Endoscopic Features of Gastric Mucosa in Children Having Pathohistological Evidence of Helicobacter Pylori Infection

Infection with Helicobacter pylori (Hp) is common in children from developing countries, particularly in adolescents. It is associated with chronic gastritis and stomach cancer. A characteristic endoscopic finding in children is nodular gastritis. The aim of this study was to assess and confirm association of nodular gastritis, mainly of anthral mucosa, with Hp infection in children. A total of 195 children 1 to 15 years of age were studied during a two-year period (2004–2006). There were 107 girls (54.9%) and 88 boys (45.1%). The patients presented with recurrent epigastric pain, nausea, vomiting, heartburn, sour mouth, regurgitation, bloating or other dyspeptic symptoms. The complaints were recorded by a structured interview with parents and older children. Upper endoscopy was performed in all children. The presence and degree of mucosal granulation was recorded and two samples of mucousa from the antrum and the small curvature were taken. Biopsy material was processed for histology as usual, stained with 2% Giemsa and examined by a pathologist for the presence of Hp. A total of 40 of 195 children (20.5%) have had positive Hp infection and a 27 of 40 (67.5%) have had a granular aspect of anthral mucosa at the endoscopy. Sensitivity of the finding was 87.5%, specificity 93.5%, positive predictive value 73%, negative predictive value 91.8%, p<0.05. Average age of those patients was 11.5±3.0 years. Subjective symptoms of dyspepsia (as recorded by the questionnaire) were often associated with Hp positivity, but short of statistical significance. No difference between boys and girls was noted. Endoscopic finding of nodular gastritis, especially in areas of antrum and small curvature, showed a highly positive correlation with Hp infection

Nitrozaminska onečišćenja u lijekovima

In 2018, some sartan medicinal products were reported to be contaminated with nitrosamine compounds, which are potent mutagenic carcinogens. Two nitrosamines received particular attention: N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA). These have since been confirmed in different types of medicinal products, including ranitidine and metformin. Consequently, the European Medicines Agency (EMA) started an investigation into the cause of contamination and an assessment of the risk to patients taking contaminated medicinal products. The main source of contamination were changes in production, which involves combinations of amines and nitrogen compounds and the use of specific catalysts and reagents. Withdrawals of medicinal products that took place in Croatia did not lead to a shortage of sartan- or metformin-containing medicines. Moreover, ranitidine had been preventively withdrawn all over the EU, including Croatia, creating shortages at the time, but was subsequently replaced with therapeutic alternatives.Nitrozaminski su spojevi jaki kancerogeni i njihova je prisutnost potvrđena 2018. u nekim lijekovima s djelatnom tvari iz skupine sartana. Dva predstavnika nitrozamina, najčešće detektirana kao onečišćenja u lijekovima, jesu N-nitrozodimetilamin (NDMA) i N-nitrozodietilamin (NDEA). Od tada je njihova prisutnost potvrđena u različitim skupinama lijekova, što upućuje na njihovu učestalost. Slijedom toga, Europska agencija za lijekove (EMA) pokrenula je istragu uzroka onečišćenja te procjenu rizika kojima su pacijenti koji su uzimali lijekove onečišćenih serija bili izloženi. Glavni uzrok onečišćenja djelatne tvari uključuje promjene u proizvodnom postupku koji sadržava smjesu amina I dušikovih spojeva uz uporabu specifičnih katalizatora i reagensa. Nitrozamini su također pronađeni u gotovim lijekovima. Povlačenje lijekova u Hrvatskoj nije dovelo do nestašice lijekova koji sadržavaju sartan ili metformin, a lijekovi koji sadržavaju ranitidin povučeni su iz mjera opreza iz ljekarni i u Hrvatskoj i u Europskoj uniji

Aplasia Cutis Congenita in a Newborn Child Associated with Two Fetus Papyraceous

Aplasia cutis congenita (ACC) is a rare inborn lesion, presenting with absence of skin. The etiology is unknown and is probably not attributable to a single cause but to a combination of genetic factors. Multiple causes have been suggested for ACC: syndromes and teratogens, intrauterine infection – varicella zoster virus, herpes simplex virus – fetal exposure to cocaine, heroin, alcohol, or antithyroid drugs. The most common site is the scalp. We report a case with multiple lesions on the trunk, resembling an instance with ACC group 5. This form of ACC occurs in association with the in utero death of a twin or more (in this case triple) fetus. Histological findings are available in very few reports. Therapy options depend on the characteristics of the lesion, but conservative treatment is usually chosen.</p

VAGINAL BIRTH AFTER FIVE PREVIOUS CAESAREAN SECTIONS

Zabrinjavajuće visoka učestalost carskih rezova i rizici ponovljenog zahvata opravdavaju pokušaj vaginalnog poroda nakon prethodnog carskog reza. Prikazan je uspješan vaginalni porod sedmorotkinje s teškom anemijom i ­pre­eklampsijom nakon prethodnih pet carskih rezova i jednog (prvog) vaginalnog poroda.A troubled high occurrence of cesarean sections and risks related to repeated C-sections justify an attempt to vaginal birth after prior C-section. A successful vaginal birth of a heptapara (a woman with 6 prior births) with severe anemia and preeclampsia who had 5 prior C-sections and one (first) vaginal birth is presented

COVID-19 Pandemic Alters Conventional Approach of Good Manufacturing Practice Inspection

Dobra proizvođačka praksa (GMP) je skup različitih smjernica, pravila i normi koje jamče učinkovitost, kvalitetu, sigurnost i dosljednost u proizvodnji i kontroli lijekova. Nadzor nad dobrom proizvođačkom praksom u Hrvatskoj provodi Agencija za lijekove i medicinske proizvode (HALMED). U svrhu održavanja konzistentnih inspekcijskih standarda, HALMED ima razvijen Poslovnik kakvoće izrađen u skladu s europskim smjernicama. Inspektori Agencije imaju odgovarajuća znanja i iskustvo te se trajno usavršavaju. Po obavljenoj inspekciji, HALMED izdaje proizvodnu dozvolu i potvrdu o provođenje dobre proizvođačke prakse (GMP potvrdu) za proizvođače u Republici Hrvatskoj te GMP potvrdu za proizvođače iz trećih zemalja. S obzirom na nemogućnost izlaska inspektora na teren uslijed pandemijske situacije, sve se češće pribjegava ocjeni na daljinu.Good Manufacturing Practice (GMP) is a set of different guidelines, rules and standards that guarantee effectiveness, quality, safety and consistency in manufacturing and quality control of medicinal products. To maintain consistency in inspection standards, HALMED has in place a Quality Manual developed according to European guidelines. The Agency inspectors are trained and experienced accordingly, and are permanently educated. After an inspection has been completed, HALMED issues a manufacturing license and a GMP certificate for manufacturers located in the Republic of Croatia or a GMP certificate for manufacturers from third countries. Due to the pandemic situation that prevents inspectors to travel to manufacturing sites abroad, they proceed with the distant assessment of manufacturers

Psychological Impact of Isotretinoin Treatment in Patients with Moderate and Severe Acne

Acne patients are subject to different degree of psychosocial distress. The emotional impact of acne vulgaris due to disfigurement caused by the disease is undisputed. Most common reactions to the acne are depression and anxiety. The use of isotretinoin, one of the most effective options in acne treatment, increases depression symptoms. The aim of this study was to investigate the psychological status of the patients with moderate to severe acne and to compare patients treated with isotretinoin with patients treated with vitamin C. A total of 85 patients suffering from acne vulgaris were included in the study. The results of this study do not find a significant correlation between the use of isotretinoin and the psychological effects of the drug

Strukturno-funkcijski odnos promjena pokazatelja vidnog polja s kvadrantnom i prosječnom debljinom mrežničnog sloja živčanih vlakana u očima s eksfolijacijom

The progressive nature of glaucoma suggests it should be possible to detect structural changes such as retinal nerve fiber layer (RNFL) thickness loss before the condition becomes clinically apparent with visual field (VF) impairment. Therefore, the aim was to analyze RNFL thickness and VF changes in study groups with unilateral exfoliation syndrome (XFS), bilateral XFS and bilateral exfoliative glaucoma (XFG), and compare it with controls. The study included 114 subjects (228 eyes) divided into 4 groups according to the presence of exfoliation: 30 subjects with unilateral XFS (30 with clinically visible XFS and 30 fellow eyes), 24 subjects (48 eyes) with bilateral XFS, 28 (56 eyes) subjects with bilateral XFG, and control group (32 subjects). All subjects underwent VF and RNFL measurements after ophthalmologic examination. Both eyes of unilateral XFS (clinically ­visible and fellow eye) showed positive correlation between Mean Defect (MD) and square root of Loss of Variance (sLV) and between MD and inferior quadrant RNFL thickness. In bilateral XFS and XFG, there was negative correlation between MD and inferior quadrant RNFL thickness. Inferior, superior and nasal quadrant RNFL thickness was lower in XFG group than in other groups. In bilateral XFS group, the inferior quadrant RNFL thickness was lower as compared with unilateral XFS group (in both eyes). The mean RNFL thickness negatively correlated with MD in bilateral XFS and XFG groups. In conclusion, structural changes before VF impairment have an important role in early detection of glaucoma in subjects at risk.Progresija glaukoma upućuje na to da se strukturne promjene kao što je gubitak mrežničnog sloja živčanih vlakana mogu otkriti prije nego što nastupi oštećenje vidnog polja. Cilj rada je bio analizirati debljinu sloja živčanih niti i promjene u vidnom polju u skupinama ispitanika s jednostranim i obostranim eksfolijativnim sindromom i obostranim eksfolijativnim glaukomom te ih usporediti s kontrolnom skupinom. Kod 114 ispitanika (228 očiju) podijeljenih u 4 skupine prema prisutnosti eksfolijacije: 30 ispitanika s jednostranim sindromom (30 s klinički vidljivim sindromom i 30 pratećih očiju), 24 ispitanika (48 očiju) s obostranim eksfolijativnim sindromom, 28 (56 očiju) ispitanika s obostranim glaukomom i 32 ispitanika u kontrolnoj skupini učinjeno je vidno polje i mjerenje debljine živčanog sloja mrežnice nakon oftalmološkog pregleda. Oba su oka jednostranog eksfolijativnog sindroma (klinički vidljivog i kod pratećih očiju) pokazala pozitivnu korelaciju između srednjeg defekta i pokazatelja lokaliziranog defekta vidnog polja te srednjeg defekta i donjeg kvadranta debljine mrežničnog sloja živčanih niti. U obostranom eksfolijativnom sindromu i obostranom glaukomu postojala je negativna korelacija između srednjeg defekta vidnog polja i debljine živčanih niti donjeg kvadranta. U obostranom eksfolijativnom sindromu postojalo je stanjenje mrežničnog sloja živčanih stanica donjeg kvadranta u odnosu na ispitanike s jednostranim eksfolijativnim sindromom (u oba oka). Prosječna debljina živčanog sloja mrežnice bila je u negativnoj korelaciji s prosječnim defektom vidnog polja u obostranom eksfolijativnom glaukomu i obostranom sindromu. U zaključku, strukturne promjene prije pojave oštećenja vidnog polja imaju značajnu ulogu u ranom otkrivanju glaukoma kod osoba koje spadaju u rizičnu skupinu

Biocatalytic synthesis of 4-ketopimelic acid

U današnje vrijeme sve se više pažnje u industriji posvećuje održivom razvoju. Primjer toga su strože regulacije emisije ugljikovoga dioksida kao i postroživanje regulacija kemijske industrije. Sve se više ulaže u razvitak industrijskih procesa koji su u skladu s prirodom kao što su na primjer biokatalički procesi. Nagli razvoj upotrebe enzima i biokatalize je već prisutan i očekuje se da će se ubrzati u daljnjoj budućnosti. U ovom radu je dan pregled što su to enzimi, koje su njihove prednosti i nedostatci te koji su izazovi za njihovo korištenje u industriji. Iznesene su suvremene metode koje se trenutno koriste za poboljšavanje svojstava enzima, a time i za proces biokatalize. Također je dan pregled upotrebe enzima u industriji te su spomenuti konkretni primjeri biokatalitičke sinteze s naglaskom na enzim MenD koji katalizira reakciju između akrilne kiseline i α-ketoglutarata pri čemu nastaje 4-ketopimelična kiselina. Ova reakcija predstavlja zanimljiv novi način za sintezu 4-ketopimelične kiseline koja ima primjenu kao gradivni blok. Akrilna kiselina je nefiziološki supstrat enzima MenD te je i iz tog razloga ova reakcija zanimljiva za proučavanje.In recent times a trend in which the world industry is going towards a more sustainable development can be seen. As an example of that there are stricter regulations of carbon dioxide emissions and stricter regulations in the chemical industry. More resources are devoted into processes that are in tune with nature such as the biocatalytic processes. A rapid development of the use of enzymes and biocatalysis can already be seen and it is expected to develop at an even faster pace in the near future. In this work, the definition of enzymes is given, along with their advantages and disadvantages. The challenges of their use in industry is reviewed. Methods that are currently being used for the improvement of enzymes and the process of biocatalysis are also studied. An overview of the use of enzymes in industry and specific examples of the use of biocatalytic synthesis with an emphasis on the enzyme MenD which catalyzes the reaction between acrylic acid and α-ketoglutarate in which 4-ketopimelic acid is given. This reaction presents an interesting new way of synthesis of 4-ketopimelic acid which is used as a building block for more complex molecules. Acrylic acid is a non-physiological substrate of the enzyme MenD and for that reason this reaction is interesting

Biocatalytic synthesis of 4-ketopimelic acid

U današnje vrijeme sve se više pažnje u industriji posvećuje održivom razvoju. Primjer toga su strože regulacije emisije ugljikovoga dioksida kao i postroživanje regulacija kemijske industrije. Sve se više ulaže u razvitak industrijskih procesa koji su u skladu s prirodom kao što su na primjer biokatalički procesi. Nagli razvoj upotrebe enzima i biokatalize je već prisutan i očekuje se da će se ubrzati u daljnjoj budućnosti. U ovom radu je dan pregled što su to enzimi, koje su njihove prednosti i nedostatci te koji su izazovi za njihovo korištenje u industriji. Iznesene su suvremene metode koje se trenutno koriste za poboljšavanje svojstava enzima, a time i za proces biokatalize. Također je dan pregled upotrebe enzima u industriji te su spomenuti konkretni primjeri biokatalitičke sinteze s naglaskom na enzim MenD koji katalizira reakciju između akrilne kiseline i α-ketoglutarata pri čemu nastaje 4-ketopimelična kiselina. Ova reakcija predstavlja zanimljiv novi način za sintezu 4-ketopimelične kiseline koja ima primjenu kao gradivni blok. Akrilna kiselina je nefiziološki supstrat enzima MenD te je i iz tog razloga ova reakcija zanimljiva za proučavanje.In recent times a trend in which the world industry is going towards a more sustainable development can be seen. As an example of that there are stricter regulations of carbon dioxide emissions and stricter regulations in the chemical industry. More resources are devoted into processes that are in tune with nature such as the biocatalytic processes. A rapid development of the use of enzymes and biocatalysis can already be seen and it is expected to develop at an even faster pace in the near future. In this work, the definition of enzymes is given, along with their advantages and disadvantages. The challenges of their use in industry is reviewed. Methods that are currently being used for the improvement of enzymes and the process of biocatalysis are also studied. An overview of the use of enzymes in industry and specific examples of the use of biocatalytic synthesis with an emphasis on the enzyme MenD which catalyzes the reaction between acrylic acid and α-ketoglutarate in which 4-ketopimelic acid is given. This reaction presents an interesting new way of synthesis of 4-ketopimelic acid which is used as a building block for more complex molecules. Acrylic acid is a non-physiological substrate of the enzyme MenD and for that reason this reaction is interesting

Synthesis and and structural characterization of novel 2-hydroxy substituted benzimidazole and benzothiazole amidines as biologically active compounds

U okviru ovog rada provedena je sinteza novih i potencijalno biološki aktivnih amidino supstituiranih benzimidazola 20-29, amidino supstituiranih N-metil-benzimidazola 30-34 te amidino supstituiranih benzotiazola 37-46. Navedeni spojevi priređeni su klasičnim reakcijama organske sinteze te mikrovalovima potpomognutom sintezom. Amidino supstituirani 1,2-fenilendiamini 8 i 9 kao glavni prekursori za sintezu amidino supstituiranih derivata benzimidazola 20-29 priređeni su u nekoliko sintetskih koraka iz 4-aminobenzonitrila 1. Acetiliranjem, a zatim nitriranjem 4-aminobenzonitrila 1 priređen je 4-amino-3-nitrobenzonitril 4. Pinnerovom reakcijom 4-amino-3-nitrobenzonitrila 4 u kiselom mediju, a zatim katalitičkim hidrogeniranjem dobivenog spoja 6 i 7 priređeni su ciljani prekursori 8 i 9. 4-(2-imidazolinil)-N-metil-1,2-fenilendiamin 14 kao glavni prekursor za sintezu N-metil-benzimidazola 30-34, priređen je iz 4-klor-3-nitrobenzonitrila 10. Reakcijom aminacije priređen je 4-N-metilamino-3-nitrobenzonitril 11 iz kojeg je Pinnerovom reakcijom u kiselom mediju, a zatim kataličkim hidrogeniranjem priređen ciljani prekursor 14. Ciljani spojevi 20-29 i 30-34 priređeni su reakcijom kondenzacije njihovih prekursora 8, 9 ili 11 s odgovarajućim aldehidima 15-19 uz prisustvo p-benzokinona kao oksidansa. Amidino supstituirani benzotiazoli 37-46 priređeni su reakcijom kondenzacije amidino supstituiranih benzentiolata 35 ili 36 i odgovarajućih aldehida 15-19. Ciljani spojevi priređeni su u obliku slobodne baze te su s HCl-om u vodenom mediju prevedeni u njihove hidroklorne soli. Strukture svih priređenih spojeva potvrđene su 1H i 13C NMR spektroskopijom. Tijek Pinnerovih reakcija kod priprave amidino supstituiranih prekursora, praćen je IR spektroskopijom. Svim priređenim derivatima ispitana je antiproliferativna aktivnost in vitro na osam staničnih linija humanih karcinoma. Svi ispitani spojevi pokazali su umjerenu do jaku aktivnost. Najizraženiju aktivnost pokazao je derivat benzotiazola 45 supstituiran fluorom i nesupstituiranim amidinom.This work presents the synthesis and spectroscopic caracterization of novel and potentially biologially active amidine substituted benzimidazoles 20-29, amidine substituted N-methyl-benzimidazoles 30-34 and amidine substituted benzothiazoles 37-46. These compounds were prepared by classical methods of organic synthesis and by microwave assisted reactions. Amidine substituted 1,2-phenylenediamines 8 and 9 as main precursors for the synthesis of amidine substituted benzimidazoles 20-29, were prepared in several synthetic steps starting from 4-aminobenzonitrile 1. 4-amino-3-nitrobenzotrile 4 was prepared by acetylation followed by nitration of aminobenzonitrile 1. Precursors 8 i 9 were prepared by Pinner reaction from 4-amino-3-nitrobenzotrile 4 in acidic solution, which first gave compounds 6 and 7 that were then catalytically hydrogenated to the targeted precursors. 4-(2-imidazolinyl)-N-methyl-1,2-phenylenediamine 14 as a main precursor for the synthesis of N-methyl-benzimidazoles 30-34 was prepared starting from 4-chloro-3-nitrobenzonitrile 10. By microwave assisted amination of compound 10, 4-N-methylamino-3-nitrobenzonitrile 11 was obtained, which gave by Pinner reaction and catalytic hidrogenation the targeted compound 14. Amidino substituted benzimidazoles 20-29 and 30-34 were prepared by condensation of 8, 9 or 11 with the corresponding aldehydes 15-19 using p-benzoquinone as an oxidant. Amidine substituted benzothiazoles 37-46 were prepared by condensation of amidine substituted benzenthiolates 35 or 36 with corresponding aldehydes 15-19. The targeted compounds were obtained as free bases which were then converted into hydrochloric salts with HCl in aqueous solution. The structures of all prepared compounds were confirmed by 1H and 13C NMR spectroscopy. The Pinner reaction in the preparation of amidino substituited precursors was monitored by IR spectroscopy. All prepared compounds were tested for their antiproliferative activity in vitro on eight human cancer cells. Tested compounds showed moderate to strong activity. The most significant activity was displayed by benzothiazole derivative substituted with fluorine and unsubstituted amidine group 45