Medical Science Monitor: International Medical Journal of Experimental and Clinical Research

In crisis situations, such as transportation catastrophes, terrorist attacks or contamination with chemical warfare agents, it is crucial to properly organize and sensibly conduct rescue operations. Among chemical warfare agents, the most toxic ones are the derivatives of organophosphorus compounds. An individual auto-injector kit ‘IZAS-05’ contains auto-injectors, which are devices designed for intramuscular administration of drugs in self-aid or buddy-aid on the battlefield. This paper describes in detail the components of the ‘IZAS-05’ kit, as well as its mode of use and possible contraindications.

Background The aim of this study was to investigate whether the 3 different substances that can decrease the development of atherosclerosis – nebivolol, AVE 0991 and doxycycline – could at the same time diminish the level of inflammatory indicators interleukin-6 (IL-6), interleukin-12 (IL-12), serum amyloid A (SAA), and monocyte chemotactic protein-1 (MCP-1). Material/Methods Forty 8-week-old female apoE–knockout mice on the C57BL/6J background were divided into 4 groups and put on chow diet for 4 months. Three experimental groups received the same diet as a control group, mixed with AVE 0991 at a dose 0.58 μmol per kg of body weight per day, nebivolol at a dose 2.0 μmol per kg of body weight per day, and doxycycline at a dose 1.5 mg per kg of body weight per day. At the age of 6 months, the mice were sacrificed. Results All inflammatory indicators (MCP-1, IL-6, IL-12 and SAA) were diminished by AVE 0991. There was also a tendency to lower MCP-1, IL-6, IL-12 and SAA levels by nebivolol and doxycycline; however, it did not reach statistical significance. Conclusions Of the 3 presented substances, only AVE 0991 was able to diminish the rise of inflammatory markers. Therefore, drug manipulations in the renin-angiotensin-aldosterone axis seem to be the most promising in the future treatment of atherogenesis.

Lidocaine is used as a 'test dose' to detect misplacement of epidural catheters. When administered immediately after the initiation of a combined spinal epidural for labor analgesia, it was found to interfere with motor function. The authors hypothesized that an epidural test dose of 3 ml of 1.5% lidocaine injected immediately after the initiation of combined spinal epidural analgesia and followed by a continuous epidural infusion would prolong the duration of analgesia and decrease the incidence of breakthrough pain. Sixty nulliparous parturients were recruited for this randomized controlled trial. Combined spinal epidural analgesia was performed with intrathecal levobupivacaine 2.5 mg and fentanyl 25 microg. The patients were randomized into three groups: group L receiving 3 ml of 1.5% epidural lidocaine, group S 3 ml of normal saline, and group C the control group receiving no test solution. An epidural infusion of 0.1% levobupivacaine and 2 microg of fentanyl/ml at 10 ml/hr was initiated immediately. Their need for supplementary analgesia, duration of analgesia, sensory block, motor block, side-effects, and overall satisfaction were recorded. The breakthrough pain rate in all groups were similar. Their mean duration of analgesia (mean survival times) were not significantly different. Group C had the lowest incidence of lower limb motor block. The satisfaction scores were significantly highest in group L. The administration of epidural lidocaine and saline immediately after intrathecal levobupivacaine 2.5 mg and fentanyl 25 microg did not reduce the incidence of breakthrough pain in combined spinal epidural labor.

Background Hemodynamically significant patent ductus arteriosus (hsPDA) leads to injury in tissues/organs by reducing perfusion of organs and causing oxidative stress. The purpose of this study was to evaluate the oxidant/antioxidant status in preterm infants with hsPDA by measuring the total antioxidant capacity and total oxidant status and to assess neuronal damage due to oxidant stress related to hsPDA. Material/Methods This prospective study included 37 low-birth-weight infants with echocardiographically diagnosed hsPDA treated with oral ibuprofen and a control group of 40 infants without PDA. Blood samples were taken from all infants, and than the total antioxidant capacity (TAC), total oxidant status (TOS), and S-100B protein levels were assessed and oxidative stress index was calculated before and after therapy. Results The mean pre-therapy TOS level and oxidative stress index (OSI) value of the patients with hsPDA were significantly higher, but TAC level was lower than in the control group. There were no statistically significant differences in the mean post-therapy values of TOS, TAC, OSI, and S-100B protein between the two groups. Conclusions hsPDA may cause cellular injury by increasing oxidative stress and damaging tissue perfusion; however the brain can compensate for oxidative stress and impaired tissue perfusion through well-developed autoregulation systems to decrease tissue injury.

Up to now there have been few reports about hematological alterations induced by Giardia lamblia infection. The aim of this study was to evaluate the effects of giardiasis treatment on hematological indices in children in the Khuzestan area by comparing these indices before and after treatment with metronidazole. One hundred two children ranging in age from 5 to 11 years infected with Giardia lamblia between July 2002 and July 2003 and without histories of other diseases were selected from kindergartens and primary schools in the city of Ahwaz. Diagnosis was based on stool examination. The children were treated with metronidazole (15 mg/kg/day for 5 days); hematological values were determined immediately before treatment and repeated 40-45 days after beginning treatment and compared. Iron deficiency anemia was found in 26.5% of the Giardia-infected children. Mean serum hemoglobin, serum hematocrit, serum ferritin, and the ratio of serum iron to total iron-binding capacity were increased (P<0.0001) and mean red-cell distribution width and iron-binding capacity were decreased after treatment (P<0.0001). Treating giardiasis in children with metronidazole improves iron indices and it appears that in evaluating anemia one should rule out giardiasis and treat it in asymptomatic cases to aid in better health status in pediatrics.

Background Currently, there is a wide range of products for mouth washing on the Polish market. They have different qualitative and quantitative compositions, and they differ particularly in the concentration of active substances. In antisepsis and disinfection, the significant reduction in number of cells of microorganisms in a particular environment is very crucial. The chemical agents should provide a significant decrease in number of microorganisms in a relatively short time. The purpose of this study was to examine the bactericidal activity of selected herbal products used for treatment of inflammation, and disinfection and washing of the mouth, having antibacterial activity as declared by the manufacturers. Material/Methods The study included 28 products for mouth washing and disinfection available in Poland. Bactericidal activity was studied using a quantitative suspension test according to the standard PN-EN 1040. Results Only 1 of 4 tested herbal products, registered as medicinal products, showed satisfactory antibacterial activity when they were used according to the manufacturer’s recommendations. A total of 13 preparations (48%) complied with the standard requirements against all tested strains. Up to 19% of products showed no bactericidal activity against bacterial strains, and up to 33% were only effective against certain microorganisms. Conclusions The informational literature accompanying most antiseptics should be corrected by the manufacturers, providing information about antimicrobial activity consistent with the requirements of applicable standards. The information on the packaging or in the leaflets for antiseptic products should be corrected by the manufacturers to include accurate information on antimicrobial activity.

Severe sepsis is a clinical syndrome frequently occurring in intensive care units (ICUs) when systemic infection results in multiorgan dysfunction. No Polish data concerning treatment and prognosis in this group of patients have been available to date. The Polish Working Group for Sepsis introduced in 2003 internet registration of severe sepsis cases treated in ICUs in Poland. Information about severe sepsis were entered including the type of infection, clinical course, methods and results of treatment. From 20.04.2003 to 10.01.2004, 1043 severe sepsis cases were reported by 104 ICUs. Mean age of patients was 59 years. Mean duration of treatment was 19 days, with mortality rate of 55%. In 60% dysfunction of 4 or more organs was diagnosed. In 55% the underlying disease was surgical and abdominal cavity was the primary infection site (47%). Pathogens most likely to cause severe sepsis were G- (48%) and G+ (43%) bacteria, as well as fungi (21%). Positive blood culture was obtained in 45% of patients. Treatment involved antibiotic and support of organ function. Activated protein C was used in 8.2%, causing a reduction of mortality. Severe sepsis in Polish ICUs develops most frequently in the course of intra-abdominal infections. Dysfunction of 4 or more organs caused observed high mortality (55%) Internet surveillance proved to be useful method of collecting information, widely accepted by personnel of ICUs.

Periodontitis is a multifactorial disease and its severe forms, such as aggressive periodontitis, are suggested to have a genetic basis. Among the genetic factors, polymorphisms in cytokine genes have recently been described in susceptibility to periodontitis. IL-10 is a multi-functional cytokine thought to play a role in the pathogenesis of periodontitis. A substitution G/A polymorphism in the promoter region of the IL-10 gene at position -1082 has been associated with different amounts of IL-10 production. The aim of the present study was to investigate the possible links between -1082(G/A) polymorphism of the IL-10 gene and the generalized form of aggressive periodontitis. This study included 52 Iranian Khorasanian (north-east province of Iran) subjects suffering from generalized aggressive periodontitis referred to the Periodontology Department of Mashhad Dental School. They were compared to 61 age and sex-matched healthy controls of the same race. DNA was isolated from peripheral blood cells and genotyping was performed by means of the amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method. Data were analyzed using the chi-squared test. There was no marked difference in genotype frequencies between the controls and generalized aggressive periodontitis patients (p=0.585). Moreover, no association between patients and normal subjects was found in their allele frequency (p=0.329). We conclude that the polymorphic nucleotide A at position -1082 of the IL-10 gene is not associated with generalized aggressive periodontitis in the Iranian population.

Background: Studies have assessed the association between Interleukin-10 (IL-10) -1082A/G polymorphism and diabetic nephropathy (DN) risk, but the results were inconclusive and contradictory. Therefore, we performed a meta-analysis to investigate the association between IL10-1082A/G polymorphism and DN risk. Material and methods: All relevant studies were searched by using PubMed and EMBASE. Data were extracted by 2 authors independently. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Results: Nine case-control studies with 4165 subjects were included in this meta-analysis. We found that IL10-1082A/G polymorphism was significantly associated with an increased DN risk (OR=1.21; 95% CI 1.07-1.37; P=0.002). In the subgroup analysis by race, both Caucasians and Asians with IL10-1082A/G polymorphism showed increased DN risk (OR=1.25; 95% CI 1.03-1.52; P=0.03 and OR=1.25; 95% CI 1.04-1.49; P=0.02), respectively. When we deleted the study without diabetes type, the result was not altered (OR=1.21; 95% CI 1.02-1.44; P=0.03). In the subgroup analysis by sample size, both studies with large sample size and studies with small sample size showed increased DN risk (OR=1.16; 95% CI 1.02-1.31; P=0.02 and OR=1.50; 95% CI 1.14-1.98; P=0.004), respectively. Conclusions: This meta-analysis confirmed that IL10-1082A/G polymorphism might contribute to the susceptibility for DN.

Recent studies have suggested that microRNA-10b (miR-10b) acts as a promoter of metastasis in breast cancer, although the underlying mechanism remains largely unknown. In this study, we provide the first evidence that E-cadherin (E-cad) is a potential target of miR-10b. By applying gain-of-function and loss-of-function approaches in the metastatic breast cancer cell line MDA-MB-231, we demonstrated that miR-10b is necessary and sufficient to regulate the cellular expression of E-cad and in vitro tumor cell invasion. Comparative expression analysis of miR-10b in benign breast lesions (N=16), primary breast cancers (N=21), and metastatic breast carcinomas (N=23) revealed that miR-10b transcription was uniquely up-regulated in metastatic cancers. The expression level of miR-10b positively correlated with tumor size, pathological grading, clinical staging, lymph node metastasis, Her2-positivity and tumor proliferation, but was negatively associated with estrogen receptor-positivity, progesterone receptor-positivity and E-cad mRNA and protein levels. These findings indicate the existence of a novel E-cadherin-related mechanism by which miR-10b modulates breast cancer metastasis. In addition, miR-10b may be a useful biomarker of advanced progression and metastasis of breast cancer.

Anaplastic carcinomas of the pancreas are rare aggressive tumors with survival measurable in weeks. Many terms have been applied used to describe these tumors, and anaplastic foci are identified in ductal adenocarcinomas and in ectopic pancreata, but are not the dominant pattern of growth. We herein present our experience with a case of anaplastic carcinoma of the pancreas with squamous features in order that allowed us to delineate the clinicopathologic and immunohistochemical features of this rare entity. According to imaging findings, the 77-year-old Japanese man was diagnosed as the malignant pancreatic tumor, and underwent a surgical resection. Histopathologically, anaplastic tumor cells showed focal ductal and squamous features infiltrated into pancreatic parenchyma, extrapancreatic fatty tissue, and stomach. The tumor cells showed strong reactivity for cytokeratin, alpha-SMA, vimentin, NSE, and S-100 protein. Although immunoreactivity against p53 was negative, strong positive immunostaining for proliferating cell nuclear antigen and interleukin-1 receptor type I (IL-1RI) was observed in a the majority of tumor cells, while the alpha6 integrin subunit was predominantly strong expressed in the adenocarcinomatous lesion. The patient's postoperative course was uneventful and he was treated with a chemotherapy consisting of gemcitabine. After discharging from the hospital, he had subsequently been observed as an outpatient and same chemotherapy was followed by weekly. However, the patient suffered from peritonitis carcinomatosa and re-increases of multiple liver metastases, and he died in the fourteenth month after surgery. Our immunohistochemical studies suggested that the prognosis of the case with anaplastic carcinoma presented here would be poor, due to the strong expression of integrins and IL-1RI.

Background The functional polymorphism rs4938723 in the promoter region of pri-miR-34b/c is potentially associated with susceptibility to several cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer. Here we conducted a comprehensive meta-analysis to investigate the association between rs4938723 and cancer risk. Material/Methods Eligible studies extracted from the databases of PubMed, Web of Science, and Cochrane Library were evaluated. Statistical analysis was performed using Revman 5.2 and STATA 12.0 software. Results By characterizing the extracted data, a total of 11 studies reported in 10 publications including 6169 cases and 6337 controls were selected for further analysis. Our results revealed a significant association between the rs4938723 polymorphism and cancer risk in the codominant model (TC vs. TT: OR=1.10, 95% CI=1.02–1.19, P=0.009) but not in other genetic models. In the stratified analysis of different cancer types, a significant association was found in nasopharyngeal cancer, osteosarcoma, and renal cell cancer. Furthermore, stratified analysis of ethnicity indicated that a highly significant association was shown in the Asian population in a codominant model (TC vs. TT: OR=1.13, 95% CI=1.03–1.24, P=0.007) when compared with African-Americans and Caucasians. Conclusions Overall, the current study suggests that the miR-34b/c rs4938723 polymorphism may be associated with the risk of cancers, including nasopharyngeal cancer, osteosarcoma, and renal cell cancer, and to some extent this polymorphism is closely related to cancer susceptibility in Asians.

To analyze the prognostic significance of the genes casein kinase 2 alpha subunit (CSNK2A1), anti-apoptosis clone-11 (AAC-11), and tumor metastasis suppressor NME1 in completely resected non-small cell lung cancer (NSCLC) patients. Total RNA was extracted from 145 cases of completely resected, formalin-fixed, paraffin-embedded NSCLC tissues. mRNA expression levels of CSNK2A1, AAC-11, and NME1 were detected by real-time reverse-transcriptase polymerase chain reaction. Univariate and multivariate survival analyses were used to identify factors related to prognosis. A correlation between CSNK2A1 and AAC-11 mRNA expression levels (rs=0.366, p=0.000) was found. Univariate analysis showed that high expression of CSNK2A1 and AAC-11 was predictive of poor prognosis in NSCLC patients (p=0.029 and 0.044, respectively), especially when expression levels of both genes were concomitantly high (p=0.007). Multivariate Cox regression analysis showed that high expression of CSNK2A1, or concomitantly high expression of CSNK2A1 and AAC-11, are independent prognostic factors of poor survival in NSCLC patients. However, NME1 mRNA expression level did not significantly influence survival in NSCLC patients. This retrospective study indicates that CSNK2A1 and AAC-11, especially in combination, are useful prognosis markers in NSCLC patients after complete resection, independent of lymph node metastasis status.

Hemoclip application in GI-hemorrhage has proven to be effective. Clinical experience shows that multiple clips are frequently necessary. In 2005, an easily reloadable clip-applicator was introduced. We evaluated the hemodynamic efficacy of this new device. We prospectively compared the new clipping device (Olympus HX 110/610) in a validated experimental setting using the compactEASIE®-simulator for GI bleeding. The artificial blood circulation system in the simulator was connected to a pressure transducer. Four investigators of different endoscopic experience (1000-6000 endoscopies) treated 12 bleeding sources each, with up to 6 clips for each bleeding location. Pressures were recorded to objectify the additive effects of sequential clip application on the reduction in vessel diameter. The intervention was abandoned if a maximum measurable pressure of 300 mmHg was achieved. Hemoclip application led to a significant increase of peak pressure (91±100 mmHg, p<0.001) and mean pressure (95±99 mmHg, p<0.001), representing a significant reduction in vessel diameter. Pooled data showed a significant stepwise increase in mean and maximum system pressure, resulting in reduction of vessel diameter up to the fifth hemoclip. On average, 5 clips (range 1-6) were used. More experienced endoscopists achieved a higher increase in mean pressure (167 and 118 mmHg vs 72 and 23 mmHg, p<0.05). Mean reloading time was 39 seconds (19-49 sec). Sequential application of multiple hemoclips led to an increasing effect, comparable to the results of previous clinical trials. The number of hemoclips applied correlated inversely, but not significantly, with the endoscopist´s experience. Expensive single-use clips appear dispensable in view of the short reloading time.

Polymorphisms in the IL-18 promoter region (-137, +113, and +127), with perfect linkage disequilibria (Delta=1, p<0.001) among them, were observed in Singaporean Chinese, Malays, and Indians. These polymorphisms appear to have no association with atopic phenotypes. However, functional studies indicate that IL-18 gene polymorphisms strongly affect its activity in cultured cells. The reasons for such conflicting results remain to be determined. It is likely that they are related to the responding cells or to the varying cytokine milieus in the course of the atopic diseases. In this study the effects of IL-18 gene polymorphisms in various IL-18-producing cells were investigated. Three observed alleles were cloned and transfected into HepG-2, HeLa, U937, and THP-1 cells. The transfectional activities of the cultured cells were analyzed. Inserted fragments had significant, but opposite transfectional activity in HepG-2 and HeLa cells, while there was no difference in transfectional activity in U937 and THP-1 cells. These data support the authors' previous observation in which they were unable to detect an association between IL-18 gene polymorphisms and atopic phenotypes in this population. This might be due to different regulatory elements that affect the functional assessment of polymorphisms in different IL-18-producing cells. The functional significance of genetic variants in experimental studies may not be consistent due to complex human traits, but it can also be due to variations in the experimental approaches used, such as the use of different cell or tissue types.

Bone geometry (BG) and size (BS) are important factors in determining bone fragility. Previous studies have suggested that more than half of BG and BS variation is genetically determined. The possible chromosomal locations of genes involved in BS and BG determination have not been explored. We evaluated the extent and mode of inheritance of the radiographic hand BS index (BSI) and the metacarpal cortical index (MCI), and tested the hypothesis of linkage between these traits and the 11q 12-13 chromosomal region. Hand radiographs and blood samples were collected from 1190 individuals belonging to 349 Chuvasha nuclear families (Russian Federation). Segregation analysis was conducted on a total sample. Transmission disequilibrium testing (TDT) and model-based linkage analyses (MBLA) were performed on a sub-sample of 163 families. The hypothesis of a major gene effect was confirmed for both studied traits. The best-fitting models were Mendelian, with an additive type of inheritance. The inferred major gene explained 50% of the CI and 40% of the BSI variation. The TDT and MBLA results did not permit confirmation of hypotheses about linkage between hand BSI and the 11q 12-13 chromosomal region, but a possible linkage between CI and that region cannot be ruled out. We support the hypothesis of a major gene effect in the heritability of BSI and MCI. We provide suggestive evidence for possible linkage disequilibrium between MCI and the 11q12-13 chromosomal segment (marker D11S1983), but not for a linkage between BSI and this

Background: MicroRNAs (miRNAs) are small, non-coding RNAs that may function as oncogenes or tumor suppressors. Previous studies have shown that the expression level of miR-1246 was enhanced in multiple types of cancers. However, the expression of miR-1246 in human oral squamous cell carcinoma (OSCC) and its prognostic values remain unclear. Material and methods: Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to analyze the expression of miR-1246 in 106 pairs of matched normal and tumor tissue samples. The chi-square test was used to examine the associations between miR-1246 expression and the clinicopathological characters. The survival curves were constructed by the Kaplan-Meier method. The influence of each clinical variable on survival was examined by the Cox multivariate regression analysis. Results: The expression level of miR-1246 was significantly higher in tumor tissues and oral cancer cell lines than in normal controls (p<0.01). High expression of miR-1246 was found to significantly correlate with nodal status (p=0.015), TNM stage (p=0.005), and tumor grade (p=0.002). Enhanced miR-1246 correlated significantly with patient survival (p<0.01). In multivariate analysis, we found that miR-1246 expression was an independent prognostic factor of poor patient survival (p= 0.036; HR=2.82; 95% CI=1.07-7.43). Conclusions: High miR-1246 expression is associated with poor prognosis in OSCC and may serve as a novel prognostic marker in OSCC.

This researcher previously found that serum levels of some inflammatory cytokines are elevated in patients with cardiovascular disease (CVD). Hence, this study investigated the relationship between circulating levels of pro-anti-inflammatory cytokines, T-cell activation marker and carbohydrate antigen 125 (CA 125) for the first time in obese Egyptian patients with heart failure (HF). This study included 60 HF patients, and 30 normal controls, with age range 50-70 years. HF patients were divided into 2 groups: non-obese mild HF according to clinical status (New York Heart Association Class) (NYHA class I/II) (n = 20) and obese severe HF (NYHA class III/IV) (n = 40). Serum pro-anti-inflammatory cytokine levels (TNF-α, IL-6, and IL-10), T-cell activation marker (sIL-2R/CD25), and CA 125; tumor marker were measured by ELISA. Serum levels of TNF-α, IL-6, and IL-10 as pro-anti-inflammatory cytokines, sIL-2R/CD25 as T-cell activation marker, and CA 125 as tumor marker were significantly higher in HF patients than in normal controls. Moreover, serum levels of TNF-α, IL-6, sIL-2R/CD25, and IL-10, as well as CA 125 were significantly higher in the obese than in the non-obese mild HF patients. Correlation analysis showed that CA 125 was positively related to BMI, TNF-α, IL-6, and sIL-2R/CD25 in the HF patients group. These findings show that CA 125 is markedly elevated in HF patients, and is correlated with serum TNF-α, IL-6, and sIL-2R/CD25 levels. Therefore, we can conclude that CA125, being a tumor marker, is closely related to the cytokine system.

The tumor marker Cancer Antigen 125 (CA 125), though not ovarian cancer specific, is widely used for the evaluation of suspected and under-treated ovarian cancer. Many studies show that serum CA 125 level demonstrates ovarian tumor burden and its response, but they lack quantitative correlation between the two. Instead, they rely on clinical or radiological assessment of gross tumor burden. This study examines ovarian tumor volumes and corresponding serum CA 125 values before and during chemotherapy. MATERIALS/ METHODS: Ovarian tumor volume was measured by CT scans at pre-chemotherapy and after each cycle of chemotherapy in 15 patients. Blood serum CA 125 was determined on the days of CT scans using a one-step immunoenzymatic assay. There was no statistically significant correlation (r = 0.18, p > 0.05) between ovarian tumor volumes and CA 125 among patients at pre-chemotherapy or any subsequent time. In individual patients, the reduction or increase in tumor volume correlated with the corresponding CA 125 values during chemotherapy in 85% (12 out of 14) of patients. Mean CA 125 halving time was 44.1 days, which correlated with tumor halving time (r = 0.63, p < 0.05). Values of CA 125 cannot be used for comparison of ovarian tumor mass among patients. However, serial estimation of CA 125 in individuals is fairly reliable in terms of the course of the tumor. CT scan is a more informative response indicator, but it is costly and hence may be supplemented by the easy and economical CA 125 estimation.

Serum CA-125 has been used as a biomarker of gynecological tumors. In this study, we investigated the CA-125 levels in cervical and vaginal secretions from Chinese patients with endometrial polyps, hyperplasia and carcinoma in comparison with those in endometrium and serum. An electro-chemiluminescent immunoassay was utilized to determine the levels of CA-125 in 51 healthy Chinese women and 97 patients with polyps, hyperplasia or endometrial cancer. An immunohistochemistry method was used to detect endometrial CA-125 expression in 242 subjects. Our study demonstrated that serum CA-125 levels were much lower than those in cervical and vaginal secretions in healthy and diseased women. The levels of CA-125 in serum, and cervical and vaginal secretions were significantly increased in complex hyperplasia and endometrial cancer. The increase of CA-125 content in serum, cervical and vaginal secretions was lesser significant in grade 3 cancer than that in grade 1 and 2 cancer. Generally, serum CA-125 levels correlated with those in cervical and vaginal secretions and CA-125 content in cervical secretion correlated with that in vaginal secretion. There was only a weak CA-125 expression in normal endometrium and simple endometrial hyperplasia. There was a significant difference in CA-125 expression among patients with pathological grade 1, 2 and 3 of endometrial carcinoma. Endo.metrial CA-125 expression together with its levels in the serum and cervical and vaginal secretions can be used as a potential biomarker in the diagnosis of precancerous diseases and endometrial carcinoma.

MicroRNAs (miRNAs) are small non-coding nucleotides that regulate mRNA stability and protein expression by imperfect base pairing with the 3'-untranslated region (3'UTR) of target mRNAs. Many miRNAs have been documented to be aberrantly expressed in human cancers, but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. The objective of this study was to investigate the effect of miR-125b on EEC development and to explore its molecular mechanism in EEC carcinogenesis. Real-time quantitative PCR was applied to evaluate the expression level of miRNA-125b in EEC and normal endometrium (NE) samples. The invasion ability of miR-125b in EEC HEC1B cells was analyzed by Transwell assay after pre-miR-125b or anti-miR-125b transfection. For the invasion mechanism analysis of miR-125b on HEC1B cells, miRBase, TargetScan, miRanda and PicTar were used to predict the possible target gene of miR-125b. Luciferase activities assay, cotransfection and Western blot were used to reveal that the predicted target genes of miR-125b were direct and specific. RNA interference technology was used to confirm that the invasion inhibition of miR-125b was directly induced by ERBB2. Our study showed that miR-125b was down-regulated in human EEC specimens compared to that in NC specimens. Over-expression of miR-125b in HEC1B cells inhibited EEC invasion and this inhibitory effect on HEC1B cells could be restored by miR-125b knock down. Mechanism analysis revealed that ERBB2 was a direct and specific target of miR-125b. The inhibitory effect on EEC cell invasion was mediated by miR-125b inhibition of the translation of a proto-oncogene, ERBB2. Aberrantly expressed miR-125b contributes to HEC1B cells invasion partly through directly down-regulating ERBB2 protein expression in EEC. This miRNA signature offers a novel potential therapeutic strategy for EEC.

Background Functional assessment of a patient focuses on the assessment of independence in activities of daily living. The aim of the study was to verify the usefulness of a new tool (Functional Capacity Scale – FCS) for early functional assessment of patients after surgical treatment of an intracranial aneurysm. Material/Methods The study was conducted in the Neurosurgical Department and Clinic, CM in Bydgoszcz, NCU, within a group of 128 patients after surgical treatment of an intracranial aneurysm. Direct observation and measurement were used in the study. In clinical assessment, the Hunt and Hess Scale was applied. For the final functional assessment, the Functional Capacity Scale (FCS), the Glasgow Outcome Scale, the Functional Index “Repty”, the Barthel Index, and the Rankin Scale were used. Results The study shows that on the day of discharge almost 60% of patients are independent or slightly dependent on others for functional capability, and 15% are significantly or totally dependent. FCS significantly correlates with FIR (0.93, p<0.001), GOS (0.89, p<0.01), RS (−0.88, p<0.01) and BI (0.82, p<0.001). Conclusions 1. Fifty percent of patients with intracranial aneurysm assessed at the early postoperative stage leave the ward as functionally capable of performing everyday activities. 2. There are significant correlations between FCS and the other scales used for functional assessment. 3. There is a significant relationship between functional capacity of the patient on the day of discharge and clinical condition before the surgical treatment.

Pulmonary oedema with severe, dramatic course following CNS injury was termed neurogenic pulmonary oedema (NPO). NPO was mainly described as a consequence of grand mal seizures, subarachnoid bleeding, intracranial bleeding or head injury. However, the pathogenesis of NPO is not entirely clear yet. In the majority of cases, early or classic symptoms of pulmonary oedema are evident from several minutes up to several hours after CNS damage. Dyspnoea, chest pain, bloody expectoration are observed shortly after consciousness disorders, although NPO may occasionally be diagnosed on the basis of chest x-ray in patients with no clinical symptoms. Tachypnoea, tachycardia, rales without any changes in cardiac system are usually observed during physical examination. The ailments withdraw quickly in the majority of patients, who may require oxygen therapy at most. NPO has been well-known in adults, but our knowledge of its occurrence in children is still rather sparse. The current work presents a case of a 13-year-old boy with pulmonary oedema as a post-seizure complication.

This is a prospective clinical study focusing on cytokine inhibitors (sTNFR I, sTNFR II, IL-1ra) and anti-inflammatory cytokines (IL-10, IL-13) following burn injury in children. The aim of the study was to evaluate the prognostic values of the selected cytokine-related molecules. Fifty-one patients (29 burned children and 22 controls) admitted to the Department of Pediatric Surgery and Oncology were included in this study. Serum sTNFR I, sTNFR II, IL-1ra, IL-10, IL-13, and CRP concentrations were evaluated twice using ELISA, the first determination being performed within 6-24 hrs after the burn and the second following completion of treatment and normalization of the CRP level. With the exception of IL-13, significantly higher cytokine and cytokine inhibitor levels were observed within 6-24 hours after burn compared with controls (p<0.05). Moreover, a significant attenuation of the burn-induced increases in sTNFR I, sTNFR II, IL-1ra, and IL-10 concentrations was recorded after burn therapy (p<0.05). TNF-alpha soluble receptor levels correlated significantly with serum CRP concentrations. Similarly, the levels of sTNFR I, sTNFR II, and IL-1ra significantly correlated with TBSA of the burned children. The results confirm the involvement of these markers in the pathogenesis of SIRS in this clinical entity. Their monitoring simultaneously with CRP level allows evaluating the generalized inflammatory response and may clinically support diagnostic and prognostic methods.

Background: The aim of this study was to determine how Ramadan fasting (RF) affected the recently described new obesity indices [visceral adiposity index (VAI), waist circumference to height ratio (WHtR), body adiposity index (BAI)], and serum concentration of apelin-13 (RF) in healthy adult men. Material and methods: For this purpose, 42 healthy adult men were selected. Anthropometric parameters were measured and a sample of venous blood was obtained for biochemical assays on the first and last days of Ramadan. When all subjects were evaluated, all anthropometric parameters changed except VAI. Serum apelin-13, triglyceride (TG), HDL-cholesterol (HDL-C), and insulin levels did not change. When patients were divided into 3 groups according to body mass index (BMI), BAI decreased in normal-weight subjects and WHtR decreased in other groups, but VAI and apelin-13 did not change in any groups. Results: We demonstrate for the first time that while some anthropometric parameters changed, VAI and serum apelin-13 levels did not change with RF. BMI, waist circumference (WC), TG, and HDL-C were evaluated together in calculation of VAI. TG, VAI, and HDL-C remained unchanged by RF. Even if body weight (BW) and BMI decreased, apelin-13 was not affected by RF. The data on serum apelin-13 may have been influenced by the small-percentage decrease in BW, as well as insignificant improvements in metabolic parameters such as lipid profiles, glucose, and insulin. Conclusions: We found that Ramadan fasting in healthy adult men was associated with significant decreases in BW, BMI, WHtR, and BAI, but we found no significant changes in VAI and serum apelin-13 concentrations.

Salivary gland tumors constitute a highly heterogeneous group. There are few large epidemiological studies of benign and malignant salivary gland tumors in Greece. The aim of the present study was to define the pattern of parotid gland neoplasms on the island of Crete. The medical records of 131 patients who underwent parotidectomy in the Otorhinolaryngology department of the University hospital of Heraklion over the last ten years were retrospectively reviewed. Gender and age of the patients, size, location, and histology of the tumors, as well as postoperative complications were analyzed and tabulated. There were 101 (77.1%) benign parotid gland tumors and 30 (22.9%) of malignant ones. The most common benign tumor was pleomorphic adenoma (44.2%), while the most common malignant tumor was mucoepidermoid carcinoma (5.3%). The female-to-male ratio was 1.18/1.00. Median age was 48.2 years (range: 16-75 years) in patients with benign tumors and 65.4 years (range: 27-90 years) in patients with malignancy. After superficial parotidectomy, the most common postoperative complication was Frey syndrome (8.1%), while after total parotidectomy the most frequent complication was transient facial nerve palsy (45.5%). On Crete, parotid gland tumors show epidemiological characteristics similar to studies worldwide. Benign parotid tumors are largely more frequent than malignant tumors. The most common benign parotid gland tumor was pleomorphic adenoma, while the most frequent malignant tumor was mucoepidermoid carcinoma. Future research needs to be done to better define the epidemiology of these tumors among the Greek population.

Reactive oxygen species contribute to the multiple organ failure endotoxic shock. Here we investigate the effects of a salen-manganese complex, which exhibits both superoxide dismutase and catalase activity (EUK-134), on the circulatory failure and the renal and liver injury and dysfunction caused by endotoxin in the anaesthetised (thiopentone, 120 mg/kg) rat. Male Wistar rats were anaesthetised with thiopentone sodium (120 mg/kg i.p.) and instrumented for the measurements of systemic haemodynamics. Animals received lipopolysaccharide (LPS, E. coli, 6 mg/kg i.v.) or saline and were treated with either EUK-134 (0.3 or 1 mg/kg bolus injection followed by an infusion of 0.3 or 1 mg/kg/h) or its vehicle (saline). After 6 h of endotoxaemia, blood was taken to evaluate biochemical parameters of organ injury and dysfunction. All data are mean I s.e. mean of n observations. Statistical comparisons were made with a ANOVA followed by Dunnet's test for multiple comparisons. Endotoxaemia for 6 h caused hypotension, renal dysfunction, liver injury, skeletal-muscle injury and pancreatic injury. Treatment of rats with EUK-134 attenuated the renal dysfunction as well as the liver and skeletal muscle injury (but not the pancreatic injury) caused by endotoxin. Thus, an enhanced formation of reactive oxygen species importantly contribute to the organ injury and dysfunction associated with endotoxic shock. We propose that small molecules, which have the catalytic activity of both superoxide dismutase and catalase, may represent a novel therapeutic approach for the therapy of endotoxic shock.

In cirrhosis, hepatic mitochondriae exhibit morphological and functional abnormalities. In human steatosis, ultrastructural changes are reported in the absence of ethanol. Routine evaluation of mitochondrial function is difficult. We used a breath test to explore hepatic mitochondrial oxidation in vivo. The 13C-methionine breath test was performed in healthy subjects (n=15), patients with cirrhosis (n=25), and patients with biopsy-proven severe (> 40% involved hepatocytes), non-alcoholic macrovesicular steatosis (n=18). After oral administration of 13C-methionine (200 mg), hepatic mitochondrial decarboxylation was measured by breath [13C]-C02 enrichment, expressed as dose/h and delta over base (DOB), for 1 hour, by isotope ratio infrared spectroscopy. Results were normalized against BMI. At 60 minutes, patients with steatosis had reduced exhalation of 13C02 as compared to healthy subjects (dose/h: -47%, 18.8+/-12 vs 36+/-6.1; DOB: -52%, 40.4+/-32 vs 85+/-20, p<0.05). Cirrhotics had even lower values as compared to patients with steatosis (dose/h: -60%, 7.5+/-3.4 vs 18.8+/-12, p<0.05). In cirrhosis, dose/h correlated (r=0.68) to aminopyrine breath test values, a microsomal function test, and was inversely correlated (r=-0.48) to the Child-Pugh score. Hepatic mitochondrial oxidation as reflected by the 13C-methionine breath test is impaired both in patients with pure non alcohol-related severe macrovesicular steatosis and in patients with cirrhosis of mixed etiologies. This non- invasive test can be used to monitor hepatic mitochondrial function in vivo.

To investigate if age affects the results of the 13C-mixed triglyceride (13C-MTG) breath test. Two groups of 12 healthy subjects (group Y, 25.0+/-0.7 years; group MA, 48.8+/-2.4 years), each comprising 6 men and 6 women, were examined. The fasted volunteers had a 349-kcal test breakfast of 50 g of white bread with 30 g of butter to which 300 mg of 13C-MTG was added. Then a series of samples of exhaled air for the measurement of 13CO2 concentration was collected over a period of 9 hours. A maximum momentary 13CO2 breath excretion of 9.6+/-0.5%dose/h at 295+/-19 min in the young subjects and of 9.4+/-0.4%dose/h at 270+/-15 min in the middle-aged volunteers was observed. The group curves of cumulative 13C recovery in breath air exhibited a virtually overlapping time course. The 6-h cumulative 13C recovery amounted to 32.01+/-1.78%dose and 31.84+/-1.73%dose in the Y and MA groups, respectively. Extension of the collection of breath air samples from the standard six to nine hours resulted in an increase in the cumulative 13C recovery by 51.5+/-3.2%. Accordingly, the 9-h cumulative 13C recovery was 47.59+/-2.26%dose and 48.28+/-2.36%dose in the Y and MA groups, respectively. An age difference of over two decades does not compromise intrajejunal lipolytic activity taken as a measure of pancreatic exocrine function. Therefore reference values for the 13C-MTG breath test can be obtained from a population of healthy subjects of a relatively wide age range.

Lansoprazole (LAN) is a proton pump inhibitor drug (PPI) metabolized by the P-450 liver cytochrome (CYP-450) system. LAN is used in association with antimicrobial agents in Helicobacter pylori (HP) eradication therapy. The 13C-Aminopyrine breath test (ABT) is a non-invasive tool exploring liver CYP-450 metabolic activity. Since pharmacological interactions may occur during PPI administration, we attempted to evaluate possible interference with liver CYP-450 activity during HP eradication therapy. Fourteen HP positive patients received LAN (30 mg b.i.d.), clarithromycin (500 mg b.i.d.) and metronidazole (500 mg b.i.d.) for one week. Prior to therapy, and at day 8, each patient underwent 13C-ABT. The 13CO2 concentration in breath samples was measured every 15 minutes from t0 to t120. Results are expressed as cumulative percentage of the administered dose of 13C recovered over time (% 13C dose cum), and as a percentage of the administered dose of 13C recovered per hour (% l3C dose/h). Comparisons were carried out by the Wilcoxon test. Data are presented as mean +/- SD. At day 8, mean ABT was no different from baseline values, both considering % 13C dose cum and% 13C dose/h at each sampling time (e.g.,% 13C dose cum120 which is the most expressive value of the parameters taken into consideration, baseline vs day 8: 10.88 +/- 3.81 vs 10.13 +/- 3.57). These results show that LAN administration and the concomitant use of antimicrobial drugs during HP eradication therapy do not seem to be associated with significant modifications in liver CYP-450 activity.

We evaluated the effect of age on the results of a cornflakes breath test that determines the efficiency of starch digestion. MATERIAL/METHods: Two groups of 12 fasted healthy subjects (group Y, 24.7+/-0.6 years; and group MA, 49.7+/-1.3 years) consumed a 521-kcal test breakfast of 100 g cornflakes naturally abundant in 13C (-14.00 per thousand 13C enrichment relative to the Vienna Pee Dee belemnite standard). Then, the 13CO2 concentration was measured in samples of exhaled air collected over 9 hours. We noted a maximum momentary 13CO2 breath excretion of 7.54+/-0.19% dose/h at 298 +/- 15 minutes in group Y and 7.70+/-0.27% dose/h at 305+/-10 minutes in group MA. The group curves of the cumulative 13C recovery in breath air exhibited a virtually overlapping time course. The 6-hour cumulative 13C recovery was 29.33+/-0.70%dose in group Y and 29.87+/-1.18%dose in group MA. Extending the collection period from 6 to 9 hours produced an increase in the cumulative 13C recovery of 58.4+/-2.1%. The 9-hour cumulative 13C recovery was 46.58+/-1.04%dose in the Y group and 46.93+/-1.84%dose and the MA group. An age difference of more than 2 decades was not associated with a negative impact on the in vivo ability to digest starch. The reference values of the cornflakes breath test can be derived from healthy subjects in a relatively wide age range.

Some 13CO2 breath tests require prolonged breath sampling. The study aimed to validate a meal which could be served to subjects without interference with the measured breath 13CO2 profile. Eight healthy volunteers were examined on three separate days. On two occasions they took equicaloric meals of 320 kcal composed of foodstuffs known to be poor in 13CO: cooked rice (R) or a wheat bread sandwich with butter and ham (S). On the control day they fasted. Samples of expiratory air were taken every 15 min for 6 hours. The 13CO2 concentration in the samples was measured by isotope ratio mass spectrometry. Statistical analysis involved repeated measures analysis of variance (RANOVA). The intra-subject variability of breath 13CO2 concentration was remarkably low on the three study days, as reflected by mean coefficients of variation (CV) of 0.90+/-0.32%, 0.79+/-0.19%, and 0.80+/-0.34% for the control, meal S, and meal R days, respectively (RANOVA: F2;14=0.296, p=0.75). RANOVA indicated a strong effect of a meal on inter-subject variability of breath 13CO2 concentration (F2;46=390.62 p<0.000001). Post hoc comparisons revealed a mean CV of 1.64+/-0.37% on the control day, 3.62+/-0.18% after ingestion of S, and 3.81+/-0.24% after meal R (both p=0.000128 vs. the control). Nevertheless, with neither test meal did RANOVA disclose at any time a statistically significant deviation in breath 13CO2 concentration from the basal fasted value. Both the test meals fulfilled the requirement of neutrality as concerns a null effect on the breath 13CO2 profile.

Loss of heterozygosity, frequently observed during the development of many tumor types, also occurs in larynx cancer. This disease has a very complex genetic background, with numerous alterations involving oncogenes and tumor suppressor genes. The upper parts of the respiratory-digestive tract are exposed to many carcinogens, which can result in the appearance of multiple tumors or primary tumor relapses. The examination of normal-appearing tissues makes it possible to recognize genetic events occurring at early stages. 65 larynx cancer patients were examined for loss of heterozygosity (LOH) on the 13q chromosomal arm, with the application of three microsatellite markers. The material from each patient consisted of blood, tumor, safe margin, and 1-2 clinically unchanged mucosal samples. High frequencies of LOH in tumor tissues (49-64%) were observed in both studied chromosomal regions (13q14 and 13q34). The frequency of LOH in safe margin ranged from 12 to 31%. In normal-appearing mucosa, LOH was observed less frequently: 6-26% of informative cases. The data obtained from this investigation suggest that losses in the region of the 13q arm occur frequently during larynx cancer development. Moreover, they were observed not only in tumor tissues, but also in clinically unchanged mucosa. This could be a highly reliable predictor of the occurrence of relapse or second primary tumor in this anatomical site.

Osteoporosis, especially in postmenopausal women, delineates a major health and economic problem in the world. Regarding the pathogenesis of osteoporosis and the interaction between various cells and mediators, many studies have been conducted to evaluate the benefit of different therapeutic options. Over the past several years evidence has been growing on the effects of dietary fatty acids on bone health. The objective of this paper was to provide a review of the current knowledge of dietary fatty acids and osteoporosis. Medline/Index Medicus and EMBASE/Excerpta Medica were searched for relevant papers regarding the effects of n-3 fatty acids on osteoporosis between 1963 and 2007 using the key words: osteoporosis, bone health, n-3 fatty acids, and PUFA. Bone mineral density and bone markers have been used in several animal studies to evaluate the beneficial effect of n-3 fatty acids on bone health and the prevention of osteoporosis. Generally, animal studies support the beneficial effects of n-3 fatty acids on bone health and osteoporosis; however, the dissimilar lipid metabolism in human and animals, the various study designs, and controversies over the human study outcomes make it difficult to draw a definite conclusion. The authors believe that conclusive findings in humans are still lacking in this area and it needs to be further investigated.

Unlabelled: THE PURPOSE OF THE STUDY was to provide current and reliable information about trends in the incidence rates of Type 1 Diabetes in the Upper Silesia region in children aged 0-15 years in the period of 9 years. Results: Incidence ratio in the examined population increased from 4.71 in 1989 up to 10.16/100,000/year in 1997. In the analysed group no significant statistical differences dependent on sex were found. During the examined period, the incidence ratio has increased significantly. It was observed that the extent of change varied in different age groups. The youngest children (0-4 years old) showed the greatest increase of the incidence ratio from 1.09/10(5) in 1989 up to 6.75/10(5) in 1997. The highest incidence ratio was observed in the group of 10-14 year-olds. Conclusions: In the examined period dramatic increase (more than 200%) of the incidence ratio of type 1 diabetes was reported in the children's population (0-14 year-olds) in Upper Silesia. The fastest increase in this ratio was established in the group of youngest children (0-4 years old).

The study was undertaken to establish the pharmacological basis of the stimulatory activity of galantide (M15) and galanin(1-14)-(a-aminobutyric acid8-[Abu8])scyliorhinin-I [Scy-I] in gastric smooth muscle. Isotonic contractions of the isolated, longitudinal rat gastric fundus strips were recorded. Galanin, galanin(1-15)-NH2, M15 and galanin(1-14)-[Abu8]Scy-I elicited concentration-dependent contractions. Their EC50s equaled 12.95, 174, 70.06 and 187 nM respectively. Hill's coefficients for galanin and galanin(1-15)-NH2 were not different from unity, indicating an interaction of one peptide molecule with one receptor according to the principles of classical receptor theory. Hill's coefficients were 0.73 and 1.56 for M15 and galanin (1-14)-[Abu8]Scy-I, respectively, a value significantly different from unity. Cold-storage denervation, tetrodotoxin-TTX (1 mM), spantide (100 mM) and NK1-3 receptor antagonists SR140333, 48968, 142801 (up to 10 mM) notably diminished M15, galanin(1-14)-[Abu8]Scy-I, SP(5-11) and [Abu8]-Scy-I evoked contractions without affecting activities of galanin and galanin(1-15)-NH2. Additionally, cross-desensitization experiments attenuated activity of M15 and galanin(1-14)-[Abu8]Scy-I without any noticeable action on galanin or galanin(1-15)-NH2. The action of chimeric peptides on the smooth muscle of the rat gastrointestinal tract depended not only on the myogenic interaction of those peptides with galanin binding sites, but also on the activation of tachykinin receptors or the release of endogenous mediators from the presynaptic terminals.

Osteogenic growth peptide (OGP) is an endogenous tetradecapeptide present in micromolar concentrations in mammalian serum; its carboxy-terminal pentapeptide, OGP(10-14), represents its physiologically active fragment. OGP(10-14) induces proliferation and differentiation in fibroblast and osteoblast cell lines, and it enhances hematopoiesis in vitro and in vivo. The signaling pathways triggered by OGP(10-14) are not yet fully known. In the present report, we evaluated the effect of OGP(10-14) on differentiation of a cancer megakaryoblast cell line and its involvement on RhoA and Src family kinases signaling pathway. Cell proliferation of the Mo-7e line was evaluated using the MTT test. Mo-7e differentiation was evaluated by microscopic observation of cell morphology and by expression of the factor VIII-related antigen. Involvement of RhoA and Src kinases on signaling pathways triggered by OGP(10-14) was analyzed using RhoA and Src family kinase (SFK) inhibitors (C3 and PP2) and an immunoperoxidase technique. OGP(10-14) induces expression of the factor VIII-related antigen, morphologic changes indicative of megakaryocytic differentiation, and a down-regulation of the Fyn Src kinase. These OGP(10-14) effects were prevented by C3 and enhanced by PP2. The anti-proliferative and pro-differentiating activities of OGP(10-14) on thrombopoietin (TPO)-primed Mo-7e cells are mediated by RhoA and Src kinase pathways as demonstrated by the use of C3 and PP2.

Osteogenic growth peptide (OGP) is a 14-mer peptide found in relevant concentration in blood, and its carboxy-terminal fragment [OGP(10-14)] represents the active portion of the full-length peptide. In addition to stimulating bone formation, OGP(10-14) shows hematological activity. In fact, it highly enhances hematopoiesis-affecting stem progenitors. Moreover, OGP(10-14) reduces the growth and induces the differentiation of the hematological tumour cell line trombophoietin(TPO)-primed M07-e by interfering with RhoA and Src kinase pathways. In the present report, we went deeper into this mechanism and evaluated the possible interference of the OGP(10-14) signal pathway with TGFβ1 and TPO receptor Mpl. In OGP(10-14)-treated M07-e cells cultured with or without RhoA and Src kinases inhibitors (C3 and PP2), expression of TGFβ1, Mpl, and Src kinases was analyzed by immunoperoxidase technique. Activated RhoA expression was studied using the G-LISA™ quantitative test. In M07-e cells, both OGP(10-14) and PP2 activate RhoA, inhibit Src kinases, reduce Mpl expression and increase TGFβ1 expression. OGP(10-14) and PP2 show the same behavior, causing an additive effect when associated. OGP(10-14) induces TPO-primed M07-e cells differentiation through RhoA/TGFβ1/SFKs signalling pathway. In particular OGP(10-14) acts as a Src inhibitor, showing the same effects of PP2.