Quantitation of escitalopram and its metabolites by liquid chromatography‐tandem mass spectrometry in psychiatric patients: New metabolic ratio establishment

Therapeutic drug monitoring (TDM) is used to determine the concentration of drug in plasma/serum to adjust the dose of the therapeutic drug. Selective and sensitive analytical methods are used to determine drug and metabolite levels for the successful application of TDM. The aim of the study was to develop and validate using LC‐MS/MS to analyse quantitative assay of escitalopram (S‐CT) and metabolites in human plasma samples. In order to provide a convenient and safe treatment dose, it was aimed to determine the levels of S‐CT and its metabolites in the patients’ plasma. A new method with short sample preparation and analysis time was developed and validated using LC‐MS/MS to analyse quantitative assay of S‐CT and its metabolites in plasma. Also, plasma samples of 30 patients using 20 mg S‐CT between the ages of 18 and 65 years were analysed by the validated method. The mean values of S‐CT, demethyl escitalopram and didemethyl escitalopram in plasma of patients were 27.59, 85.52 and 44.30 ng/mL, respectively. At the end of the analysis, the metabolic ratio of S‐CT and metabolites was calculated. It is considered that the method for the quantitative analysis of S‐CT and its metabolites in human plasma samples may contribute to the literature on account of its sensitive and easy application. Additionally, the use of our data by physicians will contribute to the effective drug treatment for their patients who take S‐CT.     

Low Prevalence of Hepatitis C Virus Infection Among HIV-Positive Patients: Data From a Large-Scale Cohort Study in Istanbul,Turkey

Background:

Rate of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) varies in different countries. This may be attributable to common transmission routes as well as social, economic, and cultural factors.

Objectives:

The purpose of this study was to investigate the prevalence and risk factors of HCV infection among HIV-positive patients in Istanbul, Turkey.

Patients and Methods:

Since January 2006 to November 2013, 949 HIV-positive patients that were enrolled in this study by ACTHIV-IST (Action Against HIV in Istanbul) Study Group, which consists of five centers to follow up HIV-positive patients in Istanbul. Epidemiologic and clinical data were collected retrospectively from medical records and were transferred to an HIV database system.

Results:

Among 949 patients, 84% were men and the mean age was 37.92 ± 11.54 years (range, 17-79). The most frequent route of transmission was heterosexual intercourse (48.8%), followed by men having sex with men (30.5%). Only nine patients (0.9%) had history of injection drug use (IDU). The prevalence of HIV/HCV coinfection was 0.9% (9:949). The IDU rate was 44.4% (4:9) in patients with HIV/HCV coinfection (three of them were not Turkish citizens), whereas this rate was only 0.6% (5:881) in patients with only HIV infection (P < 0.01). Genotypes 1b, 2a/2c, and 3 were determined in five, one, and two patients, respectively. Genotype could not be determined in one patient. History of residence in a foreign country (P < 0.01) and imprisonment (P < 0.01) were also considered as risk factors in terms of HIV/HCV coinfection.

Conclusions:

Prevalence of HIV/HCV coinfection is considerably low in Turkey. The extremely rare prevalence of IDU might have a role in this low prevalence.     

Reliability and validity of the Turkish version of the Falls Efficacy Scale International (FES-I) in community-dwelling older persons

The FES-I is a questionnaire which was developed to assess fear of falling. The aim of this study was to evaluate validity and reliability of a Turkish language version of the FES-I in Turkish older people. The study sample included 70 volunteers with an age range of 65-81. To assess the test-retest reliability of the Turkish FES-I, questionnaire was applied again 10-15 days after the first interview (interclass correlation: ICC). FES-I was compared with The Modified Barthel Index (MBI), the timed up and go test (TUG), and The Berg Balance Scale (BBS) for construct validity. Cronbach's alpha (α) was used to evaluate the internal consistency. The internal structure of the FES-I was examined by factor analysis. ROC plots were used to define cut-point for the FES-I scales. Cronbach's α of the Turkish FES-I was 0.94 and the individual item ICC ranged from 0.97 to 0.99. The Turkish FES-I total scores were correlated with TUG positively, and MBI, and BBS negatively. The cut-off score to differentiate between persons with fear of falling and persons without fear of falling was 24 points. It was found that the Turkish version of the FES-I was a reliable and valid measure of fear of falling in Turkish older people.     

Is auditory function affected after Le Fort I osteotomy?

The aim of this study was to evaluate changes to the Eustachian tube and middle ear function and hearing level in individuals undergoing Le Fort I osteotomy. 20 consecutive patients underwent Le Fort I maxillary osteotomy with advancement, impaction or a combination of both. All individuals underwent hearing sensitivity tests, including pure tone audiometry and acoustic impedance measurements (middle ear pressure and compliance), which were carried out by an audiologist 1 week before surgery (t(0)), and then again 1 week (t(1)) and 4 weeks (t(2)) after surgery. Regarding pure tone audiometry, the differences between t(0) and t(2) at a frequency of 125Hz (P=.002), between t(0) and t(1) and between t(0) and t(2) at a frequency of 250Hz, and between t(0) and t(1) at a frequency of 1000Hz (P=.006) were statistically significant. There was no statistically significant difference at any other frequency. Regarding middle ear pressure, no statistically significant difference was observed between t(0) and t(1), and t(0) and t(2). Following Le Fort I osteotomy, mild changes in hearing sensitivity and middle ear pressure are possible, but these changes were clinically insignificant.     

Effect of anti-TNF treatment on sleep problems in ankylosing spondylitis

Sleep disturbances and problems are increased in ankylosing spondylitis (AS). But much is not known in a quantitative way about sleep problems and effect of treatments on AS. This study is aimed first, to investigate sleep disturbances in AS and secondly, to evaluate the effects of anti-TNF treatment on SD in AS. One hundred seventy-one (Female/male: 90/81) AS patients fulfilling modified New York criteria and 86 (F/M: 56/30) age- and gender-matched controls without inflammatory diseases were included into the study. Demographic data and disease activity and treatments were recorded using The Bath Ankylosing Spondylitis Functional Index (BASFI) and The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The Medical Outcomes Study (MOS) Sleep Questionnaire was used for evaluating sleep and problems of sleep. AS patients had higher sleep disturbance scale (SDS) and sleep problem index (SPI) II scores. Group A (patients using NSAID and/or DMARD, 53.2% of patients) had higher BASDAI and BASFI compared with Group B (Patients using anti-TNF treatments) (4.29?±?2.38 vs. 2.46?±?2.32, p?<?0.001; 1.95?±?2.15 vs. 0.93?±?1.31, p?<?0.001, respectively). Whereas Group A had higher scores of SDS, awaken short of breath or headache, somnolence, and SPI-II than controls, none of the sleep parameters were statistically different between patients on anti-TNF treatments and controls. BASDAI was positively correlated with SPI-I, SPI-II, SDS, and somnolence scale. AS patients had increased sleep problems and disturbances compared with controls. Anti-TNF agents improve significantly these problems. Sleep problems are significantly correlated with the disease activity.     

Polyarteritis nodosa and Henoch–Schönlein purpura nephritis in a child with familial Mediterranean fever: a case report

Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent self-limited attacks of fever accompanied by peritonitis, pleuritis, and arthritis. Approximately 5% of individuals with familial Mediterranean fever have been reported to have Henoch–Schonlein purpura and about 1% to have polyarteritis nodosa. A 7-year-old girl presenting with complaints of purpuric rash, abdominal pain, arthritis, hematuria, and proteinuria and having IgA depositions on renal biopsy was diagnosed as Henoch–Schönlein nephritis. She had a history of recurrent fever, abdominal and joint pain and M694 V compound homozygote mutation. Colchicine treatment was started for the diagnosis of FMF. When constitutional symptoms such as myalgia, weight loss, fatigue, fever, and hypertension were added to the clinical picture, the diagnosis of polyarteritis nodosa HSP was thought and confirmed by the demonstration of microaneurisms on renal arteries. There was no response to corticosteroid and cyclophosphamide treatments; however, the symptoms were rapidly and dramatically reduced after the administration of intravenous immunoglobulin. In conclusion, polyarteritis nodosa and Henoch–Schonlein purpura can be seen together with familial Mediterranean fever. It is also suggested that IVIG might be an important adjunct therapy in selected patients with polyarteritis nodosa, especially in the lack of response to steroids and immunsuppressive drugs.     

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.     

Melatonin treatment protects against spinal cord injury induced functional and biochemical changes in rat urinary bladder

Oxidative stress induced by spinal cord injury (SCI) has deleterious effects on the function of several organ systems including the urinary bladder. In this study, we investigated the possible protective actions of melatonin on SCI-induced oxidative damage and urinary bladder dysfunction. Wistar albino rats (n = 24) were divided randomly as control, vehicle- or melatonin (10 mg/kg, ip)-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury at T10 was used. Injured animals were given either vehicle or melatonin 15 min postinjury. One week postinjury, each rat was neurologically examined and then decapitated; blood samples were taken to evaluate neuron-specific enolase (NSE) and soluble protein 100β (S-100β). Spinal cord (SC) and urinary bladder samples were taken for functional studies and histological examination or stored for the measurement of malondialdehyde (MDA), glutathione (GSH) and nerve growth factor (NGF) levels and caspase-3 activity. Isometric contractions in bladder strips were induced by carbachol. In the SCI rats, decreased contractile responses of the bladder strips were found to be restored by melatonin treatment. Serum S-100β levels and NSE activities and tissue MDA levels and caspase-3 activities, all of which were elevated in the vehicle-treated SCI animals as compared to the control values, were reversed by melatonin treatment. On the other hand, reduced GSH and NGF levels due to SCI were restored by melatonin treatment. Furthermore, melatonin treatment improved histological findings. These findings suggest that melatonin reduces SCI-induced tissue injury and improves bladder functions through its effects on oxidative stress and NGF.     

Interleukin‐2 gene polymorphism in Turkish patients with Behçet's disease and its association with ocular involvement

Behçet's disease (BD) is a chronic immune‐mediated systemic disease, characterized by oral and genital lesions and ocular inflammation. Several cytokine genes may play crucial roles in host susceptibility to BD, because the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphisms. The association of the interleukin (IL)‐2 gene polymorphisms with the susceptibility to BD was investigated in this study. DNA samples were obtained from a Turkish population of 97 patients with BD and 76 healthy control subjects. Polymorphisms of IL‐2 gene at position ?330 and +166 were determined using the polymerase chain reaction with sequence‐specific primers. In the patients with BD, there was a significantly increased frequency of IL‐2 ?330 GT genotype. Interestingly, we demonstrated that the frequencies of IL‐2 ?330 GT and IL‐2 + 166 GG genotypes were increased in BD patients with ocular involvement, whilst IL‐2 ?330 TT genotype was significantly decreased. Also, analysis of allele frequency demonstrated that the presence of G allele at position +166 of IL‐2 seems to be a risk factor for ocular involvement. These results reveal that IL‐2 ?330 GT genotype may be a susceptibility factor for BD, whereas IL‐2 ?330 TT genotype seems to display a protective association with BD. Additionally, IL‐2 gene polymorphisms might be associated with ocular involvement in BD.