DNA Damage in Major Psychiatric Diseases

Human cells are exposed to exogenous insults and continuous production of different metabolites. These insults and unwanted metabolic products might interfere with the stability of genomic DNA. Recently, many studies have demonstrated that different psychiatric disorders show substantially high levels of oxidative DNA damage in the brain accompanied with morphological and functional alterations. It reveals that damaged genomic DNA may contribute to the pathophysiology of these mental illnesses. In this article, we review the roles of oxidative damage and reduced antioxidant ability in some vastly studied psychiatric disorders and emphasize the inclusion of treatment options involving DNA repair. In addition, while most currently used antidepressants are based on the manipulation of the neurotransmitter regulation in managing different mental abnormalities, they are able to prevent or reverse neurotoxin-induced DNA damage. Therefore, it may be plausible to target on genomic DNA alterations for psychiatric therapies, which is of pivotal importance for future antipsychiatric drug development.     

The beneficial effects of 18β-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model

This study investigated the effects of 18β-glycyrrhetinic acid (GA) on neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in C57BL/J6 mice. All subjects (n = 40) were equally divided into four groups: (1) sham-operated (SH), (2) I/R, (3) GA, and (4) GA+I/R. The SH group was used as a control. In the I/R group, the bilateral carotid arteries were clipped for 15 min, and the mice were treated with the vehicle for 10 days. In the GA group, mice were given GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the GA+I/R group, the I/R model was applied to the mice exactly as in the I/R group, and they were then treated with the same dose of GA for 10 days. Cerebral I/R significantly induced oxidative stress via an increase in lipid peroxidaitons and a decrease in elements of the antioxidant defense systems. However, GA treatment was protective against the oxidative effects of I/R by inducing significant increases in antioxidant defense systems and a significant decrease of lipid peroxidations. Additionally, cerebral I/R increased the incidence of histopathological damage and apoptosis in brain tissue, but these neurodegenerative effects were eliminated by GA treatment. Therefore, the current study demonstrated that GA treatment effectively prevents oxidative and histological damage in the brain caused by global I/R. In this context, GA may be useful for the attenuation of the negative effects of global cerebral I/R and, in the future, it may be a viable and safe alternative treatment for ischemic stroke in humans.     

The value of combined peritumoral and subdermal injection techniques for lymphoscintigraphy in detection of sentinel lymph node in breast cancer

PURPOSE: The aim of this study was to evaluate the success rate of combined peritumoral and subdermal injection techniques based on our previous experience on different injection techniques for lymphoscintigraphy. PATIENTS AND METHODS: Fifty-nine women with early breast cancer (mean tumor size, 20.5 mm) were prospectively studied. On the morning of the operation, each patient had 2 injections, one peritumoral (PT) medial to the lesion and one subdermal (SD) into the skin over the tumor quadrant. Each injection consisted of 20 MBq (540 mCi) Tc-99m rhenium sulfide colloid. Early dynamic and delayed static images were obtained up to 4 hours after injections. An intraoperative gamma probe was used to explore the axillary sentinel lymph nodes (SLN). All surgical specimens were evaluated histopathologically. RESULTS: Forty patients had breast-preserving surgery and 19 had modified radical mastectomy. Thirty-eight patients had axillary dissection. All but 4 patients showed axillary lymphatic drainage. Twelve of 59 patients (20%) showed extraaxillary drainage with lymphoscintigraphy. Combined injection technique yielded a 93.2% success rate in detecting axillary SLN. In 2 of 4 patients with no drainage on lymphoscintigraphy, intraoperative gamma probe revealed SLN during the surgery. Twenty patients (33%) had positive axillary lymph nodes. In 14 of them, the SLN was the only positive node. A false-negative rate was found 1.6% (one of 59 patients). CONCLUSION: This results suggest that a combination of both PT and SD techniques increases the success rate of visualization SLN and enhances the visualization of extraaxillary nodes for further treatment planning.     

Central Nervous System Effects of Ginkgo Biloba, a Plant Extract

Extracts of Ginkgo biloba (EGb) are among the most prescribed drugs in France and Germany. EGb is claimed to be effective in peripheral arterial disorders and in "cerebral insufficiency." The mechanism of action is not yet well understood. Three of the ingredients of the extract have been isolated and found to be pharmacologically active, but which one alone or in combination is responsible for clinical effects is unknown. The recommended daily dose (3 x 40 mg extract) is based more on empirical data than on clinical dose-findings studies. However, despite these, according to double-blind, placebo-controlled clinical trials, EGb has therapeutic effects, at least, on the diagnostic entity of "cerebral insufficiency," which is used in Europe as synonymous with early dementia. To determine whether EGb has significant pharmacological effects on the human brain, a pharmacodynamic study was conducted using the Quantitative Pharmacoelectroencephalogram (QPEEG(R)) method. It was established that the pharmacological effects (based on a predetermined 7.5--13.0-Hz alpha frequency band in a computer-analyzed electroencephalogram = CEEG(R)) of EGb on the central nervous system (CNS) are significantly different than placebo, and the high and low doses could be discriminated from each other. The 120-mg, but particularly the 240-mg, single doses showed the most consistent CNS effects with an earlier onset (1 h) and longer duration (7 h). Furthermore, it was established that the electrophysiological effects of EGb in CNS are similar to those of well-known cognitive activators such as "nootropics" as well as tacrine, the only marketed "antidementia" drug currently available in the United States.     

Blood Pressure Changes in Migraine Patients before,during and after Migraine Attacks

Migraine attacks are characterized by headaches associated with neurological, gastrointestinal, and autonomic symptoms. A relationship between migraine and hypertension or hypotension is controversial. In this study, we aimed to determine if blood pressure changes were related to migraine attacks. From the outpatient clinic of our neurology department, 62 normotensive migraine patients with and without aura were chosen for study in accordance with the International Headache Society 2004 criteria. A questionnaire including general and specific questions was given to the patients to be filled out during 6 consequent migraine attacks. The patients received a fully automatic digital brachial upper arm sphygmomanometer (Omron M 4‐1) to measure the changes in their blood pressure during attacks. The patients were asked to record their blood pressure changes 3 times: (1) just before or very early, (2) during (when headache peaks), and (3) 1 hour after the attack. Twenty‐three of the 62 patients (57 women, 5 men) had migraine with aura (22 women and 1 man), and 39 of them did not have aura (35 women and 4 men). There was no statistically significant difference between systolic and diastolic values obtained before or very early, during the peak level, and 1 hour after the end of the attacks (P > 0.05). Although diastolic hypotensive values were not different statistically between groups, when all the patients were considered, diastolic hypotensive values were detected in a considerable number of patients (a total of 115 measurements). In this normotensive migrainous population, we observed that diastolic hypotension before or very early, during, and after migraine attack was the most significant result (5.1%). Although it was not statistically significant, the total number of hypotensive values was remarkable.     

<Emphasis Type="Italic">Demodex folliculorum</Emphasis> in patients with rheumatoid arthritis

The objective of this study was to investigate the incidence and density of Demodex folliculorum in the patients with rheumatoid arthritis (RA). Forty-one patients with RA and twenty-seven age and sex matched healthy controls were enrolled in this study. Disease Activity Score (DAS 28) was used for the assessment of disease activity. Out of 41 patients, 33 were females and 8 males. The mean disease duration was 10.9 ± 8.2 years. The mean DAS 28 was 3.8 ± 1.2. No statistically significant differences in the incidence and density of Demodex mites were found between patients with RA and controls. Although immunosuppression is thought to be a risk factor for the D. folliculorum infestation no such correlations could be found in the 41 immunosuppressed patients with RA, therefore, further studies with larger groups are needed.     

Facial asymmetry in young healthy subjects evaluated by statistical shape analysis

Statistical shape analysis, a relatively a new method for biological research, compares body forms by using specific landmarks determined by anatomical prominences. In this study, we aimed to identify normal facial asymmetry between the right and the left sides of the face. Facial landmark data were collected from two‐dimensional digital images of 321 young healthy subjects (150 males and 171 females). These data were analysed using Euclidean distance matrix analysis. The number of significantly asymmetric linear distances between the two halves of the face was greater in females than in males. We found that the left side of the face was most commonly dominant in both males and females. Such data may be useful in establishing a database for future similar studies.     

Relation of discoid lateral meniscus and cord-like anterior intermeniscal ligament: morphological and clinical study

Discoid lateral meniscus is a rare disorder and its association with other variations in the knee joint has been reported. The anterior intermeniscal ligament has also been described as connecting the anterior convex margin of the lateral meniscus to the anterior horn of the medial meniscus. In the normal population, it was observed at 53–94%. Although the functional properties of the anterior intermeniscal ligament are not yet clarified, two distinct types of the ligament have been described according to their morphological characteristics as cord-like and membranous types. The purpose of this study was to evaluate any possible association between morphologic types of anterior intermeniscal ligament and discoid lateral meniscus. A retrospective study was designed; 20 discoid lateral menisci were operated using routine arthroscopic examination. Upon arthroscopic examination the thickness of the ligament and associated morphological changes were recorded systematically. The cord-like anterior intermeniscal ligament was an associated structure in 15 of the 20 knees with discoid lateral meniscus (75%). Patients with discoid lateral meniscus apparently have cord-like type anterior intermeniscal ligament, thus we conclude that cord-like type of anterior intermeniscal ligament is a frequent accompanying structure to discoid lateral meniscus and may have a potential stabilizing effect on its anterior stability.     

Surveillance and oseltamivir resistance of human influenza a virus in Turkey during the 2007–2008 season

Monitoring the activity of influenza viruses is important for establishing the circulating types and for detection of the emergence of novel sub‐types and antiviral resistant strains. This is the first report from Turkey on the surveillance and oseltamivir resistance of influenza viruses in 2007–2008. Five hundred twenty‐four nasal swabs were tested from different geographical regions in Turkey during November 2007–April 2008. One hundred sixty‐three (31%) samples were positive for influenza viruses of which 111 (68%) were influenza A, 52 (31%) influenza B using an immuno‐capture ELISA. Forty isolates were selected at random from influenza A positive samples and grown in MDCK cell cultures. The supernatant of the cell cultures was used for RNA extraction followed by RT‐PCR to detect the sub‐types. Sub‐typing revealed all samples as A/H1N1. The N1 gene segment of 30 A/H1N1 samples was sequenced in part, from the 201st to 365th residue, which included the critical region for oseltamivir resistance. Then resulting sequences were analyzed with oseltamivir sensitive and resistant strains obtained from National Center for Biotechnology Information (NCBI) GenBank by CLC Main Workbench Software. H275Y (H274Y according to N2 numbering) mutation, which is known to confer resistance to oseltamivir, was detected in 6 out of 30 (20%) H1N1 isolates from four cities (Istanbul, Bursa, Ankara, and Izmir). The D354G mutation was observed in all oseltamivir resistant H1N1 isolates but not in the oseltamivir sensitive isolates. Assay of neuraminidase activity revealed that these isolates were resistant to oseltamivir, but sensitive to zanamivir. J. Med. Virol. 81:1645–1651, 2009. © 2009 Wiley‐Liss, Inc.     

Bilateral adnexal torsion due to postmenopausal hydatidiform mole

Occurrence of gestational trophoblastic neoplasia (GTN) and adnexal torsion is rare in postmenopause. We report a 58-year-old postmenopausal woman with adnexal torsion caused by hydatidiform mole. The patient was admitted to our clinic complaining of acute abdominal pain, nausea and vomiting lasting one day. Ultrasonography showed an enlarged uterus including hypo/hyperechogenous cystic areas in the endometrial cavity and bilateral adnexal masses. β-HCG level was investigated and determined as 157.000 IU/l, because of the suspicion of GTN in ultrasonography. Doppler sonography revealed enlarged left adnexa with absence of vascular flow. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. β-HCG decreased to normal ranges in the fourth postoperative week. The resected uterus contained an endometrial, cystic, grapelike tumor. The ovaries were enlarged bilaterally with necrotic appearance. Histopathology revealed complete hydatidiform mole and theca lutein cysts. To our knowledge, the present case is the first hydatidiform mole associated with bilateral adnexal torsion caused by theca lutein cysts in postmenopausal period.