Inhibitory effect of the plant proteins mixture on the specific sucrase activity in intestine of diabetic mice

Background and Purpose: Increased activity of sucrase, one of the intestinal alpha-glucosidase founded in diabetes mellitus. Inhibition of sucrase activity, plays a major role in preventing rise in postprandial glucose level in diabetics. On peer-reviewed literature could be found regarding investigation the effect of mixture plant proteins, Mw 3 – 15 kDa (MPP), isolated from Astragali radix – Astragalus membranaceus Fisch., Foenugraeci semen – Trigonella foenum graecum L., Cichorii radix – Cichorium Intybus L. and Urticae radix and herba – Urtica dioica L. on sucrase activity. This plants are used in traditional medicine of treatment of diabetes mellitus. The aim of this study was to determine activity of sucrase in small intestinal homogenates of NOD diabetic mice on feeding with and without MPP in chow. Materials and Methods: In mice diabetes was induced by i.v. injection of aloxan-monohydrate (75 mg/kg b.m.) seven days before treatment with MPP. The proteins (Mw 3 – 15 kDa), were isolated from ethanol extract, each plants separately, by gel filtration method on Sephadex G-25 column. Eluted fraction which highest absorbance on 280 nm were pooled, dialyzed, lyophilized and mixed (MPP) and before treatment in mice solvent in sterile PBS. After seven days of treatment diabetic NOD mice with MPP (1,8 g/d), the small intestine was removed and divided into three segments, from pylorus to duodenum, and two equal lengths of the jejunum and ileum and homogenized in cold 0.14M KCl. Specific sucrase activity was determined using method of Dahlquist et. al., by sucrose as substrate. Results and Conclusion: We confirmed the increased specific sucrase activity in the intestine of diabetic NOD mice. Our results also indicate that MPP have strongly inhibitory potential on intestinal sucrase activity (p<0.05) in diabetic mice. Conclusions drawn from this study should be further supported and our future experiments will be focused on determining the amino acid sequence of each protein from MPP

Neurofibromatoza tipa 1: klinička, patologijska i radiologijska korelacija

Type 1 neurofibromatosis is a phacomatosis inherited as an autosomal dominant disorder. It is characterized by the occurrence of hamartomas and tumors on the body, particularly on the nervous system and skin. The clinical criteria for its diagnosis include the following findings: six or more cafe-au-lait spots of 35 mm in diameter on the skin, two or more neurofibromas, spots in the axillary or inguinal region, optic nerve gliomas, two or more hamartomas of the iris, and characteristic changes of bones and brain. The pathologist\u27s finding is predominated by the occurrence of neurofibromas along peripheral and cranial nerves, optical gliomas, policystic astrocytomas of the brain, and hamartomas of the brain and iris. During a 15-year period, 166 children with type 1 neurofibromatosis were examined and radiologically evaluated. Classical radiological bone x-rays were made, along with brain and spine CT and MR. Dysplasia of the greater wing of the sphenoid bone was detected on bone tissue accompanied by deformation of the orbit and middle cranial fossa, wedge-formed vertebrae, expanded intervertebral foramina, and cystic masses in other bones. In the brain parenchyma, hamartomas, policystic astrocytomas and optic nerve gliomas were detected along with neurinomas of the cranial and spinal nerves. Based on the clinical, laboratory and radiologic follow-up of the patients with type 1 neurofibromatosis, the need is stressed for a multiple approach to the diagnosis and treatment of neurofibromatosis.Neurofibromatoza tipa 1 je fakomatoza koja se nasljeđuje autosomno dominantno, a obilježena je pojavom hamartoma i tumora po tijelu, poglavito živčanog sustava i kože. Klinički kriteriji za postavljanje dijagnoze temelje se na nalazima: šest ili više pjega boje bijele kave promjera većeg od 5 mm na koži, dva ili više neurofibroma, pjegavosti pazušnih i ingvinalnih regija, optičkog glioma, dva ili više hamartoma šarenice i znakovitim promjenama na kostima i mozgu. U nalazu patologa dominira pojava neurofibroma duž perifernih i kranijskih živaca, optičkih glioma, policističnog astrocitoma mozga te hamartoma mozga i šarenice. U tijeku 15-godišnjeg razdoblja pregledano je i radiološki obrađeno 166 djece s neurofibromatozom tipa 1. Primijenjene su klasične radiološke metode snimanja kostiju, CT mozga i kralješnice te MR mozga i kralješnice. Na koštanom tkivu utvrđena je displazija velikog krila sfenoida praćena deformacijom orbite i srednje lubanjske jame, klinasto oblikovani kralješci, prošireni intervertebralni otvori te cistične tvorbe u dugim kostima. U parenhimu mozga utvrđeni su hamartomi, policistieniastrocitomi i gliomi optikusa te neurinomi kranijskih i spinalnih živaca. Na temelju kliničkog, laboratorijskog i radiologijskog praćenja bolesnika s neurofibromatozom tipa 1 ukazano je na potrebu višestrukog pristupa u dijagnostici i liječenju neurofibromatoze

Paroxysmal non-epileptic disorders in children and adolescents

Cilj i metode rada: opsežnim pregledom literature opisati paroksizmalne neepileptičke napadaje (PNEP) u djetinjstvu i adolescentnoj dobi s naglaskom na semiologiju i razlikovne kliničke značajke poremećaja u odnosu na epileptičke napadaje te dati opće smjernice liječenja. Rezultati: PNEP-i se javljaju kao iznenadni, brzi napadaji koji mogu često recidivirati i mogu biti praćeni gubitkom svijesti ili bez gubitka svijesti. Imaju podrijetlo u cerebralnoj disfunkciji različitog uzroka, ali nikad u poremećaju biolektrične kortikalne aktivnosti. PNEP-i su česti u dječjoj populaciji i javljaju se u bilo kojoj dobi djeteta, od novorođenačke do adolescentne. Oni uključuju anoksično/ hipoksične paroksizmalne poremećaje, psihogene paroksizmalne napadaje, paroksizmalne napadaje u tijeku spavanja, atake sa stereotipnim promjenama pokreta i položaja tijela ili predstavljaju fiziološke oblike ponašanja. Procjenjuje se da oko 10% djece opće populacije ima nekonvulzivne atake. Nalazimo ih u čak 60% dojenčadi sa sumnjom na epileptičke napadaje, 60% djece s određenim stupnjem intelektualnih teškoća i u 20%–25% djece s urednim psihomotornim razvojem. Oko 15% pacijenata upućenih u tercijarne centre za epilepsiju zapravo imaju PNEP. Značajan broj ovih događaja ne zahtijeva specifično liječenje i tijekom vremena spontano regredira. Zaključak: Pedijatri bi trebali identificirati paroksizmalne neepileptičke događaje, izbjegavajući pogrješnu dijagnozu epilepsije i njezine implikacije kao što su nepotrebne pretrage, dugotrajna farmakoterapija te negativne psihosocijalne posljedice za bolesnika (ograničenja, stigmatizacija) i njegovu obitelj. U kliničkoj procjeni i dijagnosticiranju ovih poremećaja treba uzeti u obzir: dob djeteta, kliničku sliku napadaja i rezultate dijagnostičke obrade. Dijagnostička metoda izbora je video EEG poligrafija. U dvojbenim slučajevima najprimjerenije je ove poremećaje klasificirati kao nejasne paroksizmalne napadaje. Kliničko praćenje i ponovna procjena napadaja/događanja/stanja dovest će do ispravne dijagnoze.Aim and methods: Through an extensive review of the literature, to describe paroxysmal non-epileptic seizures(PNEP)in childhood and adolescence, with the emphasis on the semiology and distinguishing clinical features of the disorder in relation to epileptic seizures, and provide general treatment guidelines. Results: PNEPs occur as sudden onset rapid seizures which can frequently recur and may be accompanied by or without loss of consciousness.Their origin is in cerebral dysfunction of various causes but never in disorders of cortical bioelectrical activity. PNEPs are frequent in children and occur at any time in children, from newborns to adolescents. They include anoxic/hypoxic paroxysmal disorders, psychogenic paroxysmal seizures, paroxysmal seizures during sleep, attacks with stereotypical changes in movement and body posture, or represent physiological forms of behaviour. It is estimated that about 10% of children in the general population have non-convulsive attacks.We find them in as many as 60% infants with suspicion of epileptic attacks, 60% of children with a certain degree of intellectual difficulties, and in 20% to 25% of children with normal psychomotor development. About 15% of patients referred to tertiary centres for epilepsy actually have PNEP.A significant number of these events do not require specific treatment and regress spontaneously over time. Conclusion: Paediatricians should identify paroxysmal non-epileptic events, avoiding the mistaken diagnosis of epilepsy and its implications, as unnecessary tests, longterm pharmacotherapy and the negative psycho-social consequences for the patients (restrictions, stigmatization) and their families. In the clinical assessment and diagnosis of these disorders, the following should be taken into account: the child’s age, the clinical picture of the seizure, and the results of diagnostic workup.The diagnostic method of choice is video EEG polygraphy.In case of doubt, it is most appropriate to classify these disorders as paroxysmal events of unclear origin. Clinical monitoring and repeat assessment of the seizures/events/status will lead to the correct diagnosis

MASA sindrom u braće blizanaca: prikaz kliničkog praćenja kroz šesnaest godina

MASA syndrome (OMIM 303350) is a rare X-linked recessive neurologic disorder, also called CRASH syndrome, spastic paraplegia 1 and Gareis-Mason syndrome. The acronym MASA describes four major signs: Mental retardation, Aphasia, Shuffl ing gait and Adducted thumbs. A more suitable name for this syndrome is L1 syndrome because the disorder has been associated with mutations in the neuronal cell adhesion molecule L1 (L1CAM) gene. The syndrome has severe symptoms in males, while females are carriers because only one X chromosome is aff ected. The aim of this report is to show similarities and diff erences in clinical manifestations between twins with the L1CAM gene mutation and to emphasize the importance of genetic counseling. Our patients were dizygotic twins born prematurely at 35 weeks of gestation. Pregnancy was complicated with early bleeding and gestational diabetes. Immediately after birth, hypertonia of lower extremities was observed in both twins. Sixteen-year clinical follow up showed spastic paraparetic form with shuffl ing gait, clumsiness, delayed speech development, lower intellectual functioning at the level of mild to moderate mental retardation, primary nocturnal enuresis, behavioral and sleep disorder (more pronounced in the second twin). Magnetic resonance imaging of the brain showed complete agenesis of the corpus callosum, complete lack of the anterior commissure, and internal hydrocephalus. Electroencephalograms showed nonspecifi c slower dysrhythmic changes. Kidney ultrasound showed mild dilatation in the channel system of both kidneys in both twins. Ophthalmologic examination was normal. Molecular genetic testing identifi ed homozygous intron 26 L1CAM gene IVS26-12G→A mutation in both twins. The mother is carrier of the same heterozygous mutations. In conclusion, our patients, fraternal twins, show similar clinical changes typical of the MASA syndrome. After identifying the specifi c genetic mutations, this family has become eligible for genetic counseling and informative for prenatal diagnosis.Sindrom MASA (OMIM 303350), nazvan još i CRASH sindrom, nasljedna spastička paraplegija 1 i Gareis-Masonov sindrom, je X-vezana, recesivno naslijedna bolest. Akronim „MASA“ opisuje četiri glavna klinička znaka - mentalnu retardaciju, afaziju, poremećaj hoda (shuffl ing gait ), pri čemu bolesnik hoda vrlo sporo, povlači stopala, a ne odiže ih od podloge i aducirane palčeve. Pogodniji naziv za ovaj sindrom je „L1 sindrom“. Ovo odstupanje je povezano s mutacijom gena L1CAM. Budući da je zahvaćen samo jedan X kromosom , u ovom sindromu nalazimo umjerene do teške simptome u muškaraca, dok su žene prenositeljice. Cilj ovog rada je pokazati sličnosti i razlike kliničkih manifestacija u blizanaca s mutacijom gena L1CAM i istaknuti važnost genetičke obrade bolesnika za genetsko savjetovanje obitelji. Naši bolesnici, dvojajčani blizanci, rođeni prijevemeno u 35. tjednu gestacije. Trudnoća je komplicirana ranim krvarenjem i gestacijskim dijabetesom. Neposredno nakon rođenja uočen je hipertonus donjih ekstremiteta u oba blizanca. U tijeku šesnaestogodišnjeg praćenja u kliničkom statusu pokazali su motoričko odstupanje u vidu spastičkog paraparetskog obrasca hoda, nespretnost, usporen razvoj govora, intelektualno funkcioniranje na razini blaže do umjerene mentalne retardacije, primarnu noćnu enurezu, poremećaj ponašanja i spavanja (više izražene u drugog blizanca). MRI mozga blizanaca pokazao je kompletnu ageneziju korpusa kalozuma, kompletni nedostatak prednje komisure i interni hidrocefalus. U EEG-u su, uz spori osnovni ritam, registrirane dizritmične promjene. Ultrazvuk bubrega blizanaca pokazao je umjerenu dilataciju kanalnog sustava oba bubrega. Oftalmološki pregled je bio uredan. Molekularnim genetičkim testiranjem utvrđeno je da su blizanci homozigotni nositelji mutacije IVS26-12G → A u intronu 26 L1CAM gena. Majka je heterozigotna nositeljica iste mutacije. Naši bolesnici, dvojajčani blizanci, pokazali su slične kliničke značajke tipične za sindrom MASA. Nakon utvrđivanja specifi čne genske mutacije ova obitelj postala je podobna za genetsko savjetovanje i informativna za prenatalnu dijagnostiku

SPEECH AND LANGUAGE DISORDERS IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1 (NF1) – STUDY OF 112 PATIENTS

Uvod: NF1 je s kliničkog i genetskog aspekta jasno definirana autosomno dominantno nasljedna bolest, čiji se organski neurobiološki procesi ispituju više od stoljeća. Povezanost NF-a1 i govorno-jezičnih poteškoća relativno je slabije istražena. Cilj rada je prikazati učestalost govorno-jezičnih poremećaja kod djece s NF-om1. Bolesnici i metode: Iz osobnog registra bolesnika od 202-je djece s NF-om1 izdvojili smo skupinu 112-ero djece (54 djevojčice i 58 dječaka), koja su logopedski longitudinalno praćena. Dob djece na inicijalnom ispitivanju kretao se od 1godine i 9 mjeseci do 16 godina i 3 mjeseci. U ispitivanjima se analizirala semantičko-sintaktička struktura i modaliteti govornog iskaza. Artikulacija je ispitivana testom artikulacije prema Vuletiću, dok je prozodija procjenjivana subjektivno te je procjena zatim objektivizirana akustičkom analizom spektra govora. Rezultati: Različite stupnjeve usporenog ranog razvoja govora imalo je 22% bolesnika.. Najčešći poremećaj govora manifestirao se u pormećaju rezonancije (81,2%) kao pojačana nazalnost (hyperrhinophonia) i miješana nazalnost (rhinophonia mixta) - čak u 79.5%, a oslabljena nazalnost (hyporhinophonia) u 1,8% ispitanika. Artikulacijski poremećaji dijagnosticirani u 59,8% ispitanika najčešće su se manifestirali kao distorzije (51,8%). Subjektivnom procjenom glasa nađena je promuklost u 50,9%. Prozodija govora poremećena je na razini ritma govora s intraverbalnim i interverbalnim blokadama u 38.4% djece s NF-om1. Procjena čitanja i pisanja u 87-ero djece s NF-om1 pokazala je visoku učestalost poremećaja – nespecifičnih grješaka čitanja (19.5%) i pisanja (17.2%). Zaključak: Značajna učestalost govorno-jezičnih poremećaja kod djece s NF-om1 mogla bi imati bitnu ulogu u pojavi poremećaja učenja koji se pojavljuju u oko 50-60% oboljelih.Introduction: NF1 is both clinically and genetically clearly defined as an autosomal dominant hereditary disease whose organic neurobiological processes have been examined for over a century. The relationship between NF1 and speech and language disorders has been relatively less well investigated. Aim: To show the frequency of speech and language disorders in children with NF1. Patients and methods: We selected a group of 112 children (54 girls and 58 boys) from our personal registry that covers 202 children with NF1. The selected children were longitudinally monitored by a speech pathologist. The age of children on initial examination varied between 1 year 9 months and 16 years 3 months. Semantic-syntactic structure and modalities of speech were analysed. Articulation was tested with the Vuletić test of articulation, while prosody and resonance were evaluated subjectively and then objectified with an acoustic analysis of the speech spectrum. Results: 22% of patients had some degree of delayed early speech development. Speech disorders presented most often as disorders of resonance (81.2%) – hyperrhinophonia and rhinophonia mixta (79.5%) and hyporhinophonia (1.8%). Articulation disorders were diagnosed in 59.8% of patients and they were most often manifested as distortions (51.8%). Subjective evaluation of the voice found hoarseness in 50.9% of cases. Prosody was disrupted on the level of rhythm of speech with inter- and intraverbal blockades in 38.4% of children with NF1. Evaluation of reading and writing in 87 children with NF1 showed a high frequency of disorders – unspecific reading (19.5%) and writing (17.2%) errors. Conclusion: The significant frequency of speech and language disorders in children with NF1 could have an important role in the appearance of learning disorders that are found in 50-60% of patients

NEUROLOGICAL CHANGES AND COMPLICATIONS IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1 (NF1)

Neurofibromatoza tip 1 (NF1) jedna je od najčešćih autosomno dominantnih genetskih bolesti koja se očituje brojnim manifestacijama različitih organskih sustava. U ovom radu raspravlja se o učestalosti, kliničkom ispoljavanju i općim preporukama za liječenje brojnih promjena i komplikacija perifernog i središnjeg živčanog sustava u djece s NF-om1. Najčešći neurološki poremećaji NF-a1 u djetinjstvu su kognitivni deficiti i specifični poremećaji učenja (i do 80%). Periferni kutani /subkutani neurofibromi obično se javljaju u pubertetskom razdoblju, a pleksiformni neurofibromi kao prirođene lezije mogu prvih godina života biti nezamijećeni. Učestalost malignih tumora ovojnica perifernih živaca (neurofibrosarkoma ) u NF-u1 je veća nego u općoj populaciji – procjenjuje se na 2%-5%. Najčešće promjene mozga su multipli T2-hiperintenziteti prikazani na MRI-u mozga, od 43% do 93%, ovisno o dobi. Lokalizirani su najčešće u bazalnim ganglijima, moždanom deblu i malom mozgu. Njihov klinički značaj je nepoznat, pa odatle i naziv „neidentificirani svijetleći objekti“. Optički gliomi (pilocitički astrocitomi) najčešći su tumori mozga u djece s NF-om1. Njihova učestalost procjenjuje se na oko 20%. Drugi po učestalosti su tumori moždanog debla. Najčešći uzrok hipertenzivnog hidrocefalusa u djece s NF-om1 je stenoza akvedukta. Liječenje neuroloških komplikacija u djece s NF-om1 ne razlikuje se od istovrsnih neuroloških promjena u djece koja nemaju NF1.Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant genetic diseases with a variety of changes and complications of the peripheral and central nervous system. In this article we discuss the prevalence, clinical manifestations and general recommendations for the treatment of children with NF1. The most common neurological disturbances in NF during childhood are cognitive deficits and specific learning difficulties (up to 80 %). Peripheral cutaneous /subcutaneous neurofibromas are usually present in puberty, while plexiform neurofibromas, as inherited lesions in the first years of life, could remain unrecognized. Incidence of malignant peripheral nerve sheath tumors (neurofibrosarcomas) is higher in NF1 than in the general population, with an estimated value of 2%-5%. The most common brain changes are multiple T2-hyperintensities presented in 43% to 93% of children with NF1 age dependent. They are usually localized in basal ganglia, brainstem and cerebellum. Their clinical importance is still unknown which is why they are called „unidentified bright objects“. Visual pathway gliomas (pilocytic astrocytomas) are the most common brain tumors in children with NF1 with the prevalence of 20%. Second in the range are the brainstem tumors. Aqueductal stenosis is the most common reason for hypertensive hydrocephalus in children with NF1. The medical treatment of neurological complications in children with NF1 does not differ from the treatment of equivalent neurological changes in children without NF1

Evaluacija utjecaja fizioterapije na kvalitetu života i samopoimanje zdravlja osoba oboljelih od neurofibromatoze tipa 1

Uvod: Neurofibromatoza tip 1 (NF1) je autosomno dominantna genetska bolest koja je uzrokovana promjenom NF1 gena na 17. kromosomu. Bolest se javlja podjednako u oba spola. Jednako tako, može biti naslijeđena od jednog od roditelja ili se može pojaviti prvi put u obitelji kao novonastala promjena NF1 gena. Cilj: Cilj rada je utvrditi postoji li razlika u kvaliteti života između skupine ispitanika oboljelih od NF-a 1 kod kojih je primijenjena fizioterapija i ispitanika s NF-om 1 kod kojih nije primijenjena fizioterapija. Materijali i metode: Uzorak je obuhvaćao N=44 ispitanika. U istraživanju je korišten upitnik za procjenu zdravstvene kvalitete života SF-36 (engl Short form health survey-36) i vizualno analogna skala boli. Rezultati: U domenama upitnika za procjenu zdravstvene kvalitete života prosjek zadovoljstva ispitanika u obje skupine najveći je u domeni fizičkog funkcioniranja (skupina A: M=56,15, skupina B: M=81,45). Prisutna je statistički značajna razlika u stupnju boli između skupina (p<0,01). Zaključak: Rezultati provedenog istraživanja pokazali su dobru kvalitetu života u obje skupine ispitanika. Viša percepcija boli u NF1 skupini A upućuje na potrebu za daljnjim korištenjem fizioterapije, ali i prepoznavanjem emocionalnih poteškoća i depresivnosti kao mogućeg uzroka boli