Clinical response to Nabiximols correlates with the downregulation of immune pathways in multiple sclerosis.

BACKGROUND AND PURPOSE: Nabiximols (Sativex® ) is a cannabinoid-based compound used for the treatment of moderate to severe spasticity in multiple sclerosis (MS). The aim of the study was to investigate the effect of the administration of Nabiximols on blood transcriptome profile of patients with MS and to interpret it in the context of pathways and networks. METHODS: Whole-genome expression profiling was performed in whole blood of 33 subjects with MS at baseline and after 4 weeks of drug treatment. Patients were classified as responders (n = 19) and non-responders (n = 14). Pathway and network analyses on genes modulated by the drug were performed, followed by in vitro stimulation of peripheral blood mononuclear cells with pro-inflammatory agents to support the immunomodulatory properties of the drug. RESULTS: Individual effect size was modest; however, we observed a downregulation of several immune-related pathways after 4 weeks of treatment, which was more pronounced when restricting analyses to responders. Interesting hub molecules functionally related to the immune system emerged from network analysis, including NFKB1, FYN, MAP14 and TP53. The immunomodulatory properties of the drug were confirmed through in vitro assays in peripheral blood mononuclear cells collected from patients with MS. CONCLUSIONS: Our findings support the immunomodulatory activity of cannabinoids in patients with MS. Further studies in more specific cell types are needed to refine these results.

microRNA profiling for early detection of nonmelanoma skin cancer.

BACKGROUND: microRNAs (miRNAs) are single-stranded, noncoding RNA molecules. Given the vast regulatory potential of miRNAs and their often tissue-specific and disease-specific expression patterns, miRNAs are being assessed as possible biomarkers to aid diagnosis and prediction of different types and stages of cancers, including skin cancer. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common forms of nonmelanoma skin cancer (NMSC). BCC originates from the basal layer of the epidermis, while SCC arises from epidermal keratinocytes or from the dermal appendages. Although NMSCs are currently the most common types of malignancies, both BCC and SCC have a better than 95% cure rate if detected early. AIM: To identify plasma miRNAs suitable for early detection of NMSC. METHODS: Expression profiles of 741 miRNAs were evaluated using high-throughput real-time quantitative PCR from plasma samples in 42 patients with NMSC and 282 healthy controls (HCs). RESULTS: Our results demonstrated that in patients with NMSC, compared with HCs, expression levels of miR-30e-3p, miR-145-5p, miR-186-5p and miR-875-5p were significantly (P < 0.05) upregulated, while those of miR-19a-3p, miR-25-3p, miR-30a-5p, miR-451 and miR-576-3p were significantly downregulated. CONCLUSION: Our study suggests that the miRNAs with significant changes in expression (miR-19a-3p, miR-25-3p, miR-30a-5p, miR-145-5p and miR-186-5p) could serve as novel noninvasive biomarkers for detection of NMSC.

Production performance, use of nest box, and external appearance of two strains of laying hens kept in conventional and enriched cages.

The aim of this study was to investigate the differences in production performance, use of nest box, and external appearance of 2 strains of laying hens kept in conventional and enriched cages. Lohmann Brown Classic (LB, n=532) and Lohmann LSL Classic (LW, n=532) hens were housed from 16 to 73 wk in either conventional cages or enriched cages. Enriched cages had a nesting area, scratch pad, perch, and nail shortener. Body weight (BW), hen-day egg production, egg weight, feed intake, feed conversion ratio (FCR), cracked and dirty eggs, use of nest box for lay, and external appearance were determined. Laying period influenced the hen-day egg production, egg weight, feed intake, and feed conversion ratio. Cage type affected the hen-day egg production and feed conversion ratio, while strain affected the egg weight, feed intake, and feed conversion ratio. Laying period×cage type and laying period×strain interactions affected egg production, egg weight, and feed conversion ratio. Both strains preferred to lay in the nest box. Percentages of cracked and dirty eggs of LW hens in enriched cages were higher than that in conventional cages. Most of the dirty eggs laid by both strains were found outside of the nest box. The LW hens laid more dirty eggs than the LB hens. Cage type and cage type×strain interaction were important for total feather score. Final claw length was affected by cage type, strain, and cage type×strain interaction. This study suggests that cage type, strain, and also cage type×strain and period×strain interactions should be considered when alternative housing systems are used.

Circulating microRNA expression profiles in ovarian cancer.

MicroRNA (miRNA) is an abundant class of small non-coding RNAs that act as gene regulators. Recent studies have suggested that miRNA deregulation is associated with the initiation and progression of human cancer. However, information about ovarian cancer-related miRNA is mostly limited to tissue miRNA. The aim of this study was to find specific profiles of plasma-derived miRNAs of ovarian cancer. In this present study, the expression profiles of 740 miRNAs in plasma from 18 patients and 24 healthy women subjects were evaluated using microfluidic based multiplex qRT-PCR. Our results demonstrated that expression levels of eight miRNAs were significantly upregulated in patients with ovarian cancer when compared with a control group (p < 0.05). Expression levels of four miRNAs were found significantly downregulated in patients with ovarian cancer (p < 0.05). In addition, 10 miRNAs were expressed only in the ovarian cancer group and miR-138-5p of these miRNAs is ovarian specific. In conclusion, our study suggests that detecting these ovarian cancer specific miRNAs in plasma might serve as novel non-invasive biomarkers for ovarian cancer.

Does Microwave Exposure at Different Doses in the Pre/Postnatal Period Affect Growing Rat Bone Development?

Effects of pre/postnatal 2.45 GHz continuous wave (CW), Wireless-Fidelity (Wi-Fi) Microwave (MW) irradiation on bone have yet to be well defined. The present study used biochemical and histological methods to investigate effects on bone formation and resorption in the serum and the tibia bone tissues of growing rats exposed to MW irradiation during the pre/postnatal period. Six groups were created: one control group and five experimental groups subjected to low-level different electromagnetic fields (EMF) of growing male rats born from pregnant rats. During the experiment, the bodies of all five groups were exposed to 2.45 GHz CW-MW for one hour/day. EMF exposure started after fertilization in the experimental group. When the growing male rats were 45 days old in the postnatal period, the control and five experimental groups' growing male and maternal rats were sacrificed, and their tibia tissues were removed. Maternal rats were not included in the study. No differences were observed between the control and five experimental groups in Receptor Activator Nuclear factor-kB (RANK) biochemical results. In contrast, there was a statistically significant increase in soluble Receptor Activator of Nuclear factor-kB Ligand (sRANKL) and Osteoprotegerin (OPG) for 10 V/m and 15 V/m EMF values. Histologically, changes in the same groups supported biochemical results. These results indicate that pre/postnatal exposure to 2.45 GHz EMF at 10 and 15 V/m potentially affects bone development.

The effects of resveratrol and melatonin on cardiac dysfunction in diabetic elderly female rats.

We aimed to investigate the effects of melatonin and resveratrol on diabetes-related papillary muscle dysfunction and structural heart disorders. The protective effect of resveratrol and melatonin supplementation on cardiac functions was investigated in a diabetic elderly female rat model. 16-month-old rats (n=48) were allocated into 8 groups. Group1: Control, Group2: Resveratrol Control, Group3: Melatonin Control, Group4: Resveratrol and Melatonin Control, Group5: Diabetes, Group6: Diabetes Resveratrol, Group7: Diabetes Melatonin, Group8: Diabetes Resveratrol and Melatonin. Streptozotocin was injected intraperitoneally to the rats for experimental diabetes induction. Thereafter, resveratrol (intraperitoneal) and melatonin (subcutaneous) were administered for 4 weeks. Resveratrol and melatonin had a protective effect on the contractile parameters and structural properties of the papillary muscle, which was impaired by diabetes. it has been presented that diabetes impairs the contractile function of the papillary muscle for each stimulus frequency tested and the responses obtained as a result of Ca+2 uptake and release mechanisms from the Sarcoplasmic reticulum, and it has been observed that these effects are improved with resveratrol and melatonin injection. The decrease in myocardial papillary muscle strength in the diabetic elderly female rat can be reversed with the combination of resveratrol, melatonin and resveratrol+melatonin. Melatonin+resveratrol supplementation is no different from melatonin and/or resveratrol supplementation. Resveratrol and melatonin supplementation may have a protective effect on cardiac functions in a diabetic elderly female rat model.

Transport evaluation of alendronate across Caco-2 cell monolayers.

The transport of alendronate through Caco-2 monolayers in the absence and presence of absorption enhancers (sodium taurocholate-STC and dimethyl-beta-cyclodextrin-DM-beta-CD) was studied. The viability of Caco-2 cells was determined by MTT assay. The effects of the experiment period and serum existence in Dubelco's Modified Eagle's Medium (DMEM) on cell viability were examined. The least toxic concentrations of alendronate, STC and DM-beta-CD were found as 0.2% (w/v), 5 mM and 0.3% (w/v), respectively. Transport experiments were performed with these concentrations in DMEM supplemented with serum for an 8 h period. DM-beta-CD increased the transport of alendronate through Caco-2 monolayers significantly. No significance was observed with STC. Cell integrity was determined by measuring the electrical resistance values at the end of the transport experiments and found to be decreased to a greater extent with DM-beta-CD. These results indicate that DM-beta-CD is a promising agent for improving the transport of alendronate.

Seizures and loss of vision in a patient with systemic lupus erythematosus.

Posterior reversible encephalopathy syndrome (PRES) is a rare neurological condition identifiable by clinical presentation and MRI appearance.1 Patients present with headache, seizures, loss of vision and altered mental function. The pathogenesis of the syndrome is poorly understood. One hypothesis is that cerebral vasospasm results in cerebral ischaemia and subsequent development of T2 hyperintensity, and the other is a temporary failure of the autoregulatory capabilities of the cerebral vessels, leading to hyperperfusion, breakdown of the blood-brain barrier, and consequent vasogenic oedema. It is believed that a rapid rise in blood pressure overcomes cerebral autoregulatory mechanisms with abrupt dilatation of cerebral arterioles. We report a patient with systemic lupus erythematosus and PRES after recurrent spontaneous abortion.

Nosocomial meningitis in a university hospital between 1993 and 2002.

The aim of this study was to establish the relationship between nosocomial meningitis (NM) and surgical interventions, type of pathogens and other hospital infections (HIs). Fifty-one patients diagnosed with NM, according to the criteria of the Centers for Disease Control and Prevention, in the Neurosurgery Department of Ibn-i Sina Hospital of Ankara University between 1993 and 2002 were evaluated retrospectively. All individuals with NM were hospitalized in the intensive care unit. Third-generation cephalosporins were used for surgical prophylaxis and broad-spectrum antibiotics were used for treatment. NM occurred in 0.34% of all admissions and accounted for 0.53% of all HIs. Fourteen cases (28%) had at least one concurrent HI, mainly originating from surgical wounds and related secondary bacteraemia. Four cases had NM following surgical site infection with the same causative agent and three cases had bacteraemia. All the individuals had surgical interventions and 26 (51%) had operations concerning ventriculoperitoneal shunt. A positive microbiological cause was found in the cerebrospinal fluid of 49 patients, with 16 cases having a polymicrobial cause. Of all 67 micro-organisms isolated, 41 (61%) were Gram-negative bacilli, 23 (34%) were Gram-positive cocci and the remaining three (5%) were Candida spp. Staphylococci were the most common pathogens (30%), followed by non-fermentative Gram-negative bacilli (22%).

Red blood cell distribution width: can it be a predictive marker for long-term valvular involvement in children with acute rheumatic carditis?

INTRODUCTION: In this study, we aimed to evaluate Red blood cell distribution width (RDW) in patients with acute rheumatic carditis during the acute phase and after anti-inflammatory therapy. METHODS: Pediatric patients diagnosed with acute rheumatic carditis (ARC) between 2006 and 2014 and age- and sex-matched controls were retrospectively analyzed. At the time of diagnosis and after 2 months of medical therapy, we reviewed the obtained demographic features; echocardiographic data; complete blood count reports, including RDW; acute phase reactants, including C-reactive protein; and erythrocyte sedimentation rate values. RESULTS: The number of the cases with ARC and age- and sex-matched controls were 100 and 110, respectively. The mean age of patients was 11.6 ± 2.5 years. WBC and platelet counts, RDW were found to be significantly higher in patient group compared with controls at the time of diagnosis, prior to the onset of treatment. RDW, platelet count, CRP, and ESR levels significantly decreased after an 8 weeks of medical treatment. RDW values after the medical treatment were still significantly higher compared with controls. RDW values were significantly higher in patients with multiple valvular involvement both prior to and after the treatment. Moreover, we found a significant and positive correlation between the RDW and the severity of mitral regurgitation in our patients (r: 0.46, P < 0.001). CONCLUSIONS: High levels of RDW after initial medical treatment may indicate an ongoing subtle inflammatory process that leads to future stenotic valvular lesions. However, long-term follow-up studies are needed involving adulthood period to support this hypothesis.

Fresh homografts obtained through a national organ-sharing programme for repair of congenital heart disease.

Homografts have been used in congenital cardiac surgery for over 30 years. We utilized the resources of a national organ-sharing programme to obtain fresh homografts and report their use in correcting cardiac pathologies in 20 children between March 2001 and May 2003. In 16 patients, a valved conduit was used to form a connection between the pulmonary ventricle and the pulmonary artery. In three patients, a non-valved aortic conduit was used to form an extra-cardiac Fontan circulation and in one patient, non-valved pulmonary and aortic conduits were used to repair an infected aortic aneurysm. Three patients died following surgery. Survivors were followed up using echocardiography between 2 and 24 months post-surgery. Results demonstrate that, with the help of a national organ-sharing programme, the use of fresh homograft conduits is feasible in a paediatric patient population with reasonable waiting times.

An experimental set-up to test heat-moisture exchangers.

OBJECTIVES: The purpose of this study was to build an experimental set-up to assess continuously the humidification, heating and resistance properties of heat-moisture exchangers (HMEs) under clinical conditions. DESIGN: The experimental set-up consists of a patient model, measurement systems and a ventilator. SETTING: Surgical ICU, University Hospital of Rotterdam. MATERIALS: A clinically used HME. MEASUREMENTS AND RESULTS: The air flow, pressure in the ventilation circuit, pressure difference over the HME, and partial water vapour pressure and temperature at each side of the HME were measured. The resistance, absolute humidity, humidification efficiency and temperature difference at the patient side of the HME were calculated. Measurements were performed during 24 h. The temperature output, humidity output and lung mechanics of the patient model were similar to values found in mechanically ventilated patients. The measurement system was in agreement with the ISO draft standard and was capable of measuring dynamic variation of water and heat exchange over the range of a clinically used ventilator setting. CONCLUSION: The experimental set-up described is reliable for evaluating HMEs and can also be used for future clinical evaluation of HMEs. The main advantages of this set-up over those described previously are: (i) measurements of dynamic variations of water and heat exchange; (ii) on-line measurements of expiratory, as well as inspiratory resistance.

A novel method of evaluation of three heat-moisture exchangers in six different ventilator settings.

OBJECTIVE: The purpose of this study was to assess and compare the humidification, heating, and resistance properties of three commercially available heat-moisture exchangers (HMEs). To mimic clinical conditions, a previously validated, new, realistic experimental set-up and measurement protocol was used. DESIGN: Prospective, comparative experimental study. SETTING: Surgical Intensive Care Unit, University Hospital of Rotterdam. MATERIALS: An experimental set-up consisting of a patient model, measurement systems, and ventilator and three different HME types. INTERVENTIONS: The air flow, pressure in the ventilation circuit, pressure difference over the HME, and partial water vapour pressure and temperature at each side of the HMEs were measured. Measurements were repeated every 30 min during the first 2 h and every hour up to 24 h for each HME at six different ventilator settings. The mean inspiratory and maximum expiratory resistance, flow-weighted mean absolute humidity and temperature outputs, and humidification and heating efficiencies of HMEs were calculated. MEASUREMENTS AND RESULTS: The Dar Hygroster had the highest humidity output, temperature output, humidification efficiency, and heating efficiency values throughout the study (32.8 +/- 21. mg/l, 32.2 +/- 0.8 degrees C, 86.3 +/- 2.3%, and 0.9 +/- 0.01%, respectively) in comparison to the Humid-Vent Filter (25.3 +/- 3.2 mg/l, 31.9 +/- 0.8 degrees C, 72.2 +/- 5.3%, 0.9 +/- 0.02%, respectively) and the Pall Ultipor BB100 breathing circuit filter (23.4 +/- 3 mg/l, 28.3 +/- 0.7 degrees C, 68.8 +/- 5.9%, 0.8 +/- 0.02%, respectively). The inspiratory and expiratory resistance of the HMEs remained below clinically acceptable maximum values (2.60 +/- 0.04 and 2.45 +/- 0.05 cmH2O/l per s, respectively). CONCLUSION: The Dar Hygroster filter was found to have the highest humidity and temperature output of all three HMEs, the Humid-Vent filter had a satisfactory humidity output only at low tidal volume flow rate and minute volume settings, whereas the Pall Ultipore BB 100 never achieved a sufficient humidity and temperature output.

Use of alkaline comet assay (single cell gel electrophoresis technique) to detect DNA damages in lymphocytes of operating room personnel occupationally exposed to anaesthetic gases.

Here, we report the possible in vivo induction DNA damage by exposure to various waste anaesthetic gases such as halothane, nitrous oxide and isoflurane. The alkaline comet assay (single cell gel electrophoresis technique) was carried out on 66 operating room personnel (anaesthetists [doctors]; anaesthesia nurses and anaesthesia unit technicians) currently employed at the Ankara Hospital in Turkey. A significant increase in the number of lymphocytes with DNA migration was observed in operating room personnel as compared to controls. Also, the extent of damage in exposed smokers were significantly higher than exposed nonsmokers. This study supports the existence of an association between DNA damage and occupational exposure to inhalation anaesthetics.

Postoperative analgesia in children using preemptive retrobulbar block and local anesthetic infiltration in strabismus surgery.

BACKGROUND AND OBJECTIVES: Postoperative pain management in pediatric strabismus patients is infrequently studied. Pediatric patients can be mobilized earlier if postoperative pain is minimized. In this study, two different regional anesthetic techniques, retrobulbar block and local infiltration, were compared with a "no block" control group for the postoperative management of pain in pediatric patients undergoing elective strabismus surgery. METHODS: Thirty patients were randomly allocated to one of the study groups: group 1 (n=10) control, group 2 (n=10) retrobulbar block, and group 3 (n=10) subconjunctival bupivacaine infiltration. The parameters that were evaluated during the early postoperative period (6 hours) were circulatory, pain scores by Visual Analog Scale (VAS) and Modified Pediatric Objective Pain Scale (MPOPS), additional analgesic requirement, nausea, and vomiting. The parameters that were evaluated after discharge from the hospital (on postoperative days 1 and 2) through questionnaires were additional analgesic requirement, nausea, vomiting, sleep disturbances, activity, and appetite. RESULTS: Group 3 had significantly higher VAS and MPOPS scores at postoperative 120, 180, 240, 300, and 360 minutes than groups 1 and 2 (P < .05). Patients in group 2 seemed to have a higher incidence of nausea and vomiting both in the early (6 hours) and late postoperative (postoperative days 1 and 2) periods; however, the difference was not statistically significant. Group 2 required less analgesic compared with groups 1 and 3 during the late postoperative period. Late postoperative activity and appetite were better in groups 2 and 3. CONCLUSIONS: Because there was no significant difference in terms of postoperative analgesia in the retrobulbar block or subconjunctival local anesthetic infiltration groups compared with the control group, we suggest that conventional methods of pain treatment are adequate for postoperative analgesia in strabismus surgery.

Dilated cardiomyopathy as the first early complication in a 14 year-old girl with diabetes mellitus type 1.

Diabetic cardiomyopathy (DC) has been reported in type 2 diabetics with short duration of clinically overt diabetes. Impaired left ventricular function has been reported in young patients with diabetes mellitus type 1 (IDDM), but severe cardiomyopathy as the first early major complication of IDDM is very rare. We report a 14 year-old girl with a 5-year history of IDDM and very poor compliance with treatment and follow-up. She was referred to our clinic upon the development of congestive heart failure and dilated cardiomyopathy was diagnosed based on clinical findings, electrocardiogram, chest X-ray and echocardiography. She had no evidence of other major complications of IDDM such as retinopathy, nephropathy or neuropathy.

Chronic hypoxemia leads to reduced serum IGF-I levels in cyanotic congenital heart disease.

Cyanotic congenital heart disease in children commonly causes more pronounced growth retardation in comparison with acyanotic congenital heart disease. Chronic hypoxemia has been suggested as the cause of poor growth in these patients, but the relationship between serum IGF-I levels and chronic hypoxemia is unclear. Serum IGF-I concentrations, oxygen saturation and nutritional status were evaluated in 29 patients with cyanotic congenital heart disease, and serum IGF-I levels were compared with a group of 20 well-nourished, age-matched control children to assess the relationship between IGF-I levels and chronic hypoxemia. The nutritional status of each patient was determined by using anthropometric parameters and calorie and protein intake ratios. The patients were divided into malnourished and well-nourished groups (21 and 8 patients, respectively) according to their nutritional status. Serum IGF-I concentrations were measured in the two patient groups and the controls. The malnourished group had the lowest IGF-I levels (48.14 +/- 21.8 ng/ml, p<0.05). However, the well-nourished group's IGF-I levels were significantly lower than the control subjects' despite improved nutritional status (85.5 +/- 30.2 and 107 +/- 19.7 ng/ml, respectively, p<0.05). In addition, we found a positive correlation between serum IGF-I levels and oxygen saturation of the patients (r=0.402, p<0.05). These findings indicate that chronic hypoxemia has a direct or indirect effect to reduce serum IGF-I concentrations and this may be a cause of the increased growth failure in patients with cyanotic congenital heart disease.

The effects of acarbose and Rumex patientia on liver ultrastructure in streptozotocin-induced diabetic (type II) rats.

The aim of this study was to investigate the effects of acarbose and Rumex patientia on liver ultrastructure in streptozotocin (STZ)-induced diabetic (type II) rats. Forty-two-day-old, neonatal Wistar albino rats were used. They were divided into six groups. STZ was injected into groups 4, 5 and 6 on postnatal day 2. Groups 1 and 5 received water, groups 2 and 6 received 2% decoction of R. patientia grain and groups 3 and 4 received 40 mg acarbose/100 g feed. During the experimental period, blood glucose levels were checked periodically and HbA1c levels were measured from cardiac blood at the end of the experiment. In addition, liver tissue was examined by electron microscopy. Our results showed that glucose and HbA1c levels, which are increased by STZ, were decreased by acarbose and R. patientia. In group 5, most of the mitochondria of hepatocytes were swollen and some hepatocytes contained lipid granules in their cytoplasm. In group 4, no pathological changes were observed in hepatocytes, but some lysosomes were found in their cytoplasms. In group 6, mitochondrial changes were minimal compared with those in group 5, and no lipid granules were observed in hepatocytes.

C2/C3 nerve blocks and greater occipital nerve block in cervicogenic headache treatment.

In the diagnosis of cervicogenic headache, greater occipital nerve (GON), cervical nerve, minor occipital nerve, and cervical facet joint blocks are used. In our study we compared the GON and C2/C3 nerve blocks in the diagnosis and treatment of cervicogenic headache. In both cases, repeated blocks proved to have a long-lasting effect in the treatment of this disorder, with both GON and C2/C3 blocks being found to be equally effective.