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In transdermal applications of nonsteroidal anti-inflammatory drugs, the rheological and mechanical properties of the dosage form affect the performance of the drug. The aim of this study to develop emulgel and nanostructured lipid carrier NLC-based gel formulations containing ibuprofen, evaluate their mechanical properties, bioadhesive value and ex-vivo rabbit skin permeability. All formulations showed non-Newtonian pseudoplastic behavior and their viscosity values are suitable for topical application. The particle size of the nanostructured lipid carrier system was found to be 468 ± 21 nm, and the encapsulation efficiency was 95.58 ± 0.41%. According to the index of viscosity, consistency, firmness, and cohesiveness values obtained as a result of the back extrusion study, E2 formulation was found to be more suitable for transdermal application. The firmness and work of shear values of the E2 formulation, which has the highest viscosity value, were also found to be the highest and it was chosen as the most suitable formulation in terms of the spreadability test. The work of bioadhesion values of NLC-based gel and IBU-loaded NLC-based gel were found as 0.226 ± 0.028 and 0.181 ± 0.006 mJ/cm2 respectively. The percentages of IBU that penetrated through rabbit skin from the Ibuactive-Cream and the E2 were 87.4 ± 2.11% and 93.4 ± 2.72% after 24 h, respectively. When the penetration of ibuprofen through the skin was evaluated, it was found that the E2 formulation increased penetration due to its lipid and nanoparticle structure. As a result of these findings, it can be said that the NLC-based gel formulation will increase the therapeutic efficacy and will be a good alternative transdermal formulation., (© 2024. The Author(s).)

Nutrition has been acknowledged as crucial in IBD and is relevant to patients' motives behind food choices, which are affected by health engagement (HE) and food involvement (FI). This study aimed to profile IBD patients according to their levels of health engagement and food involvement to identify patterns of different motives behind food choices, particularly regarding the use of food to regulate mood. A cross-sectional study was conducted with 890 Italian IBD patients who completed an online survey in April 2021. We measured health engagement, food involvement, motives behind food choices, emotional states, and food-related quality of life (Fr-QoL). K-means cluster analysis was performed to identify participants with similar levels of health engagement and food involvement. Four clusters were identified: "Health-conscious (high HE, low FI)", "Balanced (high HE, high FI)", "Hedonist (high FI, low HE)", and "Careless (low FI, low HE)". Clusters with high FI are inclined toward seeking pleasurable food, but when supported with high health engagement, individuals were less prone to use food to manage mood. Groups with higher health engagement demonstrated lower hospitalization rates and relapses and better Fr-QoL. Profiling IBD patients regarding FI and HE could aid clinicians in identifying individuals at greater risk of maladaptive food-related behaviors.

Novel drug treatments for pediatric patients with cancer are urgently needed. Success of drug development in pediatric oncology has been promising, but many drugs still fail in translation from preclinical to clinical phases. To increase the translational potential, several improvements have been implemented, including the use of clinically achievable concentrations in the drug testing phase. Although pharmacokinetic (PK) parameters of numerous investigated drugs are published, a comprehensive PK overview of the most common drugs in pediatric oncology could guide preclinical trial design and improve the translatability into clinical trials. A review of the literature was conducted for PK parameters of 74 anticancer drugs, from the drug sensitivity profiling library of the INdividualized Therapy FOr Relapsed Malignancies in Childhood (INFORM) registry. PK data in the pediatric population were reported and complemented by adult parameters when no pediatric data were available. In addition, blood-brain barrier (BBB)-penetration assessment of drugs was provided by using the BBB score. Maximum plasma concentration was available for 73 (97%), area under the plasma concentration-time curve for 69 (92%), plasma protein binding for 66 (88%), plasma half-life for 57 (76%), time to maximum concentration for 54 (72%), clearance for 52 (69%), volume of distribution for 37 (49%), lowest plasma concentration reached by the drug before the next dose administration for 21 (28%), and steady-state concentration for 4 (5%) of drugs. Pediatric PK data were available for 48 (65%) drugs. We provide a comprehensive review of PK data for 74 drugs studied in pediatric oncology. This data set can serve as a reference to design experiments more closely mimicking drug PK conditions in patients, and may thereby increase the probability of successful clinical translation., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: We aimed to evaluate the incidence, clinical findings, and risk factors of antibiotic-associated diarrhea (AAD) in hospitalized children without known comorbid diseases., Methods: All hospitalized children during the 1-year period that fulfilled the inclusion criteria were included in this study (n = 358). AAD was defined as; ≥2 loose or watery stools per day for a minimum of 24 hours during antibiotic treatment caused by Clostridioides difficile or negative stool tests for identifiable infectious agents., Results: During hospitalization, diarrhea developed in 32 (8.93%) of the 358 patients. C. difficile toxin B was positive for 1 case. No infectious agents were detected in 21 patients. Overall, AAD was observed in 22 patients (6.14%, 95% CI: 4.09-9.13). Male sex ( P = 0.027, OR: 3.36), age between 1 month and <3 years ( P = 0.01, OR: 4.23), ibuprofen use ( P = 0.044, OR: 2.63) and late administration of antibiotics ( P = 0.001, OR: 9.5) were associated with the development of AAD., Conclusions: The incidence of AAD is low among hospitalized children without comorbid diseases, and most diarrheal episodes are mild and self-limiting. The use of probiotics in this patient group may be limited to certain specific situations., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The study reported here aimed to develop and optimize the S-SNEDDS tablet of bosentan (BOS) and to investigate its pharmacokinetic and biodistribution properties. The BOS-loaded SNEDDS have been developed and characterized in a previous study. The BOS-loaded SNEDDS formulation was converted to S-SNEDDS using Neusilin® US2. The S-SNEDDS tablets were obtained using the direct compression technique, and in vitro dissolution, in vitro lipolysis, and ex-vivo permeability studies of the tablets were performed. The S-SNEDDS tablet and reference tablet (Tracleer®) were administered to male Wistar rats at 50 mg/kg dose by oral gavage in fasted and fed state conditions. The biodistribution of the S-SNEDDS tablet was investigated in Balb/c mice using fluorescent dye. The tablets were dispersed in distilled water before administration to animals. The relationship between in vitro dissolution data and in vivo plasma concentration was examined. The S-SNEDDS tablets showed 2.47, 7.49, 3.70, and 4.39 increases in the percentages of cumulative dissolution in FaSSIF, FeSSIF, FaSSIF-V2, and FeSSIF-V2, respectively, when compared to the reference, and increased the C max and AUC 2.65 and 1.28-fold and 4.73 and 2.37-fold in fasted and fed states, respectively, when compared to the reference. S-SNEDDS tablets also significantly reduced interindividual variability in both fasted and fed states (p < 0.05). The XenoLight™ DiR and VivoTag® 680XL labeled S-SNEDDS tablet formulation increased the real-time biodistribution in the body by factors of 2.4 and 3.4 and organ uptake and total emission increased by factors of 2.8 and 3.1, respectively. The IVIVR has been successfully established for S-SNEDDS tablets (R 2  > 0.9). The present study confirms the potential of the S-SNEDDS tablet to enhance the in vitro and in vivo performance of BOS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Zeynep Safak Teksin reports financial support was provided by Scientific and Technological Research Council of Turkey. Zeynep Safak Teksin reports a relationship with Scientific and Technological Research Council of Turkey that includes: funding grants. Zeynep Safak Teksin has patent #TR201915787 issued to Zeynep Safak Teksin. Duygu Yilmaz Usta - Gazi University]., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pediatric low-grade gliomas (pLGG) show heterogeneous responses to MAPK inhibitors (MAPKi) in clinical trials. Thus, more complex stratification biomarkers are needed to identify patients likely to benefit from MAPKi therapy. Here, we identify MAPK-related genes enriched in MAPKi-sensitive cell lines using the GDSC dataset and apply them to calculate class-specific MAPKi sensitivity scores (MSSs) via single-sample gene set enrichment analysis. The MSSs discriminate MAPKi-sensitive and non-sensitive cells in the GDSC dataset and significantly correlate with response to MAPKi in an independent PDX dataset. The MSSs discern gliomas with varying MAPK alterations and are higher in pLGG compared to other pediatric CNS tumors. Heterogenous MSSs within pLGGs with the same MAPK alteration identify proportions of potentially sensitive patients. The MEKi MSS predicts treatment response in a small set of pLGG patients treated with trametinib. High MSSs correlate with a higher immune cell infiltration, with high expression in the microglia compartment in single-cell RNA sequencing data, while low MSSs correlate with low immune infiltration and increased neuronal score. The MSSs represent predictive tools for the stratification of pLGG patients and should be prospectively validated in clinical trials. Our data supports a role for microglia in the response to MAPKi., (© 2023. The Author(s).)

Objective: Cerebellar mutism syndrome (CMS) is a well-known complication after posterior fossa tumor surgery in pediatric patients. We evaluated the incidence of CMS in our institute and analyzed its association with multiple risk factors, such as tumor entity, surgical approach, and hydrocephalus., Methods: All pediatric patients who had undergone intra-axial tumor resection in the posterior fossa between January 2010 and March 2021 were included in the retrospective analysis. Various data points, including demographic, tumor-associated, clinical, radiological, surgery-associated, complications, and follow-up data, were collected and statistically evaluated for an association with CMS., Results: A total of 63 surgeries in 60 patients were included. The median patient age was 8 years. Pilocytic astrocytoma was the most common tumor type (50%), followed by medulloblastoma (28%) and ependymomas (10%). Complete, subtotal, and partial resection was achieved in 67%, 23%, and 10%, respectively. A telovelar approach had been used the most often (43%) compared with a transvermian approach (8%). Of the 60 children, 10 (17%) had developed CMS and showed marked improvement but with residual deficits. The significant risk factors were a transvermian approach (P = 0.03), vermian splitting when added to another approach (P = 0.002), an initial presentation with acute hydrocephalus (P = 0.02), and hydrocephalus present after tumor surgery (P = 0.004)., Conclusions: Our CMS rate is comparable to those described in the literature. Despite the limitations of the retrospective study design, we found that CMS was not only associated with a transvermian approach but was also associated with a telovelar approach, although to a lesser extent. Acute hydrocephalus at the initial presentation necessitating urgent management was significantly associated with a greater incidence of CMS., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Biphalangealism has been evaluated in many studies and has been shown as a common variant. Its frequency varies according to the populations. This epidemiological study aimed to determine the prevalence of biphalangealism for each toe in the Turkish population and compare it with other populations., Methods: The local hospital radiological database was searched for all consecutive foot radiographs, obtained between 2014 and 2018. Anteroposterior (AP) and oblique radiographs obtained to evaluate trauma or foot pathologies were included. Two-phalangeal toes according to radiographical views were defined as biphalangeal and other three-phalangeal toes were defined as normal., Results: A total of 2,881 radiographs of 2,710 adult patients met the incusion criteria. There were 1,558 (57.5%) female and 1,152 (42.5%) male patients. The cases were unilateral in 2,539 patients and bilateral in 171 patients. The overall prevalence of biphalangeal third toe was 0.29%, fourth toe was 1.29%, and fifth toe was 23.3%., Conclusions: The presence of pedal biphalangealism is a common variant and its frequency varies according to the populations. The exact cause is still unclear. Further studies are required to assess the clinical impact of biphalangealism.

Tablet splitting is a common practice in clinical settings to lower doses, facilitate swallowing or save costs. Splitting devices can be used when hand splitting is difficult or painful. However, data on the accuracy of tablet splitting are limited and it presents a number of patient or formulation-related problems. Thirty nebivolol IR tablets on the Turkish market were split by hand, a tablet cutter (Rabır®) or a knife, and tested for weight variation, loss of mass, disintegration, and friability. The accuracy of split tablets was in the range of 75.4-121, 82.4-115, and 86.9-115% when split by hand, the cutter, and knife, respectively. No significant difference in accuracy was determined between the left and right sides split by the cutter (p = 0.222). The differences were significant for hand and knife splittings (p < 0.005). The precision was 9.02, 7.87, and 6.11% (CV%) for hand, tablet cutter, and knife, respectively. Only hand splitting failed to comply with the subdivision test of European Pharmacopoeia. The split portions met USP standards for friability (<1%). Splitting decreased the disintegration time (4.5 vs. 2.2 min). Overall, the accuracy of the tablet cutter was more favorable than hand splitting and knife. The study demonstrated that the splitting technique may result in inaccurate dosing and significant drug fluctuations for nebivolol tablets., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V. on behalf of King Saud University.)

Objectives: Most patients with type 1 diabetes (T1D) experience a transient phase of partial remission (PR). This study aimed to identify the demographic and clinical factors associated with PR., Methods: This was a longitudinal retrospective cohort study of 133 children and adolescents with T1D. PR was defined by the gold standard insulin dose-adjusted hemoglobin A1c (HbA1c) (IDAA1c) of ≤9., Results: Remission was observed in 77 (57.9%) patients. At diagnosis, remitters had significantly higher pH (7.3 ± 0.12 vs. 7.23 ± 0.15, p=0.003), higher C-peptide levels (0.45 ± 0.31 ng/mL vs. 0.3 ± 0.22, p=0.003), and they were significantly older (9.3 ± 3.6 years vs. 7.3 ± 4.2, p=0.008) compared with non-remitters. PR developed more frequently in patients without diabetic ketoacidosis (DKA) (p=0.026) and with disease onset after age 5 (p=0.001). Patients using multiple daily insulin regimen were more likely to experience PR than those treated with a twice daily regimen (63.9 vs. 32%, p=0.004). Only age at onset was an independent predictor of PR (OR: 1.12, 95% CI: 1-1.25; p=0.044). Remitters had lower HbA1c levels and daily insulin requirement from diagnosis until one year after diagnosis (p<0.001). PR recurred in 7 (9%) patients. The daily insulin requirement at three months was lower in remitters with PR recurrence compared to those without (0.23 ± 0.14 vs. 0.4 ± 0.17 U/kg/day, p=0.014)., Conclusions: Addressing factors associated with the occurrence of PR could provide a better comprehension of metabolic control in T1D. The lack of DKA and higher C-peptide levels may influence PR, but the main factor associated with PR presence was older age at onset. PR may recur in a small proportion of patients., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The sensitivity of myelocytomatosis oncogene (MYC) amplified medulloblastoma to class I histone deacetylase (HDAC) inhibition has been shown previously; however, understanding the underlying molecular mechanism is crucial for selection of effective HDAC inhibitors for clinical use. The aim of this study was to investigate the direct molecular interaction of MYC and class I HDAC2, and the impact of class I HDAC inhibition on MYC function., Methods: Co-immunoprecipitation and mass spectrometry were used to determine the co-localization of MYC and HDAC2. Chromatin immunoprecipitation (ChIP) sequencing and gene expression profiling were used to analyze the co-localization of MYC and HDAC2 on DNA and the impact on transcriptional activity in primary tumors and a MYC amplified cell line treated with the class I HDAC inhibitor entinostat. The effect on MYC was investigated by quantitative real-time PCR, western blot, and immunofluorescence., Results: HDAC2 is a cofactor of MYC in MYC amplified medulloblastoma. The MYC-HDAC2 complex is bound to genes defining the MYC-dependent transcriptional profile. Class I HDAC inhibition leads to stabilization and reduced DNA binding of MYC protein, inducing a downregulation of MYC activated genes (MAGs) and upregulation of MYC repressed genes (MRGs). MAGs and MRGs are characterized by opposing biological functions and by distinct enhancer-box distribution., Conclusions: Our data elucidate the molecular interaction of MYC and HDAC2 and support a model in which inhibition of class I HDACs directly targets MYC's transactivating and transrepressing functions., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pilocytic astrocytomas as well as other pediatric low-grade gliomas (pLGG) exhibit genetic events leading to aberrant activation of the MAPK pathway. The most common alterations are KIAA1549:BRAF fusions and BRAF V600E and NF1 mutations. Novel drugs targeting the MAPK pathway (MAPKi) are prime candidates for the treatment of these single-pathway diseases. We aimed to develop an assay suitable for preclinical testing of MAPKi in pLGGs with the goal to identify novel MAPK pathway-suppressing synergistic drug combinations. A reporter plasmid (pDIPZ) with a MAPK-responsive ELK-1-binding element driving the expression of destabilized firefly luciferase was generated and packaged using a lentiviral vector system. Pediatric glioma cell lines with a BRAF fusion (DKFZ-BT66) and a BRAF V600E mutation (BT-40) background, respectively, were stably transfected. Modulation of the MAPK pathway activity by MAPKi was measured using the luciferase reporter and validated by detection of phosphorylated protein levels. A screening of a MAPKi library was performed, and synergy of selected combinations was calculated. Screening of a MAPKi library revealed MEK inhibitors as the class inhibiting the pathway with the lowest IC 50 s, followed by ERK and next-generation RAF inhibitors. Combination treatments with different MAPKi classes showed synergistic effects in BRAF fusion as well as BRAF V600E mutation backgrounds. Here, we report a novel reporter assay for medium- to high-throughput preclinical drug testing in pLGG cell lines. The assay confirmed MEK, ERK, and next-generation RAF inhibitors as potential treatment approaches for KIAA1549:BRAF and BRAF V600E -mutated pLGGs. In addition, the assay revealed that combination treatments synergistically suppressed MAPK pathway activity., (©2020 American Association for Cancer Research.)

Purpose: Pilocytic astrocytoma is the most common childhood brain tumor, characterized by constitutive MAPK activation. MAPK signaling induces oncogene-induced senescence (OIS), which may cause unpredictable growth behavior of pilocytic astrocytomas. The senescence-associated secretory phenotype (SASP) has been shown to regulate OIS, but its role in pilocytic astrocytoma remains unknown. Experimental Design: The patient-derived pilocytic astrocytoma cell culture model, DKFZ-BT66, was used to demonstrate presence of the SASP and analyze its impact on OIS in pilocytic astrocytoma. The model allows for doxycycline-inducible switching between proliferation and OIS. Both states were studied using gene expression profiling (GEP), Western blot, ELISA, and cell viability testing. Primary pilocytic astrocytoma tumors were analyzed by GEP and multiplex assay., Results: SASP factors were upregulated in primary human and murine pilocytic astrocytoma and during OIS in DKFZ-BT66 cells. Conditioned medium induced growth arrest of proliferating pilocytic astrocytoma cells. The SASP factors IL1B and IL6 were upregulated in primary pilocytic astrocytoma, and both pathways were regulated during OIS in DKFZ-BT66. Stimulation with rIL1B but not rIL6 reduced growth of DKFZ-BT66 cells and induced the SASP. Anti-inflammatory treatment with dexamethasone induced regrowth of senescent cells and inhibited the SASP. Senescent DKFZ-BT66 cells responded to senolytic BCL2 inhibitors. High IL1B and SASP expression in pilocytic astrocytoma tumors was associated with favorable progression-free survival., Conclusions: We provide evidence for the SASP regulating OIS in pediatric pilocytic astrocytoma, with IL1B as a relevant mediator. SASP expression could enable prediction of progression in patients with pilocytic astrocytoma. Further investigation of the SASP driving the unpredictable growth of pilocytic astrocytomas, and its possible therapeutic application, is warranted., (©2018 American Association for Cancer Research.)

Nowadays pharmaceutical industries and regulatory authorities suggest new approaches such as Quality by Design principles to reduce experiments of formulation studies, improve product quality, save cost and time. SeDeM Expert System is a predictive approach for the preformulation studies and it provides information about suitability of API for direct compression by evaluating 12 parameters. The system also allows selecting appropriate excipients by determining same parameters to improve compressibility of API. The objective of this study was to develop direct compressed memantine orally disintegrating tablets using SeDeM Expert System. Memantine was found to have poor flow and compressibility properties. Three different direct compressibility and super disintegrating agents (Ludiflash ® , Ludipress ® and Parteck ® ) were used to improve compressibility of memantine and according to SeDeM diagrams, Parteck ® was selected for final formulation. Memantine direct compressed tablets showed proper friability, hardness and thickness. The disintegration time of the tables were found below 15 s which was suitable for ODTs. It was found that SeDeM Expert System was easy to use and application of this method provided to develop memantine direct compressed ODT formulation was successful.

Being exposed to traumatic experiences is rather common in patients with schizophrenia. Adverse experiences may induce the onset of psychotic symptoms or trigger current symptoms to be exacerbated. Eye Movement Desensitization Reprocessing (EMDR) is an effective therapy in the treatment of incidences with underlying traumatic experiences, there by it can be conducted on various cases in addition to other treatments such as psycho-medication or another therapy method. It was developed by Shapiro in 1980s. Although desensitization is widely applied on patients with Post-Traumatic Stress Disorder, it is unusual for EMDR therapy to be safely and effectively performed in the treatment of psychotic disorder sor symptoms. In the present case study, EMDR treatment process and course of psychiatric state in a patient with history of child hood abuse and forced psychiatric residency will be discussed. The patient who had a diagnosis of schizophrenia for 8 years was treated with antipsychotic treatment as well as 2 sessions of EMDR, and as a result, a positive change was observed in her general clinical course. Our thoughts on this phenomenon are that EMDR treatment is an effective, safe and short-term intervention in the comorbidity of PTSD and psychotic disorders. However, the literature about the place of EMDR in the treatment of schizophrenia cases is rather limited and much more research is needed.

Pilocytic astrocytoma (PA) is the most frequent pediatric brain tumor. Activation of the MAPK pathway is well established as the oncogenic driver of the disease. It is most frequently caused by KIAA1549:BRAF fusions, and leads to oncogene induced senescence (OIS). OIS is thought to be a major reason for growth arrest of PA cells in vitro and in vivo, preventing establishment of PA cultures. Hence, valid preclinical models are currently very limited, but preclinical testing of new compounds is urgently needed. We transduced the PA short-term culture DKFZ-BT66 derived from the PA of a 2-year old patient with a doxycycline-inducible system coding for Simian Vacuolating Virus 40 Large T Antigen (SV40-TAg). SV40-TAg inhibits TP53/CDKN1A and CDKN2A/RB1, two pathways critical for OIS induction and maintenance. DNA methylation array and KIAA1549:BRAF fusion analysis confirmed pilocytic astrocytoma identity of DKFZ-BT66 cells after establishment. Readouts were analyzed in proliferating as well as senescent states, including cell counts, viability, cell cycle analysis, expression of SV40-Tag, CDKN2A (p16), CDKN1A (p21), and TP53 (p53) protein, and gene-expression profiling. Selected MAPK inhibitors (MAPKi) including clinically available MEK inhibitors (MEKi) were tested in vitro. Expression of SV40-TAg enabled the cells to bypass OIS and to resume proliferation with a mean doubling time of 45h allowing for propagation and long-term culture. Withdrawal of doxycycline led to an immediate decrease of SV40-TAg expression, appearance of senescent morphology, upregulation of CDKI proteins and a subsequent G1 growth arrest in line with the re-induction of senescence. DKFZ-BT66 cells still underwent replicative senescence that was overcome by TERT expression. Testing of a set of MAPKi revealed differential responses in DKFZ-BT66. MEKi efficiently inhibited MAPK signaling at clinically achievable concentrations, while BRAF V600E- and RAF Type II inhibitors showed paradoxical activation. Taken together, we have established the first patient-derived long term expandable PA cell line expressing the KIAA1549:BRAF-fusion suitable for preclinical drug testing.

Objective: The aim of this study was to investigate Legg-Calvé-Perthes disease (PD) pathogenesis by comparing absolute circulating endothelial progenitor cell (EPC) counts, serum levels of vascular endothelial growth factor-A (VEGF-A) and immunoglobulins between PD patients and controls., Methods: The study included 28 PD cases (mean age: 8 ± 3.8) and 25 healthy age-matched control subjects. EPC, serum VEGF-A and immunoglobulin levels were measured in peripheral blood samples. Comparisons and correlation analysis were performed., Results: In the PD group, 17 subjects were in the fragmentation stage and 11 in the healing stage. Four patients had bilateral disease and 14 had hypogammaglobulinemia. Median EPC count of the PD group was 80 and was significantly higher than those of the control group (p=0.011). No significant difference was determined in serum VEGF-A levels (p=0.354). EPC count were inversely correlated with serum IgG levels of the PD group (r=0.403, p=0.03). Absolute EPC count was also significantly higher in the fragmentation stage than in the healing stage and were also greater in bilaterally affected than in unilaterally affected patients. Circulating EPC count was correlated to the serum VEGF-A levels in patients with fragmentation stage of PD (r=0.605, p=0.01) and in those with hypogammaglobulinemia (r=0.599, p=0.001)., Conclusion: High EPC count at the fragmentation stage of PD and relatively higher counts in bilateral disease suggest that EPC may be a valuable marker in the diagnosis and follow-up of PD. Additional studies are needed to explain the strong correlation between EPC and serum VEGF-A level in the fragmentation stage and in the presence of hypogammaglobulinemia.

Toxicity of organophosphorus insecticides is mainly due to the inhibition of acetylcholinesterase, but, oxidative stress may be involved in the toxicity of this pesticides. Therefore, it was investigated whether diazinon, a commonly used organophosphate, may induce oxidative stress and cholinesterase inhibition in different tissues of Cyprinus carpio. Sublethal concentrations of diazinon (0.0036, 0.018 and 0.036ppb) were administired to C. carpio L. for 5, 15 and 30 days. The study was made by measuring biochemical stress responses of C. carpio L. spectrophotometrically taking into account acetylcholinesterase (AChE), Na(+)K(+)-adenosine triphosphatase (Na(+)K(+)-ATPase) and other antioxidant enzyme activities, as well as malondialdehyde and protein contents in gill, muscle and kidney tissues of the fish. Results of the study suggest that AChE (in gill and muscle tissues) and Na(+)K(+)-ATPase (in muscle and kidney tissues) activities decreased; that antioxidant enzymes, in particular superoxide dismutase (SOD), increased in gill, kidney and muscle tissues. We also observed the existence of a protective function of antioxidant enzymes against lipid peroxidation in muscle tissue. The changes in MDA content varied between increases and decreases in kidney tissue. In gill tissue, however, lipid peroxidation could not be prevented despite induction of SOD and glutathione peroxidase activities. We could see that the protein content decreased only in gill tissue as diazinon dosage was gradually increased until the 15th day of the experiment. During the period between 15th and the 30th days, the protein level in the fish was observed to have reached to that of the control group. This change in protein level can be attributed to adjustment of the fish to its new environmental conditions. Considering most of the parameters in tissues, it can be stated that diazinon exerted its effect at low concentration and during a long period of time, and its toxicity increased dose dependently. This study reveals that C. carpio developed tissue-specific adaptive response to neutralize the oxidative stress following pesticide exposure depending on different antioxidant levels in tissues and that SOD can be used as a biomarker in determining diazinon toxicity due to its early response at even low concentration levels., (Copyright © 2006 Elsevier B.V. All rights reserved.)

The aim of this study was to investigate the effects of organophosphorus (OP) pesticide diazinon on acetylcholinesterase (AChE: EC 3.1.1.7) activity and its relationship to lipid peroxidation (LPO) in the brain of a freshwater fish, Oreochromis niloticus. Malondialdehyde (MDA) content was used as biomarker for LPO. Fish were exposed to 1 and 2mg/L sublethal concentrations of diazinon for 1, 7, 15 and 30 days. In the entire experimental group, AChE activity in brain significantly decreased (up to 93% of control), whereas MDA content decreased after 1 day, and increased after 7 and 15 days of exposures. MDA was in similar level with the control group after diazinon exposure of 30 days. The findings of the present study show that diazinon inhibited AChE activity and it has LPO-inducing potential in fish. The inhibition of AChE activity in the brain of O. niloticus correlated with increased MDA levels after 7 and 15 days diazinon exposures (r=-0.661, P<0.019; r=-0.652, P<0.022, respectively).

During the last week of December 1989, an outbreak of respiratory system infection involved 32 hospital personnel and 2 patients was detected in Gazi University Medical Faculty Hospital. White blood cells count of the patients were either normal or there were a slight leucopenia. Throat cultures of the most patients were normal. Serum ASO, CRP, bilirubin, AST and ALT were usually within normal limits. According to symptoms, signs and laboratory data we considered a viral disease, especially influenza. All patients recovered without any sequelae. Of 34 in-patients, 8 paired sera, 2 acute phase sera, and 10 convalescent phase sera were tested for the presence of Hemagglutination Inhibition (HI) antibody to three influenza virus strains recommended by WHO in the 1989-1990 season: Influenza A/Taiwan/1/86 (H1 N1), Influenza A/Shanghai/11/87 (H3 N2), Influenza B/Victoria/2/87. All of the sera were negative for Influenza B/Victoria/2/87. There were no significant rises in HT antibody titer for Influenza A/Taiwan/1/86 (H1 N1). The sera for 4 of 8 patients examined both acute and convalescent phase sera had fourfold or greater rise in HI antibody for Influenza A/Shanghai/11/87 (H3 N2). Four patients examined only convalescent sera had 1/40 or greater rises in HI antibody for this influenza subtype. It was considered that this influenza outbreak was probably caused by Influenza A/Shanghai/11/87 (H3 N2).

In this paper, a food poisoning outbreak of 42 people who ate the sucuk (Turkish sausage flavored with garlic) which was made of the same meat has been described. Salmonella typhimurium was isolated from the stool of 20 patients and from the sucuk. Efficacy rate of Ofloxacin was 75 percent in these 20 patients treated Ofloxacin.