Evaluation of airway responsiveness and pulmonary function test results among obese and non-obese patients with obstructive sleep apnea syndrome.

OBJECTIVE: In this research, we aimed to elucidate the effect of obstructive sleep apnea syndrome (OSAS) and obesity on pulmonary volumes and bronchial hyperreactivity, and particularly the effect of supine position on pulmonary volume and functions. PATIENTS AND METHODS: This was a prospective, cross-sectional study with a total of 96 patients (age range, 20-65 years). Based on the body mass index (BMI) and Apnea-Hypopnea Index (AHI) scores, the patients were divided into four groups: Group 1: AHI≥15/h, BMI≥30 kg/m2 (n=24), Group 2: AHI≥15/h, BMI<30 kg/m2 (n=24), Group 3: AHI<15/h, BMI≥30 kg/m2 (n=24), and Group 4: AHI<15/h, BMI<30 kg/m2 (n=24). All patients first had static and dynamic pulmonary function tests and carbon monoxide diffusion tests (TLco and Kco) in the sitting and supine positions. A bronchial provocation test with methacholine was applied to all patients in the sitting position one day later. Analysis of variance (ANOVA) and multivariate linear regression was used in the statistical analysis. RESULTS: Airway responsiveness was observed in 4 of the patients included in the study, and there was no statistically significant difference between the groups. A statistically significant decrease was observed in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), total lung capacity (TLC) and functional residual capacity (FRC), especially in  Group 1 in sitting position compared to Group 4 (p=0.001, p=0.001, p=0.025, p=0.043, and p=0.001, respectively). Changes in pulmonary functions in the transition from sitting to a supine position did not show any significant difference in the study groups (p<0.05). We observed no difference in the diffusion capacity in the sitting and supine positions among the groups (p<0.05). CONCLUSIONS: The severity of AHI and BMI particularly affect the lower airway, but changes in the position did not show any significant difference in the study groups.

Expression of angiogenic growth factors in canine squamous cell cancers.

Skin and subcutaneous tissue tumors are the most common neoplasms in dogs. The most common sites of origin in dogs include digits, skin and the oral cavity including cheek and retromandibular area. We investigated canine squamous cell carcinoma (SCC) samples from 15 dogs and classified them histopathologically according to the degree of differentiation. bFGF, VEGF-C, TGF-ß, PDGF-A, PDGF-C and PDGFR-α expressions were assessed using immunohistochemistry to determine the roles of growth factors during SCC. We found that TGF-ß1 immunolabeling was elevated significantly compared to healthy controls in SCC originating from nailbeds, while expression of other growth factors did not change significantly. Our findings might explain the role of TGF-ß1 in the infiltrative and malignant behavior of SCC originating from nailbeds.

Late effects of cutaneous 3-methylcholanthrene exposure on DNA damage-related pleiotropic growth factors and oxidative stress markers in mice.

BACKGROUND: Skin is the body's first defence against direct exposure to variety of chemicals. Polycyclic aromatic hydrocarbons such as 3-methylcholanthrene (3-MC) are common in polluted urban air and have a potential of producing harmful effects. Moreover, their late effects can occur months or years after exposure. OBJECTIVES: We aimed to investigate the long-term effects of 3-MC induced dermal toxicity on the expression of markers of apoptosis, pleiotropic cytokines, and oxidative stress and to determine the protective effect of cisplatin. METHODS: Groups were designed as control (group 1), 3-MC applied (group 2) and 3-MC+cisplatin applied mice (group 3). Cutaneous expressions of TGFß, PDGFA, PDGFC, bFGF, PDGFRα, USP28, and Ki67 were evaluated with qPCR. Total oxidant (TOS), total antioxidant (TAS) and oxidative stress index (OSI) values were determined in liver and kidney tissues. RESULTS: The expression levels of TGFß, PDGFRα, USP-28, Ki67, and PDGFA were decreased significantly in MC applied groups. Renal TAS levels were significantly lower in group-3. Liver and kidney OSI values were increased in both groups 2 and 3. CONCLUSION: The results indicated that low dose 3-MC caused oxidative stress and downregulated apoptotic and cytokine markers in the long term and cisplatin had no ameliorative effects on this degeneration processes (Tab. 3, Fig. 3, Ref. 32). Text in PDF www.elis.sk.

Primary Unilateral Small Cell Neuroendocrine Carcinoma of the Kidney in a Dog.

Primary small cell carcinomas are rare in domestic animals. A mass measuring 15 × 20 × 9 cm was detected in the left abdominal cavity of a 7.5-year-old female golden retriever. The cut surface of the excised mass showed a tumour replacing the left kidney. Microscopically, the mass was composed of polymorphic, small basophilic cells with a high nuclear to cytoplasmic ratio and round, oval or short slender fusiform nuclei with condensed or finely granular chromatin, absent or inconspicuous nucleoli, and scant, faintly eosinophilic cytoplasm with poorly defined cytoplasmic borders. Immunohistochemically, most of the neoplastic cells were immunoreactive for thyroid transcription factor 1 and CD56, moderately positive for vimentin and weakly or sparsely labelled for chromogranin A, synaptophysin, Wilms' tumour 1 protein, neuron-specific enolase, pan-cytokeratin (CK) AE1/AE3 and epithelial membrane antigen. The tumour cells were negative for glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1, CK7, CK20, CD3, CD45 and CD99. These findings indicated a neuroendocrine origin of the tumour. To the best of author's knowledge, this is the first report of a small cell neuroendocrine carcinoma originating as a primary tumour in the kidney of a dog.

Significance of Angiogenic Growth Factors in Bovine Ocular Squamous Cell Carcinoma.

Bovine ocular squamous cell carcinoma (BOSCC) is the most common and economically significant neoplasm of the eye in cattle. This study investigated the role of angiogenic growth factors in the pathogenesis of BOSCC. Eighteen cases of BOSCC were classified histopathologically according to the degree of differentiation. Normal upper and lower eyelids and third eyelids collected from the right and left eyes of six healthy cattle aged 1-3 years, that had been presented for slaughter to abattoirs, served as controls. Transcription of genes encoding the angiogenic growth factors vascular endothelial growth factor-C (VEGF-C), basic fibroblast growth factor (bFGF), platelet-derived growth factor-C (PDGF-C) and platelet-derived growth factor receptor-α (PDGFR-α) was determined by quantitative real-time polymerase chain reaction (RT-PCR) in tissue obtained from paraffin wax blocks. Immunohistochemistry (IHC) was utilized to detect intensity of expression and tissue distribution of these growth factors. IHC results revealed that bFGF and PDGF-C were elevated significantly (P >0.05) and VEGF-C expression was decreased in BOSCC compared with healthy control tissue. PDGR-α expression was elevated; however, the difference, compared with control tissues, was not significant. RT-PCR results showed an inverse relationship to the results of IHC; where protein levels were elevated their corresponding mRNA levels were decreased or vice-versa. Angiogenic regulators therefore appear to play a role in the pathogenesis of BOSCC.

Periostin alters transcriptional profile in a rat model of isoproterenol-induced cardiotoxicity.

Periostin is an extracellular matrix protein from the fasciclin family that guides cellular trafficking and extracellular matrix organization. Periostin stimulates mature cardiomyocytes to reenter the cell cycle. The molecular mechanism behind such stimulation remains to be explored. A DNA microarray technology constituting 30,429 gene-level probe sets was utilized to investigate effects of recombinant murine periostin peptide on the gene expression pattern in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague-Dawley rats in four groups ( n = 21): (1) control group, (2) only periostin applied group, (3) ISO cardiotoxicity group, and (4) ISO + periostin group. The experiment was continued for 28 days, and rats were killed on days 1, 7, and 28 ( n = 7). Microarray analyses revealed that periostin significantly altered the expression of at least ±2-fold of 2474 genes in the ISO + periostin group compared to the ISO cardiotoxicity group of which 521 genes altered out of 30,429 gene-level probe sets. Ingenuity pathway analysis indicated that multiple pathway networks were affected by periostin, with predominant changes occurring in the expression of genes involved in oxidative phosphorylation, oxidative stress, fatty acid metabolism, and TNF-α NF-κB signaling pathways. These findings indicate that periostin alters gene expression profile in the ISO-induced myocardial injury and modulates local myocardial inflammation, possibly mitigating inflammation through TNF-α NF-κB signaling pathway along with a decreased Casp7 activity and apoptotic cell death.

Effects of Plantago lanceolata L. extract on full-thickness excisional wound healing in a mouse model.

Wound healing requires cells that increase both collagen production as a result of inflammatory events and regeneration of epithelial tissue. The Plantago species of herbs have been used in traditional treatment of skin disorders and infectious diseases, and digestive, respiratory, reproductive and circulatory conditions. We investigated the efficacy of different concentrations of Plantago lanceolata L. extract (PLE) for wound healing owing to its anti-inflammatory, anti-bacterial, anti-fungal, anti-oxidant, anti-ulcerative, analgesic and immunomodulatory properties. We used 72 mice in four groups of 18. An excisional 1 cm wound was created in the skin on the back of the mice in all groups. An ointment containing 10% PLE was applied to the wound in group 1, an ointment containing 20% PLE was applied in group 2 and vaseline was applied in group 3. In group 4, no treatment was applied to the wound. On days 7, 14, and 21 of the experiment, six animals in each group were sacrificed after the wounds were photographed and specimens from the wound sites were examined. On day 14, epithelialization was more prominent in group 2, while vascularization and collagen deposition was more advanced in groups 1 and 2 compared to the other groups. Immunohistochemical examination revealed that TGF-ß1 expression was elevated on day 14 in all groups; however, this elevation was more limited in groups 1 and 2 than in groups 3 and 4. Although ANGPT-2 expression increased in groups 1 and 4 on day 14, it decreased significantly in groups 2 and 3. We found that different concentrations of PLE exhibited positive effects on wound healing. Application of 10% PLE ointment may be a useful strategy for wound healing.

Periostin normalizes levels of cardiac markers in rats with experimental isoproterenol cardiotoxicity.

BACKGROUND: Although the molecular mechanism of cardiac healing is not fully understood, myocardial infarction is one of the most usual diagnoses in hospitalized patients in industrialized nations while periostin has been recently suggested to have a potential in tissue repairing following myocardial ischemia. OBJECTIVES: To investigate the effects of periostin on the levels of selected cardiac parameters (cardiac troponin I and T, creatine kinase and creatine kinase isoenzyme-MB), antioxidant/lipid peroxidation parameters (superoxide dismutase, catalase, and malondialdehyde), hepatic parameters (alkaline phosphatase, lactate dehydrogenase, aspartate and alanine transaminases) as well as lipids (total cholesterol, triglyceride, high, low and very­low­density lipoproteins) in a rat model of isoproterenol---induced myocardial injury. METHODS: A total of 84 male rats were grouped into saline (Group I), periostin (Group II), isoproterenol (Group III) and isoproterenol+periostin (Group IV) groups (n = 21). Isoproterenol (85 mg/kg/day) and periostin groups were both injected intraperitoneally (1 µg/kg). RESULTS: Our results revealed that periostin has a positive reducing effect on the levels of analysed parameters especially on cardiac troponins and creatine kinases on days 7 and 28 of the recovery period following the induced experimental heart damage in rats. CONCLUSION: It is concluded that periostin could have a potential to increase the rate of myocardial recovery after myocardial infarction (Tab. 5, Ref. 28).

An evaluation of cause-of-death trends from recent decades based on registered deaths in Turkey.

OBJECTIVES: Although cause-of-death analyses are very important to define public health policy priorities and to evaluate health programs, there is very limited knowledge about mortality profiles and trends in Turkey. The aim of this study was to measure the trends in mortality within three broad cause-of-death groups and their distribution by age groups and gender and to describe the changes of leading causes of death between 1980 and 2013 in Turkey. STUDY DESIGN: Descriptive study. METHODS: In the study, data on the number of deaths by year, gender, age and cause was obtained from the Turkish Statistical Institute. The causes of death were classified as group I: communicable, maternal, perinatal, and nutritional conditions; group II: non-communicable diseases (NCDs); and group III: injuries. Unknown or ill-defined causes of death were distributed within group I and group II. The percentage distribution of the cause-of-death groups by gender and age groups between 1980 and 2013 was identified. Age-standardized mortality rates (ASMRs) per 100,000 of broad causes-of-death groups were calculated using European Standard Population 1976 between 1980 and 2008. Changes in mortality rates per hundred were calculated using the formula ([the rate of last year of the period-the rate of the first year of the period]/the rate of the first year of the period). Gender and age-specific data were analyzed using the Joinpoint software to examine trends and significant changes in trends of mortality rates. RESULTS: Crude death rates for group I, group II, and group III were 157.3, 147.2, and 21.4 per 100,000 in 1980 and 35.3, 377.5, and 15.8 in 2008 for males; 161.8, 120.2, and 5.8 in 1980 and 38.6, 318.4, and 6.4 in 2008 for females, respectively. ASMRs for group I, group II, and group III were 146.3, 394.3, and 29.3 per 100,000 in 1980 and 49.7, 723.6, and 18.8 in 2008 for males; 138.0, 291.5, and 7.6 per 100,000 in 1980 and 47.7, 478.8, and 7.2 in 2008 for females, respectively. The mortality rates of group I for almost all age groups particularly below 5 years of age decreased significantly. CONCLUSION: This study indicates that Turkey is at an advanced stage in the epidemiological transition, with the majority of the causes of death from NCDs. Considering the regional differences, it is necessary to carry out studies on the specific details of epidemiological transition and the social determinants of deaths in Turkey.

Kisspeptin-10 and the G protein-coupled receptor 54 are differentially expressed in the canine pregnant uterus and trophoblast cells.

Uterine tissue was collected from bitches after ovariohysterectomy at different times after ovulation. Samples were assigned to four groups: metestrous non-pregnant, day 10-12, n = 4; pre-implantation, day 10-12, n = 9; post-implantation, day 18-25, n = 13; mid-gestation, day 30-40, n = 7. RT-qPCR detection was performed for kiss1 and the G protein-coupled receptor 54 (GPR54, specific receptor for kisspeptin). In addition, immunohistochemistry was performed for detection of kisspeptin-10 (KP-10), GPR54, as well as pan-cytokeratin and vimentin. The latter two were included to differentiate the different placental cell types. The percentage of positive stained cells was evaluated, and an immunoreactivity score (IRS) was obtained by multiplying the labelling intensity score (0-3) with the percentage of immunolabelled cells (range: 0-300). In non-pregnant and pre-implantation tissues, gene expression was highly variable for kiss1 and GPR54. Expression of GPR54 was higher before embryo adhesion than during post-implantation and mid-gestation (p < .05), whereas there was no difference found between groups for kiss1. Except during the pre-implantation period, KP-10 expression was higher in the non-pregnant uterus compared to all gestational periods investigated, indicating a pregnancy-related downregulation. In the pre-implantation period, KP-10 was present in larger vessels only, whereas the presence of GPR54 in vessels was found in all samples, with most labelling in the post-implantation period. KP-10 was present in superficial uterine glands, GPR54 in superficial and deep uterine glands of the post-implantation uterus. In myocytes, the highest staining for KP-10 was seen in the non-pregnant uterus, whereas the highest staining for GPR54 was seen in post-implantation and mid-gestation. Syncytiotrophoblast cells stained for both KP-10 and GPR54 in post-implantation and mid-gestation, with maximum intensity for GPR54 in the latter. We conclude that KP-10 and GPR54 are expressed in the canine uterus and trophoblast cells. However, during pregnancy, expression of both proteins seems to be differentially regulated.

Immunohistochemical detection of autophagy-related microtubule-associated protein 1 light chain 3 (LC3) in the cerebellums of dogs naturally infected with canine distemper virus.

We investigated the expression of microtubule-associated protein 1 light chain 3 (LC3) protein in the cerebellums of dogs infected with canine distemper virus (CDV) using immunohistochemistry to detect autophagy. The cerebellums of 20 dogs infected with CDV were used. Specimens showing demyelination of white matter were considered to have an acute infection, whereas specimens showing signs of severe perivascular cuffing and demyelination of white matter were classified as having chronic CDV. Cerebellar sections were immunostained with CDV and LC3 antibodies. The cytoplasm of Purkinje cells, granular layer cells, motor neurons in large cerebellar ganglia and some neurons in white matter were positive for the LC3 antibody in both the control and CDV-infected dogs. In the infected cerebellums, however, white matter was immunostained more intensely, particularly the neurons and gemistocytic astrocytes in the demyelinated areas, compared to controls. Autophagy also was demonstrated in CDV-positive cells using double immunofluorescence staining. Our findings indicate that increased autophagy in the cerebellum of dogs naturally infected with CDV may play a role in transferring the virus from cell to cell.

Phosphodiesterase type 5 inhibition attenuates cyclosporine A induced nephrotoxicity in mice.

We investigated the renal protective effects of phophodiesterase type 5 (PDE5) inhibitors in mice with cyclosporine A (CyA; a calcineurin phosphatase inhibitor) induced nephrotoxicity. Fifty male mice were divided into five groups of 10. Group 1 received no treatment, group 2 received only saline orally, group 3 received 30 mg/kg/day CyA by subcutaneous injection, group 4 received only 30 mg/kg/day vardenafil orally, and group 5 received 30 mg/kg/day CyA by subcutaneous injection and 30 mg/kg/day vardenafil orally. At 28 days, platelet-derived growth factor A (PDGF-A) and C (PDGF-C), transforming growth factor-beta 1 (TGF-ß1), cyclo-oxygenase 1 and 2 (COX-1 and COX-2), and P glycoprotein (Pgp) expression levels were measured in the renal tissues. In addition, expressions of COX-1 and COX-2 genes were determined using real-time PCR. PDE5 inhibitor administration ameliorated decreased PDGF-A and C, TGF-ß1, COX-1 and -2, and Pgp expression levels by modulation of cyclic guanosine monophosphate (cGMP) activity in kidneys. The relative expressions of COX-1 and COX-2 genes to GAPDH revealed that the maximum increase was obtained in the group treated with CyA and vardenafil for both COX-1 and COX-2 genes. Our study revealed that long term oral treatment with vardenafil protects kidneys from CyA induced nephrotoxicity. We showed that long term oral treatment with PDE5 prevents pathological kidney changes caused by CyA induced nephrotoxicity.

Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats.

We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats.

Distribution of glutathione peroxidase 1 in liver tissues of healthy and diabetic rats treated with capsaisin.

We investigated the immunohistochemical localization of glutathione peroxidase 1 (GPx 1) and the structural changes that occur in the livers of healthy and diabetic rats that were treated with capsaisin (CAP). Fifty female rats were divided into five groups: group 1, sham; group 2, untreated control; group 3, CAP-treated; group 4, streptozotocin (STZ) diabetic; group 5, STZ diabetic + CAP-treated. STZ was administered to groups 4 and 5; after verifying diabetes, CAP was administered daily for 2 weeks to groups 3 and 5. Diffuse, microvesicular and some macrovesicular fatty degeneration were observed in the cytoplasms of hepatocytes in the livers of the diabetic group. In the CAP-treated diabetic group, fat degeneration in the livers decreased slightly by day 7. Irregularity of the external contours of nuclei of the hepatocytes, swelling of the nuclei, and slight anisocytosis and anisokaryosis were observed in the hepatocytes of the diabetic group. In the CAP-treated diabetic groups, the severity of anisocytosis and anisokaryosis decreased slightly by day 7. In all groups, GPx 1 showed similar immunolocalization, but in the diabetic and diabetic + CAP groups, GPx 1 immunoreactivity was less than in the other groups. GPx 1 immunoreactivity in the CAP-treated diabetic group was weaker than in the diabetic group. In all groups, GPx 1 immunoreactivity was diffusely cytoplasmic in some of the hepatocytes, and diffusely cytoplasmic and diffusely nuclear in other hepatocytes. Also, GPx 1 immunoreactivity in the liver was more intense in the hepatocytes around Kiernan's space. We found that CAP caused a decrease in GPx 1.

The effects of kefir, koumiss, yogurt and commercial probiotic formulations on PPARα and PPAR-ß/δ expressions in mouse kidney.

Commercial probiotic capsules that contain probiotic bacteria, kefir, koumiss and yogurt contain beneficial microorganisms that affect cholesterol levels and immune response, and are used for treatment of some diseases. We investigated using immunohistochemistry the effects of kefir, koumiss, yogurt and a commercial probiotic formulation on the expression levels of peroxisome proliferator-activated receptor-α (PPARα) and peroxisome proliferator-activated receptor-ß/δ (PPAR-ß/δ), which are members of the nuclear steroid hormone receptor superfamily in mouse kidney. Mice were assigned to five groups: group 1, commercial probiotic capsules; group 2, kefir; group 3, koumiss; group 4, yogurt; group 5, control. After oral administration for 15 days, body weights were recorded and kidney tissue samples were obtained. Hematoxylin & eosin staining and the streptavidin-biotin peroxidase complex (ABC) method were applied to tissue sections to examine histology and to determine the localization of PPARα and PPAR-ß/δ in the kidneys. We found that the weights of the mice in the kefir, koumiss, yogurt and commercial probiotic capsules groups were increased compared to controls. No differences in kidney histology were observed in any of the experimental groups. Kefir, koumiss, yogurt and the commercial probiotic preparation increased PPARα and PPAR-ß/δ expressions.

Immunohistochemical characterization of peroxisome proliferator-activated receptors in canine normal testis and testicular tumours.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Recent studies have demonstrated that PPARs regulate lipid metabolism and are expressed in various cancers. The aim of the present study was to investigate the expression of PPAR-α, -ß and -γ in normal canine testicular tissue and canine testicular tumours (CTTs). Expression of PPAR-α, -ß and -γ was greater (P <0.05) than in normal testicular tissue. PPARs were therefore induced in CTTs and they may play a role in the biology of these tumours.

An investigation of growth factors and lactoferrin in naturally occurring ovine pulmonary adenomatosis.

Ovine pulmonary adenomatosis (OPA), also known as jaagsiekte, is a transmissible beta retrovirus-induced lung tumour of sheep that has several features resembling human bronchoalveolar carcinoma (BAC). Angiogenesis has been suggested to be one of the most important factors underlying tumour growth and invasion. This process involves the action of growth factors including vascular endothelial growth factor (VEGF)-C, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-C and its receptor (PDGFR-α). Bovine lactoferrin (bLF), an iron and heparin-binding glycoprotein secreted into various biological fluids, has been implicated in innate immunity and has anti-inflammatory and anti-tumour functions. Tissues from 16 cases of OPA were compared with tissues from seven healthy control sheep by immunohistochemistry. Expression of the markers was assessed semi-quantitatively by ascribing an immunoreactivity score (IRS) with a maximum value of 300. VEGF-C, bFGF, PDGF-C, PDGFR-α and bLF signals were detected in 10/16, 15/16, 12/16, 15/16 and 10/16 of the OPA cases studied, respectively. bLF expression was weak in the neoplastic epithelial cells (IRS 21.4 ± 10.0) in contrast to high levels detected in infiltrating macrophages and plasma cells (IRS 141.3 ± 24.8 and 140.0 ± 25.1, respectively). The PDGFR-α IRS was elevated for neoplastic epithelial cells (108.9 ± 18.2) and was lowest for macrophages and plasma cells (20.4 ± 13.1 and 13.7 ± 12.4, respectively). These results suggest that bFGF, VEGF-C and PDGF-C have roles in the pathogenesis of OPA. bLF may activate macrophages and plasma cells in these lesions, but limited expression of bLF by neoplastic cells may be a consequence of defective or impaired function of this molecule.

Fibroblast growth factor-2 and vascular endothelial growth factor expression in the ileocecal region of quail (Coturnix coturnix japonica).

We undertook this study to immunolocalize in quail vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) in the ileocecal region, which is a significant entry point for intestinal immunity. Diffuse cytoplasmic reaction for FGF-2 and VEGF was observed in the epithelial cells of the distal ileum and proximal cecal mucosa. VEGF immunoreactive cells, which give strong intracytoplasmic immunoreaction, were observed in the lamina propria of both intestinal parts. FGF-2 immunoreactive cells were seen in the lamina propria and germinative centers of lymph follicles in the cecum mucosa. Expressions of FGF-2 and VEGF in healthy quail intestines indicate that these factors have physiological roles in quail.

Cyclin A expression is associated with apoptosis and mitosis in murine 3-methylcholanthrene-induced fibrosarcomas.

The chemical carcinogen MCA induces fibrosarcoma and tissue damage at the injection site. Despite the importance of ROS in the development of cancer, little is known about the pattern of expression of ROS in MCA-induced fibrosarcomas. To gain some insight into the biological significance of iNOS and Cu/Zn-SOD, comparative immunohistochemical analyses were performed to characterize their expression in MCA-induced fibrosarcomas. Cyclin A is overexpressed in various tumors, but its expression in MCA-induced fibrosarcoma in mice and its correlation to mitosis and apoptosis are unclear. The presence of apoptotic cell death was evaluated using the TUNEL method and findings were compared with cyclin A expression and mitotic count of fibrosarcomas. Subcutaneous application of MCA caused fibrosarcoma development in 14 of 20 mice (70%) in 26 weeks. Limited cytoplasmic Cu/Zn-SOD and iNOS immunostainings were detected in 13 of 14 and 9 of 14 tumors with median immunoreactive scores of 2 and 1, respectively. Prominent nuclear cyclin A immunostaining and TUNEL-positive reactions were seen in all the fibrosarcoma cases. Cyclin A immunoreaction significantly correlated with the TUNEL index (P<0.01) and MC (P<0.001). The present findings show a low level of iNOS expression in neoplastic cells indicating limited synthesizing capacity of tumor cells. Limited Cu/Zn-SOD reaction could be associated with an imbalance in between pro-oxidant/antioxidant levels. Furthermore, it was shown that cyclin A is overexpressed in MCA-induced fibrosarcomas and possibly plays a significant role in the pathogenesis of fibrosarcomas. Cyclin A could be useful for detecting the S phase of the cell cycle and could also indicate that cyclin A may induce S phase arrest associated with apoptosis in the MCA-induced fibrosarcomas.