Stomatološko liječenje kod osteogenesis imperfecta

Osteogenesis imperfecta is a very rare heterogeneous genetic disorder associated with the development of connective tissue resulting in fragile bones and frequent fractures. More than 50% of patients aff ected with osteogenesis imperfecta have a hereditary developmental disorder known as dentinogenesis imperfecta. Dentinogenesis imperfecta is caused by irregularities in the formation, composition and organization of dentin matrix during tooth development. It is caused by mutations of the genes that encode basic proteins of the organic matrix, collagens and phosphoproteins. The purpose of this review is to describe the histopathologic and clinical features of teeth typical of dentinogenesis imperfecta type I, which occurs within osteogenesis imperfecta, with special emphasis on targeted dental treatment to achieve optimal rehabilitation of the masticatory system.Osteogenesis imperfecta je vrlo rijetka heterogena genetička bolest udružena s razvojem vezivnog tkiva, što rezultira krhkim kostima i čestim prijelomima. Više od 50% bolesnika s osteogenesis imperfecta ima nasljedni razvojni poremećaj poznat kao dentinogenesis imperfecta. Dentinogenesis imperfecta je uzrokovana nepravilnostima u stvaranju, sastavu i organizaciji zubnog matriksa tijekom razvoja zuba. Uzrokuju ju mutacije gena koji kodiraju osnovne bjelančevine organskog matriksa, kolagena i fosfoproteina. Namjera ovog pregleda je opisati histopatološka i klinička obilježja zubiju koja su tipična za dentinogenesis imperfecta tip I koji se javlja u sklopu osteogenesis imperfecta, s naglaskom na ciljano stomatološko liječenje kako bi se postigla optimalna rehabilitacija žvačnoga sustava

Development of suitable working Protocol for in vitro Tape Stripping: A Case Study with biocompatible Aceclofenac-loaded topical Nanoemulsions

Considering the numerous organizational and legislative issues associated with in vivo studies, the present study aimed to develop in vitro tape stripping protocol that could serve as a prospective technique for skin penetration studies. The research was mainly focused on the suitability of transepidermal water loss (TEWL) measurements, as a barrier integrity test for porcine ear skin subjected to freezing/thawing procedure, as well as on the selection of the most suitable device for pressing adhesive tapes onto the porcine ear surface during skin stripping procedure. Obtained results suggest that TEWL measurements were able to detect the damage of the stratum corneum (SC) caused by physical impairment (using adhesive tapes) and tissue degradation/dehydration (prolonged storage at –20ºC/ambient conditions). Penetration profiles of aceclofenac from nanoemulsions based on sucrose esters or polysorbate 80 as coemulsifiers, obtained in vitro (using a roller as pressure device), were in a good agreement with data obtained in vivo on humans, supporting the use of developed in vitro tape-stripping protocol in skin formulation development and optimization

Expression of gap junction protein, connexin 43, in primary and metastatic non-small cell lung carcinomas

direktnu komunikaciju između susednih ćelija i između ćelija i matriksa, što je značajno u ćelijskom rastu i diferencijaciji. Međutim, uloga koneksina 43 u nastanku i progresiji tumora je kontradiktorna. Posebno su oskudni podaci o ekspresiji i značaju koneksina 43 u karcinomima pluća. Ciljevi: Ciljevi ovog istraživanja su bili da se ispitaju ekspresija i razlika u ekspresiji koneksina 43 u različitim histopatološkim tipovima nesitnoćelijskog karcinoma pluća; da se ispita ekspresija koneksina 43 u invazivnom tumorskom frontu i centralnom delu tumora kod primarnog nesitnoćelijskog karcinoma pluća; da se utvrdi povezanost ekspresije koneksina 43 sa markerima epitelnomezenhimne tranzicije kod nesitnoćelijskog karcinoma pluća; i da se ispitaju razlike u ekspresiji koneksina 43 između primarnog nesitnoćelijskog karcinoma pluća i njegovih limfogenih i hematogenih metastaza. Metode: U ovom istraživanju korišćene su dve grupe uzoraka. Prvu grupu su činili parafinski kalupi tkivnih uzoraka hirurških resekcija 88 pacijenata (45 muških i 43 ženskih; 61,9±7,4 godina) sa nesitnoćelijskim karcinomom pluća (52 adenokarcinoma i 36 skvamoznih karcinoma) sa pripadajućim limfnim čvorovima operisanih u Kliničko-bolničkom centru „Bežanijska kosa“ u Beogradu u periodu između 2012. i 2016. godine. Drugu grupu su činili parafinski kalupi tkivnih uzoraka primarnog nesitnoćelijskog karcinoma pluća (19 adenokarcinoma i 10 skvamoznih karcinoma) kao i prisutnih limfogenih i hematogenih metastaza dobijenih sa obdukcija 29 osoba (18 muških i 11 ženskih; 68,8±10,1 godina) obdukovanih na Institutu za patologiju Medicinskog fakulteta u Beogradu u periodu između 2016. i 2020. godine. Ispitivana je imunohistohemijska ekspresija koneksina 43 kao i markera epitelnomezenhimne tranzicije kod adenokarcinoma i skvamoznog karcinoma pluća, u zoni invazivnog tumorskog fronta i centralnoj zoni tumora, kao i u metastazama. Za bojenje i analizu su korišćeni celi preseci kao i tkivni mikroniz. Rezultati: Analiza ekspresije koneksina 43 u nesitnoćelijskim karcinomima pluća je pokazala da i skvamozni karcinom i adenokarcinom mogu da eksprimiraju koneksin 43. Međutim, skvamozni karcinom je pokazao značajno veći stepen ekspresije kao i veći intenzitet ekspresije koneksina 43 u odnosu na adenokarcinom (p<0,05). Ekspresija koneksina 43 u nesitnoćelijskim karcinomima pluća je često aberantna po lokalizaciji, tj. koneksin 43 je eksprimiran u citoplazmi ili čak u jedru. Pored izolovane membranske, citoplazmatske, i nuklearne ekspresije, bili su prisutni i slučajevi kombinovane, uglavnom membranskocitoplazmatske ekspresije. Lokalizacija ekspresije koneksina 43 kod skvamoznih karcinoma je najčešće bila kombinovana, dok je kod adenokarcinoma podjednako često bila čisto citoplazmatska i kombinovana (p<0,05). Analiza ekspresije koneksina 43 u nesitnoćelijskim karcinomima pluća je pokazala da i invazivni front i centralni deo tumora često eksprimiraju koneksin 43, ali nije nađena statistički značajna razlika u ekspresiji koneksina 43 između ovih delova tumora. Ekspresija koneksina 43 je korelirala sa ekspresijom markera epitelnomezenhimne tranzicije kod nesitnoćelijskog karcinoma pluća, ali su uočeni različiti obrasci korelacije između adenokarcinoma i skvamoznog karcinoma...Background: Connexin 43, the protein that forms gap junctions and hemichannels, allows direct communication between neighboring cells and between cells and the matrix, which is important in cell growth and differentiation. However, the role of connexin 43 in tumor development and progression is still purely understood and contradictory. Data on the expression and significance of connexin 43 in lung cancer are particularly scarce. Objectives: The objectives of this study were to examine the expression and difference in the expression of connexin 43 in different histopathological types of non-small cell lung cancer; to examine the expression of connexin 43 in the invasive tumor front and central part of the tumor in primary non-small cell lung cancer; to determine the association of the expression of connexin 43 with markers of epithelial mesenchymal transition in non-small cell lung cancer; and to examine differences in the expression of connexin 43 between primary non-small cell lung cancer and its lymphogenic and hematogenous metastases. Methods: Two groups of samples were used in this study. The first group consisted of paraffin blocks of tissue samples of surgical resections of 88 patients (45 male and 43 female; 61.9 ± 7.4 years) with non-small cell lung cancer (52 adenocarcinomas and 36 squamous cell carcinomas) with corresponding lymph nodes, who were operated at the University Hospital "Bežanijska kosa" in Belgrade in the period between 2012 and 2016. The second group consisted of paraffin blocks of tissue samples of primary non-small cell lung cancer (19 adenocarcinomas and 10 squamous cell carcinomas) as well as lymphogenic and hematogenous metastases obtained from autopsies of 29 individuals (18 male and 11 female; 68.8 ± 10.1 years) at the Institute of Pathology, Faculty of Medicine in Belgrade in the period between 2016 and 2020. We analyzed the immunohistochemical expression of connexin 43 and markers of epithelial–mesenchymal transition in adenocarcinoma and squamous cell carcinoma of the lungs, in the zone of invasive tumor front and central zone of tumor as well as in metastases. Entire sections and tissue microarrays were used for staining and analysis. Results: Analysis of connexin 43 expression in non-small cell lung carcinomas showed that both squamous cell carcinoma and adenocarcinoma can express connexin 43. However, squamous cell carcinoma showed a significantly higher degree of expression as well as a higher intensity of connexin 43 expression compared to adenocarcinoma (p<0.05). The expression of connexin 43 in non-small cell lung cancer is often aberrant by localization, i.e., connexin 43 is expressed in the cytoplasm or even in the nucleus. In addition to isolated membranous, cytoplasmic, and nuclear expression, there were cases of combined, mostly membranous–cytoplasmic expression. The localization of connexin 43 expression in squamous cell carcinomas was most often combined, while in adenocarcinomas it was equally often purely cytoplasmic and combined. Analysis of the expression of connexin 43 in non-small cell lung cancer showed that both the invasive front and the central part of the tumor often express connexin 43, but no statistically significant difference in the expression of connexin 43 was found between these parts of the tumor. The expression of connexin 43 correlated with the expression of markers of epithelial–mesenchymal transition in non-small cell lung cancer, but different patterns of correlation were observed between adenocarcinoma and squamous cell carcinoma..

The implications of regulatory framework for topical semisolid drug products: From critical quality and performance attributes towards establishing bioequivalence

Due to complex interdependent relationships affecting their microstructure, topical semisolid drug formulations face unique obstacles to the development of generics compared to other drug products. Traditionally, establishing bioequivalence is based on comparative clinical trials, which are expensive and often associated with high degrees of variability and low sensitivity in detecting formulation differences. To address this issue, leading regulatory agencies have aimed to advance guidelines relevant to topical generics, ultimately accepting different non-clinical, in vitro/in vivo surrogate methods for topical bioequivalence assessment. Unfortunately, according to both industry and academia stakeholders, these efforts are far from flawless, and often upsurge the potential for result variability and a number of other failure modes. This paper offers a comprehensive review of the literature focused on amending regulatory positions concerning the demonstration of (i) extended pharmaceutical equivalence and (ii) equivalence with respect to the efficacy of topical semisolids. The proposed corrective measures are disclosed and critically discussed, as they span from mere demands to widen the acceptance range (e.g., from 10% to 20%/25% for rheology and in vitro release parameters highly prone to batch-to-batch variability) or reassess the optimal number of samples required to reach the desired statistical power, but also rely on specific data modeling or novel statistical approaches

Towards optimal ph of the skin and topical formulations: From the current state of the art to tailored products

Acidic pH of the skin surface has been recognized as a regulating factor for the maintenance of the stratum corneum homeostasis and barrier permeability. The most important functions of acidic pH seem to be related to the keratinocyte differentiation process, the formation and function of epidermal lipids and the corneocyte lipid envelope, the maintenance of the skin microbiome and, consequently, skin disturbances and diseases. As acknowledged extrinsic factors that affect skin pH, topically applied products could contribute to skin health maintenance via skin pH value control. The obtained knowledge on skins’ pH could be used in the formulation of more effective topical products, which would add to the development of the so-called products ‘for skin health maintenance’. There is a high level of agreement that topical products should be acidified and possess pH in the range of 4 to 6. However, formulators, dermatologists and consumers would benefit from some more precise guidance concerning favorable products pH values and the selection of cosmetic ingredients which could be responsible for acidification, together with a more extensive understanding of the mechanisms underlaying the process of skin acidification by topical products

Sub testu: preparation of Roman food under a clay dome

Among the multitude of ceramic fragments, there occasionally appear handles of unusual shapes, or the remains of large dome-shaped lids. Such vessels were used for food preparation in kitchens with open hearths. Ever since prehistory, they have represented a kitchen appliance in daily use to the present day, and they appear in Roman kitchens as well. Various sources refer to this method of food preparation as sub testu. These vessels’ segments have also been archaeologically confirmed on Roman sites in Pannonia Inferior and Moesia Superior. There is a type of dish called patina in Roman cuisine, similar to modern-day souffle, which was presumably prepared on plates with a flat bottom and curved, convex, or concave walls

A comparison of Myribase and Doublebase gel: Does qualitative similarity of emollient products imply their direct interchangeability in everyday practice?

Emollients are acknowledged as a part of standard care in therapeutic and prevention protocols as well as a part of everyday skin care routine. When it comes to making a final decision between two emollient products, the ingredient list, that is, the formulation composition could be the determining factor. In such cases the consumer, and some healthcare providers, believe that products with the same qualitative composition (ingredient list) must have the same efficacy. In this study, we have investigated the skin hydration performance of two emollient preparations (DBG and MBG), which appear to contain the same ingredients, and hence, could be considered interchangeable in everyday practice. Our studies showed that the effects of DBG were overall superior to the ones attributed to MBG at each investigated time point (1, 2, 4, and 24 h post application) when tested on normal and dry skin. Consequently, it is shown that two apparently qualitatively identical products do not necessarily provide matching efficacy

Expression of small heat shock proteins and heat tolerance in potato (Solanum tuberosum L.)

We have examined the correlation between heat tolerance and small heat shock protein (sHSP) expression under heat stress conditions in potato (Solanum tuberosum L.). The relative heat tolerance of nine potato cultivars grown under greenhouse conditions was determined using the electrolyte leakage assay (ELA), a standard quantitative assay for heat tolerance. Three cultivars differing in heat tolerance were selected and designated as heat-tolerant (‘Laura’), moderately sensitive (‘Liseta’) and heat-sensitive (‘Agria’) genotypes. The expression of cytosolic HSP18 and chloroplast HSP21 was analyzed at the protein level in the leaves of selected cultivars, both ex vitro- and in vitro-grown, after heat stress or control treatment. Immunoblot analysis revealed heat-induced HSP18 and HSP21 expression in all examined genotypes. A similar pattern of examined sHSP expression was observed ex vitro and in vitro: heat-tolerant ‘Laura’ accumulated higher levels of both HSP18 and HSP21 compared to heat-sensitive ‘Liseta’ and ‘Agria’. Our results indicate that ELA combined with immunoblot analysis of sHSP accumulation under HS conditions, might be considered as a reliable procedure in screening potato genotypes for heat tolerance. To our knowledge, this is the first study where sHSP expression between ex vitro- and in vitro-grown potato plants was compared