impact on health
This work highlights some of the recently isolated and identified substances of higher Basidiomycetes mush-
rooms origin that express promising antitumor, immune modulating, cardiovascular and hypercholesterolemic, antivi-
ral, antibacterial, antiparasitic, antifungal, antiinfective, antioxidative, vasoprotective, antiaging and other actions 
Medicinal mushrooms have a long history of use in folk medicine. In particular, mushrooms useful against
cancers of the stomach, esophagus, lungs, etc. are known in China, Russia, Japan, Korea, as well as the U.S.A. and
Canada. There are no data about the usage of the medicinal mushrooms in Republic of Macedonia. There are about
200 species of mushrooms that have been found to markedly inhibit the growth of different kinds of tumors. Searching
for new antitumor and other medicinal substances from mushrooms and to study the medicinal value of these mush-
rooms have become a matter of great significance. However, most of the mushroom origin antitumor substances
have not been clearly defined. Several antitumor polysaccharides such as hetero-beta-glucans and their protein com-
plexes, as well as dietary fibers, lectins, and terpenoids have been isolated from medicinal mushrooms. They are
considered as a potential biological and pharmacological active compounds. In Japan, Russia, China, and the U.S.A.
several different polysaccharide antitumor agents have been developed from the fruiting body, mycelia, and culture
medium of various medicinal mushrooms (Lentinus edodes, Ganoderma lucidum, Schizophyllum commune, Trametes
versicolor, Inonotus obliquus, and Flammulina velutipes). Both cellular components and secondary metabolites of
a large number of mushrooms have been shown to effect the immune system of the host and therefore could be used
to treat a variety of disease states. 
In this work selection has been made of biological active compounds with medicinal effects of mushrooms,
isolated from the medicinal species of macromycetes recorded in the Republic of Macedonia. Some of the registered
medicinal species: Armillaria mellea s.l., Fomes fomentarius, Marasmius alliaceus, Stereum hirsutum, Trametes ver-
sicolor etc, very frequently could be found on beech and oak forests in mass quantities on the territory of the Republic
of Macedonia.
Their large number will facilitate selection of those characterised by a significant medicinal quality for our
further investigations.
Macedonian pharmaceutical bulletin 53 (1,2) 278-279 (2007)
SOP - 9
278
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Medicinski gabi kako izvor na biolo{ki aktivni komponenti
i nivno korisno vlijanie vrz zdravjeto
Biljana Bauer Petrovska
1
, Mitko Karadelev
2
, Svetlana Kulevanova
1
1
Farmacevtski fakultet, Univerzitet Sv. Kiril i Metodij, Vodwanska 17; 
2
Institut za Biologija, Prirodno - matemati~ki fakultet, 
Univerzitet Sv. Kiril i Metodij, Gazi Baba bb, P. Fah 162; 1000 Skopje, Republika Makedonija
Iako brojot na gabi na zemjata e procenet na 140,000 vida, dosega mo`ebi samo 10% (pribli`no
14,000 odredeni vida) se poznati. Vrz osnova na najnovite istra`uvawata vo Republika Makedonija dosega,
e utvrdeno prisustvo na okolu 1200 vidovi makromiceti. Od niv na klasata Ascomycetes i pripa|aat 130
vida, a na Basidiomycetes 1050. Od poslednata, najmnogu vidovi se registrirani od redovite Aphyllophorales
(450) i Agaricales (550). Se pretpostavuva deka ovoj broj e deset pati pogolem vo Republika Makedonija,
sporedeno so drugi zemji, so sli~na golemina i klimatski uslovi.
Gabite pretstavuvaat ogromen i dosega glavno neistra`en izvor na mo}ni aktivni supstancii.
Osobeno i mo{ne zna~ajno za modernata medicina e toa {to tie pretstavuvaat neograni~en izvor na
biolo{ki aktivni komponenti so korisno biolo{ko i farmakolo{ko vlijanie vrz ~ovekot.
Osnovna cel na ovaa studija e da se prika`at nekoi izolirani i identifikuvani supstancii od
vi{ite Bazidiomiceti koi poka`uvaat antitumorno, imunomodulatorno, kardiovasularno i hiper-
holerolemi~no, antiviralno, antibakterisko, antifungalno, antiparazitno, antiinfektivno, antiok-
sidativno, vazoprotektorno i drugi dejstva. 
Medicinskite gabi imaat dolga istorija na upotreba vo tradicionalnata medicina. Osobeno
upotrebata na gabite protiv tumori vo `eludnik, hranoprovodnik, beli drobovi i dr., se poznati vo Kina,
Rusija, Japonija, Koreja kako i vo Amerika i Kanada. Kaj nas nema podatoci za upotreba na gabite za leku-
vawe. Postojat okolu 200 vida na gabi za koi e ustanoveno deka vpe~atlivo go inhibiraat rastot na
razli~ni tumori. Prou~uvaweto na novi antitumorni i drugi medicinski supstancii vo gabi i
istra`uvawe na nivnata medicinska vrednost stana predmet na osoben interes. Me|utoa, pove}eto od
gabite poseduvaat antitumorni supstancii koi hemiski ne se jasno definirani. Poedini antitumorni
polisaharidi kako hetero - beta - glukani i nivni proteinski kompleksi kako i dietetskite vlakna,
lecitini i terpenoidi se izolirani od medicinskite gabi i se smetaat za potencijalni biolo{ki i far-
makolo{ki aktivni supstancii. Vo Japan, Rusija, Kina i SAD poedini razli~ni polisaharidni antitu-
morni agensi se izolirani vo plodonosni tela, miceliumi i kulturi na razli~ni medicinski gabi (Lentinus
edodes, Ganoderma lucidum, Schizophyllum commune, Trametes versicolor, Inonotus obliquus Flammulina velutipes).
Kleto~nite komponenti i sekundarnite metabolite na pogolem broj gabi poka`uvaat efekt vrz imuniot
sistem i zatoa mo`at da se upotrebat za tretirawe na razli~ni zaboluvawa. 
Vo ovaa studija e napraven izbor na biolo{ki aktivni komponenti so medicinski efekt izoli-
rani od makromiceti prisutni vo fungijata na Republika Makedonija. Nekoi od registriranite medi-
cinski vidovi kako na primer: Armillaria mellea s.l., Fomes fomentarius, Marasmius alliaceus, Stereum hirsutum,
Trametes versicolor i dr. mnogu ~esto mo`at da se najdat vo bukovi i dabovi {umi vo golemi koli~ini na
teritorijata na Republika Makedonija. 
Nivniot golem broj }e ovozmo`i izbor na onie koi se karakteriziraat so zna~aen medicinski
kvalitet za na{ite ponatamo{ni istra`uvawa.
Macedonian pharmaceutical bulletin 53 (1,2) 278-279 (2007)
SOP - 9
279
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

Distribution and Ecology of Human-Toxic Macromycetes 
in the Republic of Macedonia
Mitko Karadelev
1
, Sami Sulejmani
2, 
Biljana Bauer Petrovska
3
1
Institute of Biology, Faculty of Natural Science and Mathematics, Ss Ciryl and Methodius University, 
Gazi Baba bb, P.O .Box 162, 1000 Skopje; 
2
Faculty of Natural Science and Mathematics, State University of Tetovo, 1200 Tetovo; 
3
Faculty of Pharmacy, Ss Ciryl and Methodius University, Vodnjanska 17; 1000 Skopje, Republic of Macedonia
According to the recent research into fungi diversity of R. Macedonia, 1,250 species have been registered.
A part of these fungi, 117 species, show proved poisonous effects. These species mainly belong to the following gen-
era: Clitocybe, Cortinarius, Entoloma, Inocybe, Amanita, Lepiota, Russula, Psilocybe, Tricholoma, Lactarius,
Scleroderma and Mycena. Fungi toxicity manifests through the following syndromes: Phalloidine syndrome, Orellanine
syndrome, Gyromitrin syndrome, Muscarine syndrome, Gastrointestinal irritants and Coprinus syndrome. In most
of them, these effects are due to the presence of toxic compounds such as phalotoxins, amatoxins, orellanin, gyromitrin,
muscarin, coprinmin, and different hallucinogenic and psychotropic compounds. 
From the species containing phalloidous toxins (phallotoxins and amatoxins) and causing phalloidous syn-
drom in Macedonia are found: Amanita phalloides, A. verna, A. virosa, Galerina autumnalis, G. marginata, G. venena-
ta, Lepiota brunneo-incarnata, L. castanea, L. helveola, L. josserandii and L. ochraceofulva. Species from the complex
genus Cortinarius (C. orellanus, C. speciosissimus and C. splendens) produce orellanine syndrom. From the species
containing the thermo-labile mycotoxin gyromitrine, the following are present in Macedonia: Gyromitra esculenta,
G.gigas and G.infula. The muscarinic syndrom (lethality 8 %) is caused by fungi from a number of genera. This
includes representatives of the genera Inocybe (I. patouillardi, I. fastigiata, I. umbrina), Clitocybe (C. cerussata, C.
dealbata, C. candicans, C. rivulosa) and Amanita (A. muscaria). A similar one to this syndrom, but with lesser lethal-
ity (2%), is the pantherine syndrom produced by the frequent fungus Amanita pantherina
A large number of fungi are gastrointestinal irritants. They seldom cause death, and the symptoms usually
disappear in a few minutes up to 4 hours. This group includes representatives from various fungi genera existing in
Macedonia: Agaricus (A. silvicola, A. xanthodermus), Boletus (B. luridus, B. satanas), Entoloma (E. lividum, E.
nidorosum, E. rhodopolium), Hebeloma (H. sinapizans, H. crustuliniforme), Lactarius (L. chrysorheus, L. glaucescens,
L. helvus, L. rufus, L. scrobiculatus, L. torminosus, L. uvidus), Lepiota (L. clypeolaria, L. cristata, L. naucina),
Naematoloma fasciculare, Paxilus involutus, Pholiota (Ph. aurea, Ph. squarosa), Albatrelus cristatus, Meripilus
giganteus, Phaeolus schweinitzii, Laetiporus sulphureus, Ramaria formosa, Russula emetica, Scleroderma auran-
tium, Tricholoma (T. pardinum, T. nudum, T. saponaceum, T. sulphureum, T. sejunctum) and Verpa bohemica. 
Of the species causing a coprinus syndrom (appearing in 5-10 minutes after the consuming if in the last 24
hours the person has consumed alcohol) in Macedonia are found Coprinus atramentarius, Coprinus micaceus and
Clitocybe clavipes.
A total of 30 fungi species with hallucinogenic properties have been recorded in the Republic of Macedonia.
These species belong to the genera Claviceps, Elaphomyces, Panaeolus, Psathyrella, Gymnopilus, Amanita, Pluteus,
Psilocybe, Stropharia, Hygrocybe, Mycena, Rickenella and Vascellum. Due to the presence of various compounds
in their fruit bodies, these fungi can cause the syndromes psilocin–psilocybin, muscarine and ergotism. 
Most of the species are widespread, and grow on various substrates, such as soil, dung and enriched soil.
There are representatives that are lignicolous, mycorrhizal, parasitic and some are hypogeic. However, this is not a
final list of the toxic fungi in the Republic of Macedonia, and there are only a small number of localities of most of
the species. The further investigation into the fungi diversity of Macedonia would contribute for a more complete
picture of the distribution of these organisms, and would ascertain the precise number of toxic species. 
Macedonian pharmaceutical bulletin 53 (1,2) 280-281 (2007)
SOP - 10
280
^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO
FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION

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