The roles of Klotho and FGF-23 in bipolar manic episode.

OBJECTIVE: Bipolar disorder (manic episode) is an essential psychiatric disorder with unknown etiology, in which inflammation is considered to play a role. Klotho and FGF-23 are known to be associated with inflammation. Therefore, this study aimed to determine the link between Klotho and FGF-23 levels and bipolar disorder. PATIENTS AND METHODS: In this study, 42 men with BD and 41 healthy controls were enrolled, followed up, and/or treated at the High-Security Forensic Psychiatry Clinic. Sociodemographic data form, Young Mania Rating Scale, and Hamilton Depression Rating Scale were applied to all participants. RESULTS: Klotho and FGF-23 levels were significantly increased in patients with BD manic episodes. There was no correlation between Klotho and FGF-23 levels and clinical parameters. For Klotho and FGF-23, cutoff values of 69 and 1,646 yielded 67.4% sensitivity and 72.1% specificity and 81.4% sensitivity and 51.2% specificity, respectively. CONCLUSIONS: Klotho and FGF-23 may play critical roles in the etiopathology of manic episodes and are potential candidate biomarkers for bipolar disorder. This relationship might contribute to the etiopathogenesis of the disease and determine its treatment. Anti-Klotho and anti-FGF-23 administration may be a future treatment for controlling the course of the disease.

The effects and mechanisms of the action of galangin on spatial memory in rats.

BACKGROUND: Galangin, a flavonoid compound with acetylcholinesterase inhibitory activity, may improve cognitive functions by enhancing cholinergic transmission. OBJECTIVES: We aimed to investigate the effects of galangin on spatial memory impairment in rats. METHODS: The effects of galangin (50 and 100 mg/kg) and reference anti-dementia drug donepezil (1mg/kg) administrations were examined on memory impairment induced by the muscarinic cholinergic receptor antagonist scopolamine or the nicotinic cholinergic receptor antagonist mecamylamine in the Morris water maze (MWM) test. Hippocampal acetylcholine concentrations were also determined. RESULTS: Galangin 50 and 100 mg/kg significantly decreased the mean distance to platform and increased the time spent in the escape platform quadrant in scopolamine-treated rats. Galangin 100 mg/kg significantly decreased the mean distance to platform and increased the time spent in the escape platform quadrant in mecamylamine-treated rats. The effects of galangin in the MWM were comparable with donepezil. Scopolamine and mecamylamine decreased acetylcholine concentrations, whereas galangin both alone and with mecamylamine or scopolamine administration increased acetylcholine concentrations. CONCLUSION: Galangin improved memory impairment comparable to donepezil and nicotinic and muscarinic receptors may be involved in this effect. Galangin may be considered as a promising flavonoid in the prevention and treatment of memory impairment in Alzheimer's disease and other dementias (Fig. 7,Ref. 37).

Primary angiosarcoma of the breast: Diagnosis with computer-assisted MRI-guided radio-guided occult lesion localization (ROLL) technique.

Primary angiosarcoma of the breast is a rare type of breast cancer that represents approximately 0.04% of all primary breast tumors. We report herein a case of primary breast angiosarcoma that was only visible on magnetic resonance imaging (MRI) examination. The patient presented with a palpable right breast lump that was not visible either on ultrasonography and mammography. MRI showed a lesion of the right breast that presented washout kinetics. MRI-guided biopsy allowed histopathological examination of the tumor that was further confirmed as primary angiosarcoma. Subsequently, MRI guided ROLL (radio-guided occult lesion localization) technique was used for localizing the lesion prior to surgery.

Dual false positive of 68Ga-DOTA-TATE PET/CT scan in a patient with a history of pancreatic neuroendocrine tumor: A case report / Doble falso positivo de 68Ga-DOTA-TATE PET/CT en una paciente con antecedente de tumor neuroendocrino en páncreas: un caso clínico

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Angiotensin-converting enzyme gene insertion/deletion polymorphism with metabolic syndrome in Turkish patients.

BACKGROUND: The ACE gene has received substantial attention in recent years as candidate for a variety of diseases. The most common polymorphism in ACE gene is the Insertion/Deletion (I/D, rs4646994) polymorphism located on intron 16. AIM: We investigated the association between metabolic syndrome (MS) and the insertion (I) - deletion (D) polymorphisms in the angiotensin converting enzyme (ACE) gene in south-east of Turkey. SUBJECTS AND METHODS: One hundred and sixty subjects, with 101 cases of MS and 59 age- and gender-matched healthy controls were included in the study. RESULTS: The frequency of ACE I/D polymorphism was found to be 49.5% for DD, 36.6% for ID, and 13.9% for II in the MSstudy group and 44.1% for DD, 42.4% for ID and 13.5% for II in the control group. Allele frequencies were found to be 0.68% for D and 0.32% for I allele in the study group with MS and 0.65% for D, 0.35% for I allele in the control group. The I/D polymorphism of the ACE gene, DD, ID, and II genotypes occurred with similar frequencies in the study group with MS and the control group with no significant differences (p<0.05). On applying one-way analysis of variance to different ACE gene polymorphic groups in patients with MS were not significantly associated to ACE gene polymorphism and waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HDL, and LDL (p<0.05). CONCLUSIONS: Further studies of patients in larger numbers and of different ethnic backgrounds may be necessary to elucidate the association between the ACE I/D gene polymorphism and MS.

Takayasu arteritis and ulcerative colitis; coexistence or misdiagnosis?

Takayasu arteritis is a chronic inflammatory disease that primarily affects large arteries such as the aorta and its proximal branches. The association between Takayasu arteritis and ulcerative colitis is an extremely rare condition. Ulcerative colitis is an inflammatory bowel disease, clinical presentation is not specific and may mimic Crohn's disease, radiation colitis, ischemic colitis, a variety of infectious processes, and colitis related to medications. Herein we report a case of Takayasu arteritis who had been misdiagnosed and treated as ulcera-

Radio-guided occult lesion localisation for breast lesions under computer-aided MRI guidance: the first experience and initial results.

OBJECTIVE: The purpose of this study was to present an alternative technique for the pre-operative localisation of solely MRI-detected suspicious breast lesions using a computer-assisted MRI-guided radio-guided occult lesion localisation (ROLL) technique. METHODS: Between January 2009 and June 2010, 25 females with a total of 25 suspicious breast lesions that could be detected only by MRI, and for whom breast surgery was planned, underwent the computer-assisted MRI-guided ROLL technique. A seven-channel biopsy breast array coil and computerised diagnostic workstation were used for the localisation procedure. Three-phase dynamic contrast-enhanced axial images were taken. After investigating the localisation co-ordinates with the help of intervention software on a workstation, an 18 G coaxial cannula was placed in the exact position determined. Following verification of the cannula position by additional axial scans, (99m)Tc-labelled macroalbumin aggregate and MRI contrast material were injected. Post-procedure MRI scans were used to confirm the correct localisation. RESULTS: All the procedures were technically successful. The mean lesion size was 10.8 mm (range: 4-25 mm). The mean total magnet and the mean localisation times were 28.6 min (range: 18-46 min) and 13.1 min (range: 8-20 min), respectively. Grid and pillar methods were used for localisation in 24 procedures and 1 procedure, respectively. On histopathological examination, 6 malignant, 10 high-risk and 9 benign lesions were identified. All patients tolerated the procedure well. There were no major complications. CONCLUSION: This is the first report documenting the application of MRI-guided ROLL. Based on our preliminary results, this technique is very efficient and seems to be a good alternative to wire localisation.

Gadolinium-enhanced MR cisternography to evaluate dural leaks in intracranial hypotension syndrome.

BACKGROUND AND PURPOSE: We evaluated the use of MR cisternography after intrathecal administration of gadopentetate dimeglumine to detect the presence and localization of CSF leaks in 19 patients diagnosed with spontaneous intracranial hypotension syndrome according to the criteria of International Headache Society. MATERIALS AND METHODS: Lumbar puncture with an injection of 0.5 mL of gadopentetate dimeglumine into the subarachnoid space in the lumbar area was performed. MR images of the cervical, thoracic, and lumbar regions in axial, coronal, and sagittal planes with fat-saturated T1-weighted images were acquired. RESULTS: We observed objective CSF leakage in 17 (89%) of 19 patients. In 14 of these 17 patients, the site of dural tear was demonstrated accurately. In 3 of these 17 patients, the contrast leakage was diffuse, and site of the leak could not be located accurately. No leakage was observed in 2 patients. No complications were detected in any of the patients during the first 24 hours after the procedure or during the 6- to 12-month follow-up. CONCLUSION: The current results demonstrate the relative safety, accuracy, and feasibility of intrathecal gadolinium-enhanced MR cisternography to evaluate dural leaks.

Spontaneous intracranial hypotension after labor without spinal intervention.

We present a 29-year-old woman admitted with severe postural headache after spontaneous term labor. Lactation ceased for the duration of headache. Magnetic resonance imaging (MRI) revealed dural thickening that is suggestive of spontaneous intracranial hypotension. CT-cisternography disclosed cervicodorsal dural leak. She was treated with a high-volume epidural blood patch (EBP) and her symptoms were relieved. Lactation returned to normal after EBP. She had normal findings on follow-up MRI examination at 6 months.

Plasma serotonin levels and the platelet serotonin transporter.

Serotonin (5HT) is a platelet-stored vasoconstrictor. Altered concentrations of circulating 5HT are implicated in several pathologic conditions, including hypertension. The actions of 5HT are mediated by different types of receptors and terminated by a single 5HT transporter (SERT). Therefore, SERT is a major mechanism that regulates plasma 5HT levels to prevent vasoconstriction and thereby secure a stable blood flow. In this study, the response of platelet SERT to the plasma 5HT levels was examined within two models: (i) in subjects with chronic hypertension or normotension; (ii) on platelets isolated from normotensive subjects and pretreated with 5HT at various concentrations. The platelet 5HT uptake rates were lower during hypertension due to a decrease in Vmax with a similar Km; also, the decrease in Vmax was primarily due to a decrease in the density of SERT on the platelet membrane, with no change in whole cell expression. Additionally, while the platelet 5HT content decreased 33%, the plasma 5HT content increased 33%. Furthermore, exogenous 5HT altered the 5HT uptake rates by changing the density of SERT molecules on the plasma membrane in a biphasic manner. Therefore, we hypothesize that in a hypertensive state, the elevated plasma 5HT levels induces a loss in 5HT uptake function in platelets via a decrease in the density of SERT molecules on the plasma membrane. Through the feedback effect of this proposed mechanism, plasma 5HT controls its own concentration levels by modulating the uptake properties of platelet SERT.

At diabetes-like concentration, glucose down-regulates the placental serotonin transport system in a cell-cycle-dependent manner.

Serotonin [5-hydroxytryptamine (5HT)] is a vasoconstrictor that also acts as a developmental signal early in embryogenesis. The 5HT transporter (SERT) on the membranes of the placental trophoblast cells controls 5HT levels in the maternal bloodstream to maintain stable transplacental blood flow and simultaneously provide 5HT to the embryo. The 5HT uptake rate of placental SERT is important for both the mother and the developing embryo. The impact of glucose on the placental SERT system during diabetic pregnancy is not known. The present in vitro study investigated this important issue in human placental choriocarcinoma (JAR) cells that were cultured for 24-96 h in a medium containing either 5.5 (physiologic concentration) or 25 mmol/L D-glucose (diabetic-like concentration). The 5HT uptake rates of the cultured cells were not altered at exogenous D-glucose concentrations in the range of 5.5-15 mmol/L, but were decreased significantly at a diabetic-like concentration (>or=25 mmol/L). To understand better the role of glucose on the placental 5HT system, we first characterized SERT in JAR cells at different cell-cycle phases and then determined the expression levels of SERT on the plasma membrane and in the intracellular pools of JAR cells at the late-S and G2 phases, where the uptake rates were decreased 73% under diabetic-like glucose concentrations. Finally, the importance of self-association of SERT molecules was examined. In JAR cells co-expressing Flag- and myc-tagged SERT, myc-antibody precipitated 70% of Flag-SERT, indicating that a large percentage of SERT proteins exist as oligomers in situ. Under diabetic conditions, myc-antibody no longer precipitated Flag-SERT, suggesting a disruption in the aggregation of SERT molecules. Therefore, we propose that under uncontrolled diabetic conditions, glucose down-regulates 5HT uptake rates of placental SERT by interfering with its functional expression in a cell-cycle-dependent manner.

Insulin resistance is not related to plasma homocysteine concentration in healthy premenapausal women.

This study was performed to test whether plasma homocysteine concentrations are related to insulin resistance in healthy premenopausal women. For this purpose, the relationship between insulin resistance (as assessed by HOMA index) and fasting plasma homocysteine level was determined in 83 healthy volunteers. The results indicated that homocysteine concentrations did not vary as a function of HOMA index (r = -0.147). Plasma homocysteine concentrations also did not vary as a function of other parameters of insulin resistance such as HDL-cholesterol and triglycerides, which they correlated inversely with body mass index (BMI). Furthermore, when individuals were classified according to quartiles of insulin resistance (HOMA index), plasma homocysteine concentrations from the lowest to the highest quartiles were not significantly different. On the other hand, the HOMA index correlated significantly with triglyceride concentrations (r = 0.377, p< 0.001), HDL-cholesterol (r = -0.310, p< 0.01) and BMI (r = 0.468, p< 0.001). These results suggest that plasma homocysteine concentrations are not related to insulin resistance and/or metabolic abnormalities associated with it in premenopausal women.

The effects of verapamil on stress- and histamine-induced gastric lesions in rats.

The influence of verapamil on stress-induced and histamine-induced gastric ulcers was investigated in rats. The influence of verapamil was also examined on various biochemical parameters that affect the development of these ulcer models. The animals were pretreated with intraperitoneal verapamil (1, 5, 25 mg/kg) by injection 1 h before the induction of experimental ulceration. The gastric lesions were induced by cold-restraint stress or intraperitoneal injection of histamine (300 mg/kg). The gastroprotective effects of verapamil were evaluated by determining the ulcer index, gastric mucus content, free and total acidity, lipid peroxidation and non-protein sulfhydryl content. Verapamil pretreatment at a dose of 25 mg/kg significantly reduced stress-induced ulcers. Verapamil enhanced mucus secretion, reduced total acidity and lipid peroxidation and decreased non-protein sulfhydryl content in a dose-dependent fashion. On the other hand, pretreatment with verapamil at any dose had no significant effect on histamine-induced ulcers. L-Arginine (L-A) (100 mg/kg) or L-nitroarginine (L-NNA) (100 mg/kg) were also injected i.p. to the animals 1 h before stress to test the role of nitric oxide (NO) in the mechanism of the gastroprotective activity of verapamil (25 mg/kg). The results suggested that verapamil stimulates gastric NO production, but the overproduction of NO worsens gastric ulcers. The effects of verapamil on experimentally induced ulcers may be related to its ability to induce biochemical alterations in the parameters measured in gastric tissue.

Functional consequences of homo- but not hetero-oligomerization between transporters for the biogenic amine neurotransmitters.

Before this study, the human norepinephrine transporter (hNET) was the only member of the biogenic amine neurotransmitter transporter family that had not been demonstrated to be a functional homo-oligomer. Here, using two forms of the transporter, I155C and hNET-myc, with distinct antigenicity and inhibitor sensitivity, we demonstrated that hNET exists as a homo-oligomer. hNET I155C is a functional mutant and is sensitive to inactivation by the sulfhydryl reagent [2-(trimethylammonium)ethyl]methanethiosulfonate, while hNET-myc is resistant to inactivation by this reagent. Coimmunoprecipitation of these two forms demonstrated that a physical interaction exists between norepinephrine transporter monomers. Further characterization of this physical interaction has revealed that the activity of norepinephrine transporters depends on interactions between monomers. Because norepinephrine transporters and serotonin transporters are the only two members of the neurotransmitter transporter family endogenously expressed in the cell membrane of the same cells, placental syncytiotrophoblasts, we tested the ability of norepinephrine transporters and serotonin transporters to associate and function in a hetero-oligomeric form. Similarly, coexpression of hNET-myc with serotonin transporter-FLAG showed a physical interaction in coimmunoprecipitation assays. However, coexpression of serotonin and norepinephrine transporters did not sensitize norepinephrine transporter activity to inhibition by citalopram, a selective serotonin transport inhibitor. Thus, the norepinephrine transporter-serotonin transporter physical association did not produce functional consequences. Based on this, we propose that the transporters for biogenic amine neurotransmitters interact functionally in homo- but not hetero-oligomeric forms.

The effects of vitamin E in ovalbumin-sensitized guinea pigs.

It has been suggested that epithelium destruction, mucus secretion, edema and bronchoconstriction may play a role in asthma pathogenesis. Additionally, histamine, serotonine, leukotrienes and other mediators are released and free oxygen radicals are produced during bronchoconstriction. We studied the role of antioxidants on the treatment of asthma by testing alpha-tocopherol (vitamin E; 5, 25, 50 and 100 mg/kg/day i.p.), a scavenger of oxygen radicals, on male Guinea pigs. The animals were sensitized by injecting ovalbumin. After sensitization, isolated tracheal preparations were studied in vitro. The effects of carbachol 10(-4) M, ovalbumin 10(-3) M and vitamin E (10(-5) M, 10(-4) M, 10(-3) M concentrations) were evaluated in an isolated organ bath. It was observed that alpha-tocopherol reduced the contractile effects of ovalbumin and carbachol. The 5, 25 and 50 mg/kg/day doses of vitamin E were injected intraperitoneally to Guinea pigs that were sensitized with ovalbumin. We observed significant differences between the contractile responses to carbachol and vitamin E with carbachol. These treatments significantly reduced the contractility of tracheal preparations (p < 0.001). There was no significant difference with the 100 mg/kg/day i.p. dose of vitamin E in the contractile response to carbachol E (p > 0.05). The upper part of the tracheal preparations was the most sensitive region to the contractile effect of 10(-3) M ovalbumin in all groups (p < 0.001). The contractile response to 10(-3) M ovalbumin was reduced by 25 and 50 mg/kg/day doses of vitamin E (p < 0.001).

Synthesis and in vitro calcium antagonist activity of 4-aryl-7,7-dimethyl/1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione derivatives.

In this study, a series of 4-aryl-7,7-dimethyl and 1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones (1-25) were synthesized by condensing urea or N-methylurea with 5,5-dimethyl-1,3-cyclohexanedione and appropriate aromatic aldehydes according to the Biginelli reaction. The structures of the compounds were confirmed by spectral data and elementary analysis. The calcium antagonist activity of the compounds was tested in vitro on isolated rat ileum and lamb carotid artery. Compounds 16 and 19 were the most active derivatives on isolated rat ileum compared with the standard nicardipine. On isolated aortic strips of lamb the calcium antagonist activity of compound 16 (maximum relaxant effect: 38.83+/-5.84%) was found as high as that of nicardipine (maximum relaxant effect: 35.50+/-4.16%) used as a reference drug.