Cell cycle markers have different expression and localization patterns in neuron-like PC12 cells and primary hippocampal neurons

Recent studies have indicated that bone marrow stromal cells (BMSCs) have significant tropism towards glioma which makes them play an important role in carrying genes/drugs to inhibit the growth of glioma as cell vehicles. But BMSCs may differentiate into neural cells under entocranial environment and few researches support the idea that neurally differentiated bone marrow stromal cells (N-D-BMSCs) still hold the capacity of migrating to the tumor sites. The aim of our study was to investigate the tropism of N-D-BMSCs towards C6 glioma. In vitro migration assay was employed by transwell co-culture system and Student's t-test analysis indicated that N-D-BMSCs had the significant tropism towards C6 glioma-conditioned medium (GCM) (P < 0.01). Furthermore, the vascular endothelial growth factor (VEGF) bioactivity of the C6 GCM was neutralized by the anti-rat VEGF antibody and our data suggested that the VEGF from C6 GCM hold chemoattraction for N-D-BMSCs and some other cytokines from the C6 GCM may be responsible for the chemoattraction for N-D-BMSCs. In vivo migration assay was carried out with cells transplantation and one way ANOVA analysis indicated that the tropism of N-D-BMSCs towards C6 glioma sites presented time variation (P-value = 2.9E−20). Moreover, multiple comparisons for the time variables with the Student's t-test and the results suggested that the migration capacity of N-D-BMSCs towards C6 glioma sites reach the peak on the 7th day after transplantation. These results demonstrate that N-D-BMSCs as well as BMSCs have significant tropism towards C6 glioma.     

Automated discrimination of psychotropic drugs in mice via computer vision-based analysis

We developed an inexpensive computer vision-based method utilizing an algorithm which differentiates drug-induced behavioral alterations. The mice were observed in an open-field arena and their activity was recorded for 100 min. For each animal the first 50 min of observation were regarded as the drug-free period. Each animal was exposed to only one drug and they were injected (i.p.) with either amphetamine or cocaine as the stimulant drugs or morphine or diazepam as the inhibitory agents. The software divided the arena into virtual grids and calculated the number of visits (sojourn counts) to the grids and instantaneous speeds within these grids by analyzing video data. These spatial distributions of sojourn counts and instantaneous speeds were used to construct feature vectors which were fed to the classifier algorithms for the final step of matching the animals and the drugs. The software decided which of the animals were drug-treated at a rate of 96%. The algorithm achieved 92% accuracy in sorting the data according to the increased or decreased activity and then determined which drug was delivered. The method differentiated the type of psychostimulant or inhibitory drugs with a success ratio of 70% and 80%, respectively. This method provides a new way to automatically evaluate and classify drug-induced behaviors in mice.     

Hereditary neuropathies

PURPOSE OF REVIEW: The purpose of this review is to help neurologists understand new concepts in hereditary neuropathies, from the clinician's point of view, in the molecular era after the burst of information regarding peripheral nerve biology. RECENT FINDINGS: Recent studies have focused on understanding the pathomechanisms involved in hereditary neuropathies. In the past year identification of new genes has slowed down since scientists have concentrated more on the function of genes causing Charcot-Marie-Tooth disease and Schwann cell-axon interactions to reveal the molecular cell biology of the disease. Animal models for the most common subtypes of human Charcot-Marie-Tooth disease are now available. SUMMARY: Rapid advances in the molecular genetics and cell biology of hereditary neuropathies have highlighted the great genetic complexity of Charcot-Marie-Tooth disease. The evolution from a simple clinical classification to a complex molecular one has not facilitated our understanding of the disease. Moreover, the new molecular classification is not simple to use as different mutations of the same gene produce a range of phenotypes. The clinicians have to look for specific clinical and electrophysiological clues to direct the patient to appropriate genetic testing.     

Comparative effects of risedronate,atorvastatin, estrogen and SERMs on bone mass and strength in ovariectomized rats

Objective

The aim of this study was to investigate bone protective effects of risedronate, atorvastatin, raloxifene and clomiphene citrate in ovariectomized rats.

Methods

Our study was conducted on 63 rats at Experimental Research Center of Celal Bayar University. Six-month-old rats were divided into seven groups. There were five drug administered ovariectomized groups, one ovariectomized control group without drug administration and one non-ovariectomized control group without drug administration. Eight weeks postovariectomy, rats were treated with the bisphosphonate risedronate sodium, the statin atorvastatin, the estrogen 17β-estradiol and the selective estrogen receptor modulators (SERMs) raloxifene hydrochloride and clomiphene citrate by gavage daily for 8 weeks. At the end of the study, rats were killed under anesthesia. For densitometric evaluation, left femurs and tibiae were removed. Left femurs were also used to measure bone volume. Right femurs were used for three-point bending test.

Results

Compared to ovariectomized group, femur cortex volume increased significantly in non-ovariectomized group (p = 0.016). Compared to non-ovariectomized group, distal femoral metaphyseal and femur midshaft bone mineral density values were significantly lower in ovariectomized group (p = 0.047). In ovariectomy + atorvastatin group, whole femur and femur midshaft bone mineral density and three-point bending test maximal load values were significantly higher than ovariectomized group (p = 0.049, 0.05, and 0.018). When compared to the ovariectomized group, no significant difference was found with respect to femoral maximum load values in groups treated with risedronate, estrogen, raloxifene and clomiphene (p = 0.602, 0.602, 0.75, and 0.927). In ovariectomy + risedronate group, femur midshaft bone mineral density values were significantly higher than the values in ovariectomized group (p = 0.023). When compared to ovariectomized group, no significant difference was found with respect to femur midshaft bone mineral density values in groups treated with estrogen, raloxifene and clomiphene (p = 0.306, 0.808, and 0.095).

Conclusions

While risedronate sodium prevented the decrease in bone mineral density in ovariectomized rats, atorvastatin maintained mechanical characteristics of bone and also prevented the decrease in bone mineral density as risedronate sodium.     

Management of neuroendocrine carcinomas of the breast: A rare entity

Neuroendocrine (NE) carcinoma of the breast is extremely rare and constitutes less than 0.1% of all breast tumors. Only a few studies are currently available in the literature and a standard approach to treating this tumor has yet to be established. The aim of this study was to apply pathological treatment modalities in clinical practice and to select the most appropriate treatment accordingly. Six female patients were diagnosed with primary NE carcinoma of the breast. The patients underwent modified radical mastectomy with axillary dissection. Pathological specimens were stained with hematoxylin and eosin and an immunohistochemical panel of antibodies [neuron-specific enolase (NSE), chromogranin, synoptophysin, estrogen and progesterone receptor, c-erbB2 and Ki-67]. The results showed that tumor size ranged from 2 to 4.5?cm in diameter. Lymph node metastasis was detected in 4 (67%) patients. Estrogen and progesterone receptor expression was found in 5 (83%) patients. None of the patients expressed c-erbB2. Chromogranin was found to be positive in 5 (83%) patients. Synoptophysin expression was detected in 5 (83%) patients. NSE was stained in 4 (67%) patients. An intraductal component was found in 5 (83%) patients. Lymphovascular invasion was found in 5 (83%) patients. Adjuvant chemotherapy was administered to patients with a Ki-67 index of ≥10%. Radiotherapy was administered to 4?(67%)?patients, and 4?(67%) patients received hormonal therapy. The mean follow-up time was 31.1?months (range?12-52). All 6 patients survived, although following chemotherapy and tamoxifen, the disease progressed in 1?patient who received second-line hormonal therapy. In conclusion, NE carcinoma of the breast is a distinct entity. Management of this rare tumor may include surgery and radiotherapy depending on the size of the tumor and lymph node status. However, the exact role of chemotherapy and hormonal therapy has yet to be established. Adjuvant chemotherapy is recommended for patients with a Ki-67 index of ≥10%, and hormonal treatment appears to be feasible in patients who are positive for estrogen and/or progesterone receptor.     

Induction chemotherapy with triweekly docetaxel and cisplatin followed by concomitant chemoradiotherapy with or without surgery in stage III non-small-cell lung cancer: a phase II study

Background

The main goal of this study was to evaluate the feasibility and effectivity of triweekly docetaxel/cisplatin followed by weekly docetaxel/cisplatin concomitantly with radiotherapy with or without surgery in locally advanced non–small-cell lung cancer (NSCLC) patients.

Materials and Methods

Thirty five patients with locally advanced NSCLC were enrolled. Combination chemotherapy with triweekly docetaxel/cisplatin (75 mg/m²) was administered as induction regimen. After induction chemotherapy, patients were evaluated for surgery if their disease subsequently downstaged. Six cycles of weekly docetaxel/cisplatin (20 mg/m²) concurrently with radiotherapy up to a 60 Gy were administered after induction chemotherapy with or without surgery. Response, toxicity, time-to-progression and overall survival were evaluated.

Results

Twelve patients with stage IIIA-N2 and 23 patients with stage IIIB-T4N0-2 were evaluated (median age, 54 years). After 94 cycles of induction chemotherapy, partial response was achieved in 20 patients, 9 patients had stable disease and six had progressive disease. After overall treatment, 6 patients achieved complete response, 19 patients had partial response, 8 patients had progressive disease, and 2 patients had stable disease. Two patients experienced grade 3-4 pulmonary toxicity and 1 patient experienced grade 3 esophageal toxicity. Six patients underwent surgery. Median overall survival for all patients was 15 months and time-to-progression was 13 months with a median follow-up of 22 months.

Conclusion

Triweekly docetaxel plus cisplatin followed by weekly docetaxel plus cisplatin concomitantly with radiotherapy is effective and feasible and seems to be an alternative option for patients who have locally advanced NSCLC. Surgery may provide additional benefit for patients whose disease adequately downstaged after induction chemotherapy.     

Does adenosine A1 receptor stimulation causes QRS prolongation by blocking beta adrenergic receptors in amitriptyline poisoning?

Aims

To investigate the role of beta receptor blockade via adenosine A₁ receptor stimulation on amitriptyline-induced QRS prolongation.

Methods

Isolated rat hearts were randomized into three groups (n = 8 for each group). After pretreatment with 5% dextrose (control) or DPCPX (8-cyclopentyl-1,3-dipropylxanthine), or propranolol + DPCPX, amitriptyline infusion was given to all groups. Intact beta adrenergic receptor response was verified with a bolus dose of isoproteranol (3 × 10⁻⁵ M).

Results

Amitriptyline (5.5 × 10⁻⁵ M) infusion following pretreatment with 5% dextrose or 10⁻⁴ M DPCPX prolonged QRS by 40–110% and 30–75%, respectively. After the beta receptor blockade with 10⁻² M propranolol bolus, amitriptyline infusion following pretreatment with DPCPX prolonged QRS by 40–130%. Amitriptyline infusion following pretreatment with DPCPX (10⁻⁴ M) shortened the QRS at 40, 50 and 60  min significantly when compared to propranolol + DPCPX group (168.8 ± 4.9%, p < 0.05; 170.8 ± 6.9%, p < 0.01; 174.0 ± 6.9%, p < 0.01, respectively). Amitriptyline infusion following pretreatment with 5% dextrose prolonged QRS duration significantly at 50th minutes (209.5 ± 6.1%, p < 0.05) compared to DPCPX pretreatment group.

Conclusion

DPCPX pretreatment shortened amitriptyline-induced QRS prolongation. Beta adrenergic receptor blockade enhanced QRS prolongation shortened by DPCPX pretreatment. Adenosine A₁ receptor stimulation related to beta adrenergic receptor blockade may play a role in amitriptyline-induced QRS prolongation in isolated rat hearts.     

Sense of coherence and social support predict living liver donors' emotional stress prior to living-donor liver transplantation

Abstract:  The protection of the donors from physical or emotional harm has been a fundamental principle in living-donor liver donation from the beginning. Psychosomatic donor evaluation aims at the selection of eligible donors and the screening and exclusion of psychiatrically vulnerable donors. As clinical interviews may include subjective biases, efforts should be made to establish objective criteria for donor assessment. In recent research, protective factors have been reported to be a significant force behind healthy adjustment to life stresses and can be investigated as possible predictors of donors' eligibility. Being the central construct of Antonovsky's theory of salutogenesis, the sense of coherence is one of the most surveyed protective factors and a good predictor of individuals' stability when experiencing stress. Furthermore, family support has been shown to be a valuable protective resource in coping with stress. This study surveyed whether sense of coherence and social support predict donors' emotional strain prior to transplantation. Seventy-one donor candidates were included in the study during the donor evaluation prior to living-donor liver transplantation. Sense of coherence proved to be a significant predictor for all criterion variables, namely anxiety, depression and mental quality of life. In addition to this, donor candidates who were classified as eligible for donation in the psychosomatic interview had significantly higher values on sense of coherence total scores compared with rejected donors. In a multiple regression analysis, sense of coherence and social support together yielded a prediction of depression with an explained variance of 22% ( R ²  = 0.22). Sense of coherence and social support can be implemented as self-rating instruments in the psychosomatic selection of donors and would help to further objectify donors' eligibility.