Effects of chronic noise stress on spatial memory of rats in relation to neuronal dendritic alteration and free radical-imbalance in hippocampus and medial prefrontal cortex

Spatial memory is coordinated with different brain regions especially hippocampus (HIP) and medial prefrontal cortex (mPFC). Influence of noise stress on working and reference memory error in rats was evaluated by radial eight-arm maze experiment. Changes in the dendritic count were observed in the brain regions such as CA1, CA3 regions of HIP and layers II, III of mPFC. In order to understand the possible mechanism behind noise stress-induced changes, free radical status and acetylcholinesterase (AChE) activity in HIP and mPFC were evaluated. Plasma corticosterone level was also evaluated. Results obtained in this study showed that after noise-stress exposure, 100 dBA/4h per day for 30 days, working and reference memory error increased significantly (P < 0.05) when compared to control animals. Neuronal dendritic count in the HIP was reduced in the 2nd and 3rd order dendrites but not in the mPFC. Superoxide dismutase, lipid peroxidation, plasma corticosterone level and AChE activity were significantly increased in the 1 day, 15 days and 30 days stress groups animal significantly. Catalase and glutathione peroxidase activity were increased in the 1 day and 15 days noise-stress groups but decreased in the 30 days noise-stress group and GSH level was decreased in all the stress exposed animals. In conclusion, oxidative stress, increased AChE activity, reduced dendritic count in HIP, mPFC regions and elevated plasma corticosterone level which develops in long-term noise-stress exposed rats, might have caused the impairment of spatial memory.     

Complement mediators in ischemia-reperfusion injury

BACKGROUND: Ischemia-reperfusion (I/R) injury occurs when a tissue is temporarily deprived of blood supply and the return of the blood supply triggers an intense inflammatory response. Pathologically, increased complement activity can cause substantial damage to blood vessels, tissues and also facilitate leukocyte activation and recruitment following I/R injury. Herein, previously published studies are reported and critically reviewed. METHODS: Medline and the World Wide Web were searched and the relevant literature was classified under the following categories: (1) Complement pathways; (2) The complement system and the inflammatory response; (3) Complement in ischemia-reperfusion injuries; and (4) Therapeutic approaches against complement in I/R injuries. RESULTS AND CONCLUSIONS: I/R injury is a common clinical event with the potential to seriously affect, and sometimes kill, the patient and is a potent inducer of complement activation that results in the production of a number of inflammatory mediators. Complement activation leads to the release of biologically active potent inflammatory complement substances including the anaphylatoxins (C3a and C5a) and the cytolytic terminal membrane attack complement complex C5b-9 (MAC). The use of specific complement inhibitors to block complement activation at various levels of the cascade has been shown to prevent or reduce local tissue injury after I/R. Several agents that inhibit all or part of the complement system, such as soluble complement receptor type 1 (sCR1), C1 inhibitor (C1-INH), C5a monoclonal antibodies, a C5a receptor antagonist and soluble CD59 (sCD59) have been shown to reduce I/R injury of various organs. The novel inhibitors of complement products may eventually find wide clinical application because there are no effective drug therapies currently available to treat I/R injuries.     

Trauma-induced cell swelling in cultured astrocytes

Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury that account for most early deaths after traumatic brain injury. An important component of brain edema after traumatic brain injury is astrocyte swelling (cytotoxic edema). To examine the pathophysiologic mechanisms of trauma-induced astrocyte swelling, we used an in vitro fluid percussion trauma model. Exposure of cultured rat astrocytes to 5 atm of pressure resulted in significant cell swelling at 1 to 24 hours posttrauma that was maximal at 3 hours. Because oxidative/nitrosative stress, mitochondrial permeability transition (mPT), and mitogen-activated protein kinases (MAPKs) have been implicated in astrocyte swelling in other neurologic conditions, we examined their potential roles in this model. We previously showed increased free radical generation after in vitro trauma and show here that trauma to astrocytes increased the production of nitric oxide. Trauma also induced mPT and increased phosphorylation (activation) of MAPKs (extracellular signal-regulated kinase 1/2, c-Jun-N-terminal kinase, and p38-MAPK); these changes were diminished by antioxidants and the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. Antioxidants, N-nitro-l-arginine methyl ester, the mPT inhibitor cyclosporin A, and inhibitors of MAPKs all significantly diminished trauma-induced astrocyte swelling. These findings demonstrate that direct mechanical injury to cultured astrocytes brings about cell swelling, and that blockade of oxidative/nitrosative stress, mPT, and MAPKs significantly reduce such swelling.     

Role of Immediate Pre-Operative Tympanometry in Cochlear Implantation: MERF Protocol and Experience

(1) To study the association between an immediate pre-operative tympanometric profile in patients undergoing cochlear implantation with their intraoperative findings. (2) To analyse the intraoperative middle ear findings that require a staged cochlear implantation in patients presenting with a B-type tympanogram. (3) To study the complications in this group of patients during the 1-year follow-up. This retrospective non-interventional cohort study is done over a period of 6 years. Bilaterally profound deaf children, less than 6 years of age, and no history of otitis media with effusion were included in the study. Children who met the inclusion criteria were divided into 4 groups based on their tympanometric profiles that are A, As, B, and C type tympanogram and, their intraoperative findings were categorized as normal, mild oedema, minimal granulation with mild oedema, moderate to extensive granulation with or without oedematous mucosa and glue. Then finally, depending on the intraoperative middle ear and mastoid finding, a single-stage surgery or a two stage surgery was decided upon. A total of 1025 patients were implanted during the study period, 975 patients met our inclusion criteria. In our series, we found a statistically significant difference (p < 0.0001) between the tympanograms and their respective intra-operative middle ear findings. A statistically significant difference was seen (p < 0.0001) between patients who underwent a single-stage cochlear implant and those who underwent a two-staged surgery, regarding their intraoperative middle ear findings. No statistical significance was seen in the occurrence of complications between the groups undergoing a single stage and a two-staged surgery (p > 0.5). This study showcases the importance of immediate pre-operative tympanometry in cochlear implant surgeries. Two-stage surgery is a decision taken on the operating table, depending on the extent of pathology and visibility of the round window niche.     

Rectal cancer: incidence of pulmonary metastases on thoracic CT and correlation with T staging

PURPOSE: The aim of the study was to evaluate the incidence of pulmonary metastases detected on thoracic computed tomography in patients with rectal cancer and assess the association between the incidence of pulmonary metastases and the stage of the rectal tumor. MATERIALS AND METHODS: Fifty-six consecutive patients who were diagnosed with rectal cancer over a 22-month period were included in the study. These patients had local tumor staging with a pelvic magnetic resonance imaging and staging computed tomographic scan of the chest and upper abdomen immediately after the magnetic resonance imaging. Two radiologists retrospectively reviewed all the thoracic imaging performed on these patients for the presence of metastases. The presence of a parenchymal lung nodule (greater than or equal to 1 cm if single and 0.5 cm if multiple) with a soft tissue component without calcification on lung and mediastinal window settings was considered positive for the presence of metastasis. All other patients were considered as not having any lung metastases. RESULTS: Of the 56 patients, 10 (17.9%) had evidence of pulmonary metastases on computed tomography. Of the 56 patients, there were 3 patients with stage T1, 24 with T2, 26 with T3, and 3 with stage T4 tumors. Of these 10 patients, 1 had a stage T2 tumor, 7 had T3, and 2 had stage T4 tumors. Statistical analysis using exact logistic regression showed the odds of getting lung metastases is an increasing function of tumor grade. CONCLUSIONS: There is a high incidence of lung metastases in patients with rectal cancer, and thoracic computed tomographic scanning should be performed as part of a staging protocol in all patients before any form of treatment is planned. There is a higher incidence of lung metastases with higher T stage.     

Enhanced lipid peroxidation and nitric oxide products with deranged antioxidant status in patients with head and neck squamous cell carcinoma

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can function both as initiators and promoters in carcinogenesis. Antioxidants provide protection against cellular and molecular damage caused by ROS and RNS. We conducted a study to evaluate the levels of lipid peroxidation products, nitric oxide (NO) products and antioxidants in patients with head and neck squamous cell carcinoma (HNSCC). Fifty one HNSCC patients, 33 healthy tobacco smokers/chewers as tobacco user controls, and 37 non-smokers/chewers as normal controls were recruited for this study. Lipid peroxidation products, NO products and antioxidants were measured using spectrophotometric methods. Lipid peroxidation products, including lipid hydroperoxide (LHP) and malondialdehyde (MDA), nitric oxide (NO) products, including nitrite (NO(2)(-)), nitrate (NO(3)(-)), and total nitrite (TNO(2)(-)) were found to be significantly elevated with a concomitant depletion of antioxidants in HNSCC patients as compared to tobacco users and normal controls. These derangements were also evident albeit to a lesser degree in tobacco users as compared to normal controls. Results from this study demonstrate a potential involvement of both ROS and RNS in the pathogenesis of HNSCC and also illustrate the risk of ROS/RNS induced damage healthy tobacco users are exposed to, implicating their higher risk for upper aerodigestive tract cancer.