Association of maternal pancreatic function and foetal growth in rats treated with DFU, a selective cyclooxygenase-2 inhibitor

Constitutive (COX-1) and inducible (COX-2) cyclooxygenase isoforms have been detected in various mammalian tissues. Their activity is blocked by non-steroidal anti-inflammatory drugs that may induce various side reactions. The aim of the study was to evaluate the effects of DFU, a selective COX-2 inhibitor, on exocrine and endocrine pancreatic function and the immunoexpression of both COX isoforms in maternal and foetal rat pancreases. The compound was administered to pregnant Wistar rats once daily from the 8th to the 21st day of gestation. Glucose level and amylase activity were determined in the maternal sera. Maternal and foetal pancreases were examined histologically. Immunoexpression of COX-1 and COX-2 was also evaluated. Both biochemical parameters, as well as the histological structure of the pancreas were undisturbed in the dams and their foetuses. The maternal glucose level was found to be an important factor for foetal growth. Strong cytoplasmic COX-1 immunostaining was observed in acinar secretory cells, whereas in islets the immune reaction was weak. Endocrine cells also revealed strong cytoplasmic COX-2 staining in the maternal and foetal pancreases. Acinar cells exhibited nuclear reaction, which was strong in the foetal but weak in the maternal pancreases. No differences in COX immunoexpression were found between the DFU-exposed and the control groups in either mothers or foetuses. It should be stressed that DFU administered throughout mid and late pregnancy in rats did not change maternal or foetal pancreatic morphology or immunoexpression of either of the main COX isoforms in the organ

242. Analiza ekspresji EGFR i angiogenezv w utkaniu niedrobnokomórkowego raka płuc oraz związku z czasem przeżycia pacjentów w stadiach zaawansowania klinicznego I-IIIA

Cel pracyWciąż niezadowalające wskaźniki przeżycia pacjentów z rakiem płuca, mimo radykalnego leczenia operacyjnego, skłaniają do poszukiwań nowych czynników prognostycznych. Wiadomym jest, że receptor naskórkowego czynnika wzrostu (EGFR) wpływa na wzrost komórek guza i jego progresję, jak również tworzenie przerzutów – głównie poprzez oddziaływanie na tworzenie nowych naczyń krwionośnych. Jego prognostyczna rola u pacjentów z niedrobnokomórkowym rakiem płuca (NRP) jest niejasna. Natomiast gęstość naczyń krwionośnych (GNK), będąca miernikiem angiogenezy w guzie, jest podawana jako marker prognostyczny w wielu nowotworach. Celem naszego badania była ocena zależności między ekspresją EGFR i GNK w utkaniu guza nowotworowego a przeżyciem pacjentów z NRP.Materiał i metodyBadaniem objęto 75 pacjentów z NRP w stadiach zaawansowania klinicznego I-IIIA. Wycinki z guza pobierano z materiału operacyjnego, utrwalonego w formalinie. Na uzyskanych skrawkach parafinowych wykonywano odczyny immunohistochemiczne z zastosowaniem monoklonalnego przeciwciała przeciw receptorowi naskórkowego czynnika wzrostu oraz monoklonalnego przeciwciała przeciw CD31.WynikiWśród 75 pacjentów było 5 kobiet (6.7%) i 70 mężczyzn (93.3%) w wieku od 42 lat do 74 lat (średnio 59 lat). W badanej grupie chorych stwierdzono raka płaskonabłonkowego u 53 pacjentów (70.7%), gruczolakoraka u 11 chorych (14.7%) i raka wielkokomórkowego także u 11 pacjentów. Analizując uzyskane dane nie stwierdzono istotności statystycznej między ekspresją EGFR i czasem przeżycia pacjentów. Również GNK nie miała istotnego wpływu na przeżycie pacjentów. Jedynie stan węzłów chłonnych (cecha N; p<0.05), typ histologiczny raka (p<0.001) oraz wiek (p<0.05) w badanej grupie chorych miały istotny statystycznie wpływ na czas przeżycia.WnioskiUzyskane w tym badaniu wyniki nie są zgodne z wynikami innych doniesień mówiących o tym, że ekspresja EGFR i GNK w NRP mogą być traktowane jako czynniki prognostyczne. Należy jednak podkreślić, że analizowana grupa pacjentów była mała, a większość chorych (59 pacjentów, 78.7%) znajdowała się w stadium znacznego zaawansowania nowotworu

Immunoexpression of constitutive and inducible cyclo-oxygenase isoforms in the rat foetal and maternal digestive tract

Cyclo-oxygenase (COX), which catalyses the conversion of arachidonic acid to prostaglandin endoperoxide and prostanoids, is widely expressed in mammalian organs. The aim of the study was to evaluate the immunoexpression of the constitutive and inducible cyclo-oxygenase isoforms (COX-1 and COX-2 respectively) in the oesophagus, stomach and the small and large bowels of untreated rat dams and foetuses on gestational day 21. The localisation of the COX isoforms was similar in the maternal and foetal organs, although the intensity of the reaction for COX-2 was stronger in the foetuses. Cytoplasmic COX-1 immunostaining was found in myocytes of the muscularis propria, muscularis mucosae and the blood vessels. It was also positive in the endothelial cells, scattered stromal cells of the lamina propria and the ganglion cells of the nerve plexus in the bowels. Apart from the keratinised layer, a strong reaction was revealed in the stratified squamous epithelium of the oesophagus and forestomach. Negative or weakly positive staining was found in the mucus-secreting cells covering the surface, gastric pits and pyloric glands, as well as in the parietal cells and the chief cells. Weakly positive COX-1 immunostaining was observed in epithelial cells of the small intestine crypts, but in some cases enterocytes and goblet cells covering villi were also positive. In the colonic mucosa weak COX-1 staining was typical of the absorptive, and goblet cells. The COX-2 immunostaining was nuclear and/or cytoplasmic. An inconsistent positive reaction was seen in the muscle of the muscularis mucosae, muscularis propria and the blood vessels. Positive staining was also found in scattered stromal cells of the lamina propria and adventitia and the ganglion cells. Weak nuclear staining was found in the stratified squamous epithelium of the oesophagus and forestomach. Unlike the strong foetal reactivity in the epithelial cells of the glandular stomach, a negative or weakly positive reaction was seen in the maternal parietal and/or mucous-secreting surface stomach cells. Some epithelial cells of the crypts both in the small and large bowel were also COX-2 positive. In conclusion, constitutive and inducible COX isoforms were detected in the digestive tract of pregnant female and in foetuses. COX-1 was the predominant isoform in both the adult and foetal organs. (Folia Morphol 2008; 67: 24-31)

Morphological studies in modern teratological investigations

Despite the variety of modern molecular techniques available, examination of foetal anatomy is still a fundamental part of teratological studies in evaluating the developmental toxicity of xenobiotics or other non-chemical factors. The article presents contemporary methods of embryotoxicity and foetotoxicity assessment. A single alizarin red S and double alcian blue followed by alizarin red S staining, as well as various methods of soft tissue examination are discussed