Effects of Melatonin and Adrenomedullin in Reducing the Cardiotoxic Effects of Doxorubicin in Rats.

The main disadvantage of doxorubicin (DOX) is that it has cardiotoxic side effects. Our aim is to evaluate the cardioprotective effects of adrenomedullin (ADM) and to compare these effects with melatonin (MEL), it's cardioprotective effects are well known. Rats were divided into four groups: Control group (0.9% NaCl solution, intravenously), Doxorubicin group (45 mg/kg DOX, intravenously), Doxorubicin + Melatonin group (DOX + MEL, 10 mg/kg melatonin, intraperitoneally), Doxorubicin + Adrenomedullin group (DOX + ADM, 12 µg/kg adrenomedullin, intraperitoneally). A single dose of DOX was injected to the experimental groups on day 5, and a single dose of 0.9% NaCl solution was injected to the control group through the tail vein. The animals were anesthetized and ECG recordings were obtained on day 8. For the purpose of biochemical and histological analysis, cardiac tissue biopsy was obtained after ECG recordings. Compared to the control group, the DOX group had significantly increased duration of QRS complex, PR interval, QT interval and QTc interval. QRS complex, QT interval and QTc interval were prolonged with the administration of DOX and shortened with the administration of ADM. MEL weakened the toxic effects of DOX on the cardiac tissue and it is shown histologically. DOX increased interleukins (IL-1α, IL-6, IL-18), tumor necrosis factor-α (TNF-α), hypoxia-inducible factor 1-alpha (HIF-1α), malondialdehyde (MDA), nitric oxide (NO), creatine kinase myocardial band (CK-MB), and total oxidant status (TOS) levels in cardiac tissue, while reducing total antioxidant status (TAS), superoxide dismutase (SOD) and catalase (CAT) levels. MEL administration decreased the levels of CK-MB, MDA, IL-1α, IL-6, IL-18, NO, and TNF-α, whereas ADM only decreased IL-1α, IL-18, MDA and TNF-α levels. In summary, these results show that DOX has toxic effects on rat cardiac tissue which is documented histologically, electrocardiographically and biochemically. MEL alleviated histological damage and showed improvement on the several biochemical parameters of cardiac tissue. ADM brought several electrocardiographic and biochemical parameters closer to normal values.

High PI3K/mTOR and low MAPK/JNK activity results in decreased apoptosis and autophagy in nasal polyposis.

INTRODUCTION: Nasal polyposis is a progressive inflammatory disease that reduces the quality of life. The role of apoptotic and autophagic pathways in nasal polyposis pathogenesis is not yet clearly known. OBJECTIVE: In this study we aimed to investigate apoptotic (MAPK/JNK), anti-apoptotic (PI3K/mTOR) and autophagic (LC3) pathways which are related each other in the nasal polyposis tissues. METHODS: Twenty patients with nasal polyps and fifteen patients going through an inferior turbinate reduction were included in this study. Patients with asthma, Samter triad and allergic fungal sinusitis were excluded from the study. The apoptotic and autophagic pathways were investigated in paraffin-embedded nasal tissue sections of 20 NP and 15 samples from inferior turbinate reduction by H&E and immunohistochemistry with h-score. TUNEL method with apoptotic index was used to demonstrate apoptotic cells. RESULTS: Decreased immunoreactivity of P38 MAPK (p < 0.005) and JNK (p < 0.005) were observed in nasal polyposis compared to material from inferior turbinate reduction. This decrease may indicate a downregulation of apoptosis as demonstrated by decreased TUNEL staining in nasal polyposis (p < 0.005). The PI3K (p < 0.002) and mTOR (p < 0.005) immunoreactivities were increased in nasal polyposis. This increase indicates a downregulation of autophagy as demonstrated by decreased LC3 staining in nasal polyposis (p < 0.001). CONCLUSION: Deficient apoptosis and autophagy through MAPK/JNK and PI3K/mTOR pathways may have a role in the pathogenesis of nasal polyposis.

The Effect of Atmospheric Pressure Cold Plasma Application on Titanium Barriers: A Vertical Bone Augmentation.

OBJECTIVE: The aim of the present, microcomputed tomographic (µCT) and histological study, was to evaluate the effect of surface modification by atmospheric pressure cold plasma (APCP) on vertical guided bone regeneration in a rabbit calvaria model. MATERIAL-METHODS: The experimental study was conducted on 12 male New Zealand rabbits with healing periods of 45 and 90 days. Following surgical exposure of the calvarium, 4 customized titanium cylindricalders were fixed. Surface modification was achieved by application of APCP on 2 of cylinders (P+) in each calvarium and other cylinders were set as control (P-). In both experimental and control groups, one of the cylinders was filled with bone graft (G+) while the other one was left empty (G-). To evaluate short term effects, randomly selected 6 animals were sacrificed at the end of 45 days and remaining 6 animals were left for observing long term effects. Histological and µCT evaluations were used to examine new bone formation. RESULTS: In µCT imaging; the bone volume was greater (P < 0.05) in grafted groups than nongrafted groups in both short and long term. The bone height values were significantly different in (P-G-) group than other groups (P < 0.05) in both evaluation periods. The histological evaluations revealed significant differences between P+G+ group and other groups but in long term both plasma treated groups revealed more bone formation than non plasma treated groups. CONCLUSION: Modification of the surfaces of titanium cylinders by APCP treatment, accelerated the bone regeneration either bone graft used or not in a rabbit calvaria model.

Akt and estrogen receptor expression in nasal polyps.

BACKGROUND: Nasal polyps (NP) is a common chronic inflammatory disease of the mucous membranes in the nose and paranasal sinuses. The underlying mechanisms of pathologic conditions to NP formation remains unclear. The aim of this study is to evaluate the expression of Akt and estrogen receptor (ER) in nasal polyps. MATERIAL AND METHODS: We respectively obtained 20 nasal polyp tissue and 15 concha from patients undergoing endoscopic polyp biopsy and turbinate resection. All samples were fixed in 10% formalin for 24 h and embedding in paraffin was using routine protocol for histological prepation. Sections 5 µm thick were cut and stained H&E. Tissue samples were stained with anti-ER and anti-Akt primary antibody, ER and Akt were evaluated immunohistochemically. There is a relationship between the estrogen receptor and PI3K/Akt signaling pathway in malignansy. In this study, it showed the effect of estrogen on the activation of Akt signaling pathway in nasal polyps. Mann- Whitney-U test was applied to evaluate the statistical differences between nasal polyp and control group, (P < 0.05) was accepted as significant. RESULTS: In H&E stained sections we observed a lot of inflamatory cells and eosinophils in the mucosa, submucosal connective tissue and around the glandular epithelium in nasal polyps. The mucosa and submucosal connective tissue was seen normally in control group in H&E stained. We determined that ER and Akt were intensely expressed in nasal polyps. Expression is localized especially in epithelial and glandular epithelium cells and submucosal connective tissue. In contrast, expression of ER and Akt were mildly expressed in turbinate resection samples. CONCLUSION: The expression of ER and Akt might be important factors in nasal polyp pathogenesis and may shed new light on clinical approaches in nasal polyp treatment.

Effect of nitrergic system on colonic motility in a rat model of irritable bowel syndrome.

AIM: The aim of this study is to investigate whether nitric oxide (NO)-mediated colonic motility was altered in rat irritable bowel syndrome (IBS) model, using different isoforms of NO-synthase (NOS) inhibitors. MATERIALS AND METHODS: The animal model of IBS-like visceral hypersensitivity was induced by intra-colonic infusion of 0.5% acetic acid (AA) in saline once daily from postnatal days 8 to 21. Control animals received saline instead of AA. Experiments were performed at the end of 8 weeks. Distal colon tissues were resected and direct effects of different NOS inhibitors; N-omega-nitro-L-arginine methyl ester hydrochloride, (L-NAME), ARL-17477 dihydrochloride hydrate (ARL 17477), N-[3-(Aminomethyl) phenyl] methyl]-ethanimidamidedihydrochloride (1400 W), and N5-(1-Iminoethyl)-L-ornithine dihydrochloride (L-NIO) were evaluated concentration-dependently in vitro tissue bath. Besides, morphology of both groups was assessed with hematoxylin and eosin (H and E) staining and the impact of NO antibodies was determined using the immunohistochemical method. RESULTS: The mean pressure values of spontaneous contractions and KCL (80 mmol/L) responses of distal colonic segments were similar in normal and IBS rats. L-NAME and ARL-17477 significantly increased the mean pressure of spontaneous colonic contractions in normal rats versus own base values (P < 0.05), but this increase did not significantly different when compared to IBS rats. In H and E staining, there was no difference with regard to morphology between two groups. Neuronal NOS (nNOS) immunoreactivity was found to be significantly decreased in IBS when compared to control groups (P < 0.05). CONCLUSION: L-NAME and ARL-17477 mediated mean pressure values were found to be slightly decreased in IBS rats. These findings may be related to a decrease in nNOS level in IBS.

Sheehan's syndrome as a rare cause of anaemia secondary to hypopituitarism.

Although its exact mechanism is unclear, anaemia is well recognised as a feature of hypopituitarism; and anaemia is associated with Sheehan's syndrome (SS). We aimed to evaluate the frequency and severity of anaemia and other haematological changes among patients with Sheehan's syndrome, in comparison with healthy controls. Sixty-five SS patients and 55 age-matched female healthy controls were included. Biochemical and hormonal assessments and haematological evaluations were carried out, and groups were compared. The mean number of red blood cells, as well as mean haemoglobin, iron and erythropoietin levels, total iron-binding capacity and transferrin saturation were all significantly lower in SS patients compared to controls. SS patients had significantly higher rates of anaemia (80.0% vs. 25.5%, p = 0.0001), iron deficiency (44.6% vs. 5.4%, p = 0.001), leukopenia (20.0% vs. 5.4%, p = 0.015), thrombocytopenia (9.2% vs. 0.0%, p = 0.028) and bicytopenia (21.5% vs. 1.8%, p = 0.001) compared to controls. Anaemic SS patients had normochromic-normocytic anaemia (55%) or hypochromic-microcytic anaemia (45%). Anaemia is frequently associated with Sheehan's syndrome and responds to appropriate replacement therapy. Hypopituitarism should be considered as a possible cause of anaemia, and a hormone examination should be undertaken promptly, particularly in patients with anaemia resistant to therapy and/or with a history suggestive of Sheehan's syndrome.

Levels of proinflammatory cytokines and hs-CRP in patients with homozygous familial hypercholesterolaemia.

OBJECTIVE: Homozygous familial hypercholesterolemia (FH) is an extremely rare (1/1,000,000) condition characterized by markedly increased LDL cholesterol levels and a significantly increased risk of premature coronary heart disease (CHD). We aimed to evaluate the levels of high-sensitivity C-reactive protein (hs-CRP) and proinflammatory cytokines, which are known to be associated with atherogenesis, in patients with this condition. METHOD AND RESULTS: A total of 10 patients with homozygous FH (5 women and 5 men, mean age 17.0 +/- 6.9 years, body mass index (BMI) (18.8 +/- 1.9 kg/m2) and 16 healthy controls were included. hs-CRP levels, proinflammatory cytokine levels and lipid parameters were measured and compared between patients and control subjects. Homozygous FH patients had significantly higher total cholesterol, LDL-cholesterol and Lp(a) levels and significantly lower triglyceride and HDL cholesterol levels, compared to controls (P = 0.0001, for all). Serum hs-CRP (3.7 +/- 1.3 mg/L vs. 0.6 +/- 0.6 mg/L) and IL-1beta, IL-2R, IL-6, IL-8, IL-10, TNF-alpha levels were all significantly higher in the homozygous FH group, compared to controls (P = 0.0001, for all). CONCLUSIONS: Homozygous FH patients have significantly higher levels of hs-CRP and circulating proinflammatory cytokines, which may explain their increased risk of atherosclerotic disease. hs-CRP is an important biomarker that may be helpful in the identification of asymptomatic CHD in FH patients.

Ultrastructural evaluation of the effects of cinnamon on the nervus ischiadicus in diabetic rats.

OBJECTIVE: To investigate the effects of oral cinnamon supplementation on the nervus ischiadicus at the electron microscopical level in rats. METHODS: This study was performed between 2004-2006 in Dicle University School of Medicine, Diyarbakir, Turkey in 15 adult Sprague-Dawley rats. Rats were divided into 3 groups; control (C) (n=5), diabetic without cinnamon (D) (n=5), and diabetic with cinnamon (D-C) (n=5). Diabetes was induced with intraperitoneal alloxan administration. All diabetic rats were treated with human insulin. All rats were fed with standard pellet chow. The D-C group rats were fed with standard pellet chow plus Cinnamomum cassia at the dose of 400mg/kg. All rats were sacrificed after 3 months and we obtained the nervus ischiadicus of all rats. Contrast stained thin sections evaluated by Jeol-TEM-1010 electron microscope, were not statistically different in both groups and photo samples were obtained. RESULTS: Mean blood glucose, hemoglobin A1C, and lipid profile were not statistically different in both groups. Marked detachment of myelin lamellae at Schmidt-Lanterman clefts, lysis in cristae mitochondrialis and degenerative changes, severe dispersion of organelles in neurolemma, mesoaxon region, and remarkable edema at the endoneurium were found in diabetic rats. On the contrary, mesoaxon, nucleus, nucleolus and myelin sheet were almost of normal appearance at the ultra-structural level in the D-C group. CONCLUSION: Cinnamon extracts may have beneficial effects on the development of diabetic neuropathy in alloxan induced diabetic rats.

The demonstration of changes in bulbar conjunctiva surface epithelium in the psoriatic patients treated with PUVA.

We investigated the effects of disease itself and PUVA treatment on surface epithelium of conjunctiva in psoriatic patients (PP) before PUVA and after PUVA therapy and in 32 healthy volunteers. Squamous metaplasia was detected in PP both before and after PUVA therapy. We concluded that PUVA treatment applied together with preventive measures, would lead to less severe ocular side effects.

Evaluation of effects of memantine on cerebral ischemia in rats.

OBJECTIVE: To evaluate the effects of memantine on infarct size in cerebral ischemia and on neurological outcome after temporary middle cerebral artery occlusion (MCAO) and reperfusion in rats. METHODS: In this study, performed between 2002-2004 in Dicle University School of Medicine, Diyarbakir, Turkey, 30 adult Sprague-Dawley rats were used. Cerebral ischemia was constituted by the intraluminal filament method with a 4-0 nylon suture. Reperfusion was started after 2 hours of MCAO. The rats were randomly divided into 2 groups as control and memantine. Saline 0.9% (0.5 ml/kg) and memantine (30 mg/kg) were administered via nasogastric intubations. Three coronal slices of 2 mm thickness were obtained from cerebrum, cerebellum, and brain stem, and were stained with a 2% solution of triphenyltetrazolium chloride. Transparent sheets were placed over each section and the areas of the brain and infarct were measured. RESULTS: Forty-five slices from each group (total 90) were obtained. Percent of ischemic area (%) in cerebrum, cerebellum, and brain stem level in memantine was lower than those of the control group (p<0.0001). In addition, we determined an improvement in neurological score at 24th and 72nd hours in the rats that have been given memantine. The memantine group showed significantly better recovery than the control group (p<0.0001). CONCLUSION: We concluded that memantine may decrease ischemic area in experimental cerebral ischemia in rats and it seems that memantine may be beneficial in cerebral ischemia.

A rare embryological malformation of brain - Dandy-Walker syndrome - and its association with Kallmann's syndrome.

BACKGROUND & AIM: Dandy-Walker malformation, a rare congenital brain malformation, is described as a triad of cystic dilatation of the fourth ventricle, complete or partial agenesis of the cerebellar vermis, and an enlarged posterior fossa with elevated tentorium. We aimed to report an association of Kallmann's syndrome and Dandy-Walker malformation. CASE: A fifteen years old boy was referred to endocrinology department due to delayed puberty. Stages of male genital development according to Marshall and Tanner, was stage G1 and P1 respectively. In the LHRH test, peak LH level was 40th min.:15.3 IU/ml. Peak growth hormone with insulin tolerance test was 14.5 microg/L. Olfactory test revealed light anosmia. With these findings the patient was accepted as isolated gonadotropin deficiency (Kalmann's syndrome). In computed tomography of the brain, cerebellar vermis was found to be hypoplastic and 4th ventricle was large and in posterior fossa broad hypodens area with cerebrospinal fluid density were seen (Dandy-Walker malformation). CONCLUSION: We reported an association of Kallmann's syndrome and Dandy-Walker malformation. This is second reported case probably.

Evaluation of erythropoietin effects on cerebral ischemia in rats.

OBJECTIVE: Majority of severe disabilities in adults are caused by stroke. The aim of our study is to learn the effects of erythropoietin (EPO), on infarct size in cerebral ischemia and to determine neurological behavioral scores and histopathological evaluation. MATERIAL & METHODS: In this study 30 adult Sprague-Dawney rats were used. Cerebral ischemia was constituted by intraluminal filament method with a 4-0-nylon suture. Reperfusion was started after two hours of middle cerebral artery occlusion. The rats were randomly divided into two groups as follow: control and EPO groups. Saline 0.9% (0.5 ml/kg) and EPO (5 000 U/kg) was administered intraperitoneally in the groups. Three coronal slices in two millimeters thickness were obtained from cerebrum, cerebellum and brain stem, and were stained with a 2% solution of triphenyltetrazolium chloride. Transparent sheets were placed over each section and the areas of the brain and infarct were measured. The neurological scores were determined at 24th, 48th and 72nd hours after reperfusion. RESULTS: Percent of ischemic area (%) in cerebrum, cerebellum and brain stem level in EPO groups were less than those of control group (p<0.0001). In addition, we determined that EPO group was better than controls of neurologic score and histopathologically after cerebral ischemia. CONCLUSIONS: We concluded that EPO may decrease ischemic area in experimental cerebral ischemia in rats and it seems that EPO may be beneficial.