The antidepressant agomelatine blocks the adverse effects of stress on memory and enables spatial learning to rapidly increase neural cell adhesion molecule (NCAM) expression in the hippocampus of rats

Agomelatine, a novel antidepressant with established clinical efficacy, acts as a melatonin receptor agonist and 5-HT(2C) receptor antagonist. As stress is a significant risk factor in the development of depression, we sought to determine if chronic agomelatine treatment would block the stress-induced impairment of memory in rats trained in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. Moreover, since neural cell adhesion molecule (NCAM) is known to be critically involved in memory consolidation and synaptic plasticity, we evaluated the effects of agomelatine on NCAM, and polysialylated NCAM (PSA-NCAM) expression in rats given spatial memory training with or without predator stress. Adult male rats were pre-treated with agomelatine (10 mg/kg i.p., daily for 22 d), followed by a single day of RAWM training and memory testing. Rats were given 12 training trials and then they were placed either in their home cages (no stress) or near a cat (predator stress). Thirty minutes later the rats were given a memory test trial followed immediately by brain extraction. We found that: (1) agomelatine blocked the predator stress-induced impairment of spatial memory; (2) agomelatine-treated stressed, as well as non-stressed, rats exhibited a rapid training-induced increase in the expression of synaptic NCAM in the ventral hippocampus; and (3) agomelatine treatment blocked the water-maze training-induced decrease in PSA-NCAM levels in both stressed and non-stressed animals. This work provides novel observations which indicate that agomelatine blocks the adverse effects of stress on hippocampus-dependent memory and activates molecular mechanisms of memory storage in response to a learning experience.     

Evaluation of total oxidative and antioxidative status in pediatric patients undergoing laparoscopic surgery

Objective

Reactive oxygen species (ROS) induced by several diseases can trigger oxidative stress. During laparoscopy, increased intraabdominal pressure caused by pneumoperitoneum may lead to splanchnic ischemia followed by reperfusion because of deflation. Because ischemia reperfusion creates oxidative stress, in this study, we aimed to investigate the oxidative-antioxidative status of the pediatric patients with laparoscopic surgery.

Methods

The children underwent laparoscopic procedures under general anesthesia, and they were mechanically ventilated. Blood samples were obtained after induction of anesthesia, at the end of the surgery, and were centrifuged at 3000 revolutions per minute for 10 minutes to separate plasma. The plasma total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were determined.

Results

Plasma TOS and OSI levels were significantly higher at the end of the surgery than after induction of anesthesia (P < .05 and P < .01, respectively). On the other hand, plasma TAS levels were lower in the end of the surgery than after induction of anesthesia (P < .05).

Conclusions

These results suggest that ROS are generated during the laparoscopic procedure, possibly as a result of an ischemia-reperfusion phenomenon induced by the inflation and deflation of the pneumoperitoneum, which causes oxidative stress and consume plasma antioxidants.     

Mechanical failure with malleable penile prosthesis

Mechanical failure with a malleable penile prosthesis is very rare, and no mechanical failure has been reported with the AMS 650 malleable penile prosthesis. A 67-year-old man, using the AMS 650 malleable penile prosthesis without a problem since 1999, presented with right penile deformity and difficulty in sexual intercourse for the preceding 2 months. Physical examination showed dislocation of the right rod of the penile prosthesis, and surgical exploration revealed a fracture in the rod. The malfunctioning right penile prosthesis was removed, and a new AMS 650 malleable penile prosthesis was implanted. The patient did not have any problem at 1-year follow-up.     

Risk assessment study of the pressure ulcers in intensive care unit patients

In this research, we studied the incidence of pressure ulcer and risk factors and screening of the patients for pressure ulcers at intensive care unit on the first day of admission in 142 patients. All patients were evaluated according to National Pressure Ulcer Advisory Panel during the ICU period strictly. Pressure ulcer risk evaluation was performed according to Norton Scale. Nutritional state was evaluated according to nutritional risk screening 2002. Age, hospitalization period, mean arterial pressure, pressure ulcer degree, hemoglobin and albumin levels, body mass index, APACHE-II scores and comorbidities were evaluated. In the following parameters, first value represents PU (+) cases, and second value represents PU (?) cases. On the admittance: 14 (9.8%) patients had PU (prevalence). NRS-2002: 5.4 ± 1.9 and 4.3 ± 2.1 (p < 0.05), Norton score: 8.4 ± 4.7 and 13.9 ± 4.6 (p < 0.05), albumin 2.7 ± 0.7 g/dl and 3.2 ± 0.8 g/dl (p < 0.05). MAP and hemoglobin levels were not different (p > 0.05). Mean pressure ulcer degree was 2.15. On the discharge: first values represent new developed PU (+) patients and second values represent PU (?) cases. 25 (17.6%) patients had PU. Incidence was 7.8%. NRS-2002: 6.4 and 3.6 (p < 0.05), Norton score: 7.1 and 14.4 (p < 0.05), albumin 2.2 g/dl and 3.0 g/dl (p < 0.05). MAP 55.15 ± 24.10 mm Hg and 79.76 ± 18.12 mm Hg (p < 0.05), APACHE-II score 22.3 ± 4.2 and 18.2 ± 6.2 (p < 0.05). Hospitalization period: 18.3 ± 10.3 days and 6.6 ± 4.3 days (p < 0.05) respectively. BMI and hemoglobin levels were not different (p > 0.05). Two or more co morbidity, neurophyschiatric disorders, infections and medications were more prevalent in PU (+) group (p < 0.05).Results of this study show us the PU incidence of ICU patients may be low if we perform PU screening all patients at the admission and put into practice NPUAP strictly. Age, low Norton score, hospitalization period, high APACHE-II score, hypotension, malnutrition and hypoalbuminemia were significant in patients with PU; however, BMI and hemoglobin were not significant. The studies focusing on the relation between the effect of optimization of these parameters from the first day of admittance and pressure ulcer are required.     

Long term effects of hormone replacement therapy on heart rate variability, QT interval, QT dispersion and frequencies of arrhythmia

BACKGROUND: The aim of the study was to investigate the effects of a long term (1 year) hormone replacement therapy (HRT) on QT interval, QT dispersion (QTd) frequencies of arrhythmia and heart rate variability (HRV) parameters. METHODS: Forty-six healthy postmenopausal women (mean age; 55.34+/-4.21) as a hormone replacement therapy group and 25 healthy premenopausal women (mean age; 35.36+/-6.06) as a control group were prospectively enrolled to the study. Hormone replacement therapy group was divided into two groups; estrogen replacement therapy (ERT) group (n=23) and progestin-estrogen replacement therapy (PERT) group (n=23). Standard 12 lead electrocardiograms and 24-h ambulatory Holter recording were obtained to evaluate the effects of one year of ERT and PERT on QT intervals, QTd, frequencies of arrhythmias and HRV parameters. RESULTS: Long term use of ERT increases QT interval, QTd, in the frequencies of arrhythmia and HRV indexes of parasympathetic activity; however, the increase in frequencies of arrhythmia was not statistically significant (p>0.05). Long term use of PERT did not effected QT interval, QTd, frequencies of ventricular arrhythmia and HRV parameters (p>0.05). Frequency of supraventricular tachycardia increased in post-treatment PERT group was compared with pre-treatment PERT group. CONCLUSION: These findings supported the hypothesis that estrogen may directly modulate ventricular repolarization. But progestin do not effect the ventricular repolarization. However, these findings must be supported with a large-scale study.     

Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene

Hereditary juvenile megaloblastic anemia due to vitamin B12 (cobalamin) deficiency is caused by intestinal malabsorption of cobalamin. In Imerslund-Grasbeck syndrome (IGS), cobalamin absorption is completely abolished and not corrected by the administration of intrinsic factor (IF); if untreated, the disease is fatal. Biallelic mutations either in the cubilin (CUBN) or amnionless (AMN) gene cause IGS. In a series of families clinically diagnosed with likely IGS, at least six displayed no evidence of mutations in CUBN or AMN. A genome-wide search for linkage followed by mutational analysis of candidate genes was performed in five of these families. A region in chromosome 11 showed evidence of linkage in four families. The gastric IF (GIF) gene located in this region harbored homozygous nonsense and missense mutations in these four families and in three additional families. The disease in these cases therefore should be classified as hereditary IF deficiency. Clinically, these patients resembled those with typical IGS; radiocobalamin absorption tests had been inconclusive regarding the nature of the defect. In the diagnosis of juvenile cobalamin deficiency, mutational analysis of the CUBN, AMN, and GIF genes provides a molecular characterization of the underlying defect and may be the diagnostic method of choice.     

Therapeutic potential of antiviral drugs targeting chemorefractory colorectal adenocarcinoma cells overexpressing endogenous retroviral elements

Background

Endoretroviruses account for circa 8 % of all transposable elements found in the genome of humans and other animals. They represent a genetic footprint of ancestral germ-cell infections of exoviruses that is transmittable to the progeny by Mendelian segregation. Traces of human endogenous retroviruses are physiologically expressed in ovarial, testicular and placental tissues as well as in stem cells. In addition, a number of these fossil viral elements have also been related to carcinogenesis. However, a relation between endoretroviruses expression and chemoresistance has not been reported yet.

Methods

Twenty colorectal carcinoma patient samples were scrutinized for HERV-W_E1 and HERV-FRD₁ endoretroviruses using immunohistochemical approaches. In order to search for differential expression of these elements in chemotherapy refractory cells, a resistant HCT8 colon carcinoma subline was developed by serial etoposide exposure. Endoretroviral elements were detected by immunocytochemical staining, qPCR and ELISA. IC₅₀-values of antiviral and cytostatic drugs in HCT8 cells were determined by MTT proliferation assay. The antivirals-cytostatics interaction was evaluated by the isobologram method.

Results

In this work, we show for the first time that HERV-W_E1, HERV-FRD₁, HERV-3₁, and HERV-V₁ are a) simultaneously expressed in treatment-naïve colon carcinoma cells and b) upregulated after cytostatic exposure, suggesting that these retroviral elements are intimately related to chemotherapy resistance. We found a number of antiviral drugs to have cytotoxic activity and the ability to force the downregulation of HERV proteins in vitro. We also demonstrate that the use of different antiviral compounds alone or in combination with anticancer agents results in a synergistic antiproliferative effect and downregulation of different endoretroviral elements in highly chemotherapy-resistant colorectal tumor cells.

Conclusions

Enhanced HERV-expression is associated with chemoresistance in colon carcinomas which can be overcome by antiviral drugs alone or in combination with anticancer drugs. Therefore, the introduction of antiviral compounds to the current chemotherapy regimens potentially improves patient outcomes.

Electronic supplementary material

The online version of this article (doi:10.1186/s13046-015-0199-5) contains supplementary material, which is available to authorized users.     

Thoracodorsal artery perforator fasciocutaneous flap: A versatile alternative for coverage of various soft tissue defects

Objective:

The thoracodorsal artery perforator (TDAP) flap has contributed to the efficient reconstruction of tissue defects that require a large amount of cutaneous tissue. The optimal reconstruction method should provide thin, and well-vascularized tissue with minimal donor-site morbidity. The indications for the use of this particular flap with other flaps are discussed in this article.

Materials and Methods:

Thirteen patients underwent soft tissue reconstruction using TDAP flaps between 2009 and 2011. Of those, there were four cases of antecubital burn contracture, three cases of axillary burn contracture, two cases of giant hair cell nevus of upper extremity, two cases of axillary reconstruction following severe recurrent hidradenitis, and two cases of crush injury. All patients were male and their ages ranged from 20 to 23 (average, 21 years). The mean follow-up period was 8 months (range, 4-22 months).

Results:

All reconstructive procedures were completed without any major complications. Minor complications related to transfered flaps were wound dehiscence in one case, transient venous congestion in two cases. Minor complication related to the donor site was seroma in one case. The success rate was 100%, with satisfactory cosmetic results.

Conclusions:

The TDAP flap is a safe and extremely versatile flap that offers significant advantages in acute and delayed reconstruction. Although the vascular anatomy may be variable, free and pedicled TDAP flap is a versatile alternative for soft tissue defects. It adapts very well to the soft tissue defects with acceptable donor site scar.KEY WORDS: Burn contracture, hidradenitis suppurativa, soft tissue defects, the thoracodorsal artery perforator, thoracodorsal artery perforator flap     

Inter- and intraobserver reliability of the Crowe and Hartofilakidis classifications in the assessment of developmental dysplasia of the hip in adult patients

Background

The purpose of this study is to investigate the inter- and intraobserver reliability of Crowe and Hartofilakidis classifications in the assessment of developmental dysplasia of the hip in adult patients.

Materials and methods

Two consultant orthopedic surgeons classified 141 dysplastic hips on 103 standard anterior–posterior pelvis radiographs according to the Crowe and Hartofilakidis classifications. Assessments were performed in random order by each observer on two separate occasions, at least 4?weeks apart. Kappa statistics were used to establish a relative level of agreement between observers for the two readings and between separate readings by the same observer.

Results

At the first readings, interobserver reliability analysis revealed kappa coefficient of 0.71 for the Crowe classification and 0.54 for the Hartofilakidis classification. At the second reading, the kappa coefficient was 0.72 for the Crowe classification and 0.75 for the Hartofilakidis classification. Intraobserver reliability analysis revealed kappa coefficients of 0.71 for the Crowe and 0.80 for the Hartofilakidis classification for observer A, and 0.76 and 0.70 for observer B.

Conclusions

In conclusion, we have found substantial inter- and intraobserver agreement for Crowe classification and substantial to moderate agreement for Hartofilakidis classification in this study. Both classification systems assess the different aspects of developmental dysplasia of hip in adults. Each system has advantages and disadvantages. We suggest using both of these classifications together to increase the accuracy.