Evaluation of MicroRNA-124 Expression in Renal Cell Carcinoma.

The Wingless/INT (WNT) signaling network has roles in renal cancer development. It was shown that the tumor-suppressor microRNA-124 (miR-124) is associated with the Wnt pathway. Thus, we aimed to measure miR-124 expression levels to evaluate whether it is a prognostic marker or a potential treatment strategy. Thirty tumor and 30 surrounding healthy kidney tissues from the same subjects diagnosed with renal cell carcinoma (RCC), were included in the study. The expression levels of miR-124 were measured with real-time polymerase chain reaction (qPCR) and determined by the 2-ΔΔCT method. The Statistical Package for Social Science (SPSS) version 22 program was used for statistical analyses and a p value of 0.05 was considered to be statistically significant. The expression levels of miR-124 was found to be about 3-fold lower in tumors than in healthy tissues (p 0.001) and decreased expression levels correlated with tumor stage, tumor diameter, body mass index (BMI) and neutrophil values (p 0.05). Our results showed that miR-124 expression levels are associated with RCC. MicroRNA-124 may be assessed as a biomarker in prognosis and the restoration of miR-124 expression might be effective in the treatment of RCC.

rs3918242 variant genotype frequency and increased TIMP-2 and MMP-9 expression are positively correlated with cancer invasion in urinary bladder cancer.

To study the role of MMP9 and TIMP2 genotypes and expression in predisposition to bladder cancer and relation with metastasis. 100 urinary bladder cancer patients and 100 healthy controls were included in the study. rs3918242 and rs8179090 genotypes were determined with PCR-RFLP. Quantitative real-time polymerase chain reaction was employed to assess the MMP-9 and TIMP-2 expression in tumors and adjacent healthy tissues. Variant genotype (TT) for rs3918242 polymorphism and rs8179090 variant genotype are not associated with bladder cancer risk. rs3918242 genotype was significantly associated with tumor invasion. In contrast with this, rs8179090 genotype has not shown a significant association with tumor invasion. Both SNPs did not show a significant association with metastatic status. MMP-9 was upregulated in tumors in comparison to cancer free tissues. Significant increase in the expression of MMP-9 was also observed in invasive tumors. TIMP-2 expression was significantly increased in tumors in comparison to cancer free tissues and in metastatic tumors in comparison to non-metastatic tumors. Tissues with rs3918242 variant genotype have shown increased MMP-9 expression.  rs3918242 promoter polymorphism of MMP-9 is significantly associated with tumor invasion, however; there is no positive correlation between TIMP-2 rs8179090 promoter polymorphism variant frequency and invasion. MMP-9 and TIMP-2 genes are upregulated in cancerous tissues when compared to normal bladder tissues.

Deregulation of seven CpG island-harboring miRNAs in bladder cancer: miR-155 and miR-23b as the most promising oncomiRs.

Analyses of differential miRNA expressions in tumor and normal tissues can identify specific miRNAs involved in cancer pathogenesis, which can then be used as diagnostic, therapeutic and prognostic biomarkers. In this respect, we aimed to investigate expression levels of seven CpG island-harboring miRNAs in 50 paired UBC tissues by qRT-PCR. miR-21 and miR-155 were found to be significantly upregulated, and miR-23b, miR-126, miR-129-5p, miR-143a and miR-218-5p were downregulated. ROC analysis indicated miR-155 as the most promising candidate for discrimination of tumors from healthy tissue, and miR-23b for the discrimination of early stage from late stage tumors.

Efficacy and cost of single-dose rasburicase in prevention and treatment of adult tumour lysis syndrome: a meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Single-dose rasburicase for the treatment and prevention of hyperuricaemia in adult and paediatric patients with cancer at high risk of tumour lysis syndrome (TLS) has been widely adopted in pharmacy practice as unlabelled use with limited clinical evidence. This meta-analysis study evaluated the efficacy and cost savings of a single-dose rasburicase (SDR) regimen compared with the Food and Drug Administration-approved daily dosing of rasburicase (DDR) for 5 days or the traditional treatment with allopurinol in adult cancer patients with hyperuricaemia or at high risk for TLS. METHODS: Prospective and retrospective studies were retrieved from a systemic search of major electronic data sources. Studies included in the meta-analysis were those with SDR for the prophylaxis of high-risk TLS or treatment of hyperuricaemia in adult patients with cancer. The results of response rate and controlling of time-dependent plasma uric acid (UA) reduction were pooled and compared with the results from patients treated with DDR for 5 days or patients treated with allopurinol. A cost analysis was performed to analyse the treatment costs for adults with hyperuricaemia or at high risk for TLS. RESULTS AND DISCUSSION: Ten studies (eight retrospective and two prospective) evaluated the SDR response rate and plasma UA level reduction over time. The pooled total number of patients treated with SDR (from 0·05 mg/kg to 0·20 mg/kg) was 269. The pooled response rate of the SDR arm was not significantly different than that of DDR (0·2 mg/kg) arm (88·15% vs. 90·18%, P = 0·542), but significantly stronger than that of allopurinol (300 mg/day orally days 1 to 5) arm (response rate: 88·15% vs. 66%, P < 0·0005). Pooled SDR group efficiently controlled the plasma uric acid (UA) level below 4·5 mg/dL over 24 h, 48 h and 72 h, whereas DDR reduced plasma UA levels to hypouricaemia level (<2 mg/dl). In addition, cost analysis demonstrated that standard-dose SDR (≥6 mg) has non-inferior clinical benefit and significant cost savings compared with the DDR regimen. WHAT IS NEW AND CONCLUSION: Single-dose rasburicase (SDR) for adult cancer patients with hyperuricaemia or at high risk for TLS demonstrated better response rate and stronger control of uric acid level compared with allopurinol. SDR response rate was not inferior to that of DDR, and the standard-dose SDR generates more cost savings compared with the DDR. It suggests that the single-dose rasburicase is clinically effective and cost efficient for the prophylaxis of high-risk TLS and the treatment of hyperuricaemia in adult patients with cancer. Additional randomized control studies are needed to confirm the findings of this meta-analysis study.

SodiumPhosphate (NaP) versus polyethylene glycol-electrolyte lavage solution (PEG-ELS) tolerability: a prospective randomized study in patients with gynecological malignancy.

PURPOSE: The aim of the study was to evaluate patient tolerability and compliance to two bowel cleansing agents (PEG-ELS and NaP) as well as to compare the cost effectiveness. METHODS: Three hundred and forty-three consecutive patients were randomized to receive either the standard 4 1 of polyethylene glycol and electrolyte lavage solution (PEG-ELS) or 90 ml of sodium phosphate (NaP). All patients were advised to be on a clear liquid diet one day before starting the bowel cleansing regimen and to take ornidazole orally (3 x 2 tablets) 24 hours before surgery. Patient tolerabilty and compliance to the regimens were assessed based on complaints of nausea, vomiting and the need of antiemetics. In addition completion of the regimens was evaluated in both groups. RESULTS: The need for antiemetics because of nausea and vomiting was statistically higher in the PEG-ELS group than the NaP group (p = 0.000). Regimen completion rate was statistically higher in the NaP group than in the PEG-ELS group (p = 0.000). NaP is more cost effective than PEG-ELS. CONCLUSION: NaP was rated superior to PEG-ELS in terms of patient tolerability, compliance, completion of the regimen and cost effectiveness and should be the first-choice treatment.

Changes in nitric oxide levels in striated muscles of rats following different types of death.

BACKGROUND: Nitric oxide is a signal molecule regulating the organism functions in living bodies. The aim of this study was to investigate the NO levels of striated muscles after different types of death in rats. METHODS: Nitric oxide levels in the muscles of masseter, triceps, and quadriceps obtained from right and left sides of 24 Spraque-Dawley rats following death were investigated. The rats were divided into three groups as cervical dislocation (control) group, electric shock group, and drowning group. After applying a light anesthesia, the rats were killed by cervical dislocation, electric shock and drowning. The samples were taken immediately and 120 minutes after death. RESULTS: In all muscle types of all groups, NO concentrations were lower in samples obtained 120 minutes after death than in those obtained immediately after death. NO concentrations were lower in the electric shock and drowning group than in the control group for both times. CONCLUSION: We can conclude that the type of death may affect the occurrence of rigor mortis and NO measurement may give an important clue in evaluation the mode of death.

Association of immune function with bone mineral density and biochemical markers of bone turnover in patients with anklylosing spondylitis.

The lymphocyte-osteoclast interaction has recently been described. The aim of this study was to investigate the possible relationship between ankylosing spondylitis (AS) and bone metabolism. Bone metabolism was evaluated in the blood of 49 patients with AS by means of biochemical markers and bone mineral density (BMD) with a Lunar device. Bone formation markers, bone specific alkaline phosphatase (BALP), osteocalcin (BGP), bone resorption markers, pyridinoline (Pyd), deoxypyridinoline (Dpyd) and lymphocyte surface markers (CD3, CD19, CD4, CD8, CD16+56) were analysed with ELISA and flow-cytometry methods. The patients had significantly lower femoral neck and trochanter BMD than the controls. Dpyd concentrations were negatively correlated to CD3+% and CD3-/CD16+56% cells. Neither mineral nor hormone levels were significantly correlated with absolute T scores of BMD of the hip sites. BALP and BGP were negatively correlated to BMD when expressed as T scores. We conclude that AS is related to accelerated osteoclastic activity. Many lymphokines and growth factors produced by lymphocytes can influence osteoclastogenesis and probably play a role in rheumatologic/inflammatory disorders.

The effect of smoking and caffeine on the fetus and placenta in pregnancy.

The aim of this study was to determine the effects of tobacco use and consumption of caffeine in pregnancy on the fetus and placenta by measuring the body weights, head circumferences, and lengths of newborns, and also weights and diameters of placentas. In this prospective study, two main groups were chosen for the study: Group I: A total of 63 pregnant non-smokers; were separated into two subgroups according to their daily caffeine intake; less than 300 mg (Ia) (n = 44), and more than 300 mg (Ib) (n = 19). Group II: 60 pregnant smokers were also separated into two subgroups; daily caffeine intake less than 300 mg (IIa) (n = 43), and more than 300 mg (IIb) (n = 17). The newborns and placentas of both groups were examined. The body weights, lengths, and head circumferences of newborns and also weights and diameters of placentas were measured. The pregnant non-smokers consuming caffeine more than 300 mg/day had statistically significant lower weights of newborns and placentas (p < 0.05). However, there was no significant difference between groups according to the lengths, head circumferences of newborns and diameters of placentas. There were significantly lower body weights of newborns and placentas in pregnant smokers (p < 0.05). There was no difference according to the diameters of placentas, and lengths and head circumferences of newborns in either group. In conclusion, it is suggested that smoking in pregnancy should be prevented both for the health of newborns and mothers, and also caffeine including beverages like tea and coffee should be limited in pregnancy.

Determination of plasma fibronectin and serum C-reactive protein in patients with cerebrovascular events.

The relationship between the levels of C-reactive protein (CRP) and fibronectin (FN) and atherosclerotic diseases such as coronary heart disease has already been studied, but their relationship with cerebrovascular events has not. The aim of this study was to determine the levels of plasma FN and serum CRP in cerebrovascular events, and their relationship with the outcome of the disease. CRP and FN levels were analysed in 133 patients with acute cerebrovascular disease, together with 66 healthy controls. Cerebrovascular event patients were divided into subgroups according to disease severity. FN and CRP levels in patients with cerebrovascular disease were found to be significantly elevated compared with the control group (p<0.001). CRP levels correlated with disease severity, in contrast to FN levels. We conclude that FN is not a clinically useful marker in patients with acute differentiative cerebrovascular events, in contrast to CRP which may be useful in such cases.

The effect of delivery on umbilical arterial cord blood gases and lipid peroxides: comparison of vaginal delivery and cesarean section.

Umbilical arterial blood gas analysis is the most objective method to assess fetal well being at birth, is the gold standard assessment of uteroplacental function and fetal oxygenation/acid-base status at birth, and it excludes the diagnosis of birth asphyxia in approximately 80% of depressed newborns at term. This study was designed to determine the effect of the type of delivery on umbilical cord blood gases and on free radical activity together with antioxidation in the fetus. Ninety-six pregnant women between 37 and 42 weeks of gestation were included to the study and randomly assigned to the one of three groups: Group 1 (n = 40) were vaginally delivered, Group 2 (n = 26) had cesarean section with epidural anaesthesia, and Group 3 (n = 30) had cesarean section under general anaesthesia. Umbilical artery blood gas analysis was performed just after the delivery of the fetus together with melondealdehyde and glutathione. The umbilical arterial PO2 was found to be higher in Group 3, and malondealdehyde and glutathione levels were lower in newborns of Group 2. It can be concluded that cesarean section with epidural anaesthesia is safer when lipid peroxides are concerned.

Cancer pain, pathophysiology, characteristics and syndromes.

In this study the pathophysiology and characteristics of cancer pain together with cancer pain syndromes and guidelines of management are reviewed. Tumour-associated pain may be nociceptive (somatic or visceral) if the sustaining mechanisms are related to ongoing tissue pathology, or neuropathic when pain is associated with injury to neural tissues. The mechanism by which tumours produce pain include obstruction of lymphatic and vascular channels, distension of a hollow viscous, oedema and tissue inflammation or necrosis. Injury to tissues results in the local release of numerous chemicals that mediate transmission of pain stimulus. Cancer pain syndromes result from one or more of three fundamental causes; direct tumour involvement of tissues, cancer-directed therapy, and mechanisms unrelated to cancer or its treatment. Cancer pain syndromes are also classified as acute or chronic. Cancer pain characteristics provide some of the data essential for syndrome identification. These characteristics include intensity, quality, distribution and temporal relationships. The principles of tumour-directed pain control include modifying the source of pain by treating the cancer and the inflammatory response to cancer, altering the central perception of pain and interfering with nociceptive transmission within the central nervous system.

Effects of metamizol and magnesium sulfate on enzyme activity of glucose 6-phosphate dehydrogenase from human erythrocyte in vitro and rat erythrocyte in vivo.

OBJECTIVE: Effects of metamizol and magnesium sulfate on erythrocyte glucose 6-phosphate dehydrogenase enzyme activity were investigated in in vitro and in vivo conditions. METHODS: For in vitro studies, glucose 6-phosphate dehydrogenase was purified from human erythrocyte and rats were used for in vivo studies. Enzyme activity was determined according to the Beutler method by using a spectrophotometer at 340 nm. RESULTS: The results of in vitro study showed that their mean K(i) values were 6.35 x 10(-3) M for metamizol and 1.32 x 10(-2) M for magnesium sulfate and their inhibition types were uncompetitive. I(50) value was 17 mM for metamizol and 50 mM for magnesium sulfate in in vitro study. In the case of in vivo studies, 200 mg/kg metamizol inhibited the enzyme activity by 40% during the first 1.5 h (p < 0.05), and 225 mg/kg magnesium sulfate significantly inhibited the enzyme activity throughout 24 h (p < 0.01). CONCLUSION: The results of this study suggested that metamizol and magnesium sulfate have significant inhibition effect on the activity of glucose 6-phosphate dehydrogenase enzyme in both in vivo and in vitro.

Determination of serum B12 vitamin and folic acid levels in patient with stroke.

The aim of this study is to evaluate whether any relationship between stroke and vitamin B12, folic acid concentration. We examined 50 patients with stroke (male: 26 and female: 24) aged between (mean +/- SD, year) 59 +/- 14 and 16 control subjects (male: 6 and female: 10) aged between (mean +/- SD, year) 53 +/- 11. Patients were classified into two groups as infarct and hemorrhagic by using Computerised Brain Tomography and Cranial Nuclear Magnetic Resonance Imaging techniques. The percentage of patients with infract was 47.5% in female and 52.5% in male while it was 40% in female and 60% in male with hemorrhagic. The vitamin B12 levels of patients with infarct, hemorrhagic and control group were found as mean +/- SEM, 355 +/- 47 pg/ml, 313 +/- 58 pg/ml, 1569 +/- 258 pg/ml and folic acid levels 13.4 +/- 2.6 ng/ml, 7.7 +/- 1.0 ng/ml, 14.8 +/- 4.0 ng/ml, respectively. The significant difference was found between subgroups of patients with stroke and control group in both folic acid and B12 vitamin levels (p < 0.001 and p < 0.0001, respectively). But, there was no significant difference between vitamin B12 and folic acid levels of patients with hemorrhagic and infarct. In order to well understand the effects of these vitamin in patients with stroke, more detailed follow up studies with long period are needed.

Visual evoked potential changes in migraine. Influence of migraine attack and aura.

OBJECTIVE: To assess the visual evoked potential (VEP) changes in migraines with and without aura. STUDY DESIGN: A clinical study in which the VEP results of 45 migraineurs (study group) and 22 healthy volunteers (control group) were compared. Of 45 migraineurs, 29 had migraine with aura (MA) and 16 had migraine without aura (MOA), and they were examined both during and between the migraine attacks. METHODS: The patients and healthy controls underwent VEP assessment. On VEP recording, mono-ocular stimulation was performed by means of the pattern reversal check board. The latencies of N1, P1 and N2, and the N1--P1 amplitude were noted. The following comparisons were made between NI, P1 and N2 latencies and N1--P1 amplitudes of the migraine and control groups; during and between attack the VEP results of the patients with MA and MOA. RESULTS: The VEP results of the migraineurs and healthy controls were similar (P>0.05). The during attack results of MA, during and between attack results of MOA, and the results of the control group were also similar (P>0.05). N2 latency significantly elongated in patients with MA in the attack free period than it was during the attack (P=0.01), and was also longer than it was in the control group (P=0.01). CONCLUSIONS: There is involvement of the visual pathway in MA rather than MOA, and differentiation between these subtypes of the migraine disease may be performed on the basis of VEP findings manifesting by the prolongation of the N2 wave latency. This contention should be confirmed by further studies.

The prenatal attenuation of brain/body development through interactions between growth hormone, triiodothyronine and testosterone during prenatal development of female neonates.

The relations of serum growth hormone (GH), free testosterone (T), and free triiodothyronine (T3) concentrations to the head circumference, height, and weight were studied in the human neonates. Blood was taken from the umbilical cord immediately after the birth, to measure the hormone concentrations. GH was found to be inversely correlated with the bodily measures in the female neonates; there were no significant correlations between these variables in males. In females, free T3 negatively linearly correlated with GH, and positively linearly correlated with the neonatal head circumference, height, and weight. Serum free T levels was found to be positively linearly correlated with GH, and negatively linearly correlated with the neonatal body measures in the same subjects. It was suggested that GH may exert growth reducing effects through T3 and T during perinatal development.

Pancreastatin stimulates secretion from neonatal rat atrial cells.

Atrial myocardial cells store atrial natriuretic factor and secrete the peptide in response to extracellular stimulation. Ventricular myocardial cells also exhibit stimulated secretion of atrial natriuretic factor but with little or no intracellular storage. The stimulated secretion of other proteins from these cells is poorly characterized. In the present study the secretion of sulfated macromolecules from Na2(35)SO4 labeled atrial and ventricular myocardial cells was quantitated. Both cell types secreted a chondroitin sulfate proteoglycan, as evidenced by glycanase digestion. Endothelin-1, a known stimulator of ANF secretion, stimulated secretion from atrial cells about 70% but had no effect on ventricular cell secretion. The differential stimulation of atrial and ventricular cell secretion was not due to the absence of a regulated secretory pathway in the latter cell type since phorbol ester stimulated secretion from both cell types. This result indicates that differences exist in the early steps of signal transduction between atrial and ventricular cells. Pancreastatin, a regulatory peptide derived from chromogranin A, stimulated atrial cell secretion 90%. This result suggests that chromogranin A, which has been identified in atrial secretory granules, may play an autoregulatory role in atrial secretion.

Hypertonic saline: patterns of and guidelines for use.

Guidelines for appropriate use of hypertonic (3%) saline (HS) for the treatment of hyponatremia are ill-defined. We reviewed each infusion of HS in a 400-bed university hospital over a 1-year period. Of the 14 infusions, the hyponatremia (average serum sodium [Na+] 19.9 +/- 6.7 mEq/L) was chronic in 11 cases and acute in only 3. In only 2 patients were there symptoms possibly attributable to hyponatremia. On the average, more than 5 hours elapsed from the last measured serum Na+ level to the initiation of HS infusion, and the next measured serum Na+ value came more than 6 hours later. HS should be reserved for symptomatically hyponatremic patients, most of whom become acutely hyponatremic. A target level for the serum Na+ should be determined and a time-course for correction set. The infusion should be started promptly and monitored frequently for the effect on the serum Na+ level and patient symptoms.

Medical nomenclature and common conventions for trauma registries.

A trauma registry has been created containing lexicons of terms arranged to foster the adoption of standardized and extensible terminology for the nature and mode of injury. Identification of attribute sets for the nature-of-injury (body region:detailed part:type of injury) and for the mode-of-injury (mechanism:agent:activity:intent:setting) allows the assembly of a clear, concise, easily usable, nad extensible format for representing the appropriate level of detail for nomenclature or classification. This ability allows the use of a common list of terms that is adaptable for case records used in patient care as well as in trauma registry statistics. Several examples of reports using these attributes are shown.