Cellular immunity to nucleoproteins (NP) of Crimean-Congo hemorrhagic fever virus (CCHFV) and Hazara Virus (HAZV).

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a globally significant vector-borne pathogen with no internationally-licensed preventative and therapeutic interventions. Hazara virus (HAZV), on the other hand, a related Orthonairovirus, has not been reported as a human pathogen. HAZV has been proposed as a surrogate model for studying CCHFV, bisosafety level 4 (BSL-4) agent. Previously, we investigated the humoral immune responses between NPs of these viruses and in this study, we extended the scrutiny to cellular immune responses elicited by NPs of CCHFV and HAZV. Here, mice were immunized with recombinant CCHFV NP and HAZV NP to evaluate the correlates of cell-mediated immunity (CMI). Delayed-type hypersensitivity (DTH) responses were assessed by challenging immunized mice with CCHFV-rNP or HAZV-rNP on the footpad and lymphocyte proliferation assays (LPAs) were performed by stimulating splenocytes in vitro with CCHFV-rNP or HAZV-rNP to compare cellular immune responses. In all test groups, strong DTH and LPA responses were detected against homologous and heterologous challenging antigens. To assess the cytokine response, an RT-qPCR -specific for cytokine mRNAs was utilized. Interestingly, CCHFV NP stimulated groups exhibited a significantly elevated mRNA level of interleukin 17 A (IL-17) compared to HAZV NP, indicating a notable difference in immune responses. This study presents comparison between CMI elicited by NPs of CCHFV and HAZV and contributes to the understanding of a highly pathogenic virus, particularly in the context of the declaration of CCHFV by World Health Organization's (WHO) as a major viral threat to the world.

The NF1 gene mutations and co-mutations in lung adenocarcinomas with brain metastasis.

BACKGROUND: The co-occurrence of lung adenocarcinoma and brain metastasis remains a significant cause of morbidity and mortality despite advancements in cancer treatment. The activity of neurofibromin, the product of Neurofibromatosis Type 1 gene (NF1), is crucial in regulating the RAS/MAPK pathway. The NF1 somatic mutations are significant in conditions such as melanoma, lung cancer, breast cancer, neuroblastoma, and central nervous system tumors. OBJECTIVE: Therefore, this research aims to uncover the profile of NF1 mutations and co-mutations in patients with brain metastases from lung adenocarcinoma, shedding light on their role in the pathophysiology of metastatic lung cancer. MATERIALS AND METHODS: In this study, a total of 131 (31 females, 90 males) patients diagnosed with metastatic lung adenocarcinoma who were examined in the Molecular Pathology Laboratory between 2019 and 2022 were retrospectively analyzed. The NF1 somatic mutations and co-mutations were evaluated using the NGS lung panel on the MiniSEQ NGS platform. RESULTS: The average age of the 131 patients (31 females, 90 males) retrospectively examined in the study was 62.05 years. The ages of the cases included in the study followed a normal distribution according to Kolmogorov-Smirnov test (P = 0.200). Lymph node metastasis was detected in 48 patients (36.6%), while distant organ metastasis was observed in 81 patients (61.83%). Metastases were more frequently seen in males. No statistically significant difference was found between metastases and gender (P > 0.05). Distant organ metastasis (n = 26, 19.8%) and NF1 mutations (n = 8/26, 30.77%) were most commonly observed in the brain. The most common NF1 pathogenic variants in brain metastases were c.2325 + 3A > G (p.M1205fs*12) (n = 6/26, 23.07%) and c.1400C > T (p.T4671) (n = 5/26, 19.23%). There was no statistically significant relationship observed between patients' age, gender, brain metastasis, and NF1 mutation types (respectively, P = 0.98, P = 0.63, and P = 0.87). The mutations that showed the most association with NF1 mutations in brain metastases were PTEN and TP53. CONCLUSIONS: Somatic NF1 mutations and co-mutations can play a critical driving force in metastatic lung adenocarcinoma and may contribute to treatment resistance. The mutational landscape of somatic NF1 mutations and co-mutations can provide new insights into the pathophysiology of metastatic lung cancer, especially those that have metastasized to the brain.

Evaluation of New Generation Sequencing (NGS)-Based Somatic Gene Variations and Real-Time Polymerase Chain Reaction (PCR)-Based Gene Fusions in Elderly and Young Acute Leukemia Patients: A Retrospective View.

Malignant diseases occurring in elderly patients follow a different course from younger patients and show different genetic structures. Therefore, in this retrospective study, the somatic gene variant profile and fusion gene profiles of elderly and young acute leukemia patients were determined to draw attention to the existing genetic difference, and the results were compared. In this study, the records of 204 acute leukemia patients aged 18+ who were referred to the Molecular Pathology Laboratory from the Hematology Clinic between 2018 and 2022 were reviewed retrospectively. Fusion gene detection in patients was performed with the HemaVision®-28Q Panel. The NGS Myeloid Neoplasms Panel was conducted using the MiniSEQ NGS platform according to the manufacturer's protocol. When all cases are evaluated together, the most frequently diagnosed acute leukemia is acute myeloid leukemia (85.8%). Both groups had a similar fusion gene profile; however, the fusion burden was higher in the elderly group. When the groups were evaluated in terms of somatic gene variations, there were differences between the groups, and the variation load was higher in the elderly group. Considering the different somatic gene variation profiles, it is understood that the genetic structure of tumor cells is different in elderly patients compared to young cases.

Geriatric Importance of Histopathological Parameters Evaluated in Thyroidectomy Specimens: A Single Center Retrospective Analysis.

Nowadays, the aging human population exerts a notable influence on the treatment of thyroid diseases. The most appropriate approach for the treatment of benign and malignant thyroid diseases in older adults has not yet been determined. The aim of our study is to evaluate the effect of thyroidectomies in geriatric patients considering age, sex and histopathological parameters and to determine the importance of thyroidectomy as a treatment option in the geriatric population. A total of 910 cases from all age groups were included, for which thyroidectomies were examined and reported. In accordance with the College of American Pathologists Cancer Protocol for thyroid reporting, considering geriatric patients, the rate of Thyroid Follicular Nodular Disease was significantly higher among the tumor types in the benign tumor group (p = 0.033), while Anaplastic Thyroid Carcinoma rate was higher in the malignant tumor group. The diagnosis rate of malignant tumors was higher in males, reflecting a more advanced pT stage (p < 0.001), larger tumor size (p < 0.001) and increased lymph node involvement rate (p = 0.039). Given that increasing age is associated with a heightened incidence of thyroid disease, the safety of surgery for geriatric patients is an important issue. Thyroidectomy should be considered in the treatment of these patients, especially in males, as the rate of malignant diagnosis and worse histopathological parameters are seen with increasing age.

Mutation Profile via Next-Generation Sequencing in Patients with Colorectal Adenocarcinoma and Its Clinicopathological Correlation.

BACKGROUND/AIMS: Recent studies that reveal the molecular profiles of colorectal carcinomas have demonstrated tumor heterogeneity. Characterization of colorectal carcinoma-specific genomic alterations is essential for developing more successful and targeted treat- ment protocols. Moreover, it is vital in elucidating the pathogenesis and mechanisms of resistance against treatment and predicting prognosis. MATERIALS AND METHODS: The study included 73 cases diagnosed with colorectal carcinomas and subjected to molecular analysis by the next-generation sequencing. The association between the clinicopathologic parameters and pathogenic mutations detected in 32 genes was evaluated. RESULTS: Pathogenic mutations were determined in a total of 24 genes. The Cell Division Cycle 27 (CDC27), Kirsten rat sarcoma viral proto-oncogene (KRAS), serine/threonine protein kinase B-raf (BRAF), phosphatase and tensin homolog, breast cancer 2 (BRCA2), and phosphotidylinositol-4,5-biphosphate 3-kinase (PIK3CA) mutations were determined at higher rates, with the adenomatous polypo- sis coli mutation determined at a lower rate than in the literature. There were significant positive correlations between CDC27 and phosphatase and tensin homolog (PTEN), PTEN and BRCA2, and PTEN and adenomatous polyposis coli (APC) concomitant muta- tions, whereas negative correlations were present between BRAF and KRAS. Statistically significant relationships were present between KRAS exon 2 and mucinous morphology, PIK3CA and absence of perineural invasion, BRAF and tumor differentiation/localization, MutS homolog 3 (MSH3) and tumor diameter, and BRCA2 and absence of lymph node metastasis. CONCLUSION: It is necessary to have a comprehensive database of genomic alterations of colorectal carcinomas to interpret mutations more accurately clinically. There are no studies on the frequency of mutations in colorectal carcinomas in the Turkish population; thus, follow-up and treatment protocols are organized following the European and American databases and guidelines. A comprehensive study of the colorectal carcinoma patients' mutation profile in the Turkish patient cohort by the next-generation sequencing method will help to provide significant therapeutic, prognostic, and predictive data and design more successful treatment and follow-up strategies.

Occupational Silica Exposure as a Potential Risk for Microscopic Polyangiitis.

Microscopic polyangiitis is an important and common component of cytoplasmic antibody-associated vasculitides that can lead to serious morbidity and even death. A clear causative etiology has not been identified. Although silica is well known to produce lung damage, the negative renal effects of silica exposure should not be overlooked. We present a case of renal dysfunction associated with silica exposure, its diagnosis by renal biopsy, and the treatment method used. Environmental or occupational silica exposure can cause microscopic polyangiitis. Working in occupations with increased risk of silica exposure may result in serious medical problems.

Neutralization of Wild-Type and Alpha SARS-CoV-2 Variant by CoronaVac® Vaccine and Natural Infection- Induced Antibodies.

One of the immune responses desired to be achieved by SARS-CoV-2 vaccination is to create neutralizing antibodies (nAbs), thus preventing the development and spread of infection. The aim of this study was to investigate the seropositivity rate, anti-spike antibody levels, and neutralizing capacity of these antibodies against wild type (WT) and alpha variants in serum samples of individuals who had been naturally infected or vaccinated with CoronaVac®. Total anti-spike antibody levels were determined in all samples. Neutralization assays were performed by the reduction of the cytopathic effect in Vero-E6 cells with infectious WT and alpha SARS-CoV-2 variants. Although both naturally infected and vaccinated individuals were all seropositive for antispike antibodies, 84.8% of the vaccinated group, and 89.3% of the naturally infected group had detectable nAbs. The nAbs titers were significantly higher in the naturally infected group for both WT and alfa variant of the virus as compared to the vaccinated individuals. In this study, it was observed that all individuals became seropositive six weeks after exposure to the vaccine or the virus. Moreover, naturally infected individuals had higher levels of nAbs than those vaccinated. The presence of nAbs against the alpha variant in both naturally infected and vaccinated individuals suggests that these antibodies may also be protective against infections, which may be caused by other variants, such as delta and omicron.

Evaluation of the Mutation Profile via Next-Generation Sequencing in a Turkish Population With Non-small Cell Lung Cancer.

BACKGROUND: Lung cancer is the most common cancer type worldwide, with non-small cell lung cancer being the most frequently studied. Identifying of cancer-related genes in non-small cell lung cancer is crucial for developing individualized treatment, particularly as mutation profiles can vary by country and ethnicity. AIMS: To identify comprehensive mutation profiles in a cohort of Turkish patients with non-small cell lung cancer using the next-generation sequencing. STUDY DESIGN: Retrospective cross-sectional study. METHODS: In total, 72 cancer-related genes and 4149 variants were recorded in the non-small cell lung cancer panel, and their relationship with clinical and histopathological features was investigated through next-generation sequencing. RESULTS: Among 507 patients, 420 (82.8%) were males and 87 (17.2%) were females. Percentages of phosp hatid ylino sitol -4,5- bisph ospha te 3-kinase catalytic subunit alpha (11%), B-Raf proto-oncogene, serine/threonine kinase (8%), and neurofibromatosis type 1 (6%) mutations were higher than those reported in the literature. Males had a higher rate of Kirsten rat sarcoma 2 viral oncogene homolog mutations (P = .102), whereas epidermal growth factor receptor mutations were statistically more common in females (P = .001). Multiple variants of strong significance were identified in 6.3% patients diagnosed with adenocarcinoma, most of whom were smokers. Kirsten rat sarcoma 2 viral oncogene homolog and phosp hatid ylino sitol -4,5- bisph ospha te 3-kinase catalytic subunit alpha mutations were most commonly observed. CONCLUSION: This study shows that Turkish patients have higher rates of PIK3CA, BRAF and NF1 mutations compared to the literature. Studies to determine the molecular profile specific to Turkish people will guide clinicians in treatment and contribute significantly to determining priorities in diagnosis.

Immune responses in multiple hosts to Nucleocapsid Protein (NP) of Crimean-Congo Hemorrhagic Fever Virus (CCHFV).

In 2019, the World Health Organization declared 3 billion to be at risk of developing Crimean Congo Hemorrhagic Fever (CCHF). The causative agent of this deadly infection is CCHFV. The data related to the biology and immunology of CCHFV are rather scarce. Due to its indispensable roles in the viral life cycle, NP becomes a logical target for detailed viral immunology studies. In this study, humoral immunity to NP was investigated in CCHF survivors, as well as in immunized mice and rabbits. Abundant antibody response against NP was demonstrated both during natural infection in humans and following experimental immunizations in mice and rabbits. Also, cellular immune responses to recombinant NP (rNP) was detected in multispecies. This study represents the most comprehensive investigation on NP as an inducer of both humoral and cellular immunity in multiple hosts and proves that rNP is an excellent candidate warranting further immunological studies specifically on vaccine investigations.

Borate reduces experimental supra-celiac aortic clamping-induced oxidative stress in lung and kidney, but fails to prevent organ damage.

BACKGROUND: This study aims to investigate the effects of 2-aminoethoxydiphenyl borate (2-APB) on aortic clamping-induced lung and kidney tissue oxidation, tissue inflammation, and histological damage in a rat model. METHODS: A total of 28 adult female Wistar albino rats were randomly allocated to four equal groups: Control group, ischemia-reperfusion group, dimethyl sulfoxide group, and 2-APB group. Animals in the control group underwent median laparotomy. In the remaining groups, supra-celiac aorta was clamped for 45 min and, then, reperfusion was constituted for 60 min. The 2-APB (2 mg/kg) was administered before clamping. The remaining groups received saline (ischemia-reperfusion group) or dimethyl sulfoxide (dimethyl sulfoxide group). Kidney and lung tissue samples were harvested at the end of reperfusion. RESULTS: Aortic occlusion caused increased tissue total oxidant status and reduced total antioxidant status and glutathione levels in the ischemia-reperfusion and dimethyl sulfoxide groups. Tissue interleukin-1 beta and tumor necrosis factor-alpha levels, nuclear factor kappa beta activation, and histological damage severity scores were also higher in these groups. The 2-APB treatment eliminated the increase in total oxidant status and the decrease in total antioxidant status and glutathione levels. It also caused a decrease in the interleukin-1 beta levels, although it did not significantly alter the tumor necrosis factor-alpha levels, nuclear factor kappa beta immunoreactivity, and histological damage scores. CONCLUSION: Borate exerted a beneficial antioxidant effect as evidenced by reduced oxidative stress; however, it did not inhibit nuclear factor kappa beta activation and prevent histological damage in supra-celiac aortic clamping-induced kidney and lung injury in rats.

Probiotic Saccharomyces boulardii Alleviates Lung Injury by Reduction of Oxidative Stress and Cytokine Response Induced by Supraceliac Aortic Ischemia-Reperfusion Injury in Rats

Abstract Objectives: Ischemia-reperfusion injury is an important cause of multiple organ failure in cardiovascular surgery. Our aim is to investigate the effect of the probiotic Saccharomyces boulardii on oxidative stress, inflammatory response, and lung injury in an experimental model of aortic clamping. Methods: Twenty-one Wistar rats were randomized into three groups (n=7). Control group animals received saline gavage for a week before undergoing median laparotomy. In other groups, supraceliac aorta was clamped for 45 minutes to induce ischemia followed by reperfusion for 60 minutes. In the ischemia-reperfusion group, saline gavage was given preoperatively for one week. Ischemia-reperfusion+probiotic group rats received probiotic gavage for seven days before aortic clamping. The levels of oxidative stress markers and pro-inflammatory cytokines were determined in both serum and lung tissue samples. Ileum and lung tissues were harvested for histological examination. Results: Ischemia-reperfusion caused severe oxidative damage and inflammation evident by significant increases in malondialdehyde and cytokine levels (tumor necrosis factor alpha and interleukin-1 beta) and decreased glutathione levels in both serum and lung tissues. There was severe histological tissue damage to the lung and ileum in the ischemia-reperfusion group. Probiotic pretreatment before aortic clamping caused significant suppression of increases in serum and lung tissue malondialdehyde and tumor necrosis factor alpha levels. Histological damage scores in tissue samples decreased in the ischemia-reperfusion+probiotic group (P<0,005). Conclusions: Oral supplementation of probiotic S. boulardii before supraceliac aortic ischemia-reperfusion in rats alleviates lung injury by reducing oxidative stress, intestinal cellular damage, and modulation of inflammatory processes.

Cross-Reactive anti-Nucleocapsid Protein Immunity against Crimean-Congo Hemorrhagic Fever Virus and Hazara Virus in Multiple Species.

The World Health Organization estimates that there may be three billion people at risk of infection by Crimean-Congo Hemorrhagic Fever Virus (CCHFV), a highly lethal, emerging orthonairovirus carried by ticks. On the other hand, the closely related Hazara virus (HAZV), a member of the same serogroup, has not been reported as a pathogen for humans. Given the structural and phylogenetic similarities between these two viruses, we evaluated the immunological similarities of the nucleocapsid protein (NP) of these two viruses in multiple species. Strong antigenic similarities were demonstrated in anti-NP humoral immune responses against HAZV and CCHFV in multiple species using convalescent human CCHF sera, rabbit and mouse polyclonal antiserum raised against CCHFV, and mouse polyclonal antiserum against CCHFV-NP in enzyme immunoassays. We also report a convincing cross-reactivity between NPs in Western blots using HAZV-infected cell lysate as antigen and inactivated CCHFV and CCHFV-NP-immunized mice sera. These results suggest that NPs of HAZV and CCHFV share significant similarities in humoral responses across species and underline the potential utility of HAZV as a surrogate model for CCHFV.IMPORTANCE CCHFV and HAZV, members of the Nairoviridae family, are transmitted to mammals by tick bites. CCHFV is considered to be a severe threat to public health and causes hemorrhagic diseases with a high mortality rate, and there are neither preventative nor therapeutic medications against CCHFV disease. HAZV, on the other hand, is not a pathogen to humans and can be studied under BSL-2 conditions. The antigenic relationship between these viruses is of interest for vaccines and for preventative investigations. Here, we demonstrate cross-reactivity in anti-NP humoral immune response between NPs of HAZV and CCHFV in multiple species. These results underline the utility of HAZV as a surrogate model to study CCHFV infection.

Probiotic Saccharomyces boulardii Alleviates Lung Injury by Reduction of Oxidative Stress and Cytokine Response Induced by Supraceliac Aortic Ischemia-Reperfusion Injury in Rats.

OBJECTIVES: Ischemia-reperfusion injury is an important cause of multiple organ failure in cardiovascular surgery. Our aim is to investigate the effect of the probiotic Saccharomyces boulardii on oxidative stress, inflammatory response, and lung injury in an experimental model of aortic clamping. METHODS: Twenty-one Wistar rats were randomized into three groups (n=7). Control group animals received saline gavage for a week before undergoing median laparotomy. In other groups, supraceliac aorta was clamped for 45 minutes to induce ischemia followed by reperfusion for 60 minutes. In the ischemiareperfusion group, saline gavage was given preoperatively for one week. Ischemia-reperfusion+probiotic group rats received probiotic gavage for seven days before aortic clamping. The levels of oxidative stress markers and pro-inflammatory cytokines were determined in both serum and lung tissue samples. Ileum and lung tissues were harvested for histological examination. RESULTS: Ischemia-reperfusion caused severe oxidative damage and inflammation evident by significant increases in malondialdehyde and cytokine levels (tumor necrosis factor alpha and interleukin-1 beta) and decreased glutathione levels in both serum and lung tissues. There was severe histological tissue damage to the lung and ileum in the ischemia-reperfusion group. Probiotic pretreatment before aortic clamping caused significant suppression of increases in serum and lung tissue malondialdehyde and tumor necrosis factor alpha levels. Histological damage scores in tissue samples decreased in the ischemia-reperfusion+probiotic group (P<0,005). CONCLUSIONS: Oral supplementation of probiotic S. boulardii before supraceliac aortic ischemia-reperfusion in rats alleviates lung injury by reducing oxidative stress, intestinal cellular damage, and modulation of inflammatory processes.

Discordance between Serum Neutralizing Antibody Titers and the Recovery from COVID-19.

The recent pandemic of COVID-19 has caused a tremendous alarm around the world. Details of the infection process in the host have significant bearings on both recovery from the disease and on the correlates of the protection from the future exposures. One of these factors is the presence and titers of neutralizing Abs (NAbs) in infected people. In the current study, we set out to investigate NAbs in the recovered subjects discharged from the hospital in full health. Serum samples from a total of 49 documented consecutive COVID-19 subjects were included in the study. All the subjects were adults, and serum samples collected during the discharge were tested in viral neutralization, enzyme immunoassay (EIA), and Western immunoblot tests against viral Ags. Even though a majority of the recovered subjects had raised significant NAb titers, there is a substantial number of recovered patients (10 out of 49) with no or low titers of NAbs against the virus. In these cohorts as well as in patients with high NAb titers, viral Ag binding Abs were detectable in EIA tests. Both NAb titers and EIA detectable Abs are increased in patients experiencing a severe form of the disease, and in older patients the Ab titers were heightened. The main conclusion is that the recovery from SARS-CoV-2 infection is not solely dependent on high NAb titers in affected subjects, and this recovery process is probably produced by a complex interplay between many factors, including immune response, age of the subjects, and viral pathology.

Effect of Curcumin on the Formation of Epidural Fibrosis in an Experimental Laminectomy Model in Rats.

AIM: To clarify the effects of topical application of curcumin on the prevention of epidural fibrosis. MATERIAL AND METHODS: Twenty-one rats were randomly divided into three equal groups (control, spongostan, local curcumin) and a laminectomy procedure was performed between T11 and L1 in all rats. Subsequently, spongostan soaked with curcumin (100 mg/kg) was applied topically. After four weeks, the vertebral column from T9 to L3, which included the paraspinal muscles and epidural scar tissue, was removed as a single piece and the epidural fibrosis and arachnoidal scarring were graded and histopathological analysis carried out accordingly. Kruskal-Wallis and Pearson Chi-Square tests were used for statistical analysis. A p-value of less than 0.05 was considered to be significant. RESULTS: The grading of epidural fibrosis was far lower in the experimental group with curcumin compared to the control and spongostan groups, but the difference was not statistically significant. CONCLUSION: The findings of this study show that local curcumin decreases the formation of epidural fibrosis and this effect of curcumin is thought to be mediated by reducing the functions of inflammatory cells such as macrophages, neutrophils and fibroblasts, and the anti-inflammatory and antioxidant effects.

Effect of Tarantula Cubensis Extract (Theranekron) on Peripheral Nerve Healing in an Experimental Sciatic Nerve Injury Model in Rats.

AIM: To investigate the effects of systemic application of Theranekron on peripheral nerve healing after compression type peripheral nerve injury. MATERIAL AND METHODS: Twenty-one female Wistar albino rats were randomly divided into 3 groups (n=7): Control (C), injury (I), and Theranekron (T). The right sciatic nerves of rats in the I and T groups were compressed via an aneurysm clip for 5 minutes and 0.3 ml Theranekron D6 was applied via subcutaneous administration once a week in the T group for a total period of four weeks. Nerve conduction velocity and proximal and distal latency of the rats were measured at the end of day 30. The right sciatic nerves of the rats were then removed and myelin damage grading, axon counting, fibrosis assessment, caspase-3, and NF-kB immunochemical staining were performed. The data were analysed statistically and a p value of less than 0.05 was considered to be significant. RESULTS: Axonal degeneration, vacuolization and myelin destruction were found to be markedly greater in group T. Fibrosis and caspase-3 immunoreactivity were less intense in group T. There was a statistically significant difference in the electrophysiological results of groups I and T. However, there were no statistically significant differences in axon number and NF-kB immunochemical evaluation of groups I and T. CONCLUSION: The findings of this study show that Theranekron decreases axonal and myelin damage after sciatic nerve injury and that this neuroprotective effect of Theranekron can be attributed to its anti-inflammatory effect on pro-inflammatory cytokine levels.

Ozone Partially Decreases Axonal and Myelin Damage in an Experimental Sciatic Nerve Injury Model.

AIM: To investigate the effects of ozone in experimental acute sciatic nerve injury. MATERIAL AND METHODS: Twenty-eight male rats were divided into four groups (n = 7): control (C), ozone (O), injury (SNI), and treatment with ozone after injury (SNI + Ozone). Sciatic nerve injury was generated by compressing the right sciatic nerve for 90 s using a Yasargil aneurysm clip in groups SNI and SNI + Ozone. A 70 µg/ml concentration of ozone was given four times (once a day at 1st, 24th, 48th, and 72th h) at a dose of 0.5 mg/kg to groups O and SNI + Ozone after injury by an intraperitoneal injection. Nerve conduction velocities of all rats were measured by in vivo electrophysiological tests at the end of the day 4. Then, plasma malondialdehyde, total oxidant and antioxidant status were measured and also axonal and myelin changes in sciatic nerves of histopathological examination were performed. The data were analyzed by Kolmogorov Smirnov test, Mann-Whitney U-test, and Chi square test. p <.05 was considered statistically significant. RESULTS: The proximal and distal latency difference were higher and nerve conduction velocity were lower in SNI group than C and O groups, and the myelin structure was found to be broken in group SNI compared to groups C and O. However, the amplitude of the compound action potential, the nerve conduction velocity were significantly higher in group SNI + Ozone than in group SNI. Moreover, myelin injury was significantly lower in group SNI + Ozone compared to group SNI. Total oxidant status in group SNI was significantly higher than in groups C, O, and SNI + Ozone. But, total antioxidant status in group SNI was significantly lower than in groups C, O, and SNI + Ozone. CONCLUSION: This study showed that the administration of ozone at a dose of 0.5 mg/kg after peripheral nerve injury in rats reduces myelin and axonal injury.

Predicting critical duration and reversibility of damage in acute mesenteric ischemia: An experimental study.

BACKGROUND: The objective of the current study was to investigate the value of the ischemic biomarkers endothelial cell-specific molecule-1 (endocan) and signal peptide-CUB-EGF domain-containing protein-1 (SCUBE-1) in the diagnosis and assessment of earlystage and irreversible damage in acute mesenteric ischemia. METHODS: An experimental mesenteric ischemia reperfusion model was designed using 54 rats. Nine groups were created: Three sham groups [Groups I (30th minute), IV (2nd hour), and VII (6th hour)], in which only blood and tissue specimens were sampled; 3 ischemia groups [Groups II (30th minute), V (2nd hour), and VIII (6th hour)], in which blood and tissue specimens were sampled after ligation of the superior mesenteric artery (SMA); and 3 reperfusion groups [Groups III (30th minute), VI (2nd hour), and IX (6th hour)], in which blood and tissue specimens were sampled after declamping the SMA and reperfusion for 1 hour. SCUBE-1 and endocan samples obtained from blood and tissue were examined histopathologically. RESULTS: The SCUBE-1 level was higher in the ischemia groups when compared with the sham groups (p<0.05), and the endocan level was markedly different in the late ischemia (6th hour) group. When these 2 markers were used together to assess irreversible mesenteric damage in the histopathological examination, the sensitivity in distinguishing between reversible or irreversible damage was 94.1% with a specificity of 73.7%. CONCLUSION: The elevation of SCUBE-1 alone seems to be significant for predicting early mesenteric ischemia in laboratory rats. The combination of SCUBE-1 and endocan may be useful to detect irreversible intestinal damage.

Common Methylenetetrahydrofolate Reductase Polymorphisms (A1298C & C677T) in Ectopic Trophoblasts and Methotrexate Treatment Failure in Tubal Pregnancies.

OBJECTIVES: The success rate of methotrexate (MTX) therapy varies among tubal ectopic pregnancies. Common methylenetetrahydrofolate reductase (MTHFR) polymorphisms (C677T&A1298C) have been suggested to alter MTX effect. This study aimed to assess and compare MTX treatment failure rates with respect to MTHFR polymorphisms in trophoblasts of ectopic tubal pregnancies. MATERIAL AND METHODS: A retrospective chart review of tubal ectopic pregnancies was conducted and 34 eligible cases were found. Paraffinized blocks of ectopic trophoblastic tissues were retrieved from the archives of pathology department. Common MTHFR polymorphisms were studied on microdissected trophoblastic tissues. Sixteen cases with history of failed MTX therapy (study group) and 18 control cases were compared for their pertinent clinical characteristics and common MTHFR polymorphisms (C677T&A1298) data. RESULTS: In the study group, there were 8 (50%) C677T single nucleotide polymorphisms (SNP) and 9 (56.7%) A1298C SNP. Polymorphism rates were not found to be different between two groups for neither polymorphism (p > 0.05 for both). Number of compound heterozygotes was 3 (18.7%) in study group and 5 (27.7%) in controls (p = 0.693). In addition, MTHFR polymorphism presence seemed to have no effect on interval serum ß-hCG concentration change in MTX-fail group (p=0.693). CONCLUSIONS: Our data implied that common MTHFR polymorphisms of ectopic trophoblastic tissue are not associated with MTX failure in patients with tubal pregnancies. Additionally, serum ß-hCG concentration changes caused by MTX treatment and studied MTHFR polymorphisms are likely independent.

Utilizing prestin as a predictive marker for the early detection of outer hair cell damage.

PURPOSE: To evaluate prestin as a biomarker for the identification of early ototoxicity. MATERIALS AND METHODS: Rats (n = 47) were randomly assigned to five groups: low-dose (LAG) or high-dose (HAG) amikacin (200 and 600 mg/kg/day, respectively, for 10 days), low-dose (LCIS)or high-dose (HCIS) cisplatin (single doses of 5 and 15 mg/kg, respectively, for 3 days), and control (n = 8). At the end of the experiment, measurement of distortion product-evoked otoacoustic emissions (DPOAE) were performed to evaluate hearing, then blood samples and both ear tissues were collected under anesthesia. Prestin levels were determined by ELISA. Cochlear damage was evaluated histologically using a 4-point scoring system. RESULTS: The mean serum prestin levels were 377.0 ±â€¯135.3, 411.3 ±â€¯73.1, 512.6 ±â€¯106.0, 455.0 ±â€¯74.2 and 555.3 ±â€¯47.9 pg/ml for control, LCIS, HCIS, LAG and HAG groups, respectively. There was significant difference between prestin levels of Control-LCIS-HCIS groups (p = 0.031) and prestin levels of Control-LAG-HAG groups (p = 0.003). There were also significant differences in prestin levels between the low- and high-dose cisplatin and amikacin groups (p = 0.028 and p = 0.011, respectively). Each group had significantly lower DPOAE results at 4, 6 and 8 kHz than control groups (p < 0.001). The LAG, HAG, LCIS and HCIS groups had significantly higher cochlear damage scores than the control group (p < 0.05). CONCLUSIONS: Higher doses of cisplatin and amikacin were associated with the greatest increases in serum prestin level and cochlear damage score. The results of this study suggest that prestin is a promising early indicator of cochlear damage.