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The foramen magnum is an important anatomical opening in the base of the skull through which the posterior cranial fossa communicates with the vertebral canal. It is also related to a number of pathological conditions including Chiari malformations, various tumours, and occipital dysplasias. The aim of the study was to evaluate the morphology of the foramen magnum in adult individuals in relation to sex.The morphology of the foramen magnum was evaluated using 3D computer tomography images in 313 individuals (142 male, 171 female) aged 20-30 years.The mean values of the foramen length (37.06 ± 3.07 vs. 35.47 ± 2.60 mm), breadth (32.98 ± 2.78 vs. 30.95 ± 2.71 mm) and area (877.40 ± 131.64 vs. 781.57 ± 93.74 mm2) were significantly higher in males than in females. A significant, positive correlation was found between foramen length and breadth. Significant correlations were reported for breadth and area of the foramen magnum and corresponding external cranial diameters in females. Round as well as longitudinal and horizontal oval-like types of the foramen shape were established according to the breadth/length index of the structure. All the cranial and foramen measurements were significantly higher in individuals with round-like type of the foramen magnum.There was a sexual dimorphism of the foramen magnum among the examined individuals. It was related mainly to its linear diameters and area, not to the shape. Unlike males, female skulls had higher correlation between the examined parameters of the foramen and proper external cranial measurements, which indicates more homogeneous growth in girls.

The aim of the study was to present the classification of anatomical variants of the operated stomach, based on radiological and historical data. Different anatomical variants of the operated organ were found in 431 out of 2034 patients examined in the years 2006-2010. Four main groups were established: abnormal position along longitudinal (I) and horizontal axis (II), as well as abnormal shape (III) and stomach connections (IV). An additional group (V) encloses mixed forms that combine features of two or more of the main groups. The first group contains the partial and total translocation of the stomach into the thoracic cavity after the partial or total oesophagectomy. Depending on the applied surgical techniques used during the total oesophagectomy, the stomach could be located anteriorly or posteriorly to the pericardial sac. An elongated and gastrectatic form often with signs of pylorostenosis is visible in patients treated by vagotomy. The consequences of fundoplication included: lack of or narrow cardiac angle, and often a mild form of stomach cascade. The most common abnormal shape of the stomach was secondary to gastrectomy and gastric bending. The final organ shape depends on the type of applied surgical procedure that maintains physiological connection with the duodenum or an un-anatomical one, mostly with the jejunal loop. In banding, the body of the stomach forms an hourglass at the level of the artificial adjustable band, typically applied in surgical treatment of obesity (slim surgery).

A case of accessory spleen located in the tail of the pancreas in a stillbirth male foetus is reported. The congenital anomaly was revealed at autopsy. The intrapancreatic spleen was well demarcated and was composed of red and white pulp; however, same pancreatic ducts were intermingled with the splenic parenchyma. As well as the intrapancreatic lesion another minute accessory spleen was also found at the hilum of the proper organ. Since a lack of morphological features of trisomy 13 syndrome were found in the foetus, the ectopic spleens were regarded as incidental findings.

The aim of the study was the retrospective morphological analysis of selected structures of the middle cranial fossa, i.e. foramen ovale and superior orbital fissure, in relation to the external head and cranial diameters in adults from the Lublin region (Poland). The study was performed on data collected during computed tomography examinations of 60 individuals (age 20-30 years), without any cranial or brain abnormalities. Based on the post-processing reconstructions, 3-dimensional views of the skull and head were obtained. The length and width of both structures, as well as thickness of the frontal, temporal, and occipital squamae, were measured. The morphology of the ovale foramina and superior orbital fissures were checked. The length and width of the skull and head were the only parameters that significantly differed between males and females. The thickness of the frontal and temporal squama was insignificantly lower in males than in females. Almond and oval shapes were the most typical for the foramen ovale. The superior orbital fissure was found as a wide form - with or without accessory spine originating from its lower margin or as a laterally narrowed form. The length and width of the foramen ovale were insignificantly higher in males than in females. The same results were found for the area of the right superior orbital fissure. The thickness of the frontal and occipital squamae influenced the thickness of the temporal squama. The analysed individuals had asymmetrical, oval, or almond-shape ovale foramina. Unlike the seldom visible laterally narrowed form of the superior orbital fissure, a wide form with or without accessory spine was the most commonly observed. The diameters of both superior orbital fissures and ovale foramina indicated the asymmetry of the neurocranium.

Sebaceous glands have been extremely rare findings in the female genital system. Excluding the vulva and recent findings, very few cases have been described. The origin of the lesions remains a topic of speculation. However, it appears that prolonged irritation induces a metaplastic response in the ectocervical epithelium. A new case of sebaceous glands in the ectocervix of a 46-year-old woman is reported. The lesions were unexpectedly found in a hysterectomy specimen. The procedure was carried out for multiple leiomyomas of the uterine corpus. Histological examination revealed three mature sebaceous glands located distally to the transformation zone, which opened directly onto the surface epithelium. It could be concluded that sebaceous glands in the ectocervix are rare lesions of unclear origin and low clinical significance. However, the glands could potentially be associated with sebaceous carcinoma of that anatomical site.

Breast neoplasm may develop in ectopically located glandular tissue. This paper presents an interesting and rare case of a 50-year-old female who despite regular mammography screening examination developed an invasive accessory breast cancer. Clinical examination revealed a 2 cm – tumour localized 4 cm below the left inframammary fold. The lesion was immobile, the skin and the atrophic nipple were retracted, the tumour infiltrated the thoracic wall. Oligobiopsy and additional examinations showed an invasive stage IIIB ductal breast cancer (Bloom II, G-2). The receptor status was: ER(+), PGR(+), HER2(-). The increased level of cancer antigen 15.3 was found. The patient was submitted to pre-operative chemotherapy. She also underwent surgery and subsequently post-operative chemotherapy and radiotherapy. On the basis of the presented case, it could be concluded that the accessory mammary glands are out of the image of screening breast examinations. Accessory breast cancer is usually diagnosed by clinical examination and ultrasonography. Preventive resection of accessory breast in women at high risk of developing breast cancer can be considered as the treatment of choice in most patients.

Joint formation is a developmental process regulated by various factors including bone morphogenetic proteins, transforming and growth factors, etc. Recently, a high expression of cyclooxygenase (COX) isoforms in the foetal cartilaginous elements was also revealed. On the other hand, various joint and skeletal abnormalities were seen in laboratory animal and human offspring, exposed in utero to several COX inhibitors. Immunoexpression of constitutive (COX-1) and inducible (COX-2) cyclooxygenase isoforms was evaluated in various articular structures of untreated and unfamiliar 21-day-old male rat foetuses. Both COX isoforms were detected in the articular cartilage and joint capsule, as well as in the intra-articular disc of the temporomandibular joint and meniscus of the knee joint. COX-1 immunostaining was revealed in the anterior and posterior cruciate ligament of the knee joint and the labrum of the hip and shoulder, whereas COX-2 immunoreactivity in those structures was not found. It could be concluded that both constitutive and inducible COX isoforms are physiologically expressed in various structures of synovial joints in rat foetuses at the end of prenatal development.

The aim of the present study was to examine the morphology of root canals in premolar teeth with completely formed root apices. The material consisted of 139 extracted premolar teeth, including 83 first premolars (59.7%) and 56 second premolars (40.3%). Maxillary teeth made up 64% of the material and mandibular teeth 36%. In order to measure the actual root canal length an endodontic instrument was inserted into the root canal (in teeth with a single root canal this was instrument no. 25 and in teeth with two or three root canals no. 20) until its tip was visible in the anatomical foramen. The silicone limit was fixed at a reference point on the dental crown, and after removal of the instrument the real length was read using an endodontic ruler. The results were presented using descriptive statistical measures (mean, maximum, minimum, median value and quartiles). In order to compare mean values of root canal lengths the z test was used. Of the first maxillary premolars, 91% had two root canals and 9% had three root canals. As far as the second upper premolars are concerned, 14.7% were teeth with single root canals while as many as 85.3% were teeth with two root canals. The majority of the first lower premolars (89.3%) had one root canal and 10.7% of these teeth had two root canals. Most of the second lower premolars (68.2%) had a single root canal, while the remaining 31.8% had two root canals. None of the mandibular premolars examined had three root canals.

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.

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.

Cathepsin D is a cysteine endopeptidase that belongs to the lysosomal enzyme family. The aim of the study was to evaluate the enzyme immunoexpression and activity in selected male genital organs in mature Wistar rats. The activity of cathepsin D was measured spectrophotometrically in homogenates of the testis, epididymis, seminal vesicle and prostate. Immunohistochemical staining was also performed in the ductus deferens. Enzyme activity was found in the following sequence: testisepididymisdorsal prostatic lobeseminal vesiclelateral prostatic lobeventral prostatic lobe. Although there were differences in enzyme activity between various organs of the male reproductive system, cathepsin D immunoreactivity was seen exclusively in the Sertoli and Leydig cells in the testis.

The progress made in recent years in the diagnostics of breast cancer, the universal character of mammographic and ultrasonographic screening examinations and the growth of social awareness with respect to this disease have caused a great deal of diagnostic problems. Cases of big, ulcerating cancer tumours, which infiltrate skin have now become history, and are reported sporadically. However, physicians are now facing the problem, which is the diagnosis of 1-5 mm changes detected in examinations. The necessity to diagnose small tumours in combination with 80-90% mammographic sensitivity reported compelled clinical physicists to verify these changes with histopathological examination. In the cases when the clinical examination, the result of a mammographic examination and that of fine needle aspiration biopsy do not provide a coherent picture, a surgeon has to qualify a patient for tumorectomy with an intra-operative study. In the years 1997-2000, 173 breast tumorectomies were made. Patients with benign neoplasm (e.g. adenofibroma, papilloma mammae) or patients with arousing suspicion of oncological anxiety breast tumour were qualified for surgical procedures. Operations were performed in one-day surgery conditions and intra-operative examination was performed in every case. In cases of non-palpable tumours, which were visible in ultrasonography or mammography the changes were marked by an "anchor" in order to be removed and examined histopathologically. The operated patients were 17-89 years old. In the obtained 173 tissue fragments dysplasia benign was recognized in 47.98% of cases, in 42.2% adenofibroma, in 2.31% papilloma mammae, in 1.73% mastitis chronica, in 4.62% ca ductale invasivum and in 1.16% ca ductale in situ has been observed.

The aim of the study was to evaluate the toxic effect of acetaminophen on rat fetuses. Acetaminophen, suspended in Tween 80 solution, was administered once a day, orally by a stomach tube to pregnant Wistar rats from day 8th to 14th of pregnancy at the dose: 3.5 (P1), 35.0 (P2), 350.0 mg/kg (P3). The pregnant females were terminated on day 21st of pregnancy and the number of corpora lutea, implants, resorptions, and fetuses was counted. The fetuses and the placentas were weighed and the length of the fetuses and their tails were checked. The slides of the fetal liver were examined via light microscopy in four stains: hematoxylin and eosin, silver Gomorii, van Giesson, and periodic acid-Schiff. There was a statistical (p0.05) difference in fetal body length in group P3 without any macroscopic malformation, except for the non-statistical number of subcutaneous ecchymoses. Histological adaptive changes of the fetal liver were observed occasionally in all the studied groups. In conclusion, the oral administration of acetaminophen caused an embryotoxic effect in the highest doses without any macroscopic malformation, and only slightly impaired morphology of the rat fetal liver.

The first laparoscopic cholecystectomy was performed thirteen years ago and rapidly became the preferred way of operation in patients suffering from cholelithiasis. The pneumoperitoneum can be responsible for haemodynamic disorders. The abdominal wall lift is an alternative way for pneumoperitoneum during laparoscopic cholecystectomy. The aim of this study was the comparative analysis of operative trauma response in the patients treated by laparoscopic cholecystectomy using abdominal wall lift and in cases which underwent open cholecystectomy or laparoscopic operation using pneumoperitoneum. The concentration of C-reactive protein was measured in patient serum before and twice after surgery. The obtained data underwent a statistic analysis. In all cases the surgery caused the marked changes of CRP-concentration. The mean level of CRP was higher three times in patients after open cholecystectomy than in cases treated by laparoscopic cholecystectomy with the use of abdominal wall lift or with performed pneumoperitoneum. During the experiment the statistically significant different between laparoscopic surgery with the use of the laparolift and laparoscopic with earlier performed pneumoperitoneum was observed. The stress and inflammatory response in cholecystectomy using abdominal wall lift was significant but smaller than the response noted in open cholecystectomy and similar to the response observed after pneumoperitoneum. The replacement of pneumoperitoneum by abdominal wall lift does not change the operative stress in laparoscopic cholecystectomy.

The aim of this study was to establish and quantify changes in the activities of total, free and bound fractions of pancreatic lipase, galactoso-6-sulphatase, beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase in the course of alloxan-induced diabetes mellitus. Rabbits were divided into a control group and groups injected with alloxan on the 21st, 42nd, 90th and the 180th day, after which blood samples were taken and the rabbits sacrificed by decapitation. The pancreas was removed and the glucose level measured. Enzyme activities were assayed by spectrophotometric methods. The total activities of N-acetyl-beta-D-glucosaminidase and beta-D-galactosidase were the lowest on day 42 of the test, and the total activity of lipase was the highest at this point of time, as compared to the other periods of the study. We conclude that in the course of alloxan-induce diabetes activities of pancreatic lipase and sulphatase were increasing following the levels of glucose, whilst activities of beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase were declining, being inversely correlated to the level of glucose and activities of the first two mentioned enzymes. Above alterations in activity of lysosomal pancreatic enzymes of alloxan induced diabetic rabbits may be responsible for some aspects of previously reported diabetic enteropathy and chronic complications, or may provide a mechanism for the pancreatic beta-cells to moderate their insulin content.

Diverticula of the upper part of the alimentary tract, irrespective of their etiology, are frequently observed benign changes of the pharynx, oesophagus, stomach and duodenum. In the present work, patients of the II General Surgery Department of the Medical University of Lublin, with radiologically or endoscopically proved diverticula of the upper part of the alimentary tract, were examined. The presence of diverticula of such localisation was an indication for supplementary endoscopic or radiological examination. The localisation, size, diameter of the opening, mucosal relief of diverticula and its contiguity were checked and analysed. Our data suggest that both medical procedures are complementary to each other. All previously observed changes in diverticula of the thoracic part of the oesophagus and the infradiaphragm part of the alimentary tract were fully proved. The radiological examination gave a better view of Zenker's diverticulum, especially in short and obese patients. Sampling and better visualisation of the diverticula opening testify to the unquestionable superiority of endoscopy. However, precise evaluation by radiological process fully completes the diagnostic protocol. Both diagnostic procedures are usually supplemented by manometric examination of the oesophagus and superior and inferior oesophageal sphincters. This enables the accurate diverticula etiology to be stated.

Ibuprofen is a non-selective cyclooxygenase (COX) inhibitor with analgesic, antipyretic and antiinflammatory activity. Experimental, clinical and epidemiological studies, led on a wide scale, showed high therapeutically activity and good drug tolerability, especially for low doses in adult and children older then 6 months. Those data let to positioned ibuprofen to over-the-counter (OTC) drugs. However, unlike well-documented tolerability studies of the postnatal period the prenatal data are still unclear. Results of experimental studies showed ibuprofen-dependent: implantation disturbances, blocking of parturition, and contraction of ductus arteriosus what could produce persistent pulmonary hypertension. These data has been partially confirmed in human studies. Lack teratogenic effect was observed in in vivo animal studies. Gastroschisis is the only congenital ibuprofen-related malformation that was proved in big epidemiological human studies. Other congenital anomalies and disturbances, such as oligohydramnion, associated with maternal ibuprofen ingestion, and reported in available literature, have not been established in epidemiological studies.

Acetylsalicylic acid is frequently ingested over-the-counter (OTC) drug, either as single or in combination with other drugs. It has been used in various diseases including that complicated pregnancy, such as preeclampsia and fetal grow retardation. Analgesic, antipyretic, especially anti-inflammatory activity occurs in high therapeutic doses. In low-dose acetylsalicylic acid is used to block production of thromboxane A2. Big epidemiological data suggest that low-dose of acetylsalicylic acid, even taken chronically, is safe for mother and fetus. However, animal and various human data have shown that high doses of the drug could produce different congenital malformations. The current literature suggests that acetylsalicylic acid should be given in pregnancy only if the potential benefit justifies the potential risk to the fetus. Anti-inflammatory doses should be stopped in the third trimester of gestation or given if the drug is needed in life-threatening situation or for serious disease for which safer drugs can not be used or are ineffective.

Background Etanercept interferes with the tumor necrosis factor (TNF) and is widely used in various autoimmune diseases. However, its developmental toxicity has not been fully established. Objectives To analyze the effects of etanercept, new generation biological agent used in the therapy of rheumatoid arthritis, on the selected parameters of rat placenta – both in healthy females and in animals with experimentally induced arthritis. Methods This study included seven groups of Wistar rats: 1) with experimentally induced arthritis (group R), 2-3) with the arthritis treated with etanercept (0.4 or 4.0 mg/kg b.w.; groups RE1 and RE2), 4-5) receiving etanercept despite the lack of arthritis (E1, E2), and 6-7) controls receiving placebo (C1, C2). Female rats were immunized according to the Trentham9s method. The drug (0.4 and 4.0 mg/kg) was subcutaneously injected to animals that exhibited one or higher severity score in the visual system for evaluation of CIA rodent model. After the last injection all the females were inseminated and pregnant animals were kept without any xenobiotics until gestational day 21 when cesarean section was performed. Parallel CIA, etanercept-exposed animals without CIA and untreated (sham operated) females were also examined. Morphological and histological structure of placenta, immunohistochemical reaction of placental homogenates to genes encoding tumor necrosis factor (TNF), cyclooxygenase 1 (COX-1), and proliferating cells nuclear antigen (PCNA), concentration of TNF in placental homogenates, placental expression of interleukin encoding genes: IL1α, IL1β, LTβ, IL6, COX-1, and TNF. Results Concentrations of TNF were significantly higher in placental homogenates from females with experimentally induced arthritis (groups R, RE1, and RE2). On detailed analysis of these three groups, the concentration of examined cytokine proved significantly higher in animals that did not receive etanercept (group R). The only significant intergroup difference in qualitative expression of examined genes pertained to IL1α gene, the presence of which could be observed solely in placentas of rats from group R. Conclusions Experimentally induced arthritis causes inflammatory response within the placenta. This effect is partially reversed by etanercept administration; the application of this agent does not negatively affect placental function and morphology. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5644

The article describes present knowledge of teratogenicity, which final manifestation are functional disorders, growth retardation, fetal carcinogenesis, malformation and death.

Omeprazole is a proton pump inhibitor of increasingly wide application in the treatment of different gastroenterological diseases. The purpose of the study was to evaluate the effect of omeprazole (O) on the level of plasma malondialdehyde (MDA).Omeprazole was administered intraperitoneally to male Wistar rats twice a day, for 3 days, in two doses: O1-0.57 mg/kg body weight (b.w.), O2-5.71 mg/kg b.w. Twelve hours after the last injection half of the animals were terminated (I). The remaining rats were kept for the next 6 weeks without any xenobiotics (II). The blood was taken from the still beating heart and then centrifuged. The plasma level of MDA was determined and compared to the 1 mg of the blood protein.A significant (p0.05) increase of MDA level was found in the O2II group, as compared with the O2I group. The level of MDA was higher after 6 weeks' period in relation to the animals that were terminated on the 4th day of the experiment.Three-day omeprazole administration did not change the MDA level in the rat plasma.

The study evaluates the effect of cimetidine (C), ranitidine (R) and famotidine (F) on the level of the plasma malondialdehyde (MDA). The tested drugs were given intraperitoneally to the male Wistar rats twice a day, during 6 weeks' period, in two doses. CI--2.85 mg/kg body weight (b.w.), R1--0.71 mg/kg b.w., F1--0.28 mg/kg b.w. The second doses (C2, R2, F2) were 10 times higher than C1, R1, F1. At the end of the 6th week of the experiment half of the animals were terminated. The remaining rats were kept for the next 6 weeks without any medications and were killed at the end of 12th week of the experiment. Blood was taken from still beating heart and centrifuged. The level of the MDA was determined from the plasma and compared to the 1 mg of the blood protein. None of administered H2 blockers changed the malondialdehyde level in serum of the experimental rats.

Caffeine is a widespread natural methylaxanthine which easily crosses the placenta. In studies on animals, high doses of caffeine are associated with an embryotoxic effect and an increase in congenital malformations. However, those date have not been fully confirmed in the human. The article presents the current knowledge about the prenatal toxicity of caffeine.

Isopropylantipyrine (IPA, propyphenazone) is a pyrazolone derivative, widely used as an antipyretic and analgesic drug. The aim of the study was to evaluate the influence of propyphenazone on rat development. IPA was administered to pregnant rats from day 8 to day 14 of pregnancy once a day, orally by a stomach tube at doses of 2.10 (R1), 21.0 (R2), and 210.0 mg/kg/day (R3). The dams were sacrificed on day 21 of gestation and corpora luteum, implants, resorptions, and live foetuses were counted. The weight of foetuses and placentas, the length of foetuses and their tails were checked. The foetuses were fixed in alcohol and skeletons were stained with alizarin. There was a statistical difference in body length in R1, R2 and numbers of subcutaneous ecchymose in R1. External and skeletal examination of the foetuses revealed no evidence of teratogenesis. It can be concluded that IPA has no harmful effects on the prenatal development of the rat offspring at doses used in the present study.

Omeprazole is one of the substituted benzimidazoles, which is not free of side effects. The aim of the study was to evaluate the influence of omeprazole therapy on pancreas. Omeprazole was administered intraperitoneally, twice a day, for 3 days to the male rats in 0.571 mg/kg b.w. and 5.71 mg/kg b.w. doses. Half of animals were sacrificed in the 4th day of the experiment. The remaining rats were raised for another 6 weeks, without any xenobiotics, and sacrificed on the 47th day. The activity of acid phosphatase, beta-galactosidase, cathepsin B, and L, lipase, N-acetyl-glucosaminidase, and sulphatase was evaluated. The slides of the pancreas were examined in light microcopy in hematoxylin-eosin, asan, periodic acid-Schiff (paS) stains. Statistical increase in total activities of acid phosphatase, beta-galactosidase, lipase, N-acetyl-glucosaminidase, sulphatase, and acute inflammatory infiltration in peripancreatic fat tissue without histological pancreas impairment, were observed after the higher dose on the 4th day of experiment. Histological picture and enzymatic profiles were normalized during the next 6 weeks. We concluded that intraperitoneal administration of omeprazole causes tissue inflammation in the peripancreatic lipid tissue and reactive elevation of some pancreatic lysosomal enzymes.

The study was undertaken to evaluate the effect of paracetamol on skeleton in Wistar rats. The drug was administered orally, once a day, in three doses: P1--3.5 mg/kg, P2--35.0 mg/kg, P3--350.0 mg/kg. The foetuses were delivered by laparotomy on the 21st day of pregnancy and fixed in alcohol. The skeletons were stained with alizarin. Insignificant differences of bone malformations were found.

The aim of the study was to evaluate the influence of caffeine on skeleton ossification in rats. Caffeine was administered in Tween 80 solution, once daily, in oral bolus, during the whole second trimester, in three doses: C1--0.7 mg/kg, C2--7.0 mg/kg, C3--70.0 mg/kg. On the 21st day of gestation the pumps were delivered. The fetuses were fixed in Bouin's solution and subsequently observed for external and internal malformation or in alcohol for skeleton malformation. The skeletons were stained with alizarin red-S. The examination showed an insignificant (P0.05) number of skeleton malformations, external haematomas and any internal malformations.

The aim of this study was to establish and quantify changes in the activities of the some lysosomal enzymes and to determine the type of changes in the ultrastructure of the submandibular gland in rabbits caused during progression of diabetes. The experiment was conducted on 89 New Zealand rabbit males. Diabetes was induced by the intravenous administration of 10% alloxan solution at a dose of 10-mg/kg-body weight. On the seventh day after alloxan administration, the level of glucose in blood was determined. Rabbits were divided into five groups: intact (n=18), 21-day diabetes (n=18), 42-day diabetes (n=17), 90-day diabetes (n=19) and 180-day diabetes (n=17). From killed animals in each group, the submandibular glands were removed and fixed or stored. Enzyme activities were assayed by spectrophotometric methods using substrates (Sigma) which release 4-methyloumbeliferol when they react with the proteases. Fixation procedure was done according to standard methods. Semi-thin and ultra-thin specimens were prepared by use of clearly visible after 42 days of diabetes. Mitochondria were damaged, accumulation of large amounts of lipids in the intracellular spaces was observed. After 90 days the presence of vacuoli and swollen lysosomes were observed, some cells also contained myelin figures. After 180 days the greatest changes were observed in the blood vessels, which had thickened walls and were often occluded. We concluded that the total activity of acid phosphatase and beta-N-acetyl-glucosaminidase in the submandibular gland was correlated with the level of glucose but there was no correlation between total beta-galactosidase activity and the serum concentration level of glucose has been detected during course of diabetes. The activities of the free fractions of acid phosphatase, beta-galactosidase and beta-N-acetyl-glucosaminidase in the submandibular gland were higher than the bound fractions in all groups of rabbits. The changes in the ultrastructure of the submandibular gland were correlated with changes in serum glucose level and with lysosomal enzymes activities during progression of experimental diabetes in rabbits.

Paracetamol is common used over-the-counter (OTC) nonnarcotic analgesic and antipyretic drug during pregnancy. Several animal and human studies on reproductive effect of paracetamol have been done and the overall results do not implicate paracetamol as a teratogen. However, there are some dates that paracetamol administration during pregnancy may have an effect on lowering body birth weight and length.

The aim of this study was to establish and quantify the changes of the level of cathepsin B, D and L in the spleen during experimental pancreatitis. The experiment was carried out in 115 male Wistar rats, randomly divided into three groups: intact (n = 15), injected with 0.9% NaCl solution into the common bile pancreatic duct (n = 50) and injected with 5% sodium taurocholate into this duct to induce acute pancreatitis (n = 50). After 2, 6, 12, 24 and 48 hours rats were anaesthetised, and blood was taken for amylase determination from the heart, and the spleen was removed. Alpha-amylase level in the blood serum samples was measured by enzymatic method. Cathepsin activity was established by spectrophotometric methods using substrates which form coloured complexes when they react with these proteases. The specific free fraction activity of cathepsin B, D and L in the spleen changed during the course of experiment, but there was no correlation between their activity and the intensity of pancreatitis established by serum amylase level.

Cel Ocena zalezności miedzy immunoekspresją katepsyny D w rakach plaskonablonkowych przelyku a wybranymi parametrami kliniczno-morfologicznymi oraz przezyciem pacjentow. Katepsyna D jako lizosomalna proteaza uczestnicząca m.in. w degradacji blony podstawnej i elementow macierzy zewnątrzkomorkowej, pelni wazną role w inwazji nowotworow i powstawaniu przerzutow. Material i metodyka Badania przeprowadzono na materiale pochodzącym od 38 pacjentow z zaawansowanym rakiem plaskonablonkowym środkowej cześci przelyku leczonych wylącznie operacyjnie. Odczyny immunohistochemiczne wykonano na skrawkach parafinowych przy uzyciu zestawu z przeciwcialem monoklonalnym przeciwko katepsynie D (NCL-CathD-Paraffin, Novocastra). W analizie statystycznej zastosowano test Chi2 z poprawką Yates’a oraz test Kplana-Meiera. Dla celow statystycznych za dodatnie uznawano przypadki, w ktorych przynajmniej 10% komorek nowotworowych wykazywalo odczyn dodatni. Wyniki Immunoekspresje katepsyny D stwierdzono w 19 rakach (50.0%). Nie wykazano istotnych statystycznie roznic i korelacji miedzy ekspresją katepsyny D a wszystkimi badanymi parametrami kliniczno-morfologicznymi tj. wiekiem pacjentow, wielkością i stopniem zaawansowania raka, obecnością przerzutow w wezlach chlonnych i liczbą zajetych wezlow, stopniem zroznicowania raka, sposobem naciekania, obecnością inwazji naczyn, naciekow wokol struktur nerwowych i stopniem nasilenia reakcji zapalnej wokol guza, jak rowniez calkowitym przezyciem pacjentow. Wnioski Katepsyna D nie odgrywa prawdopodobnie istotnej roli w inwazyjności zaawansowanych rakow plaskonablonkowych przelyku, a immunoekspresja katepsyny D nie moze byc uznana za czynnik prognostyczny w odniesieniu do calkowitego przezycia pacjentow z tej grupy.

Carcinoma of unknown primary (CUP) is a heterogeneous group of oncological diseases in which it is impossible to determine the primary tumor. The incidence is 3-5% of oncologic patients, but the survival time varies from 6 weeks to 5 months. The diagnostics should begin with a clinical evaluation and basic laboratory tests. For CUP placed in head and neck the positron emission tomography - computed tomography is recommended; pancreatic or lung neoplasms are diagnosed with the computed tomography as well. Recently, the magnetic resonance, especially whole-body diffusion-weighted imaging has been introduced to the imaging panel. The lesion obtained during surgically removed metastases or biopsy material should be histopathological and molecularly examined to define the type of tumor. The basic immunoexpression panel should include cytokeratin-5/6, -7 and -20, EMA, synaptophysin, chromogranin, vimentin and GATA3 and molecular expression of ERBB2, PIK3CA, NF1, NF2, BRAF, IDH1, PTEN, FGFR2, EGFR, MET and CDK6. During the accurate diagnostics enable to classify malignancy of undefined primary origin as provisional CUP or finally confirmed CUP in which the primary place of tumor remains undetectable. The detailed diagnostics should be performed in highly specified centers to establish an accurate diagnosis and to initiate personalized treatment. Majority of patients are diagnosed with adenocarcinoma (70%), undifferentiated carcinoma (20%), squamous cell or transitional cell/uroepithelial carcinoma (5-10%), neuroendocrine tumor (5%) and with minor incidence other histological types, including melanoma.