Evidence that membrane-bound G protein-coupled melatonin receptors MT1 and MT2 are not involved in the neuroprotective effects of melatonin in focal cerebral ischemia

Melatonin is synthesized and released by the pineal gland in a circadian rhythm, and many of its peripheral actions are mediated via membrane MT1 and MT2 receptors. Apart from its metabolic functions, melatonin is a potent neuroprotective molecule owing to its antioxidative actions. The roles of MT1 and MT2 in the neuroprotective effects of melatonin and cell signaling after cerebral ischemia remain unknown. With the use of MT1 and MT2 knockout (mt1/2(-/-) ) mice treated with melatonin, we evaluated brain injury, edema formation, inducible nitric oxide synthase (iNOS) activity, and signaling pathways, including CREB, ATF-1, p21, Jun kinase (JNK)1/2, p38 phosphorylation, resulting from ischemia/reperfusion injury. We show that the infarct volume and brain edema do not differ between mt1/2(-/-) and wild-type (WT) animals, but melatonin treatment decreases infarct volume in both groups and brain edema in WT animals after middle cerebral artery occlusion. Notably, melatonin's neuroprotective effect was even more pronounced in mt1/2(-/-) animals compared to that in WT animals. We also demonstrate that melatonin treatment decreased CREB, ATF-1, and p38 phosphorylation in both mt1/2(-/-) and WT mice, while p21 and JNK1/2 were reduced only in melatonin-treated WT animals in the ischemic hemisphere. Furthermore, melatonin treatment lowered iNOS activity only in WT animals. We provide evidence that the absence of MT1 and MT2 has no unfavorable effect on ischemic brain injury. In addition, the neuroprotective effects of melatonin appear to be mediated through a mechanism independent of its membrane receptors. The underlying mechanism(s) should be further studied using selective melatonin receptor agonists and antagonists.     

Effect of Agitation of EDTA with 808-Nanometer Diode Laser on Removal of Smear Layer

Introduction

Near-infrared diode lasers can be used for several applications, which range from disinfection to smear layer removal in endodontics. This study evaluated the efficacy of agitation of 15% EDTA with an 808-nm diode laser on removal of the smear layer.

Methods

Sixty extracted human maxillary central incisor teeth were instrumented up to ProTaper F4 (Dentsply Maillefer, Ballagues, Switzerland) and then randomly divided into 6 groups (n = 10 for each group) according to the different final irrigating protocols as follows: 5% sodium hypochlorite for 120 seconds performed with the NaviTip (Dentsply Maillefer, Ballaigues, Switzerland) (control group); 15% EDTA for 120 seconds performed with the NaviTip; and agitation of 15% EDTA with an 808-nm diode laser for 10, 20, 30, and 40 seconds. Specimens were observed under a scanning electron microscope, and open dentinal tubules were counted using Adobe Photoshop software (Adobe Systems, San Jose, CA). The data were analyzed with 1-way analysis of variance and Tukey post hoc tests (P = .05).

Results

The number of open dentinal tubules was higher in the middle thirds than in the apical thirds. The differences between the apical and middle thirds were statistically significant (P < .05). Statistically significant differences were also found between the control group and the other groups in both the middle and apical thirds of the root canals (P < .05).

Conclusions

The results indicated that agitation of 15% EDTA with an 808-nm diode laser for 20 seconds was effective in removing the smear layer in the apical thirds of root canals.     

Synergistic effect of multiple predisposing risk factors on the development of bezoars

AIM: To describe the clinical characteristics of patients with gastric or intestinal bezoars recently treated in our hospital.METHODS: In this study, a retrospective chart review of consecutive patients with gastrointestinal bezoars, who were treated at the Samsun Education and Research Hospital between January 2006 and March 2011, was conducted. Data on demographic characteristics, clinical presentation, history of risk factors, diagnostic procedures, localization of bezoars, treatment interventions, and postoperative morbidity and mortality rates were collected and evaluated.RESULTS: Forty-two patients [26 (61.9%) males and 16 (31.1%) females] with a mean ± SD (range) age of 55.8 ± 10.5 (37-74) years were enrolled in this study. Thirty-six patients (85.7%) had one or more predisposing risk factors for gastrointestinal bezoars. The most common predisposing risk factor was a history of previous gastric surgery which was identified in 18 patients (42.8%). Twenty three patients (54.8%) had multiple predisposing risk factors. Phytobezoars were identified in all patients except one who had a trichobezoar in the stomach. Non-operative endoscopic fragmentation was performed either initially or after unsuccessful medical treatment in 14 patients with gastric bezoars and was completely successful in 10 patients (71.5%). Surgery was the most frequent treatment method in our study, which was required in 28 patients (66.7%). Intestinal obstruction secondary to bezoars was the most common complication (n = 18, 42.8%) in our study.CONCLUSION: The presence of multiple predisposing factors may create a synergistic effect in the development of bezoars.     

Serum adipokines and low density lipoprotein subfraction profile in hypopituitary patients with growth hormone deficiency

The aim was to evaluate the concentrations of lipid subfractions in relation to adipokines and metabolic parameters in adult growth hormone (GH)-deficient hypopituitary patients on conventional replacement therapy. The study included 21 GH deficient-hypopituitary patients (age: 36.0 ± 15.1 years, male/female: 7/14) on conventional replacement therapy other than GH and 20 comparable controls (age: 37.3 ± 14.0 years, male/female: 6/14). Lipid subfractions (Lipoprint system), serum adipokine (leptin, adiponectin, resistin) concentrations, body composition, a surrogate marker for insulin resistance (HOMA) and conventional lipid profile were evaluated. No statistically significant difference was found with respect to HOMA, adipokine concentrations and anthropometric parameters between patients and controls except for significantly increased waist-to-hip ratio in hypopituitary group. Total and LDL cholesterol concentrations were significantly higher in the patients. LDL particle size (268.88 ± 3.16 vs. 271.31 ± 3.11 ?, P = 0.151) and small-dense LDL subfraction did not differ significantly. According to logistic regression analysis, triglyceride concentrations ≥1.69 mmol/L was the sole parameter significantly and independently predicted small (<268 ?) LDL particle size (P = 0.019) in the whole group. Increased triglyceride concentrations affect LDL particle size in GH-deficient hypopituitary patients. Small dense LDL seems not directly contribute to atherogenic potential in hypopituitarism.     

Digoxin intoxication: An old enemy in modern era

Objectives Although development of new treatment modalities limited digoxin usage, digoxin intoxication is still an important issue which could be easily overlooked. In this report we analyzed a case series definitively diagnosed as digoxin intoxication in the modern era. Methods We analyzed 71 patients hospitalized with digoxin intoxication confirmed by history, complaints, clinical and electrocardiograph (ECG) findings, and serum digoxin levels > 2.0 ng/mL, during a five year period. The demographic and clinical data, indications for digoxin use, digoxin dosage, concurrent medications, laboratory data, hospital monitoring, and ECG findings were obtained from all patients. Results Thirty-eight of 71 patients (53.5%) had symptoms of heart failure during admission or later. Sixty-four percent of patients were older than 75 years. The percentage of females was 67%. Atrial fibrillation, hypertension and gastrointestinal complaints were more frequent in the females (64% in females, 30% in males, P = 0.007; 81% in female, 52% in males, P = 0.01; 50% in female, 17.3% in males, P = 0.008, respectively). The mortality rate during the hospital course was 7%. Conclusion This report demonstrated the reduced mortality rates in patients with digoxin intoxication over the study period. Gastrointestinal complaints are the most common symptoms in this population.     

The Relationship between the MEFV Genotype,Clinical Features,and Cytokine-Inflammatory Activities in Patients with Familial Mediterranean Fever

Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by periodic attacks of fever and polyserositis. The effects of the MEFV genotype differences on clinical picture and inflammatory activity have not been well documented. The aim of this study was to investigate levels of conventional inflammation markers, procalcitonin, interleukin levels, TNF-alpha, and C5a levels in patients with FMF who had different MEFV genotypes and compare them with those of healthy subjects. The study consisted of 41 patients with FMF (F/M: 23/18), and 31 healthy subjects (F/M: 18/13). Tests were performed during the attack-free period.

White-blood cell count, CRP and IL-8 levels were higher in patients with FMF than in healthy subjects (p < 0.05) and also higher in M680I carriers than in the patients with M694V allele carriers. However, ESR, fibrinogen, procalcitonin, IL-6, C5a, TNF-alpha, and IgD levels were not significantly different between patients and healthy subjects (p > 0.05). Arthralgia or arthritis was significantly higher in M694V carriers than in non-M694V carriers (p < 0.05). It is concluded that the clinical features and inflammatory-cytokine activities were higher in patients with FMF during the attack-free period than in healthy subjects, and the different genotype might be related to different clinical pictures.     

Comparison of microscopic (pT3a) and gross extravesical extension (pT3b) in pathological staging of bladder cancer: analysis of patient outcomes

Objective

To determine the prognostic value of pT3 bladder urothelial carcinoma substaging in patients without lymphatic involvement.

Patients and methods

Pathologic and clinical data were reviewed on patients who underwent radical cystectomy for urothelial carcinoma between 1991 and 2010. Of the 460 reviewed patients, 74 patients were diagnosed with pathologic T3No urothelial carcinoma of the bladder. The impact of pathologic substaging (pT3a vs. pT3b) was examined to determine the effect on overall and disease-specific survival.

Results

Five years disease-specific and overall survival rates were 46.9 % and 39.6 % for patients with pT3aNo tumor, whereas these ratios were 34.4 and 30.3 %, respectively, for patients with pT3bNo tumor (p > 0.05). Mean disease-specific survival time was 43.94 ± 6.50 months for pT3aNo, while it was 39.01 ± 7.19 months for pT3bNo (p = 0.539). In multivariate cox regression analysis, age (p = 0.459), gender (p = 0.710), urinary diversion type (p = 0.088), and pT3 substaging (p = 0.554) were not noticed as an independent predictive factor for survival.

Conclusion

Macroscopic extravesical extension (pT3b) is not associated with a worse outcome than pT3a disease in lymph node-negative cases of bladder urothelial carcinoma.     

A rare inguinal mass: Round ligament leiomyoma

INTRODUCTIONLeiomyoma of the round ligament is a rare condition and usually appears like an inguinal hernia.PRESENTATION OF CASEWe report a case of a 40 year-old women found to have an inguinal mass which it was finally diagnosed as leiomyoma.The patient was admitted to our hospital with a history of painless groin mass. The mass was thought to be irreducible inguinal hernia. Surgical exploration demonstrated a round ligament leiomyoma.DISCUSSIONA smooth muscle tumor in the round ligament of the uterus in the inguinal region is a rare entity and can be mistaken for an irreducible inguinal hernia. It is a rare condition occurring predominantly in premenopausal middle-aged women. Abdominal, inguinal, and vulvar locations have been described. Surgical excision is the curative treatment.CONCLUSIONLeiomyoma of the round ligament should be entertained as a possible etiology of inguinal mass.     

Spectroscopic,antiproliferative and antiradical properties of Cu(II), Ni(II), and Zn(II) complexes with amino acid based Schiff bases

Novel six Cu(II), Ni(II), and Zn(II) complexes with Schiff bases derived from 4-aminobenzoic acid with terephtaldehyde and amino acids (glycine, β-alanine). Structures have been proposed from elemental analysis, UV–Vis, IR, NMR, TGA, DTA, and magnetic measurements. Spectroscopic studies suggest that coordination occurs through azomethine nitrogen, hydroxyl group, and carbonyl oxygen of the ligands to the metal ions. The elemental analyses of the complexes where L is Schiff base ligands, are confined to the stoichiometry of the type M₂L₂(CH₃COO)₂ [M = Cu(II)]; and M₂L(CH₃COO)₂ [M = Ni(II) and Zn(II)]. The cytotoxicity activities of the compounds against human breast carcinoma MCF-7 cell line have been studied. Ligands and their Zn(II) compounds inhibited cell proliferation of MCF-7 cancer cell lines in a dose- and time-dependent manner. The free radical scavenging activity was measured by 1,1-diphenyl-2-picryl-hydrazil. Our results show that the synthesized compounds induced oxidative damage by increasing the lipid peroxidation in yeast since MDA formation was increased, and it could be concluded that the synthesized compounds caused oxidative stress. In addition, the antioxidant activities of the synthesized compounds were very much lower than those of standard antioxidants.